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1. Pediatric chronic spontaneous urticaria: a brief clinician’s guide

Author

Martina Votto, Giovanna Achilli, Maria De Filippo, Amelia Licari, Alessia Marseglia, Alice Moiraghi, Antonio Di Sabatino, and Gian Luigi Marseglia

Subjects
Adult, Urticaria, Anti-Allergic Agents, Chronic Disease, Immunology, Quality of Life, COVID-19, Humans, Immunology and Allergy, Chronic Urticaria, Omalizumab, Child, Pandemics
Abstract

Chronic urticaria (CU) appears with daily or intermittent/recurrent wheals with/without angioedema for more than six weeks. When no specific eliciting factors are found, chronic urticaria is defined as spontaneous (CSU). Up to 50% of patients with CSU do not respond to therapy, leading to a prolonged disease course and the need for expensive therapies, impacting the quality of life (QoL) and healthcare resources.Diagnosis of CSU is made when other potential causes of chronic urticaria are excluded. CSU therapy aims to achieve complete control of symptoms and normalization of QoL. Current treatment options for urticaria aim to target mast cell mediators such as histamine, or activators, such as autoantibodies. Guidelines recommend starting with second generation antihistamines (sgAHs) and adding omalizumab therapy if symptoms are not controlled. This review aims to provide a practical guide for CSU in the pediatric population.Treatment options for pediatric CSU are primarily based on adult data that have been extrapolated for children. Current guidelines should be reevaluated based on pediatric data, new biological treatments, and the COVID-19 pandemic. Future research is needed to investigate strategies to personalize current treatments and identify potential predictive biomarkers.

Published
2022

2. The diverse genetic origins of a Classical period Greek army

Author

Laurie J. Reitsema, Alissa Mittnik, Britney Kyle, Giulio Catalano, Pier Francesco Fabbri, Adam C. S. Kazmi, Katherine L. Reinberger, Luca Sineo, Stefano Vassallo, Rebecca Bernardos, Nasreen Broomandkhoshbacht, Kim Callan, Francesca Candilio, Olivia Cheronet, Elizabeth Curtis, Daniel Fernandes, Martina Lari, Ann Marie Lawson, Matthew Mah, Swapan Mallick, Kirsten Mandl, Adam Micco, Alessandra Modi, Jonas Oppenheimer, Kadir Toykan Özdogan, Nadin Rohland, Kristin Stewardson, Stefania Vai, Chiara Vergata, J. Noah Workman, Fatma Zalzala, Valentina Zaro, Alessandro Achilli, Achilles Anagnostopoulos, Cristian Capelli, Varnavas Constantinou, Hovirag Lancioni, Anna Olivieri, Anastasia Papadopoulou, Nikoleta Psatha, Ornella Semino, John Stamatoyannopoulos, Ioanna Valliannou, Evangelia Yannaki, Iosif Lazaridis, Nick Patterson, Harald Ringbauer, David Caramelli, Ron Pinhasi, David Reich, Reitsema, Laurie J, Mittnik, Alissa, Kyle, Britney, Catalano, Giulio, Fabbri, Pier Francesco, Kazmi, Adam C S, Reinberger, Katherine L, Sineo, Luca, Vassallo, Stefano, Bernardos, Rebecca, Broomandkhoshbacht, Nasreen, Callan, Kim, Candilio, Francesca, Cheronet, Olivia, Curtis, Elizabeth, Fernandes, Daniel, Lari, Martina, Lawson, Ann Marie, Mah, Matthew, Mallick, Swapan, Mandl, Kirsten, Micco, Adam, Modi, Alessandra, Oppenheimer, Jona, Özdogan, Kadir Toykan, Rohland, Nadin, Stewardson, Kristin, Vai, Stefania, Vergata, Chiara, Workman, J Noah, Zalzala, Fatma, Zaro, Valentina, Achilli, Alessandro, Anagnostopoulos, Achille, Capelli, Cristian, Constantinou, Varnava, Lancioni, Hovirag, Olivieri, Anna, Papadopoulou, Anastasia, Psatha, Nikoleta, Semino, Ornella, Stamatoyannopoulos, John, Valliannou, Ioanna, Yannaki, Evangelia, Lazaridis, Iosif, Patterson, Nick, Ringbauer, Harald, Caramelli, David, Pinhasi, Ron, and Reich, David

Subjects
Europe, Warfare, Multidisciplinary, Military Personnel, Archaeology, Greece, Classical world, Humans, history, Settore BIO/08 - Antropologia, ancient DNA, ancient warfare, History, Ancient
Abstract

Trade and colonization caused an unprecedented increase in Mediterranean human mobility in the first millennium BCE. Often seen as a dividing force, warfare is in fact another catalyst of culture contact. We provide insight into the demographic dynamics of ancient warfare by reporting genome-wide data from fifth-century soldiers who fought for the army of the Greek Sicilian colony of Himera, along with representatives of the civilian population, nearby indigenous settlements, and 96 present-day individuals from Italy and Greece. Unlike the rest of the sample, many soldiers had ancestral origins in northern Europe, the Steppe, and the Caucasus. Integrating genetic, archaeological, isotopic, and historical data, these results illustrate the significant role mercenaries played in ancient Greek armies and highlight how participation in war contributed to continental-scale human mobility in the Classical world.

Published
2022

3. Mid-term oncological outcomes after complete versus conventional mesocolic excision for right-sided colon cancer: a propensity score matching analysis

Author

Alessandro Giani, Camillo Leonardo Bertoglio, Michele Mazzola, Irene Giusti, Pietro Achilli, Pietro Carnevali, Matteo Origi, Carmelo Magistro, and Giovanni Ferrari

Subjects
Kidney Neoplasms, Cohort Studies, Postoperative Complications, Treatment Outcome, Colonic Neoplasms, Humans, Lymph Node Excision, Laparoscopy, Surgery, Propensity Score, Carcinoma, Renal Cell, Colectomy, Mesocolon, Retrospective Studies
Abstract

The correct extent of mesocolic dissection for right-sided colon cancer (RCC) is still under debate. Complete mesocolic excision (CME) has not gained wide diffusion, mainly due to its technical complexity and unclear oncological superiority. This study aims to evaluate oncological outcomes of CME compared with non-complete mesocolic excision (NCME) during resection for I-III stage RCC.Prospectively collected data of patients who underwent surgery between 2010 and 2018 were retrospectively analysed. 1:1 Propensity score matching (PSM) was used to balance baseline characteristics of CME and NCME patients. The primary endpoint of the study was local recurrence-free survival (LRFS). The two groups were also compared in terms of short-term outcomes, distant recurrence-free survival, disease-free survival, and overall survival.Of the 444 patients included in the study, 292 were correctly matched after PSM, 146 in each group. The median follow-up was 45 months (IQR 33-63). Conversion rate, complications, and 90-day mortality were comparable in both groups. The median number of lymph nodes harvested was higher in CME patients (23 vs 19, p = 0.034). 3-year LRFS rates for CME patients was 100% and 95.6% for NCME (log-rank p = 0.028). At 3 years, there were no differences between the groups in terms of overall survival, distant recurrence-free survival, and disease-free survival.Our PSM cohort study shows that CME is safe, provides a higher number of lymph nodes harvested, and is associated with better local recurrence-free survival.

Published
2022

4. Structural influence of antibody recruiting glycodendrimers (ARGs) on antitumoral cytotoxicity

Author

Eugénie Laigre, Benjamin Liet, Biagio Todaro, David Goyard, Claire Tiertant, Nathalie Berthet, Silvia Achilli, Olivier Renaudet, Todaro, B., Achilli, S., Liet, B., Laigre, E., Tiertant, C., Goyard, D., Berthet, N., Renaudet, O., Département de Chimie Moléculaire (DCM), Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM), and Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Biomedical Engineering, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ligands, 010402 general chemistry, 01 natural sciences, Antibodies, Cell Line, Flow cytometry, chemistry.chemical_compound, Cell Line, Tumor, Settore BIO/10 - Biochimica, Dendrimer, medicine, Humans, General Materials Science, Cytotoxicity, Melanoma, Ternary complex, medicine.diagnostic_test, biology, 010405 organic chemistry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Settore CHIM/06 - Chimica Organica, Flow Cytometry, 3. Good health, 0104 chemical sciences, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Cell culture, Polylysine, Cancer cell, Biophysics, biology.protein, Antibody
Abstract

International audience; The recruitment of endogenous antibodies against cancer cells has become a reliable antitumoral immunotherapeutic alternative over the last decade. The covalent attachment of antibody and tumor binding modules (ABM and TBM) within a single, well-defined synthetic molecule was indeed demonstrated to promote the formation of an interacting ternary complex between both the antibodies and the targeted cell, which usually results in the simultaneous immune-mediated cellular destruction. In a preliminary study, we have described the first Antibody Recruiting Glycodendrimers (ARGs), combining cRGD as ligands for the α V β 3-expressing melanoma cell line M21 and Rha as ligand for natural IgM, and demonstrated that multivalency is an essential requirement to form this complex. In the present study, we synthesized a new series of ARGs composed of ABMs, i.e. self-condensed rhamnosylated cyclopeptide and polylysine dendrimer, which have been conjugated to the TBM with or without spacer. Flow cytometry and confocal microscopy experiments with human serum and different cell lines revealed that the ABM geometry significantly influences the ternary complex formation in M21, whereas no significant binding occurs in BT 549 having low integrin expression. In addition, we demonstrate with a cellular viability assay that ARGs induce high level of cytotoxicity against M21 which is also in close correlation with the ABM structure. In particular, we have shown that ARG combining cyclopeptide core and branches, with or without spacer, induce 40-57% of selective cytotoxicity against M21 cells in the presence of human serum as the unique source of immunity effectors. Finally, we also highlight that the spacer between ABM and TBM enables an increase of the immune-mediate cytotoxicity even with ABM of lower valency.

Published
2021

5. The Mitogenome Relationships and Phylogeography of Barn Swallows (Hirundo rustica)

Author

Gianluca Lombardo, Nicola Rambaldi Migliore, Giulia Colombo, Marco Rosario Capodiferro, Giulio Formenti, Manuela Caprioli, Elisabetta Moroni, Leonardo Caporali, Hovirag Lancioni, Simona Secomandi, Guido Roberto Gallo, Alessandra Costanzo, Andrea Romano, Maria Garofalo, Cristina Cereda, Valerio Carelli, Lauren Gillespie, Yang Liu, Yosef Kiat, Alfonso Marzal, Cosme López-Calderón, Javier Balbontín, Timothy A. Mousseau, Piotr Matyjasiak, Anders Pape Møller, Ornella Semino, Roberto Ambrosini, Andrea Bonisoli-Alquati, Diego Rubolini, Luca Ferretti, Alessandro Achilli, Luca Gianfranceschi, Anna Olivieri, Antonio Torroni, Lombardo G., Rambaldi Migliore N., Colombo G., Capodiferro M.R., Formenti G., Caprioli M., Moroni E., Caporali L., Lancioni H., Secomandi S., Gallo G.R., Costanzo A., Romano A., Garofalo M., Cereda C., Carelli V., Gillespie L., Liu Y., Kiat Y., Marzal A., Lopez-Calderon C., Balbontin J., Mousseau T.A., Matyjasiak P., Moller A.P., Semino O., Ambrosini R., Bonisoli-Alquati A., Rubolini D., Ferretti L., Achilli A., Gianfranceschi L., Olivieri A., and Torroni A.

Subjects
Settore BIO/07 - Ecologia, haplogroup, Hirundo rustica subspecie, Asia, mitogenome, Animal, barn swallow phylogeny, mitochondrial, Phylogeography, Swallows, Hirundo rustica subspecies, haplogroups, Africa, animals, female, humans, phylogeography, genome, mitochondrial, swallows, Genome, Mitochondrial, Genetics, Animals, Humans, Female, genome, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Human
Abstract

The barn swallow (Hirundo rustica) poses a number of fascinating scientific questions, including the taxonomic status of postulated subspecies. Here, we obtained and assessed the sequence variation of 411 complete mitogenomes, mainly from the European H. r. rustica, but other subspecies as well. In almost every case, we observed subspecies-specific haplogroups, which we employed together with estimated radiation times to postulate a model for the geographical and temporal worldwide spread of the species. The female barn swallow carrying the Hirundo rustica ancestral mitogenome left Africa (or its vicinity) around 280 thousand years ago (kya), and her descendants expanded first into Eurasia and then, at least 51 kya, into the Americas, from where a relatively recent (

Published
2022

6. Liver-spleen axis dysfunction in COVID-19

Author

Sara Cococcia, Giovanna Achilli, Federica Borrelli de Andreis, Marco Vincenzo Lenti, Giovanni Santacroce, and Antonio Di Sabatino

Subjects
White pulp, Asplenia, medicine.medical_specialty, medicine.medical_treatment, Spleen, Liver transplantation, Chronic liver disease, Gastroenterology, Transaminase, Liver disease, Atrophy, Internal medicine, medicine, Humans, business.industry, SARS-CoV-2, IgM memory B cell, Liver Diseases, COVID-19, Minireviews, General Medicine, medicine.disease, medicine.anatomical_structure, Cytokine storm, business
Abstract

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an acute infectious disease that spreads mainly through the respiratory route. Besides interstitial pneumonia, a number of other clinical manifestations were noticed in COVID-19 patients. In particular, liver and spleen dysfunctions have been described both as complications of COVID-19 and as potential predisposing factors for severe COVID-19. Liver damage is rather common in COVID-19 patients, and it is most likely multifactorial, caused by the direct insult of SARS-CoV-2 to the liver by the cytokine storm triggered by the virus, by the use of hepatotoxic drugs, and as a consequence of hypoxia. Although generally mild, liver impairment has been found to be associated with a higher rate of intensive care unit admission. A higher mortality rate was reported among chronic liver disease patients. Instead, spleen impairment in patients with COVID-19 has been poorly described. The main anatomical changes are the architectural derangement of the B cell compartment, white pulp atrophy, and reduction or absence of lymphoid follicles, while, from a functional point of view, the IgM memory B cell pool is markedly depleted. The outcome of COVID-19 in asplenic or hyposplenic patients is yet to be defined. In this review, we will summarise the current knowledge regarding the impact of SARS-CoV-2 on the liver and spleen function, as well as the outcome of patients with a pre-existent liver disease or defective spleen function.

Published
2021

7. Quality of Life in Older Adults After Major Cancer Surgery: The GOSAFE International Study

Author

Montroni, Isacco, Ugolini, Giampaolo, Saur, Nicole M, Rostoft, Siri, Spinelli, Antonino, Van Leeuwen, Barbara L, De Liguori Carino, Nicola, Ghignone, Federico, Jaklitsch, Michael T, Somasundar, Ponnandai, Garutti, Anna, Zingaretti, Chiara, Foca, Flavia, Vertogen, Bernadette, Nanni, Oriana, Wexner, Steven D, Audisio, Riccardo, A Giovanni Taffurelli, Davide, Zattoni, Paola, Tramelli, Giacomo, Sermonesi, Giorgio, Ercolani, Francesca, Tauceri, Barbara, Perenze, Daniela Di Pietrantonio, Mariateresa, Mirarchi, Gianluca, Garulli, Vincenzo, Alagna, Lucchi, Andrea, Basilio, Pirrera, Francesco, Monari, Luigi, Conti, Patrizio, Capelli, Andrea, Romboli, Gerardo, Palmieri, Filippo, Banchini, Francesca Di Candido, Michele, Carvello, Matteo, Sacchi, DE LUCIA, Francesca, Caterina, Foppa, Luigi, Marano, Spaziani, Alessandro, Giampaolo, Castagnoli, Bartoli, Alberto, Laura, Frain, Sam, W Fox, Kristin, Cardin, Luis, E De Leon, Mario, Trompetto, Gallo, Gaetano, Alberto Realis Luc, Giuseppe, Clerico, Giuseppe, Sammarco, Raffaele De Luca, Michele, Simone, Rocco, Lomonaco, Michael, Fejka, Joshua I, S Bleier, Matthijs, Plas, Hanneke van der Wal-Huisman, Andrea, Costanzi, Giulio, Mari, Dario, Maggioni, Pellegrino, Roberta, Pietro, Ascheri, Jakub, Kenig, Kinga, Szabat, Stefano, Scabini, Davide, Pertile, Lorenzo, Epis, Andrea, Massobrio, Domenico, Soriero, Arild, Nesbakken, Ingeborg Flåten Backe, Mariann, Lønn, Ferrari, Giovanni, Michele, Mazzola, Carmelo, Magistro, Pietro, Achilli, Alessandro, Giani, Orestis, Ioannidis, Lydia, Loutzidou, Konstantinos, Galanos-Demiris, Balducci, Genoveffa, Frezza, Barbara, Lucarini, Alessio, Claudia, Santos, Diogo, Cardoso, Isabela, Gil, Vasco, Cardoso, Lisa, Cooper, Baha, Siam, Yochai, Levy, Baruch, Brenner, Hanoch, Kashtan, Valerio, Belgrano, Franco, Decian, Beatrice, Palermo, Roberto, Eggenhöffner, Manuela, Albertelli, Luis, Sánchez-Guillén, Antonio, Arroyo, Francisco, López-Rodríguez, Sandra, Lario, DI LILLO, Cristina, Minas, Baltatzis, Anthony K, C Chan, Ajith, K Siriwardena, Giovanna Da Silva, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Subjects
Cancer Research, aged, Oncology, male, quality of life, geriatric assessment, 80 and over, neoplasms, pain, frailty, humans, aged, 80 and over
Abstract

Background Accurate quality of life (QoL) data and functional results after cancer surgery are lacking for older patients. The international, multicenter Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) Study compares QoL before and after surgery and identifies predictors of decline in QoL. Methods GOSAFE prospectively collected data before and after major elective cancer surgery on older adults (≥70 years). Frailty assessment was performed and postoperative outcomes recorded (30, 90, and 180 days postoperatively) together with QoL data by means of the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L), including 2 components: an index (range = 0-1) generated by 5 domains (mobility, self-care, ability to perform the usual activities, pain or discomfort, anxiety or depression) and a visual analog scale. Results Data from 26 centers were collected (February 2017-March 2019). Complete data were available for 942/1005 consecutive patients (94.0%): 492 male (52.2%), median age 78 years (range = 70-95 years), and primary tumor was colorectal in 67.8%. A total 61.2% of all surgeries were via a minimally invasive approach. The 30-, 90-, and 180-day mortality was 3.7%, 6.3%, and 9%, respectively. At 30 and 180 days, postoperative morbidity was 39.2% and 52.4%, respectively, and Clavien-Dindo III-IV complications were 13.5% and 18.7%, respectively. The mean EQ-5D-3L index was similar before vs 3 months but improved at 6 months (0.79 vs 0.82; P Conclusions GOSAFE shows that older adults’ preoperative QoL is preserved 3 months after cancer surgery, independent of their age. Frailty screening tools, patient-reported outcomes, and goals-of-care discussions can guide decisions to pursue surgery and direct patients’ expectations.

Published
2022

9. Mitochondrial genomes from modern horses reveal the major haplogroups that underwent domestication

Author

Achilli, Alessandro, Olivieri, Anna, Soares, Pedro, Lancioni, Hovirag, Kashani, Baharak Hooshiar, Perego, Ugo A., Nergadze, Solomon G., Carossa, Valeria, Santagostino, Marco, Capomaccio, Stefano, Felicetti, Michela, Al-Achkar, Walid, Penedo, M. Cecilia T., Verini-Supplizi, Andrea, Houshmand, Massoud, Woodward, Scott R., Semino, Ornella, Silvestrelli, Maurizio, Giulotto, Elena, Pereira, Luísa, Bandelt, Hans-Jürgen, and Torroni, Antonio

Published
2012

10. Functional and Short-term Outcomes in Elective Laparoscopic Colectomy for Symptomatic Diverticular Disease With Either Low Ligation or Inferior Mesenteric Artery Preservation: A Randomized Trial

Author

Giampaolo Ugolini, Giovanni Ferrari, Andrea Costanzi, Matteo Origi, Jacopo Crippa, Dario Maggioni, Pietro Achilli, Giulio Mari, and Isacco Montroni

Subjects
medicine.medical_specialty, Anastomosis, Inferior mesenteric artery, law.invention, 03 medical and health sciences, 0302 clinical medicine, Sigmoidectomy, Quality of life, Randomized controlled trial, law, medicine.artery, medicine, Humans, Ligation, Colectomy, Diverticular Diseases, business.industry, Genitourinary system, Mesenteric Artery, Inferior, Surgery, 030220 oncology & carcinogenesis, Quality of Life, Diverticular disease, Laparoscopy, 030211 gastroenterology & hepatology, business
Abstract

BACKGROUND The current treatment of symptomatic diverticular disease is left colectomy/sigmoidectomy with low ligation of the inferior mesenteric artery versus the inferior mesenteric artery preservation. Up to now, there is no strong evidence in favor of one of the 2 strategies. The aim of this study is to compare the bowel-specific quality of life and functional outcomes between these 2. METHODS Between June 2015 and February 2019, patients were randomly assigned to inferior mesenteric artery low ligation or inferior mesenteric artery preservation during elective laparoscopic sigmoidectomy for diverticular disease. Gastrointestinal, genitourinary functions and surgical outcomes were compared postoperatively between groups. RESULTS One-hundred sixty-eight patients were randomized providing 2 homogenous groups. Gastrointestinal and genitourinary functions were not significantly different between groups after 1 and 6 months postoperative. In both groups, the function was restored to the preoperative level 6 months after surgery. There was no statistically significant difference in terms of conversion rate, blood loss, length of surgery, between groups. There was no difference in the overall complication rate and the anastomotic leak rate among groups. CONCLUSIONS Inferior mesenteric artery low ligation or inferior mesenteric artery preservation during elective laparoscopic sigmoidectomy for a diverticular disease can be considered equivalent in affecting the postoperative bowel-related quality of life, genitourinary function, and surgical outcomes.

Published
2020

11. Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction—Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial

Author

Christiane Otto, Michael Becka, Raymond J. Kim, Eugenia Nikolsky, Katia Orvin, Ran Kornowski, Dan Admon, Mercedes Roque, Savina Nodari, Sadrack Oumbe Tiam, Hans-Dirk Duengen, Johann Bauersachs, Ivo Podpera, Felice Achilli, Borja Ibanez, Friederike Kanefendt, Yaron Arbel, Gian Carlo Silvio Marenzi, Gonzalo Calvo Rojas, Petr Hájek, Doron Zahger, Michele Senni, Petr Ostadal, Bernhard Reimers, Hana Linkova, Manuel Martinez Selles, Niels Menck, Avraham Shimony, Jiri Kettner, Jan Fuisting, Tal Hasin, Andrés Íñiguez Romo, Vicente Miro Palau, Duengen, H, Kim, R, Zahger, D, Orvin, K, Kornowski, R, Admon, D, Kettner, J, Shimony, A, Otto, C, Becka, M, Kanefendt, F, Romo, A, Hasin, T, Ostadal, P, Rojas, G, Senni, M, and GROUP investigators of the CHIARA MIA, 2

Subjects
Male, medicine.medical_specialty, Heart Ventricles, Magnetic Resonance Imaging, Cine, 030204 cardiovascular system & hematology, Placebo, Ventricular Function, Left, Heart Ventricle, law.invention, 03 medical and health sciences, Chymases, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Risk factor, Heart Failure, Ejection fraction, Ventricular Remodeling, medicine.diagnostic_test, business.industry, Chymase, Stroke Volume, Magnetic resonance imaging, Middle Aged, medicine.disease, Treatment Outcome, Heart failure, Cardiology, ST Elevation Myocardial Infarction, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract

Background Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). Methods In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. Results Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ± 5.4%, placebo: 4.0% ± 5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ± 13.3 mL/m2, placebo: 5.1 ± 18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ± 11.2 mL/m2, placebo: 0.6 ± 14.8 mL/m2, P = .56) were observed in both treatment arms. Conclusion Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.

Published
2020

12. Robotic surgery for rectal cancer as a platform to build on: review of current evidence

Author

David W. Larson, Pietro Achilli, and Fabian Grass

Subjects
Laparoscopic surgery, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Operative Time, 03 medical and health sciences, 0302 clinical medicine, Robotic Surgical Procedures, medicine, Humans, Robotic surgery, Laparoscopy, Digestive System Surgical Procedures, Quality of Health Care, medicine.diagnostic_test, business.industry, General surgery, Margins of Excision, Cancer, Workload, Health Care Costs, General Medicine, Length of Stay, medicine.disease, Total mesorectal excision, Colorectal surgery, Treatment Outcome, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Surgery, Colorectal Neoplasms, business, Learning Curve
Abstract

Laparoscopy in colorectal surgery reduces the rate of postoperative complications, shortens the length of stay in hospital, and improves the quality of patient care. Despite these established benefits, the technical challenges of rectal resection for cancer have resulted in most operations being performed through open surgery in the USA. Moreover, controversy in the current literature questions the oncologic safety of a laparoscopic approach for rectal cancer. How then can surgeons innovate to overcome the technical challenges while preserving the critical oncological outcomes of high-quality rectal cancer surgery? Robotics may be a platform that allows us to overcome the technical challenges in the pelvis while maintaining both oncological outcomes and the benefits of a minimally invasive technique. Current evidence suggests that the quality of total mesorectal excision, the rates of circumferential margin involvement, and postoperative outcomes are comparable between robotic and laparoscopic surgery. While a robotic approach demonstrates lower conversion rates and reduced surgeon workload, the operative time is longer and initial costs are higher; however, time and future science will determine its true benefits. We review the current state of robotic surgery and its impact on rectal cancer surgery.

Published
2020

13. Modest agreement between magnetic resonance and pathological tumor regression after neoadjuvant therapy for rectal cancer in the real world

Author

Pietro Achilli, Carmelo Magistro, Mohamed A. Abd El Aziz, Giacomo Calini, Camillo L. Bertoglio, Giovanni Ferrari, Giulio Mari, Dario Maggioni, Georgios Peros, Sara Tamburello, Elisabetta Coppola, Antonino Spinelli, Fabian Grass, David Martin, Dieter Hahnloser, Andrea Salvatori, Silvia De Simoni, Shannon P. Sheedy, Joel G. Fletcher, and David W. Larson

Subjects
Adult, Cancer Research, Magnetic Resonance Spectroscopy, Rectal Neoplasms, Chemoradiotherapy, Magnetic Resonance Imaging, Neoadjuvant Therapy, Cohort Studies, Rare Diseases, Treatment Outcome, Oncology, Chemoradiotherapy/methods, Humans, Magnetic Resonance Imaging/methods, Neoadjuvant Therapy/methods, Neoplasm Staging, Rare Diseases/pathology, Rectal Neoplasms/drug therapy, Rectal Neoplasms/therapy, Retrospective Studies, agreement analysis, magnetic resonance, neoadjuvant therapy, rectal cancer, tumor regression grade
Abstract

Magnetic resonance imaging (MRI) is routinely used for preoperative tumor staging and to assess response to therapy in rectal cancer patients. The aim of our study was to evaluate the accuracy of MRI based restaging after neoadjuvant chemoradiotherapy (CRT) in predicting pathologic response. This multicenter cohort study included adult patients with histologically confirmed locally advanced rectal adenocarcinoma treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019 at four academic high-volume institutions. Magnetic resonance tumor regression grade (mrTRG) and pathologic tumor regression grade (pTRG) were reviewed and compared for all the patients. The agreement between radiologist and pathologist was assessed with the weighted k test. Risk factors for poor agreement were investigated using logistic regression. A total of 309 patients were included. Modest agreement was found between mrTRG and pTRG when regression was classified according to standard five-tier systems (k = 0.386). When only two categories were considered for each regression system, (pTRG 0-3 vs pTRG 4; mrTRG 2-5 vs mrTRG 1) an accuracy of 78% (95% confidence interval [CI] 0.73-0.83) was found between radiologic and pathologic assessment with a k value of 0.185. The logistic regression model revealed that "T3 greater than 5 mm extent" was the only variable significantly impacting on disagreement (OR 0.33, 95% CI 0.15-0.68, P = .0034). Modest agreement exists between mrTRG and pTRG. The chances of appropriate assessment of the regression grade after neoadjuvant CRT appear to be higher in case of a T3 tumor with at least 5 mm extension in the mesorectal fat at the pretreatment MRI.

Published
2022

14. Overview of the Americas’ First Peopling from a Patrilineal Perspective: New Evidence from the Southern Continent

Author

Giulia Colombo, Luca Traverso, Lucia Mazzocchi, Viola Grugni, Nicola Rambaldi Migliore, Marco Rosario Capodiferro, Gianluca Lombardo, Rodrigo Flores, Monika Karmin, Siiri Rootsi, Luca Ferretti, Anna Olivieri, Antonio Torroni, Rui Martiniano, Alessandro Achilli, Alessandro Raveane, and Ornella Semino

Subjects
Male, Chromosomes, Human, Y, Y-chromosome variation, peopling of the Americas, haplogroups C and Q, phylogeny, inland migrations, Haplotypes, Human Migration, Genetics, Humans, Americas, Phylogeny, Genetics (clinical), humanities
Abstract

Uniparental genetic systems are unique sex indicators and complement the study of autosomal diversity by providing landmarks of human migrations that repeatedly shaped the structure of extant populations. Our knowledge of the variation of the male-specific region of the Y chromosome in Native Americans is still rather scarce and scattered, but by merging sequence information from modern and ancient individuals, we here provide a comprehensive and updated phylogeny of the distinctive Native American branches of haplogroups C and Q. Our analyses confirm C-MPB373, C-P39, Q-Z780, Q-M848, and Q-Y4276 as the main founding haplogroups and identify traces of unsuccessful (pre-Q-F1096) or extinct (C-L1373*, Q-YP4010*) Y-chromosome lineages, indicating that haplogroup diversity of the founder populations that first entered the Americas was greater than that observed in the Indigenous component of modern populations. In addition, through a diachronic and phylogeographic dissection of newly identified Q-M848 branches, we provide the first Y-chromosome insights into the early peopling of the South American hinterland (Q-BY104773 and Q-BY15730) and on overlying inland migrations (Q-BY139813).

Published
2022
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16. Completely intracorporeal anastomosis in robotic left colonic and rectal surgery: technique and 30-day outcomes

Author

Kevin T. Behm, William Perry, Pietro Achilli, Scott R. Kelley, Mohamed A. Abd El Aziz, Fabian Grass, and David W. Larson

Subjects
Anastomosis, Surgical, Colectomy, Colon/surgery, Humans, Laparoscopy, Postoperative Complications/epidemiology, Retrospective Studies, Robotic Surgical Procedures, Treatment Outcome, Colorectal surgery, Extracorporeal anastomosis, Intracorporeal anastomosis, Robotic surgery, Short-term outcomes, medicine.medical_specialty, Colon, Anastomosis, Malignancy, Extracorporeal, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Blood loss, medicine, Rectal surgery, business.industry, medicine.disease, Surgery, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business
Abstract

As robotic surgery continues to disseminate into the field of colon and rectal surgery, there is a growing interest in the utilization of intracorporeal anastomosis to potentially improve surgical outcomes. The purpoe of this study was to compare feasibility, safety, and short-term outcomes of robotic sigmoid and low anterior resections performed with completely intracorporeal anastomosis (CICA) technique to the traditional extracorporeal assisted anastomosis (ECAA) technique. Consecutive series of patients who underwent elective robotic sigmoid or low anterior resections for benign or malignant disease utilizes either CICA or ECAA between August 2017 and November 2019. Surgical complications were assessed until 30 postoperative days and compared between the two groups. A total of 160 patients were identified; 73 (45.6%) in the CICA group and 87 (54.4%) in the ECAA group. Most of the procedures were performed for malignancy (76%). Estimated blood loss was lower in the CICA group (80.7 mL vs. 110.2 mL; p = 0.048), while operative times were longer (5.9 ± SD hours vs. 4.9 ± SD hours; p = < 0.001). Overall conversion rate was 1.9%, with no conversions in the CICA group. Overall complications occurred in 54 patients (33.8%) with 13 (8.3%) representing major complications. There were no significant differences in 30 day outcomes between the two groups. This study demonstrates the feasibility and safety of robotic sigmoid and low anterior resections with CICA. Outcomes for robotic sigmoid and low anterior resections are encouraging regardless of anastomotic technique (CICA vs ECAA).

Published
2021

17. Cochlear Implant Surgery: How to Fix Receiver/Stimulator Avoiding Extrusion

Author

Vittorio Pietro Achilli, Simone Zucchini, Annalisa Gatto, Jamile Karina Antonio, Giancarlo Tirelli, Alice Piccinato, Margherita Tofanelli, Gatto, Annalisa, Tofanelli, Margherita, Piccinato, Alice, Antonio, Jamile Karina, Zucchini, Simone, Achilli, Vittorio Pietro, and Tirelli, Giancarlo

Subjects
Adult, Male, medicine.medical_specialty, Hearing loss, medicine.medical_treatment, Pilot Projects, Postoperative Complications, Suture Anchors, Cochlear implant, medicine, Humans, postoperative complication, hearing loss, fixation technique, business.industry, Suture Techniques, cochlear implant, hearing lo, Cochlear Implantation, Surgery, Cochlear implant surgery, Cochlear Implants, Otorhinolaryngology, receiver/stimulator extrusion, postoperative complications, Female, medicine.symptom, business
Abstract

Cochlear implant (CI) surgery is generally safe and associated with a limited number of complications, among which the extrusion of the receiver/stimulator (R/S) or the electrode misplacement and migration might require a CI re-implantation. The aim of this pilot study is to describe a new technique to firmly fix the R/S using the Mitek suture anchors system (Depuy Mitek Surgical Products, Inc. Raynham, Massachusetts). We tested two different models and in our experience, the web of suture created with this device can improve the stability of the bond of the R/S to the underlying curved bone surface. So, this system resulted in a less laborious manner keeping low the complication rate.

Published
2021

18. MRI-Pathology Agreement in Rectal Cancer: Real-World Data from a Prospective Rectal Cancer Registry

Author

Giulia Peveri, Vincenzo Bagnardi, Antonio Ziccarelli, Roberto Petri, Jacopo Crippa, Giovanni Ferrari, Carmelo Magistro, Dario Maggioni, Giacomo Calini, Mattia Berselli, Eugenio Cocozza, Matteo Origi, Massimo Oldani, Mauro Totis, Isacco Montroni, Giulio Mari, Pietro Achilli, Giacomo Borroni, Nicolò Tamini, Sara Crestale, Mari, G, Crippa, J, Montroni, I, Maggioni, D, Calini, G, Totis, M, Tamini, N, Oldani, M, Cocozza, E, Berselli, M, Borroni, G, Magistro, C, Ferrari, G, Achilli, P, Petri, R, Ziccarelli, A, Crestale, S, Bagnardi, V, Peveri, G, and Origi, M

Subjects
Pathology, medicine.medical_specialty, medicine.diagnostic_test, Colorectal cancer, business.industry, Rectal Neoplasms, Concordance, Cancer, Magnetic resonance imaging, Chemoradiotherapy, medicine.disease, Magnetic Resonance Imaging, Treatment Outcome, Neoadjuvant chemoradiation therapy, Rectal cancer, medicine, T-stage, Humans, Surgery, In patient, Prospective Studies, Registries, business, Real world data
Abstract

Introduction: Magnetic Resonance Imaging (MRI) is routinely used in preoperative rectal cancer staging. The concordance of MRI staging with final pathologic exam, albeit improved, has not yet reached perfection. The aim of this study is to analyze the agreement between MRI and pathologic exam in patients operated on for mid-low rectal cancer. Material and Method: Patients undergoing neoadjuvant chemoradiation therapy (nCRT) or upfront surgery were analyzed. Between January 2019 to December 2019, 140 patients enrolled in the AIMS Academy rectal cancer registry were analyzed. Sixty-two patients received nCRT and 78 underwent upfront surgery. Results: Overall, the agreement between MRI and pathologic exam on T stage and N stage were 64.7% and 69.2%, respectively. The agreement between MRI and pathologic exam on T stage was 62.7% for patients who did not receive nCRT and 67.4% for patients who received nCRT (p = 0.62). The agreement on N stage was 76.3% for patients who did not receive nCRT and 60.0% for patients who received nCRT (p = 0.075). Conclusions: Real-world data shows MRI is still far from being able to correlate with the pathology findings which raises questions about the accuracy of the real-life decision-making process during cancer boards.

Published
2021

20. Weaving Mitochondrial DNA and Y-Chromosome Variation in the Panamanian Genetic Canvas

Author

Jorge Motta, Luca Ferretti, Ana Maria Chero Osorio, Marco Rosario Capodiferro, Alessandro Raveane, Anna Olivieri, Giulia Colombo, Maria Garofalo, Nicole E. Smith-Guzmán, Ugo A. Perego, Richard G. Cooke, Tomás Mendizábal, Nicola Rambaldi Migliore, Lucia Mazzocchi, Antonio Torroni, Bethany Aram, Maribel Tribaldos, Alessandro Achilli, Stella Gagliardi, Gianluca Lombardo, Alejandro García Montón, Viola Grugni, Cristina Cereda, and Ornella Semino

Subjects
Male, Mitochondrial DNA, Genotype, Panama, Population, Black People, mitochondrial DNA, QH426-470, Biology, phylogeography, Y chromosome, DNA, Mitochondrial, Indigenous, Article, Isthmus of Panama, uniparental transmission, indigenous American lineages and genetic history, sex bias, Genetics, Humans, education, Indigenous Peoples, Genetics (clinical), Africa South of the Sahara, education.field_of_study, Chromosomes, Human, Y, Racial Groups, Genetic Variation, Gene Pool, Sequence Analysis, DNA, Pedigree, Phylogeography, Evolutionary biology, Genetic structure, Female, Sample collection
Abstract

The Isthmus of Panama was a crossroads between North and South America during the continent's first peopling (and subsequent movements) also playing a pivotal role during European colonization and the African slave trade. Previous analyses of uniparental systems revealed significant sex biases in the genetic history of Panamanians, as testified by the high proportions of Indigenous and sub-Saharan mitochondrial DNAs (mtDNAs) and by the prevalence of Western European/northern African Y chromosomes. Those studies were conducted on the general population without considering any self-reported ethnic affiliations. Here, we compared the mtDNA and Y-chromosome lineages of a new sample collection from 431 individuals (301 males and 130 females) belonging to either the general population, mixed groups, or one of five Indigenous groups currently living in Panama. We found different proportions of paternal and maternal lineages in the Indigenous groups testifying to pre-contact demographic events and genetic inputs (some dated to Pleistocene times) that created genetic structure. Then, while the local mitochondrial gene pool was marginally involved in post-contact admixtures, the Indigenous Y chromosomes were differentially replaced, mostly by lineages of western Eurasian origin. Finally, our new estimates of the sub-Saharan contribution, on a more accurately defined general population, reduce an apparent divergence between genetic and historical data., Universidad Pablo Olavide. Departamento de Geografía, Historia y Filosofía

Published
2021

21. Biomolecular insights into North African-related ancestry, mobility and diet in eleventh-century Al-Andalus

Author

Anna Olivieri, Ali Madour, Tarek Shoeib, Martin B. Richards, João Guimarães, Marina Silva, Gonzalo Oteo-García, Pierre Justeau, Pedro Soares, António Brehm, Antònia Flaquer, Krista McGrath, Douglas J. Clarke, Antonio Torroni, Antonio Salas, Alessandro Achilli, Francesca Gandini, Peter Ditchfield, Alessandro Fichera, Alexandra Rosa, Katharina Dulias, Teresa Rito, Jarosław Bryk, Alberto Gómez-Carballa, Michelle Alexander, Bobby Yau, Amparo Barrachina, Vicente Palomar, Maria Pala, Ceiridwen J. Edwards, M. George B. Foody, Rui Martiniano, Matthew von Tersch, Apollo - University of Cambridge Repository, and Universidade do Minho

Subjects
Humanidades::História e Arqueologia, Population genetics, Immigration, Eleventh, Africa, Northern, Peninsula, Phylogeny, media_common, education.field_of_study, Multidisciplinary, geography.geographical_feature_category, article, Islam, GF, FOS: Sociology, Phylogeography, Archaeology, 631/181/19, GN, Medicine, Genetic Background, media_common.quotation_subject, Science, Human Migration, Population, Ancient history, Evolutionary genetics, Mosaic, 631/181/27, QH301, Humans, 631/181/457, education, QH426, geography, Ciências Naturais::Ciências Biológicas, Science & Technology, Genome, Human, QH, History, Medieval, QR, Diet, Ancient DNA, Genetics, Population, 631/181/2474, Spain, Anthropology
Abstract

Supplementary Information: The online version contains supplementary material available at https://doi.org/ 10.1038/s41598-021-95996-3., Sequence data for UE2298/MS060 can be downloaded from the European Nucleotide Archive (accession number: PRJEB47085). Newly reported present-day mtDNA sequences are deposited into GenBank (MZ920249 - MZ921390). Additional requests should be addressed to: marina.silva@crick.ac.uk; gonzalo.oteo-garcia@hud. ac.uk; m.b.richards@hud.ac.uk., Historical records document medieval immigration from North Africa to Iberia to create Islamic al-Andalus. Here, we present a low-coverage genome of an eleventh century CE man buried in an Islamic necropolis in Segorbe, near Valencia, Spain. Uniparental lineages indicate North African ancestry, but at the autosomal level he displays a mosaic of North African and European-like ancestries, distinct from any present-day population. Altogether, the genome-wide evidence, stable isotope results and the age of the burial indicate that his ancestry was ultimately a result of admixture between recently arrived Amazigh people (Berbers) and the population inhabiting the Peninsula prior to the Islamic conquest. We detect differences between our sample and a previously published group of contemporary individuals from Valencia, exemplifying how detailed, small-scale aDNA studies can illuminate fine-grained regional and temporal differences. His genome demonstrates how ancient DNA studies can capture portraits of past genetic variation that have been erased by later demographic shifts-in this case, most likely the seventeenth century CE expulsion of formerly Islamic communities as tolerance dissipated following the Reconquista by the Catholic kingdoms of the north., We thank the Museo Municipal de Arqueologia y Etnologia de Segorbe for granting access to their collections and the Conselleria d'Educacio, Investigacio, Cultura i Esport de la Generalitat Valenciana for granting the permissions for the study. We thank Lara Cassidy, Valeria Mattiangeli and Dan Bradley for valuable advice and technical support. Part of this work was delivered via the BBSRC National Capability in Genomics and Single Cell Analysis (BBS/E/T/000PR9816) at Earlham Institute by members of the Genomics Pipelines and Core Bioinformatics Groups. We wish to acknowledge the use of the Orion High Performance Computing cluster at the School of Applied Sciences, University of Huddersfield. M.S., G.O.G., A.Fi., P.J., M.G.B.F., K.D., B.Y. were supported by a Leverhulme Doctoral Scholarship awarded to M.B.R. and M.P. P.S., M.B.R., and M.P. acknowledge FCT (Fundacao para a Ciencia e a Tecnologia) support through project PTDC/EPH-ARQ/4164/2014, partially funded by FEDER funds (COMPETE 2020 project 016899). P.S., A.Br., A.R. and T.R. acknowledge FCT support through project PTDC/SOC-ANT/30316/2017. P.S. acknowledges the "Contrato-Programa" UIDB/04050/2020 and contract CEECINST/0007772018 funded by FCT I.P. A.A., A.O., and A.T. acknowledge the support of the Italian Ministry of Education, University and Research for the projects "Dipartimenti di Eccellenza" Program (2018-2022) -Department of Biology and Biotechnology "L. Spallanzani," University of Pavia and PRIN2017 20174BTC4R. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum Munchen -German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC Health), LudwigMaximilians-Universitat, as part of LMUinnovativ.

Published
2021
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22. The Mitochondrial DNA Landscape of Modern Mexico

Author

Martin Bodner, Ricardo M. Cerda-Flores, Scott R. Woodward, J. Edgar Gomez, Walther Parson, Ugo A. Perego, Alessandro Achilli, and Nicola Rambaldi Migliore

Subjects
Male, forensic science, Population, Black People, Biology, phylogeography, QH426-470, Colonialism, Population stratification, phylogeny, DNA, Mitochondrial, Article, White People, Indigenous, Haplogroup, Genetics, Humans, quality control, education, Mexico, American Indian or Alaska Native, Genetics (clinical), education.field_of_study, Gene Pool, Archaeology, Phylogeography, Genetics, Population, Haplotypes, MtDNA database, haplogroups, Biological dispersal, Ethnology, Female, Gene pool, EMPOP
Abstract

Mexico is a rich source for anthropological and population genetic studies with high diversity in ethnic and linguistic groups. The country witnessed the rise and fall of major civilizations, including the Maya and Aztec, but resulting from European colonization, the population landscape has dramatically changed. Today, the majority of Mexicans do not identify themselves as Indigenous but as admixed, and appear to have very little in common with their pre-Columbian predecessors. However, when the maternally inherited mitochondrial (mt)DNA is investigated in the modern Mexican population, this is not the case. Control region sequences of 2021 samples deriving from all over the country revealed an overwhelming Indigenous American legacy, with almost 90% of mtDNAs belonging to the four major pan-American haplogroups A2, B2, C1, and D1. This finding supports a very low European contribution to the Mexican gene pool by female colonizers and confirms the effectiveness of employing uniparental markers as a tool to reconstruct a country’s history. In addition, the distinct frequency and dispersal patterns of Indigenous American and West Eurasian clades highlight the benefit such large and country-wide databases provide for studying the impact of colonialism from a female perspective and population stratification. The importance of geographical database subsets not only for forensic application is clearly demonstrated.

Published
2021

23. The clinical relevance of oliguria in the critically ill patient: analysis of a large observational database

Author

Vincent J. -L., Ferguson A., Pickkers P., Jakob S. M., Jaschinski U., Almekhlafi G. A., Leone M., Mokhtari M., Fontes L. E., Bauer P. R., Sakr Y., Tomas E., Bibonge E. A., Charra B., Faroudy M., Doedens L., Farina Z., Adler D., Balkema C., Kok A., Alaya S., Gharsallah H., Muzha D., Temelkov A., Georgiev G., Simeonov G., Tsaryanski G., Georgiev S., Seliman A., Vrankovic S., Vucicevic Z., Gornik I., Barsic B., Husedzinovic I., Pavlik P., Manak J., Kieslichova E., Turek R., Fischer M., Valkova R., Dadak L., Dostal P., Malaska J., Hajek R., Zidkova A., Lavicka P., Starkopf J., Kheladze Z., Chkhaidze M., Kaloiani V., Medve L., Sarkany A., Kremer I., Marjanek Z., Tamasi P., Krupnova I., Vanags I., Liguts V., Pilvinis V., Vosylius S., Kekstas G., Balciunas M., Kolbusz J., Kubler A., Mielczarek B., Mikaszewska-Sokolewicz M., Kotfis K., Tamowicz B., Sulkowski W., Smuszkiewicz P., Pihowicz A., Trejnowska E., Hagau N., Filipescu D., Droc G., Lupu M. N., Nica A., Stoica R., Tomescu D. R., Constantinescu D. L., Valcoreanu Zbaganu G. M., Slavcovici A., Bagin V., Belsky D., Palyutin S., Shlyapnikov S., Bikkulova D., Gritsan A., Natalia G., Makarenko E., Kokhno V., Tolkach A., Kokarev E., Belotserkovskiy B., Zolotukhin K., Kulabukhov V., Soskic L., Palibrk I., Jankovic R., Jovanovic B., Pandurovic M., Bumbasirevic V., Uljarevic B., Surbatovic M., Ladjevic N., Slobodianiuk G., Sobona V., Cikova A., Gebhardtova A., Jun C., Yunbo S., Dong J., Feng S., Duan M., Xu Y., Xue X., Gao T., Xing X. Z., Zhao X., Li C. H., Gengxihua G., Tan H., Xu J., Jiang L., Tiehe Q., Bingyu Q., Shi Q., Lv Z., Zhang L., Jingtao L., Zhen Z., Wang Z., Wang T. H., Yuhong L., Zhai Q., Chen Y., Wang C., Jiang W., Ruilan W., Xiaobo H., Ge H., Yan T., Yuhui C., Zhang J., Jian-Hong F., Zhu H., Huo F., Wang Y., Li C., Zhuang M., Ma Z., Sun J., Liuqingyue L., Yang M., Meng J., Ma S., Kang Y., Yu L., Peng Q., Wei Y., Zhang W., Sun R., Yeung A., Wan W. L., Sin K. K. C., Lee K. L., Wijanti M., Widodo U., Samsirun H., Sugiman T., Wisudarti C., Maskoen T. T., Hata N., Kobe Y., Nishida O., Miyazaki D., Nunomiya S., Uchino S., Kitamura N., Yamashita K., Hashimoto S., Fukushima H., Adib N. A. N., Tai L. L., Tony B., Bigornia R. R., Palo J. E., Chatterjee S., Tan B. H., Kong A., Goh S., Lee C. -C., Pothirat C., Khwannimit B., Theerawit P., Pornsuriyasak P., Piriyapatsom A., Mukhtar A., Hamdy A. N., Hosny H., Ashraf A., Nowruzinia S., Lotfi A. H., Zand F., Nikandish R., Moghaddam O. M., Cohen J., Sold O., Sfeir T., Hasan A. Y., Abugaber D., Ahmad H., Tantawy T., Baharoom S., Algethamy H., Amr A., Almekhlafi G., Coskun R., Sungur M., Cosar A., Gucyetmez B., Demirkiran O., Senturk E., Ulusoy H., Atalan H. K., Serin S., Kati I., Alnassrawi Z., Almemari A., Krishnareddy K., Kashef S., Alsabbah A., Poirier G., Marshall J. C., Herridge M., Fernandez-Medero R., Fulda G., Banschbach S., Quintero J., Schroeder E., Sicoutris C., Gueret R., Kashyap R., Bauer P., Nanchal R., Wunderink R. G., Jimenez E., Ryan A., Prince D., Edington J., Van Haren F., Bersten A., Hawkins D. J., Kilminster M., Sturgess D., Ziegenfuss M., O' Connor S., Lipman J., Campbell L., McAllister R., Roberts B., Williams P., Parke R., Seigne P., Freebairn R., Nistor D., Oxley C., Young P., Valentini R., Wainsztein N., Comignani P., Casaretto M., Sutton G., Villegas P., Galletti C., Neira J., Rovira D., Hidalgo J., Sandi F., Caser E., Thompson M. M., D'Agostino Dias M., Lunardi M. C., Youssef N. C., Lobo S., Silva R., Sales J. A., Melo L. M. C., Oliveira M., Fonte M., Grion C., Feijo C., Rezende V., Assuncao M., Neves A. P., Gusman P., Dalcomune D., Teixeira C., Kaefer K., Maia I., Dantas V. S., Filho R. C., Amorim F., Assef M., Schiavetto P., Houly J., Bianchi F., Dias F., Avila C., Rego L., Castro P., Passos J., Mendes C., Mecatti G. C., Ferrreira M., Irineu V., Guerreiro M., Ugarte S., Tomicic V., Godoy C., Samaniego W., Escamilla I., Castro Castro L. F., Duque G. L., Diaz-Guio D., Benitez F., Urrego A. G., Buitrago R., Ortiz G., Villalba Gaviria M. C., Salas D., Ramirez-Arce J., Salgado E., Morocho D., Vergara J., Sang M. C., Orellana-Jimenez C., Garrido L., Diaz O., Resiere D., Osorio C., De La Vega A., Carrillo R., Sanchez V., Villagomez A., Zubieta R. M., Sandia M., Zalatiel M., Poblano M., Gonzalez D. R., Arrazola F., Juan Francisco L. L., Namendys-Silva S. A., Moya R. G., Hernandez M., Rodriguez Cadena D. M., Islas I. L., Ballesteros Zarzavilla C. M., Matos A., Oyanguren I., Cerna J., Sierra R. Q., Jimenez R., Castillo L., Ocal R., Sencan A., Mareque Gianoni S. M., Deicas A., Hurtado J., Burghi G., Martinelli A., Von Der Osten I., Du Maine C., Bhattacharyya M., Bandyopadhyay S., Yanamala S., Gopal P., Sahu S., Ibrahim M., Rathod D., Mukundan N., Dewan A., Amin P., Samavedam S., Shah B., Gurupal G., Lahkar B., Mandal A. K., Sircar M., Ghosh S., Balasubramani V., Kapadia F., Vadi S., Nair K., Tripathy S., Nandakumar S., Sharma J., Kar A., Jha S., Zirpe K., Patel M., Bhavsar A., Samaddar D. P., Kulkarni A., Hashmi M., Ali W., Nadeem S., Indraratna K., Margarit A., Urbanek P., Schlieber J., Reisinger J., Auer J., Hartjes A., Lerche A., Janous T., Kink E., Krahulec W., Smolle K. -H., Van Der Schueren M., Thibo P., Vanhoof M., Ahmet I., Gadisseux P., Dufaye P., Jacobs O., Fraipont V., Biston P., Dive A., Bouckaert Y., Gilbert E., Gressens B., Pinck E., Collin V., De Waele J. J., Rimachi R., Gusu D., De Decker K., Mandianga K., Heytens L., Wittebole X., Spapen H., Van Collie O., Vandenheede W., Rogiers P., Kolodzeike P., Kruse M., Andersen T., Harjola V. -P., Saarinen K., Durocher A., Moulront S., Lepape A., Losser M. -R., Cabaret P., Kalaitzis E., Zogheib E., Charve P., Francois B., Lefrant J. -Y., Beilouny B., Forceville X., Misset B., Jacobs F., Floccard B., Payen D., Wynckel A., Castelain V., Faure A., Lavagne P., Lepoivre T., Moussa M. D., Vieillard-Baron A., Durand M., Gainnier M., Ichai C., Arens S., Hoffmann C., Kaffarnik M., Scharnofske C. -J., Voigt I., Peckelsen C., Weber M., Gille J., Lange A., Schoser G., Sablotzki A., Bluethgen A., Vogel F., Tscheu A., Fuchs T., Wattenberg M., Helmes T., Scieszka S., Heintz M., Sakka S., Kohler J., Fiedler F., Danz M., Riessen R., Kerz T., Kersten A., Tacke F., Marx G., Volkert T., Schmutz A., Nierhaus A., Kluge S., Abel P., Janosi R. A., Utzolino S., Bracht H., Toussaint S., Peftoulidou M. G., Myrianthefs P., Armaganidis A., Routsi C., Xini A., Mouloudi E., Kokoris I., Kyriazopoulos G., Vlachos S., Lavrentieva A., Partala P., Nakos G., Moller A., Stefansson S. O., Barry J., O'Leary R. A., Motherway C., Faheem M., Dunne E., Donnelly M., Konrad T., Bonora E., Achilli C., Rossi S., Castiglione G., Peris A., Albanese D., Stocchetti N., Citerio G., Mozzoni L., Sisillo E., De Negri P., Savioli M., Vecchiarelli P., Puflea F., Stankovic V., Minoja G., Montibeller S., Calligaro P., Sorrentino R., Feri M., Zambon M., Colombaroli E., Giarratano A., Pellis T., Capra C., Antonelli M., Gullo A., Chelazzi C., De Capraris A., Patroniti N., Girardis M., Franchi F., Berlot G., Buttigieg M., Ponssen H., Ten Cate J., Bormans L., Husada S., Buise M., Van Der Hoven B., Reidinga A., Kuiper M., Kluge G., Den Boer S., Kesecioglu J., Van Leeuwen H., Flaatten H., Mo S., Branco V., Rua F., Lafuente E., Sousa M., Catorze N., Barros M., Pereira L., De Oliveira A. V., Gomes J., Gaspar I., Pereira M. F., Cymbron M., Dias A., Almeida E., Beirao S., Serra I., Ribeiro R., Povoa P., Faria F., Costa-E-Silva Z., Nobrega J. J., Fernandes F., Gabriel J., Voga G., Rupnik E., Kosec L., Povsic M. K., Osojnik I., Tomic V., Sinkovic A., Gonzalez J., Zavala E., Valenzuela J. P., Marina L., Vidal-Cortes P., Posada P., Martin-Loeches I., Guillen N. M., Palomar M., Sole-Violan J., Torres A., Gonzalez Gallego M. A., Aguilar G., Allue R. M., Argueso M., Parejo M., Navarro M. P., Jose A., Nin N., Lerma F. A., Martinez O., Lozano E. T., Lopez S. A., Perez Granda M. J., Moreno S., Llubia C., Martos C. D. L. F., Gonzalez-Arenas P., Fernandez N. L., Rueda B. G., Pons I. E., Cruza N., Maroto F., Estella A., Ferrer A., Fraile L. I., Quindos B., Quintano A., Tebar M. T., Cardinal P., Reyes A., Rodriguez A., Abella A., Del Valle S. G., Yus S., Maseda E., Berezo J. A., Pedregosa A. T., Laplaza C., Ferrer R., Rico-Feijoo J., Rodriguez M., Monedero P., Eriksson K., Lind D., Chabanel D., Zender H., Heer K., Frankenberger B., Jakob S., Haller A., Matthew S., Downes R., Groba C. B., Johnston A., Meacher R., Keays R., Haji-Michael P., Tyler C., Jones S., Tyl D., Ball A., Vogel J., Booth M., Downie P., Watters M., Brett S., Garfield M., Everett L., Heenen S., Dhir S., Beardow Z., Mostert M., Brosnan S., Pinto N., Harris S., Summors A., Norton A., Rose A., Appelboam R., Davies O., Vickers E., Agarwal B., Szakmany T., Wimbush S., Welters I., Pearse R., Hollands R., Kirk-Bayley J., Fletcher N., Bray B., Brealey D., Alexander P., Henderson S., Hargreaves C., Black H., Gowda K, Citerio G, Université libre de Bruxelles (ULB), Belfast City Hospital, Department Intensive Care Medicine, Center of Infectious Diseases, Radboudumc, Nijmegen, The Netherlands., University of Bern [Bern, Switzerland] (University Hospital Bern ), Universität Augsburg [Augsburg], Prince Sultan university (saudi Arabia), Riyadh, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Mayo Clinic, Jena University Hospital [Jena], Supporting clinical sciences, Intensive Care, Internal Medicine Specializations, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, UCL - (SLuc) Service de soins intensifs, Vincent, J. -L., Ferguson, A., Pickkers, P., Jakob, S. M., Jaschinski, U., Almekhlafi, G. A., Leone, M., Mokhtari, M., Fontes, L. E., Bauer, P. R., Sakr, Y., Tomas, E., Bibonge, E. A., Charra, B., Faroudy, M., Doedens, L., Farina, Z., Adler, D., Balkema, C., Kok, A., Alaya, S., Gharsallah, H., Muzha, D., Temelkov, A., Georgiev, G., Simeonov, G., Tsaryanski, G., Georgiev, S., Seliman, A., Vrankovic, S., Vucicevic, Z., Gornik, I., Barsic, B., Husedzinovic, I., Pavlik, P., Manak, J., Kieslichova, E., Turek, R., Fischer, M., Valkova, R., Dadak, L., Dostal, P., Malaska, J., Hajek, R., Zidkova, A., Lavicka, P., Starkopf, J., Kheladze, Z., Chkhaidze, M., Kaloiani, V., Medve, L., Sarkany, A., Kremer, I., Marjanek, Z., Tamasi, P., Krupnova, I., Vanags, I., Liguts, V., Pilvinis, V., Vosylius, S., Kekstas, G., Balciunas, M., Kolbusz, J., Kubler, A., Mielczarek, B., Mikaszewska-Sokolewicz, M., Kotfis, K., Tamowicz, B., Sulkowski, W., Smuszkiewicz, P., Pihowicz, A., Trejnowska, E., Hagau, N., Filipescu, D., Droc, G., Lupu, M. N., Nica, A., Stoica, R., Tomescu, D. R., Constantinescu, D. L., Valcoreanu Zbaganu, G. M., Slavcovici, A., Bagin, V., Belsky, D., Palyutin, S., Shlyapnikov, S., Bikkulova, D., Gritsan, A., Natalia, G., Makarenko, E., Kokhno, V., Tolkach, A., Kokarev, E., Belotserkovskiy, B., Zolotukhin, K., Kulabukhov, V., Soskic, L., Palibrk, I., Jankovic, R., Jovanovic, B., Pandurovic, M., Bumbasirevic, V., Uljarevic, B., Surbatovic, M., Ladjevic, N., Slobodianiuk, G., Sobona, V., Cikova, A., Gebhardtova, A., Jun, C., Yunbo, S., Dong, J., Feng, S., Duan, M., Xu, Y., Xue, X., Gao, T., Xing, X. Z., Zhao, X., Li, C. H., Gengxihua, G., Tan, H., Xu, J., Jiang, L., Tiehe, Q., Bingyu, Q., Shi, Q., Lv, Z., Zhang, L., Jingtao, L., Zhen, Z., Wang, Z., Wang, T. H., Yuhong, L., Zhai, Q., Chen, Y., Wang, C., Jiang, W., Ruilan, W., Xiaobo, H., Ge, H., Yan, T., Yuhui, C., Zhang, J., Jian-Hong, F., Zhu, H., Huo, F., Wang, Y., Li, C., Zhuang, M., Ma, Z., Sun, J., Liuqingyue, L., Yang, M., Meng, J., Ma, S., Kang, Y., Yu, L., Peng, Q., Wei, Y., Zhang, W., Sun, R., Yeung, A., Wan, W. L., Sin, K. K. C., Lee, K. L., Wijanti, M., Widodo, U., Samsirun, H., Sugiman, T., Wisudarti, C., Maskoen, T. T., Hata, N., Kobe, Y., Nishida, O., Miyazaki, D., Nunomiya, S., Uchino, S., Kitamura, N., Yamashita, K., Hashimoto, S., Fukushima, H., Adib, N. A. N., Tai, L. L., Tony, B., Bigornia, R. R., Palo, J. E., Chatterjee, S., Tan, B. H., Kong, A., Goh, S., Lee, C. -C., Pothirat, C., Khwannimit, B., Theerawit, P., Pornsuriyasak, P., Piriyapatsom, A., Mukhtar, A., Hamdy, A. N., Hosny, H., Ashraf, A., Nowruzinia, S., Lotfi, A. H., Zand, F., Nikandish, R., Moghaddam, O. M., Cohen, J., Sold, O., Sfeir, T., Hasan, A. Y., Abugaber, D., Ahmad, H., Tantawy, T., Baharoom, S., Algethamy, H., Amr, A., Almekhlafi, G., Coskun, R., Sungur, M., Cosar, A., Gucyetmez, B., Demirkiran, O., Senturk, E., Ulusoy, H., Atalan, H. K., Serin, S., Kati, I., Alnassrawi, Z., Almemari, A., Krishnareddy, K., Kashef, S., Alsabbah, A., Poirier, G., Marshall, J. C., Herridge, M., Fernandez-Medero, R., Fulda, G., Banschbach, S., Quintero, J., Schroeder, E., Sicoutris, C., Gueret, R., Kashyap, R., Bauer, P., Nanchal, R., Wunderink, R. G., Jimenez, E., Ryan, A., Prince, D., Edington, J., Van Haren, F., Bersten, A., Hawkins, D. J., Kilminster, M., Sturgess, D., Ziegenfuss, M., O' Connor, S., Lipman, J., Campbell, L., Mcallister, R., Roberts, B., Williams, P., Parke, R., Seigne, P., Freebairn, R., Nistor, D., Oxley, C., Young, P., Valentini, R., Wainsztein, N., Comignani, P., Casaretto, M., Sutton, G., Villegas, P., Galletti, C., Neira, J., Rovira, D., Hidalgo, J., Sandi, F., Caser, E., Thompson, M. M., D'Agostino Dias, M., Lunardi, M. C., Youssef, N. C., Lobo, S., Silva, R., Sales, J. A., Melo, L. M. C., Oliveira, M., Fonte, M., Grion, C., Feijo, C., Rezende, V., Assuncao, M., Neves, A. P., Gusman, P., Dalcomune, D., Teixeira, C., Kaefer, K., Maia, I., Dantas, V. S., Filho, R. C., Amorim, F., Assef, M., Schiavetto, P., Houly, J., Bianchi, F., Dias, F., Avila, C., Rego, L., Castro, P., Passos, J., Mendes, C., Mecatti, G. C., Ferrreira, M., Irineu, V., Guerreiro, M., Ugarte, S., Tomicic, V., Godoy, C., Samaniego, W., Escamilla, I., Castro Castro, L. F., Duque, G. L., Diaz-Guio, D., Benitez, F., Urrego, A. G., Buitrago, R., Ortiz, G., Villalba Gaviria, M. C., Salas, D., Ramirez-Arce, J., Salgado, E., Morocho, D., Vergara, J., Sang, M. C., Orellana-Jimenez, C., Garrido, L., Diaz, O., Resiere, D., Osorio, C., De La Vega, A., Carrillo, R., Sanchez, V., Villagomez, A., Zubieta, R. M., Sandia, M., Zalatiel, M., Poblano, M., Gonzalez, D. R., Arrazola, F., Juan Francisco, L. L., Namendys-Silva, S. A., Moya, R. G., Hernandez, M., Rodriguez Cadena, D. M., Islas, I. L., Ballesteros Zarzavilla, C. M., Matos, A., Oyanguren, I., Cerna, J., Sierra, R. Q., Jimenez, R., Castillo, L., Ocal, R., Sencan, A., Mareque Gianoni, S. M., Deicas, A., Hurtado, J., Burghi, G., Martinelli, A., Von Der Osten, I., Du Maine, C., Bhattacharyya, M., Bandyopadhyay, S., Yanamala, S., Gopal, P., Sahu, S., Ibrahim, M., Rathod, D., Mukundan, N., Dewan, A., Amin, P., Samavedam, S., Shah, B., Gurupal, G., Lahkar, B., Mandal, A. K., Sircar, M., Ghosh, S., Balasubramani, V., Kapadia, F., Vadi, S., Nair, K., Tripathy, S., Nandakumar, S., Sharma, J., Kar, A., Jha, S., Zirpe, K., Patel, M., Bhavsar, A., Samaddar, D. P., Kulkarni, A., Hashmi, M., Ali, W., Nadeem, S., Indraratna, K., Margarit, A., Urbanek, P., Schlieber, J., Reisinger, J., Auer, J., Hartjes, A., Lerche, A., Janous, T., Kink, E., Krahulec, W., Smolle, K. -H., Van Der Schueren, M., Thibo, P., Vanhoof, M., Ahmet, I., Gadisseux, P., Dufaye, P., Jacobs, O., Fraipont, V., Biston, P., Dive, A., Bouckaert, Y., Gilbert, E., Gressens, B., Pinck, E., Collin, V., De Waele, J. J., Rimachi, R., Gusu, D., De Decker, K., Mandianga, K., Heytens, L., Wittebole, X., Spapen, H., Van Collie, O., Vandenheede, W., Rogiers, P., Kolodzeike, P., Kruse, M., Andersen, T., Harjola, V. -P., Saarinen, K., Durocher, A., Moulront, S., Lepape, A., Losser, M. -R., Cabaret, P., Kalaitzis, E., Zogheib, E., Charve, P., Francois, B., Lefrant, J. -Y., Beilouny, B., Forceville, X., Misset, B., Jacobs, F., Floccard, B., Payen, D., Wynckel, A., Castelain, V., Faure, A., Lavagne, P., Lepoivre, T., Moussa, M. D., Vieillard-Baron, A., Durand, M., Gainnier, M., Ichai, C., Arens, S., Hoffmann, C., Kaffarnik, M., Scharnofske, C. -J., Voigt, I., Peckelsen, C., Weber, M., Gille, J., Lange, A., Schoser, G., Sablotzki, A., Bluethgen, A., Vogel, F., Tscheu, A., Fuchs, T., Wattenberg, M., Helmes, T., Scieszka, S., Heintz, M., Sakka, S., Kohler, J., Fiedler, F., Danz, M., Riessen, R., Kerz, T., Kersten, A., Tacke, F., Marx, G., Volkert, T., Schmutz, A., Nierhaus, A., Kluge, S., Abel, P., Janosi, R. A., Utzolino, S., Bracht, H., Toussaint, S., Peftoulidou, M. G., Myrianthefs, P., Armaganidis, A., Routsi, C., Xini, A., Mouloudi, E., Kokoris, I., Kyriazopoulos, G., Vlachos, S., Lavrentieva, A., Partala, P., Nakos, G., Moller, A., Stefansson, S. O., Barry, J., O'Leary, R. A., Motherway, C., Faheem, M., Dunne, E., Donnelly, M., Konrad, T., Bonora, E., Achilli, C., Rossi, S., Castiglione, G., Peris, A., Albanese, D., Stocchetti, N., Citerio, G., Mozzoni, L., Sisillo, E., De Negri, P., Savioli, M., Vecchiarelli, P., Puflea, F., Stankovic, V., Minoja, G., Montibeller, S., Calligaro, P., Sorrentino, R., Feri, M., Zambon, M., Colombaroli, E., Giarratano, A., Pellis, T., Capra, C., Antonelli, M., Gullo, A., Chelazzi, C., De Capraris, A., Patroniti, N., Girardis, M., Franchi, F., Berlot, G., Buttigieg, M., Ponssen, H., Ten Cate, J., Bormans, L., Husada, S., Buise, M., Van Der Hoven, B., Reidinga, A., Kuiper, M., Kluge, G., Den Boer, S., Kesecioglu, J., Van Leeuwen, H., Flaatten, H., Mo, S., Branco, V., Rua, F., Lafuente, E., Sousa, M., Catorze, N., Barros, M., Pereira, L., De Oliveira, A. V., Gomes, J., Gaspar, I., Pereira, M. F., Cymbron, M., Dias, A., Almeida, E., Beirao, S., Serra, I., Ribeiro, R., Povoa, P., Faria, F., Costa-E-Silva, Z., Nobrega, J. J., Fernandes, F., Gabriel, J., Voga, G., Rupnik, E., Kosec, L., Povsic, M. K., Osojnik, I., Tomic, V., Sinkovic, A., Gonzalez, J., Zavala, E., Valenzuela, J. P., Marina, L., Vidal-Cortes, P., Posada, P., Martin-Loeches, I., Guillen, N. M., Palomar, M., Sole-Violan, J., Torres, A., Gonzalez Gallego, M. A., Aguilar, G., Allue, R. M., Argueso, M., Parejo, M., Navarro, M. P., Jose, A., Nin, N., Lerma, F. A., Martinez, O., Lozano, E. T., Lopez, S. A., Perez Granda, M. J., Moreno, S., Llubia, C., Martos, C. D. L. F., Gonzalez-Arenas, P., Fernandez, N. L., Rueda, B. G., Pons, I. E., Cruza, N., Maroto, F., Estella, A., Ferrer, A., Fraile, L. I., Quindos, B., Quintano, A., Tebar, M. T., Cardinal, P., Reyes, A., Rodriguez, A., Abella, A., Del Valle, S. G., Yus, S., Maseda, E., Berezo, J. A., Pedregosa, A. T., Laplaza, C., Ferrer, R., Rico-Feijoo, J., Rodriguez, M., Monedero, P., Eriksson, K., Lind, D., Chabanel, D., Zender, H., Heer, K., Frankenberger, B., Jakob, S., Haller, A., Matthew, S., Downes, R., Groba, C. B., Johnston, A., Meacher, R., Keays, R., Haji-Michael, P., Tyler, C., Jones, S., Tyl, D., Ball, A., Vogel, J., Booth, M., Downie, P., Watters, M., Brett, S., Garfield, M., Everett, L., Heenen, S., Dhir, S., Beardow, Z., Mostert, M., Brosnan, S., Pinto, N., Harris, S., Summors, A., Norton, A., Rose, A., Appelboam, R., Davies, O., Vickers, E., Agarwal, B., Szakmany, T., Wimbush, S., Welters, I., Pearse, R., Hollands, R., Kirk-Bayley, J., Fletcher, N., Bray, B., Brealey, D., Alexander, P., Henderson, S., Hargreaves, C., Black, H., Gowda, K., Vincent, J, Ferguson, A, Pickkers, P, Jakob, S, Jaschinski, U, Almekhlafi, G, Leone, M, Mokhtari, M, Fontes, L, Bauer, P, Sakr, Y, Tomas, E, Bibonge, E, Charra, B, Faroudy, M, Doedens, L, Farina, Z, Adler, D, Balkema, C, Kok, A, Alaya, S, Gharsallah, H, Muzha, D, Temelkov, A, Georgiev, G, Simeonov, G, Tsaryanski, G, Georgiev, S, Seliman, A, Vrankovic, S, Vucicevic, Z, Gornik, I, Barsic, B, Husedzinovic, I, Pavlik, P, Manak, J, Kieslichova, E, Turek, R, Fischer, M, Valkova, R, Dadak, L, Dostal, P, Malaska, J, Hajek, R, Zidkova, A, Lavicka, P, Starkopf, J, Kheladze, Z, Chkhaidze, M, Kaloiani, V, Medve, L, Sarkany, A, Kremer, I, Marjanek, Z, Tamasi, P, Krupnova, I, Vanags, I, Liguts, V, Pilvinis, V, Vosylius, S, Kekstas, G, Balciunas, M, Kolbusz, J, Kubler, A, Mielczarek, B, Mikaszewska-Sokolewicz, M, Kotfis, K, Tamowicz, B, Sulkowski, W, Smuszkiewicz, P, Pihowicz, A, Trejnowska, E, Hagau, N, Filipescu, D, Droc, G, Lupu, M, Nica, A, Stoica, R, Tomescu, D, Constantinescu, D, Valcoreanu Zbaganu, G, Slavcovici, A, Bagin, V, Belsky, D, Palyutin, S, Shlyapnikov, S, Bikkulova, D, Gritsan, A, Natalia, G, Makarenko, E, Kokhno, V, Tolkach, A, Kokarev, E, Belotserkovskiy, B, Zolotukhin, K, Kulabukhov, V, Soskic, L, Palibrk, I, Jankovic, R, Jovanovic, B, Pandurovic, M, Bumbasirevic, V, Uljarevic, B, Surbatovic, M, Ladjevic, N, Slobodianiuk, G, Sobona, V, Cikova, A, Gebhardtova, A, Jun, C, Yunbo, S, Dong, J, Feng, S, Duan, M, Xu, Y, Xue, X, Gao, T, Xing, X, Zhao, X, Li, C, Gengxihua, G, Tan, H, Xu, J, Jiang, L, Tiehe, Q, Bingyu, Q, Shi, Q, Lv, Z, Zhang, L, Jingtao, L, Zhen, Z, Wang, Z, Wang, T, Yuhong, L, Zhai, Q, Chen, Y, Wang, C, Jiang, W, Ruilan, W, Xiaobo, H, Ge, H, Yan, T, Yuhui, C, Zhang, J, Jian-Hong, F, Zhu, H, Huo, F, Wang, Y, Zhuang, M, Ma, Z, Sun, J, Liuqingyue, L, Yang, M, Meng, J, Ma, S, Kang, Y, Yu, L, Peng, Q, Wei, Y, Zhang, W, Sun, R, Yeung, A, Wan, W, Sin, K, Lee, K, Wijanti, M, Widodo, U, Samsirun, H, Sugiman, T, Wisudarti, C, Maskoen, T, Hata, N, Kobe, Y, Nishida, O, Miyazaki, D, Nunomiya, S, Uchino, S, Kitamura, N, Yamashita, K, Hashimoto, S, Fukushima, H, Adib, N, Tai, L, Tony, B, Bigornia, R, Palo, J, Chatterjee, S, Tan, B, Kong, A, Goh, S, Lee, C, Pothirat, C, Khwannimit, B, Theerawit, P, Pornsuriyasak, P, Piriyapatsom, A, Mukhtar, A, Hamdy, A, Hosny, H, Ashraf, A, Nowruzinia, S, Lotfi, A, Zand, F, Nikandish, R, Moghaddam, O, Cohen, J, Sold, O, Sfeir, T, Hasan, A, Abugaber, D, Ahmad, H, Tantawy, T, Baharoom, S, Algethamy, H, Amr, A, Coskun, R, Sungur, M, Cosar, A, Gucyetmez, B, Demirkiran, O, Senturk, E, Ulusoy, H, Atalan, H, Serin, S, Kati, I, Alnassrawi, Z, Almemari, A, Krishnareddy, K, Kashef, S, Alsabbah, A, Poirier, G, Marshall, J, Herridge, M, Fernandez-Medero, R, Fulda, G, Banschbach, S, Quintero, J, Schroeder, E, Sicoutris, C, Gueret, R, Kashyap, R, Nanchal, R, Wunderink, R, Jimenez, E, Ryan, A, Prince, D, Edington, J, Van Haren, F, Bersten, A, Hawkins, D, Kilminster, M, Sturgess, D, Ziegenfuss, M, O' Connor, S, Lipman, J, Campbell, L, Mcallister, R, Roberts, B, Williams, P, Parke, R, Seigne, P, Freebairn, R, Nistor, D, Oxley, C, Young, P, Valentini, R, Wainsztein, N, Comignani, P, Casaretto, M, Sutton, G, Villegas, P, Galletti, C, Neira, J, Rovira, D, Hidalgo, J, Sandi, F, Caser, E, Thompson, M, D'Agostino Dias, M, Lunardi, M, Youssef, N, Lobo, S, Silva, R, Sales, J, Melo, L, Oliveira, M, Fonte, M, Grion, C, Feijo, C, Rezende, V, Assuncao, M, Neves, A, Gusman, P, Dalcomune, D, Teixeira, C, Kaefer, K, Maia, I, Dantas, V, Filho, R, Amorim, F, Assef, M, Schiavetto, P, Houly, J, Bianchi, F, Dias, F, Avila, C, Rego, L, Castro, P, Passos, J, Mendes, C, Mecatti, G, Ferrreira, M, Irineu, V, Guerreiro, M, Ugarte, S, Tomicic, V, Godoy, C, Samaniego, W, Escamilla, I, Castro Castro, L, Duque, G, Diaz-Guio, D, Benitez, F, Urrego, A, Buitrago, R, Ortiz, G, Villalba Gaviria, M, Salas, D, Ramirez-Arce, J, Salgado, E, Morocho, D, Vergara, J, Sang, M, Orellana-Jimenez, C, Garrido, L, Diaz, O, Resiere, D, Osorio, C, De La Vega, A, Carrillo, R, Sanchez, V, Villagomez, A, Zubieta, R, Sandia, M, Zalatiel, M, Poblano, M, Gonzalez, D, Arrazola, F, Juan Francisco, L, Namendys-Silva, S, Moya, R, Hernandez, M, Rodriguez Cadena, D, Islas, I, Ballesteros Zarzavilla, C, Matos, A, Oyanguren, I, Cerna, J, Sierra, R, Jimenez, R, Castillo, L, Ocal, R, Sencan, A, Mareque Gianoni, S, Deicas, A, Hurtado, J, Burghi, G, Martinelli, A, Von Der Osten, I, Du Maine, C, Bhattacharyya, M, Bandyopadhyay, S, Yanamala, S, Gopal, P, Sahu, S, Ibrahim, M, Rathod, D, Mukundan, N, Dewan, A, Amin, P, Samavedam, S, Shah, B, Gurupal, G, Lahkar, B, Mandal, A, Sircar, M, Ghosh, S, Balasubramani, V, Kapadia, F, Vadi, S, Nair, K, Tripathy, S, Nandakumar, S, Sharma, J, Kar, A, Jha, S, Zirpe, K, Patel, M, Bhavsar, A, Samaddar, D, Kulkarni, A, Hashmi, M, Ali, W, Nadeem, S, Indraratna, K, Margarit, A, Urbanek, P, Schlieber, J, Reisinger, J, Auer, J, Hartjes, A, Lerche, A, Janous, T, Kink, E, Krahulec, W, Smolle, K, Van Der Schueren, M, Thibo, P, Vanhoof, M, Ahmet, I, Gadisseux, P, Dufaye, P, Jacobs, O, Fraipont, V, Biston, P, Dive, A, Bouckaert, Y, Gilbert, E, Gressens, B, Pinck, E, Collin, V, De Waele, J, Rimachi, R, Gusu, D, De Decker, K, Mandianga, K, Heytens, L, Wittebole, X, Spapen, H, Van Collie, O, Vandenheede, W, Rogiers, P, Kolodzeike, P, Kruse, M, Andersen, T, Harjola, V, Saarinen, K, Durocher, A, Moulront, S, Lepape, A, Losser, M, Cabaret, P, Kalaitzis, E, Zogheib, E, Charve, P, Francois, B, Lefrant, J, Beilouny, B, Forceville, X, Misset, B, Jacobs, F, Floccard, B, Payen, D, Wynckel, A, Castelain, V, Faure, A, Lavagne, P, Lepoivre, T, Moussa, M, Vieillard-Baron, A, Durand, M, Gainnier, M, Ichai, C, Arens, S, Hoffmann, C, Kaffarnik, M, Scharnofske, C, Voigt, I, Peckelsen, C, Weber, M, Gille, J, Lange, A, Schoser, G, Sablotzki, A, Bluethgen, A, Vogel, F, Tscheu, A, Fuchs, T, Wattenberg, M, Helmes, T, Scieszka, S, Heintz, M, Sakka, S, Kohler, J, Fiedler, F, Danz, M, Riessen, R, Kerz, T, Kersten, A, Tacke, F, Marx, G, Volkert, T, Schmutz, A, Nierhaus, A, Kluge, S, Abel, P, Janosi, R, Utzolino, S, Bracht, H, Toussaint, S, Peftoulidou, M, Myrianthefs, P, Armaganidis, A, Routsi, C, Xini, A, Mouloudi, E, Kokoris, I, Kyriazopoulos, G, Vlachos, S, Lavrentieva, A, Partala, P, Nakos, G, Moller, A, Stefansson, S, Barry, J, O'Leary, R, Motherway, C, Faheem, M, Dunne, E, Donnelly, M, Konrad, T, Bonora, E, Achilli, C, Rossi, S, Castiglione, G, Peris, A, Albanese, D, Stocchetti, N, Citerio, G, Mozzoni, L, Sisillo, E, De Negri, P, Savioli, M, Vecchiarelli, P, Puflea, F, Stankovic, V, Minoja, G, Montibeller, S, Calligaro, P, Sorrentino, R, Feri, M, Zambon, M, Colombaroli, E, Giarratano, A, Pellis, T, Capra, C, Antonelli, M, Gullo, A, Chelazzi, C, De Capraris, A, Patroniti, N, Girardis, M, Franchi, F, Berlot, G, Buttigieg, M, Ponssen, H, Ten Cate, J, Bormans, L, Husada, S, Buise, M, Van Der Hoven, B, Reidinga, A, Kuiper, M, Kluge, G, Den Boer, S, Kesecioglu, J, Van Leeuwen, H, Flaatten, H, Mo, S, Branco, V, Rua, F, Lafuente, E, Sousa, M, Catorze, N, Barros, M, Pereira, L, De Oliveira, A, Gomes, J, Gaspar, I, Pereira, M, Cymbron, M, Dias, A, Almeida, E, Beirao, S, Serra, I, Ribeiro, R, Povoa, P, Faria, F, Costa-E-Silva, Z, Nobrega, J, Fernandes, F, Gabriel, J, Voga, G, Rupnik, E, Kosec, L, Povsic, M, Osojnik, I, Tomic, V, Sinkovic, A, Gonzalez, J, Zavala, E, Valenzuela, J, Marina, L, Vidal-Cortes, P, Posada, P, Martin-Loeches, I, Guillen, N, Palomar, M, Sole-Violan, J, Torres, A, Gonzalez Gallego, M, Aguilar, G, Allue, R, Argueso, M, Parejo, M, Navarro, M, Jose, A, Nin, N, Lerma, F, Martinez, O, Lozano, E, Lopez, S, Perez Granda, M, Moreno, S, Llubia, C, Martos, C, Gonzalez-Arenas, P, Fernandez, N, Rueda, B, Pons, I, Cruza, N, Maroto, F, Estella, A, Ferrer, A, Fraile, L, Quindos, B, Quintano, A, Tebar, M, Cardinal, P, Reyes, A, Rodriguez, A, Abella, A, Del Valle, S, Yus, S, Maseda, E, Berezo, J, Pedregosa, A, Laplaza, C, Ferrer, R, Rico-Feijoo, J, Rodriguez, M, Monedero, P, Eriksson, K, Lind, D, Chabanel, D, Zender, H, Heer, K, Frankenberger, B, Haller, A, Matthew, S, Downes, R, Groba, C, Johnston, A, Meacher, R, Keays, R, Haji-Michael, P, Tyler, C, Jones, S, Tyl, D, Ball, A, Vogel, J, Booth, M, Downie, P, Watters, M, Brett, S, Garfield, M, Everett, L, Heenen, S, Dhir, S, Beardow, Z, Mostert, M, Brosnan, S, Pinto, N, Harris, S, Summors, A, Norton, A, Rose, A, Appelboam, R, Davies, O, Vickers, E, Agarwal, B, Szakmany, T, Wimbush, S, Welters, I, Pearse, R, Hollands, R, Kirk-Bayley, J, Fletcher, N, Bray, B, Brealey, D, Alexander, P, Henderson, S, Hargreaves, C, Black, H, and Gowda, K

Subjects
Male, umrljivost, medicine.medical_treatment, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], udc:616.1/.4, Critical Care and Intensive Care Medicine, urologic and male genital diseases, akutna ledvična odpoved, renal insufficiency, law.invention, 0302 clinical medicine, law, Oliguria, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030212 general & internal medicine, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, lcsh:Medical emergencies. Critical care. Intensive care. First aid, oligurija, nadomestno zdravljenje ledvične odpovedi, Acute Kidney Injury, Middle Aged, kidney diseases, Intensive care unit, urine, 3. Good health, urine output, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Mortality, Renal replacement therapy, Urine output, Female, oliguria, medicine.symptom, renal replacement therapy, Adult, kidney, medicine.medical_specialty, oskrba kritično bolnih, urin, Critical Illness, 610 Medicine & health, Statistics, Nonparametric, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, acute kidney failure, medicine, critical illness, Humans, Clinical significance, In patient, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ddc:610, Renal replacement therapy, izločanje urina, Mortality, Urine output, Aged, Observational database, Analysis of Variance, Critically ill, business.industry, Research, renalna insuficienca, Médecine pathologie humaine, 030208 emergency & critical care medicine, lcsh:RC86-88.9, mortality, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, critical care, bolezni ledvic, Emergency medicine, kritično stanje, ledvica, business
Abstract

BackgroundUrine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis.ResultsOf the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient—oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged—oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent—oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19–1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97–1.34], p = 0.103).ConclusionsOliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome., 0, info:eu-repo/semantics/published

Published
2019

24. GOSAFE - Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery: early analysis on 977 patients

Author

Barbara Frezza, Giampaolo Castagnoli, Genoveffa Balducci, Valentina Riggio, G. Ugolini, Antonio Arroyo, Gianluca Garulli, Caterina Foppa, Kristin Cardin, Matthijs Plas, Gaetano Gallo, Francesca De Lucia, Francisco López-Rodríguez, Sandra Lario, Franco De Cian, Flavia Foca, Alberto Realis Luc, Paola Tramelli, Roberta Pellegrino, Giacomo Sermonesi, Stefano Sfondrini, Federico Ghignone, Orestis Ioannidis, Nicole M. Saur, Michael David Fejka, Basilio Pirrera, Bruno Alampi, Siri Rostoft, Sam Fox, Chiara Zingaretti, Ingeborg Flåten Backe, Alessandro Spaziani, Barbara Perenze, Minas Baltatzis, Riccardo A. Audisio, Claudia Santos, Luigi Marano, Mariann Lønn, Stefano Scabini, Andrea Massobrio, Patrizio Capelli, Isacco Montroni, Luis E. De León, Cristina Lillo, Alessio Lucarini, Valerio Belgrano, Antonino Spinelli, Daniela Di Pietrantonio, Nicola de Liguori Carino, Davide Pertile, Luigi Conti, Andrea Romboli, Giuseppe Sammarco, Hanoch Kashtan, Baha Siam, Michael T. Jaklitsch, Arild Nesbakken, Michele De Simone, Oriana Nanni, Filippo Banchini, Ajith K. Siriwardena, Giorgio Ercolani, Pietro Achilli, Davide Zattoni, Bernadette Vertogen, Steven D. Wexner, Laura Frain, Konstantinos Galanos-Demiris, Dario Maggioni, Baruch Brenner, Gerardo Palmieri, Giovanni Taffurelli, Barbara L. van Leeuwen, Manuela Albertelli, Gianluca Pellino, Anthony Chan, Alberto Bartoli, Emanuela Stratta, Mario Trompetto, Anna Garutti, Francesca Tauceri, Michele Mazzola, Beatrice Palermo, G. Clerico, Jakub Kenig, Yochai Levy, Graziana Barile, Vincenzo Alagna, Giulio Mari, Roberto Eggenhöffner, Joshua I. S. Bleier, Giovanni Ferrari, Andrea Costanzi, Michele Carvello, Francesca Di Candido, Francesco Monari, Ponnandai Somasundar, Kinga Szabat, Matteo Sacchi, Luis Sánchez-Guillén, Lydia Loutzidou, Lisa Cooper, Hanneke van der Wal-Huisman, Mariateresa Mirarchi, Domenico Soriero, Raffaele De Luca, Andrea Lucchi, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Montroni I., Rostoft S., Spinelli A., Van Leeuwen B.L., Ercolani G., Saur N.M., Jacklitsh M.T., Somasundar P.S., de Liguori Carino N., Ghignone F., Foca F., Zingaretti C., Audisio R.A., Ugolini G., Garutti A., Taffurelli G., Zattoni D., Tramelli P., Sermonesi G., Di Candido F., Carvello M., Sacchi M., De Lucia F., Foppa C., Plas M., Van der Wal-Huisman H., Tauceri F., Perenze B., Di Pietrantonio D., Mirarchi M., Fejka M., Bleier J.I.S., Frain L., Fox S.W., Cardin K., De Leon L.E., Baltatzis M., Chan A.K.C., Siriwardena A.K., Vertogen B., Nanni O., Garulli G., Alagna V., Pirrera B., Lucchi A., Monari F., Conti L., Capelli P., Romboli A., Palmieri G., Banchini F., Marano L., Spaziani A., Castagnoli G., Bartoli A., Trompetto M., Gallo G., Luc A.R., Clerico G., Sammarco G., De Luca R., Barile G., Simone M., Costanzi A., Mari G., Maggioni M., Pellegrino R., Riggio V., Kenig J., Szabat K., Scabini S., Pertile D., Stratta E., Massobrio A., Soriero D., Nesbakken A., Lonn M., Backe I.F., Ferrari G., Mazzola M., Alampi B.D.A., Achilli P., Sfondrini S., Ioannidis O., Loutzidou L., Galanos-Demiris K., Pellino G., Balducci G., Frezza B., Lucarini A., Santos C., Cooper L., Siam B., Levy Y., Brenner B., Kashtan H., Belgrano V., De Cian F., Palermo B., Eggenhoffner R., Albertelli M., Sanchez-Guillen L., Arroyo A., Lopez-Rodriguez F., Lario S., Lillo C., Wexner S.D., Montroni, I., Rostoft, S., Spinelli, A., Van Leeuwen, B. L., Ercolani, G., Saur, N. M., Jacklitsh, M. T., Somasundar, P. S., de Liguori Carino, N., Ghignone, F., Foca, F., Zingaretti, C., Audisio, R. A., Ugolini, G., Garutti, A., Taffurelli, G., Zattoni, D., Tramelli, P., Sermonesi, G., Di Candido, F., Carvello, M., Sacchi, M., De Lucia, F., Foppa, C., Plas, M., Van der Wal-Huisman, H., Tauceri, F., Perenze, B., Di Pietrantonio, D., Mirarchi, M., Fejka, M., Bleier, J. I. S., Frain, L., Fox, S. W., Cardin, K., De Leon, L. E., Baltatzis, M., Chan, A. K. C., Siriwardena, A. K., Vertogen, B., Nanni, O., Garulli, G., Alagna, V., Pirrera, B., Lucchi, A., Monari, F., Conti, L., Capelli, P., Romboli, A., Palmieri, G., Banchini, F., Marano, L., Spaziani, A., Castagnoli, G., Bartoli, A., Trompetto, M., Gallo, G., Luc, A. R., Clerico, G., Sammarco, G., De Luca, R., Barile, G., Simone, M., Costanzi, A., Mari, G., Maggioni, M., Pellegrino, R., Riggio, V., Kenig, J., Szabat, K., Scabini, S., Pertile, D., Stratta, E., Massobrio, A., Soriero, D., Nesbakken, A., Lonn, M., Backe, I. F., Ferrari, G., Mazzola, M., Alampi, B. D. A., Achilli, P., Sfondrini, S., Ioannidis, O., Loutzidou, L., Galanos-Demiris, K., Pellino, G., Balducci, G., Frezza, B., Lucarini, A., Santos, C., Cooper, L., Siam, B., Levy, Y., Brenner, B., Kashtan, H., Belgrano, V., De Cian, F., Palermo, B., Eggenhoffner, R., Albertelli, M., Sanchez-Guillen, L., Arroyo, A., Lopez-Rodriguez, F., Lario, S., Lillo, C., and Wexner, S. D.

Subjects
Geriatric Oncology, Surgical Assessment, Functional Recovery, Pre&postoperative testing, Surgery morbidity, Surgery mortality, Male, medicine.medical_specialty, Surgery morbidity, MEDLINE, MULTICENTER, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Pre&postoperative testing, Quality of life, aged, aged, 80 and over, female, geriatric assessment, humans, male, neoplasms, postoperative complications, prospective studies, quality of life, Functional Recovery, Internal medicine, Neoplasms, medicine, 80 and over, Humans, 030212 general & internal medicine, Prospective Studies, Elective surgery, Geriatric Assessment, cancer, geriatric, outcome, Aged, Aged, 80 and over, business.industry, Surgical Assessment, Cancer, Functional recovery, medicine.disease, CANCER, Geriatric Oncology, Surgery mortality, Oncology, Geriatric oncology, 030220 oncology & carcinogenesis, Quality of Life, Observational study, Female, Geriatrics and Gerontology, business, Early analysis
Abstract

Objective: Older patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. Materials & Methods: GOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (≥70 years) from 26 international units. Short−/mid−/long-term surgical outcomes were recorded with QoL and FR data. Results: 1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70–94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had ≥ 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 ≤ 14(68.4%), fTRST ≥ 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. Conclusion: The GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR.

Published
2019

25. Being a Doctor Will Never Be the Same After the COVID-19 Pandemic

Author

Giampaolo Ugolini, Paolo Bonfanti, Patrizio Capelli, Andrea Mariani, Dario Maggioni, Isacco Montroni, Mari Giulio, Felice Achilli, Lorenzo Ceppi, Giulio, M, Maggioni, D, Montroni, I, Ugolini, G, Capelli, P, Ceppi, L, Bonfanti, P, Mariani, A, and Achilli, F

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, COVID-19, General Medicine, Virology, humanities, Patient Care Management, Betacoronavirus, Italy, contagion, Pandemic, Humans, Medicine, Coronavirus Infections, Physician's Role, business, Pandemics, COVID
Published
2020
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26. Spontaneous rupture of a non-functioning pancreatic neuroendocrine tumor A case report of a rare cause of acute abdomen

Author

Pietro Achilli, Chiarelli, M., Giustizieri, U., Burati, M., Tagliabue, F., Maternini, M., Terragn, S., Guttadauro, A., Achilli, P, Chiarelli, M, Giustizieri, U, Burati, M, Tagliabue, F, Maternini, M, Terragn, S, and Guttadauro, A

Subjects
Abdomen, Acute, Adult, Pancreatic Neoplasms, Neuroendocrine Tumors, Rupture, Spontaneous, Humans, Female, Abdominal pain, acute abdomen, Hemorrhagic shock, Pancreatic neuroendocrine tumor
Abstract

BACKGROUND: I tumori neuroendocrini del pancreas (PNET) sono un gruppo di tumori rari che rappresentano il 2% di tutte le neoplasie del pancreas, anche se la loro incidenza è aumentata negli ultimi 20 anni. La maggior parte dei PNET sono sporadici e tendono a colpire gli individui più anziani. A differenza dei tumori funzionali, che si presentano con i sintomi derivanti dall’ormone specifico in fase di elaborazione, i tumori neuroendocrini del pancreas non funzionanti (NF-PNET) presentano tipicamente sintomi correlati all’effetto massa locale o a malattia metastatica. Oggi, a causa del crescente uso di imaging addominale, i NF-PNET presentano un’incidenza aumentata. CASE REPORT: Una donna di 32 anni è giunta al nostro pronto soccorso per l’aggravarsi di un dolore addominale irradiantesi alla schiena. Poco dopo l’ammissione, lo stato della paziente peggiora ulteriormente sviluppando segni di shock e peritonite. Una scansione tomografica computerizzata addominale ha mostrato una massa solida (9 x 12 cm) della coda del pancreas con emoperitoneo. La paziente è stata sottoposta a laparotomia esplorativa e successiva splenopancreasectomia distale per un tumore sanguinante. Il rapporto istopatologico ha mostrato un tumore neuroendocrino ben differenziato (G1). Il decorso postoperatorio è stato regolare, la paziente è stata dimessa in X giornata post-operatoria. CONCLUSIONE: la rottura spontanea di neoplasie neuroendocrine solide del pancreas può causare addome acuto con effetti potenzialmente devastanti. BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a group of rare tumors that account for 2% of all pancreatic malignancies, even though their incidence has been increasing over the past 20 years. Most PNETs are sporadic and tend to affect older individuals. Differently from functional tumors, which present with symptoms resulting from the specific hormone being elaborated, non-functioning pancreatic neuroendocrine tumors (NF-PNETs) typically present with symptoms related to local mass effect or metastatic disease. Today, due to the increasing use of abdominal imaging, NFPNETs are frequently discovered incidentally. CASE REPORT: A 32-year-old woman was admitted to our emergency department for worsening upper abdominal pain radiating to the back. Shortly after the admission, shock and peritoneal signs developed. An abdominal computerized tomography scan showed a solid mass (9 x 12 cm) of the pancreatic tail with severe hemoperitomeum. Exploratory laparotomy and subsequent distal splenopancreasectomy were performed for a bleeding tumor. Histopathological report showed a neuroendocrine, well differentiated tumor (G1). The postoperative course was uneventful and the patient was successfully discharged on 10th postoperative day. CONCLUSION: Spontaneous rupture of solid neuroendocrine neoplasms of the pancreas can cause acute abdomen with potentially devastating effects. KEY WORDS: Abdominal pain, acute abdomen, Hemorrhagic shock, Pancreatic neuroendocrine tumor.

Published
2020

27. Haplogroup J mitogenomes are the most sensitive to the pesticide rotenone: Relevance for human diseases

Author

Antonio Torroni, Anna Ghelli, Alessandro Achilli, Andrea Martinuzzi, Leonardo Caporali, Luisa Iommarini, Monica Montopoli, Valerio Carelli, Anna Olivieri, Daniela Strobbe, Alessandra Maresca, Strobbe, Daniela, Caporali, Leonardo, Iommarini, Luisa, Maresca, Alessandra, Montopoli, Monica, Martinuzzi, Andrea, Achilli, Alessandro, Olivieri, Anna, Torroni, Antonio, Carelli, Valerio, and Ghelli, Anna

Subjects
0301 basic medicine, Mitochondrial DNA, Cybrids, genetic structures, Cell Survival, media_common.quotation_subject, Population, Cybrid, Biology, DNA, Mitochondrial, Haplogroup, Protein Structure, Secondary, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Oxygen Consumption, Rotenone, Genetic variation, Complex I, Missense mutation, Humans, Parkinson Disease, Secondary, Pesticides, education, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Phylogeny, media_common, Genetics, education.field_of_study, Longevity, Fibroblasts, Penetrance, eye diseases, 030104 developmental biology, Haplotypes, Neurology, Haplogroups, Genome, Mitochondrial, 030217 neurology & neurosurgery, Human mitochondrial DNA haplogroup
Abstract

There is growing evidence that the sequence variation of mitochondrial DNA (mtDNA), which clusters in population- and/or geographic-specific haplogroups, may result in functional effects that, in turn, become relevant in disease predisposition or protection, interaction with environmental factors and ultimately in modulating longevity. To unravel functional differences between mtDNA haplogroups we here employed transmitochondrial cytoplasmic hybrid cells (cybrids) grown in galactose medium, a culture condition that forces oxidative phosphorylation, and in the presence of rotenone, the classic inhibitor of respiratory Complex I. Under this experimental paradigm we assessed functional parameters such as cell viability and respiration, ATP synthesis, reactive oxygen species production and mtDNA copy number. Our analyses show that haplogroup J1, which is common in western Eurasian populations, is the most sensitive to rotenone, whereas K1 mitogenomes orchestrate the best compensation, possibly because of the haplogroup-specific missense variants impinging on Complex I function. Remarkably, haplogroups J1 and K1 fit the genetic associations previously established with Leber's hereditary optic neuropathy (LHON) for J1, as a penetrance enhancer, and with Parkinson's disease (PD) for K1, as a protective background. Our findings provide functional evidences supporting previous well-established genetic associations of specific haplogroups with two neurodegenerative pathologies, LHON and PD. Our experimental paradigm is instrumental to highlighting the subtle functional differences characterizing mtDNA haplogroups, which will be increasingly needed to dissect the role of mtDNA genetic variation in health, disease and longevity.

Published
2018

28. Streptococcus agalactiae infective endocarditis complicated by multiple mycotic hepatic aneurysms and massive splenic infarction: a case report

Author

F Gabrielli, Pietro Achilli, Luca Fumagalli, Matilde De Simone, Angelo Guttadauro, Marco Chiarelli, Ugo Cioffi, Sabina Terragni, Paolo Bonfanti, Achilli, P, Guttadauro, A, Bonfanti, P, Terragni, S, Fumagalli, L, Cioffi, U, Gabrielli, F, De Simone, M, and Chiarelli, M

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Splenectomy, Infective endocarditi, Case Report, Hepatic artery aneurysm, 030204 cardiovascular system & hematology, medicine.disease_cause, Splenic infarction, Streptococcus agalactiae, 03 medical and health sciences, 0302 clinical medicine, Medicine, Endocarditis, Humans, 030212 general & internal medicine, lcsh:RC799-869, medicine.diagnostic_test, business.industry, Liver Diseases, Gastroenterology, Streptococcus infection, Interventional radiology, General Medicine, Endocarditis, Bacterial, Mycotic aneurysm, Middle Aged, medicine.disease, Surgery, Anti-Bacterial Agents, Infective endocarditis, lcsh:Diseases of the digestive system. Gastroenterology, business, Aneurysm, Infected
Abstract

Background The burden of disease caused by Streptococcus agalactiae has increased significantly among older adults in the last decades. Group B streptococcus infection can be associated with invasive disease and severe clinical syndromes, such as meningitis and endocarditis. Case presentation We present the case of a 56-year-old man who developed multiple mycotic aneurysms of the right hepatic artery and massive splenic infarction as rare complications of Streptococcus agalactiae infective endocarditis. The patient underwent urgent right hepatic artery ligation and splenectomy. The postoperative course was complicated by an episode of hemobilia due to the rupture of a partially thrombosed mycotic aneurysm into the biliary tree. Thus, selective radiological embolization of the left hepatic artery branches was necessary. Conclusion To our knowledge, this is the first case reported of infected aneurysms of visceral arteries caused by Group B streptococcus infection. Clinical and laboratory findings were non-specific, while imaging features with computed tomography scan and angiography were highly suggestive. In our case, early recognition, culture-specific intravenous antibiotics and urgent surgical treatment combined with interventional radiology played a decisive role in the final result.

Published
2017

29. Autoimmune diseases associated with common variable immune deficiency

Author

Marco Vincenzo Lenti, Antonio Di Sabatino, Giovanna Achilli, and Jessica Savioli

Subjects
Delayed Diagnosis, Evans syndrome, Autoimmune Gastritis, Immunology, Population, Autoimmunity, medicine.disease_cause, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, education, Immunodeficiency, Purpura, Thrombocytopenic, Idiopathic, education.field_of_study, business.industry, Common variable immunodeficiency, Autoantibody, medicine.disease, Common Variable Immunodeficiency, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Anemia, Hemolytic, Autoimmune, Autoimmune hemolytic anemia, business
Abstract

Common variable immunodeficiency (CVID) is the most prevalent primary immune deficiency, affecting roughly 2-4/100 000 individuals in the general population. The etiology is currently unknown, even if several genetic mutations have been described, and no single clinical feature or single laboratory test can establish the diagnosis, which is based on multiple criteria. CVID is characterized by B- and T-cell dysfunction that predisposes to an increased risk of infections, with the typical involvement of the respiratory and gastrointestinal tracts. Besides this well-established complication, though the coexistence of immunodeficiency and autoimmunity appears paradoxical, two-thirds of CVID patients present concomitant autoimmune disorders. Of note, autoimmunity can often be the only clinical manifestation of CVID at the time of diagnosis. The most common autoimmune disorders associated with CVID are autoimmune cytopenias, that is, immune thrombocytopenic purpura and autoimmune hemolytic anemia, either as separate entities or as concurrently (Evans syndrome). CVID patients can also manifest rheumatologic diseases (eg, arthritis, Sjogren's disease, systemic lupus erythematosus, vasculitis, Behçet's syndrome) and gastrointestinal autoimmune disorders (eg, ulcerative colitis, autoimmune atrophic gastritis, celiac disease). This latter may pose a particular diagnostic challenge, as celiac-specific autoantibodies can be absent in CVID patients. Understanding the molecular basis and the clinical impact of autoimmunity in CVID patients might help manage CVID, thus reducing its diagnostic delay and preventing its complications.

Published
2020

30. The hidden hypothesis: A disseminated tuberculosis case

Author

Maria Rita Perego, Anna Casati, Felice Achilli, Sergio Foresti, Manuela Carugati, Andrea Gori, Cristina Malafronte, Raffaele Badolato, and Marco Manzoni

Subjects
0301 basic medicine, Microbiology (medical), Constrictive pericarditis, Male, Bayes, medicine.medical_specialty, Tuberculosis, Diagnostic performance, medicine.medical_treatment, 030106 microbiology, Pericardial effusion, QuantiFERON, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Pericarditis, 0302 clinical medicine, Tuberculosis diagnosis, Internal medicine, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, Pericardiectomy, Aged, medicine.diagnostic_test, business.industry, Bayes Theorem, General Medicine, Mycobacterium tuberculosis, Pericarditis, Tuberculous, medicine.disease, Infectious Diseases, Erythrocyte sedimentation rate, business
Abstract

Case presentation: 77-year-old former smoker admitted because of fatigue and abdominal distention. Past medical history positive for two previous hospitalizations for pericardial and pleural effusions (no diagnosis achieved). At admission erythrocyte sedimentation rate was 122 mm per hour. Baseline investigations revealed ascitic, pleural and pericardial effusion. Effusions were tapped: neoplastic cells and acid-fast bacilli (AFB) were not identified, aerobic and mycobacterial culture resulted negative. QuantiFERON TB-Gold test was negative. Total body PET-CT and autoimmunity panel were negative. A neoplastic process was considered the most likely explanation. Before signing off the patient to comfort care, a reassessment was performed and an exposure to tuberculosis during childhood was documented. Because of constrictive pericarditis, pericardiectomy was performed: histologic examination showed chronic pericardial inflammation without granulomas, but Ziehl-Neelsen stain identified AFB and PCR was positive for Mycobacterium tuberculosis complex. Patient was started on anti-TB therapy with resolution of the effusions in the following months. Genes associated with defects in innate immunity were sequences and dentritic cells were studied, but no alterations were identified. Discussion: A Bayesian approach to clinical decision making should be recommended. Interpretation of diagnostic tests should take into account the imperfect diagnostic performance of the majority of these tests. Further studies to investigate genetic susceptibility to tuberculosis are needed. Keywords: Tuberculosis, Diagnostic performance, Bayes

Published
2019

31. A worldwide perspective of sepsis epidemiology and survival according to age: Observational data from the ICON audit

Author

Kotfis, K., Wittebole, X., Jaschinski, U., Sole-Violan, J., Kashyap, R., Leone, M., Nanchal, R., Fontes, Le, Sakr, Y., Vincent, Jl, Tomas, E., Bibonge, Ea, Charra, B., Faroudy, M., Doedens, L., Farina, Z., Adler, D., Balkema, C., Kok, A., Alaya, S., Gharsallah, H., Muzha, D., Temelkov, A., Georgiev, G., Simeonov, G., Tsaryanski, G., Georgiev, S., Seliman, A., Vrankovic, S., Vucicevic, Z., Gornik, I., Barsic, B., Husedzinovic, I., Pavlik, P., Manak, J., Kieslichova, E., Turek, R., Fischer, M., Valkova, R., Dadak, L., Dostal, P., Malaska, J., Hajek, R., Zidkova, A., Lavicka, P., Starkopf, J., Kheladze, Z., Chkhaidze, M., Kaloiani, V., Medve, L., Sarkany, A., Kremer, I., Marjanek, Z., Tamasi, P., Krupnova, I., Vanags, I., Liguts, V., Pilvinis, V., Vosylius, S., Kekstas, G., Balciunas, M., Kolbusz, A., Kubler, A., Mielczarek, B., Mikaszewska-Sokolewicz, M., Tamowicz, B., Sulkowski, W., Smuszkiewicz, P., Pihowicz, A., Trejnowska, E., Hagau, N., Filipescu, D., Droc, G., Lupu, M., Nica, A., Stoica, R., Tomescu, D., Constantinescu, D., Zbaganu, Gv, Slavcovici, A., Bagin, V., Belsky, D., Palyutin, S., Shlyapnikov, S., Bikkulova, D., Gritsan, A., Natalia, G., Makarenko, E., Kokhno, V., Tolkach, A., Kokarev, E., Belotserkovskiy, B., Zolotukhin, K., Kulabukhov, V., Soskic, L., Palibrk, I., Jankovic, R., Jovanovic, B., Pandurovic, M., Bumbasirevic, V., Uljarevic, B., Surbatovic, M., Ladjevic, N., Slobodianiuk, G., Sobona, V., Cikova, A., Gebhardtova, A., Jun, C., Yunbo, S., Dong, U., Feng, S., Duan, M., Xu, Y., Xue, X., Gao, T., Xing, X., Zhao, X., Li, C., Gengxihua, G., Tan, H., Xu, J., Jiang, L., Tiehe, Q., Bingyu, Q., Shi, Q., Lv, Z., Zhang, L., Jingtao, L., Zhen, Z., Wang, Z., Wang, T., Yuhong, L., Zhai, Q., Chen, Y., Wang, C., Jiang, W., Ruilan, W., Xiaobo, H., Ge, H., Yan, T., Yuhui, C., Zhang, J., Jian-Hong, F., Zhu, H., Huo, F., Wang, Y., Zhuang, M., Ma, Z., Sun, J., Liuqingyue, L., Yang, M., Meng, J., Ma, S., Kang, Y., Yu, L., Peng, Q., Wei, Y., Zhang, W., Sun, R., Yeung, A., Wan, W., Sin, K., Lee, K., Wijanti, M., Widodo, U., Samsirun, H., Sugiman, T., Wisudarti, C., Maskoen, T., Hata, N., Kobe, Y., Nishida, O., Miyazaki, D., Nunomiya, S., Uchino, S., Kitamura, N., Yamashita, K., Hashimoto, S., Fukushima, H., Adib, Nn, Tai, L., Tony, B., Bigornia, R., Palo, J., Chatterjee, S., Tan, B., Kong, A., Goh, S., Lee, C., Pothirat, C., Khwannimit, B., Theerawit, P., Pornsuriyasak, P., Piriyapatsom, A., Mukhtar, A., Dsicu, Hamdy, An, Hosny, H., Ashraf, A., Mokhtari, M., Nowruzinia, S., Lotfi, A., Zand, F., Nikandish, R., Moghaddam, Om, Cohen, J., Sold, O., Sfeir, T., Hasan, A., Abugaber, D., Ahmad, H., Tantawy, T., Baharoom, S., Algethamy, H., Amr, A., Almekhlafi, G., Coskun, R., Sungur, M., Cosar, A., Gucyetmez, B., Demirkiran, O., Senturk, E., Ulusoy, H., Atalan, H., Serin, S., Kati, I., Alnassrawi, Z., Almemari, A., Krishnareddy, K., Kashef, S., Alsabbah, A., Poirier, G., Marshall, J., Herridge, M., Fernandez-Medero, R., Fulda, G., Banschbach, S., Quintero, J., Schroeder, E., Sicoutris, C., Gueret, R., Bauer, P., Wunderink, R., Jimenez, E., Ryan, A., Prince, D., Edington, J., Haren, F., Bersten, A., Hawkins, Dj, Kilminster, M., Sturgess, D., Ziegenfuss, M., O Connor, S., Lipman, J., Campbell, L., Mcallister, R., Roberts, B., Williams, P., Parke, R., Seigne, P., Freebairn, R., Nistor, D., Oxley, C., Young, P., Valentini, R., Wainsztein, N., Comignani, P., Casaretto, M., Sutton, G., Villegas, P., Galletti, C., Neira, J., Rovira, D., Hidalgo, J., Sandi, F., Caser, E., Thompson, M., Dias, Md, Fontes, L., Lunardi, M., Youssef, N., Lobo, S., Silva, R., Sales, J., Melo, Lmc, Oliveira, M., Fonte, M., Grion, C., Feijo, C., Rezende, V., Assuncao, M., Neves, A., Gusman, P., Dalcomune, D., Teixeira, C., Kaefer, K., Maia, I., Dantas, Vs, Filho, Rc, Amorim, F., Assef, M., Schiavetto, P., Houly, J., Bianchi, F., Dias, F., Avila, C., Gomez, J., Rego, L., Castro, P., Passos, J., Mendes, C., Mecatti, Gc, Ferrreira, M., Irineu, V., Guerreiro, M., Ugarte, S., Tomicic, V., Godoy, C., Samaniego, W., Escamilla, I., Castro, Lc, Duque, Gl, Diaz-Guio, D., Benitez, F., Urrego, Ag, Buitrago, R., Ortiz, G., Gaviria, Mv, Salas, D., Ramirez-Arce, J., Salgado, E., Morocho, D., Vergara, J., Sang, Mc, Carlos E. Orellana-Jimenez, Garrido, L., Diaz, O., Resiere, D., Osorio, C., La Vega, A., Carrillo, R., Sanchez, V., Villagomez, A., Zubieta, Rm, Sandia, M., Zalatiel, M., Poblano, M., Gonzalez, Dr, Arrazola, F., Francisco, Lj, Liamendys-Silva, Sa, Hernandez, M., Cadena, Dr, Islas, Il, Zarzavilla, Cb, Matos, A., Oyanguren, I., Cerna, J., Sierra, Rq, Jimenez, R., Castillo, L., Ocal, R., Sencan, A., Gianoni, Sm, Deicas, A., Hurtado, J., Burghi, G., Martinelli, A., Osten, I., Du Maine, C., Bhattacharyya, M., Bandyopadhyay, S., Yanamala, S., Gopal, P., Sahu, S., Ibrahim, M., Rathod, D., Mukundan, N., Dewan, A., Amin, P., Samavedam, S., Shah, B., Gurupal, D., Lahkar, B., Mandal, A., Sircar, M., Ghosh, S., Balasubramani, V., Kapadia, F., Vadi, S., Nair, K., Tripathy, S., Nandakumar, S., Sharma, J., Kar, A., Jha, S., Gurav, Kz, Patel, M., Bhaysar, A., Samaddar, D., Kulkarni, A., Hashmi, M., Ali, W., Nadeem, S., Indraratna, K., Margarit, A., Urbanek, P., Schlieber, J., Reisinger, J., Auer, U., Hartjes, A., Lerche, A., Janous, T., Kink, E., Krahulec, W., Smolle, K., Schueren, M., Thibo, P., Vanhoof, M., Ahmet, I., Gadisseux, P., Dufaye, P., Jacobs, O., Fraipont, V., Biston, P., Dive, A., Bouckaert, Y., Gilbert, E., Gressens, B., Pinck, E., Collin, V., Waele, J., Rimachi, R., Gusu, D., Decker, K., Mandianga, K., Heytens, L., Spapen, H., Olivier, V., Vandenheede, W., Rogiers, P., Kolodzeike, P., Kruse, M., Andersen, T., Harjola, V., Saarinen, K., Durocher, A., Moulront, S., Lepape, A., Losser, M., Cabaret, P., Kalaitzis, E., Zogheib, E., Charve, P., Francois, B., Lefrant, Jy, Beilouny, B., Forceville, X., Misset, B., Jacobs, F., Floccard, B., Payen, D., Wynckel, A., Castelain, V., Faure, A., Lavagne, P., Thierry, I., Moussa, M., Vieillard-Baron, A., Durand, M., Gainnier, M., Ichai, C., Arens, S., Hoffmann, C., Kaffarnik, M., Scharnofske, C., Voigt, I., Peckelsen, C., Weber, M., Gille, J., Lange, A., Schoser, G., Sablotzki, A., Bluethgen, A., Vogel, F., Tscheu, A., Fuchs, T., Wattenberg, M., Helmes, T., Scieszka, S., Heintz, M., Sakka, S., Kohler, J., Fiedler, F., Danz, M., Riessen, R., Kerz, T., Kersten, A., Tacke, F., Marx, G., Volkert, T., Schmutz, A., Nierhaus, A., Kluge, S., Abel, P., Janosi, R., Utzolino, S., Bracht, H., Toussaint, S., Peftoulidou, Mg, Myrianthefs, P., Armaganidis, A., Routsi, C., Xini, A., Mouloudi, E., Kokoris, I., Kyriazopoulos, G., Vlachos, S., Lavrentieva, A., Partala, P., Nakos, G., Moller, A., Stefansson, S., Barry, J., O Leary, R., Motherway, C., Faheem, M., Dunne, E., Donnelly, M., Konrad, T., Bonora, E., Achilli, C., Rossi, S., Castiglione, G., Penis, A., Albanese, D., Stocchetti, N., Citerio, G., Mozzoni, L., Sisillo, E., Negri, P., Savioli, M., Vecchiarelli, P., Puflea, F., Stankovic, V., Minoja, G., Montibeller, S., Calligaro, P., Sorrentino, R., Feri, M., Zambon, M., Colombaroli, E., Giarratano, A., Pellis, T., Capra, C., Antonelli, M., Gullo, A., Chelazzi, C., Capraris, A., Patroniti, N., Girardis, M., Franchi, F., Berlot, G., Buttigieg, M., Ponssen, H., Cate, Jt, Bormans, L., Husada, S., Buise, M., Hoven, B., Reidinga, A., Kuiper, M., Pickkers, P., Kluge, G., Den Boer, S., Kesecioglu, J., Leeuwen, H., Flaatten, H., Mo, S., Branco, V., Rua, F., Lafuente, E., Sousa, M., Catorze, N., Barros, M., Pereira, L., Oliveira, Av, Gomes, J., Gaspar, I., Pereira, M., Cymbron, M., Dias, A., Almeida, E., Beirao, S., Serra, I., Ribeiro, R., Povoa, P., Faria, F., Costa-E-Silva, Z., Nobrega, A., Fernandes, F., Gabriel, J., Voga, G., Rupnik, E., Kosec, L., Povsic, Mk, Osojnik, I., Tomic, V., Sinkovic, A., Gonzalez, J., Zavala, E., Valenzuela, Ap, Marina, L., Vidal-Cortes, P., Posada, I., Martin-Loeches, Ai, Guillen, Nm, Palomar, M., Sole-Violan, U., Torres, A., Gallego, Mg, Aguilar, G., Allue, Rm, Argueso, M., Parejo, M., Navarro, Mp, Jose, A., Nin, N., Lerma, Fa, Martinez, O., Lozano, Et, Lopez, Sa, Granda, Mp, Moreno, S., Llubia, C., Martos, Cd, Gonzalez-Arenas, P., Fernandez, Nl, Rueda, Bg, Pons, Ie, Cruza, N., Maroto, F., Estella, A., Ferrer, A., Fraile, Li, Quindos, B., Quintano, A., Tebar, M., Cardinal, I., Reyes, A., Rodriguez, A., Abella, A., Del Valle, Sg, Yus, S., Maseda, E., Berezo, U., Pedregosa, At, Laplaza, C., Ferrer, R., Rico-Feijoo, U., Rodriguez, M., Monedero, P., Eriksson, K., Lind, D., Chabanel, D., Zender, H., Heer, K., Frankenberger, B., Jakob, S., Mathew, S., Downes, R., Groba, Cb, Johnston, A., Meacher, R., Keays, R., Haji-Michael, P., Tyler, C., Ferguson, A., Jones, S., Tyl, D., Ball, A., Vogel, U., Booth, M., Downie, P., Watters, M., Brett, S., Garfield, M., Everett, L., Heenen, S., Dhir, S., Beardow, Z., Mostert, M., Brosnan, S., Pinto, N., Harris, S., Summors, A., Andrew, N., Rose, A., Appelboam, R., Davies, O., Vickers, E., Agarwal, B., Szakmany, T., Wimbush, S., Welters, I., Pearse, R., Hollands, R., Kirk-Bayley, U., Fletcher, N., Bray, B., Brealey, D., Intensive Care, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (SLuc) Service de soins intensifs, UCL - (MGD) Services des soins intensifs, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], and University of Wisconsin School of Medicine and Public Health

Subjects
Adult, Male, medicine.medical_specialty, Critical Illness, Medizin, Audit, Critical Care and Intensive Care Medicine, Sepsis, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Epidemiology, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, In patient, Hospital Mortality, Prospective Studies, Mortality, ComputingMilieux_MISCELLANEOUS, Outcome, Aged, computer.programming_language, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Critically ill, ICU, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Hospitalization, Intensive Care Units, Increased risk, 030228 respiratory system, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Observational study, Icon, business, computer
Abstract

Purpose: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world., Methods: We performed a secondary analysis of data from the prospective ICON audit, in which all adult ( >16 years ) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - 80 years. Sepsis was defined as infection plus at least one organ failure., Results: A total of 2963 patients had sepsis, with similar proportions across the age groups (80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients 70 years was independently associated with increased risk of dying., Conclusions: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years. (C) 2019 Elsevier Inc. 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Amisi] Clin Univ Kinshasa, Kinshasa, DEM REP CONGO., [Charra, B.] Chu Ibn Rochd Casablanca, Casablanca, Morocco., [Faroudy, M.] Ibn Sina Hosp, Rabat, Morocco., [Doedens, L.] Chris Hani Baragwanath Acad Hosp, Soweto, South Africa., [Farina, Z.] Grays Hosp, Pietermaritzburg, South Africa., [Adler, D.] Sandton Medi Clin, Sandton, South Africa., [Balkema, C.] Tygerberg Hosp, Cape Town, South Africa., [Kok, A.] Union Hosp Alberton, Alberton, South Africa., [Alaya, S.] Bizerte Hosp, Bizerte, Tunisia., [Gharsallah, H.] Mil Hosp Tunis, Tunis, Tunisia., [Muzha, D.] Natl Trauma Ctr & Mil Hosp, Tirana, Albania., [Temelkov, A.] Alexandrovska Univ Hosp, Sofia, Bulgaria., [Georgiev, G.] Emergency Univ Hosp Pirogov, Sofia, Bulgaria., [Simeonov, G.] Tokuda Hosp Sofia, Sofia, Bulgaria., [Tsaryanski, G.] Uh St Ekaterina Sofia, Sofia, Bulgaria., [Georgiev, S.] Univ Hosp Obstet & Gynaecol, Sofia, Bulgaria., [Seliman, A.] Univ Hosp Sveta Marina Varna, Varna, Bulgaria., [Vrankovic, S.] Gen Hosp Siben, Shibenik, Croatia., [Vucicevic, Z.] Univ Hosp Ctr Sestre Milosrdnice, Zagreb, Croatia., [Gornik, I] Univ Hosp Ctr Zagreb, Zagreb, Croatia., [Barsic, B.] Univ Hosp Infect Dis, Zagreb, Croatia., [Husedzinovic, I] Univ Hosp Dubrava, Zagreb, Croatia., [Pavlik, P.] Ctr Cardiovasc & Transplant Surg, Prague, Czech Republic., [Manak, J.] Charles Univ Hosp, Prague, Czech Republic., [Kieslichova, E.] IKEM, Prague, Czech Republic., [Turek, R.] KNTB Zlin AS, Prague, Czech Republic., [Fischer, M.] Krajska Nemocnice Liberec, Prague, Czech Republic., [Valkova, R.] Masarykova Nemocnice V Usti Labem, Labem, Czech Republic., [Dadak, L.] St Annes Univ Hosp Brno, Brno, Czech Republic., [Dostal, P.] Univ Hosp Haradec Kralove, Haradec Kralove, Czech Republic., [Malaska, J.] Univ Hosp Brno, Brno, Czech Republic., [Hajek, R.] Univ Hosp Olomouc, Olomouc, Czech Republic., [Zidkova, A.] Univ Hosp Plzen, Plzen, Czech Republic., [Lavicka, P.] Charles Univ Hosp Plzen, Plzen, Czech Republic., [Starkopf, J.] Tartu Univ Hosp, Tartu, Estonia., [Kheladze, Z.] Crit Care Med Inst, Gainesville, Georgia., [Chkhaidze, M.] Jo Ann Med Ctr, Tbilisi, Georgia., [Kaloiani, V] Kipshidze Cent Univ Hosp, Tbilisi, Georgia., [Medve, L.] Dr Kenessey Albert Hosp, Balassagyarmat, Hungary., [Sarkany, A.] Fejer Cty St George Teaching Hosp, Szekesfehervar, Hungary., [Kremer, I] Flor Ferenc Cty Hosp, Budapest, Hungary., [Marjanek, Z.] Javorszky Odon Hosp, Vac, Hungary., [Tamasi, P.] Peterfy Hosp Budapest, Budapest, Hungary., [Krupnova, I] Infectol Ctr Latvia, Riga, Latvia., [Vanags, I] Paul Stradins Clin Univ Hosp, Riga, Latvia., [Liguts, V] Riga East Clin Univ Hosp, Riga, Latvia., [Pilvinis, V] Hosp Lithuanian Univ Hlth Sci Kauno Klinikos, Kaunas, Lithuania., [Vosylius, S.] Vilnius Univ Hosp, Vilnius, Lithuania., [Kekstas, G.] HSICU, Vilnius Univ Hosp Santariskiu Clin, Vilnius, Lithuania., [Balciunas, M.] CICU, Vilnius Univ Hosp Santariskiu Clin, Vilnius, Lithuania., [Kolbusz, A.] Csk Mswia, Warsaw, Poland., [Kubler, A.] Med Univ, Wroclaw, Poland., [Mielczarek, B.] Med Univ Wroclaw, Wroclaw, Poland., [Mikaszewska-Sokolewicz, M.] Med Univ Warsaw, Warsaw, Poland., [Kotfis, K.] Pomeranian Med Univ, Szczecin, Poland., [Tamowicz, B.] Reg Hosp Poznan, Poznan, Poland., [Sulkowski, W.] Szpital Powiatowy W Ostrowi Mazowieckiej, Ostrow Mazowiecka, Poland., [Smuszkiewicz, P.] Univ Hosp, Poznan, Poland., [Pihowicz, A.] Wojewodzki Szpital Zakazny, Torun, Poland., [Trejnowska, E.] Wojewodzkie Ctr Med, Warsaw, Poland., [Hagau, N.] Emergency Cty Hosp Cluj, Cluj Napoca, Romania., [Filipescu, D.] Emergency Inst Cardiovasc Dis, Bucharest, Romania., [Droc, G.] Fundeni Clin Inst, Bucharest, Romania., [Lupu, M.] Galati Hosp, Bucharest, Romania., [Nica, A.] Lnbi Prof Dr Matei Bals, Bucharest, Romania., [Stoica, R.] Inst Pulmonol Marius Nasta, Bucharest, Romania., [Tomescu, D.] Inst Clin Fundeni, Bucharest, Romania., [Constantinescu, D.] Sfantul Pantelimon Hosp, Bucharest, Romania., [Zbaganu, G. Valcoreanu] Spitalul Cf 2 Bucuresti, Bucharest, Romania., [Slavcovici, A.] Iuliu Hatieganu Univ Med & Pharm, Teaching Hosp Infect Dis, Cluj Napoca, Romania., [Bagin, V] City Clin Hosp 40, St Petersburg, Russia., [Belsky, D.] City Hosp 40, St Petersburg, Russia., [Palyutin, S.] Clin Hosp NVNV Solovyev, Yaroslavl, Russia., [Shlyapnikov, S.] Emergency Res Inst NA Djanelidze, St Petersburg, Russia., [Bikkulova, D.] Fed Res Ctr Paediat Haematol Oncol & Immunol, Moscow, Russia., [Gritsan, A.] Krasnoyarsk State Med Univ, Krasnoyarsk Reg Hosp, Krasnoyarsk, Russia., [Natalia, G.] Med Assoc Novaya Bolnitsa, Ekaterinburg, Russia., [Makarenko, E.] Mil Med Acad, Ekaterinburg, Russia., [Kokhno, V] Novosibirsk Med Univ, Novosibirsk, Russia., [Tolkach, A.] Omsk Reg Clin Hosp, Omsk, Russia., [Kokarev, E.] Railway Hosp Khabarovsk, Khabarovsk, Russia., [Belotserkovskiy, B.] St Alexy Hosp, St Louis, France., [Zolotukhin, K.] State Dist Hosp, Moscow, Russia., [Kulabukhov, V] Vishnevsky Inst Surg, Moscow, Russia., [Soskic, L.] Clin Ctr Serbia, Clin Cardiac Surg, Belgrade, Serbia., [Palibrk, I] Clin Ctr Serbia, Clin Digest Surg, Belgrade, Serbia., [Jankovic, R.; Jovanovic, B.] Clin Ctr Nis, Clin Vasc Surg, Nish, Serbia., [Pandurovic, M.] Clin Ctr Serbia, Emergency Ctr, Belgrade, Serbia., [Bumbasirevic, V] Clin Ctr Belgrade, Emergency Ctr, Belgrade, Serbia., [Uljarevic, B.] Gen Univ Hosp, Belgrade, Serbia., [Surbatovic, M.] Mil Med Acad, Belgrade, Serbia., [Ladjevic, N.] Urol Hosp, Belgrade, Serbia., [Slobodianiuk, G.] Dist Hosp, Bratislava, Slovakia., [Sobona, V] Fac Hosp, Bratislava, Slovakia., [Cikova, A.] Univ Hosp Bratislava, Hosp Ruzinov ICU, Bratislava, Slovakia., [Gebhardtova, A.] Univ Hosp Ruzinov Bratislava, Bratislava, Slovakia., [Jun, C.] Qingdao Univ, Tertiary Hosp, Qingdao, Shandong, Peoples R China., [Yunbo, S.] Qingdao Univ, Affiliated Hosp, Med Coll, Qingdao, Shandong, Peoples R China., [Dong, U.] Beijing Canc Hosp, Beijing Inst Canc Res, Beijing, Peoples R China., [Feng, S.] Beijing Chaoyang Hosp, Beijing, Peoples R China., [Duan, M.] Beijing Friendship Hosp, Beijing, Peoples R China., [Xu, Y.] Capital Med Univ, Beijing Tongren Hosp, Beijing, Peoples R China., [Xue, X.] Beijing Univ Peoples Hosp, Beijing, Peoples R China., [Gao, T.] Beijing Luhe Hosp, Beijing, Peoples R China., [Xing, X.] Chinese Acad Med Sci, Canc Hosp, Beijing, Peoples R China., [Zhao, X.] China Acad Chinese Med Sci, Guang An Men Hosp, Beijing, Peoples R China., [Li, C.] Peoples Hosp, Chuxiong, Yunnan, Peoples R China., [Gengxihua, G.] Donge Cty Peoples Hosp Shandong Prov, Liaocheng, Shandong, Peoples R China., [Tan, H.] Chinese Acad Med Sci, Fu Wai Hosp, Beijing, Peoples R China., [Xu, J.] Fujian Prov Hosp, Fuzhou, Fujian, Peoples R China., [Jiang, L.] Capital Med Univ, Fuxing Hosp, Beijing, Peoples R China., [Tiehe, Q.] Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China., [Bingyu, Q.] Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China., [Shi, Q.] Xi An Jiao Tong Univ, Coll Med, Xian, Shaanxi, Peoples R China., [Lv, Z.] Kunming Third Peoples Hosp, Kunming, Yunnan, Peoples R China., [Zhang, L.] Lanzhou Univ, Hosp 2, Lanzhou, Gansu, Peoples R China., [Jingtao, L.] 309th Hosp, Beijing, Peoples R China., [Zhen, Z.] China Med Univ, Hosp 1, Beijing, Peoples R China., [Wang, Z.] Peking Univ, Shougang Hosp, Beijing, Peoples R China., [Wang, T.] Peking Univ, Hosp 3, Beijing, Peoples R China., [Yuhong, L.] Pla Navy Gen Hosp, Beijing, Peoples R China., [Zhai, Q.] Shandong Univ, Qilu Hosp, Jinan, Shandong, Peoples R China., [Chen, Y.] Jiaotong Univ, Affiliated Med Sch, Ruijin Hosp, Shanghai, Peoples R China., [Wang, C.] Shandong Prov Hosp, Jinan, Shandong, Peoples R China., [Jiang, W.] Shanghai 10th Peoples Hosp, Shanghai, Peoples R China., [Ruilan, W.] Shanghai First Peoples Hosp, Shanghai, Peoples R China., [Chen, Y.; Xiaobo, H.] Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China., [Ge, H.] Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China., [Yan, T.] Affiliated Guiyang Med Coll, Guiyang, Guizhou, Peoples R China., [Yuhui, C.] Fudan Univ, Peoples Hosp Shanghai 5, Shanghai, Peoples R China., [Zhang, J.] Dalian Med Univ, Affiliated Hosp 1, Dalian, Peoples R China., [Jian-Hong, F.] Suzhou Univ, Affiliated Hosp 1, Suzhou, Peoples R China., [Zhu, H.] Xinjiang Med Univ, Affiliated Hosp 1, Urumqi, Peoples R China., [Huo, F.; Wang, Y.] Jilin Univ, Hosp 1, Changchun, Jilin, Peoples R China., [Li, C.] First Peoples Hosp Kunming, Kunming, Yunnan, Peoples R China., [Zhuang, M.] Gen Hosp Shenyang Mil Reg, Shenyang, Liaoning, Peoples R China., [Ma, Z.] Peoples Hosp Cangzhou, Cangzhou, Peoples R China., [Sun, J.] Jilin Univ, Hosp 2, Changchun, Jilin, Peoples R China., [Liuqingyue, L.] Second Peoples Hosp Liaocheng City Shandong Prov, Liaocheng, Shandong, Peoples R China., [Yang, M.] Third Xiangya Hosp, Changsha, Hunan, Peoples R China., [Meng, J.] Tongde Hosp Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China., [Ma, S.] Tongji Univ, Shanghai East Hosp, Shanghai, Peoples R China., [Kang, Y.] West China Hosp, Scu, Peoples R China., [Yu, L.] Wuhan Ctr Hosp, Wuhan, Hubei, Peoples R China., [Peng, Q.] Xiangya Hosp, Changsha, Hunan, Peoples R China., [Wei, Y.] Yantai Yuhuangding Hosp, Yantai, Peoples R China., [Zhang, W.] Yantaishan Hosp, Yantai, Shandong, Peoples R China., [Sun, R.] Zhejiang Prov Peoples Hosp, Hangzhou, Zhejiang, Peoples R China., [Yeung, A.] Pamela Youde Nethersole Eastern Hosp, Hong Kong, Peoples R China., [Wan, W.] Princess Margaret Hosp, Hong Kong, Peoples R China., [Sin, K.] Queen Elizabeth Hosp, Hong Kong, Peoples R China., [Lee, K.] United Christian Hosp Hong Kong SAR, Hong Kong, Peoples R China., [Wijanti, M.] Anestesi, Yogyakarta, Indonesia., [Widodo, U.] Pku Muhammadiyah Bantu, Yogyakarta, Indonesia., [Samsirun, H.] Rd Mattaher Hosp Jambi, Jambi City, Indonesia., [Sugiman, T.] Rumah Sakit Pantai Lndah Kapuk, North Jakarta, Indonesia., [Wisudarti, C.] Sardjito Hosp, Yogyakarta, Indonesia., [Maskoen, T.] Sch Med Unpad, Hasan Sadikin Hosp, Bandung, Indonesia., [Hata, N.] Nippon Med Sch, Chiba Hokusoh Hosp, Inzai, Japan., [Kobe, Y.] Chiba Univ Hosp, Chiba, Japan., [Nishida, O.] Fujita Hlth Univ, Sch Med, Toyoake, Aichi, Japan., [Miyazaki, D.] Japanese Red Cross Maebashi Hosp, Maebashi, Gumma, Japan., [Nunomiya, S.] Jichi Med Univ Hosp, Shimotsuke, Japan., [Uchino, S.] Jikei Univ, Sch Med, Tokyo, Japan., [Kitamura, N.] Kimitsu Chuo Hosp, Kisarazu, Japan., [Yamashita, K.] Kochi Med Sch, Nankoku, Kochi, Japan., [Hashimoto, S.] Kyoto Prefectural Univ Med, Kyoto, Japan., [Fukushima, H.] Nara Med Univ Hosp, Kashihara, Nara, Japan., [Adib, N. Nik] Hosp Sultanah Nur Zahirah, Kuala Terengganu, Terengganu, Malaysia., [Tai, L.] Kuala Lumpur Hosp, Kuala Lumpur, Malaysia., [Tony, B.] Queen Elizabeth Hosp 2, Kota Kinabalu, Malaysia., [Bigornia, R.] Cebu Velez Gen Hosp, Cebu, Philippines., [Bigornia, R.] Perpetual Succour Hosp, Cebu, Philippines., [Palo, J.] Med City, Pasig, Philippines., [Chatterjee, S.] Alexandra Hosp, Singapore, Singapore., [Tan, B.] Natl Univ Hlth Syst, Singapore, Singapore., [Kong, A.] Singapore Gen Hosp, Singapore, Singapore., [Goh, S.] Tan Tock Seng Hosp, Singapore, Singapore., [Lee, C.] Natl Taiwan Univ Hosp, Taipei, Taiwan., [Pothirat, C.] Chiaingmai Univ, Maharaj Nakorn Chiangmai Hosp, Chiang Mai, Thailand., [Khwannimit, B.] Prince Songkla Univ, Hat Yai, Thailand., [Theerawit, P.] Ramathibodi Hosp, Bangkok, Thailand., [Pornsuriyasak, P.] Ramathibodi Hosp, Somdech Phra Debaratana Med Ctr, Bangkok, Thailand., [Piriyapatsom, A.] Mahidol Univ, Siriraj Hosp, Bangkok, Thailand., [Mukhtar, A.] Cairo Univ, Giza, Egypt., [Dsicu] Demerdash Surg Intens Care Unit, Cairo, Egypt., [Hamdy, A. Nabil] Ain Shams Fac Med, Cairo, Egypt., [Hosny, H.] Zaitoun Specialized Hosp, Cairo, Egypt., [Ashraf, A.] Gums, Tehran, Iran., [Mokhtari, M.] Sbums, Imam Hossein Hosp, Tehran, Iran., [Nowruzinia, S.] Imamreza Hosp, Mashhad, Razavi Khorasan, Iran., [Lotfi, A.] Laleh Hosp, Tehran, Iran., [Zand, F.] Shiraz Anesthesiol & Crit Care Res Ctr, Shiraz, Iran., [Nikandish, R.] Shiraz Univ Med Sci, Shiraz, Iran., [Moghaddam, O. Moradi] Tehran Med Sci Univ, Tehran, Iran., [Cohen, J.] Rabin Med Ctr, Petah Tiqwa, Israel., [Sold, O.] Sourasky Tel Aviv Med Ctr, Tel Aviv, Israel., [Sfeir, T.] Ctr Hosp Nord, Ettelbruck, Luxembourg., [Hasan, A.] Sohar Hosp, Sohar, Oman., [Abugaber, D.] Specialized Arab Hosp, Nablus, Palestine., [Ahmad, H.] Almana Gen Hosp, Khobar, Saudi Arabia., [Tantawy, T.] KFSHRC, Riyadh, Saudi Arabia., [Baharoom, S.] King Abdulaziz Med City Riyadh, Riyadh, Saudi Arabia., [Algethamy, H.] King Abdulaziz Univ, Jeddah, Saudi Arabia., [Amr, A.] King Saud Med City, Riyadh, Saudi Arabia., [Almekhlafi, G.] Riyadh Mil Hosp, Riyadh, Saudi Arabia., [Coskun, R.] Erciyes Univ, Med Fac, Kayseri, Turkey., [Sungur, M.] Erciyes Univ, Med Sch, Kayseri, Turkey., [Cosar, A.] Gulhane Mil Med Acad, Ankara, Turkey., [Gucyetmez, B.] Int Hosp, Istanbul, Turkey., [Demirkiran, O.] Istanbul Univ, Cerrahpasa Med Sch Hosp, Istanbul, Turkey., [Senturk, E.] Istanbul Univ, Istanbul Med Fac, Istanbul, Turkey., [Ulusoy, H.] Karadeniz Tech Univ, Med Fac, Trabzon, Turkey., [Atalan, H.] Mem Atasehir Hosp, Istanbul, Turkey., [Serin, S.] Pamukkale Univ, Denizli, Turkey., [Kati, I] Yuzuncu Yil Univ, Med Fac, Van, Turkey., [Alnassrawi, Z.] Dubai Hosp, Dubai, U Arab Emirates., [Almemari, A.] Mafraq Hosp, Abu Dhabi, U Arab Emirates., [Krishnareddy, K.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates., [Kashef, S.] Tawam Hosp, Al Ain, U Arab Emirates., [Alsabbah, A.] City Hosp, Dubai, U Arab Emirates., [Poirier, G.] Hop Charles Lemoyne, Longueuil, PQ, Canada., [Marshall, J.] St Michaels Hosp, Toronto, ON, Canada., [Herridge, M.] Toronto Gen Hosp, Toronto, ON, Canada., [Herridge, M.] Toronto Western Hosp, Toronto, ON, Canada., [Fernandez-Medero, R.] San Juan Hosp, San Juan, PR USA., [Fulda, G.] Christiana Care Hlth Syst, Newark, DE USA., [Banschbach, S.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA., [Quintero, J.] El Camino Hosp, Mountain View, CA USA., [Schroeder, E.] George Washington Hosp, Washington, DC USA., [Sicoutris, C.] Hosp Univ Penn, Philadelphia, PA 19104 USA., [Gueret, R.] John H Stroger Hosp Cook Cty, Chicago, IL USA., [Kashyap, R.] Mayo Clin, CCM, Rochester, MN USA., [Bauer, P.] Mayo Clin, PCC, Rochester, MN USA., [Nanchal, R.] Med Coll Wisconsin, Milwaukee, WI 53226 USA., [Wunderink, R.] Northwestern Mem Hosp, Chicago, IL 60611 USA., [Jimenez, E.] Orlando Reg Med Ctr Inc, Orlando, FL USA., [Ryan, A.] Washington Hosp Ctr, Washington, DC 20010 USA., [Ryan, A.] Washington Hosp Ctr, 2H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 2G, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 3H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 3G, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 4H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, CVRR, Washington, DC USA., [Prince, D.] Armadale Hlth Serv, Mount Nasura, WA, Australia., [Edington, J.] Bendigo Hosp, Bendigo, Vic, Australia., [Van Haren, F.] Canberra Hosp, Canberra, ACT, Australia., [Bersten, A.] Flinders Med Ctr, Bedford Pk, SA, Australia., [Hawkins, D. J.] Joondalup Hlth Campus, Joondalup, WA, Australia., [Kilminster, M.] Lismore Base Hosp, Lismore, NSW, Australia., [Sturgess, D.] Mater Adult Hosp, South Brisbane, Qld, Australia., [Ziegenfuss, M.] Prince Charles Hosp, Brisbane, Qld, Australia., [O'Connor, S.] Royal Adelaide Hosp, Adelaide, SA, Australia., [Lipman, J.] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia., [Campbell, L.] Royal Darwin Hosp, Tiwi, NT, Australia., [Mcallister, R.] Royal Hobart Hosp, Hobart, Tas, Australia., [Roberts, B.] Sir Charles Gairdner Hosp, Nedlands, WA, Australia., [Williams, P.] Queen Elizabeth Hosp, Woodville, SA, Australia., [Parke, R.] Auckland Dist Hlth Board, Auckland, New Zealand., [Seigne, P.] Christchurch Hosp, Christchurch, New Zealand., [Freebairn, R.] Hawkes Bay Hosp, Hastings, New Zealand., [Nistor, D.] Palmerston North Hosp, Midcent Hlth, Palmerston North, New Zealand., [Oxley, C.] Middlemore Hosp, Auckland, New Zealand., [Young, P.] Wellington Hosp, Wellington, New Zealand., [Valentini, R.] Cemic, Buenos Aires, DF, Argentina., [Wainsztein, N.] Fleni, Buenos Aires, DF, Argentina., [Comignani, P.] Hosp Aleman, Buenos Aires, DF, Argentina., [Casaretto, M.] Hosp Cent San Isidro, Buenos Aires, DF, Argentina., [Sutton, G.] Hosp Fernandez, Buenos Aires, DF, Argentina., [Villegas, P.] Hosp Francisco Lopez Lima Area Programa Gen Roca, Gen Roca, Argentina., [Galletti, C.] Sanatorio Allende, Cordoba, Argentina., [Neira, J.] Sanatorio Trinidad Palermo, Buenos Aires, DF, Argentina., [Rovira, D.] Sanatorio Julio Corzo Rosario, Rosario, Santa Fe, Argentina., [Hidalgo, J.] Karl Heusner Mem Hosp, Belize City, Belize., [Hidalgo, J.] Belize Healthcare Partner, Belize City, Belize., [Sandi, F.] Hosp Obrero 1, La Paz, Bolivia., [Caser, E.] Cias Unimed Vitoria, Vitoria, ES, Brazil., [Thompson, M.] Evangelical Hosp Cachoeiro De Itapemirim, Cachoeiro De Itapemirim, Brazil., [D'agostino Dias, M.] Hosp 9 Julho, Sao Paulo, Brazil., [Fontes, L.] Hosp Alcides Carneiro, Petropolis, Brazil., [Lunardi, M.] Hosp Clin Luzia De Pinho Melo, Mogi Das Cruzes, Brazil., [Youssef, N.] Hosp Nacoes Curitiba, Curitiba, Parana, Brazil., [Lobo, S.] Hosp Base Famerp, Sao Jose Do Rio Preto, Brazil., [Silva, R.] Hosp Clin Niteroi, Niteroi, RJ, Brazil., [Sales Jr, J.] Hosp Clin Padre Miguel, Rio De Janeiro, Brazil., [Madeira Campos Melo, L.] Hosp Terapia Intens, Sao Paulo, Brazil., [Oliveira, M.] Hosp Trabalhador, Curitiba, Parana, Brazil., [Fonte, M.] Hosp Esperanza, Olinda, PE, Brazil., [Grion, C.] Hosp Evangel Londrina, Londrina, Brazil., [Feijo, C.] Hosp Geral Fortaleza, Fortaleza, Ceara, Brazil., [Rezende, V] Hosp Geral Roraima, Boa Vista, Brazil., [Assuncao, M.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil., [Neves, A.] Hosp Mater Dei, Belo Horizonte, MG, Brazil., [Gusman, P.; Dalcomune, D.] Hosp Meridional, Cariacica, ES, Brazil., [Teixeira, C.] Hosp Moinhos Vento, Porto Alegre, RS, Brazil., [Kaefer, K.] Hosp Municipal Ruth Cardoso, Balneario, Brazil., [Maia, I] Hosp Nereu Ramos, Florianopolis, SC, Brazil., [Souza Dantas, V] Hosp Pasteur, Rio De Janeiro, Brazil., [Costa Filho, R.] Hosp Pro Cardiaco, Rio De Janeiro, Brazil., [Amorim, F.] Hosp Reg Samambaia, Brasilia, DF, Brazil., [Assef, M.] Hosp Reg Hans Dieter Schmidt, Joinville, Brazil., [Schiavetto, P.] Hosp Santa Casa Campo Mourao, Campo Mourao, PR, Brazil., [Houly, J.] Hosp Santa Paula, Sao Paulo, SP, Brazil., [Houly, J.] Hosp Santapaula, Sao Paulo, Brazil., [Bianchi, F.] Hosp Sao Jose Avai, Itaperuna, RJ, Brazil., [Dias, F.] Hosp Sao Lucas Pucrs, Porto Alegre, RS, Brazil., [Avila, C.] Hosp Sao Vicente Paula, Rio De Janeiro, RJ, Brazil., [Gomez, J.] Hosp Sao Vicente Paulo, Rio De Janeiro, Brazil., [Rego, L.] Hosp Saude Mulher, Belem, Para, Brazil., [Castro, P.] Hosp Tacchini, Bento Goncalves, RS, Brazil., [Passos, J.] Hosp Unimed Costa Do Sol Macae Rj, Macae, RJ, Brazil., [Mendes, C.] Hosp Univ Ufpb Joao Pessoa, Joao Pessoa, Paraiba, Brazil., [Grion, C.] Hosp Univ Londrina, Londrina, Brazil., [Colozza Mecatti, G.] Hosp Univ Sao Francisco, Braganca Paulista, SP, Brazil., [Ferrreira, M.] Santa Casa Caridade Diamantina, Diamantina, MG, Brazil., [Irineu, V] Santa Casa Misericordia Tatui, Tatui, Brazil., [Guerreiro, M.] Sao Francisco de Paula Hosp, Sao Francisco De Paula, RS, Brazil., [Ugarte, S.] Clin Indisa, Providencia, Chile., [Tomicic, V] Clin Las Lilas, Providencia, Chile., [Godoy, C.] Hosp Carlos Van Buren, Valparaiso, Chile., [Samaniego, W.] Hosp Trabajador Santiago, Santiago, Chile., [Escamilla, I] Hosp El Pino, San Bernardo, Chile., [Escamilla, I] Hosp Mutual De Seguridad, Santiago, Chile., [Castro Castro, L.] Ctr Med Imbanaco, Valle Del Cauca, Colombia., [Libreros Duque, G.] Clin Colombia Cali, Cali, Colombia., [Diaz-Guio, D.] Clin Del Cafe, Armenia, Colombia., [Benitez, F.] Clin La Estancia SA, Popayan, Colombia., [Guerra Urrego, A.] Clin Medellin, Medellin, Colombia., [Buitrago, R.] Fdn Clin Shaio, Bogota, Colombia., [Ortiz, G.] Hosp Santa Clara, Bogota, Colombia., [Villalba Gaviria, M.] Hosp Univ Fdn Santa Fe De Bogota, Bogota, Colombia., [Salas, D.] Calderon Guardia Hosp, San Jose, Costa Rica., [Ramirez-Arce, J.] Hosp Dr Rafael Angel Varlderon Guardia Ccss, San Jose, Costa Rica., [Salgado, E.] Clin La Merced, Quito, Ecuador., [Morocho, D.] Hosp Eugenio Espejo, Quito, Ecuador., [Vergara, J.] Hosp Luis Vernaza, Quito, Ecuador., [Chung Sang, M.] Shdug Sistema Hosp Docente De La Univ Guayaquil, Quito, Ecuador., [Orellana-Jimenez, C.] Gen Hosp, San Salvador, El Salvador., [Garrido, L.] Hosp Ctr Med, Guatemala City, Guatemala., [Diaz, O.] Inst Hondureno Seguro Social, La Ceiba, Honduras., [Resiere, D.] Ctr Hosp Univ Ft De France, Fort De France, Martinique, France., [Osorio, C.] Ctr Estatal Cuidados Crit, Salamanca, Mexico., [De La Vega, A.] Ctr Med Nacl 20 Noviembre Issste, Mexico City, DF, Mexico., [Carrillo, R.] Fdn Clin Med Sur, Mexico City, DF, Mexico., [Sanchez, V] Hosp San Jose TEC Monterrey, Monterrey, Mexico., [Villagomez, A.] Hosp 1 Octubre, Issste, Mexico., [Martinez Zubieta, R.] Hosp Espanol Mexico, Mexico City, DF, Mexico., [Sandia, M.] Hosp Gen Ajusco Medio, Mexico City, DF, Mexico., [Zalatiel, M.] Hosp Gen Guadalupe Victoria, Texcoco, Mexico., [Poblano, M.] Hosp Juarez Mexico, Mexico City, DF, Mexico., [Rodriguez Gonzalez, D.] Hosp Civil Guadalajara, Hspitaljuan I Menchaca, Guadalajara, Jalisco, Mexico., [Arrazola, F.; Juan Francisco, L.] Inst Mexicano Seguro Social, Mexico City, DF, Mexico., [Liamendys-Silva, S. A.] Inst Nacl Cancerol, Mexico City, DF, Mexico., [Hernandez, M.] ISSSTE Guerra Moya, Mexico City, DF, Mexico., [Hernandez, M.] Med Ctr ISSEMYM Toluca, Mexico City, DF, Mexico., [Rodriguez Cadena, D.] Mixta, Mexico City, DF, Mexico., [Lopez Islas, I.] Secretaria Salud Dist Fed, Mexico City, DF, Mexico., [Ballesteros Zarzavilla, C.] Hosp Santo Comas, Panama City, Panama., [Matos, A.] Social Secur Hosp, La Chorrera, Panama., [Oyanguren, I] Clin Anglo Amer, Lima, Peru., [Cerna, J.] Essalud, Lima, Peru., [Quispe Sierra, R.] Hosp Nacl Dos De Mayo, Lima, Peru., [Jimenez, R.] Hosp Rebagliati, Lince Dist, Peru., [Castillo, L.] Inst Nacl Enfermedades Neoplas, Surquillo, Peru., [Ocal, R.] Gulhane Med Fac, Istanbul, Turkey., [Sencan, A.] Izmir Ataturk Educ & Res Hosp, Izmir, Turkey., [Gianoni, S. Mareque] CAMS, Montevideo, Uruguay., [Deicas, A.] CASMU, Montevideo, Uruguay., [Hurtado, J.] Hosp Espanol Asse, Montevideo, Uruguay., [Burghi, G.] Hosp Maciel, Montevideo, Uruguay., [Martinelli, A.] Ctr Med Caracas, Caracas, Venezuela., [Von der Osten, I] Hosp Miguel Perez Carreno, Caracas, Venezuela., [Du Maine, C.] MSF Trauma Hosp Kunduz, Kunduz, Afghanistan., [Bhattacharyya, M.] Amri Hosp, Kolkata, India., [Bandyopadhyay, S.] Amri Hosp Salt Lake, Kolkata, W Bengal, India., [Yanamala, S.] Apollo Hosp, Hyderabad, India., [Gopal, P.] Apollo Hosp, Bangalore, Karnataka, India., [Sahu, S.] Apollo Hosp, Bhubaneswar, India., [Ibrahim, M.] Apollo Special Hosp, Chennai, Tamil Nadu, India., [Rathod, D.] Asian Heart Inst, Mumbai, Maharashtra, India., [Mukundan, N.] Baby Mem Hosp Ltd, Calicut, Kerala, India., [Dewan, A.] Batra Hosp & Mrc, New Delhi 110062, India., [Amin, P.] Bombay Hosp Inst Med Sci, Mumbai, Maharashtra, India., [Samavedam, S.] Care Hosp, Hyderabad, India., [Shah, B.] Cims Hosp, Ahmadabad, Gujarat, India., [Gurupal, D.] Columbiaasia Hosp, Mysore, Karnataka, India., [Lahkar, B.] Dispur Hosp, Gauhati, India., [Mandal, A.] Fortis Hosp, Bangalore, Karnataka, India., [Sircar, M.] Fortis Hosp, Noida, India., [Ghosh, S.] Fortis Escorts Hosp, Faridabad, India., [Balasubramani, V] Ganga Med Ctr & Hosp P Ltd, Coimbatore, Tamil Nadu, India., [Kapadia, F.] Hinduja Hosp, Mumbai, Maharashtra, India., [Vadi, S.] KDAH, Mumbai, Maharashtra, India., [Nair, K.] Kerala Inst Med Sci, RMCC, Thiruvananthapuram, Kerala, India., [Tripathy, S.] Kalinga Inst Med Sci, DTEM, Bhubaneswar, Odisha, India., [Nandakumar, S.] Kovai Med Ctr & Hosp, Coimbatore, Tamil Nadu, India., [Sharma, J.] Medanta Medic, Gurgaon, India., [Kar, A.] Med Superspecialty Hosp, Kolkata, W Bengal, India., [Jha, S.] Metro Heart Inst Multispecial, Faridabad, India., [Gurav, K. Zirpe] Ruby Hall Pune, Pune, Maharashtra, India., [Patel, M.] Saifee Hosp, Mumbai, Maharashtra, India., [Bhaysar, A.] Spandan Multispecial Hosp, Vadodara, India., [Samaddar, D.] Tata Main Hosp, Jamshedpur, Jharkhand, India., [Kulkarni, A.] Tata Mem Hosp, Mumbai, Maharashtra, India., [Hashmi, M.] Aga Khan Univ, Karachi, Pakistan., [Ali, W.] Hearts Int Hosp, Rawalpindi, Pakistan., [Nadeem, S.] Liaquat Natl Hosp, Karachi, Pakistan., [Indraratna, K.] Sri Jayewardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka., [Margarit, A.] Hosp Nostra Senyora Meritxell, Les Escaldes, Andorra., [Urbanek, P.] Akh Wien, Vienna, Austria., [Schlieber, J.] Allgemeines & Orthopad Landeskrankenhaus Stolzalp, Stolzalpe, Austria., [Reisinger, J.] Barmherzige Schwestern Linz, Linz, Austria., [Auer, U.] Gen Hosp Braunau, Braunau, Austria., [Hartjes, A.] Krankenhaus D Barmherzigen Schwestern Ried II, Ried Im Innkreis, Austria., [Lerche, A.] Krankenhaus Floridsdorf, Vienna, Austria., [Janous, T.] LK Gmund Waidhofen Thaya Zwettl, Standort Zwettl, Austria., [Kink, E.] LKH Horgas Enzenbach, Gratwein, Austria., [Krahulec, W.] LKH West, Graz, Austria., [Smolle, K.] Univ Hosp, Graz, Austria., [Van der Schueren, M.] AZ Groeninge Kortrijk, Kortrijk, Belgium., [Thibo, P.] AZ Jan Palfijn Gent, Ghent, Belgium., [Vanhoof, M.] AZ Turnhout, Turnhout, Belgium., [Ahmet, I] Bracops Anderlecht, Anderlecht, Belgium., [Gadisseux, P.] Ctr Hosp Mouscron, Mouscron, Belgium., [Dufaye, P.] CH Peltzer La Tourelle, Verviers, Belgium., [Jacobs, O.] Chirec Edith Cavell, Auderghem, Belgium., [Fraipont, V] CHR Citadelle, Liege, Belgium., [Biston, P.] CHU Charleroi, Charleroi, Belgium., [Dive, A.] CHU Mt Godinne, Yvoir, Belgium., [Bouckaert, Y.] CHU Tivoli, La Louviere, Belgium., [Gilbert, E.] CHwapi, Tournai, Belgium., [Gressens, B.] Clin St Pierre Ottignies, Ottignies, Belgium., [Pinck, E.] Clin Maternite St Elisabeth, Namur, Belgium., [Collin, V] Clin Europe St Michel, Etterbeek, Belgium., [Vincent, J. L.] Erasme Univ Hosp, Anderlecht, Belgium., [De Waele, J.] Ghent Univ Hosp, Ghent, Belgium., [Rimachi, R.] Moliere Hosp, Forest, Belgium., [Gusu, D.] Notre Dame, Brussels, Belgium., [De Decker, K.] Onze Lieve Vrouw Hosp, Aalst, Belgium., [Mandianga, K.] Ixelles Hosp, Ixelles, Belgium., [Heytens, L.] Sint Augustinus, Antwerp, Belgium., [Wittebole, X.] St Luc Univ Hosp UCL, Brussels, Belgium., [Spapen, H.] UZ Brussel, Brussels, Belgium., [Olivier, V] Vivalia Site Libramt, Libramont, Belgium., [Vandenheede, W.] VZW Gezondheidszorg Oostkust Knokke Heist, Knokke Heist, Belgium., [Rogiers, P.] ZNA Middelheim, Antwerp, Belgium., [Kolodzeike, P.] Herning Hosp, Herning, Denmark., [Kruse, M.] Hjoerring Hosp, Hjorring, Denmark., [Andersen, T.] Vejle Hosp, Vejle, Denmark., [Harjola, V] Helsinki Univ Cent Hosp, Helsinki, Finland., [Saarinen, K.] Seinajoki Cent Hosp, Seinajoki, Finland., [Leone, M.] Aix Marseille Univ, Hop Nord, Marseille, France., [Durocher, A.] Calmette Hosp, Lille, France., [Moulront, S.] Ctr Hosp Dunkerque, Dunkerque, France., [Lepape, A.] Ctr Hosp Lyon Sud, Lyon, France., [Losser, M.] CHU Nancy Brabois, Nancy, France., [Cabaret, P.] CH St Philibert, GHICL, Lille, France., [Kalaitzis, E.] CHR Dax, Dax, France., [Zogheib, E.] CHU Amiens, Amiens, France., [Charve, P.] CHU Dijon, Dijon, France., [Francois, B.] CHU Dupuytren, Limoges, France., [Lefrant, J. Y.] CHU Nimes, Nimes, France., [Beilouny, B.] Ctr Hosp Troyes, Troyes, France., [Forceville, X.] Ctr Hosp Meaux, Grp Hosp Est Francilien, Meaux, France., [Misset, B.] Grp Hosp Paris St Joseph, Paris, France., [Jacobs, F.] Hop Antoine Beclere, Clamart, France., [Floccard, B.] Hop Edouard Herriot, Lyon, France., [Payen, D.] Hop Lariboisere, AP HP, Paris, France., [Wynckel, A.] Hop Maison Blanche, Reims, France., [Castelain, V] Hop Univ Strasbourg, Strasbourg, France., [Faure, A.] Hosp Civils Lyon, Lyon, France., [Lavagne, P.] CHU Grenoble, Grenoble, France., [Thierry, I] CHU Nantes, Nantes, France., [Moussa, M.] CHRU Lille, Reanimat Chirurg Cardiovasc, Lille, France., [Vieillard-Baron, A.] Univ Hosp Ambroise Pare, Boulogne, France., [Durand, M.] Univ Hosp Grenoble, La Tronche, France., [Gainnier, M.] Univ Hosp Marseille, Marseille, France., [Ichai, C.] Univ Nice, Nice, France., [Arens, S.] Alexianer Krefeld Gmbh, Krefeld, Germany., [Hoffmann, C.] Charite Hochschulmed Berlin, Berlin, Germany., [Kaffarnik, M.] Charite, Berlin, Germany., [Scharnofske, C.] Diakoniekrankenhaus Henriettenstiftung Gmbh, Hannover, Germany., [Voigt, I] Elisabeth Krankenhaus Essen, Essen, Germany., [Peckelsen, C.] Munich Municipal Hosp Grp, Harlaching Hosp, Munich, Germany., [Weber, M.] Helios St Johannes Klin, Duisburg, Germany., [Gille, J.] Hosp St Georg Leipzig, Leipzig, Germany., [Lange, A.] Klin Hennigsdorf Oberhavel Kliniken Gmbh, Hennigsdorf, Germany., [Schoser, G.] Klin Tettnang, Tettnang, Germany., [Sablotzki, A.] Klinikum St Georg Leipzig, Leipzig, Germany., [Jaschinski, U.; Bluethgen, A.] Klinikum Augsburg, Augsburg, Germany., [Vogel, F.] Klinikum Bremen Mitte, Bremen, Germany., [Tscheu, A.] Klinikum Bremen Ost, Bremen, Germany., [Fuchs, T.] Klinikum Heidenheim, Heidenheim, Germany., [Wattenberg, M.] Klinikum Links Weser Gmbh, Bremen, Germany., [Helmes, T.] Klinikum Luedenscheid, Luedenscheid, Germany., [Scieszka, S.] Krankenhaus Neuwerk, Monchengladbach, Germany., [Heintz, M.] Marienkrankenhaus Schwerte, Schwerte, Germany., [Sakka, S.] Med Ctr Cologne Merheim, Cologne, Germany., [Kohler, J.] Schwarzwald Baar Klinikum Villingen Schwenningen, Villingen Schwenningen, Germany., [Fiedler, F.] St Elisabeth Krankenhaus Koln Hohenlind, Cologne, Germany., [Danz, M.] St Martinus Hosp Olpe, Olpe, Germany., [Sakr, Y.] Uniklinikum Jena, Jena, Germany., [Riessen, R.] Univ Klinikum Tubingen, Tubingen, Germany., [Kerz, T.] Univ Med Mainz, Mainz, Germany., [Kersten, A.] Univ Hosp Aachen, CPACC, Aachen, Germany., [Tacke, F.] Univ Hosp Aachen, DMIII, Aachen, Germany., [Marx, G.] Univ Hosp Aachen, OIC, Aachen, Germany., [Volkert, T.] Univ Hosp Muenster, Munster, Germany., [Schmutz, A.] Univ Med Ctr Freiburg, Fr

Published
2019

32. Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas

Author

Fulvio Cruciani, Marco Rosario Capodiferro, Ugo A. Perego, Viola Grugni, Luca Ferretti, Maribel Tribaldos, Alessandro Achilli, Alessandro Raveane, Giulia Colombo, Ornella Semino, Vincenza Battaglia, Scott R. Woodward, Jorge Motta, Beniamino Trombetta, Antonio Torroni, Linda Ongaro, and Anna Olivieri

Subjects
Genetics and Molecular Biology (all), Mesoamerica, Physiology, Human Y-chromosome variation, Haplogroup Q phylogeny, Plant Science, Biochemistry, Haplogroup, Origin of Eurasians, Origin of Native Americans, Peopling of the Americas, Biotechnology, Structural Biology, Ecology, Evolution, Behavior and Systematics, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Developmental Biology, Cell Biology, 0302 clinical medicine, lcsh:QH301-705.5, Holocene, Phylogeny, 0303 health sciences, education.field_of_study, Ecology, Population size, Europe, Gene pool, General Agricultural and Biological Sciences, Research Article, Evolution, Population, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, White People, 03 medical and health sciences, Behavior and Systematics, Population growth, Humans, education, 030304 developmental biology, Chromosomes, Human, Y, Haplotype, Genetic Variation, Genetics, Population, Haplotypes, lcsh:Biology (General), Evolutionary biology, Indians, North American, Americas, 030217 neurology & neurosurgery
Abstract

Background Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America. Results Our analyses of 1.5 Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a “coastal and inland routes scenario” for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe. Conclusions We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples. Electronic supplementary material The online version of this article (10.1186/s12915-018-0622-4) contains supplementary material, which is available to authorized users.

Published
2019

33. Assessing temporal and geographic contacts across the Adriatic Sea through the analysis of genome-wide data from Southern Italy

Author

Alessandro Raveane, Ludovica Molinaro, Serena Aneli, Marco Rosario Capodiferro, Luciana de Gennaro, Linda Ongaro, Nicola Rambaldi Migliore, Sara Soffiati, Teodoro Scarano, Antonio Torroni, Alessandro Achilli, Mario Ventura, Luca Pagani, Cristian Capelli, Anna Olivieri, Francesco Bertolini, Ornella Semino, and Francesco Montinaro

Subjects
Ancestry, aDNA, Genome, Human, Genetic population structure, Iran, Archaeology, Italy, Mediterranean Area, Population genomics, Selection, Genetics, Humans, DNA, Ancient
Abstract

Southern Italy was characterised by a complex prehistory that started with different Palaeolithic cultures, later followed by the Neolithization and the demic dispersal from the Pontic-Caspian Steppe during the Bronze Age. Archaeological and historical evidences point to a link between Southern Italians and the Balkans still present in modern times. To shed light on these dynamics, we analysed around 700 South Mediterranean genomes combined with informative ancient DNAs. Our findings revealed high affinities of South-Eastern Italians with modern Eastern Peloponnesians, and a closer affinity of ancient Greek genomes with those from specific regions of South Italy than modern Greek genomes. The higher similarity could be associated with a Bronze Age component ultimately originating from the Caucasus with high Iranian and Anatolian Neolithic ancestries. Furthermore, extremely differentiated allele frequencies among Northern and Southern Italy revealed putatively adapted SNPs in genes involved in alcohol metabolism, nevi features and immunological traits.

Published
2022

34. Surgical Approach to Transverse Colon Cancer: Analysis of Current Practice and Oncological Outcomes Using the National Cancer Database

Author

Courtney N. Day, Kellie L. Mathis, Giulio M. Mari, Kevin T. Behm, Pietro Achilli, David W. Larson, Jacopo Crippa, William S. Harmsen, and Fabian Grass

Subjects
Male, medicine.medical_specialty, Databases, Factual, Treatment outcome, Adenocarcinoma, Patient Readmission, 03 medical and health sciences, 0302 clinical medicine, medicine, Overall survival, Humans, Postoperative Period, Practice Patterns, Physicians', Colectomy, Aged, Neoplasm Staging, Retrospective Studies, Gynecology, Aged, 80 and over, Surgical approach, Practice patterns, business.industry, Gastroenterology, Cancer, Margins of Excision, General Medicine, Length of Stay, Middle Aged, medicine.disease, Survival Rate, Treatment Outcome, Current practice, 030220 oncology & carcinogenesis, Case-Control Studies, Colonic Neoplasms, Adenocarcinoma/diagnosis, Adenocarcinoma/surgery, Colectomy/methods, Colectomy/trends, Colon, Transverse/pathology, Colonic Neoplasms/mortality, Colonic Neoplasms/surgery, Female, Length of Stay/statistics & numerical data, Neoplasm Staging/methods, Patient Readmission/statistics & numerical data, Practice Patterns, Physicians'/statistics & numerical data, Practice Patterns, Physicians'/trends, Survival Rate/trends, 030211 gastroenterology & hepatology, Transverse colon cancer, business, Colon, Transverse
Abstract

BACKGROUND Surgical treatment for transverse colon cancer involves either extended colectomy or segmental resection, depending on the location of the tumor and surgeon perspective. However, the oncological safety of segmental resection has not yet been established in large cohort studies. OBJECTIVE This study aims to compare segmental resection versus extended colectomy for transverse colon cancer in terms of oncological outcomes. DESIGN This was a retrospective cohort study. SETTINGS This study was conducted using a nationwide cohort. PATIENTS A total of 66,062 patients who underwent colectomy with curative intent for transverse stage I to III adenocarcinoma were identified in the National Cancer Database (2004-2015). MAIN OUTCOME MEASURES Patients were divided in 2 groups based on the type of surgery received (extended versus segmental resection). The primary outcome was overall survival. Secondary outcomes were 30- and 90-day mortality, length of hospital stay, and readmission rate within 30 days of surgical discharge. RESULTS Extended colectomy was performed in 44,417 (67.2%) patients, whereas 21,645 (32.8%) patients underwent segmental resection. Extended colectomy was associated with lower survival at multivariate analysis (HR, 1.07; 95% CI, 1.04-1.10; p < 0.001). The subgroup analysis showed that extended resection was independently associated with poorer survival in mid transverse colon cancers (HR, 1.08; 95% CI, 1.04-1.12; p < 0.001) and in stage III tumors (HR, 1.11; 95% CI, 1.04-1.18; p < 0.001). The number of at least 12 harvested lymph nodes was an independent predictor of improved survival in both overall and subgroup analyses. LIMITATIONS This study was limited by its retrospective design. CONCLUSION Extended colectomy was not associated with a survival advantage compared with segmental resection. On the contrary, extended colectomy was associated with slightly poorer survival in mid transverse cancers and locally advanced tumors. Segmental resection was found to be safe when appropriate margins and adequate lymph node harvest were achieved. See Video Abstract at http://links.lww.com/DCR/B454. ABORDAJE QUIRRGICO DEL CNCER DE COLON TRANSVERSO ANLISIS DE LA PRCTICA ACTUAL Y LOS RESULTADOS ONCOLGICOS UTILIZANDO LA BASE DE DATOS NACIONAL DE CNCER ANTECEDENTES:El tratamiento quirurgico para el cancer de colon transverso implica colectomia extendida o reseccion segmentaria, segun la ubicacion del tumor y la perspectiva del cirujano. Sin embargo, la seguridad oncologica de la reseccion segmentaria aun no se ha establecido en estudios de cohortes grandes.OBJETIVO:Este estudio tiene como objetivo comparar la reseccion segmentaria versus la colectomia extendida para el cancer de colon transverso en terminos de resultados oncologicos.DISENO:Este fue un estudio de cohorte retrospectivo.ESCENARIO:Este estudio se realizo utilizando una cohorte a nivel nacional.PACIENTES:Un total de 66,062 pacientes que se sometieron a colectomia con intencion curativa por adenocarcinoma de colon transverso en estadio I-III fueron identificados en la Base de Datos Nacional del Cancer (2004-2015).PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes se dividieron en dos grupos segun el tipo de cirugia recibida (reseccion extendida versus reseccion segmentaria). El resultado primario fue la supervivencia global. Los resultados secundarios fueron la mortalidad a los 30 y 90 dias, la duracion de la estancia hospitalaria y la tasa de reingreso dentro de los 30 dias posteriores al alta quirurgica.RESULTADOS:Se realizo colectomia extendida en 44,417 (67.2%) casos, mientras que 21,645 (32.8%) pacientes fueron sometidos a reseccion segmentaria. La colectomia extendida se asocio con una menor supervivencia en el analisis multivariado (HR 1.07 IC 95% 1.04-1.10; p

Published
2021

35. Anti-pesticide DNA aptamers fail to recognize their targets with asserted micromolar dissociation constants

Author

Eric Peyrin, Silvia Achilli, Jean-Jacques Toulmé, Lorena Zara, Emmanuelle Fiore, Benoit Chovelon, and Corinne Ravelet

Subjects
Analyte, Aptamer, 02 engineering and technology, Biosensing Techniques, Dissociative Disorders, 01 natural sciences, Biochemistry, Analytical Chemistry, Transduction (genetics), chemistry.chemical_compound, Environmental Chemistry, Humans, Pesticides, Spectroscopy, Oligonucleotide, Chemistry, 010401 analytical chemistry, Isothermal titration calorimetry, DNA, Aptamers, Nucleotide, 021001 nanoscience & nanotechnology, Combinatorial chemistry, 0104 chemical sciences, 0210 nano-technology, Biosensor, Fluorescence anisotropy
Abstract

Herein, we originally aimed at developing fluorescence anisotropy biosensor platforms devoted to the homogeneous-phase detection of isocarbophos and phorate pesticides by using previously isolated DNA aptamers. To achieve this, two reporting approaches displaying very high generalizability features were implemented, based on either the complementary strand or the SYBR green intercalator displacement strategies. Unfortunately, none of the transduction methods led to phorate-dependent signals. Only the SYBR green displacement method provided a small output in the presence of isocarbophos, but at an analyte concentration greater than 100 μM. In order to identify the origin of such data, isothermal titration calorimetry (ITC) experiments were subsequently performed. It was shown that aptamers bind neither isocarbophos nor phorate in free solution with the claimed micromolar dissociation constants. This work puts forward some doubts about the previously described aptasensors that rely on the use of these functional DNA molecules. It also highlights the need to carefully investigate the binding capabilities of aptamers after their isolation and to include appropriate control experiments with scrambled or mutated oligonucleotides.

Published
2021

36. Prevalence of diabetic and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities

Author

H Appeltants, C Boesch, I Cromarty, D Carretta, S Romanov, U Windstetter, F Mibach, Jens Refsgaard, S Lebedev, F Proietti, M Y Tamimi, M C Gamboa, M Novikova, E Prada, K H Sim, E Messas, E Zherlitsyna, A Kalampalikis, N Nevolina, N Trocan, J Cohen, G Szto, R Gilabert Gómez, M Omelchenko, A Pinzani, D Goodwin, J Umaran Sánchez, Kim Fox, S H Dong, K Kronberg, E Castillo Lueña, T Ignatieva, S Joubert, C Macchi, S Lee, S Eidelman, F Alizon, S Chandra, M Akbar, D M Colquhoun, G Yanes Bowden, J de Juan Baguda, M Sebastian, C Wernham, K Miedema, R La Greca, C Morton, B S Jheeta, A C Tran, T Q Do, O Rodrigues, J Yan, S H Kim, R Jurgaitienė, Jean-Claude Tardif, R Baleón, D Hay, V Hennebelle, F Fazekas, R Davies, P Gratia, L Sorodoc, S Y Wu, C Martínez Sánchez, L Lopes Antunes, T H T Pham, I Suliman, M J Gómez Martinez, A Pernat, S H Hur, M Alanazy, L Zhabina, M Stanley, J Rogers, Y J Kim, S Geffroy, L K Andersen, S Coman, V Pedrosa del Moral, Y Garaud, J Krupicka, O Dzhkha, C Paul, M Jeżewska, B Mahler Mioto, V Abduvalieva, P Morra, L Kucheryava, C La Rosa, B Chan, M Wrębiak-Trznadel, A Kozlowski, M Sharif, L López Barreiro, V Kolesnikov, M Lawrence, A Tucker, C Okawabata, B La Hay, E Sadauskienė, B K Nguyen, L Bui, A Said, M E Ruíz Esparza, R K Saran, M S C Ho, E Homs Espinach, J R Romo Santana, J Forte De Carvalho, I Pattison, H H Phan, L Baleeva, L Kisiel, A López Granados, C Raters, F Paganelli, R Haberl, A P T Wong, D Xu, R Jagathesan, L Grekhova, H Stursova, Q B Truong, P Raymond, Y Sosnova, N H Khong, J Zarauza Navarro, C Florescu, L Gorshkova, N Saaidin, E Gordillo Higuero, L Davin, I Budanova, C Lavicka, L Gruznykh, P Bogdański, A Dufka, I Arroja, H A R Tahir, G Wilson, G Kolios, S J Yoon, Simon Cattan, K Berdnik, A Serrano, B Sievers, A Rodríguez Almodóvar, L A Holden, F O'Reilly, D Verleyen, H Hafez, K Nehrig, S M Kang, S Berrisch-Rahmel, E Meyer-Michael, P Samama, L Soares, A K Nguyen, F Tuktarova, C Weytjens, E Sandoval Rodriguez, J Cheng, F M Villasenor, João Morais, B Sullivan, R Zimoląg, Albert V. Smith, S F Ding, J C Louchart, G Guardigli, R Furtak, P Azzolini, S Chushak, J L Delgado Prieto, S Kornienko, K K Sia, J H Shin, F Baylac Domengetroy, P Błaszczak, M Saade, N Černič-Šuligoj, K Coetzee, A Kadleckova, V Scollo, O Larina, R Pal, M M Singh, N Nosova, R Burns, B S Yoo, O Gukov, F Massari, V Antia, A Brattström, G Holt, M Scherbak, V Firastrau, Y J Li, E Mikhailova, L Machado Cesar, C García García, J Pjontek, C Everton Biglow, G Pes, C Brown, A Bumbu, S Felis, R Bosch, M Lazaro, Luigi Tavazzi, R Engel, I Romeo Castillejo, Y S Byun, F Matias, I Grushetskaya, C Mestre-Fernandes, T Kheliya, S Schlesingerova, G Theodorakis, I Tsamopoulos, R Pedretti, A Puente Barragán, M P Vo, B Lammens, T Carruthers, J S Bhatt, A Khodanov, N Pasechnaya, I Petrova, G Boutros, I A Khan, E Le Moal, D Garofalo, H R Malaterre, A Bahal, J F Martínez González, H N Dinh, N V Pham, C Barjhoux, I Gilmour, C Soriano Navarro, O D Chioncel, K Tóth, N Borodina, P Khanoyan, B Sevilla Toral, H H Kim, C M A Bui, C Dernedde, N Eliseeva, M Galinier, E Kosachek, M M Doohan, L Potapska, M Tennekoon, R Nourallah, L Perez De Isla, K H Chee, E Panova, D M Walker, G Glanowska, G Hua, A Silvestre, W Wang, Matthew A. 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Velez Edwards, A Buakhamsri, N Bazargani, U Spengler, M Toringhibel, M A Matos, I Skoczylas, V Arrarte Esteban, J Fuertes Beneitez, V Gil, L U P Tran, A Mehta, A Álvarez Sangabriel, P Di Pasquale, K Egstrup, P Choudhury, S Whetstone, T S Chee, M Elkohen, P Martina, J Martínez Rivero, C Arden, J Walczewska, I Benett, R Silvestri, V García Saavedra, J Słaboszewska, A Thomson, S Revienė, A Szpak, V Challenor, F Saporito, P Ruiz Pérez, Vives, H M Li, I Sadykova, D Lawton, T Kuzmina, R Elias, D Troup, P Dehayes, J Vavougios, V Pernice, P Tanielian, R Cabrera Solé, T Pitsch, R Nethononda, P Poinson, A Tavares E Taveira, J Yi-MingCha, J Y Hwang, T Haghfelt, C García Pindado, N Bilous, A Kotsalos, M Bariaud, A Drzewiecka, L Polkina, V Arfaras, P Vymetal, J Rawal, A Aumjaud, H P Wang, L Wu Amen, J Fernandes, F Howie, A Ouguoujil, M H Ngo, J A Bertarini, A Malysheva, G De Geeter, N Aimouch, R Parkin, H Taylor, M Kittipovanonth, A Gupte, S Ramanaidu, L Basto, A Zherebtsova, T Arsentieva, V Männl, Y L Cham, J J Gómez Doblas, D Ennouchi, Iveta Mintale, A Vance, R Jirmar, L Boikova, D T Le, P Srivastava, L Tonet, M Liautard, C Proto, Q H Do, Mª A Pérez Martínez, R Stankevičius, L Semedo, M Anghel, I Nikolaeva, J Janes, H Al-Backer, M C Escourrou Berdou, O Leshchuk, D Reshotko, V P Dang, I Édes, L Schlueter, B Sikorska-Buczkowska, K Hatalova, I Marozsán, S Gessner, J Gmehling, M Kuzmicheva, Z Huang, L Kosareva, D K Kumbla, A Baika, F El-Shaer, T Voronova, J M Chopo Alcubilla, A Veternik, S Mohr, D Garcia, J Y Rhew, C K Yeo, C De Niel, H K N Nguyen, E Orts Soler, J Dubrava, S Natarajan, M S H Khan, U Kossowska, J P Detienne, T T H Nguyen, I Centa, M G Millauer, Jose Lopez-Sendon, J T Counsell, E Galehr, T Schröder, L Frost, P P Singh, C Moya López, R Beyer, L Carpentier, J Carrillo Calvillo, Z M Du, R Steeds, E Horstkotte, P Kindler, P Johnson, M Sander, I Rodríguez Tejero, F Azar Manzur, S Brown, M Odín de los Ríos Ibarra, C K Choor, M A Sadiq, D B Gysan, V B Doan, A Gueusquin, M Andrews, L L Feng, B Martina-Hooi, S R Shetty, Y Dascotte, E T Ch'ng, P Dematteo, A Woodall, S Gabriilidis, Jean Ferrières, S K Oh, J Lindford, S Blignaut, L Macedo, R Carrillo Cardoso, Y C Lai, C Lang, S R Jayasinghe, B Bastian, V Sanfins, J de Jeús Zuñiga, F X Meriaux, G Sepp, S Molotyagina, S García Ortego, T Perger, Y Lukina, J H Wirtz, A Regulska, P Durand, P Loheac, J Sinnadurai, S Avlonitis, J García-Moll Marimón, J Bradley, K Pareathumby, L Latyntseva, D Stergiou, K Ling, S K Hong, N S Chonkar, C Goldie, C C Koo, A Salustri, Y Peneva, I Rodríguez Briones, P Ferreira, L Franskyavichene, G Bragança, C Rodrigues, S H Lee, L Dang, B J Lubelsky, L Weinrich, E Hoffer, J Tricoire, M Marachli, O Smirnova, C Falces Salvador, A Mobeirek, M Fagan, A Serazhim, M M W Yeung, F Petitjean, I Cullen, J Benacka, Yañez Wonenburger, D Gentille Lorente, J Ferreira Dos Santos, F Bosa Ojeda, N Marchionni, L Brottier, P Keelan, D Kerö, L Moretti, R Seabra Gomes, I Jasinkevica, P Purnode, D Relange, H N Luqman, A Petit, I Hamilton-Craig, E Kochurov, P Berry, P Aguar Carrascosa, M Noble, S Yvorra, N Razzaq, J M Walch, L Lenartowska, R Sethi, W Kim, C Killeen, S Kurochkina, N Capuano, P Sampson, K H Mak, T Bouchaya, J Hellermann, M Geneves, F Ramos Ariznabarreta, J L Mougeolle, J Ferreira, T Roy, J de Andrés Novales, J F Monteiro Ferreira, M S Mayer, N Lopez Cabanillas, P Touzet, K H Ng, F Pelier, T K Huynh, J Schindler, T Krechunova, A Gaglione, Z Fras, P Haralambus, R Pradhan, L P Low, G Odent, M Sidor, R Sopia, D Janody, T K Ong, K Adamaszek, G Vives Boniato, T Maxwell, H Charles, D Gough, O Dibon, A A Abdul Rahim, H B Liew, S Tikhonova, I Bläse, J Chambel De Aguiar, E Santas Olmeda, M Rosseel, R Angela, D Savard, C Cernetti, O Huttin, J Calder, O Kilaberiya, A Elkrail, I I Tulevski, A Ilyukhina, E Chalkiadakis, R Antonicelli, H C Gwon, G Bautista López, G Brown, J Kojelienė, R Zeitouni, J Mimoso, N Better, N H Vu, H Abdel Wahab, B Poprawa, F Weber, A Ghicu, K Rybak, G Fouquet, C Pindado Rodríguez, A Salakhova, L Isaeva, M H Fallacher, J Placke, G McCansh, V D Tran, O Gusev, D Enayat, P Khera, E Brice, G Levesque, A Alvarez Auñon, M A Arnau, M A López Aranda, E Andreicheva, I Kruck, R Grigoriu, I Sainz Hidalgo, M Węglarz, A Ajani, I Khudina, T Makhieva, V D Dang, R Testa, E Cisowska-Drozd, F Giacomazzi, R Cierpka, Nicola Greenlaw, P Wong, L Simões, L Tsaryabina, O Gureeva, R Raffelsberger, H Luquez, A Rainbird, D Evéquoz, M A Balice-Pasquinelli, R Massay, K L Joseph, I H Chae, R Herrmann, I Salecker, A Montero Gaspar, P F Fonseca, A Martin, W Czarnecki, R Motomancea, E Dechoux, M Shamsuzzaman, M Leandri, D Marzal Martín, C Navas Navas, C Beaurain, T Gkinis, K Shetty, P A Jeannerat, D S Wong, A Gonzaga, W Kulig, J F Millet, E Jankauskienė, E Anastasiou, A I Ruhani, N Aksyutina, O Kolesova, K Yared, M Panajatovic, Y L Zhou, S Thurston, T Alekseeva, S Preston, N Mai, M Kuzyakina, D Rechtman, T Boonyasirinant, J Nobre Dos santos, A Ahuad Guerrero, M Al-Shamiri, M Feldner-Busztin, S Godart, S Liandrat, A Narayan, L Burlakova, M J García Martínez, C Militaru, J Chávez Paez, H B Matheson, D Meddah, P Brindle, N Petrova, A Nicolino, D Spensieri, A Giuca, E Molina Laborda, J Moreno Arribas, V Martinho, T Mularek-Kubzdela, S K Chua, G A Dan, N T H Tu, V T Nguyen, M Alcocer Gamba, J Costa, H Milligan, R Badr-Eslam, E Variava, A Merkhi, C Mays, R De Castro Aritmendiz, A K Mohamed Yusof, A Hamer, R McNeilly, S Dedkova, D Rousson, K Chamou, A Mahr, D C Dan, R Till, T L Yang, M Vida Gutiérrez, D Piyayotai, É Bajcsi, D Zaronskienė, I Alexopoulos, Y Huo, H S Zeng, P Rowe, S Fleming, D B Vu, Á Dongó, C Hand, J C S Leong, M Claeys, S Hood, J Bozkova, G Vieyra, G Unger, A Liqui-Lung, D Cremer Luengo, M Castillo Orive, S Muth, M Joseph, P L Torres Díaz, C Zakopoulos, D Cross, F Trujillo Berraquero, F Sattar, H A Boyrazian, T B Le, M Mantcheva, M Constantinescu, P Gosse, U Keil, G F Vaz, M Bdeir, T S Pham, M J García González, J K Ryu, D W Jeon, Zs Malkócs, J Á Perea Egido, R Izquierdo González, V Probst, E Wellenkamp, C Boureux, M Czarnecka, C Vaughan, H Falconer, H Brunner, G Peña Pérez, E Nelböck-Huber, E Blanc, F Thomas-Richard, A L R Ng, M Provvidenza, R Gascueña Rubia, J Freitas, A Dabboura, B Mörz-Proszowski, A Utech, C Alves, C M David, J A Lastra Galán, L Oliveira, T A Nguyen, I Ghaly, A Hofmeister, I Gorodilova, P Szałkowski, M S Hiremath, G Golovina, C Daly, M Tardy, S Kostomarova, J-P Salembier, P Zagožen, D Wang, M Vogel, J Borbola, I Chlewicka, K-H Schmitz, C Pappas, J Victory, M Garandeau, P Wiggers, C Piñero Ramírez, L Tkhorzhevskaya, E Suglobova, V Samakhovets, P Surmont, H A Ramírez Reyes, M Winter, F Prunier, B Cavert, B Salaun, J M Roca Catalán, A Beinhauer, Ian Ford, K Elsby, V Knyazeva, C Tamburino, V Khoury, A Felice Castro Issa, B Marchenko, K König, A Kennedy, J M Alegret Colomer, T Gillet, Clarify Investigators, B Maheu, A Troncoso Gil, N Haldane, B Koujan, T Mouhat, A Waldman, J Robert, J Campbell, A Kokis, M Micheals, P Gori, P Ramoutar, M Al Zaibag, V Ryzhkova, M Kazakovtseva, C Bernardeau, B Ferreiro Rodríguez, Y Voloshko, S Szabo, I Jarvis, Y N Ke, J Donetti, A Serrano-Garcia, R Ketelers, S Grigoryan, V Kulik, P Zündorf, L Kleemann, J McPherson, M Luaces Méndez, F Mouquet, L G Xiong, T H Tran, P Costello, A Potter, M Cinteza, F Colivicchi, E Nowicka, O Greiner, G Reddy, M Martins Oliveira, F Fernandes De Sousa, P Nocon, R Sewell, I Nikodemska, R Tadeu Munhoz, T Gilbert, I Laizane, M Maroun, B Demianiuk, A Bolidai, R Kacorzyk, R Fernández Mouzo, K Karastanev, J Blanco Castiñeiras, P Messali, R Schwarz, M Vardhani, O Gouli, C Thelemann, A Forclaz, G Khaznadar, G Eisele, P Sosner, M L Bourachot, N Pontikakis, S Heinemann-Meerz, E Zatsarina, E Smrckova, P Calmettes, D H Kang, M L Santos Iglesias, S M Marinescu, A Heap, Melnikova, N F Strathmore, S Tolpygina, M Yang, M Naisseh, E George, J Banach, E Delcoulx, E Teijeira Fernández, J Poles, P Saunders, S Haddad, T Q Luu, A Dhesi, O Prikolota, M Baar, P Lafontaine, C O'Dong, I Petropoulos, B-M Altevogt, D Warden, T De Backer, G Miñana Escrivá, T L Mai, U Schlesinger-Irsch, M M Gomaa, E Moksyuta, M Drexler, P Monteiro, P Grooterhorst, J Moolman, P McAlavey, J O'Shea, L P Quinn, F Crespo, K Srinivasa Reddy, T Shokina, Ellen M. Schmidt, M H Jeong, K Denef, A Pleskof, I Takács, Y Tikhonov, O Ushakov, L Stevens, J Ezcurdia Sasieta, L Nkombua, O Henne Otero, J Y Fraboulet, D S Kim, G Hoh, A Tamm, M Sardon, G Chatzioakim, M A Ulecia Martínez, S Reymond, M Myint, G Proença, R Massabie, E Foster, H Dougall, Anjan Kumar Roy, C Franco Aranda, M Getman, E Filippova, C Aguiar, X D Pu, N Voronina, L L Chen, M Szulc, L Bayakhchan, M J Pinto Vaz, C Niederberger, N Vites, I Sen, Paul R. Kalra, J A Castillo Moreno, W K Ng, C Brunschwig, D Morgan, A Concepción Clemente, N Yakimova, J M Guy, A H Jaafar, J Badarienė, N Taylor, L Compson, R Amor, A Maximovitch, J L Bardají Mayor, E Marín Araez, N H Chau, N Srtumilenko, K Kelly, A Papathanasioy, S Erofeev, B Mamez, A Ribeiro, M Micko, N Alvarenga Recalde, K Atueva, Z Sebõk, P Kycina, A K Gupta, A Laucevičius, R Ahuja, A Prokop, P Stadler, S De Ridder, L Zhang, F B Ramadan, L Kapustina, V Fedoskin, A Bateman, C A Nacht, R Musetescu, M Aparici Feal, A Büttl, S Ross, M Rau, P Federico Zaragoza, G Brisson, M Zagreanu, T T H Pham, F Dominé, N Davydova, N Petrochenko, N Paul, P H Truong, S Frickel, W Bryl, G Brouillette, A Stumpp, M Barrera Bustillos, C Ziccarelli, O Zalyzniak, M eatherhead, N Watkins, G Riccioni, l Kudryavtsev, R Carvalho, J P S Sawhney, V González Toda, P Matos Dias, M Giorgadze, I Rodriguez Marrero, W Gritsch, K Lee, G W Kellam, I Parker, V Ecina, Mª I Soto Ruiz, C Delhomme, T Ivaschenko, Y W Cheah, I Grudtsina, R Chehayeb, T Dookie, O Krasnoslobodskaya, P Jarmużek, F Van den Branden, A M F Vandeplas, A Rocha De Almeida, M Espiga De Macedo, E Łotocka, K Nagy, R Paliulionienė, J L Leyva Pons, N Fedorova, Y Yanina, O Stasuk, Z Vlasuk, P Lim, P Egloff, T Berezhna, A Faria, J Cerda Rojas, E Moser, H G Jin, S J Oh, G Arquero García, K H Karner, I Leontaridis, A Banikova, J Fridrich, H Lesseliers, I Pokrovskaya, P Astridge, H Abdul Manap, R Daniel, C A Almeida Fernández, A Nowowiejska-Wiewióra, B Carvalho De Moura, M Malden, H Rosenstein, S Dixon, G Balogh, M Adam-Blanpain, A Sandalian, H Gervas Pavón, G A Antoniadis, N Naberezhnova, A Amlaiky, P Terrosu, K K H Lau, B Chartier, X Su, O Kovyrshyna, G Beale, P Primot, M H Chen, S S Ramesh, R Chyrek, E Gómez Álvarez, J Rodríguez Collado, G Sibilio, R Jeremiasz, R Colin, C Lalla, G M Fullerton, M P Samal, H Thümmel, R P Patel, J Takhar, H M Kwon, T A Cieza Lara, F Magliari, J Morrell, M Rayo Gutiérrez, T L Orenstein-Lyall, H Choi, S Kulinich, A Aftab, A Wallace, B B Abdul Kareem, S Kwok, A Królak, A Grover, Laurent Fauchier, Mª J Pinilla Lozano, G Sengupta, D Paris, M Al Dhanki, J Milewski, F Petersen Aranguren, H Brufau Redondo, H Mayr, A Arias Mendoza, M Ducoudre, A Correia, J S Awtar Singh, P Aylward, E Brscic, J Du Plooy, J L Arenas León, G Silva Alves, L Sreenivasa Murthy, P Dendale, F La Varra, S Minkin, T Eggeling, A Jamiel, G Lebischak, E Andreev, T V A Tuong, V Chaithiraphan, O Duprez, S Higgins, F Chometon, Y Cottin, A Bonny, C Guyetand, J Matos, F Henpin Yue Cesena, L Polyaeva, M Drijfhout, J Toplak, G E Vertes, N F Wang, J Doucet, A K Trivedi, P Turek, G Chouinard, A Al Lawati, W Filip, F Kovar, T J Cha, A Belanger, H L Cong, J F Robert, D López Gómez, J L Sanz Rodríguez, H Simper, P Shetty, A Chukwu, E Bukanina, C Amoros Galito, H MacCowan, T T T Tran, A Singal, K C Vu, O Ismail, A Ardiaca Capell, P Bousquet, F Goss, Z Galeeva, Maxime Guenoun, B Rijavec, Z Lazerevic, A McCracken, A C Motoc, Y Sharapova, S Wright, A J Paule Sánchez, L Mainar Latorre, I Sirazov, X L Yang, S E Paget, G Berkenboom, J Markenvard, I Surovtseva, S K George, Matthias Simon, M L Fuantos Delgado, C Christoforidis, M Lagares Carballo, P Alvarez García, J Könemann, L Crawford, I Gonos, D Saulnier, E Szabó, L Ardouin, J Bhayat, F J Abardía Oliva, X Bernard, O Sirbu, P Boutsikos, N Khmelevskikh, E Tavlueva, P LeBouthillier, I Bourazanis, A Sequeira, M López Martínez, C P Paulus, R K M Bhaskaran, F Pellerin, B Brown, B Saleh, A Lacchè, R Sola Casado, E Kaźmierczak, M Weingrod, and G Vijayaraghavan

Subjects
medicine.medical_specialty, Cardiac & Cardiovascular Systems, Epidemiology, LONG-TERM, medicine.medical_treatment, Chronic coronary syndromes, Coronary Artery Disease, Revascularization, Ventricular Function, Left, GLUCOSE, MELLITUS, Risk Factors, Internal medicine, Diabetes mellitus, Diabetes Mellitus, Ethnicity, Prevalence, medicine, Humans, ARTERY-DISEASE, Myocardial infarction, Stroke, RISK, OUTCOMES, Ejection fraction, Science & Technology, business.industry, Proportional hazards model, CLARIFY Investigators, Hazard ratio, Diabetes, Stroke Volume, Geographical disparities, Syndrome, medicine.disease, MIDDLE-EAST, EUROPEAN-SOCIETY, Treatment Outcome, MYOCARDIAL-INFARCTION, Heart failure, CLARIFY registry, Cardiovascular System & Cardiology, HEART-FAILURE, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine
Abstract

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Published
2021

37. Archaeogenomic distinctiveness of the Isthmo-Colombian area

Author

Ugo A. Perego, Antonio Torroni, Juan Guillermo Martín, Francesco Bertolini, Juan Miguel Pascale, Christiana L. Scheib, Linda Ongaro, Gaetano S. Grieco, Viola Grugni, Garrett Hellenthal, Richard G. Cooke, Francesco Montinaro, Alessandra Modi, Gianluca Lombardo, Tomás Mendizábal, Mait Metspalu, Alessandro Raveane, Marco Rosario Capodiferro, Giulia Colombo, Martina Lari, Maribel Tribaldos, Ronny Friedrich, Jorge Motta, Anna Olivieri, Alessandro Achilli, Javier Rivera, Alberto Gómez-Carballa, Ripan S. Malhi, Bethany Aram, Nicola Rambaldi Migliore, David Caramelli, Cristina Cereda, Hongjie Li, Luca Pagani, Iosvany Hernández-Mora, Corina Knipper, Ornella Semino, and Antonio Salas

Subjects
Pleistocene, Population genetics, Panama, Population, Biology, Colonialism, DNA, Mitochondrial, Article, Indigenous Americans, General Biochemistry, Genetics and Molecular Biology, Indigenous, 03 medical and health sciences, 0302 clinical medicine, Archaeogenomics, Humans, archaeogenomics, education, American Indian or Alaska Native, Phylogeny, Holocene, Genomic variation, 030304 developmental biology, 0303 health sciences, education.field_of_study, Anthropology and history, Genome, Human, ancient and modern DNA, population genetics, Genetic Variation, archaeology, Central America, Genomics, indigenous Americans, 15. Life on land, anthropology and history, Ancient and modern DNA, Haplotypes, Archaeology, Evolutionary biology, Genetic structure, genomic variation, 030217 neurology & neurosurgery, Isthmian populations
Abstract

Summary The recently enriched genomic history of Indigenous groups in the Americas is still meager concerning continental Central America. Here, we report ten pre-Hispanic (plus two early colonial) genomes and 84 genome-wide profiles from seven groups presently living in Panama. Our analyses reveal that pre-Hispanic demographic events contributed to the extensive genetic structure currently seen in the area, which is also characterized by a distinctive Isthmo-Colombian Indigenous component. This component drives these populations on a specific variability axis and derives from the local admixture of different ancestries of northern North American origin(s). Two of these ancestries were differentially associated to Pleistocene Indigenous groups that also moved into South America, leaving heterogenous genetic footprints. An additional Pleistocene ancestry was brought by a still unsampled population of the Isthmus (UPopI) that remained restricted to the Isthmian area, expanded locally during the early Holocene, and left genomic traces up to the present day., Graphical abstract, Highlights • Ancient Isthmian genomes address anthropological questions on pre-contact burials • The comparison with modern Panamanians highlights genomic structure on the Isthmus • A genomic component drives the Isthmian groups on a distinctive variability axis • A previously unknown Pleistocene ancestry identified in the Isthmo-Colombian area, Pre-contact and modern genomes from Panama highlight the distinctiveness of the Isthmo-Colombian area; detail number, source, and impact of Indigenous American genomic ancestries at the continental level; and explain complex pre-Hispanic burials.

Published
2021

38. Prognostic value of pathological tumor regression grade in locally advanced gastric cancer: New perspectives from a single-center experience

Author

Monica Gualtierotti, Paolo De Martini, Camillo Leonardo Bertoglio, Carmelo Magistro, Michele Mazzola, Annabella Curaba, Pietro Maria Lombardi, Pietro Achilli, Maria Costanza Aquilano, and Giovanni Ferrari

Subjects
Oncology, Male, medicine.medical_specialty, medicine.medical_treatment, Adenocarcinoma, Single Center, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, medicine, Humans, Radical surgery, Stage (cooking), Lymph node, Aged, Retrospective Studies, Tumor Regression Grade, Chemotherapy, Univariate analysis, business.industry, Cancer, General Medicine, Middle Aged, medicine.disease, Neoadjuvant Therapy, Survival Rate, medicine.anatomical_structure, Treatment Outcome, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Surgery, Female, Neoplasm Grading, business, Follow-Up Studies
Abstract

BACKGROUND AND OBJECTIVE Perioperative chemotherapy (PC) with radical surgery represents the gold standard of treatment for resectable advanced gastric cancer (GC). The prognostic value of pathological tumor regression grade (TRG) induced by neoadjuvant chemotherapy (NACT) is not clearly established. This study aimed to investigate the correlation between TRG and survival in GC. METHODS Patients affected by advanced GC undergoing PC and radical surgery were considered. TRG was assessed for each patient according to Becker's grading system. The correlation between TRG and survival was investigated. RESULTS One-hundred patients were selected; 25 showed a good response (GR) (TRG 1a/1b), while 75 had a poor response (PR) (TRG 2/3) to NACT. GR patients showed better disease-free survival (DFS) (52 vs. 19 months, p

Published
2020

39. Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest

Author

Cristina Malafronte, Francesca Cesana, P Cozzolino, Andrea Mauro, Anna Coppo, Giuseppe Foti, Elena Maggioni, Laura Garatti, Stefano Righetti, Federica Soffici, Felice Achilli, Leonello Avalli, Elisabetta Scanziani, Endrit Sulmina, Veronica Bozzon, I. Calchera, Cesana, F, Avalli, L, Garatti, L, Coppo, A, Righetti, S, Calchera, I, Scanziani, E, Cozzolino, P, Malafronte, C, Mauro, A, Soffici, F, Sulmina, E, Bozzon, V, Maggioni, E, Foti, G, and Achilli, F

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, ischemic cardiac arrest, medicine.medical_treatment, Ischemia, 030204 cardiovascular system & hematology, Return of spontaneous circulation, Coronary Angiography, Critical Care and Intensive Care Medicine, cardiac arrest outcome, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Refractory, Risk Factors, Retrospective Studie, Internal medicine, medicine, Extracorporeal membrane oxygenation, Humans, Extracorporeal cardiopulmonary resuscitation, Cardiopulmonary resuscitation, Retrospective Studies, Aged, business.industry, Risk Factor, 030208 emergency & critical care medicine, General Medicine, extracorporeal membrane oxygenation, Middle Aged, medicine.disease, Refractory cardiac arrest, Cardiopulmonary Resuscitation, Heart Arrest, Survival Rate, extracorporeal-cardiopulmonary resuscitation, Treatment Outcome, Coronary Occlusion, Italy, Coronary occlusion, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Clinical death, Human
Abstract

Background: Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. Methods: We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011–2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). Results: Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 pConclusions: Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection fraction. Survivors after extracorporeal cardiopulmonary resuscitation have a neurological outcome and recovery of heart function comparable to subjects with return of spontaneous circulation. Total cardiac arrest time is the only predictor of survival after cardiopulmonary resuscitation in both groups.

Published
2017

40. Comparison of European ICU patients in 2012 (ICON) versus 2002 (SOAP)

Author

Vincent, J. -L., Lefrant, J. -Y., Kotfis, K., Nanchal, R., Martin-Loeches, I., Wittebole, X., Sakka, S. G., Pickkers, P., Moreno, R., Sakr, Y., Pavlik, P., Manak, J., Kieslichova, E., Turek, R., Fischer, M., Valkova, R., Dadak, L., Dostal, P., Malaska, J., Hajek, R., Židková, A., Lavicka, P., Medve, L., Sarkany, A., Kremer, I., Marjanek, Z., Tamasi, P., Kolbusz, J., Kübler, A., Mielczarek, B., Mikaszewska-Sokolewicz, M., Tamowicz, B., Sulkowski, W., Smuszkiewicz, P., Pihowicz, A., Trejnowska, E., Hagau, N., Filipescu, D., Droc, G., Lupu, M., Nica, A., Stoica, R., Tomescu, D., Constantinescu, D., Valcoreanu Zbaganu, G., Slavcovici, A., Soskic, L., Palibrk, I., Jankovic, R., Jovanovic, B., Pandurovic, M., Bumbasirevic, V., Uljarevic, B., Surbatovic, M., Ladjevic, N., Slobodianiuk, G., Sobona, V., Cikova, A., Gebhardtova, A., Cohen, J., Sold, O., Urbanek, P., Schlieber, J., Reisinger, J., Auer, J., Hartjes, A., Lerche, A., Janous, T., Kink, E., Krahulec, W., Smolle, K., Van Der Schueren, M., Thibo, P., Vanhoof, M., Ahmet, I., Philippe, G., Dufaye, P., Jacobs, O., Fraipont, V., Biston, P., Dive, A., Bouckaert, Y., Gilbert, E., Gressens, B., Pinck, E., Collin, V., Vincent, J. L., De Waele, J., Rimachi, R., Gusu, D., De Decker, K., Mandianga, K., Heytens, L., Herbert, S., Olivier, V., Vandenheede, W., Rogiers, P., Kolodzeike, P., Kruse, M., Andersen, T., Harjola, V., Saarinen, K., Leone, M., Durocher, A., Moulront, S., Lepape, A., Losser, M., Cabaret, P., Kalaitzis, E., Zogheib, E., Charve, P., Francois, B., Lefrant, J. Y., Beilouny, B., Forceville, X., Misset, B., Jacobs, F., Bernard, F., Payen, D., Wynckel, A., Castelain, V., Faure, A., Lavagne, P., Thierry, L., Moussa, M., Vieillard-Baron, A., Durand, M., Gainnier, M., Ichai, C., Arens, S., Hoffmann, C., Kaffarnik, M., Scharnofske, C., Voigt, I., Peckelsen, C., Weber, M., Gille, J., Lange, A., Schoser, G., Sablotzki, A., Jaschinski, U., Bluethgen, A., Vogel, F., Tscheu, A., Fuchs, T., Wattenberg, M., Helmes, T., Scieszka, S., Heintz, M., Sakka, S., Kohler, J., Fiedler, F., Danz, M., Riessen, R., Kerz, T., Kersten, A., Tacke, F., Marx, G., Volkert, T., Schmutz, A., Nierhaus, A., Kluge, S., Abel, P., Janosi, R., Utzolino, S., Bracht, H., Toussaint, S., Giannakou Peftoulidou, M., Myrianthefs, P., Armaganidis, A., Routsi, C., Xini, A., Mouloudi, E., Kokoris, I., Kyriazopoulos, G., Vlachos, S., Lavrentieva, A., Partala, P., Nakos, G., Barry, J., O’Leary, R., Motherway, C., Faheem, M., Dunne, E., Donnelly, M., Konrad, T., Bonora, E., Achilli, C., Rossi, S., Castiglione, G., Peris, A., Albanese, D., Stocchetti, N., Citerio, G., Mozzoni, L., Sisillo, E., De Negri, P., Savioli, M., Vecchiarelli, P., Puflea, F., Stankovic, V., Minoja, G., Montibeller, S., Calligaro, P., Sorrentino, R., Feri, M., Zambon, M., Colombaroli, E., Giarratano, A., Pellis, T., Capra, C., Antonelli, M., Gullo, A., Chelazzi, C., De Capraris, A., Patroniti, N., Girardis, M., Franchi, F., Berlot, G., Ponssen, H., Ten Cate, J., Bormans, L., Husada, S., Buise, M., Van Der Hoven, B., Reidinga, A., Kuiper, M., Kluge, G., Den Boer, S., Kesecioglu, J., Van Leeuwen, H., Flaatten, H., Mo, S., Branco, V., Rua, F., Lafuente, E., Sousa, M., Catorze, N., Barros, M., Pereira, L., Vintém De Oliveira, A., Gomes, J., Gaspar, I., Pereira, M., Cymbron, M., Dias, A., Almeida, E., Beirao, S., Serra, I., Ribeiro, R., Povoa, P., Faria, F., Costa-E-Silva, Z., Nóbrega, J., Fernandes, F., Gabriel, J., Voga, G., Rupnik, E., Kosec, L., Kerin Povšic, M., Osojnik, I., Tomic, V., Sinkovic, A., González, J., Zavala, E., Pérez Valenzuela, J., Marina, L., Vidal-Cortés, P., Posada, P., Ignacio Martin-Loeches, A., Muñoz Guillén, N., Palomar, M., Sole-Violan, J., Torres, A., Gonzalez Gallego, M., Aguilar, G., Montoiro Allué, R., Argüeso, M., Parejo, M., Palomo Navarro, M., Jose, A., Nin, N., Alvarez Lerma, F., Martinez, O., Tenza Lozano, E., Arenal López, S., Perez Granda, M., Moreno, S., Llubia, C., De La Fuente Martos, C., Gonzalez-Arenas, P., Llamas Fernández, N., Gil Rueda, B., Estruch Pons, I., Cruza, N., Maroto, F., Estella, A., Ferrer, A., Iglesias Fraile, L., Quindos, B., Quintano, A., Tebar, M., Cardinal, P., Reyes, A., Rodríguez, A., Abella, A., García Del Valle, S., Yus, S., Maseda, E., Berezo, J., Tejero Pedregosa, A., Laplaza, C., Ferrer, R., Rico-Feijoo, J., Rodríguez, M., Monedero, P., Eriksson, K., Lind, D., Chabanel, D., Zender, H., Heer, K., Frankenberger, B., Jakob, S., Haller, A., Mathew, S., Downes, R., Barrera Groba, C., Johnston, A., Meacher, R., Keays, R., Haji-Michael, P., Tyler, C., Ferguson, A., Jones, S., Tyl, D., Ball, A., Vogel, J., Booth, M., Downie, P., Watters, M., Brett, S., Garfield, M., Everett, L., Heenen, S., Dhir, S., Beardow, Z., Mostert, M., Brosnan, S., Pinto, N., Harris, S., Summors, A., Andrew, N., Rose, A., Appelboam, R., Davies, O., Vickers, E., Agarwal, B., Szakmany, T., Wimbush, S., Welters, I., Pearse, R., Hollands, R., Kirk-Bayley, J., Fletcher, N., Bray, B., Brealey, D., Delle Karth, G., Draxler, V., Filzwieser, G., Heindl, W., Kellner, G., Lenz, K., Rossmann, E., Wiedermann, C., Chochrad, D., Damas, P., Decruyenaere, J., Hoste, E., Devriendt, J., Espeel, B., Installe, E., Malbrain, M., Nollet, G., Preiser, J. C., Raemaekers, J., Roman, A., Simon, M., Spapen, H., Swinnen, W., Vallot, F., Chytra, I., Herold, I., Polak, F., Sterba, M., Bestle, M., Espersen, K., Guldager, H., Welling, K. -L., Nyman, D., Ruokonen, E., Annane, D., Catogni, P., Colas, G., Coulomb, F., Dorne, R., Garrouste, M., Isetta, C., Larché, J., LeGall, J. -R., Lessire, H., Malledant, Y., Mateu, P., Ossart, M., Schlossmacher, P., Timsit, J. -F., Winnock, S., Sollet, J. -P., Mallet, L., Maurer, P., Sab, J. M., Sollet, J. P., Aykut, G., Brunkhorst, F., Lauterbach, M., Ragaller, M., Gatz, R., Gerlach, H., Henzler, D., Hopf, H. -B., Hueneburg, H., Karzai, W., Keller, A., Bauer, T., Kuhlmann, U., Langgartner, J., Manhold, C., Reith, B., Schuerholz, T., Spies, C., Stögbauer, R., Unterburger, J., Clouva-Molyvdas, P. -M., Giokas, G., Ioannidou, E., Lahana, A., Liolios, A., Marathias, K., Tasiou, A., Tsangaris, H., Marsh, B., Power, M., Sprung, C., Biagioli, B., Bobbio Pallavicini, F., Pesenti, A., Della Corte, F., Donadio, P. P., Donati, A., Giorgio, T., Giudici, D., Greco, S., Guadagnucci, A., Lapichino, G., Livigni, S., Moise, G., Nardi, G., Panascia, E., Pizzamiglio, M., Ranieri, V. M., Rosi, R., Sicignano, A., Solca, M., Vignali, G., Volpe Rinonapoli, I., Barnas, M., De Bel, E. E., De Pont, A. -C., Groeneveld, J., Nijsten, M., Sie, L., Zandstra, D. F., Harboe, S., Lindén, S., Lovstad, R. Z., Moen, H., Smith-Erichsen, N., Piotrowski, A., Karpel, E., Pais-De-Lacerda, A., Paiva, J. A., Pimentel, A., Jovanovic, K., Malik, P., Lucka, K., Aldecoa Alvarez-Santullano, C., Artigas, A., Escorsell, A., Nicolas, J., Izura Cea, J. J., Montejo, J., Palencia, E., Santos, F., Sierra-Camerino, R., Sipmann, F., Brodersen, K., Haggqvist, J., Hermansson, D., Hjelmqvist, H., Loderer, G., Maggiorini, M., Andrews, P., Appadu, B., Bewley, J., Burchett, K., Chambers, P., Coakley, J., Doberenz, D., Eastwood, N., Fielden, J., Gedney, J., Gunning, K., Harling, D., Jankowski, S., Jayson, D., Kilner, A., Krishna-Kumar, V., Lei, K., Mackenzie, S., Macnaughton, P., McCulloch, C., Morgan, P., Rhodes, A., Roberts, C., Russell, M., Tupper-Carey, D., Wright, M., Twohey, L., Watts, J., Webster, R., Williams, D., on behalf of the ICON and SOAP investigators and SOAP investigators, Vincent, J.-L., Lefrant, J.-Y., Kotfis, K., Nanchal, R., Martin-Loeches, I., Wittebole, X., Sakka, S.G., Pickkers, P., Moreno, R., Sakr, Y., Pavlik, P., Manak, J., Kieslichova, E., Turek, R., Fischer, M., Valkova, R., Dadak, L., Dostal, P., Malaska, J., Hajek, R., Židková, A., Lavicka, P., Medve, L., Sarkany, A., Kremer, I., Marjanek, Z., Tamasi, P., Kolbusz, J., Kübler, A., Mielczarek, B., Mikaszewska-Sokolewicz, M., Tamowicz, B., Sulkowski, W., Smuszkiewicz, P., Pihowicz, A., Trejnowska, E., Hagau, N., Filipescu, D., Droc, G., Lupu, M., Nica, A., Stoica, R., Tomescu, D., Constantinescu, D., Valcoreanu Zbaganu, G., Slavcovici, A., Soskic, L., Palibrk, I., Jankovic, R., Jovanovic, B., Pandurovic, M., Bumbasirevic, V., Uljarevic, B., Surbatovic, M., Ladjevic, N., Slobodianiuk, G., Sobona, V., Cikova, A., Gebhardtova, A., Cohen, J., Sold, O., Urbanek, P., Schlieber, J., Reisinger, J., Auer, J., Hartjes, A., Lerche, A., Janous, T., Kink, E., Krahulec, W., Smolle, K., Van Der Schueren, M., Thibo, P., Vanhoof, M., Ahmet, I., Philippe, G., Dufaye, P., Jacobs, O., Fraipont, V., Biston, P., Dive, A., Bouckaert, Y., Gilbert, E., Gressens, B., Pinck, E., Collin, V., Vincent, J.L., De Waele, J., Rimachi, R., Gusu, D., De Decker, K., Mandianga, K., Heytens, L., Herbert, S., Olivier, V., Vandenheede, W., Rogiers, P., Kolodzeike, P., Kruse, M., Andersen, T., Harjola, V., Saarinen, K., Leone, M., Durocher, A., Moulront, S., Lepape, A., Losser, M., Cabaret, P., Kalaitzis, E., Zogheib, E., Charve, P., Francois, B., Lefrant, J.Y., Beilouny, B., Forceville, X., Misset, B., Jacobs, F., Bernard, F., Payen, D., Wynckel, A., Castelain, V., Faure, A., Lavagne, P., Thierry, L., Moussa, M., Vieillard-Baron, A., Durand, M., Gainnier, M., Ichai, C., Arens, S., Hoffmann, C., Kaffarnik, M., Scharnofske, C., Voigt, I., Peckelsen, C., Weber, M., Gille, J., Lange, A., Schoser, G., Sablotzki, A., Jaschinski, U., Bluethgen, A., Vogel, F., Tscheu, A., Fuchs, T., Wattenberg, M., Helmes, T., Scieszka, S., Heintz, M., Sakka, S., Kohler, J., Fiedler, F., Danz, M., Riessen, R., Kerz, T., Kersten, A., Tacke, F., Marx, G., Volkert, T., Schmutz, A., Nierhaus, A., Kluge, S., Abel, P., Janosi, R., Utzolino, S., Bracht, H., Toussaint, S., Giannakou Peftoulidou, M., Myrianthefs, P., Armaganidis, A., Routsi, C., Xini, A., Mouloudi, E., Kokoris, I., Kyriazopoulos, G., Vlachos, S., Lavrentieva, A., Partala, P., Nakos, G., Barry, J., O’Leary, R., Motherway, C., Faheem, M., Dunne, E., Donnelly, M., Konrad, T., Bonora, E., Achilli, C., Rossi, S., Castiglione, G., Peris, A., Albanese, D., Stocchetti, N., Citerio, G., Mozzoni, L., Sisillo, E., De Negri, P., Savioli, M., Vecchiarelli, P., Puflea, F., Stankovic, V., Minoja, G., Montibeller, S., Calligaro, P., Sorrentino, R., Feri, M., Zambon, M., Colombaroli, E., Giarratano, A., Pellis, T., Capra, C., Antonelli, M., Gullo, A., Chelazzi, C., De Capraris, A., Patroniti, N., Girardis, M., Franchi, F., Berlot, G., Ponssen, H., Ten Cate, J., Bormans, L., Husada, S., Buise, M., Van Der Hoven, B., Reidinga, A., Kuiper, M., Kluge, G., Den Boer, S., Kesecioglu, J., Van Leeuwen, H., Flaatten, H., Mo, S., Branco, V., Rua, F., Lafuente, E., Sousa, M., Catorze, N., Barros, M., Pereira, L., Vintém De Oliveira, A., Gomes, J., Gaspar, I., Pereira, M., Cymbron, M., Dias, A., Almeida, E., Beirao, S., Serra, I., Ribeiro, R., Povoa, P., Faria, F., Costa-E-Silva, Z., Nóbrega, J., Fernandes, F., Gabriel, J., Voga, G., Rupnik, E., Kosec, L., Kerin Povšic, M., Osojnik, I., Tomic, V., Sinkovic, A., González, J., Zavala, E., Pérez Valenzuela, J., Marina, L., Vidal-Cortés, P., Posada, P., Ignacio Martin-Loeches, A., Muñoz Guillén, N., Palomar, M., Sole-Violan, J., Torres, A., Gonzalez Gallego, M., Aguilar, G., Montoiro Allué, R., Argüeso, M., Parejo, M., Palomo Navarro, M., Jose, A., Nin, N., Alvarez Lerma, F., Martinez, O., Tenza Lozano, E., Arenal López, S., Perez Granda, M., Moreno, S., Llubia, C., De La Fuente Martos, C., Gonzalez-Arenas, P., Llamas Fernández, N., Gil Rueda, B., Estruch Pons, I., Cruza, N., Maroto, F., Estella, A., Ferrer, A., Iglesias Fraile, L., Quindos, B., Quintano, A., Tebar, M., Cardinal, P., Reyes, A., Rodríguez, A., Abella, A., García Del Valle, S., Yus, S., Maseda, E., Berezo, J., Tejero Pedregosa, A., Laplaza, C., Ferrer, R., Rico-Feijoo, J., Rodríguez, M., Monedero, P., Eriksson, K., Lind, D., Chabanel, D., Zender, H., Heer, K., Frankenberger, B., Jakob, S., Haller, A., Mathew, S., Downes, R., Barrera Groba, C., Johnston, A., Meacher, R., Keays, R., Haji-Michael, P., Tyler, C., Ferguson, A., Jones, S., Tyl, D., Ball, A., Vogel, J., Booth, M., Downie, P., Watters, M., Brett, S., Garfield, M., Everett, L., Heenen, S., Dhir, S., Beardow, Z., Mostert, M., Brosnan, S., Pinto, N., Harris, S., Summors, A., Andrew, N., Rose, A., Appelboam, R., Davies, O., Vickers, E., Agarwal, B., Szakmany, T., Wimbush, S., Welters, I., Pearse, R., Hollands, R., Kirk-Bayley, J., Fletcher, N., Bray, B., Brealey, D., Delle Karth, G., Draxler, V., Filzwieser, G., Heindl, W., Kellner, G., Lenz, K., Rossmann, E., Wiedermann, C., Chochrad, D., Damas, P., Decruyenaere, J., Hoste, E., Devriendt, J., Espeel, B., Installe, E., Malbrain, M., Nollet, G., Preiser, J.C., Raemaekers, J., Roman, A., Simon, M., Spapen, H., Swinnen, W., Vallot, F., Chytra, I., Herold, I., Polak, F., Sterba, M., Bestle, M., Espersen, K., Guldager, H., Welling, K.-L., Nyman, D., Ruokonen, E., Annane, D., Catogni, P., Colas, G., Coulomb, F., Dorne, R., Garrouste, M., Isetta, C., Larché, J., LeGall, J.-R., Lessire, H., Malledant, Y., Mateu, P., Ossart, M., Schlossmacher, P., Timsit, J.-F., Winnock, S., Sollet, J.-P., Mallet, L., Maurer, P., Sab, J.M., Sollet, J.P., Aykut, G., Brunkhorst, F., Lauterbach, M., Ragaller, M., Gatz, R., Gerlach, H., Henzler, D., Hopf, H.-B., Hueneburg, H., Karzai, W., Keller, A., Bauer, T., Kuhlmann, U., Langgartner, J., Manhold, C., Reith, B., Schuerholz, T., Spies, C., Stögbauer, R., Unterburger, J., Clouva-Molyvdas, P.-M., Giokas, G., Ioannidou, E., Lahana, A., Liolios, A., Marathias, K., Tasiou, A., Tsangaris, H., Marsh, B., Power, M., Sprung, C., Biagioli, B., Bobbio Pallavicini, F., Pesenti, A., Della Corte, F., Donadio, P.P., Donati, A., Giorgio, T., Giudici, D., Greco, S., Guadagnucci, A., Lapichino, G., Livigni, S., Moise, G., Nardi, G., Panascia, E., Pizzamiglio, M., Ranieri, V.M., Rosi, R., Sicignano, A., Solca, M., Vignali, G., Volpe Rinonapoli, I., Barnas, M., De Bel, E.E., De Pont, A.-C., Groeneveld, J., Nijsten, M., Sie, L., Zandstra, D.F., Harboe, S., Lindén, S., Lovstad, R.Z., Moen, H., Smith-Erichsen, N., Piotrowski, A., Karpel, E., Pais-De-Lacerda, A., Paiva, J.A., Pimentel, A., Jovanovic, K., Malik, P., Lucka, K., Aldecoa Alvarez-Santullano, C., Artigas, A., Escorsell, A., Nicolas, J., Izura Cea, J.J., Montejo, J., Palencia, E., Santos, F., Sierra-Camerino, R., Sipmann, F., Brodersen, K., Haggqvist, J., Hermansson, D., Hjelmqvist, H., Loderer, G., Maggiorini, M., Andrews, P., Appadu, B., Bewley, J., Burchett, K., Chambers, P., Coakley, J., Doberenz, D., Eastwood, N., Fielden, J., Gedney, J., Gunning, K., Harling, D., Jankowski, S., Jayson, D., Kilner, A., Krishna-Kumar, V., Lei, K., Mackenzie, S., Macnaughton, P., McCulloch, C., Morgan, P., Rhodes, A., Roberts, C., Russell, M., Tupper-Carey, D., Wright, M., Twohey, L., Watts, J., Webster, R., Williams, D., on behalf of the ICON and SOAP investigators and SOAP investigators, Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), University of Wisconsin School of Medicine and Public Health, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Cliniques universitaires St Luc [Bruxelles], University Hospital of Cologne [Cologne], Radboud university [Nijmegen], Centro Hospitalar de Lisboa Central E.P.E, Intensive Care, Vincent, J, Lefrant, J, Kotfis, K, Nanchal, R, Martin-Loeches, I, Wittebole, X, Sakka, S, Pickkers, P, Moreno, R, Sakr, Y, Pavlik, P, Manak, J, Kieslichova, E, Turek, R, Fischer, M, Valkova, R, Dadak, L, Dostal, P, Malaska, J, Hajek, R, Zidkova, A, Lavicka, P, Medve, L, Sarkany, A, Kremer, I, Marjanek, Z, Tamasi, P, Kolbusz, J, Kubler, A, Mielczarek, B, Mikaszewska-Sokolewicz, M, Tamowicz, B, Sulkowski, W, Smuszkiewicz, P, Pihowicz, A, Trejnowska, E, Hagau, N, Filipescu, D, Droc, G, Lupu, M, Nica, A, Stoica, R, Tomescu, D, Constantinescu, D, Valcoreanu Zbaganu, G, Slavcovici, A, Soskic, L, Palibrk, I, Jankovic, R, Jovanovic, B, Pandurovic, M, Bumbasirevic, V, Uljarevic, B, Surbatovic, M, Ladjevic, N, Slobodianiuk, G, Sobona, V, Cikova, A, Gebhardtova, A, Cohen, J, Sold, O, Urbanek, P, Schlieber, J, Reisinger, J, Auer, J, Hartjes, A, Lerche, A, Janous, T, Kink, E, Krahulec, W, Smolle, K, Van Der Schueren, M, Thibo, P, Vanhoof, M, Ahmet, I, Philippe, G, Dufaye, P, Jacobs, O, Fraipont, V, Biston, P, Dive, A, Bouckaert, Y, Gilbert, E, Gressens, B, Pinck, E, Collin, V, De Waele, J, Rimachi, R, Gusu, D, De Decker, K, Mandianga, K, Heytens, L, Herbert, S, Olivier, V, Vandenheede, W, Rogiers, P, Kolodzeike, P, Kruse, M, Andersen, T, Harjola, V, Saarinen, K, Leone, M, Durocher, A, Moulront, S, Lepape, A, Losser, M, Cabaret, P, Kalaitzis, E, Zogheib, E, Charve, P, Francois, B, Beilouny, B, Forceville, X, Misset, B, Jacobs, F, Bernard, F, Payen, D, Wynckel, A, Castelain, V, Faure, A, Lavagne, P, Thierry, L, Moussa, M, Vieillard-Baron, A, Durand, M, Gainnier, M, Ichai, C, Arens, S, Hoffmann, C, Kaffarnik, M, Scharnofske, C, Voigt, I, Peckelsen, C, Weber, M, Gille, J, Lange, A, Schoser, G, Sablotzki, A, Jaschinski, U, Bluethgen, A, Vogel, F, Tscheu, A, Fuchs, T, Wattenberg, M, Helmes, T, Scieszka, S, Heintz, M, Kohler, J, Fiedler, F, Danz, M, Riessen, R, Kerz, T, Kersten, A, Tacke, F, Marx, G, Volkert, T, Schmutz, A, Nierhaus, A, Kluge, S, Abel, P, Janosi, R, Utzolino, S, Bracht, H, Toussaint, S, Giannakou Peftoulidou, M, Myrianthefs, P, Armaganidis, A, Routsi, C, Xini, A, Mouloudi, E, Kokoris, I, Kyriazopoulos, G, Vlachos, S, Lavrentieva, A, Partala, P, Nakos, G, Barry, J, O'Leary, R, Motherway, C, Faheem, M, Dunne, E, Donnelly, M, Konrad, T, Bonora, E, Achilli, C, Rossi, S, Castiglione, G, Peris, A, Albanese, D, Stocchetti, N, Citerio, G, Mozzoni, L, Sisillo, E, De Negri, P, Savioli, M, Vecchiarelli, P, Puflea, F, Stankovic, V, Minoja, G, Montibeller, S, Calligaro, P, Sorrentino, R, Feri, M, Zambon, M, Colombaroli, E, Giarratano, A, Pellis, T, Capra, C, Antonelli, M, Gullo, A, Chelazzi, C, De Capraris, A, Patroniti, N, Girardis, M, Franchi, F, Berlot, G, Ponssen, H, Ten Cate, J, Bormans, L, Husada, S, Buise, M, Van Der Hoven, B, Reidinga, A, Kuiper, M, Kluge, G, Den Boer, S, Kesecioglu, J, Van Leeuwen, H, Flaatten, H, Mo, S, Branco, V, Rua, F, Lafuente, E, Sousa, M, Catorze, N, Barros, M, Pereira, L, Vintem De Oliveira, A, Gomes, J, Gaspar, I, Pereira, M, Cymbron, M, Dias, A, Almeida, E, Beirao, S, Serra, I, Ribeiro, R, Povoa, P, Faria, F, Costa-E-Silva, Z, Nobrega, J, Fernandes, F, Gabriel, J, Voga, G, Rupnik, E, Kosec, L, Kerin Povsic, M, Osojnik, I, Tomic, V, Sinkovic, A, Gonzalez, J, Zavala, E, Perez Valenzuela, J, Marina, L, Vidal-Cortes, P, Posada, P, Ignacio Martin-Loeches, A, Munoz Guillen, N, Palomar, M, Sole-Violan, J, Torres, A, Gonzalez Gallego, M, Aguilar, G, Montoiro Allue, R, Argueso, M, Parejo, M, Palomo Navarro, M, Jose, A, Nin, N, Alvarez Lerma, F, Martinez, O, Tenza Lozano, E, Arenal Lopez, S, Perez Granda, M, Moreno, S, Llubia, C, De La Fuente Martos, C, Gonzalez-Arenas, P, Llamas Fernandez, N, Gil Rueda, B, Estruch Pons, I, Cruza, N, Maroto, F, Estella, A, Ferrer, A, Iglesias Fraile, L, Quindos, B, Quintano, A, Tebar, M, Cardinal, P, Reyes, A, Rodriguez, A, Abella, A, Garcia Del Valle, S, Yus, S, Maseda, E, Berezo, J, Tejero Pedregosa, A, Laplaza, C, Ferrer, R, Rico-Feijoo, J, Rodriguez, M, Monedero, P, Eriksson, K, Lind, D, Chabanel, D, Zender, H, Heer, K, Frankenberger, B, Jakob, S, Haller, A, Mathew, S, Downes, R, Barrera Groba, C, Johnston, A, Meacher, R, Keays, R, Haji-Michael, P, Tyler, C, Ferguson, A, Jones, S, Tyl, D, Ball, A, Vogel, J, Booth, M, Downie, P, Watters, M, Brett, S, Garfield, M, Everett, L, Heenen, S, Dhir, S, Beardow, Z, Mostert, M, Brosnan, S, Pinto, N, Harris, S, Summors, A, Andrew, N, Rose, A, Appelboam, R, Davies, O, Vickers, E, Agarwal, B, Szakmany, T, Wimbush, S, Welters, I, Pearse, R, Hollands, R, Kirk-Bayley, J, Fletcher, N, Bray, B, Brealey, D, Delle Karth, G, Draxler, V, Filzwieser, G, Heindl, W, Kellner, G, Lenz, K, Rossmann, E, Wiedermann, C, Chochrad, D, Damas, P, Decruyenaere, J, Hoste, E, Devriendt, J, Espeel, B, Installe, E, Malbrain, M, Nollet, G, Preiser, J, Raemaekers, J, Roman, A, Simon, M, Spapen, H, Swinnen, W, Vallot, F, Chytra, I, Herold, I, Polak, F, Sterba, M, Bestle, M, Espersen, K, Guldager, H, Welling, K, Nyman, D, Ruokonen, E, Annane, D, Catogni, P, Colas, G, Coulomb, F, Dorne, R, Garrouste, M, Isetta, C, Larche, J, Legall, J, Lessire, H, Malledant, Y, Mateu, P, Ossart, M, Schlossmacher, P, Timsit, J, Winnock, S, Sollet, J, Mallet, L, Maurer, P, Sab, J, Aykut, G, Brunkhorst, F, Lauterbach, M, Ragaller, M, Gatz, R, Gerlach, H, Henzler, D, Hopf, H, Hueneburg, H, Karzai, W, Keller, A, Bauer, T, Kuhlmann, U, Langgartner, J, Manhold, C, Reith, B, Schuerholz, T, Spies, C, Stogbauer, R, Unterburger, J, Clouva-Molyvdas, P, Giokas, G, Ioannidou, E, Lahana, A, Liolios, A, Marathias, K, Tasiou, A, Tsangaris, H, Marsh, B, Power, M, Sprung, C, Biagioli, B, Bobbio Pallavicini, F, Pesenti, A, Della Corte, F, Donadio, P, Donati, A, Giorgio, T, Giudici, D, Greco, S, Guadagnucci, A, Lapichino, G, Livigni, S, Moise, G, Nardi, G, Panascia, E, Pizzamiglio, M, Ranieri, V, Rosi, R, Sicignano, A, Solca, M, Vignali, G, Volpe Rinonapoli, I, Barnas, M, De Bel, E, De Pont, A, Groeneveld, J, Nijsten, M, Sie, L, Zandstra, D, Harboe, S, Linden, S, Lovstad, R, Moen, H, Smith-Erichsen, N, Piotrowski, A, Karpel, E, Pais-De-Lacerda, A, Paiva, J, Pimentel, A, Jovanovic, K, Malik, P, Lucka, K, Aldecoa Alvarez-Santullano, C, Artigas, A, Escorsell, A, Nicolas, J, Izura Cea, J, Montejo, J, Palencia, E, Santos, F, Sierra-Camerino, R, Sipmann, F, Brodersen, K, Haggqvist, J, Hermansson, D, Hjelmqvist, H, Loderer, G, Maggiorini, M, Andrews, P, Appadu, B, Bewley, J, Burchett, K, Chambers, P, Coakley, J, Doberenz, D, Eastwood, N, Fielden, J, Gedney, J, Gunning, K, Harling, D, Jankowski, S, Jayson, D, Kilner, A, Krishna-Kumar, V, Lei, K, Mackenzie, S, Macnaughton, P, Mcculloch, C, Morgan, P, Rhodes, A, Roberts, C, Russell, M, Tupper-Carey, D, Wright, M, Twohey, L, Watts, J, Webster, R, Williams, D, Supporting clinical sciences, Other departments, CHU Lille, Université de Lille, Unité de réanimation médicale [CHU de Carémeau, Nîmes], West Pomeranian University of Technology Szczecin, Universität Witten Herdecke, Radboud University [Nijmegen], Faculdade de Medicina de São José do Rio Preto [FAMERP], Jena University Hospital [Jena], Vincent, J. -L., Lefrant, J. -Y., Sakka, S. G., Zidkova, A., Kubler, A., O'Leary, R., Vintem De Oliveira, A., Nobrega, J., Kerin Povsic, M., Gonzalez, J., Perez Valenzuela, J., Vidal-Cortes, P., Munoz Guillen, N., Montoiro Allue, R., Argueso, M., Arenal Lopez, S., Llamas Fernandez, N., Rodriguez, A., Garcia Del Valle, S., Rodriguez, M., Preiser, J. C., Welling, K. -L., Larche, J., Legall, J. -R., Timsit, J. -F., Sollet, J. -P., Sab, J. M., Hopf, H. -B., Stogbauer, R., Clouva-Molyvdas, P. -M., Donadio, P. P., Ranieri, V. M., De Bel, E. E., De Pont, A. -C., Zandstra, D. F., Linden, S., Lovstad, R. Z., Paiva, J. A., Izura Cea, J. J., Mcculloch, C., Vincent J.-L., Lefrant J.-Y., Kotfis K., Nanchal R., Martin-Loeches I., Wittebole X., Sakka S.G., Pickkers P., Moreno R., Sakr Y., Pavlik P., Manak J., Kieslichova E., Turek R., Fischer M., Valkova R., Dadak L., Dostal P., Malaska J., Hajek R., Zidkova A., Lavicka P., Medve L., Sarkany A., Kremer I., Marjanek Z., Tamasi P., Kolbusz J., Kubler A., Mielczarek B., Mikaszewska-Sokolewicz M., Tamowicz B., Sulkowski W., Smuszkiewicz P., Pihowicz A., Trejnowska E., Hagau N., Filipescu D., Droc G., Lupu M., Nica A., Stoica R., Tomescu D., Constantinescu D., Valcoreanu Zbaganu G., Slavcovici A., Soskic L., Palibrk I., Jankovic R., Jovanovic B., Pandurovic M., Bumbasirevic V., Uljarevic B., Surbatovic M., Ladjevic N., Slobodianiuk G., Sobona V., Cikova A., Gebhardtova A., Cohen J., Sold O., Urbanek P., Schlieber J., Reisinger J., Auer J., Hartjes A., Lerche A., Janous T., Kink E., Krahulec W., Smolle K., Van Der Schueren M., Thibo P., Vanhoof M., Ahmet I., Philippe G., Dufaye P., Jacobs O., Fraipont V., Biston P., Dive A., Bouckaert Y., Gilbert E., Gressens B., Pinck E., Collin V., De Waele J., Rimachi R., Gusu D., De Decker K., Mandianga K., Heytens L., Herbert S., Olivier V., Vandenheede W., Rogiers P., Kolodzeike P., Kruse M., Andersen T., Harjola V., Saarinen K., Leone M., Durocher A., Moulront S., Lepape A., Losser M., Cabaret P., Kalaitzis E., Zogheib E., Charve P., Francois B., Beilouny B., Forceville X., Misset B., Jacobs F., Bernard F., Payen D., Wynckel A., Castelain V., Faure A., Lavagne P., Thierry L., Moussa M., Vieillard-Baron A., Durand M., Gainnier M., Ichai C., Arens S., Hoffmann C., Kaffarnik M., Scharnofske C., Voigt I., Peckelsen C., Weber M., Gille J., Lange A., Schoser G., Sablotzki A., Jaschinski U., Bluethgen A., Vogel F., Tscheu A., Fuchs T., Wattenberg M., Helmes T., Scieszka S., Heintz M., Sakka S., Kohler J., Fiedler F., Danz M., Riessen R., Kerz T., Kersten A., Tacke F., Marx G., Volkert T., Schmutz A., Nierhaus A., Kluge S., Abel P., Janosi R., Utzolino S., Bracht H., Toussaint S., Giannakou Peftoulidou M., Myrianthefs P., Armaganidis A., Routsi C., Xini A., Mouloudi E., Kokoris I., Kyriazopoulos G., Vlachos S., Lavrentieva A., Partala P., Nakos G., Barry J., O'Leary R., Motherway C., Faheem M., Dunne E., Donnelly M., Konrad T., Bonora E., Achilli C., Rossi S., Castiglione G., Peris A., Albanese D., Stocchetti N., Citerio G., Mozzoni L., Sisillo E., De Negri P., Savioli M., Vecchiarelli P., Puflea F., Stankovic V., Minoja G., Montibeller S., Calligaro P., Sorrentino R., Feri M., Zambon M., Colombaroli E., Giarratano A., Pellis T., Capra C., Antonelli M., Gullo A., Chelazzi C., De Capraris A., Patroniti N., Girardis M., Franchi F., Berlot G., Ponssen H., Ten Cate J., Bormans L., Husada S., Buise M., Van Der Hoven B., Reidinga A., Kuiper M., Kluge G., Den Boer S., Kesecioglu J., Van Leeuwen H., Flaatten H., Mo S., Branco V., Rua F., Lafuente E., Sousa M., Catorze N., Barros M., Pereira L., Vintem De Oliveira A., Gomes J., Gaspar I., Pereira M., Cymbron M., Dias A., Almeida E., Beirao S., Serra I., Ribeiro R., Povoa P., Faria F., Costa-E-Silva Z., Nobrega J., Fernandes F., Gabriel J., Voga G., Rupnik E., Kosec L., Kerin Povsic M., Osojnik I., Tomic V., Sinkovic A., Gonzalez J., Zavala E., Perez Valenzuela J., Marina L., Vidal-Cortes P., Posada P., Ignacio Martin-Loeches A., Munoz Guillen N., Palomar M., Sole-Violan J., Torres A., Gonzalez Gallego M., Aguilar G., Montoiro Allue R., Argueso M., Parejo M., Palomo Navarro M., Jose A., Nin N., Alvarez Lerma F., Martinez O., Tenza Lozano E., Arenal Lopez S., Perez Granda M., Moreno S., Llubia C., De La Fuente Martos C., Gonzalez-Arenas P., Llamas Fernandez N., Gil Rueda B., Estruch Pons I., Cruza N., Maroto F., Estella A., Ferrer A., Iglesias Fraile L., Quindos B., Quintano A., Tebar M., Cardinal P., Reyes A., Rodriguez A., Abella A., Garcia Del Valle S., Yus S., Maseda E., Berezo J., Tejero Pedregosa A., Laplaza C., Ferrer R., Rico-Feijoo J., Rodriguez M., Monedero P., Eriksson K., Lind D., Chabanel D., Zender H., Heer K., Frankenberger B., Jakob S., Haller A., Mathew S., Downes R., Barrera Groba C., Johnston A., Meacher R., Keays R., Haji-Michael P., Tyler C., Ferguson A., Jones S., Tyl D., Ball A., Vogel J., Booth M., Downie P., Watters M., Brett S., Garfield M., Everett L., Heenen S., Dhir S., Beardow Z., Mostert M., Brosnan S., Pinto N., Harris S., Summors A., Andrew N., Rose A., Appelboam R., Davies O., Vickers E., Agarwal B., Szakmany T., Wimbush S., Welters I., Pearse R., Hollands R., Kirk-Bayley J., Fletcher N., Bray B., Brealey D., Delle Karth G., Draxler V., Filzwieser G., Heindl W., Kellner G., Lenz K., Rossmann E., Wiedermann C., Chochrad D., Damas P., Decruyenaere J., Hoste E., Devriendt J., Espeel B., Installe E., Malbrain M., Nollet G., Preiser J.C., Raemaekers J., Roman A., Simon M., Spapen H., Swinnen W., Vallot F., Chytra I., Herold I., Polak F., Sterba M., Bestle M., Espersen K., Guldager H., Welling K.-L., Nyman D., Ruokonen E., Annane D., Catogni P., Colas G., Coulomb F., Dorne R., Garrouste M., Isetta C., Larche J., LeGall J.-R., Lessire H., Malledant Y., Mateu P., Ossart M., Schlossmacher P., Timsit J.-F., Winnock S., Sollet J.-P., Mallet L., Maurer P., Sab J.M., Aykut G., Brunkhorst F., Lauterbach M., Ragaller M., Gatz R., Gerlach H., Henzler D., Hopf H.-B., Hueneburg H., Karzai W., Keller A., Bauer T., Kuhlmann U., Langgartner J., Manhold C., Reith B., Schuerholz T., Spies C., Stogbauer R., Unterburger J., Clouva-Molyvdas P.-M., Giokas G., Ioannidou E., Lahana A., Liolios A., Marathias K., Tasiou A., Tsangaris H., Marsh B., Power M., Sprung C., Biagioli B., Bobbio Pallavicini F., Pesenti A., Della Corte F., Donadio P.P., Donati A., Giorgio T., Giudici D., Greco S., Guadagnucci A., Lapichino G., Livigni S., Moise G., Nardi G., Panascia E., Pizzamiglio M., Ranieri V.M., Rosi R., Sicignano A., Solca M., Vignali G., Volpe Rinonapoli I., Barnas M., De Bel E.E., De Pont A.-C., Groeneveld J., Nijsten M., Sie L., Zandstra D.F., Harboe S., Linden S., Lovstad R.Z., Moen H., Smith-Erichsen N., Piotrowski A., Karpel E., Pais-De-Lacerda A., Paiva J.A., Pimentel A., Jovanovic K., Malik P., Lucka K., Aldecoa Alvarez-Santullano C., Artigas A., Escorsell A., Nicolas J., Izura Cea J.J., Montejo J., Palencia E., Santos F., Sierra-Camerino R., Sipmann F., Brodersen K., Haggqvist J., Hermansson D., Hjelmqvist H., Loderer G., Maggiorini M., Andrews P., Appadu B., Bewley J., Burchett K., Chambers P., Coakley J., Doberenz D., Eastwood N., Fielden J., Gedney J., Gunning K., Harling D., Jankowski S., Jayson D., Kilner A., Krishna-Kumar V., Lei K., Mackenzie S., Macnaughton P., McCulloch C., Morgan P., Rhodes A., Roberts C., Russell M., Tupper-Carey D., Wright M., Twohey L., Watts J., Webster R., and Williams D.

Subjects
Male, Original, Epidemiology, [SDV]Life Sciences [q-bio], HSJ UCI, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], MULTICENTER, clinical outcome, mortality rate, Critical Care and Intensive Care Medicine, intensive care unit, law.invention, 0302 clinical medicine, Severity of disease, law, middle aged, Medicine and Health Sciences, FAILURE, 030212 general & internal medicine, Hospital Mortality, intensive care units -- analysis -- epidemiology -- mortality, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), CODES, comparative study, intensive care, Medicine(all), multilevel analysi, Incidence, adult, Sciences bio-médicales et agricoles, Intensive care unit, 3. Good health, Europe, sepsa, Intensive Care Units, female, Cohort, enote intenzivne terapije -- analiza -- epidemiologija -- umrljivost, Human, Adult, medicine.medical_specialty, severity of disease, Critical Care, Sepsi, Intensive Care Unit, UNITED-STATES, 610 Medicine & health, INTENSIVE-CARE, European, Article, Sepsis, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, length of stay, male, Humans, Length of Stay, Anesthesiology, Intensive care, SCORE, medicine, udc:614.2, human, outcome assessment, Septic shock, business.industry, SEPTIC SHOCK, 030208 emergency & critical care medicine, medicine.disease, TRENDS, major clinical study, SEVERE SEPSIS, comorbidity assessment, Emergency medicine, Observational study, CLAIMS, business, resnost bolezni
Abstract

Purpose: To evaluate differences in the characteristics and outcomes of intensive care unit (ICU) patients over time. Methods: We reviewed all epidemiological data, including comorbidities, types and severity of organ failure, interventions, lengths of stay and outcome, for patients from the Sepsis Occurrence in Acutely ill Patients (SOAP) study, an observational study conducted in European intensive care units in 2002, and the Intensive Care Over Nations (ICON) audit, a survey of intensive care unit patients conducted in 2012. Results: We compared the 3147 patients from the SOAP study with the 4852 patients from the ICON audit admitted to intensive care units in the same countries as those in the SOAP study. The ICON patients were older (62.5 ± 17.0 vs. 60.6 ± 17.4 years) and had higher severity scores than the SOAP patients. The proportion of patients with sepsis at any time during the intensive care unit stay was slightly higher in the ICON study (31.9 vs. 29.6%, p = 0.03). In multilevel analysis, the adjusted odds of ICU mortality were significantly lower for ICON patients than for SOAP patients, particularly in patients with sepsis [OR 0.45 (0.35–0.59), p < 0.001]. Conclusions: Over the 10-year period between 2002 and 2012, the proportion of patients with sepsis admitted to European ICUs remained relatively stable, but the severity of disease increased. In multilevel analysis, the odds of ICU mortality were lower in our 2012 cohort compared to our 2002 cohort, particularly in patients with sepsis., 0, info:eu-repo/semantics/published

Published
2018

41. The Genomic Impact of European Colonization of the Americas

Author

Alessandro Raveane, Shahlo Turdikulova, Donata Luiselli, Pongsakorn Wangkumhang, Marta E. Alarcón-Riquelme, Francesco Montinaro, Guido Alberto Gnecchi-Ruscone, Damir Marjanović, Mait Metspalu, Sarabjit S. Mastana, Oleg Balanovsky, Alessandro Achilli, Antonio Torroni, Lejla Kovacevic, L. A. Atramentova, Anna Olivieri, Maria Fernanda Lima-Costa, Linda Ongaro, Cristian Capelli, Toomas Kivisild, Bernardo L. Horta, Nédio Mabunda, Marilia O. Scliar, Roy J. King, Etienne Patin, Kristiina Tambets, Garrett Hellenthal, Mauricio Lima Barreto, Celia A. May, Miguel Gonzalez-Santos, Andreja Leskovac, Andrés Moreno-Estrada, Eduardo Tarazona-Santos, Alexandre C. Pereira, Rodrigo Flores, Anastasia Kouvatsi, Luca Pagani, Stefania Sarno, Elena Balanovska, Ornella Semino, Davide Marnetto, Ongaro L., Scliar M.O., Flores R., Raveane A., Marnetto D., Sarno S., Gnecchi-Ruscone G.A., Alarcon-Riquelme M.E., Patin E., Wangkumhang P., Hellenthal G., Gonzalez-Santos M., King R.J., Kouvatsi A., Balanovsky O., Balanovska E., Atramentova L., Turdikulova S., Mastana S., Marjanovic D., Mulahasanovic L., Leskovac A., Lima-Costa M.F., Pereira A.C., Barreto M.L., Horta B.L., Mabunda N., May C.A., Moreno-Estrada A., Achilli A., Olivieri A., Semino O., Tambets K., Kivisild T., Luiselli D., Torroni A., Capelli C., Tarazona-Santos E., Metspalu M., Pagani L., Montinaro F., Institute of Genomics [Tartu, Estonia], University of Tartu, Universidade de São Paulo = University of São Paulo (USP), Dipartimento di Biologia e Biotecnologie 'Lazzaro Spallanzani' = Department of Biology and Biotechnology [Univ di Pavia] (DBB UNIPV), Università degli Studi di Pavia = University of Pavia (UNIPV), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Max Planck Institute for the Science of Human History (MPI-SHH), Max-Planck-Gesellschaft, Centre for Genomics and Oncological Reearch (GENYO), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University College of London [London] (UCL), University of Oxford, Stanford University School of Medicine [CA, USA], Aristotle University of Thessaloniki, Vavilov Institute of General Genetics, Russian Academy of Sciences [Moscow] (RAS), V.N. Karazin Kharkiv National University (KhNU), Institute of Bioorganic Chemistry [Tashkent, Uzbekistan], Academy of Sciences of Republic of Uzbekistan, Loughborough University, International Burch University [Sarajevo], University of Belgrade [Belgrade], Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Universidade Federal da Bahia (UFBA), Universidade Federal de Pelotas = Federal University of Pelotas (UFPel), Instituto Nacional de Saude [Maputo, Mozambique] (INS), University of Leicester, National Laboratory of Genomics for Biodiversity (LANGEBIO), Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Dipartimento di Biologia e Biotecnologie 'L. Spallanzani', Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Bologna/Università di Bologna, Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), University of São Paulo (USP), Dipartimento di Biologia e Biotecnologie ‘Lazzaro Spallanzani’, University of Pavia, University of Pavia, BIGEA, Department of Biological, Geological and Environmental Sciences, Alma Mater Studiorum – University of Bologna, Bologna, Italy, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], Fundação Oswaldo Cruz (FIOCRUZ), Universidade de São Paulo (USP), and University of Bologna

Subjects
0301 basic medicine, admixture history of the America, Human genetic variation, Colonialism, Atlantic Slave Trade, Gene flow, 0302 clinical medicine, Colonization, European colonization, African Continental Ancestry Group, 0303 health sciences, Genome, Middle East, Geography, Caribbean Region, Genetic structure, Ethnology, General Agricultural and Biological Sciences, Atlantic slave trade, Human, MESH: Caribbean Region, Gene Flow, American Native Continental Ancestry Group, Demographic history, European Continental Ancestry Group, Black People, Biology, General Biochemistry, Genetics and Molecular Biology, White People, 03 medical and health sciences, sex-biased admixture, Humans, admixture history of the Americas, MESH: Gene Flow, MESH: Genome, Human, American Indian or Alaska Native, 030304 developmental biology, MESH: Central America, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Central America, North America, South America, Genome, Human, MESH: South America, MESH: North America, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030217 neurology & neurosurgery
Abstract

The complexity of the admixture dynamics that shaped American populations is unveiled by Ongaro et al., where genetic data for more than 12,000 individuals from the continents are investigated. This study evaluates the dramatic impact of events after the colonial era, revealing a spatial and temporal heterogeneity and mirroring historical records. © 2019 Elsevier Ltd The human genetic diversity of the Americas has been affected by several events of gene flow that have continued since the colonial era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored. Here, we compiled a genome-wide dataset of ∼12,000 individuals from twelve American countries and ∼6,000 individuals from worldwide populations and applied haplotype-based methods to investigate how historical movements from outside the New World affected (1) the genetic structure, (2) the admixture profile, (3) the demographic history, and (4) sex-biased gene-flow dynamics of the Americas. We revealed a high degree of complexity underlying the genetic contribution of European and African populations in North and South America, from both geographic and temporal perspectives, identifying previously unreported sources related to Italy, the Middle East, and to specific regions of Africa. © 2019 Elsevier Ltd Preprint version of the article: "The genomic impact of European colonization of the Americas", posted June 28, 2019 on bioRxiv. Article is now published in Current Biology doi: [dx.doi.org/10.1016/j.cub.2019.09.076]. Published version on this repository: [http://vinar.vin.bg.ac.rs/handle/123456789/8654].

Published
2019

42. G-CSF for Extensive STEMI

Author

Achilli F., Pontone G., Bassetti B., Squadroni L., Campodonico J., Corrada E., Facchini C., Mircoli L., Esposito Giovanni, Scarpa D., Pidello S., Righetti S., Di Gennaro F., Guglielmo M., Muscogiuri G., Baggiano A., Limido A., Lenatti L., Di Tano G., Malafronte C., Soffici F., Ceseri M., Maggiolini S., Colombo G. I., Pompilio G., Achilli, F., Pontone, G., Bassetti, B., Squadroni, L., Campodonico, J., Corrada, E., Facchini, C., Mircoli, L., Esposito, Giovanni, Scarpa, D., Pidello, S., Righetti, S., Di Gennaro, F., Guglielmo, M., Muscogiuri, G., Baggiano, A., Limido, A., Lenatti, L., Di Tano, G., Malafronte, C., Soffici, F., Ceseri, M., Maggiolini, S., Colombo, G. I., and Pompilio, G.

Subjects
left ventricular remodeling, Male, Ventricular Remodeling, Heart Ventricles, percutaneous coronary intervention, Stroke Volume, Organ Size, Middle Aged, Myocardial Contraction, myocardial infarction, standard of care, Granulocyte Colony-Stimulating Factor, Humans, ST Elevation Myocardial Infarction, Female, Single-Blind Method, Prospective Studies, Aged
Abstract

In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term.The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain.Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/mEarly administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.

Published
2019

43. Population structure of modern-day Italians reveals patterns of ancient and archaic ancestries in Southern Europe

Author

Simona Barlera, Giovanni Birolo, Simon Myers, Viola Grugni, Vincenzo Lorenzo Pascali, Andrea Angius, Mait Metspalu, Francesca Brisighelli, Antonio Torroni, Francesco Montinaro, Hovirag Lancioni, Luísa Pereira, Antonella Mulas, Mohammed Melhaoui, Alessandro Achilli, Serena Aneli, Mohammed Cherkaoui, Peristera Paschou, M. Peyret-Guzzon, Pilar Galan, Giorgio B. Boncoraglio, A. M. Di Blasio, Stéphane Mazières, C. Di Gaetano, Garrett Hellenthal, Giuseppe Matullo, George Stamatoyannopoulos, Joanna Giemza, J. Di Cristofaro, Magdalena Zoledziewska, Irene Cardinali, Georgios Athanasiadis, Cristian Capelli, François-Xavier Ricaut, Jacques Chiaroni, Anna Olivieri, Alessandro Raveane, Luca Pagani, Toomas Kivisild, Abdellatif Baali, Nicolas Brucato, Christian Dina, Jean-Michel Dugoujon, Clare Bycroft, Alberto Piazza, Silvia Parolo, Francesco Cucca, Ornella Semino, Dipartimento di Biologia e Biotecnologie ‘Lazzaro Spallanzani’, University of Pavia, University of Pavia, University of Oxford [Oxford], Aarhus University [Aarhus], Istituto di Ricerche Farmacologiche Mario Negri, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione 'Istituto Neurologico Nazionale C. Mondino'-Fondazione 'Istituto Neurologico Nazionale C. Mondino', University of Turin, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Dipartimento di Genetica, Biologica e Biochimica, Università degli studi di Torino (UNITO), Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique (LERMA), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS), Georgia Tech - CNRS [Metz] (UMI2958), Ecole Nationale Supérieure des Arts et Metiers Metz-SUPELEC-Georgia Institute of Technology [Atlanta]-Georgia Institute of Technology [Lorraine, France]-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Centre National de la Recherche Scientifique (CNRS), Dipartimento di Genetica e Microbiologica, Università di Pavia, Dipartimento di Genetica e Microbiologia, Instituto de Investigação e Inovação em Saúde, Raveane, A, Aneli, S, Montinaro, F, Athanasiadis, G, Barlera, S, Birolo, G, Boncoraglio, G, Di Blasio, A, Di Gaetano, C, Pagani, L, Parolo, S, Paschou, P, Piazza, A, Stamatoyannopoulos, G, Angius, A, Brucato, N, Cucca, F, Hellenthal, G, Mulas, A, Peyret-Guzzon, M, Zoledziewska, M, Baali, A, Bycroft, C, Cherkaoui, M, Chiaroni, J, Di Cristofaro, J, Dina, C, Dugoujon, J, Galan, P, Giemza, J, Kivisild, T, Mazieres, S, Melhaoui, M, Metspalu, M, Myers, S, Pereira, L, Ricaut, F, Brisighelli, F, Cardinali, I, Grugni, V, Lancioni, H, Pascali, V, Torroni, A, Semino, O, Matullo, G, Achilli, A, Olivieri, A, Capelli, C, Mazières, Stéphane, Dipartimento di Biologia e Biotecnologie 'Lazzaro Spallanzani' = Department of Biology and Biotechnology [Univ di Pavia] (DBB UNIPV), Università degli Studi di Pavia = University of Pavia (UNIPV), University of Oxford, Università degli studi di Torino = University of Turin (UNITO), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université de Cergy Pontoise (UCP), Georgia Tech Lorraine [Metz], Ecole Nationale Supérieure des Arts et Metiers Metz-Georgia Institute of Technology [Atlanta]-Ecole Supérieure d'Electricité - SUPELEC (FRANCE)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Paris (ENS Paris), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut National de la Recherche Agronomique (INRA), HESAM Université (HESAM)-HESAM Université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Università degli Studi di Pavia, Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
SELECTION, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Distribution (economics), Population genetics, Neanderthal genome project, 0302 clinical medicine, Peninsula, HISTORY, Databases, Genetic, ADAPTATION, Research Articles, History, Ancient, media_common, Neanderthals, MODERN HUMANS, 0303 health sciences, Multidisciplinary, geography.geographical_feature_category, POPULATION GENETICS, GENOMICS, EUROPE, Population Genetic, SciAdv r-articles, ASSOCIATION, [SHS.ANTHRO-BIO] Humanities and Social Sciences/Biological anthropology, Multidisciplinary Sciences, ADMIXTURE, Geography, Italy, Ethnology, Science & Technology - Other Topics, Neanderthals / genetics, Research Article, EUROPE, MIGRATION, media_common.quotation_subject, Pastoralism, Human Genetic, Settore BIO/08 - ANTROPOLOGIA, GENETIC-STRUCTURE, SEQUENCE, White People, 03 medical and health sciences, Bronze Age, POPULATION GENETICS, Genetic variation, Animals, Humans, DNA, Ancient, European Continental Ancestry Group / genetics, 030304 developmental biology, Science & Technology, business.industry, Genome, Human, Genetic Drift, Human Genetics, Anthropology, GENOME-WIDE PATTERNS, business, GENOMICS, 030217 neurology & neurosurgery, Diversity (politics), Genome-Wide Association Study
Abstract

A population in a natural crossroad within Europe reveals multiple ancient contributions and substantial population structure., European populations display low genetic differentiation as the result of long-term blending of their ancient founding ancestries. However, it is unclear how the combination of ancient ancestries related to early foragers, Neolithic farmers, and Bronze Age nomadic pastoralists can explain the distribution of genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the continental diversity, but have been systematically understudied. Here, we characterize the ancestry profiles of Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe, and the rest of the world. Italian genomes capture several ancient signatures, including a non–steppe contribution derived ultimately from the Caucasus. Differences in ancestry composition, as the result of migration and admixture, have generated in Italy the largest degree of population structure detected so far in the continent, as well as shaping the amount of Neanderthal DNA in modern-day populations.

Published
2019

44. Ancient genomes reveal tropical bovid species in the Tibetan Plateau contributed to the prevalence of hunting game until the late Neolithic

Author

Fahu Chen, Victoria E. Mullin, Lele Ren, Ningbo Chen, Jiawen Hou, Xiaoming Zhang, Xuebin Qi, Duo Wu, Jiahui Huang, Alessandro Achilli, Guanghui Dong, Linyao Du, Chuzhao Lei, Xueye Zhao, Chunmei Li, Bing Su, and Marco Rosario Capodiferro

Subjects
0301 basic medicine, 010506 paleontology, Range (biology), Population Dynamics, Wildlife, Rhinoceros, Tibet, 01 natural sciences, DNA, Mitochondrial, Bos gaurus, Prehistory, 03 medical and health sciences, Homing Behavior, Animals, Humans, DNA, Ancient, ancient DNA, History, Ancient, Perissodactyla, 0105 earth and related environmental sciences, hunting game, Multidisciplinary, Plateau, geography.geographical_feature_category, Genome, biology, Ecology, Biodiversity, Ruminants, Population ecology, Biological Sciences, biology.organism_classification, late Neolithic, 030104 developmental biology, Geography, Ancient DNA, Animal Migration, Cattle, northeastern Tibetan Plateau
Abstract

Significance We undertook an ancient genomic DNA investigation of large animal remains dated ∼5,200 y B.P. from the Tibetan Plateau. We provide compelling evidence that the present-day low-latitude tropical inhabitants Bos gaurus and Dicerorhinus sumatrensis once roamed as far north as the margin of the northeastern Tibetan Plateau (NETP) during the late Neolithic, pushing the historical gaur distribution from ∼29°N to ∼34°N. Further multidisciplinary exploration indicates that a high summer temperature in the late Neolithic might have facilitated the northward expansion of these tropical animals to the NETP, which enriched the biodiversity of wildlife and contributed to the exploration of the Tibetan Plateau as one of the last habitats for hunting game in East Asia., Local wild bovids have been determined to be important prey on the northeastern Tibetan Plateau (NETP), where hunting game was a major subsistence strategy until the late Neolithic, when farming lifestyles dominated in the neighboring Loess Plateau. However, the species affiliation and population ecology of these prehistoric wild bovids in the prehistoric NETP remain unknown. Ancient DNA (aDNA) analysis is highly informative in decoding this puzzle. Here, we applied aDNA analysis to fragmented bovid and rhinoceros specimens dating ∼5,200 y B.P. from the Neolithic site of Shannashuzha located in the marginal area of the NETP. Utilizing both whole genomes and mitochondrial DNA, our results demonstrate that the range of the present-day tropical gaur (Bos gaurus) extended as far north as the margins of the NETP during the late Neolithic from ∼29°N to ∼34°N. Furthermore, comparative analysis with zooarchaeological and paleoclimatic evidence indicated that a high summer temperature in the late Neolithic might have facilitated the northward expansion of tropical animals (at least gaur and Sumatran-like rhinoceros) to the NETP. This enriched the diversity of wildlife, thus providing abundant hunting resources for humans and facilitating the exploration of the Tibetan Plateau as one of the last habitats for hunting game in East Asia.

Published
2020

45. Chemo‐Enzymatic Synthesis of S. mansoni O‐Glycans and Their Evaluation as Ligands for C‐Type Lectin Receptors MGL, DC‐SIGN, and DC‐SIGNR

Author

Anna Cioce, Niels-Christian Reichardt, Corinne Vivès, Anna Bernardi, Alvaro Hernández, Julie Pham, Franck Fieschi, Silvia Achilli, Giulio Goti, Michel Thépaut, CIC BiomaGUNE, CIC BiomaGUNE [Espagne], Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Università degli Studi di Milano = University of Milan (UNIMI), and Dipartimento di chimica, Universita degli Studi di Milano

Subjects
Glycan, Fucosyltransferase, Glycoconjugate, enzymes, carbohydrates, Receptors, Cell Surface, Ligands, 010402 general chemistry, 01 natural sciences, Catalysis, Polysaccharides, C-type lectin, Humans, Lectins, C-Type, Receptor, microarrays, chemistry.chemical_classification, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 010405 organic chemistry, Chemistry, Organic Chemistry, glycoconjugates, lectins, Lectin, General Chemistry, biology.organism_classification, 0104 chemical sciences, 3. Good health, DC-SIGN, carbohydrates (lipids), Biochemistry, biology.protein, Schistosoma mansoni, Cell Adhesion Molecules
Abstract

International audience; Due to their interactions with C-type lectin receptors (CLRs), glycans from the helminth Schistosoma mansoni represent promising leads for treatment of autoimmune diseases, allergies or cancer. We chemo-enzymatically synthesized nine O-glycans based on the two predominant O-glycan cores observed in the infectious stages of schistosomiasis, the mucin core 2 and the S. mansoni core. The O-glycans were fucosylated next to a selection of N-glycans directly on a microarray slide using a recombinant fucosyltransferase and GDP-fucose or GDP-6-azidofucose as donor. Binding assays with fluorescently labelled human CLRs DC-SIGN, DC-SIGNR and MGL revealed the novel O-glycan O8 as the best ligand for MGL from our panel. Significant binding to DC-SIGN was also found for azido-fucosylated glycans. Contrasting binding specificities were observed between the monovalent carbohydrate recognition domain (CRD) and the tetravalent extracellular domain (ECD) of DC-SIGNR.

Published
2020

46. Anemia in patients with Covid-19: pathogenesis and clinical significance

Author

Bergamaschi, Gaetano, Borrelli de Andreis, Federica, Aronico, Nicola, Lenti, Marco Vincenzo, Barteselli, Chiara, Merli, Stefania, Pellegrino, Ivan, Coppola, Luigi, Cremonte, Elisa Maria, Croce, Gabriele, Mordà, Francesco, Lapia, Francesco, Ferrari, Sara, Ballesio, Alessia, Parodi, Alessandro, Calabretta, Francesca, Ferrari, Maria Giovanna, Fumoso, Federica, Gentile, Antonella, Melazzini, Federica, Di Sabatino, Antonio, Bertolino, Giampiera, Codega, Silvia, Costanzo, Filippo, Cresci, Roberto, Derosa, Giuseppe, Stefano, Michele Di, Falaschi, Francesco, Iadarola, Carmine, Lovati, Elisabetta, Lucotti, Pietro Carlo, Martignoni, Alessandra, Mengoli, Caterina, Miceli, Emanuela, Mugellini, Amedeo, Muggia, Chiara, Noris, Patrizia, Pagani, Elisabetta, Palumbo, Ilaria, Pecci, Alessandro, Perrone, Tiziano, Pieresca, Carla, Preti, Paola Stefania, Russo, Maria Concetta, Sgarlata, Carmelo, Siciliani, Luisa, Staniscia, Andrea, Vjera, Francesca Torello, Achilli, Giovanna, Agostinelli, Andrea, Antoci, Valentina, Banfi, Francesco, Benedetti, Irene, Brattoli, Michele, Cambiè, Ginevra, Canta, Roberta, Cococcia, Sara, Conca, Federico, Delliponti, Mariangela, Rio, Virginia Del, Terlizzi, Francesco Di, Fiengo, Anna, Forni, Tommaso, Freddi, Giulia, Frigerio, Chiara, Fusco, Alessandra, Gabba, Margherita, Garolfi, Matteo, Gori, Giulia, Grandi, Giacomo, Grimaldi, Paolo, Lampugnani, Alice, Lepore, Federica, Lettieri, Gianluca, Mambella, Jacopo, Mercanti, Chiara, Nardone, Alba, Pace, Luca, Padovini, Lucia, Pitotti, Lavinia, Reduzzi, Margherita, Rigano, Giovanni, Rotola, Giorgio, Sabatini, Umberto, Salvi, Lucia, Santacroce, Giovanni, Savioli, Jessica, Soriano, Simone, Spataro, Carmine, and Stefani, Debora

Subjects
0301 basic medicine, Male, Comorbidity, Gastroenterology, Hemoglobins, 0302 clinical medicine, Medicine, Cholinesterases, Hematology, biology, medicine.diagnostic_test, Anemia, Iron-Deficiency, Oxygen partial pressure/oxygen concentration, Anemia, General Medicine, Middle Aged, C-Reactive Protein, 030220 oncology & carcinogenesis, Erythrocyte sedimentation rate, Original Article, Female, Adult, medicine.medical_specialty, Blood Sedimentation, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Red blood cell distribution width, Internal medicine, Humans, Clinical significance, Aged, L-Lactate Dehydrogenase, business.industry, SARS-CoV-2, C-reactive protein, COVID-19, Correction, medicine.disease, Ferritin, Oxygen, 030104 developmental biology, Ferritins, biology.protein, Erythrocyte Count, Hemoglobin, business, Anemia of inflammation, Blood Gas Monitoring, Transcutaneous
Abstract

COVID-19 patients typically present with lower airway disease, although involvement of other organ systems is usually the rule. Hematological manifestations such as thrombocytopenia and reduced lymphocyte and eosinophil numbers are highly prevalent in COVID-19 and have prognostic significance. Few data, however, are available about the prevalence and significance of anemia in COVID-19. In an observational study, we investigated the prevalence, pathogenesis and clinical significance of anemia among 206 patients with COVID-19 at the time of their hospitalization in an Internal Medicine unit. The prevalence of anemia was 61% in COVID-19, compared with 45% in a control group of 71 patients with clinical and laboratory findings suggestive of COVID-19, but nasopharyngeal swab tests negative for SARS-CoV-2 RNA (p = 0.022). Mortality was higher in SARS-CoV-2 positive patients. In COVID-19, females had lower hemoglobin concentration than males and a higher prevalence of moderate/severe anemia (25% versus 13%, p = 0.032). In most cases, anemia was mild and due to inflammation, sometimes associated with iron and/or vitamin deficiencies. Determinants of hemoglobin concentration included: erythrocyte sedimentation rate, serum cholinesterase, ferritin and protein concentrations and number of chronic diseases affecting each patient. Hemoglobin concentration was not related to overall survival that was, on the contrary, influenced by red blood cell distribution width, age, lactate dehydrogenase and the ratio of arterial partial oxygen pressure to inspired oxygen fraction. In conclusion, our results highlight anemia as a common manifestation in COVID-19. Although anemia does not directly influence mortality, it usually affects elderly, frail patients and can negatively influence their quality of life.

Published
2020

47. Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database

Author

David W. Larson, Mohamed A. Abd El Aziz, Pietro Achilli, Courtney N. Day, Anne-Lise D. D'Angelo, Jacopo Crippa, William S. Harmsen, Fabian Grass, and Kellie L. Mathis

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Adolescent, Databases, Factual, Colorectal cancer, medicine.medical_treatment, Perineural invasion, Datasets as Topic, Subgroup analysis, Kaplan-Meier Estimate, Adenocarcinoma, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Stage (cooking), Pathological, Colectomy, Aged, Neoplasm Staging, Aged, 80 and over, Adenocarcinoma/diagnosis, Adenocarcinoma/genetics, Adenocarcinoma/mortality, Adenocarcinoma/therapy, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Chemotherapy, Adjuvant/statistics & numerical data, Colonic Neoplasms/diagnosis, Colonic Neoplasms/genetics, Colonic Neoplasms/mortality, Colonic Neoplasms/therapy, Databases, Factual/statistics & numerical data, Female, Follow-Up Studies, Microsatellite Instability, Middle Aged, Treatment Outcome, United States/epidemiology, adjuvant chemotherapy, colon adenocarcinoma, high-risk features, national cancer database, overall survival, business.industry, Microsatellite instability, Cancer, medicine.disease, United States, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, business
Abstract

Utility of adjuvant chemotherapy for stage II cancer remains a matter of debate. Clinical guidelines suggest adjuvant chemotherapy for stage II tumors with high-risk features, in particular T4 tumors. However, limited consensus exists regarding the importance of other high-risk features (lymphovascular or perineural invasion, microsatellite instability). Our study aimed to investigate the impact of adjuvant chemotherapy for stage IIA (T3N0) colon cancer patients. Patients who underwent colectomy for stage IIA colon adenocarcinoma (2010-2015) were identified in the National Cancer Database (NCDB) and divided in two groups based on receipt of adjuvant chemotherapy vs observation. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed to compare overall survival between the two groups. Subgroup analysis of patients with specific high-risk features LVI, PNI and MSI was performed. Among 46 688 surgical patients with stage IIA colon adenocarcinoma 5937 (12.7%) received adjuvant chemotherapy, while 40 751 (87.3%) were observed. Five-year IPTW-adjusted survival was higher in the adjuvant chemotherapy group (79.7% [95% CI 79.1, 80.2]) compared to the observation group (70.3% [95% CI 69.7, 70.9]). Patients with high-risk pathological features showed an estimated 5-year survival benefit of 11.3% (78.2% [95% CI 77.4, 79.1] vs 66.9% [95% CI 65.9, 67.8]) when treated with adjuvant chemotherapy. This NCDB analysis revealed a survival benefit for patients with stage IIA colon adenocarcinoma and high-risk features that were treated with adjuvant chemotherapy.

Published
2020

48. Readmissions Within 48 Hours of Discharge: Reasons, Risk Factors, and Potential Improvements

Author

James Ansell, Kellie L. Mathis, Pietro Achilli, Eric J. Dozois, Martin Hübner, Jenna K. Lovely, Jacopo Crippa, Scott R. Kelley, David W. Larson, Kevin T. Behm, and Fabian Grass

Subjects
Adult, Male, Reoperation, medicine.medical_specialty, Ileus, 030230 surgery, Infections, Weight Gain, Patient Readmission, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Enhanced recovery, Risk Factors, medicine, Humans, Risk factor, Perioperative Period, Colectomy, Aged, Retrospective Studies, Gynecology, Hospital readmission, business.industry, Ileostomy, Betacoronavirus, Coronavirus Infections, Female, Infant, Newborn, Pandemics, Pneumonia, Viral, Pregnancy, Pregnant Women, Spain, Gastroenterology, Outcome measures, General Medicine, Acute Kidney Injury, Length of Stay, Middle Aged, medicine.disease, Infant newborn, Patient Discharge, Elective Surgical Procedures, 030220 oncology & carcinogenesis, business, Enhanced Recovery After Surgery, Hospital stay
Abstract

BACKGROUND Hospital readmission rate is an important quality metric and has been recognized as a key measure of hospital value-based purchasing programs. OBJECTIVE This study aimed to assess the risk factors for hospital readmission with a focus on potentially preventable early readmissions within 48 hours of discharge. DESIGN This is a retrospective cohort study. SETTINGS This study was conducted at a tertiary academic facility with a standardized enhanced recovery pathway. PATIENTS Consecutive patients undergoing elective major colorectal resections between 2011 and 2016 were included. MAIN OUTCOME MEASURES Univariable and multivariable risk factors for overall and early (

Published
2020

49. Impact of COVID-19 on liver function: results from an internal medicine unit in Northern Italy

Author

Lenti, Marco Vincenzo, Borrelli de Andreis, Federica, Pellegrino, Ivan, Klersy, Catherine, Merli, Stefania, Miceli, Emanuela, Aronico, Nicola, Mengoli, Caterina, Di Stefano, Michele, Cococcia, Sara, Santacroce, Giovanni, Soriano, Simone, Melazzini, Federica, Delliponti, Mariangela, Baldanti, Fausto, Triarico, Antonio, Corazza, Gino Roberto, Pinzani, Massimo, Di Sabatino, Antonio, Bergamaschi, Gaetano, Bertolino, Giampiera, Codega, Silvia, Costanzo, Filippo, Cresci, Roberto, Derosa, Giuseppe, Falaschi, Francesco, Iadarola, Carmine, Lovati, Elisabetta, Lucotti, Pietro Carlo, Martignoni, Alessandra, Mugellini, Amedeo, Muggia, Chiara, Noris, Patrizia, Pagani, Elisabetta, Palumbo, Ilaria, Pecci, Alessandro, Perrone, Tiziano, Pieresca, Carla, Preti, Paola Stefania, Russo, Mariaconcetta, Sgarlata, Carmelo, Siciliani, Luisa, Staniscia, Andrea, Torello Vjera, Francesca, Achilli, Giovanna, Agostinelli, Andrea, Antoci, Valentina, Ballesio, Alessia, Banfi, Francesco, Barteselli, Chiara, Benedetti, Irene, Brattoli, Michele, Calabretta, Francesca, Cambiè, Ginevra, Canta, Roberta, Conca, Federico, Coppola, Luigi, Cremonte, Elisa Maria, Croce, Gabriele, Del Rio, Virginia, Di Terlizzi, Francesco, Ferrari, Maria Giovanna, Ferrari, Sara, Fiengo, Anna, Forni, Tommaso, Freddi, Giulia, Frigerio, Chiara, Fumoso, Federica, Fusco, Alessandra, Gabba, Margherita, Garolfi, Matteo, Gentile, Antonella, Gori, Giulia, Grandi, Giacomo, Grimaldi, Paolo, Lampugnani, Alice, Lapia, Francesco, Lepore, Federica, Lettieri, Gianluca, Mambella, Jacopo, Mercanti, Chiara, Mordà, Francesco, Nardone, Alba, Pace, Luca, Padovini, Lucia, Parodi, Alessandro, Pitotti, Lavinia, Reduzzi, Margherita, Rigano, Giovanni, Rotola, Giorgio, Sabatini, Umberto, Salvi, Lucia, Savioli, Jessica, Spataro, Carmine, and Stefani, Debora

Subjects
Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, 030204 cardiovascular system & hematology, Acute respiratory failure, Chronic liver disease, Hepatitis, 03 medical and health sciences, 0302 clinical medicine, Intensive care, Internal medicine, Patients' Rooms, medicine, Internal Medicine, Humans, 030212 general & internal medicine, Pandemics, Aged, Retrospective Studies, Aged, 80 and over, Liver injury, medicine.diagnostic_test, business.industry, COVID-19, Retrospective cohort study, Middle Aged, medicine.disease, Im - Original, Coronavirus, Hospitalization, Severe acute respiratory syndrome, Italy, Liver, Emergency Medicine, Female, Liver function, Coronavirus Infections, business, Liver function tests, Liver Failure
Abstract

Little is known regarding coronavirus disease 2019 (COVID-19) clinical spectrum in non-Asian populations. We herein describe the impact of COVID-19 on liver function in 100 COVID-19 consecutive patients (median age 70 years, range 25–97; 79 males) who were admitted to our internal medicine unit in March 2020. We retrospectively assessed liver function tests, taking into account demographic characteristics and clinical outcome. A patient was considered as having liver injury when alanine aminotransferase (ALT) was > 50 mU/ml, gamma-glutamyl transpeptidase (GGT) > 50 mU/ml, or total bilirubin > 1.1 mg/dl. Spearman correlation coefficient for laboratory data and bivariable analysis for mortality and/or need for intensive care were assessed. A minority of patients (18.6%) were obese, and most patients were non- or moderate-drinkers (88.5%). Liver function tests were altered in 62.4% of patients, and improved during follow-up. None of the seven patients with known chronic liver disease had liver decompensation. Only one patient developed acute liver failure. In patients with altered liver function tests, PaO2/FiO2

Published
2020
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50. Risk of foetal harm with letrozole use in fertility treatment: a systematic review and meta-analysis

Author

Jyotsna Pundir, Priya Bhide, Chiara Achilli, Richard S. Legro, Shakila Thangaratinam, Helena J. Teede, Luk Rombauts, Javier Zamora, Luca Sabatini, and Arri Coomarasamy

Subjects
medicine.medical_specialty, medicine.drug_class, media_common.quotation_subject, Fertility, Clomiphene, 03 medical and health sciences, 0302 clinical medicine, Ovulation Induction, Pregnancy, medicine, Humans, 030212 general & internal medicine, Fertility drugs, media_common, 030219 obstetrics & reproductive medicine, Obstetrics, business.industry, Letrozole, Absolute risk reduction, Infant, Newborn, Obstetrics and Gynecology, Fertility Agents, Female, medicine.disease, Newcastle–Ottawa scale, Reproductive Medicine, Meta-analysis, Female, business, Infertility, Female, Live Birth, medicine.drug, Cohort study, Polycystic Ovary Syndrome
Abstract

BACKGROUNDThe aromatase inhibitor letrozole is increasingly recommended for ovulation induction, as it is more effective with fewer side-effects than other agents. But many clinicians are reluctant to use the drug for fertility treatment due to a strong-label warning against its use, which warns about congenital malformation risk to the foetus in women seeking pregnancy.OBJECTIVE AND RATIONALEThe aim of this study was to determine the risks of congenital malformations and pregnancy loss with letrozole compared with clomiphene primarily, and with other fertility drugs and natural conception.SEARCH METHODSA systematic review and meta-analysis using PRISMA harms guidelines. We searched MEDLINE, EMBASE and other sources from inception until January 2020, with the MeSH words for ‘letrozole’ and pregnancy OR foetal/neonatal outcome. We included studies reported on congenital malformations in foetuses born to mothers conceived after fertility treatment, with letrozole versus clomiphene, placebo, gonadotrophins, metformin, natural conception or other agents, from randomised trials, comparative cohort studies and non-comparative observational cohorts. Quality of the studies was assessed using Cochrane risk of bias tool and Newcastle Ottawa Scale. The McMaster tool was used to assess the quality of reported harm for foetal congenital malformations in the studies. We compared the absolute risk of events using risk difference measures and pooled the findings using a fixed-effect model. We evaluated the statistical heterogeneity using forest plots and the I2 statistic and funnel plot to assess publication bias. We assessed the strength of evidence for congenital malformation and pregnancy loss as per the GRADE recommendations and with the Fragility index.OUTCOMESWe included 46 studies (18 randomised trials; 21 comparative cohorts; 7 non-comparative cohorts). Overall 2.15% (101/4697; 95% CI 1.7 to 2.5) of babies conceived on letrozole for fertility treatment had congenital foetal malformations. We did not observe a significant increase in congenital malformations with letrozole versus clomiphene in the randomised trials (risk difference (RD) 0.01, 95% CI −0.02, 0.03; I2 = 0%; 14 studies) and found a significant reduction in the cohort studies (RD −0.02, 95% CI −0.04, −0.01; I2 = 0%, 11 studies). The fragility index was 44% (7/16) (either an increase in the intervention arm or a decrease in control arm was needed to alter the results). The risks of pregnancy loss were not increased with letrozole versus clomiphene in the 14 randomised trials (RD −0.01, 95% CI −0.06, 0.04; I2 = 0%), and the risks were reduced in the six cohort studies (RD −0.09, 95% CI −0.17, −0.00; I2 = 68%). The GRADE quality of evidence was low to moderate for congenital malformations and pregnancy loss. We did not find any increased congenital malformation risk with letrozole versus gonadotrophins, natural conception or natural cycle ART, but the number of studies was small.WIDER IMPLICATIONSThere is no evidence that letrozole increases the risk of congenital foetal malformation or pregnancy loss compared with clomiphene, natural conception or other fertility agents, to warrant warning against its use. Given its therapeutic benefits and lack of evidence of harm to the foetus, clinicians should consider letrozole as first-line agent for ovulation induction.

Published
2020

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