14 results on '"Leone B"'
Search Results
2. Proposal of a classification of cannulation damage in vascular access grafts based on clinical, ultrasound, and microscopic observations
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Franchin, M, Vergani, B, Huber, V, Leone, B, Villa, A, Muscato, P, Cervarolo, M, Piffaretti, G, Tozzi, M, Franchin M., Vergani B., Huber V., Leone B. E., Villa A., Muscato P., Cervarolo M. C., Piffaretti G., Tozzi M., Franchin, M, Vergani, B, Huber, V, Leone, B, Villa, A, Muscato, P, Cervarolo, M, Piffaretti, G, Tozzi, M, Franchin M., Vergani B., Huber V., Leone B. E., Villa A., Muscato P., Cervarolo M. C., Piffaretti G., and Tozzi M.
- Abstract
Introduction: Arteriovenous grafts (AVGs) serve as an alternative to native arteriovenous fistulas (AVFs) in the context of hemodialysis patient life planning. AVGs are more susceptible to developing outflow stenosis (due to intimal hyperplasia), thrombosis, and infections. However, an often overlooked contributor to AVG failure is cannulation damage. The objective of this paper is to assess the impact of cannulations on AVGs. We aim to establish a classification of AVG damage by comparing clinical data and ultrasound images with microscopic morphological findings obtained from explanted grafts.Materials and methods: This study is conducted at a single center. We included all patients who underwent AVG creation between 2011 and 2019. Comprehensive data on clinical history, follow-up, and complications were collected and reviewed. Duplex ultrasound (DUS) characteristics were documented, and all grafts explanted during the analysis period underwent optical microscopy evaluation. Finally, clinical data, along with DUS and microscopic findings, were integrated to derive a damage classification.Results: During the study period, 247 patients underwent 334 early cannulation AVGs. The median follow-up duration was 714 days (IQR 392, 1195). One hundred eleven (33%) grafts were explanted. Clinical data and DUS findings were utilized to formulate a four-grade classification system indicating increasing damage.Conclusion: Cannulation damage alone does not solely account for AVG failure. It results from a biological host-mediated process that promotes the growth of intimal hyperplasia at the cannulation sites. This process is not clinically significant within the initial 2 years after AVG creation.
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- 2024
3. High-risk HPV genotypes are associated with anal cytologic abnormalities but not with malignant histological lesions in a cohort of people with HIV (PWH)
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Squillace, N, Bernasconi, D, Cogliandro, V, Lapadula, G, Soria, A, Sabbatini, F, Colella, E, Rossi, M, Cappelletti, A, Spreafico, G, Tamburini, A, Leone, B, Malandrin, S, Cavallero, A, Di Lucia, A, Braga, M, Bonfanti, P, Bernasconi, DP, Tamburini, AM, Leone, BE, Squillace, N, Bernasconi, D, Cogliandro, V, Lapadula, G, Soria, A, Sabbatini, F, Colella, E, Rossi, M, Cappelletti, A, Spreafico, G, Tamburini, A, Leone, B, Malandrin, S, Cavallero, A, Di Lucia, A, Braga, M, Bonfanti, P, Bernasconi, DP, Tamburini, AM, and Leone, BE
- Published
- 2024
4. The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.
- Author
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Knoll, R, Helbig, ET, Dahm, K, Bolaji, O, Hamm, F, Dietrich, O, van Uelft, M, Müller, S, Bonaguro, L, Schulte-Schrepping, J, Petrov, L, Krämer, B, Kraut, M, Stubbemann, P, Thibeault, C, Brumhard, S, Theis, H, Hack, G, De Domenico, E, Nattermann, J, Becker, M, Beyer, MD, Hillus, D, Georg, P, Loers, C, Tiedemann, J, Tober-Lau, P, Lippert, L, Millet Pascual-Leone, B, Tacke, F, Rohde, G, Suttorp, N, Witzenrath, M, CAPNETZ Study Group, Pa-COVID-19 Study Group, Saliba, A-E, Ulas, T, Polansky, JK, Sawitzki, B, Sander, LE, Schultze, JL, Aschenbrenner, AC, Kurth, F, Knoll, R, Helbig, ET, Dahm, K, Bolaji, O, Hamm, F, Dietrich, O, van Uelft, M, Müller, S, Bonaguro, L, Schulte-Schrepping, J, Petrov, L, Krämer, B, Kraut, M, Stubbemann, P, Thibeault, C, Brumhard, S, Theis, H, Hack, G, De Domenico, E, Nattermann, J, Becker, M, Beyer, MD, Hillus, D, Georg, P, Loers, C, Tiedemann, J, Tober-Lau, P, Lippert, L, Millet Pascual-Leone, B, Tacke, F, Rohde, G, Suttorp, N, Witzenrath, M, CAPNETZ Study Group, Pa-COVID-19 Study Group, Saliba, A-E, Ulas, T, Polansky, JK, Sawitzki, B, Sander, LE, Schultze, JL, Aschenbrenner, AC, and Kurth, F
- Abstract
Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes. These molecular responses to dexamethasone were detected in circulating and pulmonary monocytes, and they were directly linked to survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived signatures were enriched in whole blood transcriptomes of patients with fatal outcome in two independent cohorts, highlighting the potential for identifying non-responders refractory to dexamethasone. Our findings link the effects of dexamethasone to specific immunomodulation and reversal of monocyte dysregulation, and they highlight the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches.
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- 2024
5. Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade
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Rivoltini, L, Camisaschi, C, Fucà, G, Paolini, B, Vergani, B, Beretta, V, Damian, S, Duca, M, Cresta, S, Magni, M, Leone, B, Castelli, C, de Braud, F, De Santis, F, Di Nicola, M, Rivoltini, Licia, Camisaschi, Chiara, Fucà, Giovanni, Paolini, Biagio, Vergani, Barbara, Beretta, Valeria, Damian, Silvia, Duca, Matteo, Cresta, Sara, Magni, Michele, Leone, Biagio Eugenio, Castelli, Chiara, de Braud, Filippo, De Santis, Francesca, Di Nicola, Massimo, Rivoltini, L, Camisaschi, C, Fucà, G, Paolini, B, Vergani, B, Beretta, V, Damian, S, Duca, M, Cresta, S, Magni, M, Leone, B, Castelli, C, de Braud, F, De Santis, F, Di Nicola, M, Rivoltini, Licia, Camisaschi, Chiara, Fucà, Giovanni, Paolini, Biagio, Vergani, Barbara, Beretta, Valeria, Damian, Silvia, Duca, Matteo, Cresta, Sara, Magni, Michele, Leone, Biagio Eugenio, Castelli, Chiara, de Braud, Filippo, De Santis, Francesca, and Di Nicola, Massimo
- Abstract
In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an exceptional, long-lasting, tumor complete response in a patient with metastatic TNBC treated with dual PD-1 and LAG-3 blockade within the phase I/II study CLAG525X2101C (NCT02460224) The pre-treatment tumor biopsy revealed the presence of a CD3+ and CD8+ cell infiltrate, with few PD1+ cells, rare CD4+ cells, and an absence of both NK cells and LAG3 expression. Conversely, tumor cells exhibited positive staining for the three primary LAG-3 ligands (HLA-DR, FGL-1, and galectin-3), while being negative for PD-L1. In peripheral blood, baseline expression of LAG-3 and PD-1 was observed in circulating immune cells. Following treatment initiation, there was a rapid increase in proliferating granzyme-B+ NK and T cells, including CD4+ T cells, alongside a reduction in myeloid-derived suppressor cells. The role of LAG-3 expression on circulating NK cells, as well as the expression of LAG-3 ligands on tumor cells and the early modulation of circulating cytotoxic CD4+ T cells warrant further investigation as exploitable predictive biomarkers for dual PD-1 and LAG-3 blockade. Trial registration: NCT02460224. Registered 02/06/2015.
- Published
- 2024
6. Novel cellular systems unveil mucosal melanoma initiating cells and a role for PI3K/Akt/mTOR pathway in mucosal melanoma fitness
- Author
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Monti, M, Benerini Gatta, L, Bugatti, M, Pezzali, I, Picinoli, S, Manfredi, M, Lavazza, A, Vanella, V, De Giorgis, V, Zanatta, L, Missale, F, Lonardi, S, Zanetti, B, Bozzoni, G, Cadei, M, Abate, A, Vergani, B, Balzarini, P, Battocchio, S, Facco, C, Turri-Zanoni, M, Castelnuovo, P, Nicolai, P, Fonsatti, E, Leone, B, Marengo, E, Sigala, S, Ronca, R, Perego, M, Lombardi, D, Vermi, W, Monti, Matilde, Benerini Gatta, Luisa, Bugatti, Mattia, Pezzali, Irene, Picinoli, Sara, Manfredi, Marcello, Lavazza, Antonio, Vanella, Virginia Vita, De Giorgis, Veronica, Zanatta, Lucia, Missale, Francesco, Lonardi, Silvia, Zanetti, Benedetta, Bozzoni, Giovanni, Cadei, Moris, Abate, Andrea, Vergani, Barbara, Balzarini, Piera, Battocchio, Simonetta, Facco, Carla, Turri-Zanoni, Mario, Castelnuovo, Paolo, Nicolai, Piero, Fonsatti, Ester, Leone, Biagio Eugenio, Marengo, Emilio, Sigala, Sandra, Ronca, Roberto, Perego, Michela, Lombardi, Davide, Vermi, William, Monti, M, Benerini Gatta, L, Bugatti, M, Pezzali, I, Picinoli, S, Manfredi, M, Lavazza, A, Vanella, V, De Giorgis, V, Zanatta, L, Missale, F, Lonardi, S, Zanetti, B, Bozzoni, G, Cadei, M, Abate, A, Vergani, B, Balzarini, P, Battocchio, S, Facco, C, Turri-Zanoni, M, Castelnuovo, P, Nicolai, P, Fonsatti, E, Leone, B, Marengo, E, Sigala, S, Ronca, R, Perego, M, Lombardi, D, Vermi, W, Monti, Matilde, Benerini Gatta, Luisa, Bugatti, Mattia, Pezzali, Irene, Picinoli, Sara, Manfredi, Marcello, Lavazza, Antonio, Vanella, Virginia Vita, De Giorgis, Veronica, Zanatta, Lucia, Missale, Francesco, Lonardi, Silvia, Zanetti, Benedetta, Bozzoni, Giovanni, Cadei, Moris, Abate, Andrea, Vergani, Barbara, Balzarini, Piera, Battocchio, Simonetta, Facco, Carla, Turri-Zanoni, Mario, Castelnuovo, Paolo, Nicolai, Piero, Fonsatti, Ester, Leone, Biagio Eugenio, Marengo, Emilio, Sigala, Sandra, Ronca, Roberto, Perego, Michela, Lombardi, Davide, and Vermi, William
- Abstract
Background: Mucosal Melanomas (MM) are highly aggressive neoplasms arising from mucosal melanocytes. Current treatments offer a limited survival benefit for patients with advanced MM; moreover, the lack of pre-clinical cellular systems has significantly limited the understanding of their immunobiology. Methods: Five novel cell lines were obtained from patient-derived biopsies of MM arising in the sino-nasal mucosa and designated as SN-MM1-5. The morphology, ultrastructure and melanocytic identity of SN-MM cell lines were validated by transmission electron microscopy and immunohistochemistry. Moreover, in vivo tumorigenicity of SN-MM1-5 was tested by subcutaneous injection in NOD/SCID mice. Molecular characterization of SN-MM cell lines was performed by a mass-spectrometry proteomic approach, and their sensitivity to PI3K chemical inhibitor LY294002 was validated by Akt activation, measured by pAkt(Ser473) and pAkt(Thr308) in immunoblots, and MTS assay. Results: This study reports the validation and functional characterization of five newly generated SN-MM cell lines. Compared to the normal counterpart, the proteomic profile of SN-MM is consistent with transformed melanocytes showing a heterogeneous degree of melanocytic differentiation and activation of cancer-related pathways. All SN-MM cell lines resulted tumorigenic in vivo and display recurrent structural variants according to aCGH analysis. Of relevance, the microscopic analysis of the corresponding xenotransplants allowed the identification of clusters of MITF-/CDH1-/CDH2 + /ZEB1 + /CD271 + cells, supporting the existence of melanoma-initiating cells also in MM, as confirmed in clinical samples. In vitro, SN-MM cell lines were sensitive to cisplatin, but not to temozolomide. Moreover, the proteomic analysis of SN-MM cell lines revealed that RICTOR, a subunit of mTORC2 complex, is the most significantly activated upstream regulator, suggesting a relevant role for the PI3K-Akt-mTOR pathway in these neoplasms. Co
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- 2024
7. Harnessing Stadium Roofs for Community Electrical Power: A Case Study of Rome’s Olympic Stadium Title
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Leone Barbaro, Gabriele Battista, Emanuele de Lieto Vollaro, and Roberto de Lieto Vollaro
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photovoltaic ,renewable energy community ,renewable energy ,climate change ,sport stadium ,sustainability ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Within a city, there is a lack of space for the installation of photovoltaic panels, especially in cities with significant artistic heritage. Hence, there is a need to identify new spaces for the installation of renewable energy systems capable of supplying part of the city’s energy demand. Large infrastructures for public use such as stadiums, because of their characteristics, can become an essential resource for surrounding communities by installing photovoltaic panels on their roofs. This innovative approach can supply renewable electricity to the local community, aligning with the concept of renewable energy communities (RECs). This study focuses on the Olympic Stadium in Rome, exploring a new way to produce and share the electricity generated. An energy simulation of the photovoltaic plant was carried out by means of a transient calculation tool System Advisor Model (SAM). Then, the energy output from photovoltaics was correlated with the stadium, streetlight, and household electrical energy demands. The results highlight the suitability of the photovoltaic plant and the energy, economic, and environmental advantages derived from its exploitation.
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- 2024
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8. Comparison between Direct and Indirect Heat Flux Measurement Techniques: Preliminary Laboratory Tests
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Luca Evangelisti, Leone Barbaro, Claudia Guattari, Edoardo De Cristo, Roberto De Lieto Vollaro, and Francesco Asdrubali
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heat flow meter sensor ,indirect approach for heat flow estimation ,convective and radiative coefficients ,non-destructive test ,data processing ,Technology - Abstract
Direct and indirect approaches can be employed for estimating the heat flow through components in different application fields. In the building sector, the thermometric method is often applied by professionals for thermal transmittance evaluations. However, miscalculations can derive from inaccurate total heat transfer coefficients, and a consensus regarding the appropriate value to employ remains to be determined. Here, an apparatus was realized for laboratory tests and heat flux measurements were performed following direct and indirect approaches. Data acquired through a common heat flow sensor were compared with those computed through a post-processing based on radiative and convective estimations. The results were affected by the specific correlation adopted for computing the convective coefficients, with the percentage differences ranging from −9.8% to −0.4%. New measurement systems could be designed for automatically computing heat fluxes through indirect approaches, thus providing alternative solutions in the panorama of non-destructive tests for building energy diagnosis.
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- 2024
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9. Clinical predictors of postoperative complications in the context of enhanced recovery (ERAS) in patients with esophageal and gastric cancer.
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Geroin C, Weindelmayer J, Camozzi S, Leone B, Turolo C, Hetoja S, Bencivenga M, Sacco M, De Pasqual CA, Mattioni E, de Manzoni G, and Giacopuzzi S
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- Humans, Male, Female, Aged, Middle Aged, Enhanced Recovery After Surgery, Operative Time, Esophagectomy adverse effects, Esophagectomy methods, Stomach Neoplasms surgery, Esophageal Neoplasms surgery, Postoperative Complications epidemiology, Postoperative Complications etiology
- Abstract
The overall frequency of postoperative complications in patients with esophageal and gastric cancer diverges between studies. We evaluated the frequency and assessed the relationship between complications and demographic and clinical features. For this observational study, data were extracted from the ERAS Registry managed by the University of Verona, Italy. Patients were evaluated and compared for postoperative complications according to the consensus-based classification and the Clavien-Dindo scale. The study population was 877 patients: 346 (39.5%) with esophageal and 531 (60.5%) with gastric cancer; 492 (56.2%) reported one or more postoperative complications, 213 (61.6%) of those with esophageal and 279 (52.5%) of those with gastric cancer. When stratified by consensus-based classification, patients with esophageal cancer reported general postoperative complications more frequently (p < 0.001) than those with gastric cancer, but there was no difference in postoperative surgical complications between the two groups. Multiple logistic regression models revealed an association between postoperative complications and the Charlson Comorbidity Index (adjusted odds ratio [OR] 1.22; 95% confidence interval [CI] 1.08-1.36), operation time (adjusted OR, 1.08; 95% CI 1.00-1.15), and days to solid diet intake (adjusted OR, 1.39; 95% CI 1.20-1.59). Complications in patients with esophageal and gastric cancer are frequent, even in those treated according to ERAS principles, and are often associated with comorbidities, longer operative time, and longer time to solid diet intake., (© 2024. The Author(s).)
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- 2024
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10. The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.
- Author
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Knoll R, Helbig ET, Dahm K, Bolaji O, Hamm F, Dietrich O, van Uelft M, Müller S, Bonaguro L, Schulte-Schrepping J, Petrov L, Krämer B, Kraut M, Stubbemann P, Thibeault C, Brumhard S, Theis H, Hack G, De Domenico E, Nattermann J, Becker M, Beyer MD, Hillus D, Georg P, Loers C, Tiedemann J, Tober-Lau P, Lippert L, Millet Pascual-Leone B, Tacke F, Rohde G, Suttorp N, Witzenrath M, Saliba AE, Ulas T, Polansky JK, Sawitzki B, Sander LE, Schultze JL, Aschenbrenner AC, and Kurth F
- Subjects
- Humans, Male, Female, Transcriptome, Middle Aged, Aged, Glucocorticoids therapeutic use, Glucocorticoids pharmacology, Lung pathology, Adult, Dexamethasone pharmacology, Dexamethasone therapeutic use, Monocytes metabolism, Monocytes drug effects, COVID-19 Drug Treatment, COVID-19, SARS-CoV-2 drug effects, Single-Cell Analysis
- Abstract
Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes. These molecular responses to dexamethasone were detected in circulating and pulmonary monocytes, and they were directly linked to survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived signatures were enriched in whole blood transcriptomes of patients with fatal outcome in two independent cohorts, highlighting the potential for identifying non-responders refractory to dexamethasone. Our findings link the effects of dexamethasone to specific immunomodulation and reversal of monocyte dysregulation, and they highlight the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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11. Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19.
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Essex M, Millet Pascual-Leone B, Löber U, Kuhring M, Zhang B, Brüning U, Fritsche-Guenther R, Krzanowski M, Fiocca Vernengo F, Brumhard S, Röwekamp I, Anna Bielecka A, Lesker TR, Wyler E, Landthaler M, Mantei A, Meisel C, Caesar S, Thibeault C, Corman VM, Marko L, Suttorp N, Strowig T, Kurth F, Sander LE, Li Y, Kirwan JA, Forslund SK, and Opitz B
- Subjects
- Humans, Male, Female, Middle Aged, Metabolome, Inflammation, Kynurenine metabolism, Kynurenine blood, Aged, Adult, COVID-19 microbiology, COVID-19 immunology, Tryptophan metabolism, Gastrointestinal Microbiome, Dysbiosis, SARS-CoV-2, Cytokines blood, Cytokines metabolism
- Abstract
The clinical course of COVID-19 is variable and often unpredictable. To test the hypothesis that disease progression and inflammatory responses associate with alterations in the microbiome and metabolome, we analyzed metagenome, metabolome, cytokine, and transcriptome profiles of repeated samples from hospitalized COVID-19 patients and uninfected controls, and leveraged clinical information and post-hoc confounder analysis. Severe COVID-19 was associated with a depletion of beneficial intestinal microbes, whereas oropharyngeal microbiota disturbance was mainly linked to antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine and reduced levels of several other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Moreover, reduced concentrations of various tryptophan metabolites were associated with depletion of Faecalibacterium, and tryptophan decrease and kynurenine increase were linked to enhanced production of inflammatory cytokines. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19., (© 2024. The Author(s).)
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- 2024
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12. Multicenter study on the incidence and treatment of mediastinal leaks after esophagectomy (MuMeLe 2).
- Author
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Ascari F, De Pascale S, Rosati R, Giacopuzzi S, Puccetti F, Weindelmayer J, Cusin S, Leone B, and Fumagalli Romario U
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- Humans, Male, Female, Incidence, Middle Aged, Aged, Italy epidemiology, Retrospective Studies, Esophageal Neoplasms surgery, Reoperation statistics & numerical data, Esophagectomy adverse effects, Esophagectomy methods, Anastomotic Leak epidemiology, Anastomotic Leak etiology, Anastomotic Leak therapy, Mediastinum surgery
- Abstract
Background: Management of mediastinal anastomotic leaks (MALs) after Ivor Lewis esophagectomy includes conservative, endoscopic, or surgical management. Endoscopic vacuum therapy (EVAC) is becoming a routine approach for MALs, although the outcomes have not been defined. This study aimed to describe the incidence, treatment, and outcomes of MALs in patients who underwent esophagectomy in 3 Italian high-volume centers that routinely use EVAC for MAL., Methods: Patients who underwent Ivor Lewis esophagectomy between September 2018 and March 2023 were included., Results: A total of 681 patients underwent Ivor Lewis esophagectomy, of whom 88 had MAL. The MAL rates for open, minimally invasive, and robotic esophagectomies were 11.5%, 13.4%, and 14.8%, respectively. Global and specific 30- and 90-day mortality rates for MAL were 0.9% and 2.1% and 6.8% and 15.9%, respectively. Nonoperative management (NOM) as the primary treatment was chosen for 62 patients. EVAC was the most common NOM (62.9%), and the most common operative management (OM) was anastomotic redo (53.8%). Diversion was the OM for 7 patients, of whom 3 patients died. Primary treatment proved successful in 40 patients. Among them, EVAC alone was successful in 35.9% of patients. Globally, endoscopic treatment, including EVAC, was successful in 79.0% of NOM and 55.7% of MALs. NOM and OM were chosen as secondary treatments for 27 and 10 patients, respectively. Secondary treatment proved successful in 21 patients., Conclusion: The incidence of MALs after Ivor Lewis esophagectomy is approximately 13%. Endoscopic techniques have a success rate of almost 80%, with EVAC representing a significant part of this treatment process., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)
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- 2024
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13. Percutaneous drainage and combined praziquantel-albendazole therapy: a novel approach for the treatment of simple echinococcal liver cysts.
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Richter J, Lindner AK, Geisel D, Fleckenstein FN, Torsello GF, Millet Pascual-Leone B, Ivanov O, Zöllner C, Wilde AB, and Equihua Martinez G
- Subjects
- Humans, Albendazole therapeutic use, Praziquantel therapeutic use, Neoplasm Recurrence, Local, Drainage, Ethanol, Liver, Echinococcosis drug therapy, Echinococcosis, Hepatic diagnosis, Echinococcosis, Hepatic drug therapy, Cysts drug therapy
- Abstract
Cystic echinococcosis (CE) is a worldwide helminthic zoonosis causing serious disease in humans. The WHO Informal Working Group on Echinococcosis recommends a stage-specific treatment approach of hepatic CE that facilitates the decision on what therapy option is most appropriate. Percutaneous aspiration, instillation of a scolicide, e.g., ethanol or hypertonic saline, and subsequent re-aspiration (PAIR) have been advocated for treating medium-size unilocular WHO-stage CE1 cysts. PAIR can pose a risk of toxic cholangitis because of spillage of ethanol in the case of a cysto-biliary fistula or of life-threatening hypernatriaemia when hypertonic saline is used. The purpose of our study is to develop an alternative, safe, minimally invasive method to treat CE1 cysts, avoiding the use of toxic topic scolicides.We opt for percutaneous drainage (PD) in four patients: the intrahepatic drainage catheter is placed under CT-fluoroscopy, intracystic fluid is aspirated, and the viability of intracystic echinococcal protoscolices is assessed microscopically. Oral praziquantel (PZQ) is added to albendazole (ABZ) instead of using topical scolicidals.Protoscolices degenerate within 5 to 10 days after PZQ co-medication at a cumulative dosage of 250 to 335 mg/kg, and the cysts collapse. The cysts degenerate, and no sign of spillage nor relapse is observed in the follow-up time of up to 24 months post-intervention.In conclusion, PD combined with oral PZQ under ABZ coverage is preferable to PAIR in patients with unilocular echinococcal cysts., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
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- 2024
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14. Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung.
- Author
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Dörner PJ, Anandakumar H, Röwekamp I, Fiocca Vernengo F, Millet Pascual-Leone B, Krzanowski M, Sellmaier J, Brüning U, Fritsche-Guenther R, Pfannkuch L, Kurth F, Milek M, Igbokwe V, Löber U, Gutbier B, Holstein M, Heinz GA, Mashreghi MF, Schulte LN, Klatt AB, Caesar S, Wienhold SM, Offermanns S, Mack M, Witzenrath M, Jordan S, Beule D, Kirwan JA, Forslund SK, Wilck N, Bartolomaeus H, Heimesaat MM, and Opitz B
- Subjects
- Humans, Mice, Animals, Monocytes, Klebsiella pneumoniae, Lung, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Anti-Infective Agents pharmacology
- Abstract
Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP., (© 2024. The Author(s).)
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- 2024
- Full Text
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