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1. Diagnostic accuracy of clinical signs, symptoms and point-of-care testing for early adenoviral conjunctivitis

Author: Chamila D Perera, Julia Huecker, Mae O. Gordon, Jennifer S Harthan, Tammy Than, Christina E Morettin, Mary K. Migneco, Ellen Shorter, Andrew T. E. Hartwick, Spencer Johnson, and Meredith Whiteside
Subjects: Adult, medicine.medical_specialty, Receiver operating characteristic, business.industry, Point-of-care testing, Acute Conjunctivitis, Swollen lymph nodes, Logistic regression, Conjunctivitis, Polymerase Chain Reaction, Adenovirus Infections, Human, Ophthalmology, Conjunctivitis, Viral, Point-of-Care Testing, Internal medicine, medicine, Humans, Sign/symptom, Clinical significance, medicine.symptom, Red eye, business, Optometry
Abstract: CLINICAL RELEVANCE This study identifies key signs and symptoms of acute conjunctivitis, that when combined with a point-of-care test, can improve clinician accuracy of diagnosing adenoviral conjunctivitis. BACKGROUND Adenoviral conjunctivitis is a common ocular infection with the potential for high economic impact due to widespread outbreaks and subsequent furloughs from work and school. In this report, we describe clinical signs and participant-reported symptoms that most accurately identify polymerase chain reaction (PCR)-confirmed adenoviral conjunctivitis. METHODS Adults with 'red eye' symptoms of four days or less were enrolled. Participants rated 10 ocular symptoms from 0 (not bothersome) to 10 (very bothersome), and indicated the presence or absence of systemic flu-like symptoms. Clinicians determined the presence or absence of swollen lymph nodes and rated the severity of eight ocular signs using a 5-point scale. An immunoassay targeting adenovirus antigen was utilised for the point-of-care test, and conjunctival swab samples were obtained for subsequent adenovirus detection by PCR analyses. Univariate and multivariate logistic regression models were used to identify symptoms and signs associated with PCR-confirmed adenoviral conjunctivitis. The diagnostic accuracy of these clinical findings, and the potential benefit of incorporating point-of-care test results, was assessed by calculating areas under the receiver operating characteristic curves (AUC). RESULTS Clinician-rated bulbar conjunctival redness, participant-rated eyelid swelling and overall ocular discomfort had the best predictive value in the multivariate logistic regression model with an AUC of 0.83. The addition of the point-of-care test results to these three clinical sign/symptom scores improved diagnostic accuracy, increasing the AUC to 0.94. CONCLUSIONS Conjunctival redness severity and participant-reported eyelid swelling and overall discomfort, along with adenoviral point-of-care test results, were highly predictive in identifying individuals with PCR-confirmed adenoviral conjunctivitis. Improved diagnostic accuracy by clinicians at the initial presenting visit could prevent unnecessary work furloughs and facilitate earlier treatment decisions.
Published: 2023

2. Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI)

Author: Eveline Janine Anna Wiegers, Hester Floor Lingsma, Jilske Antonia Huijben, David James Cooper, Giuseppe Citerio, Shirin Frisvold, Raimund Helbok, Andrew Ian Ramsay Maas, David Krishna Menon, Elizabeth Madeleine Moore, Nino Stocchetti, Diederik Willem Dippel, Ewout Willem Steyerberg, Mathieu van der Jagt, Joanne Brooker, Peter Bragge, Jeffrey Rosenfeld, Jamie D. Cooper, Ronny Beer, Herbert Schoechl, Martin Rusnák, Elisabeth Schwendenwein, Anna Antoni, Véronique De Keyser, Tomas Menovsky, Dominique Van Praag, Andrew I.R. Maas, Gregory Van der Steen, Paul M. Parizel, Thijs Vande Vyvere, Bart Depreitere, Wim Van Hecke, Jan Verheyden, Benoit Misset, Didier Ledoux, Steven Laureys, Alexandre Ghuysen, Hugues Maréchal, Guy-Loup Dulière, Guoyi Gao, Ji-yao Jiang, Daniel Kondziella, Martin Fabricius, Rico Frederik Schou, Morten Blaabjerg, Christina Rosenlund, Anna Piippo-Karjalainen, Rahul Raj, Matti Pirinen, Samuli Ripatti, Aarno Palotie, Peter Ylén, Jussi P. Posti, Olli Tenovuo, Riikka Takala, Jean-François Payen, Emmanuel Vega, Aurelie Lejeune, Gérard Audibert, Vincent Degos, Habib Benali, Damien Galanaud, Vincent Perlbarg, Louis Puybasset, Philippe Azouvi, Valerie Legrand, Claire Dahyot-Fizelier, Rolf Rossaint, Mark Steven Coburn, Ana Kowark, Hans Clusmann, Jens Dreier, Stefan Wolf, Peter Vajkoczy, Marc Maegele, Johannes Gratz, Nadine Schäfer, Rolf Lefering, Amra Covic, Nicole von Steinbüchel, Silke Schmidt, Monika Bullinger, Alexander Younsi, Andreas Unterberg, Julia Mattern, Oliver Sakowitz, Renan Sanchez-Porras, Natascha Perera, Romuald Beauvais, Janos Sandor, Endre Czeiter, Andras Buki, Erzsébet Ezer, Zoltán Vámos, Béla Melegh, Viktória Tamás, Abayomi Sorinola, Noémi Kovács, József Nyirádi, Krisztina Amrein, Pál Barzó, Deepak Gupta, Leon Levi, Guy Rosenthal, Alex Furmanov, Costanza Martino, Luigi Beretta, Maria Rosa Calvi, Maria Luisa Azzolini, Emiliana Calappi, Tommaso Zoerle, Fabrizio Ortolano, Marco Carbonara, Alessio Caccioppola, Alessia Vargiolu, Arturo Chieregato, Giorgio Chevallard, Francesco Della Corte, Francesca Grossi, Sandra Rossi, Paolo Persona, Maurizio Berardino, Simona Cavallo, Malinka Rambadagalla, Agate Ziverte, Lelde Giga, Egils Valeinis, Rimantas Vilcinis, Tomas Tamosuitis, Saulius Rocka, Arminas Ragauskas, Joukje van der Naalt, Bram Jacobs, Ewout W. Steyerberg, Ronald Bartels, Hugo den Boogert, Erwin Kompanje, Marjolijn Timmers, Kelly Foks, Iain Haitsma, Victor Volovici, Juanita A. Haagsma, Ana Mikolic, Hester Lingsma, Kimberley Velt, Jilske Huijben, Daphne Voormolen, Daan Nieboer, Eveline Wiegers, Charlie Sewalt, Benjamin Gravesteijn, Suzanne Polinder, Dick Tibboel, Roel van Wijk, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wilco Peul, Guus Schoonman, Kelly Jones, Valery L. Feigin, Braden Te Ao, Alice Theadom, Eirik Helseth, Cecilie Roe, Olav Roise, Nada Andelic, Lasse Andreassen, Audny Anke, Anne Vik, Toril Skandsen, Horia Ples, Cristina Maria Tudora, Ancuta Negru, Peter Vulekovic, Đula Đilvesi, Mladen Karan, Jagoš Golubovic, Veronika Rehorcíková, Mark Steven Taylor, Alexandra Brazinova, Marek Majdan, Juan Sahuquillo, Andreea Radoi, Guillermo Carbayo Lozano, Inigo Pomposo, Alfonso Lagares, Pedro A. Gomez, Ana M. Castaño-León, Pablo Gagliardo, Matej Oresic, Bo-Michael Bellander, Linda Lanyon, Pradeep George, Visakh Muraleedharan, David Nelson, Cecilia Ackerlund, Lars-Owe Koskinen, Nina Sundström, Camilla Brorsson, Antonio Belli, Alex Manara, Matt Thomas, Marek Czosnyka, Peter Smielewski, Manuel Cabeleira, Jonathan Coles, Sylvia Richardson, Frederick A. Zeiler, Emmanuel Stamatakis, Guy Williams, David Menon, Ari Ercole, Abhishek Dixit, Virginia Newcombe, Sophie Richter, Charles McFadyen, Peter J. Hutchinson, Angelos G. Kolias, Hadie Adams, Marta Correia, Jonathan Rhodes, William Stewart, Catherine McMahon, Daniel Rueckert, Ben Glocker, Christos Tolias, Helen Dawes, Patrick Esser, Caroline van Heugten, Nicola Curry, Simon Stanworth, Fiona Lecky, Olubukola Otesile, Faye Johnson, Paul Dark, Stefan Jankowski, Roger Lightfoot, Lindsay Wilson, Lindsay Horton, Robert Stevens, Jonathan Rosand, Geoffrey Manley, Mike Jarrett, Vibeke Brinck, Kevin K.W. Wang, Zhihui Yang, Paul M. Vespa, Russell L. Gruen, Peter Cameron, Emma Donoghue, Dashiell Gantner, Russel Gruen, Lynette Murray, Jeffrey V. Rosenfeld, Dinesh Varma, Tony Trapani, Shirley Vallance, Cristopher MacIsaac, Andrea Jordan, Wiegers, E. J. A., Lingsma, H. F., Huijben, J. A., Cooper, D. J., Citerio, G., Frisvold, S., Helbok, R., Maas, A. I. R., Menon, D. K., Moore, E. M., Stocchetti, N., Dippel, D. W., Steyerberg, E. W., van der Jagt, M., Brooker, J., Bragge, P., Rosenfeld, J., Cooper, J. D., Beer, R., Schoechl, H., Rusnak, M., Schwendenwein, E., Antoni, A., De Keyser, V., Menovsky, T., Van Praag, D., Van der Steen, G., Parizel, P. M., Vande Vyvere, T., Depreitere, B., Van Hecke, W., Verheyden, J., Misset, B., Ledoux, D., Laureys, S., Ghuysen, A., Marechal, H., Duliere, G. -L., Gao, G., Jiang, J. -Y., Kondziella, D., Fabricius, M., Schou, R. F., Blaabjerg, M., Rosenlund, C., Piippo-Karjalainen, A., Raj, R., Pirinen, M., Ripatti, S., Palotie, A., Ylen, P., Posti, J. P., Tenovuo, O., Takala, R., Payen, J. -F., Vega, E., Lejeune, A., Audibert, G., Degos, V., Benali, H., Galanaud, D., Perlbarg, V., Puybasset, L., Azouvi, P., Legrand, V., Dahyot-Fizelier, C., Rossaint, R., Coburn, M. S., Kowark, A., Clusmann, H., Dreier, J., Wolf, S., Vajkoczy, P., Maegele, M., Gratz, J., Schafer, N., Lefering, R., Covic, A., von Steinbuchel, N., Schmidt, S., Bullinger, M., Younsi, A., Unterberg, A., Mattern, J., Sakowitz, O., Sanchez-Porras, R., Perera, N., Beauvais, R., Sandor, J., Czeiter, E., Buki, A., Ezer, E., Vamos, Z., Melegh, B., Tamas, V., Sorinola, A., Kovacs, N., Nyiradi, J., Amrein, K., Barzo, P., Gupta, D., Levi, L., Rosenthal, G., Furmanov, A., Martino, C., Beretta, L., Calvi, M. R., Azzolini, M. L., Calappi, E., Zoerle, T., Ortolano, F., Carbonara, M., Caccioppola, A., Vargiolu, A., Chieregato, A., Chevallard, G., Della Corte, F., Grossi, F., Rossi, S., Persona, P., Berardino, M., Cavallo, S., Rambadagalla, M., Ziverte, A., Giga, L., Valeinis, E., Vilcinis, R., Tamosuitis, T., Rocka, S., Ragauskas, A., van der Naalt, J., Jacobs, B., Bartels, R., den Boogert, H., Kompanje, E., Timmers, M., Foks, K., Haitsma, I., Volovici, V., Haagsma, J. A., Mikolic, A., Lingsma, H., Velt, K., Huijben, J., Voormolen, D., Nieboer, D., Wiegers, E., Sewalt, C., Gravesteijn, B., Polinder, S., Tibboel, D., van Wijk, R., van Dijck, J. T. J. M., van Essen, T. A., Peul, W., Schoonman, G., Jones, K., Feigin, V. L., Te Ao, B., Theadom, A., Helseth, E., Roe, C., Roise, O., Andelic, N., Andreassen, L., Anke, A., Vik, A., Skandsen, T., Ples, H., Tudora, C. M., Negru, A., Vulekovic, P., Dilvesi, D., Karan, M., Golubovic, J., Rehorcikova, V., Taylor, M. S., Brazinova, A., Majdan, M., Sahuquillo, J., Radoi, A., Carbayo Lozano, G., Pomposo, I., Lagares, A., Gomez, P. A., Castano-Leon, A. M., Gagliardo, P., Oresic, M., Bellander, B. -M., Lanyon, L., George, P., Muraleedharan, V., Nelson, D., Ackerlund, C., Koskinen, L. -O., Sundstrom, N., Brorsson, C., Belli, A., Manara, A., Thomas, M., Czosnyka, M., Smielewski, P., Cabeleira, M., Coles, J., Richardson, S., Zeiler, F. A., Stamatakis, E., Williams, G., Menon, D., Ercole, A., Dixit, A., Newcombe, V., Richter, S., Mcfadyen, C., Hutchinson, P. J., Kolias, A. G., Adams, H., Correia, M., Rhodes, J., Stewart, W., Mcmahon, C., Rueckert, D., Glocker, B., Tolias, C., Dawes, H., Esser, P., van Heugten, C., Curry, N., Stanworth, S., Lecky, F., Otesile, O., Johnson, F., Dark, P., Jankowski, S., Lightfoot, R., Wilson, L., Horton, L., Stevens, R., Rosand, J., Manley, G., Jarrett, M., Brinck, V., Wang, K. K. W., Yang, Z., Vespa, P. M., Gruen, R. L., Cameron, P., Donoghue, E., Gantner, D., Gruen, R., Murray, L., Rosenfeld, J. V., Varma, D., Trapani, T., Vallance, S., Macisaac, C., Jordan, A., Public Health, Neurology, Intensive Care, Neurosurgery, Erasmus MC other, Pediatric Surgery, CENTER-TBI Collaboration Group, OzENTER-TBI Collaboration Group, Molecular Neuroscience and Ageing Research (MOLAR), Psychology 3, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, Wiegers, E, Lingsma, H, Huijben, J, Cooper, D, Citerio, G, Frisvold, S, Helbok, R, Maas, A, Menon, D, Moore, E, Stocchetti, N, Dippel, D, Steyerberg, E, van der Jagt, M, Brooker, J, Bragge, P, Rosenfeld, J, Cooper, J, Beer, R, Schoechl, H, Rusnák, M, Schwendenwein, E, Antoni, A, De Keyser, V, Menovsky, T, Van Praag, D, Van der Steen, G, Parizel, P, Vande Vyvere, T, Depreitere, B, Van Hecke, W, Verheyden, J, Misset, B, Ledoux, D, Laureys, S, Ghuysen, A, Maréchal, H, Dulière, G, Gao, G, Jiang, J, Kondziella, D, Fabricius, M, Schou, R, Blaabjerg, M, Rosenlund, C, Piippo-Karjalainen, A, Raj, R, Pirinen, M, Ripatti, S, Palotie, A, Ylén, P, Posti, J, Tenovuo, O, Takala, R, Payen, J, Vega, E, Lejeune, A, Audibert, G, Degos, V, Benali, H, Galanaud, D, Perlbarg, V, Puybasset, L, Azouvi, P, Legrand, V, Dahyot-Fizelier, C, Rossaint, R, Coburn, M, Kowark, A, Clusmann, H, Dreier, J, Wolf, S, Vajkoczy, P, Maegele, M, Gratz, J, Schäfer, N, Lefering, R, Covic, A, von Steinbüchel, N, Schmidt, S, Bullinger, M, Younsi, A, Unterberg, A, Mattern, J, Sakowitz, O, Sanchez-Porras, R, Perera, N, Beauvais, R, Sandor, J, Czeiter, E, Buki, A, Ezer, E, Vámos, Z, Melegh, B, Tamás, V, Sorinola, A, Kovács, N, Nyirádi, J, Amrein, K, Barzó, P, Gupta, D, Levi, L, Rosenthal, G, Furmanov, A, Martino, C, Beretta, L, Calvi, M, Azzolini, M, Calappi, E, Zoerle, T, Ortolano, F, Carbonara, M, Caccioppola, A, Vargiolu, A, Chieregato, A, Chevallard, G, Della Corte, F, Grossi, F, Rossi, S, Persona, P, Berardino, M, Cavallo, S, Rambadagalla, M, Ziverte, A, Giga, L, Valeinis, E, Vilcinis, R, Tamosuitis, T, Rocka, S, Ragauskas, A, van der Naalt, J, Jacobs, B, Bartels, R, den Boogert, H, Kompanje, E, Timmers, M, Foks, K, Haitsma, I, Volovici, V, Haagsma, J, Mikolic, A, Velt, K, Voormolen, D, Nieboer, D, Sewalt, C, Gravesteijn, B, Polinder, S, Tibboel, D, van Wijk, R, van Dijck, J, van Essen, T, Peul, W, Schoonman, G, Jones, K, Feigin, V, Te Ao, B, Theadom, A, Helseth, E, Roe, C, Roise, O, Andelic, N, Andreassen, L, Anke, A, Vik, A, Skandsen, T, Ples, H, Tudora, C, Negru, A, Vulekovic, P, Đilvesi, Đ, Karan, M, Golubovic, J, Rehorcíková, V, Taylor, M, Brazinova, A, Majdan, M, Sahuquillo, J, Radoi, A, Carbayo Lozano, G, Pomposo, I, Lagares, A, Gomez, P, Castaño-León, A, Gagliardo, P, Oresic, M, Bellander, B, Lanyon, L, George, P, Muraleedharan, V, Nelson, D, Ackerlund, C, Koskinen, L, Sundström, N, Brorsson, C, Belli, A, Manara, A, Thomas, M, Czosnyka, M, Smielewski, P, Cabeleira, M, Coles, J, Richardson, S, Zeiler, F, Stamatakis, E, Williams, G, Ercole, A, Dixit, A, Newcombe, V, Richter, S, Mcfadyen, C, Hutchinson, P, Kolias, A, Adams, H, Correia, M, Rhodes, J, Stewart, W, Mcmahon, C, Rueckert, D, Glocker, B, Tolias, C, Dawes, H, Esser, P, van Heugten, C, Curry, N, Stanworth, S, Lecky, F, Otesile, O, Johnson, F, Dark, P, Jankowski, S, Lightfoot, R, Wilson, L, Horton, L, Stevens, R, Rosand, J, Manley, G, Jarrett, M, Brinck, V, Wang, K, Yang, Z, Vespa, P, Gruen, R, Cameron, P, Donoghue, E, Gantner, D, Murray, L, Varma, D, Trapani, T, Vallance, S, Macisaac, C, and Jordan, A
Subjects: medicine.medical_specialty, Fluid balance and outcome in critically ill patients traumatic brain injury, Icu mortality, Traumatic brain injury, Critically ill, business.industry, INTRACRANIAL-PRESSURE, Glasgow Outcome Scale, Odds ratio, medicine.disease, GUIDELINES, Intensive care unit, law.invention, law, Emergency medicine, medicine, MANAGEMENT, Observational study, Neurology (clinical), Human medicine, business, Balance (ability)
Abstract: Background Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in fluid management policies in patients with traumatic brain injury and to study the effect of this variability on patients' outcomes.Methods We did a prospective, multicentre, comparative effectiveness study of two observational cohorts: CENTER-TBI in Europe and OzENTER-TBI in Australia. Patients from 55 hospitals in 18 countries, aged 16 years or older with traumatic brain injury requiring a head CT, and admitted to the ICU were included in this analysis. We extracted data on demographics, injury, and clinical and treatment characteristics, and calculated the mean daily fluid balance (difference between fluid input and loss) and mean daily fluid input during ICU stay per patient. We analysed the association of fluid balance and input with ICU mortality and functional outcome at 6 months, measured by the Glasgow Outcome Scale Extended (GOSE). Patient-level analyses relied on adjustment for key characteristics per patient, whereas centre-level analyses used the centre as the instrumental variable.Findings 2125 patients enrolled in CENTER-TBI and OzENTER-TBI between Dec 19, 2014, and Dec 17, 2017, were eligible for inclusion in this analysis. The median age was 50 years (IQR 31 to 66) and 1566 (74%) of patients were male. The median of the mean daily fluid input ranged from 1middot48 L (IQR 1middot12 to 2middot09) to 4middot23 L (3middot78 to 4middot94) across centres. The median of the mean daily fluid balance ranged from -0middot85 L (IQR -1middot51 to -0middot49) to 1middot13 L (0middot99 to 1middot37) across centres. In patient-level analyses, a mean positive daily fluid balance was associated with higher ICU mortality (odds ratio [OR] 1middot10 [95% CI 1middot07 to 1middot12] per 0middot1 L increase) and worse functional outcome (1middot04 [1middot02 to 1middot05] per 0middot1 L increase); higher mean daily fluid input was also associated with higher ICU mortality (1middot05 [1middot03 to 1middot06] per 0middot1 L increase) and worse functional outcome (1middot04 [1middot03 to 1middot04] per 1-point decrease of the GOSE per 0middot1 L increase). Centre-level analyses showed similar associations of higher fluid balance with ICU mortality (OR 1middot17 [95% CI 1middot05 to 1middot29]) and worse functional outcome (1middot07 [1middot02 to 1middot13]), but higher fluid input was not associated with ICU mortality (OR 0middot95 [0middot90 to 1middot00]) or worse functional outcome (1middot01 [0middot98 to 1middot03]).Interpretation In critically ill patients with traumatic brain injury, there is significant variability in fluid management, with more positive fluid balances being associated with worse outcomes. These results, when added to previous evidence, suggest that aiming for neutral fluid balances, indicating a state of normovolaemia, contributes to improved outcome. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
Published: 2021
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3. Outcomes of Salvage Robot-assisted Radical Prostatectomy After Focal Ablation for Prostate Cancer in Comparison to Primary Robot-assisted Radical Prostatectomy: A Matched Analysis

Author: Jonathan Noel, Sunil Reddy, Marco Sandri, Marcio Covas Moschovas, Travis Rogers, Vipul R. Patel, K. R. Seetharam Bhat, Roshane Perera, and Shannon Roof
Subjects: Male, medicine.medical_specialty, Urology, Urinary system, medicine.medical_treatment, Prostate cancer, Lymphocele, Robotic Surgical Procedures, Prostate, American Urological Association Symptom Score, Humans, Medicine, Retrospective Studies, Prostatectomy, business.industry, Incidence (epidemiology), Prostatic Neoplasms, Robotics, Prostate-Specific Antigen, medicine.disease, medicine.anatomical_structure, business, Body mass index
Abstract: Background Focal therapy (FT) for prostate cancer is less invasive than radical treatment but carries a risk of recurrence. Salvage robot-assisted radical prostatectomy (S-RARP) is a possible option after FT failure. Objective To evaluate the impact of FT on functional and oncological outcomes following S-RARP. Design, setting, and participants In a retrospective analysis of data from a prospectively collected institutional database, 53 patients who underwent S-RARP following failure of focal ablation were selected as group I; patients who had whole-gland ablation and external beam therapy were excluded. This group was matched to a control sample (matched at ratios of 1:1, 1:2, 1:3, 1:4) of men who had undergone primary RARP, using age, prostate-specific antigen (PSA), PSA density, body mass index, Sexual Health Inventory for Men score, American Urological Association symptom score, Charlson comorbidity index, prostate weight, preoperative Gleason score (GS), and history of smoking as variables. Surgical procedure S-RARP after FT was performed using a standardized technique developed at our institute with the da Vinci Xi Surgical System. Measurements Oncological and functional outcomes were compared between the S-RARP and primary RARP groups. Results and limitations There was no difference in estimated blood loss (p = 0.8) between the 1:1 matched groups, but operating room time was significantly longer for S-RARP (p = 0.007). The primary RARP group had a higher proportion of patients who underwent a full nerve-sparing procedure. The S-RARP group had higher incidence of positive surgical margins (40% vs 15%; p = 0.008), GS ≥8 (25% vs 15%; p = 0.07), and positive lymph node status (9.4% vs 5.7%; p = 0.02). There was no significant difference in overall complications between the groups. The primary RARP group had a higher incidence of lymphocele drainage after surgery (15% vs 0%; p = 0.006). The main limitation of the study is its retrospective design. Conclusions S-RALP after FT failure is feasible; however, surgery following FT leads to poorer oncological and functional outcomes. Despite the targeted nature of FT, significant nonfocal collateral damage is evident in tissues surrounding the prostate, which in turn translates to poorer functional outcomes after S-RARP. Patient summary We studied the surgical challenges during robot-assisted removal of the prostate after previous focal treatment (FT) for prostate cancer and compared the outcomes to those for robot-assisted prostate removal in patients who had no previous FT. We found that this technique is safe and effective with a limited risk of complications, but poor urinary and sexual functional outcomes.
Published: 2022
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4. Cardiac Complications of Common Drugs of Abuse: Pharmacology, Toxicology, and Management

Author: Luke R. Gagnon, Kevin Perera, Chandu Sadasivan, and Gavin Y. Oudit
Subjects: medicine.medical_specialty, Acute coronary syndrome, Heart disease, Substance-Related Disorders, Psychological intervention, Disease, 030204 cardiovascular system & hematology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, Young adult, Intensive care medicine, Psychotropic Drugs, biology, business.industry, biology.organism_classification, medicine.disease, 3. Good health, Substance abuse, Mental Health, Cannabis, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract: Cardiovascular complications from drugs of abuse are becoming more apparent because of increased usage worldwide. Substance abuse can cause acute and chronic cardiovascular complications and is increasing in prevalence especially in young adults. These substances contribute to the development of acute coronary syndrome, type 2 myocardial injury, arrhythmias, and cardiomyopathies, and have numerous other cardiovascular complications. Although no screening guidelines exist, clinical awareness of these potential complications and their prevention, clinical presentation, diagnosis, and treatment are critically important. Management of cardiovascular disease should be coupled with appropriate social and mental health interventions to provide sustained clinical benefit. The higher the number of substances used recreationally, the greater the risk of premature heart disease. Epidemiological studies showed that 1 in 5 young adults misuse several substances and often start using at younger ages with a greater risk for adverse health outcomes over the long term. The aim of this review is to highlight the basic epidemiology, cardiac complications, and disease-specific treatment options of commonly abused substances including methamphetamine, cocaine, alcohol, anabolic-androgenic steroids, cannabis, and tobacco.
Published: 2022
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5. Mobile Stroke Unit in the UK Healthcare System : Avoidance of Unnecessary Accident and Emergency Admissions

Author: Thomas Bertsch, Theresa Foster, Monika Bachhuber, Stefan Helwig, Chris Wiltshire, Ian Ewart, Stephen Gerry, David Sexby, Paul Guyler, David Dommett, Nisha Menon, Daniel J. Phillips, Sajid Alam, Caroline Howard, Annie Chakrabarti, Sarah Mapplebeck, Muhammad Inam Ul Haq, Shrey Mathur, Marcus Bailey, Klaus Fassbender, Iris Q. Grunwald, Fatma Merzou, Tom Davis, Wolfgang Reith, Silke Walter, Viola Wagner, James Fisher, Daniel Grün, Martin Lesmeister, Andrea Schottek, and Saman Perera
Subjects: Male, Emergency Medical Services, Time Factors, medicine.medical_treatment, 030204 cardiovascular system & hematology, Transient ischaemic attacks, State Medicine, 0302 clinical medicine, Patient Admission, Interquartile range, Emergency medical services, Medicine, Pre-hospital, Thrombolytic Therapy, Prospective Studies, Prospective cohort study, Stroke, Aged, 80 and over, Medical Audit, Thrombolysis, Catheter, Treatment Outcome, Neurology, England, Female, Cardiology and Cardiovascular Medicine, Emergency Service, Hospital, Large vessel occlusion, medicine.medical_specialty, Unnecessary Procedures, Time-to-Treatment, Diagnosis, Differential, 03 medical and health sciences, Predictive Value of Tests, Humans, Clinical Research in Stroke, Aged, business.industry, Mobile stroke unit, medicine.disease, Triage, Emergency medicine, Neurology (clinical), business, 030217 neurology & neurosurgery, Mobile Health Units
Abstract: Background: Acute stroke patients are usually transported to the nearest hospital regardless of their required level of care. This can lead to increased pressure on emergency departments and treatment delay. Objective: The aim of the study was to explore the benefit of a mobile stroke unit (MSU) in the UK National Health Service (NHS) for reduction of hospital admissions. Methods: Prospective cohort audit observation with dispatch of the MSU in the East of England Ambulance Service area in Southend-on-Sea was conducted. Emergency patients categorized as code stroke and headache were included from June 5, 2018, to December 18, 2018. Rate of avoided admission to the accident and emergency (A&E) department, rate of admission directly to target ward, and stroke management metrics were assessed. Results: In 116 MSU-treated patients, the following diagnoses were made: acute stroke, n = 33 (28.4%); transient ischaemic attacks, n = 13 (11.2%); stroke mimics, n = 32 (27.6%); and other conditions, n = 38 (32.8%). Pre-hospital thrombolysis was administered to 8 of 28 (28.6%) ischaemic stroke patients. Pre-hospital diagnosis avoided hospital admission for 29 (25.0%) patients. As hospital treatment was indicated, 35 (30.2%) patients were directly triaged to the stroke unit, 1 patient (0.9%) even directly to the catheter laboratory. Thus, only 50 (43.1%) patients required transfer to the A&E department. Moreover, the MSU enabled thrombolysis with a median dispatch-to-needle time of 42 min (interquartile range, 40–60). Conclusion: This first deployment of an MSU in the UK NHS demonstrated improved triage decision-making for or against hospital admission and admission to the appropriate target ward, thereby reducing pressure on strained A&E departments.
Published: 2023
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6. Prevalence, causes and associated mortality of hypercalcaemia in modern hospital care

Author: Nimalie Perera, Senthil Thillainadesan, and Stephen M. Twigg
Subjects: Pediatrics, medicine.medical_specialty, Hypercalcaemia, endocrine system diseases, business.industry, Retrospective cohort study, Hyperparathyroidism, Primary, medicine.disease, Malignancy, Hospitals, Neoplasms, Epidemiology, Hypercalcemia, Prevalence, Internal Medicine, medicine, Risk of mortality, Etiology, Humans, Calcium, business, Primary hyperparathyroidism, Retrospective Studies, Kidney disease
Abstract: BACKGROUND Studies examining hypercalcaemia in inpatients were largely published over 20 years ago, and it is likely the epidemiology of hypercalcaemia has changed related to increased lifespan and changes in prevalence of the underlying causes such as malignancy. AIM To explore the epidemiology of hypercalcaemia in a modern tertiary hospital setting in Australia, and evaluate the risk of mortality associated with hypercalcaemia. METHOD A retrospective study was performed in all inpatients with elevated blood calcium levels admitted from July 2013 to June 2018. ICD coding data identified primary diagnoses and mortality. Electronic medical records were reviewed in n=292 patients admitted across 12 months from January to December 2017, to determine the causes of hypercalcaemia. RESULTS Hypercalcaemia occurred in 1819 admissions (0.93% of all hospital admissions), during the 5 year period. The admission primary diagnoses were: malignancy (20% of cases), cardiovascular disease (17%), and gastrointestinal disease (11%). The top causes of hypercalcaemia among the 292 cases where electronic records were reviewed were malignancy (26%), primary hyperparathyroidism (25%) and hyperparathyroidism in the setting of chronic kidney disease (12%). Mortality occurred in 17% of these admissions. Non-survivors had significantly higher calcium levels, phosphate and white cell count, and had lower haemoglobin and albumin levels. CONCLUSION Hypercalcaemia occurred in ~1% of admissions with main causes being malignancy and primary hyperparathyroidism, similar to historical studies. Hypercalcaemia in hospitalised patients is associated with high mortality and higher levels may be a marker for more severe underlying disease. This article is protected by copyright. All rights reserved.
Published: 2022
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7. Preventive oral health care for mitigating the COVID-19 induced adverse maternal outcomes: View point from Sri Lanka on opportunities in crisis

Author: Nadisha Ratnasekera, Manosha Perera, Migara Epa, Chandana Gajanayake, and Irosha Perera
Subjects: medicine.medical_specialty, Health professionals, Coronavirus disease 2019 (COVID-19), business.industry, Family medicine, medicine, Toxic shock syndrome, Oral health care, Sri lanka, medicine.disease, business
Abstract: Pregnancy marks a unique milestone in woman’s life cycle enriched with an array of physical, psychological, social and even spiritual needs. In this context, an optimal level of oral health status has become fundamental to overall health and well-being of a pregnant woman. This is evident more than ever before, for preventing exacerbation of poor oral health in pregnancy, possible control of adverse pregnancy outcomes whilst ensuring low risk for early childhood dental caries for the offspring. Nevertheless, pregnancy renders special oral health needs for a woman compounded by changes in dietary habits, oral hygiene practices and hormonal changes thereby increasing the risk of dental caries and periodontitis. The possible link between Periodontitis and adverse outcomes in pregnancy is well known. The pandemic caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compounded by emergence more virulent strains not only indelibly impacted on population, countries, economies and health systems across the globe but exposed vulnerable population groups to pervasive health catastrophes. There is accumulating concerns on periodontitis linking with severe complications of Covid-19 attributed to commonalities of exacerbated inflammatory responses. Moreover, adverse Covid-19 induced maternal and fetal outcomes has garnered attention of researchers based on the previous knowledge indicating adverse outcomes attributed to epidemics of human corona viruses. However, it is not known how maternal oral hygiene status and burden of periodontitis impact on Covid-19 induced adverse outcomes in pregnancy. However, it could be rational to argue that poor oral health of a pregnant woman could elevate her risks for adverse health outcomes. Oral health care in pregnancy has received recognition as an essential element of comprehensive antenatal health care provision. However, the persistent global public health emergency of Covid-19 has profoundly impacted on availability of and accessibility to routine oral health care services. Therefore, accessing routine oral health care services poses serious causes for concern among pregnant women. Against this backdrop, present opinion attempts to explore and expound the potential of preventive oral health care could offer to mitigate the potential risks of Covid-19 induced adverse maternal outcomes embracing the context of Sri Lanka: a developing lower middle-income country.
Published: 2021
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8. COVID-19 in liver transplant candidates

Author: Belli, Luca Saverio, Duvoux, Christophe, Cortesi, Paolo Angelo, Facchetti, Rita, Iacob, Speranta, Perricone, Giovanni, Radenne, Sylvie, Conti, Sara, Patrono, Damiano, Berlakovich, Gabriela, Hann, Angus, Pasulo, Luisa, Castells, Lluis, Faitot, Francois, Detry, Olivier, Invernizzi, Federica, Magini, Giulia, De Simone, Paolo, Kounis, Ilias, Morelli, Maria Cristina, Díaz Fontenla, Fernando, Ericzon, Bo-Göran, Loinaz, Carmelo, Johnston, Chris, Gheorghe, Liliana, Lesurtel, Mickael, Romagnoli, Renato, Kollmann, Dagmar, Perera, M Thamara Pr, Fagiuoli, Stefano, Mirza, Darius, Coilly, Audrey, Toso, Christian, Zieniewicz, Krzysztof, Elkrief, Laure, Karam, Vincent, Adam, Rene, den Hoed, Caroline, Merli, Marco, Puoti, Massimo, De Carlis, Luciano, Oniscu, Gabriel C, Piano, Salvatore, Angeli, Paolo, Fondevila, Constantino, Polak, Wojciech G, ELITA-ELTR COVID-19 Registry, Gastroenterology & Hepatology, Surgery, Belli, L, Duvoux, C, Cortesi, P, Facchetti, R, Iacob, S, Perricone, G, Radenne, S, Conti, S, Patrono, D, Berlakovich, G, Hann, A, Pasulo, L, Castells, L, Faitot, F, Detry, O, Invernizzi, F, Magini, G, De Simone, P, Kounis, I, Morelli, M, Diaz Fontenla, F, Ericzon, B, Loinaz, C, Johnston, C, Gheorghe, L, Lesurtel, M, Romagnoli, R, Kollmann, D, Perera, M, Fagiuoli, S, Mirza, D, Coilly, A, Toso, C, Zieniewicz, K, Elkrief, L, Karam, V, Adam, R, Den Hoed, C, Merli, M, Puoti, M, De Carlis, L, Oniscu, G, Piano, S, Angeli, P, Fondevila, C, and Polak, W
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Waiting Lists, medicine.medical_treatment, liver cirrhosis, Pneumonia, Viral, Population, Liver transplantation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Cause of Death, Medicine, Humans, Viral, Registries, education, Cause of death, education.field_of_study, ddc:617, liver transplantation, liver cirrhosi, Proportional hazards model, business.industry, SARS-CoV-2, Gastroenterology, COVID-19, Pneumonia, Middle Aged, medicine.disease, Transplant Recipients, Transplantation, Europe, 030104 developmental biology, Respiratory failure, Liver cirrhosis, 030211 gastroenterology & hepatology, Female, Liver Transplantation, business, Cohort study
Abstract: ObjectiveExplore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.DesignData from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.ResultsFrom 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10–30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15–19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44–102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31–170).ConclusionsIncreased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).
Published: 2021

9. Angiografía-OCT para diagnóstico y respuesta al tratamiento de la neovascularización subretiniana secundaria a telangiectasia macular idiopática tipo 2

Author: N. Betancor Caro, M. Serrano García, C. Mantolán Sarmiento, H.E. Tapia Quijada, S. Gómez Perera, and B. Haro Álvarez
Subjects: medicine.medical_specialty, Subretinal neovascularization, Capillary plexus, genetic structures, business.industry, Disease progression, Optical coherence tomography angiography, medicine.disease, Response to treatment, eye diseases, Ophthalmology, Oct angiography, medicine, Disease process, business, Macular telangiectasia
Abstract: Idiopathic macular telangiectasia type 2 (MacTel 2) is a slow and progressive bilateral condition that affects middle-aged and elderly individuals. Vision loss is generally mild and occurs over the course of many years. The development of sub-retinal neovascularisation (SRNV) can occur late in the disease process, and lead to more dramatic vision loss. A report is presented of 2cases of MacTel 2 in which optical coherence tomography angiography (OCTA) was essential for the diagnosis of secondary SRNV. The commercially available OCTA Cirrus AngioPlex 5000 platform (Zeiss, Jena, Germany) was used. Subretinal neovascularization was detectable in both cases in OCTA at the level of the deep capillary plexus and the avascular layer. OCTA also allowed us to monitor disease progression and monitor response to anti-VEGF therapy.
Published: 2022
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10. Impact of delay from transperineal biopsy to radical prostatectomy upon objective measures of cancer control

Author: Gregory S. Jack, Melanie Evans, Susan E. Evans, Liang G. Qu, Damien M Bolton, Nathan Papa, and Marlon Perera
Subjects: Biochemical recurrence, medicine.medical_specialty, education.field_of_study, medicine.diagnostic_test, business.industry, Prostatectomy, Transperineal biopsy, medicine.medical_treatment, Population, Urology, medicine.disease, Prostate cancer, medicine.anatomical_structure, Prostate, Biopsy, Cohort, medicine, business, education
Abstract: Treatment delays in prostate cancer have been characterised, although not explicitly in men undergoing transperineal prostate biopsies. We aimed to determine if delays to radical prostatectomy correlate with adverse outcomes using a contemporary population-based cohort of men diagnosed by transperineal biopsies.This study analysed men with prostate cancer of the International Society for Urological Pathology grade group ≥2, diagnosed by transperineal prostate biopsies who underwent prostatectomy, using the prospectively data from 1 January 2014 to 30 June 2018 Prostate Cancer Outcomes Registry-Victoria. Data were analysed according to stratified demographic and disease characteristics. Time intervals from biopsy (28, 60, 90, 120, and 270 days) were compared using odds ratios and regression analyses for proportion of upgrading, early biochemical recurrence, pT3 disease at prostatectomy, and positive surgical margins.In total, 2008 men were analysed. There were 306 (16.7%) men with upgrading, 151 (8.4%) with biochemical recurrence, 1068 (54.1%) with pT3 disease, and 464 (23.1%) with positive surgical margins (percentages excluded patients with missing data). All adverse outcomes studied were significantly associated with higher prostate-specific antigen and grade at diagnosis. Delays of 120-270 days did not adversely alter the incidence of Gleason upgrading, pT3, or recurrence. Delays (most frequent 60-89 days, 28%) were associated with positive surgical margins but not monotonically. Regression modelling demonstrated no increased likelihood of most adverse outcomes for up to 270 days.Men with prostate cancer of grade group ≥2 diagnosed through transperineal biopsy may wait up to 270 days for a prostatectomy without a greater likelihood of upgrading, pT3 disease, positive surgical margins, or biochemical recurrence.
Published: 2022
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11. Diagnosis and resection of a giant ovarian cyst presenting in a young patient with contralateral back pain and lower limb deep vein thrombosis

Author: Nazneen Hoque, Duranka Perera, Khalil Razvi, and Anita Bolina
Subjects: Adult, Diagnostic Imaging, medicine.medical_specialty, Inferior vena cava filter, Case Report, Diagnosis, Differential, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Fibrinolytic Agents, medicine, Back pain, Humans, Cyst, Enoxaparin, Venous Thrombosis, Leg, 030219 obstetrics & reproductive medicine, Ovarian cyst, business.industry, Ovary, Ultrasonography, Doppler, General Medicine, medicine.disease, Thrombosis, Magnetic Resonance Imaging, Surgery, Venous thrombosis, Ovarian Cysts, Back Pain, 030220 oncology & carcinogenesis, Female, medicine.symptom, Differential diagnosis, Complication, business, Tomography, X-Ray Computed
Abstract: We present a case of a giant ovarian cyst in a 20-year-old woman who presented atypically at our Emergency Department with left-sided back pain followed by acute left leg swelling. Blood tests showed significantly raised C-Reactive Protein and D-Dimer. CT-Abdomen-Pelvis demonstrated a large mass in the region of the right ovary with suspicious heterogeneous filling defects in the left external iliac vein, confirmed as a left-sided deep-vein thrombosis on ultrasound Doppler. MRI revealed the lesion to be cystic and the deep venous thrombosis was treated with twice-daily Clexane. Prior to removal of the cyst, an Inferior Vena Cava Filter was placed to reduce thromboembolic risk. The cyst was resected without complication and the postoperative period was uneventful. This case occurred while face-to-face services were limited by COVID-19 and illustrates the need for robust systemic measures to safeguard patients against the emergency sequelae of insidious gynaecological pathology.
Published: 2023

12. Applicability of Western protocols in resource‐limited setting: Real‐world data of long‐term outcome of intensive treatment of adult acute myeloid leukaemia in Sri Lanka

Author: Ananda Wijewickrama, Thurairajah Skandarajah, Jayantha Balawardena, Lakmali Kandabadage, Godvin Constantine, Chathuri L. Jayasinghe, Saman Hewamana, Priyankara Jayawardena, Mehendra Perera, Chandana Wickramarathna, Bandula Wijesiriwardena, Chandu De Silva, Eranga Perera, Gnani Somasundaram, Mahesh Harischandra, Surjit Somiah, Sanjeewa Munasinghe, Vadivelu Srinivasan, Natasha Pieris, and Dehan Gunasekera
Subjects: medicine.medical_specialty, business.industry, Intensive treatment, medicine, Developing country, Sri lanka, Myeloid leukaemia, Intensive care medicine, business, Real world data, Outcome (game theory), Limited resources, Term (time)
Published: 2021
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13. The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study

Author: Shamira A. Perera, Hon-Tym Wong, David S. Friedman, Rajesh S. Kumar, Tin Aung, Paul J. Foster, Raghavan Lavanya, Arun Narayanaswamy, Mani Baskaran, Paul T K Chew, and Qing-Shu Lu
Subjects: medicine.medical_specialty, Intraocular pressure, genetic structures, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Hazard ratio, Glaucoma, medicine.disease, Asymptomatic, eye diseases, Confidence interval, law.invention, Ophthalmology, Randomized controlled trial, law, Gonioscopy, Medicine, sense organs, medicine.symptom, business
Abstract: Purpose To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). Design Prospective, randomized controlled trial. Participants This multicenter, randomized controlled trial ( ClinicalTrials.gov identifier, NCT00347178 ) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). Methods Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. Main Outcome Measures The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. Results Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37–0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03–1.10; P Conclusions In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.
Published: 2022
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14. Invasive and non-invasive assessment of ischaemia in chronic coronary syndromes

Author: Tim P. van de Hoef, Sven Plein, Ozan M. Demir, Divaka Perera, Javier Escaned, Haseeb Rahman, and Jan J. Piek
Subjects: medicine.medical_specialty, Ischemia, Ischaemic Heart Disease, Coronary Angiography, Coronary pressure, Angina, Coronary circulation, medicine, Humans, State of the Art Review, Coronary physiology, AcademicSubjects/MED00200, Intensive care medicine, medicine.diagnostic_test, business.industry, Microcirculation, Non invasive, Coronary Stenosis, Syndrome, medicine.disease, Review article, Clinical Practice, medicine.anatomical_structure, Angiography, Stable coronary artery disease, Cardiology and Cardiovascular Medicine, business
Abstract: Intracoronary physiology testing has emerged as a valuable diagnostic approach in the management of patients with chronic coronary syndrome, circumventing limitations like inferring coronary function from anatomical assessment and low spatial resolution associated with angiography or non-invasive tests. The value of hyperaemic translesional pressure ratios to estimate the functional relevance of coronary stenoses is supported by a wealth of prognostic data. The continuing drive to further simplify this approach led to the development of non-hyperaemic pressure-based indices. Recent attention has focussed on estimating physiology without even measuring coronary pressure. However, the reduction in procedural time and ease of accessibility afforded by these simplifications needs to be counterbalanced against the increasing burden of physiological assumptions, which may impact on the ability to reliably identify an ischaemic substrate, the ultimate goal during catheter laboratory assessment. In that regard, measurement of both coronary pressure and flow enables comprehensive physiological evaluation of both epicardial and microcirculatory components of the vasculature, although widespread adoption has been hampered by perceived technical complexity and, in general, an underappreciation of the role of the microvasculature. In parallel, entirely non-invasive tools have matured, with the utilization of various techniques including computational fluid dynamic and quantitative perfusion analysis. This review article appraises the strengths and limitations for each test in investigating myocardial ischaemia and discusses a comprehensive algorithm that could be used to obtain a diagnosis in all patients with angina scheduled for coronary angiography, including those who are not found to have obstructive epicardial coronary disease., Graphical Abstract Graphical AbstractIllustration of hierarchy of coronary indices and optimal coronary indices by coronary artery disease substrate. CFR, coronary flow reserve; CT, computed tomography; FFR, fractional flow reserve; hMR, hyperaemic microvascular resistance; hSR, hyperaemic stenosis resistance; iFR, instantaneous wave-free ratio; IMR, index of microvascular resistance; NHPR, non-hyperaemic pressure ratio; Pd/Pa, resting distal to aortic pressure ratio; QFR, quantitative flow reserve.
Published: 2022

15. Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress–Exposed Nonhuman Primates

Author: Audrey R. Tyrka, Andrea Parolin Jackowski, Jeremy D. Coplan, Tarique D. Perera, Kathryn K. Ridout, Anna V. Rozenboym, Shariful A. Syed, Hung-Teh Kao, Barbara Porton, Jean Tang, Sasha Fulton, and John G. Kral
Subjects: medicine.medical_specialty, Offspring, medicine.medical_treatment, Early life stress, RC435-571, Peptide, pGLP-1, Biology, Adversity, Insulin resistance, Internal medicine, medicine, Maltreatment, Insulin, Risk factor, Early-life stress, chemistry.chemical_classification, Adaptive calibration, Psychiatry, General Medicine, medicine.disease, Telomere, Endocrinology, chemistry, Anxiety, medicine.symptom
Abstract: Background: Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. Methods: Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD–reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD–reared groups were examined using regression modeling, controlling for sex, weight, and age. Results: VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. Conclusions: Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.
Published: 2022

16. Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial

Author: Mukul Sharma, Eric E. Smith, Lesly A. Pearce, Ashkan Shoamanesh, Kanjana S. Perera, Shelagh B. Coutts, Dorte Damgaard, Sebastian F. Ameriso, Joung-Ho Rha, Boris Modrau, Byung-Woo Yoon, Marina Romano, Steven R. Messé, Jessica Barlinn, Johann Lambeck, Feryal Saad, Scott D. Berkowitz, Hardi Mundl, Stuart J. Connolly, Robert G. Hart, T.S. Field, G.J. Stotts, D.J. Gladstone, S.J. Phillips, A. Sharrief, C. Holmstedt, N. Vora, C. Wilson, B.M. Coull, A. de Havenon, L.A. Birnbaum, N. Patel, M.S. Hussain, D. Greer, S. Chen, S. Kittner, D. Mehta, T. Lowenkopf, R. Sawyer, V. Babikian, R. Zweifler, D.L. Tirschwell, C. Sila, C. Zhang, K-S. Hong, K. Oh, J.H. Heo, H-J. Bae, M.S. Park, J.S. Kim, C-S. Chung, B-C. Lee, G.P. Povedano, J.J. Martin, G.M. Bruera, L.V. Jure, J. Marti-Fabregas, I.C. Naranjo, J.M.R. Moreno, P.C. Portela, M. Gomis, J. Serena, H. Christensen, T. Christensen, S. Knecht, M. Endres, J. Berrouschot, F. Schlachetzki, S. Wunderlich, P. Kraft, P. Guyler, RC. Veltkamp, M. Burn, K. Rashed, M.J. Macleod, C. Canepa, J. Selvarajah, D. Hargroves, Y. Behnam, T.G. Robinson, L. Roveri, G. Lembo, D.S. Toni, V. Monzani, A. Cavallini, D. Popov, M. Friedrich, C. Minelli, C. Moro, R.J. Gagliardi, A. Bacellar, R. Mikulik, J. Eckstein, G. Panczel, N. Szegedi, and M.J. O’Donnell
Subjects: Brain Infarction, Male, medicine.medical_specialty, Internationality, Tobacco use, Cohort Studies, Magnetic resonance imaging, Double-Blind Method, Rivaroxaban, Internal medicine, medicine, Humans, In patient, cardiovascular diseases, Aged, Advanced and Specialized Nursing, Aspirin, medicine.diagnostic_test, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Middle Aged, Magnetic Resonance Imaging, Embolic stroke, Stroke, Intracranial Embolism, Brain infarction, Cardiology, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Factor Xa Inhibitors, medicine.drug
Abstract: Background and Purpose: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. Methods: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. Results: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26–115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack ( P 0 ( P P =0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. Conclusions: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02313909.
Published: 2022
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17. Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

Author: Subodh Verma, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Nitish K. Dhingra, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, C. Michael Gibson, Duane Pinto, Robert P. Giugliano, Matthew J. Budoff, R. Preston Mason, Jean-Claude Tardif, Christie M. Ballantyne, Fabrice M.A.C. Martens, Astrid Schut, Brian Olshansky, Mina Chung, Al Hallstrom, Lesly Pearce, Cyrus Mehta, Rajat Mukherjee, Anjan K. Chakrabarti, Eli V. Gelfand, Megan Carroll Leary, Duane S. Pinto, Yuri B. Pride, Steven Ketchum, Ramakrishna Bhavanthula, Gertrude Chester, Christina Copland, Katelyn Diffin, Ralph Doyle, Kurt Erz, Alex Giaquinto, Paula Glanton, Angela Granger, Richard H. Iroudayassamy, Rebecca Juliano, James Jin, Dimitry Klevak, Hardik Panchal, Robert Wang, Shin-Ru Wang, Gerard Abate, Peggy J. Berry, Rene Braeckman, Declan Doogan, Anne Elson, Amy HauptmannBaker, Isabel Lamela, Catherine Lubeck, Mehar Manku, Sabina Murphy, Monica Sanford, William Stirtan, Paresh Soni, Arnaud Bastien, Demetria Foster, Evangelito Gascon, Judith Johnson, Lasbert Latona, Gang Liu, Sandra Palleja, Nelly Sanjuan, Jimmy Shi, William Stager, Mukund Venkatakrishnan, Ahmed Youssef-Agha, Julie Zhu, Leela Aertker, Suresh Ankolekar, Lisa Goldberg, Natasa Rajicic, Jianfen Shu, Heng Zou, Magdy Mikhail, Gamil Dawood, N. Mathew Koshy, Sandip K. Mukherjee, Rafik Abadier, Andrea L. Lawless, William P. McGuinn, Howard Weintraub, Kathryn Rohr, Edmund Claxton, Robert J. Weiss, Terry D. Klein, Mani Nallasivan, Stephen Crowley, Marilyn King, Anthony D. Alfieri, David Fitz-Patrick, Irving Loh, Nolan J. Mayer, Rakesh Prashad, Samuel Lederman, Debra Weinstein, Harold E. Bays, Keith Chu, Alireza Maghsoudi, Paul D. Thompson, Jeff Carstens, Anna Chang, Kenneth R. Cohen, Julius Dean, Howard S. Ellison, Bernard Erickson, Enrique A. Flores, Daniel W. Gottlieb, Paul Grena, John R. Guyton, Peter H. Jones, John M. Joseph, Norman E. Lepor, Sam Lerman, Robert D. Matheney, Theodore R. Pacheco, Michael B. Russo, John Rubino, Edward S. Pereira, Albert A. Seals, Eduardo Viera, Alan D. Steljes, Jason Thompson, Shaival Kapadia, Michael McIvor, Jorge E. Salazar, Jose O. Santiago, Ralph Vicari, Martin R. Berk, William A. Kaye, Marcus McKenzie, David Podlecki, Brian D. Snyder, Stephen Nash, David M. Herrington, Wallace Johnson, Joseph R. Lee, Ronald Blonder, Alpa M. Patel, Ramon Castello, Susan Greco, Dean J. Kereiakes, Venkatesh K. Nadar, Mark Nathan, Ranganatha P. Potu, Robert Sangrigoli, Richard Smalling, Mitchell Davis, Robert Braastad, James McCriskin, Kunal Bodiwala, Joe L. Hargrove, Mark W. Graves, George Emlein, Raegan W. Durant, James W. Clower, Rohit Arora, Narendra Singh, Lisa Warsinger Martin, W Herbert Haught, Marc P. Litt, Michael D. Klein, Peter Hoagland, Michael Goldstein, Marco S. Mazzella, Daniel H. Dunker, Brian H. Kahn, Carlos S. Ince, Frank A. McGrew, Jay Lee, David Pan, Salman A. Khan, Uri Elkayam, Wasim Deeb, Anne C. Goldberg, Christopher S. Brown, Wayne N. Leimbach, Thomas S. Backer, David R. Sutton, Joel Gellman, Anu R. George, Alan S. Hoffman, Mark Kates, Kishlay Anand, Robert Bear, Brendan J. Cavanaugh, Ramon G. Reyes, Rodolfo Sotolongo, Kenneth Sabatino, Kevin Gallagher, Ehab Sorial, Chris Geohas, Kathleen E. Magness, Bernard P. Grunstra, Frederik A. Martin, William S. Knapp, Mel E. Lucas, John J. Champlin, Jason Demattia, Patrick H. Peters, Judith Kirstein, William J. Randall, Cezar S. Staniloae, Jennifer G. Robinson, Alexander Adler, Christopher Case, Andrew J. Kaplan, Gregory F. Lakin, Krishan K. Goyle, Michael J. DiGiovanna, Chester L. Fisher, Michael Lillestol, Michael Robinson, Robert G. Perry, Lawrence S. Levinson, Brian G. Everhart, Robert D. Madder, Earl F. Martin, Earl E. Martin, Imtiaz Alam, Jose Mari L. Elacion, Robina Poonawala, Taddese T. Desta, Jerome A. Robinson, Gilbert J. Martinez, Jakkidi S. Reddy, Jeffrey D. Wayne, Samuel Mujica Trenche, Westbrook I. Kaplan, Rubin H. Saavedra, Michael D. DiGregorio, Barry D. Bertolet, Neil J. Fraser, Terence T. Hart, Ronald J. Graf, David A. Jasper, Michael Dunn, Dan A. Streja, David J. Strobl, Nan Jiang, Vicki Kalen, Richard Mascolo, Mercedes B. Samson, Michael Stephens, Bret M. Bellard, Mario Juarez, Patrick J. McCarthy, John B. Checton, Michael Stillabower, Edward Goldenberg, Amin H. Karim, Naseem Jaffrani, Robert C. Touchon, Erich R. Fruehling, Clayton J. Friesen, Pradipta Chaudhuri, Frank H. Morris, Robert E. Broker, Rajesh J. Patel, Susan Hole, Randall P. Miller, Francisco G. Miranda, Sadia Dar, Shawn N. Gentry, Paul Hermany, Charles B. Treasure, Miguel E. Trevino, Raimundo Acosta, Anthony Japour, Samuel J. Durr, Thomas Wang, Om P. Ganda, Perry Krichmar, James L. Arter, Douglas Jacoby, Michael A. Schwartz, Amer Al-Karadsheh, Nelson E. Gencheff, John A. Pasquini, Richard Dunbar, Sarah Kohnstamm, Hector F. Lozano, Francine K. Welty, Thomas L. Pitts, Brian Zehnder, Salah El Hafi, Mark A. King, Arnold Ghitis, Marwan M. Bahu, Hooman Ranjbaran Jahromi, Ronald P. Caputo, Robert S. Busch, Michael D. Shapiro, Suhail Zavaro, Munib Daudjee, Shahram Jacobs, Vipul B. Shah, Frank Rubalcava, Mohsin T. Alhaddad, Henry Lui, Raj T. Rajan, Fadi E. Saba, Mahendra Pai N Gunapooti, Tshiswaka B. Kayembe, Timothy Jennings, Robert A. Strzinek, Michael H. Shanik, Pradeep K. Singh, Alastair C. Kennedy, Howard Rubenstein, Ramin Manshadi, Joanne Ladner, Lily Kakish, Ashley Kakish, Amy L. Little, Jaime Gerber, Nancy J. Hinchion, Janet Guarino, Denise Raychok, Susan Budzinski, Kathleen Kelley-Garvin, April Beckord, Jessica Schlinder, Arthur Schwartzbard, Stanley Cobos, Deborah Freeman, David Abisalih, Dervilla McCann, Kylie Guy, Jennifer Chase, Stacey Samuelson, Madeline Cassidy, Marissa Tardif, Jaime Smith, Brenna Sprout, Nanette Riedeman, Julie Goza, Lori Johnson, Chad Kraske, Sheila Hastings, Chris Dutka, Stephanie Smith, Toni McCabe, Kathleen Maloney, Paul Alfieri, Vinay Hosemane, Chanhsamone Syravanh, Cindy Pau, April Limcoiloc, Tabitha Carreira, Taryn S. Kurosawa, Razmig Krumian, Krista Preston, Ashraf Nashed, Daria Schneidman-Fernandez, Jack Patterson, John Tsakonas, Jennifer Esaki, Lynn Sprafka, Porous Patel, Brian Mitchell, Erin M. Ross, Donna Miller, Akash Prashad, Kristina M. Feyler, Natasha Juarbe, Sandra Herrera, Sarah M. Keiran, Becky Whitehead, Whitney Asher, Coury Hobbs, Abbey Elie, Jean Brooks, Amanda L. Zaleski, Brenda Foxen, Barb Lapke, Philippa Wright, Bristol Pavol, Gwen Carangi, Marla Turner, Katharine W. Sanders, Rikita S. Delamar, Virginia L. Wilson, Sarah M. Harvel, Alison M. Cartledge, Kaitlyn R. Bailey, Kathleen Mahon, Timothy Schuchard, Jen Humbert, Mark C. Hanson, Michael P. Cecil, James S. Abraham, Lorie Benedict, Claudia Slayton, Curtis S. Burnett, Rachel W. Ono-Lim, Sharon Budzinski, Shubi A. Khan, Sharon Goss, Terry Techmanski, Farida Valliani, Rimla Joseph, Edith Flores, Laurn Contreras, Ana Aguillon, Carrie-Ann Silvia, Maria Martin, Edmund K. Kerut, Leslie W. Levenson, Louis B. Glade, Brian J. Cospolich, Maureen W. Stein, Stephen P. LaGuardia, Thelma L. Sonza, Tracy M. Fife, Melissa Forschler, Jasmyne Watts, Judy Fritsch, Emese Futchko, Sarah Utech, Scott B. Baker, Miguel F. Roura, Scott A. Segel, James S. Magee, Cathy Jackson, Rebecca F. Goldfaden, Liudmila Quas, Elizabeth C. Ortiz, Michael Simpson, Robert Foster, Christopher Brian, James Trimm, Michael Bailey, Brian Snoddy, Van Reeder, Rachel Wilkinson, Harold Settle, Cynthia Massey, Angela Maiola, Michele Hall, Shelly Hall, Wanda Hall, Mark Xenakis, Janet Barrett, Giovanni Campanile, David Anthou, Susan F. Neill, Steven Karas, Enrique Polanco, Norberto Schechtman, Grace Tischner, Kay Warren, Cynthia St Cyr, Menna Kuczinski, Latrina Alexander, Maricruz Ibarra, Barry S. Horowitz, Jaime Steinsapir, Jeanette Mangual-Coughlin, Brittany Mooney, Precilia Vasquez, Kathleen Rodkey, Alexandria Biberstein, Christine Ignacio, Irina Robinson, Marcia Hibberd, Lisa B. Hoffman, Daniel J. Murak, Raghupathy Varavenkataraman, Theresa M. Ohlson Elliott, Linda A. Cunningham, Heather L. Palmerton, Sheri Poole, Jeannine Moore, Helene Wallace, Ted Chandler, Robert Riley, Farah Dawood, Amir Azeem, Michael Cammarata, Ashleigh Owen, Shivani Aggarwal, Waqas Qureshi, Mohamed Almahmoud, Abdullahi Oseni, Adam Leigh, Erin Barnes, Adam Pflum, Amer Aladin, Karen Blinson, Vickie Wayne, Lynda Doomy, Michele Wall, Valerie Bitterman, Cindi Young, Rachel Grice, Lioubov Poliakova, Jorge Davalos, David Rosenbaum, Mark Boulware, Heather Mazzola, J. Russell Strader, Russell Linsky, David Schwartz, Elizabeth Graf, Alicia Gneiting, Melissa Palmblad, Ashley Donlin, Emily Ensminger, Hillary Garcia, Dawn Robinson, Carolyn Tran, Jeffrey Jacqmein, Darlene Bartilucci, Michael Koren, Barbara Maluchnik, Melissa Parks, Jennifer Miller, Cynthia DeFosse, Albert B. Knouse, Amy Delancey, Stephanie Chin, Thomas Stephens, Mag Sohal, Juana Ingram, Swarooparani Kumar, Heather Foley, Nina Smith, Vera McKinney, Linda Schwarz, Judith Moore, Hildreth Vernon Anderson, Stefano Sdringola-Maranga, Ali Denktas, Elizabeth Turrentine, Rhonda Patterson, John Marshall, Terri Tolar, Donna Patrick, Pamela Schwartzkopf, Anthony M. Fletcher, Frances R. Harris, Sherry Clements, Tiffany Brown, William Smith, Stacey J. Baehl, Robin Fluty, Daniel VanHamersveld, Dennis Breen, Nancy Bender, Beverly Stafford, Tamika Washington, Margaret N. Pike, Mark A. Stich, Evyan Jawad, Amin Nadeem, Jill Nyland, Rhonda Hamer, Kendra Calhoun, Charlotte Mall, Samuel Cadogan, Kati Raynes, Richard Katz, Lorraine Marshall, Rashida Abbas, Jay L. Dinerman, John T. Hartley, Beth Lamb, Lisa Eskridge, Donna Raymond, Kristy Clemmer, Denise M. Fine, Paula Beardsley, Janet Werner, Bette Mahan, Courtney VanTol, Robert Herman, Christine Raiser-Vignola, Felicia McShan, Stefanie A. Neill, David R. Blick, Michael J. Liston, Denetta K. Nelson, Sandra K. Dorrell, Patricia Wyman, Ambereen Quraishi, Fernando Ferro, Frank Morris, Vicki J. Coombs, Autumn M. Mains, Austin A. Campbell, Jeanne Phelps, Cheryl A. Geary, Ellen G. Sheridan, Jean M. Downing, Arie Swatkowski, Tish Redden, Brian Dragutsky, Susan Thomas, Candace Mitchell, Diana Barker, Elanie Turcotte, Deborah Segerson, Jill Guy, Karena De La Mora, Jennifer Hong, Dennis Do, Rose Norris, Faisal Khan, Hector Montero, Stacy Kelly-White, Alan Cleland, Rosalyn Alcalde-Crawford, Melissa Morgan, Brijmohan Sarabu, Megan Minor, Shweta Kamat, Stephanie M. Estes, Nancee Harless, Alicia Disney, Jodi L. Pagano, Chad M. Alford, Noel W. Bedwell, Warren D. Hardy, Kevin DeAndrade, Jessica G. Elmore, Eric Auerbach, Anthony W. Haney, Miriam H. Brooks, Jose Torres, Lois Roper, Terry Backer, Katie Backer, John G. Evans, Ricardo A. Silva, Lorraine H. Dajani, Veronica Yousif, Tammy Ross, Sion K. Roy, Ronald Oudiz, Sajad Hamal, Ferdinand Flores, Amor Leahy, Debra Ayer, Swapna George, Chrisi Carine Stewart, Elvira Orellana, Cristina Boccalandro, Mary Rangel, Suzanne Hennings, Carl Vanselow, Teri Victor, Darlene Birdwell, Paul Haas, Anthony Sandoval, Gina Ciavarella, Caroline Saglam, Amy Bird, Keith Beck, Brian Poliquin, David Dominguez, Brittany Tenorio, Harvonya Perkins, Esther San Roman, Paris Bransford, Christy Lowrance, Marcy Broussard, Mary Ellis, Bobbi Skiles, Jessica Hamilton, Kathryn Hall, Diego Olvera, Julee A. Hartwell, Nevien Sorial, Mary Rickman, Kevin Berman, Nirav Mehta, Annie Laborin, Rodger Rothenberger, Sarah Beauvilliers, Kathy Morrell, Michael P. Schachter, Cindy L. Perkins, Elizabeth A. Gordon, Jennifer Lauer, Kim Bichsel, Kelly Oliver, Leslie J. Mellor, Candice Demattia, Jennifer Schomburg, Yenniffer Moreno, Eduardo Mansur-Garza, Lena Rippstein, Lorie Chacon, Andrea Pena, Michelle King, Susan Richardson, Annette Jessop, Nicole Tucker, Whitney Royer, Gilbert Templeton, Ann Moell, Christine Weller, Melissa J. Botts, Gretel Hollon, Elsa Homberg-Pinassi, Paula Forest, Aref Bin Abhulhak, Devona Chun-Furlong, Deborah Harrington, Emily Harlynn, Marjorie Schmitt, Constance Shelsky, Patricia Feldick, Mary Cherrico, Courtney Jagle, Nicholas Warnecke, Debra Myer, Deanna J. Ruder, Albina Underwood, Alan Rauba, George Carr, Barbara Oberhaus, Jessica Vanderfeltz, Mary Jo Stucky-Heil, Dale R. Gibson, Vonnie Fuentes, Kimberly L. Talbot, William C. Simon, Katlyn J. Grimes, Christina R. Wheeler, Cassaundra Shultz, Rhonda A. Metcalf, Jennifer L. Hill, Michelle R. Oliver, Basharat Ahmad, Fouzal Azeem, Abdul Rahim, George H. Freeman, Dawn Bloch, Heather Freeman, Jamie Brown, Sarah Rosbach, Pamela Melander, Nick Taralson, Alex Liu, Katlyn Harms, Mahfouz Michale, Jose Lopez, Maria Revoredo, Shari Edevane, Sarah Shawley, Timothy L. Jackson, Michael J. Oliver, Dina DeSalle, Patricia J. Matlock, Ionna M. Beraun, Heather Hendrix, Garrett Bromley, Ashley Niemerski, Gabby Teran, Sonia Guerrero, Murtaza Marvi, Zehra Palanpurwala, Andrea Torres, Patty Gloyd, Michelle Conger, Aziz Laurent, Olia Nayor, Catalina S. Villanueva, Munira Khambati, Tabetha J. Mumford, Melanie J. Castillo, Taddese Desta, Jerome Robinson, La Shawn Woods, Anita Bahri, Nancy Herrera, Cecilia Casaclang, Jeffrey R. Unger, Geraldine Martinez, Mia K. Moon, Stephen M. Mohaupt, Larry Sandoval, Louisito Valenzuela, Victora Ramirez, Nelly Mata, Veronica Avila, Marisol Patino, Cynthia Montano-Pereira, Omar Barnett, William M. Webster, Lorraine M. Christensen, Leighna Bofman, Melanie Livingston, Stacey Adams, Joseph Hobbs, Leesa Koskela, Mia Katz, Samuel Mujica-Trenche, Franklin Cala, Noreen T. Rana, Jennifer Scarlett, Milagros Cala Anaya, Marsha R. Jones, Kelly D. Hollis, Debbie Roth, Kristin Eads, Tina Watts, Judy Perkins, Alice Arnold, Daniel C. Ginsberg, Denise Quinn, Nicole Cureton, David B. Fittingoff, Mohammed I. Iqbal, Stephen R. White, Edith Sisneros, Michelle Ducca, David Streja, Danny Campos, Jennifer L. Boak, Farzeen Amir, Felice Anderson, James J. Kmetzo, Mary O. Bongarzone, Dawn Scott, Mary Grace De Leon, Cynthia Buda, William Graettinger, Michelle Alex, Erika Hess, James Govoni, Melissa Bartel, Travis L. Monchamp, Julie S. Roach, Sara Gibson, Amy M. Allfrey, Kristen Timpy, Kathy Bott, Karin A. Soucy, Jean Willis, Cecilia A. Valerio, Anusha Chunduri, Rebecca Coker, Nicole Vidrine, Ellen A. Thompson, Mark A. Studeny, Melissa K. Marcum, Tammy S. Monway, Douglas L. Kosmicki, Melissa J. Kelley, Corey M. Godfrey, Susan L. Krenk, Randy R. Holcomb, Deb K. Baehr, Mary K. Trauernicht, David Rowland Lowry, Betty Bondy Herts, Jeanne E Phelps, Jean-Marie Downing, Carol Gamer Dignon, Elisabeth S. Cockrill, Pravinchandra G. Chapla, Diane Fera, Margaret Chang, Patricia Fredette, Tamie Ashby, Renee Bergin, Zebediah A. Stearns, David B. Ware, Rachael M. Boudreaux, Joanna Rodriguez, Robert McKenzie, Amanda Huber, Rebecca Sommers, Heather Rowe, Stacy McLallen, Michale Haynes, Ashley Adamson, Janice Henderson, Lori McClure, Beverly A. Harris, Laura Ference, Sue Meissner-Dengler, Lisa Treasure, Doreen Nicely, Timothy L. Light, Tracey A. Osborn, Kimberly J. Mai, Pablo Vivas, Jose Rios, Dunia Rodriguez, Roger DeRaad, James Walder, Oscar Bailon, Denice Hockett, Debbie Anderson, Kelli McIntosh, Amber Odegard, Andrew Shepherd, Mary Seifert, Laurence Kelley, Rajendra Shetty, Michael Castine, David Brill, Gregory Fisher, Nicole Richmond, Kathleen Gray, Patricia Miller, Charlene Coneys, Yarixa Chanza, Monica Sumoza, Victoria M. Caudill, Kelly D. Harris, Courtney A. Manion, Melody J. Lineberger-Moore, Julie J. Wolfe, Barbara J. Rosen, Patricia DiVito, Janet L. Moffat, Christina Michaelis, Prashant Koshy, Diana Perea, Ghaith Al Yacoub, Stephanie Sadeghi, Thomas D. LeGalley, Rudolph F. Evonich, William J. Jean, Gary M. Friesen, John M. Pap, David A. Pesola, Mark D. Cowan, Kristofer M. Dosh, Dianna Larson, Adele M. Price, Jodi A. Nease, Jane E. Anderson, Lori A. Piggott, Robert Iwaoka, Kevin Sharkey, Edward McMillan, Laurie Lowder, Latisha Morgan, Kyle Davis, Tara Caldwell, Erica Breglio, Jasmine Summers, Rachel Poulimas, Muhammad Zahid, Hamid Syed, Maria Escobar, Jacob Levy, Rahma Warsi, Carol Ma, Puxiao Cen, Kimberly A. Cawthon, Delores B. Barnes, Deanna G. Allen, Margaret L. Warrington, Carol R. Stastny, Robin J. Michaels, Mohamad Saleh, John Sorin, Sunny Rathod, Urakay Juett, Steven Spencer, Aziza Keval, Jill McBride, Shane Young, Catherine Baxter, Carol Rasmussen, Shari L. Coxe, Luis Campos, Shahin Tavackoli, Diana Beckham, Darlynee Sanchez, Karanjit Basrai, Dorian Helms, Erica Clinton, Kasie Smith, Henry Cusnir, Mary Klaus Clark, Madhavagopal V. Cherukuri, Ameta Scarfaru, Stephen D. Nash, Loretta C. Grimm, Anna Grace, Kylie McElheran, Dino Subasic, Zedrick Buhay, Janet Litvinoff, Deepak Shah, Shannon Cervantes, Freda Usher, Farra Yasser, Theodore Trusevich, Ronnie L. Garcia, Jamison Wyatt, Rahul Bose, Holllilyn Miska, Traci Spivey, Amy B. Wren, Katie E. Vance, Lani L. Holman, Pam Gibbons, Elaine Eby, Sandra Shepard, Soratree Charoenthongtrakul, Brett Snodgrass, Mohammed Nazem, Shelly Keteenburg, Prathima Murthy, Frederic Prater, Ashley Rumfelt, Christina Eizensmits, Lisa Iannuzzi, Pourus R. Patel, Clellia Bergamino, Elizabeth McFeaters, Botros Rizk, Emiljia Pflaum, Danny Kalish, Rex Ambatali, Mona Ameli, Delaina Sanguinetti, Rakesh Vaidya, Martinus A.W. Broeders, Dorman Henrikus, Adrianus F.M. Kuijper, Nadea Al-Windy, Michael Magro, Karim Hamraoui, Ismail Aksoy, Guy L.J. Vermeiren, H.W.O. Roeters van Lennep, Gerard Hoedemaker, Johannes Jacobus Remmen, Kjell Bogaard, Dirk van der Heijden, Nicole MJ Knufman, Joost Frederiks, Johannes Willem Louwerenburg, Piet van Rossum, Johannes Milhous, Peter van der Meer, Arno van der Weerdt, Rob Breedveld, Mitran Keijzers, Walter Hermans, Ruud van de Wal, Peter A.G. Zwart, Marc M.J.M. van der Linden, Gerardus Zwiers, Dirk J. Boswijk, Jan Geert Tans, Jacob van Eck, Maarten V. Hessen, Barnabas J.B. Hamer, Stieneke Zoet-Nugteren, Lucien Theunissen, E.A. van Beek, Remco Nijmeijer, Pieter R. Nierop, Gerard Linssen, H.P. Swart, Timo Lenderink, Gerard L. Bartels, Frank den Hartog, Brian J. Berg van den, Wouter van Kempen, Susanne Kentgens, Gloria M. Rojas Lingan, Martinus M. Peeters, Hilligje Keterberg, Melchior Nierman, Annemieke K. den Hollander, Jacqueline Hoogendijk, Christine Voors-Pette, Vicdan Kose, Peter Viergever, Larysa Yena, Viktor Syvolap, Mykola P. Kopytsya, Olga Barna, Svitlana S. Panina, Mykhailo I. Lutai, Oxana V. Shershnyova, Iryna Luzkiv, Larysa S. Bula, Sergii Zotov, Ivan Vyjhovaniuk, Olena Lysunets, Volodymyr I. Koshlia, Nataliya Sydor, Myroslava F. Vayda, Olexiy Ushakov, Mykola Rishko, Viktor P. Shcherbak, Yevgeniya Svyshchenko, Vira Tseluyko, Andriy Yagensky, Viktoriia I. Zolotaikina, Olga Godlevska, Larysa Ivanova, Olena Koval, Olena I. Mitchenko, Galyna Y. Kardash, Yurii S. Rudyk, Mykola Stanislavchuk, Volodymyr Ivanovych Volkov, Olena G. Karlinskaya, Susanna A. Tykhonova, Nikolay Vatutin, Ganna Smirnova, Volodymyr M. Kovalenko, Viktor Lizogub, Denys Sebov, Oleksandr Dyadyk, Svetlana Andrievskaya, Mykola P. Krasko, Alexander N. Parkhomenko, Lidiya Horbach, Iryna G. Kupnovytska, Tetyana Pertseva, Oleksandr Karpenko, Dmytro Reshotko, Svitlana V. Zhurba, Leonid Rudenko, Viktoriia Yu Zharinova, Valerii B. Shatylo, Yuriy I. Karpenko, Mariya A. Orynchak, Tatiana R. Kameneva, Elena Zherlitsina, Diana N. Alpenidze, Grigoriy P. Arutyunov, Elena Baranova, Boris Bart, Dmitriy I. Belenkiy, Svetlana A. Boldueva, Elena A. Demchenko, Vera V. Eltishcheva, Alexander M. Gofman, Boris M. Goloshchekin, Ivan Gennadyevich Gordeev, Nikolay Gratsianskiy, Gadel Kamalov, Niyaz R. Khasanov, Irina M. Kholina, Zhanna D. Kobalava, Elena V. Kobeleva, Alexandra O. Konradi, Victor A. Kostenko, Andrey Dmitrievich Kuimov, Polina Y. Ermakova, Sofia K. Malyutina, Alexey V. Panov, Natalia V. Polezhaeva, Olga Reshetko, Nataliya P. Shilkina, Sergey B. Shustov, Elena A. Smolyarchuk, Raisa I. Stryuk, Elena Yurievnar Solovieva, Andrey V. Susekov, Natalia Vezikova, Svetlana N. Ivanova, Alexander A. Petrov, Vladimir O. Konstantinov, Alina S. Agafina, Victor Gurevich, Konstantin N. Zrazhevskiy, Tatiana V. Supryadkina, Nikita B. Perepech, Vadim L. Arkhipovskiy, Dmitry Yu Butko, Irina A. Zobenko, Olga V. Orlikova, Viktor Mordovin, Olga L. Barbarash, Anastasiya Lebedeva, Vladimir Nosov, Oleg V. Averkov, Elena P. Pavlikova, Yuri B. Karpov, Marina Lvovna Giorgadze, Oleg A. Khrustalev, Mikhail Arkhipov, Tatiana A. Raskina, Julia V. Shilko, Yulia Samoilova, Elena D. Kosmacheva, Sergey V. Nedogoda, Kathleen Coetzee, Lesley J. Burgess, F.C.R. Theron, Iftikhar O. Ebrahim, Gerbrand A. Haasbroek, Maria Pretorius, Julien S. Trokis, Dorothea V. Urbach, Mark J. Abelson, Adrian R. Horak, Aysha E. Badat, Ellen M. Makotoko, Hendrik Du Toit Theron, Padaruth Ramlachan, Clive H. Corbett, Ismail H. Mitha, Hendrik F.M. Nortje, Dirkie J. Jansen van Rensburg, Peter J. Sebastian, F.C.J. Bester, Louis J. van Zyl, Brian L. Rayner, Elżbieta Błach, Magda Dąbrowska, Grzegorz Kania, Agata E. Kelm-Warchol, Leszek P. Kinasz, Janusz Korecki, Mariusz Kruk, Ewa Laskowska-Derlaga, Andrzej Madej, Krzysztof Saminski, Katarzyna Wasilewska, Katarzyna Szymkowiak, Małgorzata Wojciechowska, Natalia Piorowska, Andrzej Dyczek, Rajpal K. Abhaichand, Ramesh B. Byrapaneni, Basavanagowdappa Hattur, Malipeddi Bhaskara Rao, Nitin Ghaisas, Sujit Shankar Kadam, Jugal B. Gupta, Santhosh M. Jayadev, V.A. Kothiwale, Atul Mathur, Vijay Bhaskar, Ravi K. Aluri, Udaya P. Ponangi, Mukesh K. Sarna, Sunil Sathe, Manish K. Sharma, Jilendra Pal Singh Sawhney, Chakrabhavi B. Keshavamurthy, Arun Srinivas, Hemant P. Thacker, A. Sharda, Johny Joseph, Sunil Dwivedi, Viswanathan Mohan, Rajendra K. Premchand, Jacques Bedard, Jean Bergeron, Ronald Collette, David Crowley, Richard Dumas, Sam Henein, Geoff Moran, William F. O’Mahony, Michael O’Mahony, Sammy Chan, Mark H. Sherman, Graham C. Wong, Brian D. Carlson, Milan K. Gupta, David Borts, Sean R. Peterson, Martyn Chilvers, Allan J. Kelly, Jean C. Gregoire, Simon Kouz, Josep Rodés Cabau, Minodora Andor, Mircea Cinteza, Radu Ciudin, Radu I. Cojan, Roxana O. Darabont, Dan-Lucian Dumitrascu, Carmen Fierbinteanu-Braticievici, Ana Gabriela Fruntelata, Constantin Militaru, Bogdon E. Minescu, Doina Luminita Serban, Florin Mitu, Dorel Nastase Melicovici, Ovidiu Petrascu, Octavian M. Pirvu, Cristian Podoleanu, Calin Pop, Rodica-Valentina V. Stanescu-Cioranu, Adrian Tase, Cristina Voiculet, Constantine N. Aroney, Anthony M. Dart, Timothy Davis, Karam Kostner, David N. O’Neal, Peter W. Purnell, Bhuwanendu B. Singh, David R. Sullivan, Peter Thompson, Gerald F. Watts, Adam F. Blenkhorn, John V. Amerena, Rafeeq Samie, Randall Hendriks, Joseph Proietto, Nikolai Petrovsky, Alan Whelan, David Colquhoun, Russell S. Scott, Simon C. Young, Tammy Pegg, Samuel JS Wilson, Andrew W. Hamer, Richard A. Luke, Hamish H. Hart, Gerard P. Devlin, Gerard T. Wilkins, Ian F. Ternouth, Samraj Nandra, Bruno S. Loeprich, Nicole McGrath, Stuart L. Tie, Rob J. Bos, Alexandra Wils, Tamara Jacobs, Erik A. Badings, Lillian A. Ebels-Tuinbeek, Mayke L. Scholten, Esther Bayraktar-Verver, Debby Zweers, Manoek Schiks, Carolien Kalkman, Tineke Tiemes, Jeanette Mulderij, Katarzyna Dabrowska, Wilma Wijnakker, Riny Van de Loo, Jeanne de Graauw, Giny Reijnierse, Mirjam van der Zeijst, Mariska Scholten, Henk R. Hofmeijer, Antoinette van Dijk-van der Zanden, Dineke J. van Belle, Jan Van Es, Gera Van Buchem, Wendy Zijda, Harald Verheij, Linnea Oldenhof-Janssen, Martina Bader, Marije Löwik, Sandra Stuij, Pascal Vantrimpont, Krista van Aken, Karen Hamilton, Han Blömer, Gabriela van Laerhoven, Raymond Tukkie, Maarten Janssen, Gerard Verdel, Jon Funke Küpper, Bob van Vlies, Caroline Kalkman, Joke Vooges, Marinella Vermaas, Rachel Langenberg, Niek Haenen, Frans Smeets, Arko Scheepmaker, Marcel Grosfeld, Ilvy Van Lieshout, Marleen van den Berg, Marian Wittekoek, Petra Mol, Antionette Stapel, Margaretha Sierevogel, Nancy van der Ven, Annemiek Berkelmans, Eric Viergever, Hanneke Kramer, Wilma Engelen, Karen V. Houwelingen, Thierry X. Wildbergh, Arend Mosterd, Coriet Hobé-Rap, Marjan van Doorn, Petra Bunschoten, Michel Freericks, Mireille Emans, Petra Den Boer-Penning, Els Verlek, Christine Freericks, Cornelis de Nooijer, Christina Welten, Ingrid Groenenberg, Claudia van der Horst, Esther Vonk, Geert Tjeerdsma, Gerard M. Jochemsen, Corinne van Daalen, Ingrid Y. Danse, Lucy Kuipers, Anke Pieterse, Antonius Oomen, Daan de Waard, Willem Jan Flu, Zusan Kromhout, Petra Van der Bij, Rob Feld, Brigitta Hessels-Linnemeijer, Rob Lardinois, Jan L. Posma, Zwanette R. Aukema-Wouda, Marjolijn Hendriks-van Woerden, Desiree van Wijk, Driek P. Beelen, Ingrid H. Hendriks, Jan J. Jonker, Stefanie Schipperen, Vicdan Köse, Gloria Rojas, Linda Goedhart, Hanneke van Meurs, Jacqueline Rijssemus, Lindy Swinkels-Diepenmaat, Marloes de Louw-Jansen, Dominique Bierens-Peters, Willem W. van Kempen, Marianne E. Wittekoek, Irmaina Agous, Geert Schenk, Janneke Wittekoek, Kevin Cox, Deborah F. Julia, Jan J.C. Jonker, Roel Janssen, Melchor Nierman, Hilligje Katerberg, Irene van der Haar, Willem W. Van Kempen, Taco van Mesdag, Leyda M. Alvarez Costa, Manon Schensema, Salomé Zweekhorst, Deborah Font Julia, Lauri Hanewinckel, Joyce Olsthoorn, Johan C. Berends, Arie C. van der Spek, Roy van der Berg, Rob J. Timmermann, Ingrid Boerema, Iryna Mudruk, Anna Khrystoforova, Serhii Kyselov, Yaroslava V. Hilova, Pavlo Logoida, Nataliia A. Sanina, Ilona P. Golikova, Olena O. Nemchyna, Ivan I. Isaichikov, Olga B. Potapova, Iurii V. Gura, Larysa Berestetska, Olena O. Kulianda, Oleksandr Tantsura, Oleksandr S. Kulbachuk, Volodymyr Petsentiy, Ihor Biskub, Tetyana Handych, Oleg Lagkuti, Alyna Gagarina, Taras Chendey, Oksana F. Bilonko, Olena Matova, Larysa Bezrodna, Olena Yarynkina, Tetiana Ovdiienko, Volodymyr Randchenko, Maryna Mospan, Olena Butko, Olga Romanenko, Mykhailo Pavelko, Iryna Sichkaruk, Svitlana O. Lazareva, Olena A. Kudryk, Inessa M. Koltsun, Tetiana Magdalits, Sergei Zadorozhniy, Kira Kompaniiets, Andrii Ivanov, Sergiy Romanenko, Pavlo Kaplan, Vadym Y. Romanov, Oksana P. Mykytyuk, Nataliia S. Zaitseva, Sergiy N. Pyvovar, Lyudmyla Burdeuna, Emerita Serdobinska, Tatiana I. Shevchenko, Igor I. Ivanytskyi, Olena V. Khyzhnyak, Nataliya Kalinkina, Olena Keting, Olena Sklyanna, Olga Kashanska, Anna Shevelok, Marina Khristichenko, Ievgenii Y. Titov, Danilenko O. Oleksander, Nataliia S. Polenova, Nataliia Altunina, Viktoriia Kororaieva, Stanislav Zborovskiy, Leonid Kholopov, Iurii Suliman, Lanna Lukashenko, Stanislav Shvaykin, Olexandr M. Glavatskiy, Roman O. Sychov, Roman L. Kulynych, Oleksandr A. Skarzhevskyi, Nataliia V. Dovgan, Marta Horbach, Olga Cherkasova, Iryna Tyshchenko, Liudmyla Todoriuk, Svitlana Kizim, Nataliia Brodi, Oleksandr Ivanko, Olga Garbarchuk, Liudmyla Alieksieieva, Tetiana L. Shandra, Olena Beregova, Larisa An Bodretska, Svitlana S. Naskalova, Ivanna A. Antoniuk-Shcheglova, Olena V. Bondarenko, Natalia G. Andreeva, Iryna I. Vakalyuk, Olha S. Chovganyuk, Nataliya R. Artemenko, Kiril A. Maltsev, Natalia Kalishevich, Natalia G. Kondratyeva, Svetlana A. Nikitina, Maria V. Martjanova, Anna V. Sokolova, Dmitrii O. Dragunov, Olga Kolesnik, Vera Larina, Oxana V. Tsygankova, Maria Ivanova, Illia A. Karpov, Elena M. Aronova, Ekaterina S. Vedernikova, Ekaterina I. Lubinskaya, Taras Y. Burak, Sergey I. Skichko, Farhad Rasulev, Ekaterina B. Soldatova, Alexander L. Fenin, Ilya I. Laptev, Elena E. Luchinkina, Alexandr Akatov, Natalia V. Polenova, Natalia N. Slavina, Irina N. Korovnika, Marina Yu Prochorova, Regina Shakirova, Elena N. Andreicheva, Olga A. Krasnova, Tinatin V. Lobzhanidze, Tatiana B. Dmitrova, Viktoriya V. Stakhiv, Maria I. Pechatnikova, Alexandra V. Panova, Maria Y. Tipikina, Oxana P. Rotar, Nikolay A. Bokovin, Saule K. Karabalieva, Farid Y. Tumarov, Elena V. Vasileva, Natalya Gennadevna Lozhkina, Ekaterina V. Filippova, Alisa I. Sharkaeva, Ekanerina V. Filippova Deilik, Natalia Yu Tolkacheva, Elena N. Domracheva, Andrey N. Ryabikov, Inga T. Abesadze, Marianna Z. Alugishvili, Elena P. Nikolaeva, Nadezda V. Smirnova, Valentina I. Rodionova, Polina V. Dolovstaya, Igor E. Yunonin, Sergey V. Kadin, Tatyana S. Sveklina, Anna V. Bushmanova, Elena L. Barkova, Irina S. Gomova, Yana V. Brytkova, Tatiana B. Ivanova, Marina Y. Zubareva, Inga Skopets, Lybov A. Galashevskaya, Emilia D. Butinskaya, Olga G. Gusarova, Natalia B. Kalishevich, Yana R. Pavlova, Marianna P Serebrenitskaya, Vitalina F. Grygorieva, Gulnara R. Kuchaeva, Inna A. Vasileva, Gulnara I. Ospanova, Yulia V. Vahrusheva, Irina A. Semenova, Irina E.E. Mikhailova, Olga O. Kvasova, Valeria D. Shurygina, Alexey E. Rivin, Alexey O. Savelyev, Alexey A. Savelyev, Olesya O. Milyaeva, Nadezhda N. Lapshina, Ninel A. Lantsova, Pavel V. Alexandrov, Evgeniy A. Orlikov, Alla Falkovskaya, Tatiana Ripp, Sergei Triss, Stanislav Pekarskiy, Sitkova Ekaterina, Evgeniya N. Zhuravleva, Olga Perova, Galina Kovaleva, Liubov Koroleva, Lydia Mishchenko, Boris P. Garshin, Svetlana A. Kutuzova, Lyudmila I. Provotorova, Igor P. Zadvorny, Olga V. Okhapkina, Anatoly O. Khrustalev, Tatiana Suvorova, Elena S. Shaf, Varvara A. Vershinina, Andrey A. Kozulin, Oxana A. Oleynik, Irina Y. Martynova, Natalia V. Kizhvatova, Alla S. Salasyuk, Vera V. Tsoma, Alla A. Ledyaeva, Elena V. Chumachek, S.C. Blignaut, Tersia Y. Alexander, Chano Du Plessis, Thirumani Govender, Samatha M. Du Toit, Leya Motala, Areesh Gassiep, Christina Naude (Smit), Marli Terblanche, Marlien Snoer (Kruger), Berenice Pillay, De Vries Basson, Marisa E. Theron, Bianca Fouche, Mareli E. Coetzee, Pieter Odendall, Frederik H. Van Wijk, Anna-Mari Conradie, Trudie Van der Westhuizen, Carine Tredoux, Mohamed S. Mookdam, Andie J. Van der Merwe, Karin Snyman, Gerda Smal, Yvonne De Jager, Thomas A. Mabin, Annusca King, Lindy L. Henley, Brenda M. Zwane, Jane Robinson, Marinda Karsten, Andonia M. Page, Valerie Nsabiyumva, Charmaine Krahenbuhl, Jaiprakash D. Patel, Yunus E. Motala, Ayesha Dawood, Nondumiso B. Koza, Lenore M.S. Peters, Shavashni Ramlachan, Wilhelm J. Bodenstein, Pierre Roux, Lizelle Fouche, Cecilia M. Boshoff, Haroon M. Mitha, Fathima Khan, Henry P. Cyster, Helen Cyster, E. C. Wessels, Florence J. Jacobs, Melanie A. Sebastian, Deborah A. Sebastian, Nadia Mahomed, Ignatius P. Immink, Celia Cotzee, Tanja Cronje, Madele Roscher, Maria Le Roux, Yvonne A. Trinder, Renata Wnętrzak-Michalska, Magdalena Piszczek, Andrzej Piela, Ewa Czernecka, Dorota Knychas, Alina Walczak, Izabella Gładysz, Katarzyna Filas, Ewelina Kiluk, Krzysztof Świgło, Iwona Jędrzejczyk, Kamila Łuczyńska, Katarzyna Tymendorf, Wojciech Piesiewicz, Wojciech L. Kinasz, Stefan Samborski, Ilona Bartuś, Gramzyna Latocha Korecka, Ewa Gulaj, Jolanta Sopa, Bogusław Derlaga, Marcin Baisiak, Allicia Kowalisko, Edyta Stainszewska-Marasazlek, Bartosz Szafran, Malgorzata Swiatkiewicz, Artur Racewicz, Sławomir Grycel, Jerzy Supronik, Sylwia Walendziuk, Magdalena Tarantowicz, Agata Stasiak, Anna Sidorowicz-Białynicka, Marek Dwojak, Ewa Jaźwińska-Tarnawska, Katarzyna Kupczyk, Kamila Martowska, Kamila Kulon, Katarzyna Gajda, Bivin Wilson, Krithika Velusamy, Swaidha S. Sadhiq, Bhavani Siddeshi, M. Bhanukumar, Abhishek Srivatsav, Madhan Ramesh, Sri Harsha Chalasani, Mini Johnson, Prashanth Gopu, Jeesa George, Sowmya Reddy, Swetha Tessy Thara Eleena, Damodara Rao Kodem, Haritha N. Nakkella, Padma Kumari Mandula, Anjan Kumar Vuriya, Syamala Rajana, Aruna Kale, Tiwari Rajeev, Raina Jain, Vipin Jain, Srilakshmi Mandayam Adhyapak, Lumin Sheeba, Uma C R, Ramya R, Aditya V. Kulkarni, M.S. Ganachari, Ruma Sambrekar, Mohammad Bilal, Kalyan Chakravarthy, Ravi Badhavath, Sravan Kumar, Meenakshi Simhadri, Farooque Salamuddin, Venkat Prasad, Vivek Dwivedi, Sudha Sarna, Tilak Arora, Deepak Chawla, Archana Sathe, Chaware Gayatree, Ajeet Nanda, Ram Avtar, Jyoti Sharma, Vaibhavi P S, Sasirekha D, Deepthi Kobbajji, Ramya Ningappa, Shwetha Shree, Chandrashekar K, Nandini M R, Sowjanya S, Devika I G, Yashaswini N, Sonika G, Rathna L, Priyanka R, Rupal J. Shrimanker, Lakshmi Vinutha Reddy, K. Sumathi, Babitha Devi, Bina N. Naik, Rohini Manjunath, Rajeshwari Ashok, Tony V. Kunjumon, Jesline Thomas, Shaik Samdhani, Kasthuri Selvam, Poongothai Subramani, Nandakumar Parthasarathy, Nirmal K. Bohra, Anvesh K. Gatla, Cheryl Horbatuk, Julie Sills, E B. Davey, Liz Paramonczyk, Olga Racanelli, Sandy Strybosch, Andre Belanger, Jean Palardy, Alicia Schiffrin, Sylvie Gauthier, Norman Kalyniuk, Shawn D. Whatley, Heather Lappala, Grishma Patel, Matthew Reeve, Catherine Moran, Jody Everitt, Teresa Ferrari, Christine Bouffard, Jirir Frohlich, Gordon Francis, John Mancini, Gregory Bondy, Debbie DeAngelis, Patricia Fulton, David W. Blank, Angela Lombardo, Mylène Roy, Jackie Chow, Hyman Fox, William J. Grootendorst, Angela Hutchinson, Sharon M. Chan, Christie Fitzgerald, Lynn Wilkins, Rebecca L. Raymond, Arlene Reyes, Lavoie Marc André, Denis Fortin, Hélène Ouimet, Thanh-Thao Tôn-Nu, Martine Dussureault, Marie-Hélène Blain, Madeleine Roy, Nathalie Kopajko, Chantal Fleury, Karine Maheux, Gabriela Valentina Ciobotaru, Maria C. Constantinescu, Carmen-Lucia Gherghinescu, Ana-Maria Avram, Ioan Manitiu, Aura Sinpetrean, Lucian Pop, Delia Lupu, Radu Usvat, Ana Petrisor, Nicoleta Dumitru, Camelia Moruju, Adelina Gheorghita, Magda V. Mitu, Cosmin Macarie, Ana Maria Pop, Maria-Catalina Diaconu, Iulia Grancea, Mihaela Cosma, Mihaela Crisan, Elizabeth Herron, Paul Nestel, Sally B. Kay, Kaye S. Carter, Imran Badshah, Ashley Makepeace, Jocelyn Drinkwater, Michelle England, Azette Rafei, Kylie Patterson, Alicia Jenkins, Sybil McAuley, Sue M. Kent, Joy E. Vibert, Leonie Perrett, Thomas David, Samantha L. Kaye, Monika O’Connor, Nimalie J. Perera, Nicole T. Lai, Kerry A. Kearins, Christinia Dicamillo, Heather Anderson, Louise Ferguson, Sharon D. Radtke, Charles T. Thamarappillil, Janice M. Boys, Anita K. Long, Toni Shanahan, Michael Nyguyen, Nicole Forrest, Gill Tulloch, Della Greenwell, Sarah L. Price, Aye N. Tint, Priya K. Sumithran, Tamara L. Debreceni, Lisa Walker, Mary Caruana, Kira Edwards, Maria Stathopoulos, Cilla Haywood, Dimitar Sajkov, Sharen Pringle, Anne Tabner, Kathrina Bartolay, Chamindi Abeyratne, Kylie Bragg, Patrick Mulhern, Peter Purnell, Lyn Williams, Jane Hamlyn, Aurelia Connelly, Jan Hoffman, Samantha Bailey, Jane Kerr, Zarnia Morrison, Sarah Maeder, Roberta McEwan, Prasanna Kunasekera, Patrice McGregor, Jo Young, Sharon Berry, Rick Cutfield, Michelle Choe, Catherine McNamara, Narrinder K. Shergill, Petra Crone, Miles G. Williams, Keith Dyson, Diana H. Schmid, Audrey C. Doak, Melissa Spooner, Colin Edwards, Anne Turner, Grainne M. McAnnalley, Raewyn A. Fisher, Fraser B. Hamilton, Denis H. Friedlander, Melissa R. Kirk, Jayne E. Scales, Marguerite A. McLelland, Neelam A. Dalman, Cathy E. Vickers, Carolyn Jackson, Wendy Coleman, Phillip I. Garden, and Wendy F. Arnold
Subjects: Male, medicine.medical_specialty, Rate ratio, Double-Blind Method, Ischemia, Risk Factors, Physiology (medical), Internal medicine, medicine, Clinical endpoint, Humans, Myocardial infarction, Coronary Artery Bypass, Stroke, Aged, business.industry, Unstable angina, Hazard ratio, Absolute risk reduction, Middle Aged, medicine.disease, Eicosapentaenoic Acid, Number needed to treat, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.
Published: 2021
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18. Outcomes of surgical bleb revision at a tertiary Singapore eye hospital

Author: Ching Lin Ho, Carlo J S Rubio, Shamira A. Perera, Hla Myint Htoon, and Annabel C. Y. Chew
Subjects: Leak, medicine.medical_specialty, Dysesthesia, genetic structures, business.industry, medicine.medical_treatment, Glaucoma, Mean age, medicine.disease, eye diseases, Surgery, Ophthalmology, surgical procedures, operative, medicine, Glaucoma surgery, Trabeculectomy, sense organs, Bleb (medicine), medicine.symptom, business, Primary problem
Abstract: PURPOSE To describe the outcomes of surgical bleb revisions from a tertiary glaucoma service in Singapore. METHODS One hundred and thirty-one eyes of 129 patients who underwent surgical bleb revisions at the Singapore National Eye Centre between 2007 and 2014 were included in the study. The indications for bleb revision were: bleb-related infection (BRI), early and late bleb leak, early and late overfiltration, and bleb dysesthesia. Regression analysis was applied to elucidate risk factors. RESULTS The mean age of the patients was 66 years, 62.6% were male, and 88.5% were Chinese. The majority of the eyes had primary glaucoma (79.4%). The mean interval from the initial trabeculectomy or phaco-trabeculectomy to the bleb revision was 58.8 months. The overall success rate was 69.5%. By Kaplan-Meier survival analysis, the overall cumulative success range fell from 78.6% to 49.1% over 10 years. Eyes with early bleb leak had lower surgical success compared to eyes with late bleb leak, early overfiltration and late overfiltration (P = 0.026, log-rank test). The IOP improved significantly post-operatively for eyes with BRI, early bleb leak, late bleb leak, early overfiltration and overfiltration (P
Published: 2021
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19. Curative-Intent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck in Sri Lanka: The Impact of Radiotherapy Technique on Survival

Author: P. Abeysinghe, T. Skandarajah, K. Perera, Ananya Choudhury, Thashika Rupasinghe, Nuradh Joseph, D. Gunasekera, J. Balawardena, D.C. Silva, N. Jeyakumaran, and S. Weerasinghe
Subjects: Prognostic variable, medicine.medical_specialty, medicine.medical_treatment, Disease-Free Survival, medicine, Clinical endpoint, Humans, Radiology, Nuclear Medicine and imaging, Stage (cooking), Retrospective Studies, Sri Lanka, Chemotherapy, Squamous Cell Carcinoma of Head and Neck, business.industry, Head and neck cancer, Cancer, medicine.disease, Confidence interval, Radiation therapy, stomatognathic diseases, Oncology, Head and Neck Neoplasms, Radiotherapy, Intensity-Modulated, Radiology, Neoplasm Recurrence, Local, business
Abstract: We conducted a retrospective analysis of patients with squamous cell carcinoma of the head and neck (SCCHN) treated with curative-intent radiotherapy at the National Cancer Institute of Sri Lanka to determine the impact of the treatment technique on disease-free survival (DFS).SCCHN patients treated with radical radiotherapy or adjuvant postoperative radiotherapy from 2016 to 2017 were included in the study. Data on the following variables were collected by reviewing clinical and radiotherapy treatment records: age, gender, tumour site, stage, time to delivery of radiotherapy, use of neoadjuvant chemotherapy, use of concurrent radiosensitising chemotherapy and treatment technique. DFS, defined as the time to death, tumour recurrence or loss to follow-up, was the primary end point and outcomes were compared between patients treated with intensity-modulated radiotherapy (IMRT) in linear accelerators and those treated with conventional radiotherapy in cobalt teletherapy units. Univariate and multivariate analyses were carried out on known prognostic variables.In total, 408 patients were included in the study, with 138 (34%) being treated with IMRT in the linear accelerator. More than 75% of patients were of stage III or IV at diagnosis. The 2-year DFS of the whole cohort was 25% (95% confidence interval 21-30%). Patients treated with IMRT in the linear accelerator had a superior DFS in comparison with those treated with conventional radiotherapy in the cobalt teletherapy units (P0.001, hazard ratio 0.64, 95% confidence interval 0.5-0.82). Higher stage, cobalt treatment and use of neoadjuvant chemotherapy were adversely associated with DFS on multivariate analysis.A large proportion of patients with SCCHN treated with curative-intent radiotherapy in Sri Lanka had locally advanced disease and DFS was superior in patients treated with IMRT in the linear accelerator.
Published: 2021
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20. Appendicitis risk prediction models in children presenting with right iliac fossa pain (RIFT study): a prospective, multicentre validation study

Author: Dmitri Nepogodiev, Richard JW Wilkin, Catherine J Bradshaw, Clare Skerritt, Alasdair Ball, Waaka Moni-Nwinia, Ruth Blanco-Colino, Priyesh Chauhan, Thomas M Drake, Matteo Frasson, Oliver Gee, James C Glasbey, Jacob H Matthews, Gabriella L Morley, David N Naumann, Francesco Pata, Antonio S Soares, Aneel Bhangu, SH Abbas, AM Abdelgadir, A Abdelrahman, M Abdelrahman, A Abdelwahed, Y Abou El Ella, M Abulafi, A Acharya, ME Adam, RE Adams, SO Adegbola, A Adimonye, M Adnan, S Afshar, A Ahad, J Ahel, DP Ahern, A Ahmad Asmadi, B Ahmed, G Ahmed, OS Ahmed, S Ahmed, K Akbari, O Akinsola, W Al-Khyatt, B Al-Sarireh, M Al-Sheikh, M Alani, R Alexander, T Alhammali, M Ali, A Aljorfi, M Allen, J Allington, A Alshafei, R Amarasinghe, A Amayo, V Amin, Thuva Amuthalingam, L Anandan, O Anderson, SM Andreani, B Andrews, A Ang, B Aravind, JE Archer, MA Aremu, S Arunachalam, N Aruparayil, DL Ashmore, O Ashour, N Ashraf, N Assaf, H Avalapati, OO Awokoya, J Ayube-Brown, T Badenoch, R Bagga, A Baginski, S Bailey, STR Bailey, C Baird, B Baker, EJ Balai, A Balasubramaniam, SK Bandyopadhyay, A Banks, H Bansal, W Barnieh, A Barrie, CA Barter, J Bastianpillai, WD Beasley, CR Bell, J Bell, D Beral, BJM Berry, KE Bevan, V Bevan, Shiv Bhanderi, A Bhargava, D Bilku, A Birindelli, OD Blackford, JEM Blackwell, L Blake, Natalie S Blencowe, TD Boam, C Boereboom, M Bogdan, P Bohra, JC Bolger, W Bolton, S Bond, CM Borg, K Borghol, PR Boshier, N Bouhadiba, J Bowen, H Bowerman, CR Bowman, H Boyd-Carson, CJ Bradshaw, G Branagan, P Brennan, M Brett, HK Brewer, H Brewer, C Bronder, A Brown, AG Brown, CE Brown, M Brown, R Brown, S Buckley-Jones, A Budzanowski, W Bukhari, C Bull, JK Bullivant, KM Burns, D Burnside, A Busuttil, BE Byrne, CK Byrnes, M Caldwell, R Callan, FC Cameron, U Campbell, UM Campbell, W Campbell, CA Carden, CFW Carder, K Carney, H Cartwright, P Cay, A Chalk, B Chambers, A Champsi, D Chan, TCW Chan, SB Chandler, J Chapman, A Charalabopoulos, B Chasty, M Chatzikonstantinou, WL Cheah, CS Chean, S Cheng, SA Cheng, M Cheruvu, MY Chin, IA Chishti, S Choi, SM Chok, B Chong, JH Choong, M Chowdhary, F Chowdhury, CH Choy, L Christian, P Christopoulos, K Chui, M Cipparrone, GL Clark, SA Clarke, SJ Cleeve, KD Clement, B Clements, C Clements, JD Clements, JM Clements, JS Clements, JA Clements, R Clingan, L Cloney, ECS Clough, PO Coe, O Collier-Wakefield, DW Colliver, DA Colvin, TM Connelly, MJ Connor, V Cook, F Cooke, F Cooper, AE Cotton, DG Couch, L Cousins, D Coyle, W Creasy, RL Cresner, A Crone, K Cross, J Crozier, P Cunha, NJ Curtis, N D'Souza, H Dagash, S Dalmia, I Daniels, D Danquah-Boateng, FA Dar, K Dart, A Das, R Daureeawoo, S Davidson, JR Davidson, PL Davies, S Davis, V Daya Shetty, A De-Manzoni-Garberini, JA De-Marchi, EA Dean, S Dean, C Delimpalta, S Denley, G Dennison, AA Devine, S Dharamavaram, AA Dhari, F Di Franco, S Di Saverio, C Dobson, JA Docherty, C Doherty, G Donaldson, NO Donohoe, O Donohoe, E Douka, T Doulias, M Downey, C Doyle, N Drye, DT Du, JG Dudek, PG Dunning, ARS Dyal, NJ Eardley, L Earnshaw, S Easdon, SE Edwards, RJ Egan, S El-Masry, O El-Tayar, CR Elbourne, S Elgaddal, M Elseedawy, M Elshaer, OH Elsharnoby, WMA Elzeneini, KM Emslie, NFT Engall, B Ertansel, HD Esmail, C Ettles, J Evans, JD Evans, A Everden, M Fadel, SE Fahmy, CJ Fairfield, BF Fanibi, Valeria Farina, SM Farrell, EZ Farrow, JA Fasuyi, G Faulkner, D Fawkner-Corbett, F Fawzi, M Fehervari, N Ferguson, JG Finch, H Finlayson, T Flack, W Foers, NM Foley, K Ford, A Forgie, A Foster, JD Foster, AMW Fox, N Francis, D Franklin, H Froud, HL Fuller, E Gaines, J Galea, E Gammeri, J Garnham, J Garvin, Z Gates, R Gentry, I Ghaffari, S Ghatorae, AL Gidwani, TG Gilbert, TM Gilbert, S Gill, M Gillespie, J Gillick, A Giorga, K Gopalakrishnan, S Gopalswamy, S Gopinath, R Gormely, G Govind, C Grant, J Graveston, J Gray, RT Gray, D Griffith, JP Griffith, Ewen A Griffiths, SN Griffiths, EJ Griggs, S Grosvenor, T Grove, M Gulamhussein, J Guliani, A Gummaraju, S Gunning, SV Gurjar, S 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R., Pardy, C., Parkola, M. J., Pasquali, S., Patel, A. S., Patel, B. Y., Patel, C., Patel, H., Patel, N., Patel, R. T., Patel, S., Patel, Y., Patel, M. M., Patil, S. D., Payne, C. J., Payne, R. E., Pearce, J. C. H., Pearce, L., Pedder, A., Peirce, C. B., Peiris, G. B., Peleki, A., Pellino, G., Pento, V., Peprah, D., Perera, H. S., Perera, M. I., Phelan, L., Photiou, D., Pierre, R., Pilkington, J. P., Pinkney, T. D., Pisavadia, B., Poacher, A., Podda, M., Pollard, H., Popova, D., Poudevigne, M., Prideaux, A., Pullabatla Venkata, U. P., Quddus, A., Quill, S., Rabie, M., Rabie, M. R., Radwan, R. W., Rae, J. F., Rahim, A., Rahmani, L. S., Rajagopal, S., Rajaram, R., Rajaretnam, N., Rajjoub, Y., Rallage, H., Ramcharan, S., Ranathunga, S., Rao, M., Rao, V. S. R., Raofi, A., Rashid, M., Rate, A., Ravindran, R., Raymond, M., Raza, S. S., Reddy, A., Redman, E. P., Redmond, A. E., Rekhraj, S., Renshaw, S., Rex, D., Rezacova, M., Rezvani, S., Ribeiro, B., Rich, J. E., Richardson, T. D., Rigby, S., Rigney, B., Rinkoff, S., Robb, H. D., Robertson, C., Robinson, D., Robinson, A., Rodger, V., Rolph, R., Roomi, S., Roth, N. P. G., Rothnie, K., Roy, C., Rupani, S., Rutherford, D. G., Sacks, R., Saghir, N., Saha, A., Sahay, S. J., Sahnan, K., Salama, Y., Salim, S., Samuel, M., Sana, S., Sandu, L., Sarmah, P., Sarveswaran, J., Saunders, S. M. F., Savill, A., Savioli, F., Schuster Bruce, J. R., Sebastian, J. F., Seddon, T. C., Seneviratne, N., Seth, M., Setshwaelo, T., Sezen, E., Sgardelis, P., Sgro, A., Shah, C., Shah, J., Shah, K., Shah, S. M., Shakoor, Z., Shalaby, M. S., Shanmuganathan, V., Shanmugarajah, K., Sharma, A., Sharma, P., Sharp, O. L., Shepherd, J. A., Sherif, M. A., Shet, S., Shingler, G., Shiwani, M. H., Shreshta, D., Sian, T., Siddiqui, M. N., Siddiqui, Z. A., Siggens, K. L., Sihra, N., Silva, I., Simioni, A., Simmonds, L. F. C., Simpson, D. J., Singh, A., Singh, S., Singhal, T., Sivaloganathan, P., Sloan, K., Smallcombe, N., Smart, C. J., Smart, N. J., Smith, R., Smoker, H., Solinas, L., Souter, J. E. H., Springate, E. L., Stephens, G. F., Stevenson, R., Stewart, D. J., Stoica, I., Strachan, E., Stubbs, B. M., Stupalkowska, W., Suliman, A., Sultana, A., Sunter, H., Suriyakumar, S., Symons, N. R. A., Szentpali, K., Szucs, A., Tabain, V., Tague, L. E., Tailor, K., Tan, C. Y., Tan, S., Tang, A. M., Tarazi, M., Tay, Y. H., Tayeh, S., Taylor, M., Taylor, N. S., Taze, D., Teasdale, E., Thakral, N., Thava, B., Thavanesan, N., Thaventhiran, A. J., Theodoropoulou, K., Thomas, A. T., Thomas, L., Thompson, D. B., Thompson, R., Thoukididou, S. N., Tiboni, S. G., Tiedt, L. A., Ting, N., Tinsley, B. J., Tognarelli, J. M., Torkington, J., Torrance, A., Townsend, D. C., Tozer, P. J., Trail, M., Trew, F., Tudyka, V., Tullie, L., Turnbull, A., Turner, E. J., Twum-Barima, C. S., Tyler, R., Vakis, S., Valle, A. L., Van Boxel, G. I., Vance-Daniel, J., Varcada, M., Varma, N., Vaughan, E. M., Velchuru, V. R., Velho, R., Venkatasubramaniam, A. K., Venn, M. L., Vijay, V., Vinnicombe, Z., Vitish-Sharma, P., Wagener, S., Waite, K., Walters, K. J., Walters, U., Wardle, B. G., Wardle, S. D., Warusavitarne, J., Watfah, J., Watson, N., Wauchope, J., Weatherburn, L. W., Weegenaar, C. R., Welsh, S., Wheatstone, S., Whewell, H. E., Whitehouse, P., Whiteman, E., Whittaker, L., Wijesundera, K., Wilkinson, D., Williams, G. L., Williams, M., Williams, R., Williams, S., Wilson, E. J., Wilson, M. S. J., Winter, D. C., Winter, G., Wolff, J., Wong, A., Wong, C. L. L., Wong, S. Y., Wood, C. S., Woodrow, C., Woodward, A., Woodward, B., Wright, E., Wright, H. L., Wu, F., Yalamarthi, S., Yang, P., Yardimci, E., Yasin, T., Yen, S. K., Yoganathan, S., Yoong, S., Youssef, H., Yow, L. P. S., Zaborowski, A., Zadi, A. Z., Zarka, Z. A., Zarog, M. A., and Zhang, A. Y.
Subjects: Male, Pediatrics, medicine.medical_specialty, Validation study, Adolescent, Ultrasound scan, Pain, Risk prediction models, Risk Assessment, Sensitivity and Specificity, Cohort Studies, Ilium, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, 030225 pediatrics, Developmental and Educational Psychology, medicine, Appendectomy, Humans, Prospective Studies, 030212 general & internal medicine, Surgical emergency, Child, Ultrasonography, business.industry, Area under the curve, Appendicitis, medicine.disease, United Kingdom, Child, Preschool, Acute Disease, Pediatrics, Perinatology and Child Health, Female, Right iliac fossa pain, business, Ireland, Cohort study
Abstract: BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. METHODS: We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5-15 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. FINDINGS:15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34·5%) underwent appendicectomy. The normal appendicectomy rate was 15·9% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0·84 (95% CI 0·82-0·86). Applying score cutoffs of 3 points or lower for children aged 5-10 years and girls aged 11-15 years, and 2 points or lower for boys aged 11-15 years, the failure rate was 3·3% (95% CI 2·0-5·2; 18 of 539 patients), specificity was 44·3% (95% CI 41·4-47·2; 521 of 1176), and positive predictive value was 41·4% (38·5-44·4; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72·6%, 67·4-77·4) was similar to that of ultrasound scan (75·0%, 65·3-83·1). INTERPRETATION: The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. FUNDING: None.
Published: 2021
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21. An Interventional pilot project to expand the treatment facilities for asymptomatic COVID -19 patients by using the cost-effective strategy

Author: Dharmarathne G.S.K, Maddage A.K, Panapitiya P.W.C, Perera U.A.A.S, and Perera K.Y.D
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, medicine, medicine.symptom, Intensive care medicine, business, Asymptomatic
Published: 2020
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22. Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury

Author: Louis Jacob, Mélanie Cogné, Olli Tenovuo, Cecilie Røe, Nada Andelic, Marek Majdan, Jukka Ranta, Peter Ylen, Helen Dawes, Philippe Azouvi, Cecilia Åkerlund, Krisztina Amrein, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó9, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Iris Ceyisakar, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Ana M. Castaño-León, Marc Maegele, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P. J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Molecular Neuroscience and Ageing Research (MOLAR), Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Neurokirurgian yksikkö, Helsinki Institute for Information Technology, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Clinicum, Helsinki University Hospital Area, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Jacob, L., Cogne, M., Tenovuo, O., Roe, C., Andelic, N., Majdan, M., Ranta, J., Ylen, P., Dawes, H., Azouvi P., (CENTER-TBI Participants and Investigators), Beretta, Luigi, Jacob, L, Cogne, M, Tenovuo, O, Roe, C, Andelic, N, Majdan, M, Ranta, J, Ylen, P, Dawes, H, Azouvi, P, Akerlund, C, Amrein, K, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azzolini, M, Bartels, R, Barzo9, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Ceyisakar, I, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dilvesi, D, Dixit, A, Donoghue, E, Dreier, J, Duliere, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovacs, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lingsma, H, Maas, A, Castano-Leon, A, Maegele, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menon, D, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyiradi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnak, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Sewalt, C, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Synnot, A, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te Ao, B, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Vallance, S, Valeinis, E, Vamos, Z, van der Jagt, M, Van der Steen, G, van der Naalt, J, van Dijck, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, Vande Vyvere, T, van Wijk, R, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, von Steinbuchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Oslo University Hospital [Oslo], Oxford Brookes University, European Commission, EC: 602150, The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Data used in preparation of this article were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC Grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA), and from Integra LifeSciences Corporation (USA). Data for the CENTER-TBI study were collected through the Quesgen e-CRF (Quesgen Systems Inc, USA), hosted on the INCF platform and extracted via the INCF Neurobot tool (INCF, Sweden). The funder had no role in the study design, collection, analysis, and interpretation of the data, writing of the report, and the decision to submit the article for publication., European Project: 602150,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,CENTER-TBI(2013), Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, and Psychiatrie & Neuropsychologie
Subjects: Male, 030506 rehabilitation, Neurology, predictive factors, IMPACT, medicine.medical_treatment, CENTER-TBI, Health Services Accessibility, 3124 Neurology and psychiatry, predictive factor, Injury Severity Score, 0302 clinical medicine, Brain Injuries, Traumatic, Epidemiology, EPIDEMIOLOGY, Prospective Studies, rehabilitation, OUTCOMES, Rehabilitation, traumatic brain injury, Neurological Rehabilitation, General Medicine, Middle Aged, RECOVERY, Prognosis, 3. Good health, Hospitalization, Europe, Educational Status, international prospective study, Female, HEALTH, 0305 other medical science, Adult, Employment, medicine.medical_specialty, Traumatic brain injury, 03 medical and health sciences, Sex Factors, medicine, Humans, Glasgow Coma Scale, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, MORTALITY, 3112 Neurosciences, PATHWAYS, CARE, medicine.disease, Multicenter study, Emergency medicine, MODERATE, business, 030217 neurology & neurosurgery
Abstract: BackgroundAlthough rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care.ObjectiveTherefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI.MethodsData from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge.ResultsIn the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24).ConclusionsBased on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.
Published: 2020
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23. Prostaglandin-associated periorbitopathy syndrome (PAPS): Addressing an unmet clinical need

Author: Pei-Yao Chang, Kyung Rim Sung, Shamira A. Perera, Rei Sakata, Louis B. Cantor, Tsing-Hong Wang, and Tae Woo Kim
Subjects: Agonist, medicine.medical_specialty, business.industry, medicine.drug_class, Treatment adherence, Prostaglandin, Glaucoma, General Medicine, medicine.disease, Ophthalmology, chemistry.chemical_compound, Elevated intraocular pressure, Prostaglandin analog, chemistry, Older patients, Prostaglandins, Humans, Medicine, sense organs, business, Intensive care medicine, Antihypertensive Agents, Intraocular Pressure, Ophthalmic surgery
Abstract: Background Topical prostaglandin analogs (PGAs) are widely approved and preferred first-line options for glaucoma and elevated intraocular pressure (IOP). However, prostaglandin-associated periorbitopathy syndrome (PAPS) is now a well-recognized clinical and cosmetic concern for patients receiving PGAs, especially during long-term and unilateral therapy. PGA-associated periocular changes occur in a substantial proportion of patients, with older patients (>60 years) at greater risk of clinical presentation. PAPS may hinder long-term management of glaucoma, including treatment adherence, ophthalmic surgery outcomes, and reliable IOP measurements. Recommendation New therapeutic approaches may address this unmet clinical need. Omidenepag isopropyl (OMDI) is a novel, non-prostaglandin, selective EP2 receptor agonist in ongoing development, which provides a unique pharmacological mechanism of action. OMDI appears to provide IOP reductions comparable to PGAs, but without PAPS-related undesirable effects. OMDI may offer a suitable long-term option for patients who demonstrate decreased efficacy, or failure, of PGAs, plus patients with significant PAPS, while fulfilling international guidelines.
Published: 2021
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24. A translational model-based approach to inform the choice of the dose in phase 1 oncology trials: the case study of erdafitinib

Author: Jorge Vialard, Timothy Perera, Tinne Verhulst, Elena Maria Tosca, Paolo Magni, Nadia Terranova, Peter King, Anne-Gaëlle Dosne, Kim Stuyckens, Juan Jose Perez-Ruixo, and Italo Poggesi
Subjects: Pharmacology, Oncology, Cancer Research, medicine.medical_specialty, medicine.drug_class, business.industry, Toxicology, Tyrosine-kinase inhibitor, Erdafitinib, Pharmacokinetics, Internal medicine, Time course, medicine, Potency, Tumor growth inhibition, Pharmacology (medical), business, PK/PD models, Urothelial carcinoma
Abstract: Erdafitinib (JNJ-42756493, BALVERSA) is a tyrosine kinase inhibitor indicated for the treatment of advanced urothelial carcinoma. In this work, a translational model-based approach to inform the choice of the doses in phase 1 trials is illustrated. A pharmacokinetic (PK) model was developed to describe the time course of erdafitinib plasma concentrations in mice and rats. Data from multiple xenograft studies in mice and rats were analyzed using the Simeoni tumor growth inhibition (TGI) model. The model parameters were used to derive a range of erdafitinib exposures that might inform the choice of the doses in oncology phase 1 trials. Conversion of exposures to doses was based on preliminary PK assessments from the first-in human (FIH) study. A one-compartment PK disposition model, with linear absorption and dose-dependent clearance, adequately described the PK data in both mice and rats via an allometric scaling approach. The TGI model was able to describe tumor growth dynamics, providing quantitative measurements of erdafitinib antitumor potency in mice and rats. Based on these estimates, ranges of efficacious unbound concentration were identified for erdafitinib in mice (0.642–5.364 μg/L) and rats (0.782–2.565 μg/L). Based on the FIH data, it was possible to transpose exposures into doses and doses of above 4 mg/day provided erdafitinib exposures associated with significant TGI in animals. The findings were in agreement with the results of the FIH trial, in which the first hints of clinical activities were observed at 6 mg. The successful modeling exercise of erdafitinib preclinical data showed how translational PK-PD modeling might be a tool to help to inform the choice of the doses in FIH studies.
Published: 2021
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25. Safety of intra‐operative blood salvage during liver transplantation in patients with hepatocellular carcinoma, a propensity score‐matched survival analysis

Author: Dimitri Sneiders, Hermien Hartog, Darius F. Mirza, Oana Anisa Nutu, John Isaac, M. Thamara P. R. Perera, and Surgery
Subjects: medicine.medical_specialty, Carcinoma, Hepatocellular, Blood transfusion, medicine.medical_treatment, Liver transplantation, Gastroenterology, Risk Factors, Internal medicine, medicine, Humans, In patient, Propensity Score, Survival analysis, Retrospective Studies, Transplantation, Operative Blood Salvage, Proportional hazards model, Intraoperative blood salvage, business.industry, Liver Neoplasms, medicine.disease, Survival Analysis, Liver Transplantation, Hepatocellular carcinoma, Propensity score matching, Neoplasm Recurrence, Local, business
Abstract: Intra-operative blood salvage (IBS) reduces the use of allogeneic blood transfusion. However, safety of IBS during liver transplantation (LT) for hepatocellular carcinoma (HCC) is questioned due to fear for dissemination of circulating malignant cells. This study aims to assess safety of IBS. HCC patients who underwent LT from January 2006 through December 2019 were included. Patients in whom IBS was used were propensity score matched (1:1) to control patients. Disease-free survival and time to HCC recurrence were assessed with Cox regression models and competing risk models. IBS was used in 192/378 HCC LT recipients, and 127 patients were propensity score matched. Cumulative disease-free survival at 12 and 60 months was 85% and 63% for the IBS group versus 90% and 68% for the no-IBS group. Use of IBS was not associated with impaired disease-free survival (HR 1.07, 95%CI: 0.65–1.76, P = 0.800) nor with increased HCC recurrence (Cause-specific cox model: HR 0.79, 95%CI: 0.36–1.73, P = 0.549, Fine and Gray model: HR: 0.79, 95%CI 0.40–1.57, P = 0.50). In conclusion, IBS during LT did not increase the risk for HCC recurrence. IBS is a safe procedure in HCC LT recipients to reduce the need for allogenic blood transfusion.
Published: 2021
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26. Introduction of the Concept of Diagnostic Sensitivity and Specificity of Normothermic Perfusion Protocols to Assess High‐Risk Donor Livers

Author: A. Schlegel, Keith J. Roberts, M. Thamara P. R. Perera, Yuri L. Boteon, Paolo Muiesan, Richard W. Laing, Hynek Mergental, Darius F. Mirza, Desley Neil, Manuel Abradelo, Joseph Attard, John Isaac, James Hodson, Laine L. Walace, Darren Barton, and Simon C. Afford
Subjects: Protocol (science), Transplantation, medicine.medical_specialty, Machine perfusion, Hepatology, Surrogate endpoint, business.industry, medicine.medical_treatment, Graft Survival, Urology, Organ Preservation, Liver transplantation, Liver Transplantation, Transaminase, Perfusion, Lactate clearance, Normothermic perfusion, Liver, Living Donors, medicine, Humans, Surgery, business
Abstract: Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol.
Published: 2021
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27. Transarterial chemoembolization of hepatocellular carcinoma before liver transplantation and risk of post-transplant vascular complications

Author: Z Larghi Laureiro, Jacques Pirenne, Jan Lerut, G Tisone, Quirino Lai, Nicholas Gilbo, Hermien Hartog, Dimitri Sneiders, F Blasi, A P C S Boteon, Wojciech G. Polak, Samuele Iesari, A Orlacchio, M. T. P. R. Perera, T M Manzia, and Surgery
Subjects: Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Waiting Lists, medicine.medical_treatment, Liver transplantation, Hepatic Artery, Postoperative Complications, SDG 3 - Good Health and Well-being, Risk Factors, Preoperative Care, medicine, Humans, Vascular Diseases, Chemoembolization, Therapeutic, HCC, Propensity Score, TACE, business.industry, Incidence, Incidence (epidemiology), Carcinoma, Liver Neoplasms, Hepatocellular, Middle Aged, medicine.disease, Settore MED/18, Liver Transplantation, Surgery, Europe, Survival Rate, Transplantation, liver transplant, medicine.anatomical_structure, Hepatocellular carcinoma, Propensity score matching, Cohort, Female, Observational study, business, Artery
Abstract: Transarterial chemoembolization (TACE) in patients with hepatocellular cancer (HCC) on the waiting list for liver transplantation may be associated with an increased risk for hepatic artery complications. The present study aims to assess the risk for, primarily, intraoperative technical hepatic artery problems and, secondarily, postoperative hepatic artery complications encountered in patients who received TACE before liver transplantation.Available data from HCC liver transplantation recipients across six European centres from January 2007 to December 2018 were analysed in a 1 : 1 propensity score-matched cohort (TACE versus no TACE). Incidences of intraoperative hepatic artery interventions and postoperative hepatic artery complications were compared.Data on postoperative hepatic artery complications were available in all 876 patients (425 patients with TACE and 451 patients without TACE). Fifty-eight (6.6 per cent) patients experienced postoperative hepatic artery complications. In total 253 patients who had undergone TACE could be matched to controls. In the matched cohort TACE was not associated with a composite of hepatic artery complications (OR 1.73, 95 per cent c.i. 0.82 to 3.63, P = 0.149). Data on intraoperative hepatic artery interventions were available in 825 patients (422 patients with TACE and 403 without TACE). Intraoperative hepatic artery interventions were necessary in 69 (8.4 per cent) patients. In the matched cohort TACE was not associated with an increased incidence of intraoperative hepatic artery interventions (OR 0.94, 95 per cent c.i. 0.49 to 1.83, P = 0.870).In otherwise matched patients with HCC intended for liver transplantation, TACE treatment before transplantation was not associated with higher risk of technical vascular issues or hepatic artery complications.Lay Summary Patients with liver cancer may be treated with transarterial chemoembolization (TACE) during the period on the transplant waiting list. With TACE, chemotherapeutic coils are injected directly into the small arteries supplying the tumour, after which these vessels are closed. The aim of this therapy is to decrease the tumour size and slow down tumour growth. However, concerns are raised that manipulation of the main hepatic artery by TACE may cause damage to the artery itself. If this would result in problems during or after liver transplantation when the artery is connected to the artery supplying the donor liver, this may endanger the donor liver graft survival. The present study shows no increased risk in problems to connect the artery during liver transplantation after TACE treatment. Also, arterial complications after liver transplantation did not occur more frequently if patients had received TACE treatment. The authors therefore conclude that TACE treatment before liver transplantation could be considered a safe approach.
Published: 2021
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28. Steady-State Pattern Electroretinography in Eyes with Glaucoma and High Myopia

Author: Hla Myint Htoon, Quan V Hoang, Xian Hui Lim, Tina Tzee Ling Wong, Shamira A. Perera, Tin Aung, Rahat Husain, Monisha E. Nongpiur, Chee Wai Wong, Raymond P. Najjar, and Dan Milea
Subjects: medicine.medical_specialty, optical coherence tomography, genetic structures, business.industry, Glaucoma, Nerve fibre layer, High myopia, Clinical Ophthalmology, visual field mean deviation, Retinal, Spherical equivalent, Pattern electroretinography, medicine.disease, pattern electroretinogram, eye diseases, retinal nerve fibre layer, Absolute deviation, Ophthalmology, chemistry.chemical_compound, chemistry, Medicine, sense organs, business, Original Research
Abstract: Xian Hui Lim,1 Monisha Esther Nongpiur,1â 3 Raymond P Najjar,2,3 Quan V Hoang,1â 4 Dan Milea,1â 3 Chee Wai Wong,1â 3 Rahat Husain,1,3 Hla Myint Htoon,2,3 Tin Aung,1â 3,5 Shamira Perera,1â 3 Tina Tzee Ling Wong1â 3,5 1Singapore National Eye Centre, Singapore; 2Singapore Eye Research Institute, Singapore; 3Duke-NUS Medical School, Singapore; 4Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia College of Physicians and Surgeons, New York, NY, USA; 5Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeCorrespondence: Tina Tzee Ling WongSingapore National Eye Centre, 11 Third Hospital Avenue, 168751, SingaporeEmail tina.wong.t.l@singhealth.com.sgPurpose: To investigate features of the steady-state pattern electroretinogram (ssPERG) in subjects with glaucoma (G), high myopia (HM; spherical equivalent â¤-6D) and glaucoma with high myopia (GHM).Patients and Methods: Our study included 48 participants divided into 3 groups (G, HM, and GHM) who each underwent monocular ssPERG testing with Diopsys NOVA PERG protocols. The ConStim protocol detects distinct topographic patterns of dysfunction 16Â° and 24Â° around the central macula. MagD is the amplitude of the average signal and MagD/Mag ratio indicates the consistency of the response. ssPERG indices were compared between groups and correlated with functional (ie, visual field mean deviation (VFMD)) and structural (ie, average retinal nerve fibre layer (RNFL) thickness; Cirrus optical coherence tomography) features.Results: Participants had an average age of 59.4Â± 7.6 years. Mean Humphrey VFMD was â 14.22 Â± 2.88dB, â 2.62 Â± 1.18dB and â 12.80 Â± 2.60dB for G, HM and GHM groups, respectively. Mean RNFL thickness was 63.0 Â± 8.20Î¼m, 69.5 Â± 15.7Î¼m and 60.6 Â± 5.0Î¼m for G, HM and GHM groups, respectively. For the 24Â° setting, no significant differences were noted for any of the parameters. For the 16Â° setting, MagD was lower in the GHM group compared to the HM group (0.29Î¼V vs 0.52Î¼V; p = 0.02). Significant differences were noted for the MagD/Mag ratio between HM and G groups (0.58 vs 0.40; p = 0.02) and between HM and GHM groups (0.58 vs 0.35; p = 0.002). There were positive correlations between both MagD 16Â° and MagD/Mag ratio 16Â° with VFMD (correlation coefficient [r]=0.37, p = 0.009; and r = 0.44, p = 0.002, respectively) and RNFL (r = 0.43, p = 0.002; and r = 0.48, p = 0.001, respectively).Conclusion: MagD/Mag ratio at 16Â° was significantly lower in glaucomatous eyes (with or without high myopia) compared to those with high myopia without glaucoma, suggesting that glaucoma has a distinct impact on MagD/Mag ratio at 16Â° irrespective of the presence of myopia.Keywords: pattern electroretinogram, visual field mean deviation, optical coherence tomography, retinal nerve fibre layer
Published: 2021
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29. <scp> Helicobacter pylori </scp> antimicrobial resistance in Melbourne, Australia. Time to review therapeutic guidelines?

Author: Sadid F Khan, Lynette Waring, Chandrika Perera, Louise Prendergast, Jacinta A Holmes, and Jasmine C Teng
Subjects: education.field_of_study, medicine.medical_specialty, biology, business.industry, Population, Guideline, Amoxicillin, Helicobacter pylori, biology.organism_classification, Metronidazole, Antibiotic resistance, Clarithromycin, Internal medicine, Cohort, Internal Medicine, Medicine, business, education, medicine.drug
Abstract: Background Antimicrobial resistance (AMR) in Helicobacter pylori is a global concern. The AMR data to inform the Australian Therapeutic Guidelines is based upon data over 20 years old. Aims To evaluate the frequency of antimicrobial resistance in H. pylori isolates from gastric biopsy specimens received in our laboratory in Melbourne, Australia To review the literature on resistance rates in Australia and compare historic data. Methods A retrospective, observational study summarising AMR rates in all H. pylori isolates from our laboratory from 2015 to June 2020. Setting Microbiology laboratory in metropolitan Melbourne, Australia, receiving referrals from private hospitals, gastroenterology clinics, and endoscopy suites. Outcome measures Population minimum inhibitory concentration distributions and frequency of resistance to clarithromycin, amoxicillin, metronidazole, and tetracycline in H. pylori isolates. Results 386 H. pylori isolates with susceptibility testing data were identified. The frequency of resistance in this cohort was: clarithromycin 89.9%, amoxicillin 23.5%, metronidazole 66.1%, and tetracycline 4.4%. Comparison with historical data may suggest increasing AMR rates in Australia. Main limitation is lack of treatment history to correlate AMR results. Conclusions Definitive conclusions from this cohort cannot be made, but trends suggest rising levels of primary H. pylori AMR rates in Australia. This has important implications for empirical treatment decision making and treatment outcomes. Primary H. pylori AMR requires dedicated studies and current Australian therapeutic guideline recommendations may require re-evaluation. We propose considerations for improving the management of H. pylori in Australia. A centralised public health approach to H. pylori AMR surveillance should be established. This article is protected by copyright. All rights reserved.
Published: 2021
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30. Magnetic resonance imaging of the internal auditory meatus for vestibular schwannoma in ENT practice: a retrospective analysis with literature and guidelines review

Author: M B Perera, C Apthorp, H B Al-Deerawi, N Janjua, and R Swaminathan
Subjects: Vestibular system, medicine.medical_specialty, business.industry, General surgery, MEDLINE, Neuroma, Acoustic, General Medicine, Schwannoma, medicine.disease, Magnetic Resonance Imaging, Otorhinolaryngology, medicine, Retrospective analysis, Humans, Vestibule, Labyrinth, business, Retrospective Studies
Abstract: ObjectivesMagnetic resonance imaging scans of the internal acoustic meatus are commonly requested in the investigation of audio-vestibular symptoms for potential vestibular schwannoma. There have been multiple studies into protocols for requesting magnetic resonance imaging for vestibular schwannoma, but none have been reported based on UK National Institute for Health and Care Excellence guidelines for investigating audio-vestibular symptoms. This study intended to identify the local magnetic resonance imaging detection rates and patterns of vestibular schwannoma, and to audit the conformity of scan requests with the National Institute for Health and Care Excellence guidelines, with a review of relevant literature.MethodA retrospective analysis of 1300 magnetic resonance imaging scans of the internal acoustic meatus, compared against National Institute for Health and Care Excellence guidelines, was conducted over two years.Results and conclusionSixteen scans were positive for vestibular schwannoma, with a detection rate of 1.23 per cent. All positive cases fit the guidelines; three of these could have been missed using other criteria. A total of 281 requests did not meet the guideline criteria but revealed no positive results, supporting the use of National Institute for Health and Care Excellence guidelines in planning magnetic resonance imaging scans for audio-vestibular symptoms.
Published: 2021
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31. Cardiovascular disease and risk of incident diabetes mellitus: Findings from the<scp>Hispanic Community Health Study</scp>/<scp>Study of Latinos</scp>(<scp>HCHS</scp>/<scp>SOL</scp>)

Author: Ramon Durazo-Arvizu, Celestin Missikpode, Krista M. Perreira, Sheila F. Castañeda, Marisa J. Perera, Amber Pirzada, Linda C. Gallo, Martha L. Daviglus, Ana C. Ricardo, Matthew James OʼBrien, Maria M. Llabre, James P. Lash, Richard S. Cooper, and Gregory A. Talavera
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Disease, Young Adult, Risk Factors, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Longitudinal Studies, Propensity Score, Generalized estimating equation, Aged, business.industry, Incidence, Incidence (epidemiology), Hispanic or Latino, Odds ratio, Middle Aged, medicine.disease, United States, Confidence interval, Cardiovascular Diseases, Propensity score matching, Female, medicine.symptom, business, Weight gain
Abstract: Studies have reported an association between prevalent cardiovascular disease (CVD) and risk of diabetes mellitus (DM). However, factors that may explain the association remain unclear. We examined the association of prevalent CVD with incident DM and assessed whether weight gain and medication use may explain the association.Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008-2011) and Visit 2 (2014-2017) were used to compare incidence of DM among individuals with and without self-reported CVD at Visit 1. A total of 1899 individuals with self-reported CVD were matched to controls free of self-reported CVD at Visit 1 using 1:1 propensity score matching. Covariates included in the propensity model were sociodemographic characteristics, lifestyle factors, comorbid conditions, and study site. The effect of self-reported CVD on incident DM was examined using a generalized estimating equation. The mediating effects of weight gain and use of cardiovascular medications were evaluated.Covariate distributions were similar among individuals with and without self-reported CVD. The incidence of DM among persons with self-reported CVD was 15.3% vs 12.7% among those without self-reported CVD. Compared to individuals without self-reported CVD, individuals with self-reported CVD had a 24% increased risk for incident DM (odds ratio = 1.24, 95% confidence interval = 1.01, 1.51). The association between self-reported CVD and DM was mediated by the use of beta-blockers (proportion explained = 25.4%), statins (proportion explained = 18%), and diuretics (proportion explained = 8%). We found that weight gain did not explain the observed association.Prevalent cardiovascular disease was associated with a significant increased risk of incident diabetes. The observed association was partially explained by some medications used to manage CVD.背景: 已有研究报道流行的心血管疾病(CVD)与糖尿病(DM)风险之间存在关联。然而, 可能解释这种联系的因素仍不清楚。我们分析了流行的心血管疾病与糖尿病发病的关系, 并评估了体重增加和药物使用是否可以解释这种联系。方法: 使用西班牙裔社区健康研究/拉丁裔研究(HCHS/SOL) 2008-2011及2014-2017的数据, 比较前者中有和没有自我报告心血管疾病个体的糖尿病发病率。共有1899名自我报告心血管疾病的患者, 采用1:1倾向得分匹配的方法与无自我报告心血管疾病的对照组进行配对。倾向性模型中的协变量包括社会人口学特征, 生活方式因素, 并发症情况和研究地点。使用通用的估计方程来检验自我报告的心血管疾病对糖尿病的影响。评估体重增加和心血管药物使用的中介作用。结果: 在有和没有自我报告的心血管疾病的个体中, 协变量分布是相似的。自报心血管病患者的糖尿病发病率为15.3%, 非自报心血管病患者的糖尿病发病率为12.7%。与没有自我报告心血管疾病的个体相比, 有自我报告心血管疾病的个体发生糖尿病的风险增加24%(优势比=1.24, 95%可信区间=1.01, 1.51)。自我报告的心血管疾病和糖尿病之间的联系是通过使用β-受体阻滞剂(解释比例=25.4%), 他汀类药物(解释比例=18%)和利尿剂(解释比例=8%)来调节的。我们发现体重增加并不能解释观察到的关联。结论: 常见的心血管疾病与糖尿病发病风险显著增加相关。一些用于治疗心血管疾病的药物部分解释了观察到的关联。.
Published: 2021
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32. Understanding caregiver perspectives on challenges and solutions to pediatric asthma care for children with a previous hospital admission: a multi-site qualitative study

Author: Renee Jones, Prescilla Perera, Brittany Turner, Katherine Y H Chen, and Harriet Hiscock
Subjects: Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Multi site, Hospitals, Pediatric, medicine.disease, Asthma, Cohort Studies, Hospitalization, Caregivers, Current management, Family medicine, Pediatric hospital, Pediatrics, Perinatology and Child Health, Hospital admission, medicine, Humans, Immunology and Allergy, Child, business, Pediatric asthma, Qualitative research
Abstract: Pediatric hospital admissions for asthma provide an opportunity to trigger a review of the current management with an aim of preventing readmissions. However, caregiver voices on how best to improve care are missing.As part of a larger, mixed methods cohort study, we identified caregivers of children aged 3-18 years who had an index hospital admission to a tertiary pediatric, mixed adult and pediatric, or regional hospital in Victoria, Australia, between 1st September 2017 and 31st August 2018 with a discharge diagnosis of "Asthma" or "Wheeze" based on International Classification of Disease-10 coding. We conducted qualitative semi-structured interviews with a purposive sample of 39 caregivers. We used content analysis to identify themes from the data.Caregivers identified both challenges associated with asthma care for children with a previous hospital admission as well as solutions to improve care and potentially reduce readmissions. Key challenges included: unclear pathways for follow up care, inconsistent advice, lack of personalized management, delays in getting a diagnosis, delays in the prescription of a preventer medication, and difficulty accessing primary care during exacerbations. Follow up with an "asthma specialist", early access to a trial of preventer medication, personalized Written Asthma Action Plans and increased access to and quality of community-based asthma support services were identified as key solutions.Caregivers have identified several potential solutions that could be implemented to improve care and possibly reduce pediatric asthma hospital readmissions. The challenge now is to co-design, embed and evaluate these in healthcare systems.Supplemental data for this article can be accessed at publisher's website.
Published: 2021
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33. The Effects of Home Health Value-Based Purchasing on Home Health Care Quality in For-Profit and Nonprofit Agencies: A Comparative Interrupted Time-Series Analysis, 2012–2018

Author: Jingjing Shang, Andrew W. Dick, Uduwanage Gayani E. Perera, Ashley M. Chastain, and Patricia W. Stone
Subjects: medicine.medical_specialty, Index (economics), Quality management, Value-Based Purchasing, media_common.quotation_subject, Medicare, Article, Interrupted Time Series Analysis, Home health, Patient experience, Home Care Agencies, Humans, Medicine, Quality (business), health care economics and organizations, Aged, Quality of Health Care, media_common, business.industry, Health Policy, Home Care Services, United States, Purchasing, Family medicine, business
Abstract: Beginning in 2016, the Home Health Value-Based Purchasing (HHVBP) model incentivized U.S. Medicare-certified home health agencies (HHAs) in nine states to improve quality of patient care and patient experience. Here, we quantified HHVBP effects upon quality over time (2012–2018) by HHA ownership (i.e., for-profit vs. nonprofit) using a comparative interrupted time-series design. Our outcome measures were Care Quality and Patient Experience indices composed of 10 quality of patient care measures and five patient experience measures, respectively. Overall, 17.7% of HHAs participated in the HHVBP model of which 81.4% were for-profit ownership. Each year after implementation, HHVBP was associated with a 1.59 ( p < .001) percentage point increase in the Care Quality index among for-profit HHAs and a 0.71 ( p = .024) percentage point increase in the Patient Experience index among nonprofits. The differences of quality improvement under the HHVBP model by ownership indicate variations in HHA leadership responses to HHVBP.
Published: 2021
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34. 1 Year Surgical Outcomes and Safety of Combined Trans Pars Plana Vitrectomy with Iris Fixated Posterior Chamber Intraocular Lens for Subluxated Intraocular Lens and Cataracts

Author: Shamira A. Perera, Andrew Tsai, Tiffany Sin Hui Bong, Valencia Hui Xian Foo, and Laurence Shen Lim
Subjects: Pars plana, medicine.medical_specialty, genetic structures, medicine.medical_treatment, subluxated intraocular lenses, Intraocular lens, Vitrectomy, Cataracts, Interquartile range, Ophthalmology, medicine, secondary intraocular lens fixation, Iris (anatomy), trans pars plana vitrectomy, Original Research, business.industry, Clinical Ophthalmology, medicine.disease, eye diseases, Posterior chamber intraocular lens, medicine.anatomical_structure, iris-fixation, Intraocular lenses, sense organs, business, subluxated cataracts
Abstract: Valencia Hui Xian Foo,1 Tiffany Sin Hui Bong,1 Andrew Tsai,1,2 Laurence Shen Lim,1,2 Shamira Asith Perera1,2 1Department of Ophthalmology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; 2Eye-Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, SingaporeCorrespondence: Shamira Asith PereraSingapore National Eye Centre, 11 Third Hospital Avenue, 168751, SingaporeTel +65 6227 7255Fax +65 62263 995Email shamira.perera@singhealth.com.sgImportance/Background: To describe the characteristics and 1-year postoperative surgical outcomes of primary combined trans pars plana vitrectomy (TPPV) with iris-fixated posterior-chamber intraocular lens (IF-PCIOL) implantation for subluxated cataracts and intraocular lenses (IOLs).Methods: Consecutive cases of significantly subluxated cataracts and IOLs from January 2014 to May 2019 were included in this retrospective case series.Results: A total of 103 eyes of 103 patients were included. Median age was 67.4 (interquartile range [IQR] 27â 89) years. Thirty-two (31.1%) had subluxated cataracts, while 71 (68.9%) had subluxated IOLs. Overall median preoperative logMAR BCVA was 0.9 (IQR 0â 2.5). Median logMAR BCVA improved to 0.3 (0â 1.9) and 0.2 (0â 1.8) for the subluxated cataract and IOL groups, 81.2% and 75% of eyes achieved logMAR â¤ 0.3, and 94% and 97% achieved IOL stability at month 12, respectively. Eyes with subluxated IOLs had a significantly less myopic median SE if a new IOL was implanted compared to iris-fixating the dislocated IOL.Conclusion: Combined primary TPPV and IF-PCIOL implantation is a good surgical option for subluxated IOL or cataract without sufficient capsular support, with at least 75% achieving logMAR BCVA â¤ 0.3 and 95% IOL stability at postoperative year 1. In eyes with subluxated IOLs, explanting that IOL and iris-fixating a new IOL led to a reduced SE and better visual outcome at postoperative month 12 when compared to iris-fixating the dislocated IOL.Keywords: subluxated cataracts, subluxated intraocular lenses, secondary intraocular lens fixation, iris-fixation, trans pars plana vitrectomy
Published: 2021

35. Physiological Impact of Afterload Reduction on Cardiac Mechanics and Coronary Hemodynamics Following Isosorbide Dinitrate Administration in Ischemic Heart Disease

Author: Simon Redwood, Christopher Allen, Antonis N. Pavlidis, Brian Clapp, Hannah McConkey, Jubin Joseph, Simone Rivolo, Satpal Arri, Daniel Burkhoff, Rupert Williams, Kaleab N. Asrress, Jan Schreuder, Natalia Briceno, Tiffany Patterson, Michael S. Marber, Jack Lee, Howard Ellis, Divaka Perera, and Cardiology
Subjects: Male, Cardiac Catheterization, medicine.medical_specialty, Isosorbide, Vasodilator Agents, 0206 medical engineering, Myocardial Ischemia, Pharmaceutical Science, Hemodynamics, Pressure-volume loops, 02 engineering and technology, Isosorbide Dinitrate, 030204 cardiovascular system & hematology, Coronary artery disease, Ventricular Function, Left, 03 medical and health sciences, 0302 clinical medicine, Afterload, Coronary Circulation, Internal medicine, Genetics, Humans, Medicine, Coronary hemodynamics, Prospective Studies, Genetics (clinical), Aged, Aged, 80 and over, business.industry, Blood flow, Middle Aged, medicine.disease, 020601 biomedical engineering, Treatment Outcome, physiology, Cardiology, Molecular Medicine, Female, Original Article, Isosorbide dinitrate, Cardiology and Cardiovascular Medicine, business, Ischemic heart, medicine.drug
Abstract: Abstract Understanding the cardiac-coronary interaction is fundamental to developing treatment strategies for ischemic heart disease. We sought to examine the impact of afterload reduction following isosorbide dinitrate (ISDN) administration on LV properties and coronary hemodynamics to further our understanding of the cardiac-coronary interaction. Novel methodology enabled real-time simultaneous acquisition and analysis of coronary and LV hemodynamics in vivo using coronary pressure-flow wires (used to derive coronary wave energies) and LV pressure-volume loop assessment. ISDN administration resulted in afterload reduction, reduced myocardial demand, and increased mechanical efficiency (all Pr=0.6) following ISDN. In the presence of minimal microvascular resistance, coronary blood flow velocity exhibited an inverse relationship with LV elastance. In summary this study demonstrated a reduction in myocardial demand with ISDN, an inverse relationship between coronary blood flow velocity and LV contraction-relaxation and a direct correlation between FCW and arterial elastance. Graphical abstract The pressure volume-loop and corresponding parameters b The pressure volume loop before (solid line) and after (broken line) Isosorbide dintrate
Published: 2021
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36. Repetitive Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Meta-analysis of Randomized, Sham-Controlled Trials

Author: Aleksandra Miljevic, Paul B. Fitzgerald, Neil W. Bailey, M. Prabhavi N. Perera, Sudaraka Mallawaarachchi, and Sally E. Herring
Subjects: Obsessive-Compulsive Disorder, medicine.medical_specialty, Cognitive Neuroscience, medicine.medical_treatment, Prefrontal Cortex, Subgroup analysis, behavioral disciplines and activities, 050105 experimental psychology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Randomized controlled trial, law, Obsessive compulsive, mental disorders, medicine, Humans, Obsessive compulsive scale, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Biological Psychiatry, Randomized Controlled Trials as Topic, business.industry, 05 social sciences, Therapeutic effect, Transcranial Magnetic Stimulation, Transcranial magnetic stimulation, Dorsolateral prefrontal cortex, medicine.anatomical_structure, Meta-analysis, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Obsessive-compulsive disorder (OCD) is a chronic, disabling mental health condition with limited treatment options available to date. Numerous randomized controlled trials have explored the efficacy of repetitive transcranial magnetic stimulation (rTMS) in OCD. This meta-analysis synthesized data from selected randomized controlled trials and examined the impact of different treatment parameters to generate hypotheses that would direct future randomized controlled trials.A database search was performed to identify studies published in English up to October 2020. Randomized, sham-controlled studies that used rTMS to treat OCD were included. Effect sizes were calculated using Hedges' g for pre- to post-treatment Yale-Brown Obsessive Compulsive Scale scores. Subgroup analyses were conducted to assess the effects of variations in rTMS treatment parameters.A total of 26 studies with 781 participants were included. Overall, rTMS demonstrated a modest effect on reduction of Yale-Brown Obsessive Compulsive Scale scores (Hedges' g = 0.64, 95% confidence interval = 0.39-0.89; p.0001). The largest significant effect size was obtained by targeting the bilateral dorsolateral prefrontal cortex. High- and low-frequency rTMS showed comparable effects. Studies with follow-up data suggested that the effects of active rTMS remain significantly superior to those of sham 4 weeks after treatment.The therapeutic effects of rTMS are superior to those of sham in the treatment of OCD. Targeting the bilateral dorsolateral prefrontal cortex was the most favorable approach in administering rTMS. Further research is required to determine the optimal frequency, total pulses per session, and duration of treatment with rTMS for OCD.
Published: 2021
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37. The Role of Childhood Asthma in Obesity Development

Author: Barry M. Lester, Noel T. Mueller, Diane R. Gold, Akram N. Alshawabkeh, Assiamira Ferrara, Kiros Berhane, Aruna Chandran, Dana Dabelea, Anne L. Dunlop, Zhanghua Chen, Yue Zhang, Margaret R. Karagas, Erika Garcia, Carlos A. Camargo, Leonardo Trasande, Rosalind J. Wright, Amy J. Elliott, Allison J. Burbank, Emily Oken, Yeyi Zhu, Andrew Rundle, Thomas G. O'Connor, Augusto A. Litonjua, L. Chatzi, Rachel L. Miller, Frederica P. Perera, James E. Gern, Izzuddin M. Aris, Judy L. Aschner, Leslie D. Leve, Frank D. Gilliland, Tingju Hsu, Cindy T. McEvoy, Catherine J. Karr, Irva Hertz-Picciotto, Erika C. Claud, Kecia N. Carroll, Yunin Ludena, William A. Gower, Jody M. Ganiban, T. Michael O'Shea, Joseph B. Stanford, Katherine Rivera-Spoljaric, Nikos Stratakis, and Carrie V. Breton
Subjects: Male, Pediatric Obesity, Pediatrics, medicine.medical_specialty, Adolescent, Epidemiology, Article, Childhood obesity, Body Mass Index, Risk Factors, immune system diseases, Humans, Medicine, Child, Proportional Hazards Models, Asthma, business.industry, Proportional hazards model, Incidence, Incidence (epidemiology), Hazard ratio, medicine.disease, Obesity, Confidence interval, respiratory tract diseases, Female, business, Body mass index
Abstract: RATIONALE Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset. OBJECTIVES To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association. METHODS We studied 8,716 children between ages 6 and 18.5 years who were nonobese at study entry participating in 18 US cohorts of the Environmental influences on Child Health Outcomes program (among 7,299 children with complete covariate data mean [SD] study entry age = 7.2 [1.6] years and follow up = 5.3 [3.1] years). MEASUREMENTS AND MAIN RESULTS We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95% confidence intervals [CI] = 4, 44) higher risk for subsequently developing obesity compared with those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess hazard ratios = 0.64; 95% CI = -1.05, -0.23). CONCLUSIONS This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.
Published: 2021
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38. Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction

Author: Divaka Perera, Aish Sinha, Haseeb Rahman, Andrew J. Webb, and Ajay M. Shah
Subjects: medicine.medical_specialty, Endotype, Coronary flow reserve, Lusitropy, Myocardial Ischemia, Coronary Artery Disease, Pathogenesis, Coronary artery disease, Subendocardial ischaemia, Internal medicine, medicine, State of the Art Review, Humans, AcademicSubjects/MED00200, Heart Failure and Cardiomyopathies, Pathological, Heart Failure, Coronary microvascular disease, business.industry, Stroke Volume, medicine.disease, Pathophysiology, Heart failure with preserved ejection fraction, Quality of Life, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Coronary microvascular disease (CMD), characterized by impaired coronary flow reserve (CFR), is a common finding in patients with stable angina. Impaired CFR, in the absence of obstructive coronary artery disease, is also present in up to 75% of patients with heart failure with preserved ejection fraction (HFpEF). Heart failure with preserved ejection fraction is a heterogeneous syndrome comprising distinct endotypes and it has been hypothesized that CMD lies at the centre of the pathogenesis of one such entity: the CMD–HFpEF endotype. This article provides a contemporary review of the pathophysiology underlying CMD, with a focus on the mechanistic link between CMD and HFpEF. We discuss the central role played by subendocardial ischaemia and impaired lusitropy in the development of CMD–HFpEF, as well as the clinical and research implications of the CMD–HFpEF mechanistic link. Future prospective follow-up studies detailing outcomes in patients with CMD and HFpEF are much needed to enhance our understanding of the pathological processes driving these conditions, which may lead to the development of physiology-stratified therapy to improve the quality of life and prognosis in these patients., Graphical Abstract The mechanistic link between coronary microvascular disease and heart failure with preserved ejection fraction.
Published: 2021
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39. Characterizing Swallows From People With Neurodegenerative Diseases Using High-Resolution Cervical Auscultation Signals and Temporal and Spatial Swallow Kinematic Measurements

Author: Cara Donohue, Ervin Sejdic, James L. Coyle, Subashan Perera, Yassin Khalifa, and Shitong Mao
Subjects: Adult, Linguistics and Language, medicine.medical_specialty, Laryngeal vestibule, High resolution, Kinematics, Aspiration pneumonia, Language and Linguistics, Speech and Hearing, Physical medicine and rehabilitation, stomatognathic system, Swallowing, otorhinolaryngologic diseases, Speech, Humans, Medicine, Cervical auscultation, business.industry, digestive, oral, and skin physiology, Hyoid bone, Neurodegenerative Diseases, medicine.disease, Dysphagia, Biomechanical Phenomena, Deglutition, medicine.anatomical_structure, Auscultation, medicine.symptom, Deglutition Disorders, business
Abstract: Purpose The prevalence of dysphagia in patients with neurodegenerative diseases (ND) is alarmingly high and frequently results in morbidity and accelerated mortality due to subsequent adverse events (e.g., aspiration pneumonia). Swallowing in patients with ND should be continuously monitored due to the progressive disease nature. Access to instrumental swallow evaluations can be challenging, and limited studies have quantified changes in temporal/spatial swallow kinematic measures in patients with ND. High-resolution cervical auscultation (HRCA), a dysphagia screening method, has accurately differentiated between safe and unsafe swallows, identified swallow kinematic events (e.g., laryngeal vestibule closure [LVC]), and classified swallows between healthy adults and patients with ND. This study aimed to (a) compare temporal/spatial swallow kinematic measures between patients with ND and healthy adults and (b) investigate HRCA's ability to annotate swallow kinematic events in patients with ND. We hypothesized there would be significant differences in temporal/spatial swallow measurements between groups and that HRCA would accurately annotate swallow kinematic events in patients with ND. Method Participants underwent videofluoroscopic swallowing studies with concurrent HRCA. We used linear mixed models to compare temporal/spatial swallow measurements ( n = 170 ND patient swallows, n = 171 healthy adult swallows) and deep learning machine-learning algorithms to annotate specific temporal and spatial kinematic events in swallows from patients with ND. Results Differences ( p < .05) were found between groups for several temporal and spatial swallow kinematic measures. HRCA signal features were used as input to machine-learning algorithms and annotated upper esophageal sphincter (UES) opening, UES closure, LVC, laryngeal vestibule reopening, and hyoid bone displacement with 66.25%, 85%, 68.18%, 70.45%, and 44.6% accuracy, respectively, compared to human judges' measurements. Conclusion This study demonstrates HRCA's potential in characterizing swallow function in patients with ND and other patient populations.
Published: 2021
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40. Characterizing Effortful Swallows from Healthy Community Dwelling Adults Across the Lifespan Using High-Resolution Cervical Auscultation Signals and MBSImP Scores: A Preliminary Study

Author: James L. Coyle, Subashan Perera, Ervin Sejdic, Cara Donohue, and Yassin Khalifa
Subjects: Adult, medicine.medical_specialty, Dysphagia screening, medicine.medical_treatment, Longevity, High resolution, Biofeedback, Audiology, Cervical auscultation, Speech and Hearing, Videofluoroscopy, Modified Barium Swallow Impairment Profile, Swallowing, stomatognathic system, Machine learning, otorhinolaryngologic diseases, Medicine, Humans, business.industry, digestive, oral, and skin physiology, Gastroenterology, Dysphagia, Deglutition disorders, Deglutition, Treatment, Otorhinolaryngology, Auscultation, Original Article, Independent Living, medicine.symptom, business
Abstract: There is growing enthusiasm to develop inexpensive, non-invasive, and portable methods that accurately assess swallowing and provide biofeedback during dysphagia treatment. High-resolution cervical auscultation (HRCA), which uses acoustic and vibratory signals from non-invasive sensors attached to the anterior laryngeal framework during swallowing, is a novel method for quantifying swallowing physiology via advanced signal processing and machine learning techniques. HRCA has demonstrated potential as a dysphagia screening method and diagnostic adjunct to VFSSs by determining swallowing safety, annotating swallow kinematic events, and classifying swallows between healthy participants and patients with a high degree of accuracy. However, its feasibility as a non-invasive biofeedback system has not been explored. This study investigated 1. Whether HRCA can accurately differentiate between non-effortful and effortful swallows; 2. Whether differences exist in Modified Barium Swallow Impairment Profile (MBSImP) scores (#9, #11, #14) between non-effortful and effortful swallows. We hypothesized that HRCA would accurately classify non-effortful and effortful swallows and that differences in MBSImP scores would exist between the types of swallows. We analyzed 247 thin liquid 3 mL command swallows (71 effortful) to minimize variation from 36 healthy adults who underwent standardized VFSSs with concurrent HRCA. Results revealed differences (p
Published: 2021

41. Association of intrinsic factors with non-contact low back pain among fast bowlers aged between 15-19 years in division 1 boys’ schools in Colombo

Author: Diluka Weerasooriya, Dushan Mayura, Udeesh Satheesha Jayasinghe, Angage Dilani Priyashanthi Perera, Sachinda Bandara, Kavindi Dissanayake, and Imasha Swaris
Subjects: body regions, medicine.medical_specialty, business.industry, Physical therapy, medicine, population characteristics, Division (mathematics), medicine.symptom, General Agricultural and Biological Sciences, Association (psychology), business, Low back pain
Abstract: Background: Cricket fast bowlers are identified as the players with a higher risk of injury due to their susceptibility to develop low back pain (LBP). Aims and Objective: This study aims to investigate how intrinsic factors associate with LBP among fast bowlers aged between 15-19 years in Colombo division 1 boys’ schools in Sri Lanka. Materials and Methods: A descriptive cross-sectional study was conducted with one hundred and two (102) fast bowlers who were prospectively monitored over the competition period of 2019 cricket season and the demographic data, severity of LBP, general characteristics and intrinsic factors related data were recorded. Results: Thirty-seven (43.5%) of the subjects were presented with LBP. Reduction of quadriceps strength of dominant side, hamstring strength of non-dominant side and increased ankle dorsiflexion of non-dominant side were found to be significantly associated with non-contact LBP (P
Published: 2021
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42. Assessment of Risk of Bias in Osteosarcoma and Ewing’s Sarcoma Randomized Controlled Trials: A Systematic Review

Author: Kim Tsoi, Peter C. Ferguson, Aaron Gazendam, Anthony M. Griffin, Robert Koucheki, Jonathan R Perera, and Jay S. Wunder
Subjects: medicine.medical_specialty, Blinding, Randomization, Industry funding, Rct design, Sarcoma, Ewing, law.invention, Randomized controlled trial, Bias, law, osteosarcoma, risk of bias, Medicine, Humans, RC254-282, Randomized Controlled Trials as Topic, Cochrane collaboration, business.industry, Conflict of interest, Ewing's sarcoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, randomized controlled trial, Physical therapy, Systematic Review, Ewing’s sarcoma, business
Abstract: Aim: The aim of this study was to systematically assess the risk of bias in osteosarcoma and Ewing’s sarcoma (ES) randomized controlled trials (RCT) and to examine the relationships between bias and conflict of interest/industry sponsorship. Methods: An OVID-MEDLINE search was performed (1976–2019). Using the Cochrane Collaboration guidelines, two reviewers independently assessed the prevalence of risk of bias in different RCT design domains. The relationship between conflicts of interest and industry funding with the frequency of bias was examined. Results: 73 RCTs met inclusion criteria. Prevalence of low-risk bias domains was 47.3%, unclear-risk domains 47.8%, and 4.9% of the domains had a high-risk of bias. Domains with the highest risk of bias were blinding of participants/personnel and outcome assessors, followed by randomization and allocation concealment. Overtime, frequency of unclear-risk of bias domains decreased (χ2 = 5.32, p = 0.02), whilst low and high-risk domains increased (χ2 = 8.13, p = 0.004). Studies with conflicts of interest and industry sponsorships were 4.2 and 3.1 times more likely to have design domains with a high-risk of bias (p < 0.05). Conclusion: This study demonstrates that sources of potential bias are prevalent in both osteosarcoma and ES RCTs. Studies with financial conflicts of interest and industry sponsors were significantly more likely to have domains with a high-risk of bias. Improvements in reporting and adherence to proper methodology will reduce the risk of bias and improve the validity of the results of RCTs in osteosarcoma and ES.
Published: 2021

43. Incidence of metastasis to level V lymph nodes in clinically positive necks among Sri Lankan patients with oral squamous cell carcinoma

Author: N.T. Mannapperuma, S.R. Siriwardana, S. Wadusinghearachi, Nadeena Sri Swarnagupta Jayasuriya, Irosha Perera, S. DeSilva, A.M. Attygalla, H.G.H. Jinadasa, D.K. Dias, and R. Ekanayaka
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Context (language use), Gastroenterology, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Tongue, Internal medicine, Biopsy, medicine, Humans, 030223 otorhinolaryngology, Neoplasm Staging, Retrospective Studies, medicine.diagnostic_test, Squamous Cell Carcinoma of Head and Neck, business.industry, Incidence, Incidence (epidemiology), Cancer, Neck dissection, medicine.disease, medicine.anatomical_structure, Otorhinolaryngology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Neck Dissection, Mouth Neoplasms, Surgery, Lymph Nodes, Lymph, Oral Surgery, business
Abstract: Oral squamous cell carcinoma (OSCC) remains the most common cancer among males in Sri Lanka. Metastasis to neck is a crucial prognostic factor. A modified radical/radical neck dissection including levels I -V, was performed in patients with OSCC who had a clinically positive neck (cN+). Currently, evidence suggests that sparing level V in a cN+ may be justified due to less chance of metastasis in early stages of the disease. To the best of our knowledge, the incidence of metastasis to level V in patients with cN+s has not been previously investigated in a Sri Lankan context. We aimed to determine level V lymph node metastasis and related clinicopathological indicators in cN+s in patients with OSCC. A multicentre retrospective study investigated postoperative biopsy reports of 187 patients for five years. OSCC patients with cN+s who underwent neck dissections of levels I-V were included. Only 6.4% of patients had histopathologically positive level V lymph nodes. A total of 127 lymph nodes were harvested from level V of those who showed level V positivity and out of them 68 were positive with a third of cases showing extranodal extension (ENE). The buccal mucosa (n=4) and lateral aspect of the anterior two thirds of the tongue (n=4) were the common primary sites for level V metastasis. In patients who showed positivity in levels III and IV, a considerably higher probability of level V nodes being positive was seen, which was statistically significant (p = 0.0001). We have concluded that the routine performance of a modified radical/radical neck dissection for cN+s should be stopped, as the incidence of Level V positivity is significantly low. Assessing the cN+ for N stage, status of levels III and IV, pattern of invasion, differentiation, and the site may be used instead as predictors for level V positivity.
Published: 2021
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44. Primary versus early secondary referral to a specialized neurotrauma center in patients with moderate/severe traumatic brain injury: a CENTER TBI study

Author: Sewalt C. A., Gravesteijn B. Y., Menon D., Lingsma H. F., Maas A. I. R., Stocchetti N., Venema E., Lecky F. E., Akerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzo P., Beauvais R., Beer R., Bellander B. -M., Belli A., Benali H., Berardino M., Beretta L., Blaabjerg M., Bragge P., Brazinova A., Brinck V., Brooker J., Brorsson C., Buki A., Bullinger M., Cabeleira M., Caccioppola A., Calappi E., Calvi M. R., Cameron P., Lozano G. C., Carbonara M., Chevallard G., Chieregato A., Citerio G., Cnossen M., Coburn M., Coles J., Cooper D. J., Correia M., Covic A., Curry N., Czeiter E., Czosnyka M., Dahyot-Fizelier C., Dawes H., De Keyser V., Degos V., Corte F. D., Boogert H., Depreitere B., Dilvesi D., Dixit A., Donoghue E., Dreier J., Duliere G. -L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., Foks K., Frisvold S., Furmanov A., Gagliardo P., Galanaud D., Gantner D., Gao G., George P., Ghuysen A., Giga L., Glocker B., Golubovic J., Gomez P. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Huijben J., Hutchinson P. J., Jacobs B., Jankowski S., Jarrett M., Jiang J. -Y., Jones K., Karan M., Kolias A. G., Kompanje E., Kondziella D., Koraropoulos E., Koskinen L. -O., Kovacs N., Lagares A., Lanyon L., Laureys S., Lecky F., Lefering R., Legrand V., Lejeune A., Levi L., Lightfoot R., Lingsma H., Castano-Leon A. M., Maegele M., Majdan M., Manara A., Manley G., Martino C., Marechal H., Mattern J., McMahon C., Melegh B., Menovsky T., Mulazzi D., Muraleedharan V., Murray L., Nair N., Negru A., Nelson D., Newcombe V., Nieboer D., Noirhomme Q., Nyiradi J., Olubukola O., Oresic M., Ortolano F., Palotie A., Parizel P. M., Payen J. -F., Perera N., Perlbarg V., Persona P., Peul W., Piippo-Karjalainen A., Pirinen M., Ples H., Polinder S., Pomposo I., Posti J. P., Puybasset L., Radoi A., Ragauskas A., Raj R., Rambadagalla M., Real R., Rhodes J., Richardson S., Richter S., Ripatti S., Rocka S., Roe C., Roise O., Rosand J., Rosenfeld J. V., Rosenlund C., Rosenthal G., Rossaint R., Rossi S., Rueckert D., Rusnak M., Sahuquillo J., Sakowitz O., Sanchez-Porras R., Sandor J., Schafer N., Schmidt S., Schoechl H., Schoonman G., Schou R. F., Schwendenwein E., Sewalt C., Skandsen T., Smielewski P., Sorinola A., Stamatakis E., Stanworth S., Kowark A., Stevens R., Stewart W., Steyerberg E. W., Sundstrom N., Synnot A., Takala R., Tamas V., Tamosuitis T., Taylor M. S., Ao B. T., Tenovuo O., Theadom A., Thomas M., Tibboel D., Timmers M., Tolias C., Trapani T., Tudora C. M., Vajkoczy P., Vallance S., Valeinis E., Vamos Z., Van der Steen G., van der Naalt J., van Dijck J. T. J. M., van Essen T. A., Van Hecke W., van Heugten C., Van Praag D., Vyvere T. V., Vanhaudenhuyse A., van Wijk R. P. J., Vargiolu A., Vega E., Velt K., Verheyden J., Vespa P. M., Vik A., Vilcinis R., Volovici V., von Steinbuchel N., Voormolen D., Vulekovic P., Wang K. K. W., Wiegers E., Williams G., Wilson L., Winzeck S., Wolf S., Yang Z., Ylen P., Younsi A., Zeiler F. A., Zelinkova V., Ziverte A., Zoerle T., Sewalt, Charlie Aletta [0000-0003-3270-4814], Apollo - University of Cambridge Repository, Public Health, Anesthesiology, Neurology, Amrein, Krisztina, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Koraropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Lagares, Alfonso, Lanyon, Linda, Andelic, Nada, Laureys, Steven, Lecky, Fiona, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño-León, Ana M., Andreassen, Lasse, Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Anke, Audny, Menovsky, Tomas, Mulazzi, Davide, Muraleedharan, Visakh, Murray, Lynnette, Nair, Nandesh, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Noirhomme, Quentin, Antoni, Anna, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Audibert, Gérard, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Azouvi, Philippe, Raj, Rahul, Rambadagalla, Malinka, Real, Ruben, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Azzolini, Maria Luisa, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Bartels, Ronald, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Barzó, Pál, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Kowark, Ana, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Beauvais, Romuald, Synnot, Anneliese, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Beer, Ronny, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, Van der Steen, Gregory, van der Naalt, Joukje, Bellander, Bo-Michael, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Vyvere, Thijs Vande, Vanhaudenhuyse, Audrey, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Belli, Antonio, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Benali, Habib, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederik A., Zelinkova, Veronika, Berardino, Maurizio, Ziverte, Agate, Zoerle, Tommaso, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Cnossen, Maryse, Coburn, Mark, Coles, Jonathan, Cooper, D. Jamie, Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Åkerlund, Cecilia, Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Molecular Neuroscience and Ageing Research (MOLAR), Ročka, Saulius, Tamošuitis, Tomas, CENTER TBI Participants Investigators, Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, „Springer Nature' grupė, Sewalt, C, Gravesteijn, B, Menon, D, Lingsma, H, Maas, A, Stocchetti, N, Venema, E, Lecky, F, Akerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzo, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Chevallard, G, Chieregato, A, Citerio, G, Cnossen, M, Coburn, M, Coles, J, Cooper, D, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dawes, H, De Keyser, V, Degos, V, Corte, F, Boogert, H, Depreitere, B, Dilvesi, D, Dixit, A, Donoghue, E, Dreier, J, Duliere, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovacs, N, Lagares, A, Lanyon, L, Laureys, S, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Castano-Leon, A, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menovsky, T, Mulazzi, D, Muraleedharan, V, Murray, L, Nair, N, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Noirhomme, Q, Nyiradi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Real, R, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnak, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Kowark, A, Stevens, R, Stewart, W, Steyerberg, E, Sundstrom, N, Synnot, A, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Vallance, S, Valeinis, E, Vamos, Z, Van der Steen, G, van der Naalt, J, van Dijck, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, Vyvere, T, Vanhaudenhuyse, A, van Wijk, R, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, von Steinbuchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Sewalt, C. A., Gravesteijn, B. Y., Menon, D., Lingsma, H. F., Maas, A. I. R., Stocchetti, N., Venema, E., Lecky, F. E., Akerlund, C., Amrein, K., Andelic, N., Andreassen, L., Anke, A., Antoni, A., Audibert, G., Azouvi, P., Azzolini, M. L., Bartels, R., Barzo, P., Beauvais, R., Beer, R., Bellander, B. -M., Belli, A., Benali, H., Berardino, M., Beretta, L., Blaabjerg, M., Bragge, P., Brazinova, A., Brinck, V., Brooker, J., Brorsson, C., Buki, A., Bullinger, M., Cabeleira, M., Caccioppola, A., Calappi, E., Calvi, M. R., Cameron, P., Lozano, G. C., Carbonara, M., Chevallard, G., Chieregato, A., Citerio, G., Cnossen, M., Coburn, M., Coles, J., Cooper, D. J., Correia, M., Covic, A., Curry, N., Czeiter, E., Czosnyka, M., Dahyot-Fizelier, C., Dawes, H., De Keyser, V., Degos, V., Corte, F. D., Boogert, H., Depreitere, B., Dilvesi, D., Dixit, A., Donoghue, E., Dreier, J., Duliere, G. -L., Ercole, A., Esser, P., Ezer, E., Fabricius, M., Feigin, V. L., Foks, K., Frisvold, S., Furmanov, A., Gagliardo, P., Galanaud, D., Gantner, D., Gao, G., George, P., Ghuysen, A., Giga, L., Glocker, B., Golubovic, J., Gomez, P. A., Gratz, J., Gravesteijn, B., Grossi, F., Gruen, R. L., Gupta, D., Haagsma, J. A., Haitsma, I., Helbok, R., Helseth, E., Horton, L., Huijben, J., Hutchinson, P. J., Jacobs, B., Jankowski, S., Jarrett, M., Jiang, J. -Y., Jones, K., Karan, M., Kolias, A. G., Kompanje, E., Kondziella, D., Koraropoulos, E., Koskinen, L. -O., Kovacs, N., Lagares, A., Lanyon, L., Laureys, S., Lecky, F., Lefering, R., Legrand, V., Lejeune, A., Levi, L., Lightfoot, R., Lingsma, H., Castano-Leon, A. M., Maegele, M., Majdan, M., Manara, A., Manley, G., Martino, C., Marechal, H., Mattern, J., Mcmahon, C., Melegh, B., Menovsky, T., Mulazzi, D., Muraleedharan, V., Murray, L., Nair, N., Negru, A., Nelson, D., Newcombe, V., Nieboer, D., Noirhomme, Q., Nyiradi, J., Olubukola, O., Oresic, M., Ortolano, F., Palotie, A., Parizel, P. M., Payen, J. -F., Perera, N., Perlbarg, V., Persona, P., Peul, W., Piippo-Karjalainen, A., Pirinen, M., Ples, H., Polinder, S., Pomposo, I., Posti, J. P., Puybasset, L., Radoi, A., Ragauskas, A., Raj, R., Rambadagalla, M., Real, R., Rhodes, J., Richardson, S., Richter, S., Ripatti, S., Rocka, S., Roe, C., Roise, O., Rosand, J., Rosenfeld, J. V., Rosenlund, C., Rosenthal, G., Rossaint, R., Rossi, S., Rueckert, D., Rusnak, M., Sahuquillo, J., Sakowitz, O., Sanchez-Porras, R., Sandor, J., Schafer, N., Schmidt, S., Schoechl, H., Schoonman, G., Schou, R. F., Schwendenwein, E., Sewalt, C., Skandsen, T., Smielewski, P., Sorinola, A., Stamatakis, E., Stanworth, S., Kowark, A., Stevens, R., Stewart, W., Steyerberg, E. W., Sundstrom, N., Synnot, A., Takala, R., Tamas, V., Tamosuitis, T., Taylor, M. S., Ao, B. T., Tenovuo, O., Theadom, A., Thomas, M., Tibboel, D., Timmers, M., Tolias, C., Trapani, T., Tudora, C. M., Vajkoczy, P., Vallance, S., Valeinis, E., Vamos, Z., Van der Steen, G., van der Naalt, J., van Dijck, J. T. J. M., van Essen, T. A., Van Hecke, W., van Heugten, C., Van Praag, D., Vyvere, T. V., Vanhaudenhuyse, A., van Wijk, R. P. J., Vargiolu, A., Vega, E., Velt, K., Verheyden, J., Vespa, P. M., Vik, A., Vilcinis, R., Volovici, V., von Steinbuchel, N., Voormolen, D., Vulekovic, P., Wang, K. K. W., Wiegers, E., Williams, G., Wilson, L., Winzeck, S., Wolf, S., Yang, Z., Ylen, P., Younsi, A., Zeiler, F. A., Zelinkova, V., Ziverte, A., Zoerle, T., Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, University of Helsinki, HUS Neurocenter, Neurokirurgian yksikkö, Statistical and population genetics, Biostatistics Helsinki, Clinicum, Helsinki University Hospital Area, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, and Complex Disease Genetics
Subjects: medicine.medical_specialty, Brain Injuries, Traumatic/diagnosis, Referral, IMPACT, Traumatic brain injury, traumatic brain injury, referral, transfer, trauma system, Glasgow Outcome Scale, GUIDELINES, Critical Care and Intensive Care Medicine, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, Case mix index, Midline shift, Brain Injuries, Traumatic, medicine, EPIDEMIOLOGY, Humans, In patient, Glasgow Coma Scale, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Referral and Consultation, Original Research, OUTCOMES, RC86-88.9, business.industry, MORTALITY, 3112 Neurosciences, HEAD-INJURY, Medical emergencies. Critical care. Intensive care. First aid, PREHOSPITAL MANAGEMENT, Trauma system, CARE, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, 3. Good health, Transfer, Emergency medicine, Emergency Medicine, Human medicine, business, SYSTEM, 030217 neurology & neurosurgery
Abstract: Scandinavian journal of trauma, resuscitation and emergency medicine 29(1), 113 (2021). doi:10.1186/s13049-021-00930-1, Published by BioMed Central, London
Published: 2021
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45. Liver graft outcomes from donors with vaccine induced thrombosis and thrombocytopenia (VITT): United Kingdom multicenter experience

Author: Andreas Prachalias, Khalid Sharif, Rebecca Sanabria-Mateos, Katherine Quist, Darius F. Mirza, Owen L. Cain, Will Lester, John Forsythe, Hermien Hartog, Angus Hann, Phillip L R Nicolson, Ines Ushiro-Lumb, Anisa Nutu, George H.B. Greenhall, Douglas Thorburn, John Isaac, Ye Htun Oo, Abhishek Chauhan, M. Thamara P. R. Perera, Desley Neil, and Joerg M. Pollok
Subjects: medicine.medical_specialty, Tissue and Organ Procurement, Lymphocyte, medicine.medical_treatment, Liver transplantation, medicine.disease_cause, Gastroenterology, Autoimmunity, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Platelet, Vein, Vaccines, Transplantation, biology, business.industry, Graft Survival, Thrombosis, medicine.disease, Thrombocytopenia, Tissue Donors, medicine.anatomical_structure, Liver, biology.protein, Antibody, business, Platelet factor 4
Abstract: Vaccine-induced immune thrombosis and thrombocytopenia (VITT) syndrome is a new entity, characterised by severe thrombocytopenia and multiple sites of thrombosis1 . The presumed mechanism is driven by anti-platelet factor 4 (PF4) antibodies causing platelet activation1 . Donors with VITT syndrome have a particular relevance for liver transplantation (LT), due to the associated risk of passenger lymphocyte syndrome, and a predisposition for porto-mesenteric or hepatic vein thrombosis2 .
Published: 2022
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46. The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD)

Author: Andres Yarur, Freddy Caldera, Sirimon O'Charoen, Joshua R. Korzenik, Cecile Norris, Matthew Bohm, Monika Fischer, Sara Sweeney, Alandra Weaver, Uni Wong, Sushila Dalal, Themistocles Dassopoulos, Katerina Wells, David Hudesman, Lilani P. Perera, Shrinivas Bishu, Caren Heller, Richard H. Duerr, Tara Fehlmann, Deepak Parakkal, Raymond K. Cross, James D. Lewis, Manreet Kaur, Matthew A. Ciorba, Sumona Saha, Elizabeth A. Scoville, Laura E. Raffals, Joel Pekow, Scott B. Snapper, Angela Dobes, and Meenakshi Bewtra
Subjects: Adult, Pancolitis, medicine.medical_specialty, Colonoscopy, Disease, Inflammatory bowel disease, Cohort Studies, Crohn Disease, Clinical Research, Internal medicine, medicine, Humans, Immunology and Allergy, Osteonectin, Prospective Studies, Prospective cohort study, Crohn's disease, medicine.diagnostic_test, business.industry, Gastroenterology, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Cohort, Colitis, Ulcerative, medicine.symptom, business
Abstract: Background Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. Methods We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. Results Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn’s disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. Conclusion The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.
Published: 2021
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47. Genetic association of primary nonresponse to anti-TNFα therapy in patients with inflammatory bowel disease

Author: Wei-Qi Wei, Erin Smithberger, Jennifer A. Pacheco, Gail P. Jarvik, Madeleine Horvath, James G. Linneman, Tanima De, Loukia Parisiadou, Cristina Alarcon, Adam S. Gordon, Juan Avitia, Scott J. Hebbring, Patrick M. A. Sleiman, Chuyu Chen, Hakon Hakonarson, Sarbani Adhikari, Minoli A. Perera, Sara Kwan, Honghong Zhang, Mary Young, John H. Kwon, John B. Harley, Bianca Lec, and Frank D. Mentch
Subjects: medicine.medical_specialty, Necrosis, Inflammatory bowel disease, Gastroenterology, Article, Pathogenesis, Cohort Studies, Internal medicine, Genotype, Genetics, medicine, Humans, General Pharmacology, Toxicology and Pharmaceutics, Molecular Biology, Genetics (clinical), Genetic association, Gene knockdown, Tumor Necrosis Factor-alpha, business.industry, Autophagy, Odds ratio, Inflammatory Bowel Diseases, medicine.disease, Case-Control Studies, Immunology, Expression quantitative trait loci, Molecular Medicine, Tumor necrosis factor alpha, medicine.symptom, business, Genome-Wide Association Study
Abstract: OBJECTIVE Primary non-response (PNR) to anti-tumor necrosis factor-α (TNFα) biologics is a serious concern in patients with inflammatory bowel disease (IBD). We aimed to identify the genetic variants associated with PNR. DESIGN Patients were recruited from outpatient GI clinics and PNR was determined using both clinical and endoscopic findings. A case-control genome-wide association study was performed in 589 IBD patients and associations were replicated in an independent cohort of 293 patients. Effect of the associated variant on gene expression and TNFα secretion was assessed by cell-based assays. Pleiotropic effects were investigated by Phenome-wide Association Study (PheWAS). RESULTS We identified rs34767465 as associated with PNR to anti-TNF-α therapy (OR:2.07, 95%CI:1.46-2.94, p=2.43×10−7, [Replication OR:1.8, 95%CI:1.04-3.16, p=0.03]). rs34767465 is a multiple-tissue expression quantitative trait loci for FAM114A2. Using RNA-sequencing and protein quantification from HapMap lymphoblastoid cell lines (LCLs), we found a significant decrease in FAM114A2 mRNA and protein expression in both heterozygous and homozygous genotypes when compared to wild type LCLs. TNF-α secretion was significantly higher in THP-1 cells [differentiated into macrophages] with FAM114A2 knockdown versus controls. Immunoblotting experiments showed that depletion of FAM114A2 impaired autophagy related pathway genes suggesting autophagy mediated TNF-α secretion as a potential mechanism. PheWAS showed rs34767465 was associated with comorbid conditions found in IBD patients (derangement of joints [p=2.3×10−4], pigmentary iris degeneration [p=5.1×10−4], diverticulum of esophagus [p=6.3×10−4]). CONCLUSION We identified a variant rs34767465 associated with PNR to anti-TNFα biologics, which increases TNFα secretion through mechanism related to autophagy. rs34767465 may also explain the comorbidities associated with IBD. Significance of this study What is already known on this subject? Tumor necrosis factor (TNF) α is one of the major pro-inflammatory cytokines in the underlying pathogenesis of mucosal inflammation in inflammatory bowel disease (IBD), and has been the primary therapeutic target for IBD. Anti-TNFα biologic drugs have been shown to induce clinical response in 60-75% of the patients, and long-term maintenance of remission in a large number of patients that respond to the drug. However, approximately 30-40% of the patients fail to respond to anti-TNF α biologics (primary non-responders; PNR). What are the new findings? This is the first genome-wide association study to identify the genetic loci, rs34767465 associated with 2-fold increased risk of PNR to anti-TNFα therapy. rs34767465 is an expressed quantitative trait locus for FAM114A2, and leads to decreased expression of the gene in blood and LCLs. Knockdown of FAM114A2 in THP-1 cells-derived macrophages increase TNFα secretion through mechanism related to autophagy. Phenome-wide association study reveals association of rs34767465 with comorbid conditions like derangement of joints, pigmentary iris degeneration and diverticulum of esophagus, that are observed in IBD patients How might it impact on clinical practice in the foreseeable future? rs34767465 may help guide physicians’ drug choice and therapeutic drug monitoring to prevent PNR to anti-TNFα therapy and IBD associated comorbidities.
Published: 2021
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48. Prisoners with Attention Deficit Hyperactivity Disorder: co-morbidities and service pathways

Author: Susan Young, Philip Asherson, Andrew Forrester, Amina Rawat, Lisa Underwood, Declan G. Murphy, Ken Courtenay, Jane McCarthy, Richard Mills, Jess Sabet, Eddie Chaplin, Bhathika Perera, and Hannah Hayward
Subjects: medicine.medical_specialty, Prison population, Routine screening, High prevalence, business.industry, media_common.quotation_subject, virus diseases, Prison, social sciences, medicine.disease, behavioral disciplines and activities, Health Professions (miscellaneous), Prevalence of mental disorders, mental disorders, medicine, population characteristics, Attention deficit hyperactivity disorder, Co morbidity, National level, Psychiatry, business, media_common
Abstract: Purpose This paper aims to examine effective diagnostic and treatment pathways for attention deficit hyperactivity disorder (ADHD) in prison settings given the high prevalence of ADHD and comorbidities in the prison population. Design/methodology/approach Two studies were carried out in two separate prisons in London. Firstly, data were collected to understand the prevalence of ADHD and the comorbidities. The second study used quality improvement (QI) methodology to assess the impact of a diagnostic and treatment pathway for prisoners with ADHD. Findings Of the prisoners, 22.5% met the diagnostic criteria for ADHD. Nearly half of them were screened positive for autistic traits, with a higher prevalence of mental disorders among prisoners with ADHD compared to those without. The QI project led to a significant increase in the number of prisoners identified as requiring ADHD assessment but a modest increase in the number of prisoners diagnosed or treated for ADHD. Originality/value Despite various challenges, an ADHD diagnostic and treatment pathway was set up in a prison using adapted QI methodology. Further research is needed to explore the feasibility of routine screening for ADHD in prison and examine at a national level the effectiveness of current ADHD prison pathways.
Published: 2021
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49. Low-frequency STN-DBS provides acute gait improvements in Parkinson’s disease: a double-blinded randomised cross-over feasibility trial

Author: Peter A. Silburn, Karen O'Maley, Zachary J. Conway, Thushara Perera, and Michael H. Cole
Subjects: Balance, medicine.medical_specialty, Deep brain stimulation, Parkinson's disease, Neurology, Deep Brain Stimulation, medicine.medical_treatment, Health Informatics, Walk, Neurosciences. Biological psychiatry. Neuropsychiatry, Physical medicine and rehabilitation, medicine, Humans, Gait, Balance (ability), Sensor, UPDRS, Cross-Over Studies, business.industry, Research, Rehabilitation, Australia, Parkinson Disease, medicine.disease, Crossover study, Trunk, nervous system diseases, Clinical trial, surgical procedures, operative, nervous system, Feasibility Studies, business, Rhythmic, RC321-571
Abstract: Background Some people with Parkinson’s disease (PD) report poorer dynamic postural stability following high-frequency deep brain stimulation of the subthalamic nucleus (STN-DBS), which may contribute to an increased falls risk. However, some studies have shown low-frequency (60 Hz) STN-DBS improves clinical measures of postural stability, potentially providing support for this treatment. This double-blind randomised crossover study aimed to investigate the effects of low-frequency STN-DBS compared to high-frequency stimulation on objective measures of gait rhythmicity in people with PD. Methods During high- and low-frequency STN-DBS and while off-medication, participants completed assessments of symptom severity and walking (e.g., Timed Up-and-Go). During comfortable walking, the harmonic ratio, an objective measures of gait rhythmicity, was derived from head- and trunk-mounted accelerometers to provide insight in dynamic postural stability. Lower harmonic ratios represent less rhythmic walking and have discriminated people with PD who experience falls. Linear mixed model analyses were performed on fourteen participants. Results Low-frequency STN-DBS significantly improved medial–lateral and vertical trunk rhythmicity compared to high-frequency. Improvements were independent of electrode location and total electrical energy delivered. No differences were noted between stimulation conditions for temporal gait measures, clinical mobility measures, motor symptom severity or the presence of gait retropulsion. Conclusions This study provides evidence for the acute benefits of low-frequency stimulation for gait outcomes in STN-DBS PD patients, independent of electrode location. However, the perceived benefits of this therapy may be diminished for people who experienced significant tremor pre-operatively, as lower frequencies may cause these symptoms to re-emerge. Trial registration: This study was prospectively registered with the Australian and New Zealand Clinical Trials Registry on 5 June 2018 (ACTRN12618000944235).
Published: 2021

50. Invasive lizard has fewer parasites than native congener

Author: Isabel Damas-Moreira, D. James Harris, Beatriz Tomé, and Ana Perera
Subjects: Male, 0106 biological sciences, medicine.medical_specialty, Podarcis virescens, 010607 zoology, Genetics, Evolution, and Phylogeny - Short Communication, Zoology, Reptile, Introduced species, Podarcis siculus, 010603 evolutionary biology, 01 natural sciences, Invasive species, 18S ribosomal RNA, Medical microbiology, biology.animal, medicine, Animals, Parasite hosting, Parasites, Biological invasions, Haemogregarines, Phylogeny, Portugal, General Veterinary, biology, Lizard, Bayes Theorem, Lizards, General Medicine, biology.organism_classification, Infectious Diseases, Haplotypes, Sympatric speciation, Insect Science, Female, Parasitology, Introduced Species, Italian wall lizard
Abstract: Invasive species can carry parasites to introduced locations, which may be key to understand the success or failure of species establishment and the invasive potential of introduced species. We compared the prevalence and infection levels of haemogregarine blood parasites between two sympatric congeneric species in Lisbon, Portugal: the invasive Italian wall lizard (Podarcis siculus) and the native green Iberian wall lizard (Podarcis virescens). The two species had significant differences in their infection levels: while P. virescens had high prevalence of infection (69.0%), only one individual of P. siculus was infected (3.7%), and while P. virescens exhibited an average intensity of 1.36%, the infected P. siculus individual had an infection rate of only 0.04%. Genetic analyses of 18S rRNA identified two different haemogregarine haplotypes in P. virescens. Due to the low levels of infection, we were not able to amplify parasite DNA from the infected P. siculus individual, although it was morphologically similar to those found in P. virescens. Since other studies also reported low levels of parasites in P. siculus, we hypothesize that this general lack of parasites could be one of the factors contributing to its competitive advantage over native lizard species and introduction success.
Published: 2021
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