Author: "A. Wells" / Topic: medicine.disease - Searchworks@Jio Institute Digital Library Search Results

9,911 results on '"A. Wells"'

1. Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy

Author: Jaap J. Plomp, Dominic J. Wells, Christa L Tanganyika-de Winter, David Bull, Annemieke Aartsma-Rus, John C. W. Hildyard, Sofia Nnorom, K E Wells, Ingrid E.C. Verhaart, and Ornella Cappellari
Subjects: Research Report, 0301 basic medicine, Simvastatin, Duchenne muscular dystrophy, Inflammation, Pharmacology, medicine.disease_cause, Mice, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, polycyclic compounds, medicine, Animals, Muscular dystrophy, Muscle, Skeletal, biology, business.industry, nutritional and metabolic diseases, Muscular Dystrophy, Animal, medicine.disease, Pathophysiology, Muscular Dystrophy, Duchenne, Disease Models, Animal, 030104 developmental biology, Neurology, Mice, Inbred mdx, biology.protein, lipids (amino acids, peptides, and proteins), Neurology (clinical), medicine.symptom, business, Dystrophin, 030217 neurology & neurosurgery, Oxidative stress, medicine.drug
Abstract: Duchenne muscular dystrophy is an X-linked, recessive muscular dystrophy in which the absence of the dystrophin protein leads to fibrosis, inflammation and oxidative stress, resulting in loss of muscle tissue. Drug repurposing, i.e. using drugs already approved for other disorders, is attractive as it decreases development time. Recent studies suggested that simvastatin, a cholesterol lowering drug used for cardiovascular diseases, has beneficial effects on several parameters in mdx mice. To validate properly the effectiveness of simvastatin, two independent labs tested the effects of 12-week simvastatin treatment in either young (starting at 4 weeks of age) or adult (starting at 12 weeks of age) mdx mice. In neither study were benefits of simvastatin treatment observed on muscle function, histology or expression of genes involved in fibrosis, regeneration, oxidative stress and autophagy. Unexpectedly, although the treatment protocol was similar, simvastatin plasma levels were found to be much lower than observed in a previous study. In conclusion, in two laboratories, simvastatin did not ameliorate disease pathology in mdx mice, which could either be due to the ineffectiveness of simvastatin itself or due to the low simvastatin plasma levels following oral administration via the food.
Published: 2021
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2. Anthropometry, body composition and chronic disease risk factors among Zambian school-aged children who experienced severe malnutrition in early childhood

Author: Samuel Wells, Suzanne Filteau, Grace Munthali, Andrea M. Rehman, Molly Chisenga, Lackson Kasonka, and Jonathan C. K. Wells
Subjects: Pediatrics, medicine.medical_specialty, Population, Severe Acute Malnutrition, Zambia, Medicine (miscellaneous), Blood lipids, Overweight, Protein-Energy Malnutrition, Risk Factors, medicine, Humans, Mass index, Child, education, Glycated Hemoglobin, education.field_of_study, Nutrition and Dietetics, Anthropometry, business.industry, Malnutrition, medicine.disease, Child, Preschool, Chronic Disease, Body Composition, medicine.symptom, business, Bioelectrical impedance analysis
Abstract: There is limited information as to whether people who experience severe acute malnutrition (SAM) as young children are at increased risk of overweight, high body fat and associated chronic diseases in later life. We followed up, when aged 7–12 years, 100 Zambian children who were hospitalised for SAM before age 2 years and eighty-five neighbourhood controls who had never experienced SAM. We conducted detailed anthropometry, body composition assessment by bioelectrical impedance and deuterium dilution (D2O) and measured blood lipids, Hb and HbA1c. Groups were compared by linear regression following multiple imputation for missing variables. Children with prior SAM were slightly smaller than controls, but differences, controlling for age, sex, socio-economic status and HIV exposure or infection, were significant only for hip circumference, suprailiac skinfold and fat-free mass index by D2O. Blood lipids and HbA1c did not differ between groups, but Hb was lower by 7·8 (95 % CI 0·8, 14·7) g/l and systolic blood pressure was 3·4 (95 % CI 0·4, 6·4) mmHg higher among the prior SAM group. Both anaemia and high HbA1c were common among both groups, indicating a population at risk for the double burden of over- and undernutrition and associated infectious and chronic diseases. The prior SAM children may have been at slightly greater risk than the controls; this was of little clinical significance at this young age, but the children should be followed when older and chronic diseases manifest.
Published: 2021
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3. Impact of Lung Biopsy Information on Treatment Strategy of Patients with Interstitial Lung Diseases

Author: Leonardo Gori, Sara Tomassetti, Mauro Pavone, Sara Piciucchi, Giulio Rossi, Elisabetta Rosi, Silvia Puglisi, Carlo Vancheri, Luca Donati, Valentina Luzzi, Venerino Poletti, Alessandra Dubini, AU Wells, Thomas V. Colby, Alberto Cavazza, Federico Lavorini, Jay H. Ryu, M. Matucci-Cerinic, and Claudia Ravaglia
Subjects: Pulmonary and Respiratory Medicine, Prognosis prediction, medicine.medical_specialty, High-resolution computed tomography, Biopsy, Low Confidence, Lung biopsy, surgical lung biopsy, Text mining, Usual interstitial pneumonia, Internal medicine, Bronchoscopy, medicine, Humans, interstitial lung diseases, Lung, Retrospective Studies, IPF treatment, medicine.diagnostic_test, business.industry, transbronchial lung cryobiopsy, respiratory system, idiopathic pulmonary fibrosis, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, medicine.anatomical_structure, Treatment strategy, Lung Diseases, Interstitial, business
Abstract: Rationale: Lung biopsy (LBx) has a relevant role in the prediction of prognosis of interstitial lung diseases (ILDs), but its impact on the clinical management of patients remains unexplored. Objectives: This study evaluates whether LBx may change the therapeutic strategy and assesses the effect of diagnostic reclassification after LBx on long-term prognosis. Methods: We evaluated the LBx of 426 consecutive patients with ILDs, without a definite usual interstitial pneumonia pattern on high-resolution computed tomographic imaging. A total of 266 patients underwent transbronchial lung cryobiopsy (TBLC), and 160 patients underwent surgical lung biopsy (SLB). The multidisciplinary team (MDT) determined a diagnosis with high or low confidence, and a management strategy, both before and after the LBx data. Results: Final MDT diagnoses were 189 idiopathic pulmonary fibrosis (IPF), 143 non-IPF fibrotic ILDs, and 94 nonfibrotic ILDs. LBx data changed the management strategy in 145 cases (34%), with similar results for TBLC and SLB (the treatment strategy changed in 31.5% of TBLC cases, 84/266, P
Published: 2022
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4. Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD

Author: Charles R. Esther, Wanda K. O’Neal, Wayne H. Anderson, Mehmet Kesimer, Agathe Ceppe, Claire M. Doerschuk, Neil E. Alexis, Annette T. Hastie, R. Graham Barr, Russell P. Bowler, J. Michael Wells, Elizabeth C. Oelsner, Alejandro P. Comellas, Yohannes Tesfaigzi, Victor Kim, Laura M. Paulin, Christopher B. Cooper, MeiLan K. Han, Yvonne J. Huang, Wassim W. Labaki, Jeffrey L. Curtis, Richard C. Boucher, Mehrdad Arjomandi, Igor Barjaktarevic, Lori A. Bateman, Surya P. Bhatt, Eugene R. Bleecker, Stephanie A. Christenson, David J. Couper, Gerard J. Criner, Ronald G. Crystal, Mark T. Dransfield, Brad Drummond, Christine M. Freeman, Craig Galban, Nadia N. Hansel, Eric A. Hoffman, Yvonne Huang, Robert J. Kaner, Richard E. Kanner, Eric C. Kleerup, Jerry A. Krishnan, Lisa M. LaVange, Stephen C. Lazarus, Fernando J. Martinez, Deborah A. Meyers, Wendy C. Moore, John D. Newell, Robert Paine, Laura Paulin, Stephen P. Peters, Cheryl Pirozzi, Nirupama Putcha, Victor E. Ortega, Sanjeev Raman, Stephen I. Rennard, Donald P. Tashkin, Robert A. Wise, and Prescott G. Woodruff
Subjects: Pulmonary and Respiratory Medicine, Spirometry, Subpopulations and Intermediate Outcome Measures in COPD Study, Chronic Obstructive, Exacerbation, Chronic Obstructive Pulmonary Disease, Clinical Sciences, Respiratory System, Critical Care and Intensive Care Medicine, Cystic fibrosis, COPD: Original Research, Pulmonary Disease, Pulmonary Disease, Chronic Obstructive, mucus, Clinical Research, medicine, Humans, glutathione, Lung, COPD, medicine.diagnostic_test, business.industry, methionine salvage, Sputum, Area under the curve, medicine.disease, metabolomics, N-Acetylneuraminic Acid, Pathophysiology, respiratory tract diseases, Good Health and Well Being, adenosine, inflammation, Hypoxanthines, Immunology, Respiratory, Biomarker (medicine), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: BACKGROUND: Improved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets. RESEARCH QUESTION: Which physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations? STUDY DESIGN AND METHODS: We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations. RESULTS: Sputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations. INTERPRETATION: Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01969344; URL: www.clinicaltrials.gov
Published: 2022
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5. Significance of FEV3/FEV6 in Recognition of Early Airway Disease in Smokers at Risk of Development of COPD

Author: Russell G. Buhr, Mehrdad Arjomandi, David Couper, Russell P. Bowler, Jeffrey L. Curtis, MeiLan K. Han, Victor E. Ortega, Christopher B. Cooper, Robert Paine, Spyridon Fortis, Eric A. Hoffman, Daniela Markovic, Fernando J. Martinez, Igor Barjaktarevic, Nathan Yee, Wayne Anderson, Prescott G. Woodruff, M. Bradley Drummond, Donald P. Tashkin, James M. Wells, R. Graham Barr, and Victor Kim
Subjects: Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, Vital capacity, COPD, medicine.diagnostic_test, business.industry, Critical Care and Intensive Care Medicine, medicine.disease, respiratory tract diseases, FEV1/FVC ratio, Quality of life, DLCO, Internal medicine, Cohort, medicine, Lung volumes, Cardiology and Cardiovascular Medicine, business
Abstract: Background Small airways are known to be affected early in the course of chronic obstructive pulmonary disease (COPD); however, traditional spirometric indices may not accurately identify small airways disease. Research Question Can FEV3/FEV6 identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD? Study Design and Methods We included eight hundred thirty-two current and former smokers with post-bronchodilator FEV1/FVC ≥0.7 from the SPIROMICS cohort. Participants were classified as having a reduced pre-bronchodilator FEV3/FEV6 based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV3 and FEV6. Regression modeling was used to evaluate the relationship between baseline FEV3/FEV6 and outcome measures including functional small airways disease on thoracic imaging and respiratory exacerbations. Interval censored analysis was used to assess progression to COPD. Results FEV3/FEV6 Interpretation FEV3/FEV6 is a routinely available and repeatable spirometric index which can be useful in the evaluation of early airflow obstruction in current and former smokers without COPD. A reduced FEV3/FEV6 can identify those at risk for future development of COPD and respiratory exacerbations.
Published: 2022
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6. Adaptive Treatment for Youth With Substance Use and Depression: Early Depression Response and Short-term Outcomes

Author: Karen C. Wells, Shayna M. Cheek, John F. Curry, Adrienne Banny Inscoe, Yifrah Kaminer, Allison E. Meyer, Rebecca H. Burke, David B. Goldston, and Grace Chan
Subjects: Adult, Drug, medicine.medical_specialty, Adolescent, Urinalysis, Substance-Related Disorders, media_common.quotation_subject, medicine.medical_treatment, Alcohol abuse, Article, Young Adult, Developmental and Educational Psychology, Humans, Medicine, Child, Psychiatry, Depression (differential diagnoses), Cannabis, media_common, Cognitive Behavioral Therapy, medicine.diagnostic_test, Depression, business.industry, Odds ratio, medicine.disease, Clinical trial, Cognitive behavioral therapy, Psychiatry and Mental health, Treatment Outcome, Conduct disorder, business
Abstract: OBJECTIVE: To investigate prevalence and predictors of early depression response (EDR) in adolescents with substance use and depression receiving cognitive-behavioral therapy (CBT) for substance use; and to test the efficacy of supplemental CBT targeting depression (CBT-D) for non-EDR adolescents in an adaptive treatment approach. METHOD: Ninety-five youths at two sites (ages 14–21, mean = 17.4, SD=1.8) with alcohol or cannabis use and depressive symptoms received up to 12 sessions of CBT for substance use over 14 weeks. Assessments were at baseline, weeks four, nine, and 14. The Childrens’ Depression Rating Scale-Revised was the primary depression measure, with a reduction of 50% or more on this scale at week 4 defining EDR. The primary substance use outcomes of alcohol use, heavy alcohol use, and cannabis use frequency were assessed via interview report on the Alcohol Consumption Questionnaire and the Drug Checklist. Urinalysis provided a secondary measure of cannabis use. Non-EDR adolescents were randomized to supplemental CBT-D or enhanced depression treatment as usual (ETAU). RESULTS: Thirty-five adolescents (37%, 95% CI = 27%–47%) demonstrated EDR. Fewer days of cannabis use (OR = 0.977; 95% CI = 0.961–0.992) and absence of conduct disorder (OR = 0.149; 95% CI = 0.031–0.716) predicted EDR. Frequency of drinking (F(1,82) = 11.09, η(2) = 0.119, p = 0.001), heavy drinking (F(1, 82) = 19.91, η(2) = 0.195, p < 0.0001) and cannabis use (F(1, 220) = 35.01, η(2) = 0.137, p < 0.001) decreased over time for EDR, CBT-D and ETAU youths, with EDR adolescents evidencing earlier lower cannabis use (F(2, 220) = 4.16, η(2) = 0.036, p = 0.0169). Negative (clean) urine screens increased over time (F(1, 219) = 5.10, η(2) = 0.023, p = 0.0249). Comparison of CBT-D and ETAU indicated depression significantly decreased over time in both groups (F(1,48) = 64.20, η(2) = 0.572, p < 0.001), with no advantage for CBT-D. CONCLUSION: Approximately one-third of adolescents with substance use and depression attain EDR during substance use treatment. Less frequent cannabis use facilitates depression response. The relatively small sample may have precluded identification of additional EDR predictors. CLINICAL TRIAL REGISTRATION INFORMATION: Treatment for Teems with Alcohol Abuse and Depression; https://clinicaltrials.gov/; NCT02227589
Published: 2022
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7. The Longitudinal Course of Low-anterior Resection Syndrome

Author: Chris, Varghese, Cameron I, Wells, Greg, O'Grady, Peter, Christensen, Ian P, Bissett, Celia, Keane, and Soren, Laurberg
Subjects: bowel function, Adult, History, medicine.medical_specialty, Polymers and Plastics, Colorectal cancer, Industrial and Manufacturing Engineering, Longitudinal Course, Postoperative Complications, medicine, Humans, Bowel function, Business and International Management, rectal cancer, Low Anterior Resection, business.industry, Rectal Neoplasms, Syndrome, low anterior resection, medicine.disease, functional outcomes, Rectal Diseases, Meta-analysis, Quality of Life, Surgery, Radiology, business
Abstract: Objective:We aimed to better understand the longitudinal course of low anterior resection syndrome (LARS) to guide patient expectations and identify those at risk of persisting dysfunction.Summary Background Data:LARS describes disordered bowel function after rectal resection that significantly impacts quality of life.Methods:MEDLINE, EMBASE, CENTRAL, and CINAHL databases were systematically searched for studies that enrolled adults undergoing anterior resection for rectal cancer and used the LARS score to assess bowel function at ≥2 postoperative time points. Regression analyses were performed on deidentified patient-level data to identify predictors of change in LARS score from baseline (3-6months) to 12-months and 18-24-months.Results:Eight studies with a total of 701 eligible patients were included. The mean LARS score improved over time, from 29.4 (95% confidence interval 28.6-30.1) at baseline to 16.6 at 36-months (95% confidence interval 14.2%-18.9%). On multivariable analysis, a greater improvement in mean LARS score between baseline and 12-months was associated with no ileostomy formation [mean difference (MD) -1.7 vs 1.7, P < 0.001], and presence of LARS (major vs minor vs no LARS) at baseline (MD -3.8 vs -1.7 vs 5.4, P < 0.001). Greater improvement in mean LARS score between baseline and 18-24-months was associated with partial mesorectal excision vs total mesorectal excision (MD-8.6 vs 1.5, P < 0.001) and presence of LARS (major vs minor vs no LARS) at baseline (MD -8.8 vs -5.3 vs 3.4, P < 0.001).Conclusions:LARS improves by 18-months postoperatively then remains stable for up to 3-years. Total mesorectal excision, neoadjuvant radiotherapy, and ileostomy formation negatively impact upon bowel function recovery.
Published: 2022
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8. Comparative Impact of Depressive Symptoms and FEV1% on Chronic Obstructive Pulmonary Disease

Author: Jacqueline O’Toole, Han Woo, Nirupama Putcha, Christopher B. Cooper, Prescott Woodruff, Richard E. Kanner, Robert Paine, Russell P. Bowler, Alejandro Comellas, Karin F. Hoth, Jerry A. Krishnan, Meilan Han, Mark Dransfield, Anand S. Iyer, David Couper, Stephen P. Peters, Gerard Criner, Victor Kim, R. Graham Barr, Fernando J. Martinez, Nadia N. Hansel, Michelle N. Eakin, Neil E. Alexis, Wayne H. Anderson, Mehrdad Arjomandi, Igor Barjaktarevic, Lori A. Bateman, Surya P. Bhatt, Eugene R. Bleecker, Richard C. Boucher, Stephanie A. Christenson, Alejandro P. Comellas, David J. Couper, Gerard J. Criner, Ronald G. Crystal, Jeffrey L. Curtis, Claire M. Doerschuk, Mark T. Dransfield, Brad Drummond, Christine M. Freeman, Craig Galban, MeiLan K. Han, Annette T. Hastie, Eric A. Hoffman, Yvonne Huang, Robert J. Kaner, Eric C. Kleerup, Lisa M. LaVange, Stephen C. Lazarus, Deborah A. Meyers, Wendy C. Moore, John D. Newell, Laura Paulin, Cheryl Pirozzi, Elizabeth C. Oelsner, Wanda K. O’Neal, Victor E. Ortega, Sanjeev Raman, Stephen I. Rennard, Donald P. Tashkin, J Michael Wells, Robert A. Wise, and Prescott G. Woodruff
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, business.industry, Internal medicine, medicine, Pulmonary disease, medicine.disease, business, Depressive symptoms, Depression (differential diagnoses), respiratory tract diseases
Abstract: Rationale: Individuals with Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives:...
Published: 2022
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9. Factors Affecting Outcomes in Geriatric Traumatic Subdural Hematoma in a Neurosurgical Intensive Care Unit

Author: Kunal P. Kanakia, Shaheryar Hafeez, Samon Tavakoli-Samour, Bradley A. Dengler, Missak Tchoulhakian, Christian Kaculini, Ali Seifi, Jacob T. Boyd, Anne Marie Wells, and Brian S. Iskra
Subjects: medicine.medical_specialty, Multivariate analysis, Traumatic brain injury, Population, law.invention, Post-traumatic seizure, Hematoma, Seizures, law, Brain Injuries, Traumatic, Hematoma, Subdural, Intracranial, medicine, Humans, education, Aged, Retrospective Studies, education.field_of_study, Vascular disease, business.industry, Retrospective cohort study, medicine.disease, Intensive care unit, Intensive Care Units, Hematoma, Subdural, Emergency medicine, Surgery, Neurology (clinical), medicine.symptom, business
Abstract: Geriatric patients (age > 65 years) who sustain a traumatic brain injury (TBI) have an increased risk of poor outcomes and higher mortality compared to younger cohorts. We aimed to evaluate the risk factors for discharge outcomes in a geriatric traumatic subdural hematoma (SDH) population, stratified by age and pre-traumatic medical comorbidities. This was a single-center retrospective cohort study of geriatric patients (N = 207). Patient charts were evaluated for factors including patient characteristics, comorbidities, injury- and seizure-related factors and on neurosurgical intervention and patient disposition on discharge. Bivariate and multivariate analyses revealed that age was non-predictive of patient outcomes. Underlying vasculopathic comorbidities were the primary determinant of post-traumatic seizure (PTS), surgical, and discharge outcomes. Multifactor analysis (MFA) demonstrated that patients who went on to develop status epilepticus (N = 11) had a higher frequency of vasculopathic comorbidities with strong predictive power in poor patient outcomes. Our findings suggest a need to establish unique prognostic risk factors based on patient outcomes that guide medical and surgical treatment in geriatric patients.
Published: 2022
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10. Systematic review of the incidence and risk factors for chyle leak after pancreatic surgery

Author: Chris Varghese, Ajith K. Siriwardena, Samir Pathak, Sanjay Pandanaboyana, Cameron I. Wells, and S. Lee
Subjects: Leak, medicine.medical_specialty, Chyle, medicine.medical_treatment, Anastomotic Leak, Pancreaticoduodenectomy, Pancreatectomy, Risk Factors, medicine, Humans, Pancreas, Aged, business.industry, Incidence, Incidence (epidemiology), Anastomosis, Surgical, Age Factors, Middle Aged, medicine.disease, Confidence interval, Surgery, Pancreatic Neoplasms, Nutrition Assessment, Lymphatic system, Pancreatitis, business
Abstract: Background The incidence of and risk factors for chyle leak, as defined by the 2017 International Study Group on Pancreatic Surgery, remain unknown. Methods MEDLINE, EMBASE, and Scopus were systematically searched for studies of patients undergoing pancreatectomy that reported chyle leak according to the 2017 International Study Group on Pancreatic Surgery definition. The primary outcomes were the incidence of overall and clinically relevant chyle leak. A random-effects pairwise meta-analysis was used to calculate the incidence of chyle leak. Results Thirty-five studies including 7,083 patients were included in the meta-analysis. The weighted incidence of overall chyle leak was 6.8% (95% confidence interval 5.6–8.2), and clinically relevant chyle leak was 5.5% (95% confidence interval 3.8–7.7). Pancreaticoduodenectomy, total pancreatectomy, and distal pancreatectomy were associated with a CL incidence of 7.3%, 4.3%, and 5.8%, respectively. Fourteen individual risk factors for chyle leak were identified from included studies. Younger age, low prognostic nutritional index, para-aortic node manipulation, lymphatic involvement, and post-pancreatectomy pancreatitis were significantly associated with chyle leak, all from individual studies. Conclusion The incidence of overall chyle leak and clinically relevant chyle leak after pancreatic surgery, as defined by the 2017 International Study Group on Pancreatic Surgery, is 6.8% and 5.5%, respectively. Several risk factors for chyle leak were identified in the present review; however, larger high-quality studies are needed to more accurately define these risks.
Published: 2022
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11. Detection and Early Referral of Patients With Interstitial Lung Abnormalities

Author: Gary M. Hunninghake, Jonathan G. Goldin, Michael A. Kadoch, Jonathan A. Kropski, Ivan O. Rosas, Athol U. Wells, Ruchi Yadav, Howard M. Lazarus, Fereidoun G. Abtin, Tamera J. Corte, Joao A. de Andrade, Kerri A. Johannson, Martin R. Kolb, David A. Lynch, Justin M. Oldham, Paolo Spagnolo, Mary E. Strek, Sara Tomassetti, George R. Washko, Eric S. White, Fereidoun Abtin, Katerina Antoniou, Timothy Blackwell, Kevin Brown, Jonathan Chung, Tamera Corte, Bruno Crestani, Peter Crossno, Daniel Culver, Joao de Andrade, Anand Deveraj, Kevin Flaherty, Gunnar Gudmundsson, Hiroto Hatabu, Joe Jacob, Kerri Johansson, Jeff Kanne, Ella Kazerooni, Martin Kolb, David Lynch, Toby Maher, Fernando Martinez, Antonio Morais, Steven D. Nathan, Imre Noth, Justin Oldham, Anna Podolanczuk, Venerino Poletti, Claudia Ravaglia, Elizabetta Renzoni, Luca Richeldi, Geoffrey Rubin, Chris Ryerson, Debasis Sahoo, Rob Suh, Nicola Sverzellati, Dominique Valeyre, Simon Walsh, and George Washko
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Referral, business.industry, Interstitial lung disease, Pulmonologist, respiratory system, Critical Care and Intensive Care Medicine, medicine.disease, respiratory tract diseases, Pulmonary function testing, FEV1/FVC ratio, medicine, Honeycombing, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, Pulmonologists, Lung cancer screening
Abstract: Background Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILAs are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral. Research Question Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs? Study Design and Methods Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement. Results Fifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System “S-modifier” [which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of FVC and diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD. Interpretation Guidance for identifying clinically relevant ILA, with subsequent referral and follow-up, was established. These results lay the foundation for developing practical guidance on managing patients with ILA.
Published: 2022
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12. VTE Prophylaxis in Critically Ill Adults

Author: Karen E. A. Burns, Salmaan Kanji, Yaseen M. Arabi, Damon C. Scales, Mark Crowther, Wei Cheng, Michelle E. Kho, Sangeeta Mehta, Alexandre Tran, Deborah J. Cook, Philip S. Wells, Marc Carrier, Shane W. English, Kwadwo Kyeremanteng, Shannon M. Fernando, Robert A. Fowler, Morten Hylander Møller, Bram Rochwerg, and Behnam Sadeghirad
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, education.field_of_study, business.industry, medicine.drug_class, medicine.medical_treatment, Population, Intermittent pneumatic compression, Low molecular weight heparin, Compression stockings, Critical Care and Intensive Care Medicine, medicine.disease, Pulmonary embolism, law.invention, Randomized controlled trial, law, Heparin-induced thrombocytopenia, Meta-analysis, medicine, cardiovascular diseases, Cardiology and Cardiovascular Medicine, Intensive care medicine, education, business
Abstract: Background Critically ill adults are at increased risk of VTE, including DVT, and pulmonary embolism. Various agents exist for venous thromboprophylaxis in this population. Research Question What is the comparative efficacy and safety of prophylaxis agents for prevention of VTE in critically ill adults? Study Design and Methods Systematic review and network meta-analysis of randomized clinical trials (RCTs) evaluating efficacy of thromboprophylaxis agents among critically ill patients. We searched six databases (including PubMed, EMBASE, and Medline) from inception through January 2021 for RCTs of patients in the ICU receiving pharmacologic, mechanical, or combination therapy (pharmacologic agents and mechanical devices) for thromboprophylaxis. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates. Results We included 13 RCTs (9,619 patients). Compared with control treatment (a composite of no prophylaxis, placebo, or compression stockings only), low-molecular-weight heparin (LMWH) reduced the incidence of DVT (OR, 0.59 [95% credible interval [CrI], 0.33-0.90]; high certainty) and unfractionated heparin (UFH) may reduce the incidence of DVT (OR, 0.82 [95% CrI, 0.47-1.37]; low certainty). LMWH probably reduces DVT compared with UFH (OR, 0.72 [95% CrI, 0.46-0.98]; moderate certainty). Compressive devices may reduce risk of DVT compared with control treatments; however, this is based on low-certainty evidence (OR, 0.85 [95% CrI, 0.50-1.50]). Combination therapy showed unclear effect on DVT compared with either therapy alone (very low certainty). Interpretation Among critically ill adults, compared with control treatment, LMWH reduces incidence of DVT, whereas UFH and mechanical compressive devices may reduce the risk of DVT. LMWH is probably more effective than UFH in reducing incidence of DVT and should be considered the primary pharmacologic agent for thromboprophylaxis. The efficacy and safety of combination pharmacologic therapy and mechanical compressive devices were unclear. Trial Registry Open Science Framework; URL: https://osf.io/694aj
Published: 2022
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13. Essential Features of an Interstitial Lung Disease Multidisciplinary Meeting An International Delphi Survey

Author: Alan K. Y. Teoh, Anne E. Holland, Julie Morisset, Kevin R. Flaherty, Athol U. Wells, Simon L. F. Walsh, Ian Glaspole, Wim A. Wuyts, Tamera J. Corte, Huzaifa Adamali, J. Shirine Allam, Sofia Antillon, Katherina M. Antoniou, Rodrigo Athanazio, Sergey Avdeev, Alexander Averyanov, Arata Azuma, Bruno Baldi, Elisabetta Balestro, Rebecca Bascom, Shalini Bastiampillai, Lutz Beckert, Jü¨ergen Behr, Paul Beirne, David Bennett, Raphael Borie, Demosthenes Bouros, Ben Brockway, Kevin Brown, Francisco Javier Callejas González, Diego Castillo, Ronald Chacon Chaves, Daniel Chambers, Sally Chapman, Nazia Chaudhuri, Harold Collard, Vincent Cottin, Bruno Crestani, Jesper Rømhild Davidsen, Devesh J. Dhasmana, Sahajal Dhooria, Juan Ignacio Enghelmayer, Alexandre Todorovic Fabro, Puneet Garcha, Nicole Goh, Alejandro Gomez, Christopher Grainge, Tomohiro Handa, Tristan Huie, Gary Hunninghake, Yoshikazu Inoue, Helen Jo, Kerri Johannson, Rene Jonkers, Eoin Judge, Yasemin Kabasakal, Leticia Kawano Dourado, Gregory Keir, Nasreen Khalil, Yet Hong Khor, Melissa King Biggs, Maria Kokosi, Yasuhiro Kondoh, Vasillis Kouranos, Michael Kreuter, David Lederer, Su Ying Low, Joachim Mü¨ller Quernheim, Toby Maher, Eliane Mancuzo, George Margaritopoulos, Carol Mason, Mariano Mazeini, Nesrin Mogulkoc, Maria Molina, Yuben Moodley, António Morais, Anoop Nambiar, Imre Noth, Hilario Nunes, Takashi Ogura, Oguzhan Okutan, Nina Patel, Carlos Pereira, Wojciech Piotrowski, Venerino Poletti, Silvia Quadrelli, Elzbieta Radzikowska, Pilar Rivera Ortega, Christopher J. Ryerson, Mauricio Salinas, Rafaela Sanchez, Recep Savas, Moises Selman, Adrian Shifren, Maria Raquel Soares, Eman Sobh, Jin Woo Song, Paolo Spagnolo, Martina Sterclova, Irina Strambu, Mary E. Strek, Takafumi Suda, Gabriela Tabaj, Jasna Tekavec Trkanjec, Fatma Tokgoz Akyil, Claudia Toma, Rade Tomic, Hiromi Tomioka, Daniel Traila, Lauren Troy, Sergio Trukillo, Argyrios Tzouvelekis, Carlo Vancheri, Brenda Elena Varela, Francesco Varone, Martina Vasakova, Elizabeth Veitch, Vanesa Vicens Zygmunt, Thomas Wessendorf, Glen Westall, Marlies Wijsenbeek, Margaret L. Wilsher, Jeremy Wrobel, Cesar Yoshito Fukuda, Chris Zappala, Pulmonary Medicine, University of St Andrews. School of Medicine, University of St Andrews. Infection and Global Health Division, AII - Amsterdam institute for Infection and Immunity, Pulmonology, and AII - Inflammatory diseases
Subjects: Pulmonary and Respiratory Medicine, PNEUMONIA, medicine.medical_specialty, Respiratory System, Delphi method, NDAS, Interstitial lung disease, THORACIC SOCIETY, R Medicine (General), DIAGNOSIS, behavioral disciplines and activities, Delphi, 03 medical and health sciences, 0302 clinical medicine, Lung diseases, interstitial/diagnosis, Multidisciplinary approach, Delphi technique, Medicine, Humans, CRITERIA, Medical physics, 030212 general & internal medicine, Pulmonologists, Essential features, Science & Technology, business.industry, STATEMENT, respiratory system, medicine.disease, R1, respiratory tract diseases, body regions, surgical procedures, operative, 030228 respiratory system, AGREEMENT, Multidisciplinary meeting, business, Surveys and questionnaires, CONSENSUS, Life Sciences & Biomedicine
Abstract: Supported by the National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis (GNT1116371), and by foundation partner, Boehringer Ingelheim, and program partners, Roche and Galapagos. Rationale : The interstitial lung disease (ILD) multidisciplinary meetings (MDM), composed of pulmonologists, radiologists, and pathologists, is integral to the rendering of an accurate ILD diagnosis. However, there is significant heterogeneity in the conduct of ILD MDMs, and questions regarding their best practices remain unanswered. Objectives : To achieve consensus among ILD experts on essential components of an ILD MDM. Methods : Using a Delphi methodology, semi-structured interviews with ILD experts were used to identify key themes and features of ILD MDMs. These items informed two subsequent rounds of online questionnaires that were used to achieve consensus among a broader, international panel of ILD experts. Experts were asked to rate their level of agreement on a five-point Likert scale. An a priori threshold for consensus was set at a median score 4 or 5 with an interquartile range of 0. Results : We interviewed 15 ILD experts, and 102 ILD experts participated in the online questionnaires. Five items and two exploratory statements achieved consensus on being essential for an ILD MDM following two questionnaire rounds. There was consensus that the presence of at least one radiologist, a quiet setting with a visual projection system, a high-quality chest high-resolution computed tomography, and a standardized template summarizing collated patient data are essential components of an ILD MDM. Experts also agreed that it would be useful for ILD MDMs to undergo an annual benchmarking process and a validation process by fulfilling a minimum number of cases annually. Twenty-seven additional features were considered to be either highly desirable or desirable features based on the degree of consensus. Although our findings on desirable features are similar to the current literature, several of these remain controversial and warrant further research. The study also showed an agreement among participants on several future concepts to improve the ILD MDM, such as performing regular self-assessments and conducting research into shared practices to develop an international expert guideline statement on ILD MDMs. Conclusions : This Delphi study showed consensus among international ILD experts on essential and desirable features of an ILD MDM. Our data represent an important step toward potential collaborative research into future standardization of ILD MDMs. Postprint
Published: 2022
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14. Resident education in congenital heart surgery does not compromise outcomes

Author: Wendy J. Mack, Winfield J. Wells, Vaughn A. Starnes, John D. Cleveland, Richard W. Kim, Cynthia Herrington, Michael E. Bowdish, Kristopher Kallin, and S. Ram Kumar
Subjects: Heart Defects, Congenital, Pulmonary and Respiratory Medicine, medicine.medical_specialty, 030204 cardiovascular system & hematology, Logistic regression, Odds, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Outcome Assessment, Health Care, medicine, Humans, Hospital Mortality, Cardiac Surgical Procedures, Surgeons, Social Responsibility, business.industry, Patient Selection, Internship and Residency, Thoracic Surgery, Odds ratio, Length of Stay, medicine.disease, Comorbidity, Confidence interval, 030228 respiratory system, Cardiothoracic surgery, Preceptorship, Emergency medicine, Propensity score matching, Cohort, Surgery, Clinical Competence, Cardiology and Cardiovascular Medicine, business
Abstract: Objective Most of all congenital cardiac surgical programs participate in public outcomes reporting. The primary end point is transparency. In this era, academic programs with surgical residents face the challenge of producing outstanding results while allowing residents to learn by doing. We sought to understand the effect of education on our surgical outcomes. Methods We collected data for all American Board of Thoracic Surgery index cases done at our institution over a 10-year period. We identified 3406 cases and categorized them into 2 groups according to primary surgeon: attending (2269) versus resident (1137). In a multivariable logistic regression model we examined the effect of operating surgeon on in-hospital mortality, major morbidity, and length of stay. We used propensity score matching subsequently to balance differences between cohorts, and multivariable logistic regression was repeated. Results Using the entire cohort, multivariable logistic regression model adjusted for age, sex, weight, lack of preoperative comorbidity, presence of preoperative respiratory failure, The Society of Thoracic Surgeons--European Association for Cardio-Thoracic Surgery category, and need for deep hypothermic circulatory arrest, showed a higher odds of survival in the resident cohort (odds ratio, 1.484; 95% confidence interval, 0.998-2.206; P = .05). Propensity score matching identified 1137 pairs of attending and resident cases with well-balanced preoperative variables. Logistic regression modeling using the matched cohort showed equivalent 30-day mortality, 30-day major morbidity, and length of stay. Conclusions There was no difference in mortality, major morbidity, or length of stay when similar cases were compared that were operated on by attendings versus those by a resident. Effectively educating congenital heart surgeons without compromising an operation's quality requires thoughtful approach, including case selection and graded responsibility.
Published: 2022
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15. Effect of Metabolic Syndrome on Anatomy and Function of the Lower Urinary Tract Assessed on MRI

Author: Lu Mao, Christopher L. Brace, Alex P. Tannenbaum, Diego Hernando, Lucille E. Anzia, William A. Ricke, Matthew D Grimes, Samuel D. Koebe, Shane A. Wells, Alejandro Roldán-Alzate, and Cody Johnson
Subjects: Male, medicine.medical_specialty, Urology, Urinary system, Urinary Bladder, Article, Body Mass Index, Muscle hypertrophy, Lower Urinary Tract Symptoms, Lower urinary tract symptoms, Prostate, Bayesian multivariate linear regression, Prevalence, medicine, Humans, In patient, Correlation of Data, Metabolic Syndrome, Pelvic MRI, business.industry, Hypertrophy, Organ Size, Middle Aged, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Female, Symptom Assessment, Metabolic syndrome, business
Abstract: Objective To investigate the relationship between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) with functional and anatomic changes of the lower urinary tract with MRI. Materials and Methods The bladder and prostate of 95 subjects (56M, 39F) were segmented on T2-weighted pelvic MRI using Materialize Mimics 3D software. Bladder wall volume (BWV), post-void residual (PVR) and prostate volume (PV) were quantified from the 3D renderings. LUTS were quantified using validated questionnaires administered at the time of MRI. Wilcoxin rank sum, win ratio and chi-square tests were used to correlate symptom scores, BWV, PVR and PV in patients 1) without vs with MetS, 2) with mild (IPSS or UDI-6: 0-7) vs moderate-severe (IPSS: 8-35 or UDI-6: ≥8) and 3) normal vs enlarged prostates (>40cm3). Multivariate linear regression was used to determine predictors for BWV, PVR and PV. Results Men with MetS had increased BWV (66.8 vs 51.1cm3, P = .003), higher PVR (69.1 vs 50.5cc, P= .05) and increased PV (67.2 vs 40.1cm3, P= .01). Women without and with MetS had similar BWV, PVR and LUTS (P= .3-.78). There was no difference in prevalence of MetS, BWV, PVR or PV in men or women with mild vs moderate-severe LUTS (P = .26-.97). Men with enlarged prostates were more likely to have MetS (P = .003). There was no difference in BWV, PVR and LUTS for men with normal vs enlarged prostates (P= .44-.94). In men, BWV was highly correlated with MetS (P = .005) on regression analysis. Conclusion MetS leads to detrusor hypertrophy and may contribute to impaired bladder function, likely related to the effect on the prostate.
Published: 2022
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16. Dural arteriovenous fistulas in cerebral venous thrombosis

Author: Marcel Arnold, Maryam Mansour, Martin Punter, Christophe Cognard, Blake F Giarola, Fabiola Serrano, Mayte Sánchez van Kammen, Nicole A Chiota-McCollum, Masoud Ghiasian, Carlos Garcia-Esperon, Erik Lindgren, Katarina Jood, William Allingham, Jukka Putaala, Sini Hiltunen, Susanna M. Zuurbier, Eike I. Piechowiak, Jeremy Wells, Jonathan M. Coutinho, Mirjam Rachel Heldner, Suzanne M. Silvis, Turgut Tatlisumak, Antonio Arauz, Timothy Kleinig, Alexandros Rentzos, HUS Neurocenter, Department of Neurosciences, University of Helsinki, Neurologian yksikkö, and Clinicum
Subjects: long-term outcome, SINUS THROMBOSIS, medicine.medical_specialty, PROGNOSIS, Population, 610 Medicine & health, 030204 cardiovascular system & hematology, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, Dural arteriovenous fistulas, Interquartile range, Modified Rankin Scale, follow-up, medicine, EPIDEMIOLOGY, education, Stroke, dural arteriovenous fistula, Sigmoid sinus, education.field_of_study, business.industry, 3112 Neurosciences, cerebral venous thrombosis, NATURAL-HISTORY, IMPAIRMENT, medicine.disease, stroke, Thrombosis, 3. Good health, Surgery, Venous thrombosis, Neurology, Neurology (clinical), 610 Medizin und Gesundheit, INTRACRANIAL VASCULAR MALFORMATIONS, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND AND PURPOSE To explore the prevalence, risk factors, time correlation, characteristics and clinical outcome of dural arteriovenous fistulas (dAVFs) in a cerebral venous thrombosis (CVT) population. METHODS We included patients from the International CVT Consortium registries. Diagnosis of dAVF was confirmed centrally. We assessed the prevalence and risk factors for dAVF among consecutive CVT patients and investigated its impact on clinical outcome using logistic regression analysis. We defined poor outcome as modified Rankin Scale score 3-6 at last follow-up. RESULTS dAVF was confirmed in 29/1218 (2.4%) consecutive CVT patients. The median (interquartile range [IQR]) follow-up time was 8��(5-23) months. Patients with dAVF were older (median [IQR] 53��[44-61] vs. 41��[29-53] years; p��30 days: 39% vs. 7%; p��
Published: 2021
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17. IgE-Based Therapeutic Combination Enhances Antitumor Response in Preclinical Models of Pancreatic Cancer

Author: Kelly A. O'Connell, Manuel L. Penichet, Ying Huang, Paul M. Grandgenett, Christopher F. Nicodemus, Pankaj K. Singh, Thomas C. Caffrey, Spas Dimitrov Markov, Jill A. Poole, Prakash Radhakrishnan, Prathamesh Patil, Daisy Gonzalez, Ayrianne J. Crawford, Elizabeth M. Jaffee, Tracy R. Daniels-Wells, Surendra K. Shukla, James A. Grunkemeyer, Kamiya Mehla, Ragupathy Madiyalakan, Simon C. Shin, Ryan Hanson, Krysten E. Vance, Michael A. Hollingsworth, and Kirsten C. Eberle
Subjects: Cancer Research, biology, business.industry, medicine.medical_treatment, Cancer, Immunotherapy, Adenocarcinoma, Immunoglobulin E, medicine.disease, Article, Mice, Oncology, Pancreatic tumor, Pancreatic cancer, medicine, Cancer research, biology.protein, Animals, Humans, Antibody, business, Survival rate, MUC1, Carcinoma, Pancreatic Ductal
Abstract: Pancreatic ductal adenocarcinoma (PDAC) represents 3% of all cancer cases and 7% of all cancer deaths in the United States. Late diagnosis and inadequate response to standard chemotherapies contribute to an unfavorable prognosis and an overall 5-year survival rate of less than 10% in PDAC. Despite recent advances in tumor immunology, tumor-induced immunosuppression attenuates the immunotherapy response in PDAC. To date, studies have focused on IgG-based therapeutic strategies in PDAC. With the recent interest in IgE-based therapies in multiple solid tumors, we explored the MUC1-targeted IgE potential against pancreatic cancer. Our study demonstrates the notable expression of FceRI (receptor for IgE antibody) in tumors from PDAC patients. Our study showed that administration of MUC1 targeted-IgE (mouse/human chimeric anti-MUC1.IgE) antibody at intermittent levels in combination with checkpoint inhibitor (anti-PD-L1) and TLR3 agonist (PolyICLC) induces a robust antitumor response that is dependent on NK and CD8 T cells in pancreatic tumor-bearing mice. Subsequently, our study showed that the antigen specificity of the IgE antibody plays a vital role in executing the antitumor response as nonspecific IgE, induced by ovalbumin (OVA), failed to restrict tumor growth in pancreatic tumor-bearing mice. Utilizing the OVA-induced allergic asthma-PDAC model, we demonstrate that allergic phenotype induced by OVA cannot restrain pancreatic tumor growth in orthotopic tumor-bearing mice. Together, our data demonstrate the novel tumor protective benefits of tumor antigen-specific IgE-based therapeutics in a preclinical model of pancreatic cancer, which can open new avenues for future clinical interventions.
Published: 2021
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18. Efficacy and safety of primary thromboprophylaxis for the prevention of venous thromboembolism in patients with cancer and a central venous catheter: A systematic review and meta-analysis

Author: Rick Ikesaka, Tzu-Fei Wang, Phil Wells, Willem Brandt, Aurélien Delluc, Cameron Brown, Allen Li, and Marc Carrier
Subjects: medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Cancer, Venous Thromboembolism, Hematology, Odds ratio, equipment and supplies, Placebo, medicine.disease, law.invention, Venous thrombosis, Randomized controlled trial, law, Neoplasms, Internal medicine, Meta-analysis, Odds Ratio, medicine, Central Venous Catheters, Humans, business, Vascular Surgical Procedures, Central venous catheter
Abstract: Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer and is associated with significant morbidity and healthcare expenditure. The risk of VTE is increased following the insertion of a central venous catheter (CVC) for chemotherapy delivery and supportive care. The risks and benefits of primary thromboprophylaxis in patients with cancer and CVC are unclear.We sought to assess the rates of VTE and bleeding complications and to determine the efficacy and safety of primary thromboprophylaxis in adult patients with cancer and a CVC.A systematic search of MEDLINE, EMBASE, and all EBM was conducted. Randomized controlled trials (RCTs) of adult patients with cancer and a CVC receiving primary thromboprophylaxis compared to observation/placebo were included. The primary efficacy and safety outcomes were total VTE and major bleeding episodes, respectively.A total of 12 RCTs (3545 patients) were included in the analysis. The total rates of VTE were significantly lower in patients receiving thromboprophylaxis compared to those not receiving primary prevention (7.6% vs. 13%; Odds Ratio (OR) 0.51, 95% CI 0.32-0.82, p 0.01). The rates of major bleeding complications were not higher in patients receiving thromboprophylaxis (0.9% vs. 0.6%; OR 1.12, 95% CI 0.29-4.40, p = 0.87).Primary thromboprophylaxis significantly reduced the risk of VTE without increasing the risk of major bleeding complications in patients with cancer and CVC. Future studies are needed to confirm these findings.
Published: 2021
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19. Development of the Near Vision Presbyopia Task-based Questionnaire for use in evaluating the impact of presbyopia

Author: Nathan Johnson, Christopher J. Evans, Cheryl D. Coon, J. Jason Lundy, Ted Wells, Elaheh Shirneshan, Jonathan Stokes, Joanna Campbell, and David A Andrae
Subjects: Psychometrics, genetic structures, media_common.quotation_subject, Applied psychology, Health Informatics, Alternative assessment, Health Information Management, Cronbach's alpha, Reading (process), Qualitative research, medicine, Content validity, Psychometric analysis, Patient-reported outcome, media_common, Research, Construct validity, Presbyopia, Content-validity, medicine.disease, Public aspects of medicine, RA1-1270, Psychology, Age-related farsightedness
Abstract: Background Presbyopia is a progressive condition that reduces the eye’s ability to focus on near objects with increasing age. After a systematic literature review identified no existing presbyopia-specific patient-reported outcome (PRO) instruments meeting regulatory guidance, a new PRO instrument, the Near Vision Presbyopia Task-based Questionnaire (NVPTQ), was developed. Results To explore the patient experience with presbyopia, concept elicitation interviews were conducted with 20 presbyopic participants. The most frequently reported impacts were difficulty with reading menus/books/newspapers/magazines, reading on a cell phone/caller ID, and reading small print. Based on these results, a task-based PRO instrument (the NVPTQ) was developed instructing participants to complete four near-vision, paper-based reading tasks (book, newspaper, nutrition label, menu) under standardized settings, and subsequently assess their vision-related reading ability and associated satisfaction. The draft NVPTQ was cognitively debriefed with a sample of 20 presbyopes, which demonstrated that most participants interpreted the items as intended and endorsed the relevance of the concepts being assessed. After the qualitative research, the draft instrument was psychometrically tested using data from a Phase 2 study. Based on item-level analyses, all items in the NVPTQ demonstrated expected response option patterns and lacked substantial floor or ceiling effects. The reliability, validity, and responsiveness of the NVPTQ Performance and Satisfaction domain scores were assessed. All domains scores had large Cronbach’s coefficient α values and good test–retest statistics, indicating that the scores are internally consistent and produce stable values over time. The pattern of correlations with a concurrent measure of visual functioning (National Eye Institute Visual Function Questionnaire 25) demonstrated that the NVPTQ domain scores were related to an alternative assessment of near-vision activities. The NVPTQ domain scores were able to distinguish between groups that were known to differ on the clinical outcome of uncorrected near visual acuity, supporting the construct validity of these scores. The NVPTQ domain scores showed evidence of responsiveness to change by being able to distinguish between groups defined as improved and not improved based on patient-reported and clinical outcomes. Conclusions This research has resulted in a content-valid and psychometrically sound instrument designed to evaluate vision-related reading ability and satisfaction with vision-related reading ability. Trial registration: ClinicalTrials.gov NCT02780115. Registered 23 May 2016, https://www.clinicaltrials.gov/ct2/show/NCT02780115?term=NCT02780115&draw=2&rank=1.
Published: 2021

20. Evorpacept alone and in combination with pembrolizumab or trastuzumab in patients with advanced solid tumours (ASPEN-01): a first-in-human, open-label, multicentre, phase 1 dose-escalation and dose-expansion study

Author: Hyun Cheol Chung, Jeeyun Lee, Tracy C. Kuo, Won Seog Kim, Feng Jin, Sophia Randolph, Nehal Lakhani, Yung-Jue Bang, Rafael Santana-Davila, Philip Fanning, Wells A. Messersmith, Pierre Squifflet, Jaume Pons, Justin F. Gainor, Hong I. Wan, Keun-Wook Lee, Laura Q.M. Chow, F.S. Hodi, and Patricia LoRusso
Subjects: Male, medicine.medical_specialty, Maximum Tolerated Dose, Pembrolizumab, Neutropenia, Antibodies, Monoclonal, Humanized, Gastroenterology, Loading dose, Trastuzumab, Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Adverse effect, Lung cancer, Aged, business.industry, Middle Aged, Prognosis, medicine.disease, Immunoglobulin Fc Fragments, Oncology, Tolerability, Response Evaluation Criteria in Solid Tumors, Female, business, Follow-Up Studies, medicine.drug
Abstract: Summary Background Both innate and adaptive immune responses are important components of anticancer immunity. The CD47–SIRPα interaction could represent an important pathway used by tumour cells to evade immune surveillance. We aimed to evaluate the safety, pharmacokinetics, pharmacodynamics, and anticancer activity of evorpacept (also known as ALX148), a high-affinity CD47-blocking protein with an inactive IgG Fc region in patients with solid tumours. Methods We did a first-in-human, open-label, multicentre, phase 1 dose-escalation and dose-expansion study at nine hospitals and one clinic in the USA and Korea. Eligible patients for the dose-escalation and safety lead-in phases were aged 18 years or older with histological or cytological diagnosis of advanced or metastatic solid tumours with no available standard therapy, measurable or unmeasurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. In the dose-escalation phase, which used a 3 + 3 design, patients received intravenous evorpacept at either 0·3, 1, 3, or 10 mg/kg once per week in 21-day cycles, or 30 mg/kg once every other week in 28-day cycles. In the safety lead-in phase, patients were given the maximum tolerable dose of evorpacept from the dose-escalation phase plus either intravenous pembrolizumab (200 mg administered once every 3 weeks) or intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg once every 3 weeks). In the dose-expansion phase, additional patients aged 18 years or older with second-line or later-line advanced malignancies were enrolled into three parallel cohorts: those with head and neck squamous cell carcinoma (HNSCC) and those with non-small-cell lung cancer (NSCLC) were given the maximum tolerated dose of evorpacept plus intravenous pembrolizumab (200 mg administered once every 3 weeks), and patients with HER2-positive gastric or gastroesophageal junction cancer were given the maximum tolerated dose of evorpacept plus intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg once every 3 weeks) until disease progression, voluntary withdrawal from the study, or unacceptable toxicity. The primary endpoint was the maximum tolerated dose of evorpacept administered as a single agent and in combination with pembrolizumab or trastuzumab, measured by the occurrence of dose-limiting toxicities during the first cycle, and was assessed in all patients who had received at least one dose of evorpacept. Secondary outcomes included the safety, tolerability, and antitumour activity of evorpacept, alone or in combination with pembrolizumab or trastuzumab. The primary outcome, safety, and tolerability were assessed in all patients who had received at least one dose of evorpacept, and antitumour activity was assessed in those who recieved at least one dose of study treatment and underwent at least one post-baseline tumor assessment. This trial is registered with ClinicalTrials.gov , NCT03013218 . Findings Between March 6, 2017, and Feb 21, 2019, 110 patients received single-agent evorpacept (n=28), evorpacept plus pembrolizumab (n=52), or evorpacept plus trastuzumab (n=30), and were included in the safety analysis. Median follow-up was 29·1 months (95% CI not calculable [NC]–NC) in the single-agent cohort, 27·0 months (25·1–28·8) in the evorpacept plus pembrolizumab cohort, and 32·7 months (27·0–32·7) in the evorpacept plus trastuzumab cohort. Two (7%) dose-limiting toxicities in the first cycle were reported in patients who received single-agent evorpacept; neutropenia with an associated infection in one patient with gastroesophageal junction cancer who received 3 mg/kg once per week, and thrombocytopenia with associated bleeding in one patient with pancreatic cancer who received 30 mg/kg once every other week. No maximum tolerated dose was reached; the maximum administered doses were 10 mg/kg once per week or 30 mg/kg once every other week. The 10 mg/kg once per week dose was used in the expansion cohorts in combination with pembrolizumab or trastuzumab. The most common grade 3 or worse treatment-related adverse events were thrombocytopenia with single-agent evorpacept (two [7%] patients) and evorpacept plus pembrolizumab (two [4%]), and thrombocytopenia (two [7%]) and neutropenia (two [7%]) with evorpacept plus trastuzumab. In patients who received single-agent evorpacept, four treatment-related serious adverse events were reported. Five serious treatment-related adverse events related to evorpacept plus pembrolizumab were reported, and one serious adverse event related to evorpacept plus trastuzumab was reported. In response-evaluable patients in the dose-escalation phase (n=15) receiving single-agent evorpacept once per week, four (27%) had a best overall response of stable disease (two received 0·3 mg/kg, one received 3 mg/kg, and one received 10 mg/kg); in the 11 patients who received single-agent evorpacept at the highest dose of 30 mg/kg once every other week, two (18%) had stable disease. In the dose-expansion cohort, overall responses were recorded in four (20·0%; 95% CI 5·7–43·7) of 20 patients with HNSCC who received evorpacept plus pembrolizumab, in one (5·0%; 0·1–24·9) of 20 patients with NSCLC who received evorpacept plus pembrolizumab, and in four (21·1%; 6·1–45·6) of 19 patients with gastric or gastroesophageal junction cancer who received evorpacept plus trastuzumab. Interpretation The safety findings support the use of evorpacept in combination with pembrolizumab or trastuzumab for patients with advanced solid tumours. Preliminary antitumour activity results support future investigation of evorpacept combined with pembrolizumab or trastuzumab in patients with HNSCC, gastric or gastroesophageal junction cancer, and NSCLC. Funding ALX Oncology.
Published: 2021
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21. Exploring Culturally Responsive Religious and Spirituality Health Care Communications among African Americans with Advanced Heart Failure, Their Family Caregivers, and Clinicians

Author: Rachel Wells, Karen E. Steinhauser, Marie Bakitas, Olivio J. Clay, J. Nicholas Dionne-Odom, Raegan W. Durant, and Deborah Ejem
Subjects: Male, Gerontology, 03 medical and health sciences, 0302 clinical medicine, 030502 gerontology, Spirituality, Health care, Humans, Medicine, General Nursing, Heart Failure, business.industry, Family caregivers, Original Articles, General Medicine, Middle Aged, medicine.disease, Black or African American, Anesthesiology and Pain Medicine, Caregivers, 030220 oncology & carcinogenesis, Heart failure, Culturally responsive, Female, 0305 other medical science, business, Delivery of Health Care
Abstract: BACKGROUND: Religion and spirituality (R/S) impact how African Americans (AAs) cope with serious illness, yet are infrequently addressed in patient-clinician communication. OBJECTIVES: To explore AAs with advanced heart failure and their family caregivers' (FCGs) preferences about R/S in patient-clinician communication. METHODS: An embedded qualitative interview within a parent randomized trial about the role of R/S in the illness experience and in clinician interactions with patients and FCGs in a Southern U.S. state. Transcribed interviews were analyzed using constant comparative analysis to identify emergent themes. RESULTS: AA participants (n = 15) were a mean age of 62 years, were female (40%), and had >high school diploma/GED (87%). AA FCGs (n = 14) were a mean age of 58; were female (93%); had >high school diploma/General Education Development (GED) (93%); and were unemployed (86%). Most (63%) were patients' spouses/partners. All patients and FCGs were Protestant. Participants reported the critical role of R/S in living with illness; however, patients' and FCGs' perspectives related to inclusion of R/S in health care communications differed. Patients' perspectives were as follows: (1) R/S is not discussed in clinical encounters and (2) R/S should be discussed only if patient initiated. FCGs' perspectives about ideal inclusion of R/S represented three main diverging themes: (1) clinicians' R/S communication is not a priority, (2) clinicians should openly acknowledge patients' R/S beliefs, and (3) clinicians should engage in R/S conversations with patients. CONCLUSION: Key thematic differences about the role of R/S in illness and preferences for incorporating R/S in health care communications reveal important considerations about the need to assess and individualize this aspect of palliative care research and practice.
Published: 2021
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22. Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

Author: Stephen R Knight, Catherine A Shaw, Riinu Pius, Thomas M Drake, Lisa Norman, Adesoji O Ademuyiwa, Adewale O Adisa, Maria Lorena Aguilera, Sara W Al-Saqqa, Ibrahim Al-Slaibi, Aneel Bhangu, Bruce M Biccard, Peter Brocklehurst, Ainhoa Costas-Chavarri, Kathryn Chu, Anna Dare, Muhammed Elhadi, Cameron J Fairfield, J Edward Fitzgerald, Dhruv Ghosh, James Glasbey, Mark I. van Berge Henegouwen, J.C. Allen Ingabire, T Peter Kingham, Marie Carmela Lapitan, Ismaïl Lawani, Bettina Lieske, Richard Lilford, Janet Martin, Kenneth A McLean, Rachel Moore, Dion Morton, Dmitri Nepogodiev, Faustin Ntirenganya, Francesco Pata, Thomas Pinkney, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Aya Riad, Hosni Khairy Salem, Joana Simões, Richard Spence, Neil Smart, Stephen Tabiri, Hannah Thomas, Thomas G Weiser, Malcolm West, John Whitaker, Ewen M Harrison, Arben Gjata, Maria Marta Modolo, Sebastian King, Erick Chan, Sayeda Nazmun Nahar, Ade Waterman, Dominique Vervoort, Alemayehu Ginbo Bedada, Bernardo De Azevedo, Ana Gabriela Figueiredo, Manol Sokolov, Venerand Barendegere, Gerald Ekwen, Arnav Agarwal, Qinyang Liu, Juan Camilo Correa, Kalisya Luc Malemo, Jacques Bake, Jakov Mihanovic, Kamila Kuncarová, Julius Orhalmi, Hosni Salem, Jyri Teras, Aristotelis Kechagias, Alexis P Arnaud, Judith Lindert, Vasileios Kalles, Maria-Lorena Aguilera-Arevalo, Gustavo Recinos, Zsolt Baranyai, Basant Kumar, Harish Neelamraju Lakshmi, Sanoop Koshy Zachariah, Philip Alexander, Sunil Kumar Venkatappa, C Pramesh, Radhian Amandito, Christina Fleming, Luca Ansaloni, Gianluca Pellino, Ahmed M. Altibi, Ibrahim Nour, Intisar Hamdun, Ali M. Ghellai, Donatas Venskutonis, Tomas Poskus, Justas Zilinskas, Precious Malemia, Yong Yong Tew, Elaine Borg, Sarah Ellul, fatima Zahraa Wafqui, David W Borowski, Anne Sophie van Dalen, Cameron Wells, Harissou Adamou, Adesoji Ademuyiwa, Adewale Adisa, Kjetil Søreide, Sara Al Saqqa, Osaid Alser, Haya Tahboub, Helmut Alfredo Segovia Lohse, Sebastian Shu Yip, Piotr Major, António Sampaio Soares, Matei Razvan Bratu, Andrey Litvin, Armen Vardanyan, JC Allen Ingabire, Ahmad Gudal, Naif Albati, Jovan Juloski, Miran Rems, Sarah Rayne, Stephanie Van Straten, Yoshan Moodley, Irene Ortega Vázquez, Jaime Ruiz-Tovar, Kithsiri Janakantha Senanayake, Sujeewa Priyantha Bandara Thalgaspitiya, Omer Abdelbagi Omer, Anmar Homeida, Yucel Cengiz, Daniel Clerc, Muhammad Alshaar, Hanen Bouaziz, Yuksel Altinel, Matthew Doe, Maryna Freigofer, Ella Teasdale, Rakan Kabariti, Joshua Michael Clements, Stephen Richard Knight, Ahsan Ashfaq, Ijeoma Azodo, Gabriela Wagner, Ivan Trostchansky, Mayaba Maimbo, David Linyama, Helidon Nina, Amanda Zeko, Claudio Gabriel Fermani, Santiago Villalobos, Federico Carballo, Pablo Farina, Sebastian Guckenheimer, Marilla Dickfos, Ankit Ajmera, Chester Chong, Ralph Gourlay, Sikandar Hussaini, Yi Jia Lee, Adeeb Majid, Peter Martin, Rebecca Miles, Owen James Morris, Jamie Phua, William Ridley, Tarunpreet Saluja, Ryan Renxin Tan, Jen Teh, Anna Wells, Bharti Arora, Qaasim Dollie, Debbie Ho, Yanru Ma, Omattage Mahasha Perera, Anthony Truong, Amanda Caroline Dawson, Bryan Lim, Upuli Pahalawatta, Jacqueline Phan, Xiao-Ming Sarah Woon-Shoo-Tong, Andrea Yeoh, Lillian Charman, Andrew Drane, Sharon Laura, Charmaine Chu Wen Lo, Amy Mozes, Rita Poon, Hao Han Tan, Ellen Wall, Prakshi Chopra, Jasmine De Giovanni, Bal Dhital, Brian Draganic, Alexander Duller, Jonathan Gani, Yao Kuan Goh, Jun Young Jeong, Brendan McManus, Prakash Nagappan, Peter Pockney, Anya Rugendyke, Mahsa Sarrami, Stephen Smith, Vanessa Wills, Hsu Ven Wong, Geoffrey Ye, Geoffrey Zhang, Ethan Brooker, Daniel Feng, Bonnie Lau, Carlin Ngai, Sarah Birks, David Gyorki, Jaime Otero de Pablos, Ali Abbosh, Chris Gillespie, Ahmed Mahmoud, Bianca Kwan, Joshua Lawson, Andrea Warwick, Janne Bingham, Andrew J Cockbain, Nagendra Naidu Dudi-Venkata, Jordan Ellaby-Hall, Ben Finlay, Emily Humphries, Jade Pisaniello, Monique Pisaniello, Salma Salih, Tarik Sammour, Haidar Hadri Abd Wahab, April De Silva, Nicola Hayward, Kartik Iyer, Guy Maddern, Gian Andrea Prevost, Naga Annapureddy, Krishna Pranathi Settipalli, Jeremy Yeo, Lucy Hempenstall, Lily Pham, Shaun Purcell, Cherry Talavera, Ashish I Vaska, Gurpreet Chaggar, Phillip Chrapko, Annelise Cocco, Sarah Michelle Crystal Jade Coulter-Nile, Grahame Ctercteko, James French, Houchen Gong, Martijn Gosselink, Thuvarahan Jegathees, Ivan Jin, Michelle Kalachov, Kathryn Kiefhaber, Katherine Lee, Jason Luong, Steven Phan, Henry Pleass, Kelly Veale, Zhi Zeng, Angela Au, Ashe DeBiasio, Idy Deng, Jananee Myooran, Amrita Nair, Peter Stewart, Anton Stift, Lukas Walter Unger, Kerstin Wimmer, Nabila Ahmed, Syed Hasan, Saber Rahman, Margaret O'Shea, Greg Padmore, Adrian Peters, Pietro Perduca, Guenda Pulcina, Nicolas Tinton, Frederic Buxant, Elsa Dabin, Giulia Garofalo, Francis Dossou, Freddy Houehanou Rodrigue Gnangnon, Yacoubou Imorou Souaibou, Pako Motlaleselelo, Omphile Tlhomelang, Igor Lima Buarque, Gustavo Mendonça Ataíde Gomes, Aldo Vieira Barros, Ilia Batashki, Nikolai Damianov, Vladislav Stoyanov, Dragomir Dardanov, Svilen Maslyankov, Plamen Petkov, George Todorov, Evgeni Zhivkov, Aygulya Akisheva, Miguel Angel Castilla Moreno, Geno Genov, Ivelina Ilieva, Tsvetomir Ivanov, Martin Karamanliev, Azhar Khan, Emil Mitkov, Tsanko Yotsov, Boyko Atanasov, Nikolay Belev, Mihail Slavchev, Carlos Nsengiyumva, Elgan Jones, Simon Stock, Steve Kyota, James Brown, Tresor Mabanza K., Lemery Nigo Samuel, Chidi Otuneme, Ngwang Prosper, Franklin Umenze, Marylise Boutros, Natasha Caminsky, Sinziana Dumitra, Richard Garfinkle, Dominique Morency, Ebram Salama, Alexander Banks, Lorenzo Ferri, Haitian He, Amit Katz, Alexander Sender Liberman, Sarkis Meterissian, Allison Pang, Elena Parvez, Usmaan Hameed, Fahima Osman, Sangita Sequeira, Natalie Coburn, Alisha Jaffer, Paul Karanicolas, Matthew Mosseler, Reilly Musselman, Xinyuan Liu, Ching Wan Yip, Juan Sebastian Garces-Otero, Carolina Guzman, Sebastian Sierra, Andres Uribe Valencia, Paulo Andrés Cabrera Rivera, Saul Camelo, Andrea Gonzalez, Alejandro González-Orozco, Manuel Santiago Mosquera Paz, Carlos J- Perez Rivera, Felipe Gonzalez, Andres Isaza-Restrepo, Laura Nino- Torres, Natalia Arias Madrid, Maria Clara Mendoza Arango, Justin Tsandiraki, Damir Jemendžic, Branislav Kocman, Oliver Šuman, Renata Canic, Darko Jurišic, Ivana Karakas, Ana Krizanovic Rupcic, Vlatka Pitlovic, Josip Samardžic, Mario Kopljar, Ivan Bacic, Edgar Domini, Robert Karlo, Danijela Miljanic, Andrea Simic, Mariam Ahmed, Majdi Al Nassrallah, Rabiya Altaf, Talal Amjad, Ruba Eltoum, Heba Haidar, Alhassan Hassan, Omar Khalil, Marwan Qasem, Rommel Ramesh, Gautham Sajith, Maham Wisal, Jan Žatecký, Michele Bujda, Katerina Jirankova, Ales Paclik, Aya Abdallah, Mariam Abdulgawad Almogy, Esraa Ayman El-sawy, Ahmed Moustafa ElFayoumy, Nourhan Elghareeb, Nourhan Ahmed Esmat, Ahmed Fadel, Abdullah Habater, Heba Hamdy, Amr Hefni, Marwa Kamal, Norhan Mohamed Abobakr, Ahmed Sayed, Nancy Shaker, Ehab Taha, Hoda Tharwat, Omar Zakaria, Ibrahem Abdelmotaleb, Ali Al-Dhufri, Hamza S. Al-Himyari, Enas El sheikh, Asmaa Eldmaty, Aya Elkhalawy, Ahmed M.Elkhashen, Kithara Magdy, Safa Mostafa, Habib Doutoum Sadia, Mohamed mahmoud Saleh, Dina Samir, Mohamed Yahia Mohamed Ali, Mahmoud A. Nassar, Samar Abdelhady, Aly Abdelrazek, Israa Abdelsalam, Aya El-Sawy, Eman Essam, Mohamed Gadelkarim, Khaled Ghaly, Mohamed Hassabalnaby, Rana Masarani, Nourhan Mohamed Shaaban, Ahmed Sabry, Menatalla Salem, Nourhan Akram Soliman, Diaaaldin Zahran, Moustafa Ramadan Abou El.soud, Esraa Tarek Badr, Hala Borham, Nehal Elmeslemany, Mohammad Elsayed, Fawzia Elsherif, Sara Eslam, Gehad Gaber, Sondos Ibrahim, Yara Kamh, Abdelrahman Mahmoud, Shimaa gamal Mohamed, Eman Morshedy, Cinderella Omar, Fatima Salem Soliman, Shaza Abdelkawy, Naglaa Abdelmohsen, Mahmoud Abdelshakour, Ahmed Dahy, Norhan Gamal, Mohammed Gamal, Ahmad Hasan, Helal Hetta, Nehad Mousa, Mohamed Omar, Somia Rabie, Mahmoud Saad, Bakeer Saleh, Marwa Sayed Mohamed, Muhammad Shawqi, Heba Abdelhady Mousa, Mostafa Alnoury, Mohamed Elbealawy, Ahmed Elshafey, Muhammad Essam Ibrahim El Desouki Muhammad Ahmed, Mennatullah Ghonaim, Fawzy Hgag, Mohamed Ibrahim, Mahmoud Morsy, Mohamed Reda Loaloa, Ahmed Refaat, Hadeer Samir, Fatma Shahien, Mohamed Sobhy, Fathy Sroor, Esraa Abdellatif, Marina Adel, Amr Abdelghani Afifi, Eman Afifi, Marco Antaky, Amr Dawoud, Naira El Zoghby, Amira El-remaily, Ali Abdelazez Elzanfaly, Ahmed Gadallah, Fatma Alzahraa Gamal, Omar Hashem, Shrouk Medhat Youssef, Aliaa Muhammad Attyah, Malak Munir, Omar Shazly, Esraa Taha, Karim Wilson, Sawsan Adel, Asmaa Ali, Esraa Eid, Esraa Elhelow, Marwa Elmahdy, Bassant Elshatby, Amany Hossam el-din Zakaria, Ahmad Hossny, Eman Ibrahim, Ahmed M.Yonis, Maram Metwalli, Basant Yousry, Esraa Zid, Mina A Yacoub, Ahmed Abdelhakim, Nervana Abouelsoad, Mo'min Alkhatib, Ahmed Ashraf, Alaa Ashraf, Yasmin Elazab, Mahmoud Elfanty, Osama Elkabir, Mai Elsayed, Ahmed Elshimy, Hager Elsobky, John Eskander, Ahmed Gad, Ward Hamsho, Noura Khaled Abdelwahed, Menna Magdy, Dalia Moharam, Abeer Osama, Shereen Ramadan, Radwa Roum, Taqwa Sayed, Tarneem Shehada, Ahmed Mohy Zidan, Khalid Abbas, Amr Ali, Mohamed Attia, Mohamed Balata, Ayman El Nakeeb, Mohamed Ibrahim Elsayed Elewaily, Ahmed Elfallal, Hossam Elfeki, Ahmed Elkhadragy, Sameh Emile, Helmy Ezzat, Hasnaa Hosni, Islam Mansour, Waleed Omar, Gehad Othman, Kareem Sadek, Mostafa Shalaby, Noura Shehab-Eldeen, Rawda Anas khalifa, Helmy Badr, Mostafa Eldeep, Ahmed Eldeep, Amany Eldoseuky mohammed, Salwa Khallaf, Eman Magdy Hegazy, Rokia Mahmoud, Pola Mikhail, Mahmoud Morsi, Sara Mowafy, Dina Raafat, Amina Safy, Marwa Sera, Ahmed shible Sera, Mostafa Salim Mohamed AbdAllah, Muhammad Abdelkader, Abdulrahman Osama Abdou, Ahmedgaber Ahmed, Shireen Gaafar, Fatma Ibrahim negm, Mina Lapic, Ahmed Maher, Hagar Mahmoud, Ahmed Mostafa, Mohamed Samir, Fatma Samy, Nourhan Semeda, Hind I. Shalaby, Alaa El-taweel, Ahmed Galal Elnagar, Ahmed Gamal Hemidan, Mohamed Hussein, Ahmed.A. Kandil, Mf Moawad, Ayat Allah Nasser Hamamah, Mostafa Soliman, Mohamed Abdelkhalek, Noura Abdelmaksoud Tawakel, Ahmed Mohamed Abdelwahed, Alrawy Abdou, Khalid Atallah, Mohammed Yasser Elsherbeny, Eman Emara, Mohamed Hamdy, Omar Hamdy, Amira Haron, Salma Ismail, Islam Hany Metwally, Nihal Mohamed Hamed Elgaml, Ahmed Nassar, Basel Refky, Mirna Sadek, Mahmoud Saleh, Asmaa Yunes, Mai Zakaria, Mohammed Zuhdy, Notila Fayed, Mohammed Mustafa Hassan Mohammed, Sander Kütner, Priit Melnik, Indrek Seire, Toomas Ümarik, Eppu Ainoa, Verner Eerola, Hanna Koppatz, Laura Koskenvuo, Ville Sallinen, Sini Takala, Jevgeni Katunin, Arto Turunen, Niki Christou, Muriel Mathonnet, Vincent Lavoue, Krystel Nyangoh Timoh, Lucie Soulabaille, Romain Lesourd, Aude Merdrignac, Laurent Sulpice, Benoît André, Elodie Chantalat, Charlotte Vaysse, Bertrand Dousset, Sebastien Gaujoux, Gregory Martin, Octavian Clonda, Domantas Juodis, Klaus Kienle, Andras Mravik, Samuel Palmer, Gabor Szabadhegyi, Anita Eseenam Agbeko, Solomon Gyabaah, Frank Enoch Gyamfi, Nuhu Naabo, Atta Owusu senior, Joseph Yorke, Frank Owusu, Francis Abantanga, Theophilus Teddy Kojo Anyomih, Abdul-Jalilu Mohammed Muntaka, Emmanuel Owusu Abem, Mohammed Sheriff, Paul M. Wondoh, Dimitrios Balalis, Dimitrios Korkolis, Georgios Gkiokas, Eirini Pantiora, Theodosios Theodosopoulos, Argyrios Ioannidis, Konstantinos Konstantinidis, Sofia Konstantinidou, Nikolaos Machairas, Anna Paspala, Anastasia Prodromidou, Christos Chouliaras, Konstantinos Papadopoulos, Ioannis Baloyiannis, Ioannis Mamaloudis, George Tzovaras, Ioanna Akrida, Maria-Ioanna Argentou, Stylianos Germanos, Evangelos Iliopoulos, Ioannis Maroulis, George Skroubis, George Theofanis, Christos Chatzakis, Orestis Ioannidis, Lydia Loutzidou, Panagiotis Karathanasis, Nikolaos Michalopoulos, Charalampos Theodoropoulos, Dimitrios Theodorou, Tania Triantafyllou, Zoe Garoufalia, Natasha Hasemaki, Michalis Kontos, Gregory Kouraklis, Stylianos Kykalos, Theodore Liakakos, Eustratia Mpaili, Alexandros Papalampros, Dimitrios Schizas, Athanasios Syllaios, Ekaterini Christina Tampaki, Antonios Tsimpoukelis, Maria Ioanna Antonopoulou, Eirini Deskou, Dimitrios K. Manatakis, Dimitrios Papageorgiou, Menelaos Zoulamoglou, Christos Anthoulakis, Michalis Margaritis, Nikolaos Nikoloudis, Veronica Campo, André Ceballos, Mario-Andrés Flores, Waleska Giron, Donghyun Ko, Gabriel Martinez, Verónica Rivera Lara, Nataly Rueda, Andres Sanchez, Jorge Carlos Guillermo Tejeda Garrido, Alvaro Eduardo Alvarez Rivera, Elvis Benjamin Bamaca Ixcajoc, Lilian Elizabeth Barreda Zelaya, Patricia Chacòn-Herrera, Ligia Margarita Corea Ruiz, Guillermo Echeverria-Davila, Mario Garcia, Danilo García, Edgar Fernando Gutiérrez Mayen, Noriega José, Nery Mazariegos, Diego Méndez, Michael Paniagua Espinoza, David Bardos, Marton Benke, Kristof Illes, Balint András Kokas, Réka Szabó, Akhila Appukuttan, Anjitha Asok, Vijaykumar D.k, Kapil Malik, Praveen Ravishankaran, Ritesh Tapkire, Guru Moorthy, Joyner Abraham, Ramesh Muthuvel, John Alapatt, Abhay Kattepur, Nizamudheen Pareekutty, Mebanshanbor Garod, Caleb Harris, Cliff Wanniang, Ashish Gupta, Deepak Nehra, Sanjeev Parshad, Rajgopal Acharya, Rajendra Badwe, Manish Bhandare, Urvashi Jain, Karishma Kirti, Nita Nair, Shailesh Shrikhande, Purvi Thakkar, Premkumar Anandan, Archana C S, Arun Holenarasipur Narasannaiah, Tejaswi Jagarlamudi, Rashmi M R, Mallikarjuna Manangi, Abhishek Raghavendra, K. Seshagiri Rao, Vinay S, Vinay Sajjan, Aneesh Shenoy, Santhosh Shivashankar Chikkanayakanahalli, Kavya Tharanath, Sushmita V, Peter Adidharma, Raksheeth Agarwal, Phebe Anggita Gultom, Ghafur Rasyid Arifin, Matthew Billy, Zatira Elfizri, Alessa Fahira, Devi Felicia, Triana Hardianti Gunardi, Nadya Johanna, Nadia Rahmadiani Nugrahadi, Sonar Soni Panigoro, Siti Rahmayanti, Retta Catherina Sihotang, Santi Yuanita Brata, Hadi Winoto, Nastaran Barati, Manoochehr Karami, Hamidreza Khorshidi, Homa Naderifar, Mazin A. Abdulla, Maggie Coleman, Ronan J Doherty, Rob Hannon, Brenda Murphy, Aine Stakelum, Des Winter, Lylas Aljohmani, Richard Farnan, Yeshey Seldon, Tanna Tan, Shriya Varghese, Mohammad Alherz, Muaaz Ather, Mohammad Bajilan, Vivien Graziadei, Isobel Pilkington, Omar Quidwai, Paul Ridgway, Haaris Shiwani, Abd al-Rahman Tahir, Eimear Blunnie, Daniel Burke, Niall Kennedy, Kate Macdonagh, Maeve O'Neill, Siobhan Rooney, Giuseppe Falco, Guglielmo Ferrari, Simone Mele, Gabriela Elisa Nita, Lara Ugoletti, Maurizio Zizzo, Gianmaria Confalonieri, Giovanni Pesenti, Fulvio Tagliabue, Gianluca Baronio, Deborah Ongaro, Giacomo Pata, Bruno Compagnoni, Renato Salvadori, Lucio Taglietti, Nicola D'Alessandro, Pierpaolo Di Lascio, Giovanni Pascale, Luca Bortolasi, Tommaso Campagnaro, Massimo Carlini, Giorgio Lisi, Davide Lombardi, Corrado Pedrazzani, Domenico Spoletini, Giulia Turri, Paola Violi, Donato Francesco Altomare, Fabrizio Aquilino, Nicola Musa, Vincenzo Papagni, Arcangelo Picciariello, Leonardo Vincenti, Dario Andreotti, Savino Occhionorelli, Matteo Tondo, Stefano Maria Massimiliano. Basso, Riccardo Cirelli, Marco Enrico Mario Maino, Guglielmo Niccolò Piozzi, Emanuele Picone, Rosa Scaramuzzo, Giovanni Sinibaldi, Alfonso Amendola, Lorenzo Anastasio, Luigi Bucci, Emanuele Caruso, Antonio Castaldi, Sara Di Maso, Vincenza Paola Dinuzzi, Giovanni Esposito, Maria Gaudiello, Mariano Cesare Giglio, Paola Antonella Greco, Gaetano Luglio, Andrea Manfreda, Ester Marra, Federica Mastella, Gianluca Pagano, Roberto Peltrini, Vincenzo Pepe, Michele Sacco, Viviana Sollazzo, Giovanni Spiezio, Ettore Cianchetti, Nunzia Menduni, Michele Maria Carvello, Francesca Di Candido, Antonino Spinelli, Fabio Corsi, Luca Sorrentino, Fabio Marino, Emanuele Luigi Giuseppe Asti, Luigi Bonavina, Emanuele Rausa, Martina Asta, Andrea Belli, Francesco Bianco, Carmela Cervone, Paolo Delrio, Armando Falato, Andrea Fares Bucci, Rita Guarino, Ugo Pace, Daniela Rega, Emilia De Luca, Gaetano Gallo, Giuseppe Sammarco, Giuseppe Sena, Giuseppina Vescio, Letizia Santandrea, Giampaolo Ugolini, Davide Zattoni, Nicola Chetta, Gaetano Logrieco, Serafino Vanella, Gianluca Garulli, Nicola Zanini, Andrea Bondurri, Francesco Cammarata, Francesco Colombo, Diego Foschi, Giulia Maria Beatrice Lamperti, Anna Maffioli, Gianluca Matteo Sampietro, Al'ona Yakushkina, Gloria Zaffaroni, Enrico Cicuttin, Maria Grazia Sibilla, Harmony Impellizzeri, Marco Inama, Gianluigi Moretto, Sylvie Mochet, Elisa Ponte, Antonella Usai, Stefano Mancini, Andrea Sagnotta, Luigi Solinas, Elisa Bolzonaro, Nicolò Tamini, Gianluca Curletti, Raffaele Galleano, Michele Malerba, Sofia Campanella, Gianfranco Cocorullo, Francesco Colli, Paolino De Marco, Nicolò Falco, Tommaso Fontana, Leonel jospin Kamdem Mambou, Antonella La Brocca, Leo Licari, Brenda Randisi, Giovanna Rizzo, Giulia Rotolo, Giuseppe Salamone, Roberta Tutino, Paolina Venturelli, Stefano Malabarba, Alessandro Sgrò, Ivan Vella, Bruno Cirillo, Daniele Crocetti, Giorgio De Toma, Pierfrancesco Lapolla, Andrea Mingoli, Paolo Sapienza, Angela Belvedere, Stefania Bianchini, Margherita Binetti, Arianna Birindelli, Valeria Tonini, Mauro Podda, Fabio Pulighe, Michele De Rosa, Lorenzo Bono, Felice Borghi, Paolo Geretto, Maria Carmela Giuffrida, Corrado Lauro, Alessandra Marano, Luca Pellegrino, Paola Salusso, Diego Sasia, Michela Campanelli, Alberto Realis Luc, Mario Trompetto, Roberto Cardia, Nicola Cillara, Antonio Nicola Giordano, Antonio Costanzo, Mario Alessandro Giovilli, Luca Turati, Silvestro Canonico, Guido Sciaudone, Francesco Selvaggi, Lucio Selvaggi, Nader Albsoul, Ahmad AlBsoul, Ala'a Aldeen Alkhatib, Osama Alsallaq, Justin Z. Amarin, Rami Ayoub, Isam Bsisu, M S El Muhtaseb, Mohammad Jabaiti, Jamal Melhem, Yasmeen Z. Qwaider, Mohammad Hasan Salameh, Ahmad Suleihat, Haya H. Suradi, Mohammad Alammarin, Almoutuz Aljaafreh, Mohammad Bani hani, Zeina Bani hani, Farah Bani Hani, Toqa Fahmawee, Shadi Hamouri, Cyrine Katanani, Ra'fat Tawalbeh, Tamara Tawalbeh, Hassan Zawahrah, Mohamad K. Abou Chaar, Lana Abusalem, Mahmoud Al-Masri, Hani Al-Najjar, Lutfi Barghuthi, Zahra Ahmed, Adnan Maulana, Omar Ngotho, Charbel Kamau, Aruyaru Stanley Mwenda, Fridah Bosire, Elizabeth Mwachiro, Robert Parker, Ian Simel, Kimutai Sylvester, Abdulmunem Ahmed Mustafa Althini, Sofian Elbarouni, Aya Elseed Elbeshina, Ahmed Gwea, Ans Malek, Wedad Albashir Masoud Farag, Abdulwahab Abdalei, Abu Baker Abdel Malik, Areej Abo-khammash, Ma'aly Abuhlaiga, Nour Adnan, Marwa Albaggar, Asma Alfitory, Asma Aljanfi, Fakhruddin Almuzghi, Zohoor Altumei, Fatima Alzabti, Hana Ashoushan, Mohamed Assalhi, Joma Azzubia, Sondos Bnhameida, Malik Delhen, Houssein Elshafei, Hana Elteir, Fatima Esbaga, Abdel Aziz Gobbi, Fatma Hamouda, Hamdan Hilan, Rania Ismail, Fieruz Jebran, Muataz Kasbour, Galia Maderi, Saja Mohammad, Burooj Mohammed, Habib Murtadi, Hamassat Mustafa, Mohamed Rajab, Sarah Trenba, Mariam Wafaa, Eman Al Sagheir, Alabas Almigheerbi, Ahmed Alzahaf, Sumayyah Ghayth Bahroun, Najah Ben Dallah, Mahmoud Elshaibani, Haitem Eswaye, Maha Karar, Samah Omar, Eman Younes, Maha Younes, Dafer Zreeg, Saleh Abujamra, Firas Ashour, Mala Elgammudi, Wesal Omar F. Aljadidi, Enas Saddouh, Randa Sharif, Aya Alabuzidi, AbdulMawlay Alwerfally, Sarra Aribi, Fatma Bibas, Taha Elfaituri, Yasmine Elhajjaji, Ala Khaled, Wegdan Khalil, Tesneem Layas, Enas Soula, Ahmed Tarek, Muad fathi khalleefah Abu hallalah, Hazem Abdelkarem Ahmed, Tagwa Alsharef, Abdulsalam Ali Ben Saoud, Tasnim El Gharmoul, Ahmed Elhadi, Safa Elrais, Abdulhalim Shebani, Heba Zarti, Asaid Zeiton, Marijus Ambrazevicius, Nerijus Kaselis, Migle Stakyte, Oleg Aliosin, Agne Cizauskaite, Sarunas Dailidenas, Vitalijus Eismontas, Migle Kybransiene, Vitalija Nutautiene, Narimantas Samalavicius, Dainius Simcikas, Algirdas Slepavicius, Albinas Tamosiunas, Nerijus Ubartas, Paulius Zeromskas, Saulius Bradulskis, Edvinas Dainius, Juozas Juocas, Egle Kubiliute, Juozas Kutkevicius, Aurimas Opolskis, Audrius Parseliunas, Andrejus Subocius, Egle Virbickaite, Diana Zuikyte, Algirdas Bogusevicius, Kristina Buzaite, Daiva Cepuliene, Ieva Cesleviciene, Vaidotas Cesna, Jolanta Gribauskaite, Povilas Ignatavicius, Mantas Jokubauskas, Monika Liugailaite, Ernest Margelis, Ruta Mazelyte, Lina Pankratjevaite, Matas Pažusis, Agne Rackeviciute, Justina Saladyte, Monika Škimelyte, Vygintas Šlenfuktas, Monika Sudeikyte, Algimantas Tamelis, Tomas Vanagas, Žygimantas Žumbakys, Aivaras Atkociunas, Audrius Dulskas, Justas Kuliavas, Justas Birutis, Sigitas Paškevicius, Mindaugas Šatkauskas, Donatas Danys, Matas Jakubauskas, Lina Jakubauskiene, Marius Kryzauskas, Vytautas Lipnickas, Gabija Makunaite, Fanjandrainy Rasoaherinomenjanahary, Herizo Rasolofonarivo, Luc Hervé Samison, Bitiel Banda, Vanessa Msosa, Ahmad Imran Ahmad Izzuddin, Andre Das, Ying Yee Gan, Tan Shong Sheng, Jia yng Siaw, Mohd Fadliyazid Ab Rahim, Dyg Zahratul Hamrak Abang Jamari, Nurfariza Che Husin, Muhd Yusairi Kamarulzaman, Yi Ping Lim, Nil Amri Mohamed Kamil, Mohd Razeen Mohd Hassan, Saidah Mohd Sahid, Johari Mustafa, Elaine Hui Been Ng, Wan Khamizar Wan Khazim, Ng Chang Ern, P.g. Lingeshan, Syariz Ezuan Sulaiman, Sue Ean Ang, Muhammad Navid Bin Mohamad Sithik, Yih Jeng Cheong, Mahadevan Deva Tata, Law Jia Xian, Aravinthan Kadravello, I-Ern Koh, Li-Yen Ng, Yuki Julius Ng We Yong, Kandasami Palayan, Chi Xuan Sam, Phuah Siow Jin, Jeremy Tan Ern Hwei, Yita Tang, Alvin Zubin Ter, Michael Pak-Kai Wong, Andee Dzulkarnaen Zakaria, Zaidi Zakaria, Fitjerald Henry, Thyivya Kalaiselvan, Muhammad Fairuz Shah Abd Karim, Mohamed Rezal Abdul Aziz, Nora Abdul Aziz, Tak Loon Khong, Peng Choong Lau, Hiong Chin Lim, April Camilla Roslani, Jonathan Chen Ken Seak, Sui-Weng Wong, Lai Fen Wong, Leow Yeen Chin, Mercy Chinemerem Anyanwu, Zachary Busuttil, Thomas Calleja, Kurt Lee Chircop, Ruth Cutajar, Andrew Michael Dimech, Joseph Galea, Kiara Gascon Perai, Ruth Gatt, Lisa Kelman, Elizabeth Micallef, Favour Nwolu, Kim Sammut, Joanna Thompson, Sean Warwicker, Matthew Zammit, Fernando Cordera, Efraín Cruz González, Jorge Sánchez-García, Francisco José Barbosa Camacho, Francisco Javier Barrera López, Carlos Jose Zuloaga Fernandez del Valle, Eric Acosta, Iván Romarico González Espinoza, Perla Moreno, Ana Olivia Cortes-Flores, Clotilde Fuentes Orozco, Alejandro Gonzalez Ojeda, Samantha Corro Díaz González, Laura Martinez, Bonifacio Mosqueda Amador, Armando Novoa, Dennet Arturo Olazo Espejo, Alejandro Jimenez, Federico Lopez Rosales, Elva Gabriela Vanoye, Luis Alberto Garcia Gonzalez, Roberto Carlos Miranda-Ackerman, Manuel Solano-Genesta, Alethia Alvarez-Cano, Hector Hugo Romero-Garza, Heriberto Medina-Franco, Lorelí Mejía-Fernández, Noel Salgado-Nesme, Omar Vergara-Fernandez, Guadalupe Montserrat Gutiérrez-Mota, Francisco Xavier Hernandez Vera, Anabella Llantada Lopez, Gilberto Morgan Villela, Felipe de Jesus Ramirez Padilla, Walezka Tapia Marin, Mónica Martínez Maldonado, Ramses Sánchez Suárez, José Manuel Troche, Chaymae Benyaiche, Oumaima Outani, Souadka Amine, Amine Benkabbou, Anass Mohammed Majbar, Raouf Mohsine, Ali Rafik, Thida Oung, Moe Moe Tin, Philipp Plarre, Anna Alberga, Nina Sluiter, Jurriaan Tuynman, Robin Blok, Didem Cömert, Roel Hompes, Marianne Kalff, Merel Elisabeth Stellingwerf, Pieter Tanis, Mark van Berge Henegouwen, Elise Maria van Praag, Daan Wisselink, Michael Gerhards, Josephine Lopes Cardozo, Emma Westerduin, Joske de Jonge, Aaw van Geloven, Kaz van Schilt, Frank den Boer, Simone Stoots, Stijn Vlek, Jamie Adams, Ibrahim S. Al-Busaidi, Gabrielle Budd, Seung il Choi, Michael Jen Jie Chu, Anurag Ganugapati, Lucy McKinstry, Rebecca Pascoe, Simon Richards, Kenrick Rosser, Annie Stevenson, Rebecca White, Shebani Farik, Jin Kwun, Ahmed Murad, Sarah Cowan, Timothy Hall, Michael Hayton, Laminou Malam Sani, Souleymane Oumarou Garba, Ibrahim Amadou Magagi, Oumarou Habou, Halima Aliyu, Muhammad Daniyan, Tunde T. Sholadoye, Lawal Abdullahi, Lofty-John Anyanwu, Aminu Mohammad Mohammad, Abubakar Bala Muhammad, Abdurrahman Abba Sheshe, Ibrahim Suleiman, Alaba Adesina, Ajibola Awolowo, Clement Onuoha, Omotayo Salami, Ogechukwu Taiwo, Agboola Taiwo, Stephen Kache, Jerry Godfrey Makama, Danjuma Sale, Olajide Abiola, Akinlabi Ajao, Anthony Ajiboye, Amarachukwu Etonyeaku, Julius Olaogun, Ademola Adebanjo, Opeoluwa Adesanya, Michael Olatunji Afolayan, Olanrewaju Balogun, Ayomide Makanjuola, Samuel Nwokocha, Rufus Wale Ojewola, Thomas Olagboyega Olajide, Adewale Aderounmu, Abdul-Rashid Adesunkanmi, Augustine Agbakwuru, Adeleke Akeem Aderogba, Olusegun Isaac Alatise, Olukayode Arowolo, Oladejo Lawal, Tajudeen Mohammed, Chinedu Ndegbu, Olalekan Olasehinde, Funmilola Wuraola, Akinbolaji Akinkuolie, Arinzechukwu Mosanya, Omobolaji Ayandipo, Peter Elemile, Taiwo Akeem Lawal, Samuel Ali SANI, Stephen Garba, Rebecca Hauwa SANI, Samson Olori, Henry Onyebuashi, Ifeanyi Umoke, Adedire Adenuga, Ademola Adeyeye, Olufemi Habeeb, Bashir Lawal, Abdulrasheed Nasir, Eirik Kjus Aahlin, Didrik Kjønås, Elisabeth Myrseth, Jibran Abbasy, Abdul Alvi, Omair Saleem, Asma Afzal, Anam Nazir, Muhammad Farooq, Ayesha Liaqat, Syed Asghar Naqi, Ali Raza, Muzna Sarfraz, Muhammad Sarwar, Muntaha Banglani, Ambreen Munir, Rahmat Sehrish, Bushra Ayub, Raza Sayyed, Amna Altaf, Saima Ayub, Komal Saeed, Bilal Syed, Sana Amir Akbar, Abdul Wahid Anwer, Ruqayya Naheed Khan, Amina Iqbal Khan, Shahid Khattak, Sameen Mohtasham, Muhammad Asad Parvaiz, Aamir Ali Syed, Abdul Basit Ansari, Noman Shahzad, Tanwir Khaliq, Isbah Rashid, Shahzad Hussain Waqar, Hasan Abu Al-saleem, Amjad Abu Alqumboz, Mohammad Alqadi, Adham Amro, Rawan Assa, Eman Awesat, Rawan Ayyad, Mohammed Hammad, Ayat Haymony, Bassel Hijazi, Bara Hmeidat, Rowaa Lahaseh, Aseel Qawasmi, Alaa Rajabi, Mohammed Shehada, Sundus Shkokani, Yasmine Yaghi, Nadine Yaghi, Mohammad AlZohour, Mohammad Farid, Yousef Mahmoud Habes, Wesam Juba, Yanal Nubani, Abdelrahman Rabee, Mohammad Sa'deh, Saeed Abed, Iyad Al basos, Mohammad Alswerki, Dina Ashour, Israa Awad, Samar Diab, Alaa El Jamassi, Sahar El-Kahlout, Somaya Elhout, Ahmed N K Hajjaj, Doaa Hasanain, Baraa Nabil hajjaj, Mohammed Obaid, Eman Saikaly, Ahmed Salhi, Hiba Al-Tammam, Murad Almasri, Muath Baniowda, Doha Beshtawi, Ali Horoub, Rami Misk, Bayan Mohammad, Rami Qasrawi, Tasnim Sholi, Samar Abu-Nimeh, Abrar Abu-srour, Sadi A. Abukhalaf, Samer Adawi, Barah Alsalameh, Kholoud Ayesh, Muawiyah Elqadi, Ahmad Hammouri, Fatima Karim Mustafa, Natalie Marzouqa, Shatha Melhem, Dima Miqdad, Balqees Mohamad, Mhammed Rawhi, Ayman B. Abu Ahammala, Ahmed Abu Ataya, Israa Abu Jayyab, Samar Al-Shwaikh, Othman Alagha, Mohammed Alasttal, Haneen Awadallah, Mahmood Elblbessy, Jehad Fares, Akram Jarbou, Ibtisam Mahfouz, Moath A. Albahnasawi, Asmaa' Abo mahadi, Hasan Abuelhatal, Ayham Abuelqomboz, Abdelrahman Almoqayyad, Abdallah Alwali, Reem Balaawi, Mahmoud Hamouda, Mohammed Humeid, Abdullah Jedyan, Tasneem Mahmoud Abu hamam, Ghadeer Matar, Ali Salem, Tahani Samra, Nureddin Shaheen, Karam Shihada, Ayoob A.Nemer, Mahmoud Abu Al Amrain, Abdulwhhab Abu Alamrain, Najlaa Abu Jamie, Mohammed R. Abu-Rous, Nada Alfarra, Mohammed AlTaweel, Noor Alwhaidi, Ramadan Hamed, Bader Saqqa, Ahmad Shaheen, Dana Aljaber, Loay Aljaberi, Malak Alwaheidi, Assef Jawaada, Hani Khaldi, Rami Qahoush, Jalil Qari, Rana Saadeh, Ahlam Salim, Aseel Yacoub, Abbas Abbas, Rana Abu shua`ib, Baraa Abu Zainah, Mahmoud AbuSirrees, Basheer Babaa, Ola Barhoush, Asef Belal qadomi, Laith Daraghmeh, Reema Haji, Alaa Khatatbeh, Lana Khatib, Salsabeel Qarariah, Yara Quzmar, Khalil Safadi, Roqaya Salameh, Mohammad Hassan, Shifaa Herzallah, Loai Massad, Ahmed Nazzal, Ranin Nazzal, Dennis Escobar, Gustavo Miguel Machain V, Agustin Rodriguez Gonzalez, Jorge Emerson Chachaima Mar, Nathaly Olga Chinchihualpa Paredes, Vicente Cuba, Walter Lopez, Maria Milagros Niquen Jimenez, Nestor Alberto Sanchez Bartra, Olenka Sapallanay Ojeda, Diego Sequeiros, Andrea Toscano Pacheco, María Vergara, Sol Abarca, Rodrigo Alcorta, Giuliano Borda-Luque, Ivan Edward Eusebio Zegarra, Claudia Luján López, Mirella Marrufo, Cinthya Mogrovejo, Andrea Nomura, Yamile Rodríguez Angeles, Maitza Rosario Vidal Meza, Gabriela Zavala, José Neiser Castillo Arrascue, Jomara Caroline Hidrogo Cabrera, José Julio Mariano Larrea vera, Miguel Osorio, Edgar Alcides Ylatoma Díaz, Mark Anthony Fontanilla, Joseph Roy Fuentes, Anna Leah Salazar, Genieve Dominguez, Marc Paul Lopez, Shiela Macalindong, Mark Augustine Onglao, Arjel Ramirez, Marie Dione Sacdalan, Mayou Martin Tampo, Gemma Leonora Uy, Jeremiah Mangahas, Kenneth Yabut, Joannes Paul Cañete, Bernalynn Eris Cansana, Ernes John Castro, Maria Kaiserin Lipana, Manuel Francisco Roxas, Vlu Jean Zara, Maciej Chrol, Paula Franczak, Michal Orlowski, Piotr Budzynski, Andrzej Budzynski, Pawel Bury, Agata Czerwinska, Jadwiga Dworak, Jacek Dziedzic, Michal Kisielewski, Jan Kulawik, Anna Lasek, Piotr Malczak, Marcin Migaczewski, Michal Pedziwiatr, Magdalena Pisarska, Dorota Radkowiak, Mateusz Rubinkiewicz, Anna Rzepa, Tomasz Skoczylas, Maciej Stanek, Katarzyna Truszkiewicz, Mateusz Wierdak, Marek Winiarski, Piotr Zarzycki, Anna Zub-Pokrowiecka, Piotr Kowalewski, Rafal Roszkowski, Maciej Waledziak, Miguel Tomé, Sara Patrocinio, Ines Guerreiro, Filipe Almeida, Xavier de Sousa, Nuno Monteiro, Maria Teresa Costa Santos, Daniela de Oliveira, Marta Lopes Serra, Daniela Morgado, Christian Neves, Ana Carolina Oliveira, Alice Pimentel, Sofia Silva, Márcia Carvalho, Lúcia Carvalho, Joana Magalhães, Leonor Matos, Tânia Monteiro, Carlota Ramos, Vanessa Santos, José Barbosa, Jose Costa-Maia, Vítor Devezas, Ana Fareleira, Cristina Fernandes, Diana Gonçalves, Henrique Mora, Marina Morais, Fabiana Silva de Sousa, Sara Catarino Santos, Ana Logrado, André Tojal, Edgar Amorim, Miguel F. Cunha, Ana Fazenda, João Pedro Melo Neves, Inês Isabel Sampaio da Nóvoa Gomes Miguel, Diogo Veiga, José Azevedo, Hugo Cardoso Louro, Mariana Leite, Maria Bairos Menezes, Bárbara Gama, Diana Brito, Marta Cristina Cruz Martins, André Graça e Magalhães, Ana Catarina Longras, Rita Lourenço, Diana Matos, Luis Castro, Filipa Policarpo, Joana Romano, Cristina Monteiro, Diogo Pinto, Marina Duarte, Sónia Fortuna Martins, Mariline Oliveira, Diogo Galvão, Lisandra Martins, Anaisa Silva, Viorel Taranu, Bárbara Vieira, Jessica Neves, Simone Oliveira, Hugo Ribeiro, Margarida Cinza, Rosa Felix, Arnaldo Machado, Joana Oliveira, Joana Patrício, Rita Pedroso de Lima, Mário Pereira, Miguel Rocha Melo, Cristina Velez, Alberto Abreu da Silva, Mariana Claro, Daniel Costa Santos, Andreia Ferreira, Hugo Capote, Daniela Rosado, Filipa Taré, Oriana Nogueira, Miguel Ângelo, José Miguel Baiao, Andreia Guimarães, João Marques, Miguel Nico Albano, Marta Silva, Ana Valente da Costa, Teresa Vieira Caroço, Sara Almeida Braga, Ines Capunge, Marta Fragoso, João Guimarães, Bruno Pinto, João Ribeiro, Miguel Angel, Guilherme Fialho, Monica Guerrero, Filipa Campos Costa, Diogo Cardoso, Vasco Cardoso, Magda Alves, Inês Estalagem, Tiago Louro, Cláudia Marques, Rita Martelo, Miguel Morgado, Rita Canotilho, Ana Margarida Correia, Pedro Martins, Mariana Peyroteo, João Gomes, Rita Monteiro, Manuela Romano, Daniela Macedo Alves, Rita Peixoto, Catarina Quintela, Maria João Jervis, Débora Melo, André Pacheco, Valter Paixão, Vera Pedro, Joana Pimenta, João Pimenta de Castro, Ana Rocha, Mircea Beuran, Cezar Ciubotaru, Bogdan Diaconescu, Sorin Hostiuc, Ionut Negoi, Bogdan Stoica, NA NA, Evgeny Anokhin, Georgy Kuznetsov, Giorgi Oganezov, Fedor Paramzin, Ekaterina Romanova, Valeryan Rutkovskii, Vasilii Rutkovskii, Mikhail Shushval, Mikhail Zabiyaka, Khasan Dzhumabaev, Valerii Ivanov, Zaman Mamedli, Sergey Achkasov, Artem Balkarov, Elnur Nabiev, Marat Nagudov, Evgeny Rybakov, Karina Saifutdinova, Oleg Sushkov, Lule Joseph, Isaac Ndayishimiye, Ntirenganya Faustin, Alphonse Zeta Mutabazi, Jean Paul Mvukiyehe, Vizir J.P Nsengimana, Carine Uwakunda, Mohammad Monir Abbas, Nouf Akeel, Murad Aljiffry, Kholoud Awaji, Ali Farsi, Ghader Jamjoum, Ahmad Khoja, Ashraf Maghrabi, Nadim Malibary, Mohammed Nassif, Abdulaziz Saleem, Abdullah Sultan, Wail Tashkandi, Hanaa Tashkandi, Nora Trabulsi, Mouhamadou Bachir Ba, Adja Coumba Diallo, Abdourahmane Ndong, Vladica Cuk, Uroš Jankovic, Sharon Zhiling Koh, Frederick Koh, Kuok Chung Lee, Kai Yin Lee, Sean Lee, Wei Qi Leong, Su Ann Lui, Prajwala Prakash, Jan Grosek, Gregor Norcic, Ales Tomazic, Nicolas Fitchat, Robert Jaich, Devorah Wineberg, Modise Zacharia Koto, Daniella Baiocchi, Damian Clarke, Christina Johanna Steenkamp, Sharon Bannister, Adam Boutall, Galya Chinnery, Anna Coccia, Angela Dell, Parveen Karjiker, Christo Kloppers, Nicholas Loxton, Tumi Mabogoane, Francois Malherbe, Eugenio Panieri, Shreya Rayamajhi, Tirsa van Wyngaard, Claire Warden, T E Madiba, Nivashen Pillay, Savannah Brooks, Charlise Kruger, Lisa Hannah Van Der Merwe, Ferhana Gool, Maahir Kariem, Heather Bougard, Nazmie Kariem, Fazlin Noor, Reantha Pillay, Leandi Steynfaardt, Lucía González González, José Miguel Marín Santos, Paula Martín-Borregón, Javier Martínez Caballero, Cristina Nevado García, Pastora Rodriguez Fraga, Gonzalo De Castro Parga, Maria Pilar Fernández Veiga, Lucía Garrido López, Hugo Infante Pino, Irene Lages Cal, Marta López Otero, Manuel Nogueira Sixto, Marta Paniagua García Señorans, Laura Rodríguez Fernández, Alejandro Ruano Poblador, Erika Rufo Crespo, Raquel Sanchez-Santos, Vincenzo Vigorita, Ester Alonso Batanero, Dorisme Asnel, Isabel Cifrian Canales, Elisa Contreras Saiz, Irene De Santiago Alvarez, Tamara Díaz Vico, Sebastian Fernandez Arias, Daniel Fernández Martínez, Carmen García Bernardo, Luis Joaquín García Flórez, Carmen Garcia Gutierrez, Manuel García Munar, Carlos Alberto Márquez Zorrilla Molina, Marta Merayo, José Luis Michi Campos, Maria Moreno Gijon, Jorge L. Otero-Diez, Jose Luis Rodicio Miravalles, Lorena Solar-Garcia, Aida Suárez Sánchez, Nuria Truan, Cristina Alejandre Villalobos, Yurena Caballero Díaz, Marta Jimenez, Dacil Montesdeoca, Antonio Navarro-Sánchez, Victor Vega, Juan Beltrán de Heredia, Zahira Gómez, Carlos Jezieniecki, Ana Patricia Legido Morán, Mario Montes-Manrique, Mario Rodriguez-Lopez, María Ruiz Soriano, Jeancarlos Trujillo Díaz, Andrea Vazquez Fernandez, Nuria Argudo, Miguel Pera, Laia Torrent Jansà, Melody García Domínguez, Ignacio Goded, Marta Roldón Golet, Issa Talal El-Abur, Alejandra Utrilla Fornals, Vanesa Zambrana Campos, Maria Del Mar Aguilar Martinez, Marina Bosch, Luis García-Catalá, Luis Sánchez-Guillén, Eva Artigau, Nuria Gomez Romeu, David Julià Bergkvist, Beatriz Espina Perez, Olga Morató, Carles Olona, Beatriz Diéguez, Alexander Forero-Torres, Manuel Losada, Segundo Gomez-Abril, Paula Gonzálvez, Rosario Martinez, Sergio Navarro Martínez, Carmen Payá-Llorente, Álvaro Pérez Rubio, Sandra Santarrufina Martinez, Juan Carlos Sebastián Tomás, Ramon Trullenque Juan, Alberto Gegúndez Simón, Paloma Maté, Maria Isabel Prieto-Nieto, Ines Rubio-Perez, Aitor Urbieta, Marina Vicario Bravo, David Abelló, Matteo Frasson, Alvaro Garcia-Granero, Alfredo Abad Gurumeta, Ane Abad-Motos, Elena Lucena-de Pablo, Beatriz Nozal, Javier Ripollés-Melchor, Rut Salvachúa, Esther Ferrero, Luis Garcia-Sancho Tellez, Antonio L. Picardo, Jose Alberto Rojo López, Laura Patricia Zorrilla Matilla, Carmen Cagigas Fernandez, Sonia Castanedo Bezanilla, José Estevez Tesouro, Maria Jose Fernandez-Diaz, Juan García Cardo, Marcos Gomez Ruiz, Erik Gonzalez-Tolaretxipi, Jaime Jimeno Fraile, Cristobal Poch, Montserrat Rodriguez-Aguirre, Noemí Troche Pesqueira, Maria Soledad Trugeda-Carrera, Javier de la Torre, Ruth Blanco-Colino, Eloy Espin-Basany, Martin Espinosa-Bravo, Clara Morales Comas, Eduardo Reyes Afonso, Joaquín Rivero Déniz, Christian Siso Raber, Mireia Verdaguer Tremolosa, Pramodh Chandrasinghe, Sumudu Kumarage, Nimeshi Wijekoon Arachchilage, Ahmed Abdalla Ahmed Elkamel, Mohammed A. Adam, Nina Blomme, Anders Thorell, Fredrik Wogensen, Andreas Älgå, Dhirar Ansarei, Fuat Celebioglu, Göran Heinius, Linda Nigard, Emil Pieniowski, Sandra Ahlqvist, Ida Björklund, Andreas Frånberg, Martina Håkansson, Karin Adamo, Oskar Franklin, Malin Sund, Rebecca Wiberg, Yvette Andersson, Abbas Chabok, Maziar Nikberg, Alexander Kugelberg, Claudia Canonica, Dimitrios Christoforidis, Fabrizio Fasolini, Paolo Gaffuri, Mauro Giuliani, Francesco Meani, Sotirios Georgios Popeskou, Silvia Pozza, Wiebke Wandschneider, Lorenz Peterer, Lukas Werner Widmer, Bernd Zimmermann, Panagiotis Bakoleas, Iris Chanousi, Lydia Charalampidou, Lukasz Filip Grochola, Franziska Heid, Sotirios Ntaoulas, Michail Outos, Georgios Peros, Hanna Podolska-Skoczek, Katharina Beate Reinisch, Christian Zielasek, Nicolas Demartines, Jérôme Gilgien, Amaniel Kefleyesus, Pénélope St-Amour, Arnaud Toussaint, Maryam Alhimyar, Bayan Alsaid, Amr Alyafi, Ahmad Alkhaledi, Basel Kouz, Ahmad Omarain, Yusra Al-Sabbagh, Haya Alkhatib, Samer Sara, Ahmad Alhaj, Aghyad Danial, Lama Kadoura, Sarah Maa Albared, Yamen Monawar, Louei Nahas, Barook Abd, Ahmad Saad, Habib Wakkaf, Hatem Bouzaiene, Montassar Ghalleb, Elif Akaydin, Ata Cem Akbaba, Onur Atakul, Ege Baltaci, Sevval Besli, Gökçen Burgu, Ulukan Cenal, Cansu de Muijnck, Hasan Can Demirkaya, Alper Dogruoz, Zeynep Ipek Gezer, Yasemin Gündogdu, Merve Kara, Hasan Kürsad Korkmaz, Gökalp Kagan Kurtoglu, Volkan Ozben, Berk Baris Ozmen, Ahmet Murat Pektas, Eda Kübra Sel, Nilüfer Yenidünya, Fuat Baris Bengur, Berke Mustafa Oral, Tahir Koray Yozgatli, Seymur Abdullayev, Mehmet Emin Gunes, Nuri Alper Sahbaz, Tuba Banaz, Kübra Kargici, Omer Faruk Kuyumcu, Erkan Yanikoglu, Merve Yesilsancak, Duygu Yilmaz, Melik Kagan Aktas, Ahmet Rencuzogullari, Arda Isik, Sezai Leventoglu, Ali Yalçinkaya, Osman Yüksel, Mustafa U Kalayci, Yasin Kara, Inanc Samil Sarici, Alp Akin, Gökçe nur Alemdag, Ekin Arslan, Bahadir Emre Baki, Muhammed Selim Bodur, Adnan Calik, Bahar Candas Altinbas, Irem Cihanyurdu, Oguz Erkul, Burak Gül, Ali Guner, Beyza Köse, Anil Semiz, Sule Sevim, Serkan Tayar, Kadir Tomas, Ozan yavuz Tüfek, Serdar Türkyilmaz, Mehmet Ulusahin, Arif Usta, Reyyan Yildirim, Sertaç Ata Güler, Ozan Can Tatar, Ecenur Varol, Busenur Kirimtay, Muhammed Uysal, Alp Yildiz, Emin Kose, Ahmet Burak Ciftci, Elif Çolak, Huseyin Eraslan, Gultekin Ozan Kucuk, Kürsat Yemez, Herman Lule, Mumbere Bienfait, Emmanuel Bua, Noella Okalany, Maksym Basarab, Oleksii Bielosludtsev, Kateryna Kolhanova, Kateryna Perepelytsia, Kateryna Romanukha, Dmytro Savenkov, Stanislav Siryi, Maksym Tereshchenko, Nezamai Viacheslav, Anton Volovetskyi, Andrey Kebkalo, Yegor Tryliskyy, Volodimir Tyselskiy, Eilidh Bruce, Bing Lun Chow, Emma Iddles, Sarah McGuckin, Nicola Newall, George Ramsay, Parivrudh Sharma, Caitlin Stewart, Jeremy Wong, Abdul Badran, Michael Bath, Fanny Belais, Eman Butt, Kaustuv Joshi, Milan Kapur, Mike Shaw, Adam Townson, Christopher Yee Khang Williams, Timothy Gray, Robert Greig, Mansoor Husain, Elspeth Murray, Ahmed Mustafa, Ashar Asif, Arya Gokul, Max Shah, Mabel Temisanren Akitikori, Alexandros Charalabopoulos, Sophie Davidson, Sinead McNally, Shamil Rupani, Fatema Juma, Sarah Catherine Mills, Laura Muirhead, Kate Sellars, Una Walsh, Oliver Warren, Alice Chambers, Richard Hunt, Stephen Boyce, Hannah Cornwall, Isabel Tol, Eleftherios Orestis Argyriou, Nicola Eardley, Meical Povey, Joanna M S Aithie, Ahmer Irfan, Mari-Claire McGuigan, Robert Starr, Craig Russell Warren, Jess Archibald, Georgia Kirby, Ivan Kisyov, Chun Kheng Khoo, Rachel Lee, Dana Photiou, Rowan Davis, Uday Prasad, P Zichu Yang, Jonathan Bird, Edmund Leung, Virginia Summerour, Chelise Currow, Jianshen Kiam, Gerald Jack Soon Tan, Anitha Muthusami, Ibifunke Pegba-Otemolu, Tomas Urbonas, Joseph Nunoo-Mensah, Edgaras Smolskas, Alex Boddy, Gianpiero Gravante, David Hunter, David Andrew, Amanda Koh, Amari Thompson, Lawrence Adams, Hollie A Clements, Kasun De Silva, Ogbonnia Ekpete, Seraj Haque, Scott Henderson, Bilal Ibrahim, Thummini Jayasinghe, Jennifer Livie, Keir Mailley, Gopikrishnan Nair, Daniel Tan, Caitlin Baggaley, Aleksander Dawidziuk, Bartosz Szyszka, Charlotte Barter, Nirav Gandhi, Karen Hassell, Samantha Hitchin, Jennett Kelsall, Eva Nagy, Ashrafun Nessa, Lisa Whisker, Fady Yanni, Mahmoud Ali, Deeksha Arora, Sunanda Hediwattege, Navam Kumarasinghe, Munir Rathore, Athula Tennakoon, Syed Mustafa Ali Ahmad, Oreoluwa Bajomo, Fahema Nadira, Valerio Celentano, Ewen Griffiths, Rama Santhosh Karri, Jason Kei Chak Mak, Michelle Pipe, Muhammad Iqbal Bhatti, Mohamed Rabie, Connor Boyle, David Hamilton, Aishath Mihuna, James Chean Khun Ng, Gary Nicholson, Agata Oliwa, Robert Pearson, Anna Rose, Shun Qi Yong, Catherine Boereboom, Michael Hanna, Catherine Walter, Thomas Samuel Greensmith, Rachel Mitchell, Eimear Monaghan, James Crawford, Susan Moug, James Blackwell, Hannah Boyd-Carson, Philip Herrod, Omar Al-Allaf, Miriam Beattie, Cameron Bullock, Shivang Burman, Gemma Clark, Nicolas Flamey, Oliver Flannery, Alexander Harding, Ben Kodiatt, Samuel Lawday, Shivani Mahapatra, Navin Mukundu Nagesh, Michael Ng, Dupinderjit Rye, Andrel Yoong, Laura Clark, Chris Deans, Monisha Edirisooriya, Emma Victoria Carrington, Tsz Lun Ernest Wong, Baasil Yusuf, Carla Chamberlain, Kathryn Duke, Elizabeth Kmiotek, Azel Botes, Natalie Condie, Timothy Schrire, Reena Shah, Iolo Thomas-Jones, Charlotte Yates, Natasha Anthony, Edward Matthews, Kapil Sahnan, James Tankel, Sally Tucker, Jasmine Winter Beatty, Paul Ziprin, William Duggan, Anastasia Kantartzi, Shruthi Sridhar, Rachel Alys Khaw, Prakhar Srivastava, Charlotte Underwood, Homero Alves do Canto Brum, Sharat Chopra, Laura Davis, Rebecca Hughes, Joshua Tulley, Justin Alberts, Thomas Athisayaraj, Mojolaoluwa Olugbemi, Kasim Ahmad, Claudia Chan, Gavin Chapman, Hannah Fleming, Benjamin Fox, Julia Grewar, Kate Hulse, Duncan Rutherford, Mackay Sinead, Scott Smith, Doug Speake, Peter G Vaughan-Shaw, Natasha Christodoulides, Simrit 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A., Abu shua'ib R., Abu Zainah B., AbuSirrees M., Babaa B., Barhoush O., Belal qadomi A., Daraghmeh L., Haji R., Khatatbeh A., Khatib L., Qarariah S., Quzmar Y., Safadi K., Salameh R., Hassan M., Herzallah S., Massad L., Nazzal A., Nazzal R., Escobar D., Machain V G.M., Rodriguez Gonzalez A., Chachaima Mar J.E., Chinchihualpa Paredes N.O., Cuba V., Lopez W., Niquen Jimenez M.M., Sanchez Bartra N.A., Sapallanay Ojeda O., Sequeiros D., Toscano Pacheco A., Vergara M., Abarca S., Alcorta R., Borda-Luque G., Eusebio Zegarra I.E., Lujan Lopez C., Marrufo M., Mogrovejo C., Nomura A., Rodriguez Angeles Y., Vidal Meza M.R., Zavala G., Castillo Arrascue J.N., Hidrogo Cabrera J.C., Larrea vera J.J.M., Osorio M., Ylatoma Diaz E.A., Fontanilla M.A., Fuentes J.R., Salazar A.L., Dominguez G., Lopez M.P., Macalindong S., Onglao M.A., Ramirez A., Sacdalan M.D., Tampo M.M., Uy G.L., Mangahas J., Yabut K., Canete J.P., Cansana B.E., Castro E.J., Lipana M.K., Roxas M.F., Zara V.J., Chrol M., Franczak P., 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Adam M., Blomme N., Thorell A., Wogensen F., Alga A., Ansarei D., Celebioglu F., Heinius G., Nigard L., Pieniowski E., Ahlqvist S., Bjorklund I., Franberg A., Hakansson M., Adamo K., Franklin O., Sund M., Wiberg R., Andersson Y., Chabok A., Nikberg M., Kugelberg A., Canonica C., Christoforidis D., Fasolini F., Gaffuri P., Giuliani M., Meani F., Popeskou S.G., Pozza S., Wandschneider W., Peterer L., Widmer L.W., Zimmermann B., Bakoleas P., Chanousi I., Charalampidou L., Grochola L.F., Heid F., Ntaoulas S., Outos M., Peros G., Podolska-Skoczek H., Reinisch K.B., Zielasek C., Demartines N., Gilgien J., Kefleyesus A., St-Amour P., Toussaint A., Alhimyar M., Alsaid B., Alyafi A., Alkhaledi A., Kouz B., Omarain A., Al-Sabbagh Y., Alkhatib H., Sara S., Alhaj A., Danial A., Kadoura L., Maa Albared S., Monawar Y., Nahas L., Abd B., Saad A., Wakkaf H., Bouzaiene H., Ghalleb M., Akaydin E., Akbaba A.C., Atakul O., Baltaci E., Besli S., Burgu G., Cenal U., de Muijnck C., Demirkaya H.C., Dogruoz A., Gezer Z.I., Gundogdu Y., Kara M., Korkmaz H.K., Kurtoglu G.K., Ozben V., Ozmen B.B., Pektas A.M., Sel E.K., Yenidunya N., Bengur F.B., Oral B.M., Yozgatli T.K., Abdullayev S., Gunes M.E., Sahbaz N.A., Banaz T., Kargici K., Kuyumcu O.F., Yanikoglu E., Yesilsancak M., Yilmaz D., Aktas M.K., Rencuzogullari A., Isik A., Leventoglu S., Yalcinkaya A., Yuksel O., Kalayci M.U., Kara Y., Sarici I.S., Akin A., Alemdag G.N., Arslan E., Baki B.E., Bodur M.S., Calik A., Candas Altinbas B., Cihanyurdu I., Erkul O., Gul B., Guner A., Kose B., Semiz A., Sevim S., Tayar S., Tomas K., Tufek O.Y., Turkyilmaz S., Ulusahin M., Usta A., Yildirim R., Guler S.A., Tatar O.C., Varol E., Kirimtay B., Uysal M., Yildiz A., Kose E., Ciftci A.B., Colak E., Eraslan H., Kucuk G.O., Yemez K., Lule H., Bienfait M., Bua E., Okalany N., Basarab M., Bielosludtsev O., Kolhanova K., Perepelytsia K., Romanukha K., Savenkov D., Siryi S., Tereshchenko M., Viacheslav N., Volovetskyi A., Kebkalo A., Tryliskyy Y., Tyselskiy V., Bruce E., Chow B.L., Iddles E., McGuckin S., Newall N., Ramsay G., Sharma P., Stewart C., Wong J., Badran A., Bath M., Belais F., Butt E., Joshi K., Kapur M., Shaw M., Townson A., Williams C.Y.K., Gray T., Greig R., Husain M., Murray E., Mustafa A., Asif A., Gokul A., Shah M., Akitikori M.T., Charalabopoulos A., Davidson S., McNally S., Rupani S., Juma F., Mills S.C., Muirhead L., Sellars K., Walsh U., Warren O., Chambers A., Hunt R., Boyce S., Cornwall H., Tol I., Argyriou E.O., Eardley N., Povey M., Aithie J.M.S., Irfan A., McGuigan M.-C., Starr R., Warren C.R., Archibald J., Kirby G., Kisyov I., Khoo C.K., Lee R., Photiou D., Davis R., Prasad U., Yang P.Z., Bird J., Leung E., Summerour V., Currow C., Kiam J., Tan G.J.S., Muthusami A., Pegba-Otemolu I., Urbonas T., Nunoo-Mensah J., Smolskas E., Boddy A., Gravante G., Hunter D., Andrew D., Koh A., Thompson A., Adams L., Clements H.A., De Silva K., Ekpete O., Haque S., Henderson S., Ibrahim B., Jayasinghe T., Livie J., Mailley K., Nair G., Tan D., Baggaley C., Dawidziuk A., Szyszka B., Barter C., Gandhi N., Hassell K., Hitchin S., Kelsall J., Nagy E., Nessa A., Whisker L., Yanni F., Ali M., Arora D., Hediwattege S., Kumarasinghe N., Rathore M., Tennakoon A., Ali Ahmad S.M., Bajomo O., Nadira F., Celentano V., Griffiths E., Karri R.S., Mak J.K.C., Pipe M., Bhatti M.I., Rabie M., Boyle C., Hamilton D., Mihuna A., Ng J.C.K., Nicholson G., Oliwa A., Pearson R., Rose A., Yong S.Q., Boereboom C., Hanna M., Walter C., Greensmith T.S., Mitchell R., Monaghan E., Crawford J., Moug S., Blackwell J., Boyd-Carson H., Herrod P., Al-Allaf O., Beattie M., Bullock C., Burman S., Clark G., Flamey N., Flannery O., Harding A., Kodiatt B., Lawday S., Mahapatra S., Mukundu Nagesh N., Ng M., Rye D., Yoong A., Clark L., Deans C., Edirisooriya M., Carrington E.V., Wong T.L.E., Yusuf B., Chamberlain C., Duke K., Kmiotek E., Botes A., Condie N., Schrire T., Shah R., Thomas-Jones I., Yates C., Anthony N., Matthews E., Sahnan K., Tankel J., Tucker S., Winter Beatty J., Ziprin P., Duggan W., Kantartzi A., Sridhar S., Khaw R.A., Srivastava P., Underwood C., Alves do Canto Brum H., Chopra S., Davis L., Hughes R., Tulley J., Alberts J., Athisayaraj T., Olugbemi M., Ahmad K., Chan C., Chapman G., Fleming H., Fox B., Grewar J., Hulse K., Rutherford D., Sinead M., Speake D., Vaughan-Shaw P.G., Christodoulides N., Kudhail S., Welch M., Husaini S.M., Lambracos S., Anyanwu C., Suresh R., Thomas J.S., Gleeson E., Platoff R., Saif A., Enumah Z., Etchill E., Gabre-Kidan A., Bernstein M., Carrano F.M., Connors J., Lynn P., Melis M., Newman E., Foster D.S., Perrone K., Titan A., Ahmad S., Bafford A.C.M.D., Dal Molin M., Hanna N., Zafar S.N., Hemmila M., Napolitano L., Wong J.J., Chandler J., Wood L., Wren S., Ottesen T., You L., Yu K., Arcienega Yanez M.D.P., Ferreira Fernandes M., Gonzalez D., Cubas S., Gonzalez M.C., Zubiaurre V., Demolin R., Giroff N., Sciuto P., Campos M., Rodriguez Cantera G., Deepika G., Simuchimba E., Bulaya A., Chibuye C., Chirengendure B., Kabale M.-R., Kabongo K., Munthali J., Mweso O., Pikiti F., Otieno J., Lai L.T., Blackman B., Subramaniam S., Karim R., Kok N., Lee Y.D., Ali S., Sinha A., Corrigan R., Barnes N., Wong F., Dennis G., Jedamzik J., Phillips E., Piette W., Van hentenryck M., Koco H., Lawani S., Kassa M.W., Santos Bezerra T., Gribnev P., Dimitrov D., Krastev P., Oum S., Bonghaseh D.T., Al Farsi M., Alsharqawi N., Acevedo V., Castillo Barbosa A.C., Giron F., Leon Rodriguez J.P., Kucan D., Rosko D., Barsic N., Zupan D., Hegazi A., Truncikova V., Fryba V., Mohamed M., Nagi A., Rashad Temerik A., Elshawy M.E., Mahmoud M.I., Anwar M., Rageh T., Elmokadem A., Gaballa K., Teppo S., Pengerma P., Ballouhey Q., Bergeat D., Weyl A., Hain E., Gyedu A., Yenli E., Osei-Poku D., Rompou V.-A., Zoikas A., Gaitanidis A., Koukis G., Perivoliotis K., Tavlas P., Galanos-Demiris K., Zografos G., Karavokyros I., Xanthopoulou G., Iordanidou E., Ayau F., Garcia A., Damjan P., Wason D., B L A., Rangganata E., Kamath P., O'Connor D.B., Pinto M., Perrone F., Tropeano F.P., Troilo F., Bossi D., Scala D., Pulitano L., Carella M., Pietrabissa A., Gori A., Giraudo G., De Simone V., Russo A.A., Braccio B., Al-Taher R., Athamneh S., Parker A., Sawiee A., Kattia A., Tababa O., Shaeeb Z., Syminas V., Jurgaitis J., Damuleviciene G., Svagzdys S., Razafimanjato N.N.M., Chieng Loo L., Tiong I.C., Wan Muhmad W.F., Vijeyan H., Li Ying T., Grech G., Arrangoiz R., Jimenez Ley V.B., Arizpe D., Lagunes Lara E., Castro Lopez E.V., Eaazim J., Gordinou de Gouberville M., Bastiaenen V., Rottier S., Nahab F., Ji M.Y., Seyoji M., Nwachukwu C., Emeghara O., Muhammed S.E., Idowu A., Sowemimo O., Ogundoyin O., Akande O., Lott A., Nadeem M., Laghari A.A., Loya A., Mushtaq H., Abdullah M.T., Abuhilal B., Atawneh M., Hamdan H., Alhabil B., Srour A., Mousa I., Da Silva Medina L., Bartosiak K., Ferreira P., Francisco V., Lemos R., Frutuoso L., Fernandes S., Fonseca T., Pereira J., Rachadell J., Torre A., Madeira Martins F., Carvalho A.C., Rodrigues Ferreira J., Ribeiro da Silva B., Devesa H., Vieira A., Monica I., Amaro M., Sousa D., Reia M., Louro J., Martins A., Dominguez J., Santos I., Freitas Oliveira N.M., Pereira J.C., Silva-Vaz P., Freire L., Escrevente R., Negoita V.M., Shakhmatov D., Nezerwa Y., Radulovic R., Obery G., Viljoen F., Mendes T., Suarez A., Moncada E., Fernandez-Hevia M., Curtis Martinez C., Gil Garcia J.M., Gonzalez Zunzarren M., Idris T., Eklov K., Grahn O., Amin L., Blomqvist M., Ajani C., Kraus R., Seeger N., Willemin M., Rayya F., Ayash M., Msouti R., Kannas I., Abazid E., Esper A., Slim S., Kavcar A.S., Aytac E., Dural A.C., Ilker A., Eray I.C., Kurnaz E., Altiner S., Tepe M.D., Sahin C., Savli E., Innocent A., Babirye L., Diachenko A., Hordoskiy V., Curry H., Chau C.Y.C., Robertson H., Lennon H., Loi L., Kirkham E., McCann C., Watts D., Gurung B., Wilson M., Tribedi T., Garofalo E., Zahra B., MacDonald S., Daniels I., Ng N., Khosla S., Olivier J., Yue 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V., Ye, G., Zhang, G., Brooker, E., Feng, D., Lau, B., Ngai, C., Birks, S., Gyorki, D., Otero de Pablos, J., Abbosh, A., Gillespie, C., Mahmoud, A., Kwan, B., Lawson, J., Warwick, A., Bingham, J., Cockbain, A. J., Dudi-Venkata, N. N., Ellaby-Hall, J., Finlay, B., Humphries, E., Pisaniello, J., Pisaniello, M., Salih, S., Sammour, T., Abd Wahab, H. H., De Silva, A., Hayward, N., Iyer, K., Maddern, G., Prevost, G. A., Annapureddy, N., Settipalli, K. P., Yeo, J., Hempenstall, L., Pham, L., Purcell, S., Talavera, C., Vaska, A. I., Chaggar, G., Chrapko, P., Cocco, A., Coulter-Nile, S. M. C. J., Ctercteko, G., French, J., Gong, H., Gosselink, M., Jegathees, T., Jin, I., Kalachov, M., Kiefhaber, K., Lee, K., Luong, J., Phan, S., Pleass, H., Veale, K., Zeng, Z., Au, A., Debiasio, A., Deng, I., Myooran, J., Nair, A., Stewart, P., Stift, A., Unger, L. W., Wimmer, K., Ahmed, N., Hasan, S., Rahman, S., O'Shea, M., Padmore, G., Peters, A., Perduca, P., Pulcina, G., Tinton, N., Buxant, F., Dabin, E., Garofalo, G., Dossou, F., Gnangnon, F. H. R., Imorou Souaibou, Y., Motlaleselelo, P., Tlhomelang, O., Lima Buarque, I., Mendonca Ataide Gomes, G., Vieira Barros, A., Batashki, I., Damianov, N., Stoyanov, V., Dardanov, D., Maslyankov, S., Petkov, P., Todorov, G., Zhivkov, E., Akisheva, A., Castilla Moreno, M. A., Genov, G., Ilieva, I., Ivanov, T., Karamanliev, M., Khan, A., Mitkov, E., Yotsov, T., Atanasov, B., Belev, N., Slavchev, M., Nsengiyumva, C., Jones, E., Stock, S., Kyota, S., Brown, J., Mabanza, K. T., Nigo Samuel, L., Otuneme, C., Prosper, N., Umenze, F., Boutros, M., Caminsky, N., Dumitra, S., Garfinkle, R., Morency, D., Salama, E., Banks, A., Ferri, L., He, H., Katz, A., Liberman, A. 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A., Fadel, A., Habater, A., Hamdy, H., Hefni, A., Kamal, M., Mohamed Abobakr, N., Sayed, A., Shaker, N., Taha, E., Tharwat, H., Zakaria, O., Abdelmotaleb, I., Al-Dhufri, A., Al-Himyari, H. S., El sheikh, E., Eldmaty, A., Elkhalawy, A., M. Elkhashen, A., Magdy, K., Mostafa, S., Sadia, H. D., Saleh, M. M., Samir, D., Yahia Mohamed Ali, M., A. Nassar, M., Abdelhady, S., Abdelrazek, A., Abdelsalam, I., El-Sawy, A., Essam, E., Gadelkarim, M., Ghaly, K., Hassabalnaby, M., Masarani, R., Mohamed Shaaban, N., Sabry, A., Salem, M., Soliman, N. A., Zahran, D., Abou, El. soud M. R., Badr, E. T., Borham, H., Elmeslemany, N., Elsayed, M., Elsherif, F., Eslam, S., Gaber, G., Ibrahim, S., Kamh, Y., Mohamed, S. G., Morshedy, E., Omar, C., Salem Soliman, F., Abdelkawy, S., Abdelmohsen, N., Abdelshakour, M., Dahy, A., Gamal, N., Gamal, M., Hasan, A., Hetta, H., Mousa, N., Omar, M., Rabie, S., Saad, M., Saleh, B., Sayed Mohamed, M., Shawqi, M., Abdelhady Mousa, H., Alnoury, M., Elbealawy, M., Elshafey, A., Essam Ibrahim El Desouki Muhammad Ahmed, M., Ghonaim, M., Hgag, F., Ibrahim, M., Morsy, M., Reda Loaloa, M., Refaat, A., Samir, H., Shahien, F., Sobhy, M., Sroor, F., Abdellatif, E., Adel, M., Afifi, A. A., Afifi, E., Antaky, M., Dawoud, A., El Zoghby, N., El-remaily, A., Elzanfaly, A. A., Gadallah, A., Gamal, F. A., Hashem, O., Medhat Youssef, S., Muhammad Attyah, A., Munir, M., Shazly, O., Wilson, K., Adel, S., Ali, A., Eid, E., Elhelow, E., Elmahdy, M., Elshatby, B., Hossam el-din Zakaria, A., Hossny, A., Ibrahim, E., M. 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I., Veiga, D., Azevedo, J., Cardoso Louro, H., Leite, M., Bairos Menezes, M., Gama, B., Brito, D., Cruz Martins, M. C., Graca e Magalhaes, A., Longras, A. C., Lourenco, R., Matos, D., Castro, L., Policarpo, F., Romano, J., Monteiro, C., Pinto, D., Duarte, M., Fortuna Martins, S., Oliveira, M., Galvao, D., Martins, L., Silva, A., Taranu, V., Vieira, B., Neves, J., Oliveira, S., Ribeiro, H., Cinza, M., Felix, R., Machado, A., Oliveira, J., Patricio, J., Pedroso de Lima, R., Pereira, M., Rocha Melo, M., Velez, C., Abreu da Silva, A., Claro, M., Costa Santos, D., Ferreira, A., Capote, H., Rosado, D., Tare, F., Nogueira, O., Angelo, M., Baiao, J. M., Guimaraes, A., Marques, J., Nico Albano, M., Silva, M., Valente da Costa, A., Vieira Caroco, T., Almeida Braga, S., Capunge, I., Fragoso, M., Guimaraes, J., Pinto, B., Ribeiro, J., Angel, M., Fialho, G., Guerrero, M., Campos Costa, F., Cardoso, D., Cardoso, V., Alves, M., Estalagem, I., Louro, T., Marques, C., Martelo, R., Morgado, M., Canotilho, R., Correia, A. M., Martins, P., Peyroteo, M., Gomes, J., Monteiro, R., Romano, M., Alves, D. M., Peixoto, R., Quintela, C., Jervis, M. J., Melo, D., Pacheco, A., Paixao, V., Pedro, V., Pimenta, J., Pimenta de Castro, J., Rocha, A., Beuran, M., Ciubotaru, C., Diaconescu, B., Hostiuc, S., Negoi, I., Stoica, B., Na, N. A., Anokhin, E., Kuznetsov, G., Oganezov, G., Paramzin, F., Romanova, E., Rutkovskii, V., Shushval, M., Zabiyaka, M., Dzhumabaev, K., Ivanov, V., Mamedli, Z., Achkasov, S., Balkarov, A., Nabiev, E., Nagudov, M., Rybakov, E., Saifutdinova, K., Sushkov, O., Joseph, L., Ndayishimiye, I., Faustin, N., Mutabazi, A. 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González, María Catalina, Zubiaurre, Vanessa, Demolin, Rodrigo, Giroff, Nicolas, Sciuto, Pablo, Campos, Maite, Rodríguez Cantera, Gabriela, Deepika, Garg, Simuchimba, Elliot, Bulaya, Anadi, Chibuye, Chali, Chirengendure, Bright, Kabale, Mary-Rose, Kabongo, Kizito, Munthali, James, Mweso, Oliver, Pikiti, Francis, Otieno, James, Lai, Log Tung, Blackman, Brighid, Richards, Sophie, Subramaniam, Suren, Karim, Rafid, Kok, Nathan, Lee, Yanni Dion, Ali, Shabina, Sinha, Aanjaneya, Corrigan, Robert, Barnes, Nicole, Wong, Florence, Dennis, Grace, Jedamzik, Julia, Phillips, Emil, Piette, Wivine, Van Hentenryck, Marie, Koco, Houenoukpo, Lawani, Souliath, Kassa, Mamo Woldu, Santos Bezerra, Tainá, Gribnev, Petar, Dimitrov, Dobromir, Krastev, Panche, Oum, Sovannarith, Bonghaseh, Divine Tim, Al Farsi, Maryam, Alsharqawi, Nourah, Acevedo, Veronica, Castillo Barbosa, Andrea Carolina, Giron, Felipe, Leon Rodriguez, Jimmy Paul, Kucan, Darko, Rosko, Damir, Barsic, Neven, Župan, Domagoj, Hegazi, Amgad, Truncíková, Vendula, Fryba, Vladimir, Mohamed, Mostafa, Sultan, Ahmed, Nagi, Ahmed, Rashad Temerik, Abdallah, Elshawy, Mohamed Elemam, Mahmoud, Moustafa Ibrahim, Omar, Shrouk, Anwar, Mohamed, Rageh, Tarek, Elmokadem, Aya, Gaballa, Khaled, Teppo, Sandra, Turunen, Antti, Pengermä, Pasi, Ballouhey, Quentin, Bergeat, Damien, Weyl, Ariane, Hain, Elisabeth, Gyedu, Adam, Yenli, Edwin, Osei-Poku, Dorcas, Rompou, Vaia-Aliki, Zoikas, Athanasios, Gaitanidis, Apostolos, Koukis, Georgios, Perivoliotis, Konstantinos, Tavlas, Panagiotis, Galanos-Demiris, Konstantinos, Zografos, George, Karavokyros, Ioannis, Xanthopoulou, Georgia, Iordanidou, Eirini, Ayau, Fernanda, Garcia, Allan, Damján, Pekli, Wason, Deepender, B L, Ashika, Rangganata, Ervandy, Kamath, Prerna, O'Connor, Donal B, Pinto, Margherita, Perrone, Fabrizio, Tropeano, Francesca Paola, Troilo, Francesca, Bossi, Daniela, Scala, Dario, Pulitanò, Lucrezia, Carella, Marcella, Pietrabissa, Andrea, Gori, Alice, Giraudo, Giorgio, De Simone, Veronica, Russo, Alfio Alessandro, Braccio, Bartolomeo, Al-Taher, Raed, Athamneh, Sarah, Parker, Andrea, Sawiee, Adnan, Kattia, Amina, Salem, Malik, Tababa, Osama, Shaeeb, Zuhour, Syminas, Vilius, Jurgaitis, Jonas, Damuleviciene, Gyte, Svagzdys, Saulius, Poskus, Tomas, Razafimanjato, Narindra Njarasoa Mihaja, Chieng Loo, Ling, Tiong, Ing Ching, Wan Muhmad, Wan Farahiyah, Vijeyan, Harinthiran, Li Ying, Teoh, Grech, Gabriella, Arrangoiz, Rodrigo, Jimenez Ley, Vania Brickelia, Arizpe, Daniel, Lagunes Lara, Elizabeth, Castro López, Elizabeth Victoria, Eaazim, Jose, Gordinou de Gouberville, Marije, Bastiaenen, Vivian, Rottier, Simone, Nahab, Fouad, Ji, Maria Yeonhee, Seyoji, Mohammed, Nwachukwu, Callistus, Emeghara, Okechukwu, Muhammed, Sayyid Egbunu, Idowu, Ayodeji, Sowemimo, Olamiposi, Ogundoyin, Olakayode, Akande, Oluwatosin, Lott, Alexander, Nadeem, Maliha, Laghari, Ahsan Ali, Loya, Asif, Mushtaq, Hassan, Abdullah, Muhammad Tariq, Abuhilal, Baseel, Atawneh, Mohammad, Hamdan, Hamdan, 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Lesetedi, Chiapo, Mabedi, Charles, Magill, Laura, Makinde Alakaloko, Felix, Makupe, Alex, Monahan, Mark, Mulira, Soloman, Muller, Elmi, Musowoyo, Jospeh, Olory-Togbe, Jean Léon, Roberts, Tracey, Smith, Martin, Tayler, Viki, Windsor, John, Yepez, Raul, Sundar, Sudha, Runigamugabo, Emmy, Verjee, Azmina, Chen, José, Daya, Leonid, El Aroussi, Nouhaila, Farina, Valeria, Gnintedeme Olivier, Tchianze, Gonzales Nacarino, Mauricio, Hammani, Aamr, Honjo, Sarah, Jacobs, Rebecca, Kimura, Hitomi, Nkoronko, Mugisha, Oscullo Yepez, Jasson Javier, Pin Hung, Wei, Raj, Ankit, Romani Pozo, Alina, Rommaneh, Muna, Sassamela Fabiano, Samuel Chimbioputo, Shiroma Gago, Camila Milagros, Srinivas, Abhishekh, Sung, Chia-Yen, Tai, Aswan, Valle Aranda, Yener Cristyell, Venturini, Sara, and Wilguens Lartigue, Jean
Subjects: Pediatrics, Colorectal cancer, IMPACT, Disease, Colorectal Neoplasm, 030204 cardiovascular system & hematology, Cancer, surgery, postoperative mortality, 0302 clinical medicine, Postoperative Complications, Global health, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, General Medicine, DISEASES, Income, cancer surgery, Colorectal Neoplasms, Breast Neoplasm, Cohort study, Human, Adult, Developed Countrie, medicine.medical_specialty, Global surgery, General surgery, International multicentre study, Cancer surgery, Breast Neoplasms, Department of Error, NO, Developing Countrie, 03 medical and health sciences, Breast cancer, Stomach Neoplasms, medicine, Humans, Developing Countries, Neoplasm Staging, business.industry, Developed Countries, Odds ratio, CARE, medicine.disease, 3126 Surgery, anesthesiology, intensive care, radiology, Prospective Studie, Postoperative Complication, business
Abstract: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Background: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit.
Published: 2021
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23. The future of human malnutrition: rebalancing agency for better nutritional health

Author: David Raubenheimer, Gabriel S. Amable, Jonathan C. K. Wells, J. Jaime Miranda, Hinke Haisma, Henrik Friis, Akanksha A. Marphatia, Mario Siervo, Wells, Jonathan CK [0000-0003-0411-8025], Apollo - University of Cambridge Repository, Wells, Jonathan C. K. [0000-0003-0411-8025], and Wells, Jonathan C K [0000-0003-0411-8025]
Subjects: Double burden, future prospect, Social inequality, global health, Review, Global Health, homeostasis, Agency (sociology), Development economics, Global health, medicine, Malnutrition / epidemiology, Humans, Disease, human, Obesity, Social policy, Global Health/trends, Stunting, Health Policy, Malnutrition, Public Health, Environmental and Occupational Health, COVID-19, Undernutrition, Dual burden of malnutrition, medicine.disease, Coronavirus, Food systems, Conceptual framework, Agency, Business, physiological response, Public aspects of medicine, RA1-1270, dietary intake, Forecasting
Abstract: The major threat to human societies posed by undernutrition has been recognised for millennia. Despite substantial economic development and scientific innovation, however, progress in addressing this global challenge has been inadequate. Paradoxically, the last half-century also saw the rapid emergence of obesity, first in high-income countries but now also in low- and middle-income countries. Traditionally, these problems were approached separately, but there is increasing recognition that they have common drivers and need integrated responses. The new nutrition reality comprises a global ‘double burden’ of malnutrition, where the challenges of food insecurity, nutritional deficiencies and undernutrition coexist and interact with obesity, sedentary behaviour, unhealthy diets and environments that foster unhealthy behaviour. Beyond immediate efforts to prevent and treat malnutrition, what must change in order to reduce the future burden? Here, we present a conceptual framework that focuses on the deeper structural drivers of malnutrition embedded in society, and their interaction with biological mechanisms of appetite regulation and physiological homeostasis. Building on a review of malnutrition in past societies, our framework brings to the fore the power dynamics that characterise contemporary human food systems at many levels. We focus on the concept of agency, the ability of individuals or organisations to pursue their goals. In globalized food systems, the agency of individuals is directly confronted by the agency of several other types of actor, including corporations, governments and supranational institutions. The intakes of energy and nutrients by individuals are powerfully shaped by this ‘competition of agency’, and we therefore argue that the greatest opportunities to reduce malnutrition lie in rebalancing agency across the competing actors. The effect of the COVID-19 pandemic on food systems and individuals illustrates our conceptual framework. Efforts to improve agency must both drive and respond to complementary efforts to promote and maintain equitable societies and planetary health.
Published: 2021
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24. Pregnancy Outcomes in Women After Arterial Switch Operation for Transposition of the Great Arteries: Results From ROPAC (Registry of Pregnancy and Cardiac Disease) of the European Society of Cardiology EURObservational Research Programme

Author: Oktay Tutarel, Karishma P. Ramlakhan, Lucia Baris, Maria T. Subirana, Judith Bouchardy, Attila Nemes, Niels G. Vejlstrup, Olga A. Osipova, Mark R. Johnson, Roger Hall, Jolien W. Roos‐Hesselink, Christopher Peter Gale, Branko Beleslin, Andrzej Budaj, Ovidiu Chioncel, Nikolaos Dagres, Nicolas Danchin, David Erlinge, Jonathan Emberson, Michael Glikson, Alastair Gray, Meral Kayikcioglu, Aldo Maggioni, Klaudia Vivien Nagy, Aleksandr Nedoshivin, Anna‐Sonia Petronio, Jolien Roos‐Hesselink, Lars Wallentin, Uwe Zeymer, Joerg Stein, William Anthony Parsonage, Werner Budts, Julie De Backer, Jasmin Grewal, Ariane Marelli, Harald Kaemmerer, Guillaume Jondeau, Mark Johnson, Aldo P. Maggioni, Luigi Tavazzi, Ulf Thilen, Uri Elkayam, Catherine Otto, Karen Sliwa, A. Aquieri, A. Saad, H. Ruda Vega, J. Hojman, J. M. Caparros, M. Vazquez Blanco, M. Arstall, C. M. Chung, G. Mahadavan, E. Aldridge, M. Wittwer, Y. Y. Chow, W. A. Parsonage, K. Lust, N. Collins, G. Warner, R. Hatton, A. Gordon, E. Nyman, J. Stein, E. Donhauser, H. Gabriel, A. Bahshaliyev, F. Guliyev, I. Hasanova, T. Jahangirov, Z. Gasimov, A. Salim, C. M. Ahmed, F. Begum, M. H. Hoque, M. Mahmood, M. N. Islam, P. P. Haque, S. K. Banerjee, T. Parveen, M. Morissens, J. De Backer, L. Demulier, M. de Hosson, W. Budts, M. Beckx, M. Kozic, M. Lovric, T. Kovacevic‐Preradovic, N. Chilingirova, P. Kratunkov, N. Wahab, S. McLean, E. Gordon, L. Walter, A. Marelli, A. R. Montesclaros, G. Monsalve, C. Rodriguez, F. Balthazar, V. Quintero, W. Palacio, L. A. Mejía Cadavid, E. Munoz Ortiz, F. Fortich Hoyos, E. Arevalo Guerrero, J. Gandara Ricardo, J. Velasquez Penagos, Z. Vavera, J. Popelova, N. Vejlstrup, L. Grønbeck, M. Johansen, A. Ersboll, Y. Elrakshy, K. Eltamawy, M. Gamal Abd‐El Aziz, A. El Nagar, H. Ebaid, H. Abo Elenin, M. Saed, S. Farag, W. Makled, K. Sorour, Z. Ashour, G. El‐Sayed, M. Abdel Meguid Mahdy, N. Taha, A. Dardeer, M. Shabaan, M. Ali, P. Moceri, G. Duthoit, M. Gouton, J. Nizard, L. Baris, S. Cohen, M. Ladouceur, D. Khimoud, B. Iung, F. Berger, A. Olsson, U. Gembruch, W. M. Merz, E. Reinert, S. Clade, Y. Kliesch, C. Wald, C. Sinning, R. Kozlik‐Feldmann, S. Blankenberg, E. Zengin‐Sahm, G. Mueller, M. Hillebrand, P. Hauck, Y. von Kodolitsch, N. Zarniko, H. Baumgartner, R. Schmidt, A. Hellige, O. Tutarel, H. Kaemmerer, B. Kuschel, N. Nagdyman, R. Motz, D. Maisuradze, A. Frogoudaki, E. Iliodromitis, M. Anastasiou‐Nana, D. Triantafyllis, G. Bekiaris, H. Karvounis, G. Giannakoulas, D. Ntiloudi, S. A. Mouratoglou, A. Temesvari, H. Balint, D. Kohalmi, B. Merkely, C. Liptai, A. Nemes, T. Forster, A. Kalapos, K. Berek, K. Havasi, N. Ambrus, A. Shelke, R. Kawade, S. Patil, E. Martanto, T. M. Aprami, A. Purnomowati, C. J. Cool, M. Hasan, R. Akbar, S. Hidayat, T. I. Dewi, W. Permadi, D. A. Soedarsono, M. M. Ansari‐Ramandi, N. Samiei, A. Tabib, F. Kashfi, S. Ansari‐Ramandi, S. Rezaei, H. Ali Farhan, A. Al‐Hussein, G. Al‐Saedi, G. Mahmood, I. F. Yaseen, L. Al‐Yousuf, M. AlBayati, S. Mahmood, S. Raheem, T. AlHaidari, Z. Dakhil, P. Thornton, J. Donnelly, M. Bowen, A. Blatt, G. Elbaz‐Greener, A. Shotan, S. Yalonetsky, S. Goland, M. Biener, G. Egidy Assenza, M. Bonvicini, A. Donti, A. Bulgarelli, D. Prandstraller, C. Romeo, R. Crepaz, E. Sciatti, M. Metra, R. Orabona, L. Ait Ali, P. Festa, V. Fesslova, C. Bonanomi, M. Calcagnino, F. Lombardi, null Colli, M. W. Ossola, C. Gobbi, E. Gherbesi, L. Tondi, M. Schiavone, M. Squillace, M. G. Carmina, A. Maina, C. Macchi, E. Gollo, F. M. Comoglio, N. Montali, P. Re, R. Bordese, T. Todros, V. Donvito, W. Grosso Marra, G. Sinagra, B. D'Agata Mottolese, M. Bobbo, V. Gesuete, S. Rakar, F. Ramani, K. Niwa, D. Mekebekova, A. Mussagaliyeva, T. Lee, E. Mirrakhimov, S. Abilova, E. Bektasheva, K. Neronova, O. Lunegova, R. Žaliūnas, R. Jonkaitienė, J. Petrauskaitė, A. Laucevicius, D. Jancauskaite, L. Lauciuviene, L. Gumbiene, L. Lankutiene, S. Glaveckaite, M. Laukyte, S. Solovjova, V Rudiene, K. H. Chee, C. C.‐W. Yim, H. L. Ang, R. Kuppusamy, T. Watson, M. Caruana, M.‐E. Estensen, M. G. A. Mahmood Kayani, R. Munir, A. Tomaszuk‐Kazberuk, B. Sobkowicz, J. Przepiesc, A. Lesniak‐Sobelga, L. Tomkiewicz‐Pajak, M. Komar, M. Olszowska, P. Podolec, S. Wisniowska‐Smialek, M. Lelonek, U. Faflik, A. Cichocka‐Radwan, K. Plaskota, O. Trojnarska, N. Guerra, L. de Sousa, C. Cruz, V. Ribeiro, S. Jovanova, V. Petrescu, R. Jurcut, C. Ginghina, I. Mircea Coman, M. Musteata, O. Osipova, T. Golivets, I. Khamnagadaev, O. Golovchenko, A. Nagibina, I. Ropatko, I. R. Gaisin, L. Valeryevna Shilina, N. Sharashkina, E. Shlyakhto, O. Irtyuga, O. Moiseeva, E. Karelkina, I. Zazerskaya, A. Kozlenok, I. Sukhova, L. Jovovic, K. Prokšelj, M. Koželj, A. O. Askar, A. A. Abdilaahi, M. H. Mohamed, A. M. Dirir, K. Sliwa, P. Manga, A. Pijuan‐Domenech, L. Galian‐Gay, P. Tornos, M. T. Subirana, N. Murga, J. M. Oliver, B. Garcia‐Aranda Dominguez, I. Hernandez Gonzalez, J. F. Delgado Jimenez, P. Escribano Subias, A. Elbushi, A. Suliman, K. Jazzar, M. Murtada, N. Ahamed, M. Dellborg, E. Furenas, M. Jinesjo, K. Skoglund, P. Eriksson, T. Gilljam, U. Thilen, D. Tobler, K. Wustmann, F. Schwitz, M. Schwerzmann, T. Rutz, J. Bouchardy, M. Greutmann, B. M. Santos Lopes, L. Meier, M. Arrigo, K. de Boer, T. Konings, E. Wajon, L. J. Wagenaar, P. Polak, E. P. G. Pieper, J. Roos‐Hesselink, I. van Hagen, H. Duvekot, J. M. J. Cornette, C. De Groot, C. van Oppen, L. Sarac, O. Batukan Esen, S. Catirli Enar, C. Mondo, P. Ingabire, B. Nalwanga, T. Semu, B. T. Salih, W. A. R. Almahmeed, S. Wani, F. S. Mohamed Farook, Al Ain, F. Gerges, A. M. Komaranchath, F. Al bakshi, A. Al Mulla, A. H. Yusufali, E. I. Al Hatou, N. Bazargani, F. Hussain, L. Hudsmith, P. Thompson, S. Thorne, S. Bowater, A. Money‐Kyrle, P. Clifford, P. Ramrakha, S. Firoozan, J. Chaplin, N. Bowers, D. Adamson, F. Schroeder, R. Wendler, S. Hammond, P. Nihoyannopoulos, R. Hall, L. Freeman, G. Veldtman, J. Kerr, L. Tellett, N. Scott, A. B. Bhatt, D. DeFaria Yeh, M. A. Youniss, M. Wood, A. A. Sarma, S. Tsiaras, A. Stefanescu, J. M. Duran, L. Stone, D. S. Majdalany, J. Chapa, K. Chintala, P. Gupta, J. Botti, J. Ting, W. R. Davidson, G. Wells, D. Sparks, V. Paruchuri, K. Marzo, D. Patel, W. Wagner, S. N. Ahanya, L. Colicchia, T. Jentink, K. Han, M. Loichinger, M. Parker, C. Longtin, A. Yetman, K. Erickson, J. Cramer, S. Tsai, B. Fletcher, S. Warta, C. Cohen, C. Lindblade, R. Puntel, K. Nagaran, N. Croft, M. Gurvitz, C. Otto, C. Talluto, D. Murphy, M. G. Perlroth, ROPAC (Registry of Pregnancy and Cardiac Disease) Investigators Group, Gale, C.P., Beleslin, B., Budaj, A., Chioncel, O., Dagres, N., Danchin, N., Erlinge, D., Emberson, J., Glikson, M., Gray, A., Kayikcioglu, M., Maggioni, A., Nagy, K.V., Nedoshivin, A., Petronio, A.S., Roos-Hesselink, J., Wallentin, L., Zeymer, U., Hall, R., Stein, J., Parsonage, W.A., Budts, W., De Backer, J., Grewal, J., Marelli, A., Kaemmerer, H., Jondeau, G., Johnson, M., Maggioni, A.P., Tavazzi, L., Thilen, U., Elkayam, U., Otto, C., Sliwa, K., Aquieri, A., Saad, A., Ruda Vega, H., Hojman, J., Caparros, J.M., Vazquez Blanco, M., Arstall, M., Chung, C.M., Mahadavan, G., Aldridge, E., Wittwer, M., Chow, Y.Y., Lust, K., Collins, N., Warner, G., Hatton, R., Gordon, A., Nyman, E., Donhauser, E., Gabriel, H., Bahshaliyev, A., Guliyev, F., Hasanova, I., Jahangirov, T., Gasimov, Z., Salim, A., Ahmed, C.M., Begum, F., Hoque, M.H., Mahmood, M., Islam, M.N., Haque, P.P., Banerjee, S.K., Parveen, T., Morissens, M., Demulier, L., de Hosson, M., Beckx, M., Kozic, M., Lovric, M., Kovacevic-Preradovic, T., Chilingirova, N., Kratunkov, P., Wahab, N., McLean, S., Gordon, E., Walter, L., Montesclaros, A.R., Monsalve, G., Rodriguez, C., Balthazar, F., Quintero, V., Palacio, W., Mejía Cadavid, L.A., Munoz Ortiz, E., Fortich Hoyos, F., Arevalo Guerrero, E., Gandara Ricardo, J., Velasquez Penagos, J., Vavera, Z., Popelova, J., Vejlstrup, N., Grønbeck, L., Johansen, M., Ersboll, A., Elrakshy, Y., Eltamawy, K., Gamal Abd-El Aziz, M., El Nagar, A., Ebaid, H., Abo Elenin, H., Saed, M., Farag, S., Makled, W., Sorour, K., Ashour, Z., El-Sayed, G., Abdel Meguid Mahdy, M., Taha, N., Dardeer, A., Shabaan, M., Ali, M., Moceri, P., Duthoit, G., Gouton, M., Nizard, J., Baris, L., Cohen, S., Ladouceur, M., Khimoud, D., Iung, B., Berger, F., Olsson, A., Gembruch, U., Merz, W.M., Reinert, E., Clade, S., Kliesch, Y., Wald, C., Sinning, C., Kozlik-Feldmann, R., Blankenberg, S., Zengin-Sahm, E., Mueller, G., Hillebrand, M., Hauck, P., von Kodolitsch, Y., Zarniko, N., Baumgartner, H., Schmidt, R., Hellige, A., Tutarel, O., Kuschel, B., Nagdyman, N., Motz, R., Maisuradze, D., Frogoudaki, A., Iliodromitis, E., Anastasiou-Nana, M., Triantafyllis, D., Bekiaris, G., Karvounis, H., Giannakoulas, G., Ntiloudi, D., Mouratoglou, S.A., Temesvari, A., Balint, H., Kohalmi, D., Merkely, B., Liptai, C., Nemes, A., Forster, T., Kalapos, A., Berek, K., Havasi, K., Ambrus, N., Shelke, A., Kawade, R., Patil, S., Martanto, E., Aprami, T.M., Purnomowati, A., Cool, C.J., Hasan, M., Akbar, R., Hidayat, S., Dewi, T.I., Permadi, W., Soedarsono, D.A., Ansari-Ramandi, M.M., Samiei, N., Tabib, A., Kashfi, F., Ansari-Ramandi, S., Rezaei, S., Ali Farhan, H., Al-Hussein, A., Al-Saedi, G., Mahmood, G., Yaseen, I.F., Al-Yousuf, L., AlBayati, M., Mahmood, S., Raheem, S., AlHaidari, T., Dakhil, Z., Thornton, P., Donnelly, J., Bowen, M., Blatt, A., Elbaz-Greener, G., Shotan, A., Yalonetsky, S., Goland, S., Biener, M., Egidy Assenza, G., Bonvicini, M., Donti, A., Bulgarelli, A., Prandstraller, D., Romeo, C., Crepaz, R., Sciatti, E., Metra, M., Orabona, R., Ait Ali, L., Festa, P., Fesslova, V., Bonanomi, C., Calcagnino, M., Lombardi, F., Colli, C., Ossola, M.W., Gobbi, C., Gherbesi, E., Tondi, L., Schiavone, M., Squillace, M., Carmina, M.G., Maina, A., Macchi, C., Gollo, E., Comoglio, F.M., Montali, N., Re, P., Bordese, R., Todros, T., Donvito, V., Grosso Marra, W., Sinagra, G., D'Agata Mottolese, B., Bobbo, M., Gesuete, V., Rakar, S., Ramani, F., Niwa, K., Mekebekova, D., Mussagaliyeva, A., Lee, T., Mirrakhimov, E., Abilova, S., Bektasheva, E., Neronova, K., Lunegova, O., Žaliūnas, R., Jonkaitienė, R., Petrauskaitė, J., Laucevicius, A., Jancauskaite, D., Lauciuviene, L., Gumbiene, L., Lankutiene, L., Glaveckaite, S., Laukyte, M., Solovjova, S., Rudiene, V., Chee, K.H., Yim, C.C., Ang, H.L., Kuppusamy, R., Watson, T., Caruana, M., Estensen, M.E., Mahmood Kayani, MGA, Munir, R., Tomaszuk-Kazberuk, A., Sobkowicz, B., Przepiesc, J., Lesniak-Sobelga, A., Tomkiewicz-Pajak, L., Komar, M., Olszowska, M., Podolec, P., Wisniowska-Smialek, S., Lelonek, M., Faflik, U., Cichocka-Radwan, A., Plaskota, K., Trojnarska, O., Guerra, N., de Sousa, L., Cruz, C., Ribeiro, V., Jovanova, S., Petrescu, V., Jurcut, R., Ginghina, C., Mircea Coman, I., Musteata, M., Osipova, O., Golivets, T., Khamnagadaev, I., Golovchenko, O., Nagibina, A., Ropatko, I., Gaisin, I.R., Valeryevna Shilina, L., Sharashkina, N., Shlyakhto, E., Irtyuga, O., Moiseeva, O., Karelkina, E., Zazerskaya, I., Kozlenok, A., Sukhova, I., Jovovic, L., Prokšelj, K., Koželj, M., Askar, A.O., Abdilaahi, A.A., Mohamed, M.H., Dirir, A.M., Manga, P., Pijuan-Domenech, A., Galian-Gay, L., Tornos, P., Subirana, M.T., Murga, N., Oliver, J.M., Garcia-Aranda Dominguez, B., Hernandez Gonzalez, I., Delgado Jimenez, J.F., Escribano Subias, P., Elbushi, A., Suliman, A., Jazzar, K., Murtada, M., Ahamed, N., Dellborg, M., Furenas, E., Jinesjo, M., Skoglund, K., Eriksson, P., Gilljam, T., Tobler, D., Wustmann, K., Schwitz, F., Schwerzmann, M., Rutz, T., Bouchardy, J., Greutmann, M., Santos Lopes, B.M., Meier, L., Arrigo, M., de Boer, K., Konings, T., Wajon, E., Wagenaar, L.J., Polak, P., Pieper, EPG, van Hagen, I., Duvekot, H., Cornette, JMJ, De Groot, C., van Oppen, C., Sarac, L., Batukan Esen, O., Catirli Enar, S., Mondo, C., Ingabire, P., Nalwanga, B., Semu, T., Salih, B.T., Almahmeed, WAR, Wani, S., Mohamed Farook, F.S., Ain, A., Gerges, F., Komaranchath, A.M., Al Bakshi, F., Al Mulla, A., Yusufali, A.H., Al Hatou, E.I., Bazargani, N., Hussain, F., Hudsmith, L., Thompson, P., Thorne, S., Bowater, S., Money-Kyrle, A., Clifford, P., Ramrakha, P., Firoozan, S., Chaplin, J., Bowers, N., Adamson, D., Schroeder, F., Wendler, R., Hammond, S., Nihoyannopoulos, P., Freeman, L., Veldtman, G., Kerr, J., Tellett, L., Scott, N., Bhatt, A.B., DeFaria Yeh, D., Youniss, M.A., Wood, M., Sarma, A.A., Tsiaras, S., Stefanescu, A., Duran, J.M., Stone, L., Majdalany, D.S., Chapa, J., Chintala, K., Gupta, P., Botti, J., Ting, J., Davidson, W.R., Wells, G., Sparks, D., Paruchuri, V., Marzo, K., Patel, D., Wagner, W., Ahanya, S.N., Colicchia, L., Jentink, T., Han, K., Loichinger, M., Parker, M., Longtin, C., Yetman, A., Erickson, K., Cramer, J., Tsai, S., Fletcher, B., Warta, S., Cohen, C., Lindblade, C., Puntel, R., Nagaran, K., Croft, N., Gurvitz, M., Talluto, C., Murphy, D., Perlroth, M.G., Neurosurgery, Pediatrics, Cardiology, ACS - Heart failure & arrhythmias, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Institut Català de la Salut, [Tutarel O] Department of Congenital Heart Disease and Paediatric Cardiology German Heart Centre MunichTechnical University of Munich School of MedicineTechnical University of Munich Germany. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance Munich Germany. [Ramlakhan KP, Baris L] Department of Cardiology Erasmus University Medical Center Rotterdam the Netherlands. [Subirana MT] Unitat de Cardiopaties congènites de l’adult, Vall d'Hebron Hospital Universitari, Barcelona Spain. Hospital Sant Pau, Barcelona Spain. [Bouchardy J] Service of Cardiology University Hospital Lausanne and University of Lausanne Switzerland. Service of Cardiology University of Geneva Switzerland. [Nemes A] 2nd Department of Medicine and Cardiology Centre Medical Faculty Albert Szent-Györgyi Clinical Center University of Szeged Hungary, Szeged, Hungary, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, Transposition of Great Vessels, pregnancy outcomes, enfermedades cardiovasculares::anomalías cardiovasculares::cardiopatías congénitas::transposición de los grandes vasos [ENFERMEDADES], Disease, 030204 cardiovascular system & hematology, Sistema cardiovascular - Malalties, Ventricular tachycardia, Vasos sanguinis - Cirurgia, 0302 clinical medicine, Pregnancy, Clinical endpoint, Registries, 030212 general & internal medicine, Cardiovascular Diseases::Pregnancy Complications, Cardiovascular [DISEASES], Original Research, Aortic dissection, Pregnancy Outcome, Congenital Heart Disease, Other subheadings::Other subheadings::/surgery [Other subheadings], arterial switch operation, pregnancy and cardiac disease, transposition of the great arteries, Europe, Great arteries, Cardiology, enfermedades cardiovasculares::complicaciones cardiovasculares del embarazo [ENFERMEDADES], Female, Maternal death, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, diagnóstico::pronóstico::resultado del embarazo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Pregnancy Complications, Cardiovascular, Embaràs - Complicacions, Cardiovascular Diseases::Cardiovascular Abnormalities::Heart Defects, Congenital::Transposition of Great Vessels [DISEASES], Risk Assessment, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Heart Failure, business.industry, Infant, Newborn, Otros calificadores::Otros calificadores::/cirugía [Otros calificadores], Diagnosis::Prognosis::Pregnancy Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], medicine.disease, Arterial Switch Operation, Heart failure, Tachycardia, Ventricular, business
Abstract: Embaràs i malaltia cardíaca; Resultats de l’embaràs; Transposició de les grans artèries Embarazo y enfermedad cardíaca; Resultados del embarazo; Transposición de las grandes arterias Pregnancy and cardiac disease; Pregnancy outcomes, Transposition of the great arteries Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate. Funding from “Zabawas Foundation” and “De Hoop Foundation” in addition to the support from EURObservational Research Programme (EORP) is greatly acknowledged. Since the start of EORP, the following companies have supported the program: Abbott Vascular Int (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2019), Daiichi Sankyo Europe GmbH (2011–2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc (2014–2016), Menarini Int Op (2009–2012), MSD‐Merck & Co (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2009–2021), and Vifor (2019–2022).
Published: 2021
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25. Covid-19 Interstitial Pneumonia: Histological and Immunohistochemical Features on Cryobiopsies

Author: Vincenzo Bronte, Venerino Poletti, Stefano Maitan, Alessandra Dubini, Marco Chilosi, Franco Stella, Athol U. Wells, Claudio Doglioni, Antonio Vizzuso, Silvia Puglisi, Giovanni Pizzolo, Vanni Agnoletti, Federica Pedica, Claudia Ravaglia, Giulio Rossi, Vittorio Sambri, Giovanni Poletti, Sara Piciucchi, and Doglioni C, Ravaglia C, Chilosi M, Rossi G, Dubini A, Pedica F, Piciucchi S, Vizzuso A, Stella F, Maitan S, Agnoletti V, Puglisi S, Poletti G, Sambri V, Pizzolo G, Bronte V, Wells AU, Poletti V.
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Coronaviru, Lung biopsy, Lung injury, 03 medical and health sciences, 0302 clinical medicine, Medicine, Cryobiopsy, 030212 general & internal medicine, Diffuse alveolar damage, Lung, Acute respiratory distress syndrome, SARS-CoV-2, business.industry, CD68, pSTAT-3, Hyperplasia, medicine.disease, Coronavirus, Endothelial stem cell, Pneumonia, medicine.anatomical_structure, 030228 respiratory system, Indoleamine 2,3-dioxygenase-1, Covid-19, business
Abstract: Background: The pathogenetic steps leading to Covid-19 interstitial pneumonia remain to be clarified. Most postmortem studies to date reveal diffuse alveolar damage as the most relevant histologic pattern. Antemortem lung biopsy may however provide more precise data regarding the earlier stages of the disease, providing a basis for novel treatment approaches. Objectives: To ascertain the morphological and immunohistochemical features of lung samples obtained in patients with moderate Covid-19 pneumonia. Methods: Transbronchial lung cryobiopsy was carried out in 12 Covid-19 patients within 20 days of symptom onset. Results: Histopathologic changes included spots of patchy acute lung injury with alveolar type II cell hyperplasia, with no evidence of hyaline membranes. Strong nuclear expression of phosphorylated STAT3 was observed in >50% of AECII. Interalveolar capillaries showed enlarged lumen and were in part arranged in superposed rows. Pulmonary venules were characterized by luminal enlargement, thickened walls, and perivascular CD4+ T-cell infiltration. A strong nuclear expression of phosphorylated STAT3, associated with PD-L1 and IDO expression, was observed in endothelial cells of venules and interstitial capillaries. Alveolar spaces macrophages exhibited a peculiar phenotype (CD68, CD11c, CD14, CD205, CD206, CD123/IL3AR, and PD-L1). Conclusions: Morphologically distinct features were identified in early stages of Covid-19 pneumonia, with epithelial and endothelial cell abnormalities different from either classical interstitial lung diseases or diffuse alveolar damage. Alveolar type II cell hyperplasia was a prominent event in the majority of cases. Inflammatory cells expressed peculiar phenotypes. No evidence of hyaline membranes and endothelial changes characterized by IDO expression might in part explain the compliance and the characteristic pulmonary vasoplegia observed in less-advanced Covid-19 pneumonia.
Published: 2021
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26. Cytokine/chemokine profiles in squamous cell carcinoma correlate with precancerous and cancerous disease stage

Author: Raymond J. Steptoe, Andrew W. Lewandowski, James W. Wells, H. Peter Soyer, Fiona Simpson, Graham R. Leggatt, Ian H. Frazer, Duncan Lambie, Miko Yamada, Zewen K. Tuong, Richard Lewandowski, Jazmina L. G. Cruz, Jennifer A. Bridge, Tuong, Zewen K, Lewandowski, Andrew, Bridge, Jennifer A, Cruz, Jazmina LG, Yamada, Miko, Lambie, Duncan, Lewandowski, Richard, Steptoe, Raymond J, Leggatt, Graham R, Simpson, Fiona, Frazer, Ian H, Soyer, H Peter, Wells, James W, Tuong, Zewen K [0000-0002-6735-6808], Frazer, Ian H [0000-0002-8002-4680], Soyer, H Peter [0000-0002-4770-561X], Wells, James W [0000-0002-9618-6940], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Chemokine, Skin Neoplasms, Keratosis, medicine.medical_treatment, lcsh:Medicine, Article, Proinflammatory cytokine, Tumour biomarkers, 03 medical and health sciences, 0302 clinical medicine, Actinic Keratosis (AK), Cancer epidemiology, Squamous cell carcinoma, medicine, Carcinoma, Humans, Clinical significance, lcsh:Science, Aged, Skin, Aged, 80 and over, Intraepidermal Carcinoma (IEC), Multidisciplinary, biology, business.industry, Actinic keratosis, lcsh:R, Cancer, Middle Aged, medicine.disease, Keratosis, Actinic, stomatognathic diseases, 030104 developmental biology, Cytokine, Squamous Cell Carcinoma (SCC), 030220 oncology & carcinogenesis, Cancer research, biology.protein, Carcinoma, Squamous Cell, Disease Progression, Cytokines, Female, lcsh:Q, Chemokines, business, Precancerous Conditions, Carcinoma in Situ
Abstract: Actinic Keratosis (AK), Intraepidermal Carcinoma (IEC), and Squamous Cell Carcinoma (SCC) are generally considered to be advancing stages of the same disease spectrum. However, while AK often regress spontaneously, and IEC often regress in response to immune-activating treatments, SCC typically do not regress. Therefore, it is vital to define whether fundamental immunological changes occur during progression to SCC. Here we show that proinflammatory cytokine expression, chemokine expression, and immune cell infiltration density change during progression to SCC. Our findings suggest a switch from predominantly proinflammatory cytokine production to chemokine production is a key feature of progression from precancer to cancer. Together, these observations propose a model that can underpin current research and open new avenues of exploration into the clinical significance of these profiles with respect to immunotherapeutic or other treatment outcomes.
Published: 2019
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27. Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum

Author: Rei Matsumoto, Yun Zhu, Emily M. Mace, Michael Chait, Wen-Hsuan W. Lin, Eldad A. Hod, Didier Decimo, Branka Horvat, Matthew R. Baldwin, Steven B. Wells, Stephen A. Ferrara, Stuart P. Weisberg, Julia Davis-Porada, Pranay Dogra, Donna L. Farber, Debora Stelitano, Emma Idzikowski, Flavia Dei Zotti, Cyrille Mathieu, Francesca T. Bovier, Matteo Porotto, Zachary C. Bitan, Sandeep N. Wontakal, Francesca La Carpia, Anne Moscona, Krystalyn E. Hudson, Joshua I. Gray, Thomas J. Connors, Peter A. Szabo, Joshua D. Milner, Maya Meimei Li Poon, Columbia University Irving Medical Center (CUIMC), University of the Study of Campania Luigi Vanvitelli, Columbia University [New York], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), Mathieu, Cyrille, Weisberg, S. P., Connors, T. J., Zhu, Y., Baldwin, M. R., Lin, W. -H., Wontakal, S., Szabo, P. A., Wells, S. B., Dogra, P., Gray, J., Idzikowski, E., Stelitano, D., Bovier, F. T., Davis-Porada, J., Matsumoto, R., Poon, M. M. L., Chait, M., Mathieu, C., Horvat, B., Decimo, D., Hudson, K. E., Zotti, F. D., Bitan, Z. C., La Carpia, F., Ferrara, S. A., Mace, E., Milner, J., Moscona, A., Hod, E., Porotto, M., and Farber, D. L.
Subjects: 0301 basic medicine, ARDS, [SDV]Life Sciences [q-bio], Immunology, Population, medicine.disease_cause, Article, Serology, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Immunology and Allergy, Respiratory system, Young adult, education, Coronavirus, education.field_of_study, biology, business.industry, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, biology.protein, Antibody, business, 030215 immunology
Abstract: International audience; Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.
Published: 2020
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28. Management of COMPlicAted intra‐abdominal collectionS after colorectal Surgery (COMPASS): protocol for a multicentre, observational, prospective international study of drain placement practices in colorectal surgery

Author: Sgrò, A, Blanco‐Colino, R, Ahmed, WUR, Brindl, N, Gujjuri, RR, Lapolla, P, Mills, EC, Pérez‐Ajates, S, Soares, AS, Van Straten, S, Varghese, C, Xu, W, McLean, KA, Espín‐Basany, E, Glasbey, JC, Mihaljevic, A, Nepogodiev, D, Pata, F, Pellino, G, Pockney, P, Hodson, J, Dudi‐Venkata, N, Egoroff, N, Ludbrook, I, Raubenheimer, K, Richards, T, Delibegovic, S, Salibasic, M, Amjad, T, Dörr‐Harim, C, Gedeon, N, Gsenger, J, Tachezy, M, Bini, S, Gallo, G, Gori, A, Picciariello, A, Podda, M, Riboni, C, Machatschek, MJ, Nguyen, KAT, Jakubauskas, M, Kryzauskas, M, Poskus, T, Kuiper, SZ, Wang, J, Wells, CI, Bissett, IP, Augestad, KM, Steinholt, I, Vieira, BN, Anabitarte Bautista, O, El Kasmy, Y, Martín‐Borregón, P, Ossola Revilla, M, Aktas, MK, Baki, BE, Akhbari, M, Baker, D, Bhatia, S, Brown, S, Cambridge, W, Kamarajah, SK, Khaw, RA, Kouli, O, Murray, V, Trout, I, Yasin, I, Sgrò, A, Blanco‐colino, R, Ahmed, Wur, Brindl, N, Gujjuri, Rr, Lapolla, P, Mills, Ec, Pérez‐ajates, S, Soares, A, Van Straten, S, Varghese, C, Xu, W, Mclean, Ka, Espín‐basany, E, Glasbey, Jc, Mihaljevic, A, Nepogodiev, D, Pata, F, Pellino, G, Pockney, P, Hodson, J, Dudi‐venkata, N, Egoroff, N, Ludbrook, I, Raubenheimer, K, Richards, T, Delibegovic, S, Salibasic, M, Amjad, T, Dörr‐harim, C, Gedeon, N, Gsenger, J, Tachezy, M, Bini, S, Gallo, G, Gori, A, Picciariello, A, Podda, M, Riboni, C, Machatschek, Mj, Nguyen, Kat, Jakubauskas, M, Kryzauskas, M, Poskus, T, Kuiper, Sz, Wang, J, Wells, Ci, Bissett, Ip, Augestad, Km, Steinholt, I, Vieira, Bn, Anabitarte Bautista, O, El Kasmy, Y, Martín‐borregón, P, Ossola Revilla, M, Aktas, Mk, Baki, Be, Akhbari, M, Baker, D, Bhatia, S, Brown, S, Cambridge, W, Kamarajah, Sk, Khaw, Ra, Kouli, O, Murray, V, Trout, I, and Yasin, I
Subjects: medicine.medical_specialty, Time Factors, Ileus, collections, colorectal surgery, Drains, enhanced recovery after surgery, medicine.medical_treatment, Audit, Drain, Stoma, 03 medical and health sciences, Ileostomy, Postoperative Complications, 0302 clinical medicine, collection, medicine, Humans, Multicenter Studies as Topic, Prospective Studies, Digestive System Surgical Procedures, Protocol (science), business.industry, General surgery, Gastroenterology, Colostomy, Length of Stay, medicine.disease, Colorectal surgery, Observational Studies as Topic, 030220 oncology & carcinogenesis, Drainage, 030211 gastroenterology & hepatology, Observational study, business
Abstract: Aim Postoperative drains have historically been used for the prevention and early detection of intra-abdominal collections. However, current evidence suggests that prophylactic drain placement following colorectal surgery has no significant clinical benefit. This is reflected in the enhanced recovery after surgery (ERAS) guidelines, which recommend against their routine use. The Ileus Management International study found more than one-third of participating centres across the world routinely used drains in the majority of colorectal resections. The aim of the present study is to audit international compliance with ERAS guidelines regarding the use of postoperative drains in colorectal surgery. Method This prospective, multicentre audit will be conducted via the student- and trainee-led EuroSurg Collaborative network across Europe, South Africa and Australasia. Data will be collected on consecutive patients undergoing elective and emergency colorectal surgery with 30-day follow-up. This will include any colorectal resection, formation of colostomy/ileostomy and reversal of stoma. The primary end-point will be adherence to ERAS guidelines for intra-abdominal drain placement. Secondary outcomes will include the following: time to diagnosis of intra-abdominal postoperative collections; output and time to removal of drains; and 30-day postoperative complications defined by the Clavien-Dindo classification. Conclusion This protocol describes the methodology for the first international audit of intra-abdominal drain placement after colorectal surgery. The study will be conducted across a large collaborative network with quality assurance and data validation strategies. This will provide a clear understanding of current practice and novel evidence regarding the efficacy and safety of intra-abdominal drain placement in colorectal surgical patients.
Published: 2020
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29. Plasma DNA as a 'liquid biopsy' incompletely complements tumor biopsy for identification of mutations in a case series of four patients with oligometastatic breast cancer

Author: Ananta Bhatt, Todd W. Miller, Jason D. Wells, Nancy J. McNulty, Richard J. Barth, Jennifer R. Bean, Jiang Gui, Mary D. Chamberlin, Wendy A. Wells, Peter A. Kaufman, Jonathan D. Marotti, Michael J. Tsapakos, John M Gemery, Fred W. Kolling, Gary N. Schwartz, Kevin Shee, Bradley A. Arrick, and Heidi W. Trask
Subjects: 0301 basic medicine, Cancer Research, Breast Neoplasms, Article, DNA sequencing, Circulating Tumor DNA, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Biopsy, Biomarkers, Tumor, medicine, Humans, Neoplasm Metastasis, Liquid biopsy, Massive parallel sequencing, medicine.diagnostic_test, business.industry, Liquid Biopsy, High-Throughput Nucleotide Sequencing, Cancer, DNA, Neoplasm, Prognosis, medicine.disease, 030104 developmental biology, Oncology, Cell-free fetal DNA, DNA profiling, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, business
Abstract: PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a “liquid biopsy” for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1–3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 +/− 11.81% (mean +/− SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients, and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).
Published: 2020
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30. Immune-Mediated Glycocalyx Remodeling in Hospitalized COVID-19 Patients

Author: Scott L. Hummel, Joanna M. Wells, Sascha N. Goonewardena, Robert S. Rosenson, Olga Grushko, Lauren Herty, and Jacob M. Haus
Subjects: Inflammation, Pharmacology, ARDS, business.industry, Short Communication, Organ dysfunction, COVID-19, General Medicine, Vascular dysfunction, Glycocalyx, medicine.disease, Proinflammatory cytokine, Pathogenesis, Sepsis, Immune system, Immunology, medicine, Pharmacology (medical), Tumor necrosis factor alpha, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Purpose Vascular and immune dysfunction are hallmarks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections and coronavirus disease 2019 (COVID-19). Although our understanding of the pathogenesis of COVID-19 has rapidly evolved, much of the focus has been on the immune mechanisms underlying COVID-19. In addition to immune dysfunction, vascular injury is also associated with COVID-19 and is a major driver of clinical deterioration in SARS-CoV-2 infections. The glycocalyx (GAC), a sugar-based shell that surrounds all mammalian cells, is an important regulator of vascular and immune responses. In sepsis, vascular dysfunction contributes to acute respiratory distress syndrome (ARDS) by altering vessel integrity, promoting thrombosis, and accelerating inflammation, all of which are also present in COVID-19. Observational studies in sepsis have found an association between levels of circulating GAC degradation products with both organ dysfunction and mortality. Although vascular dysfunction is a hallmark of COVID-19, it remains unclear whether GAC disruption occurs in COVID-19 and if GAC disruption contributes to the clinical progression of COVID-19. Methods In this prospective cohort study, we measured the GAC components syndecan-1 (SDC1) and hyaluronan (Hyal) along with inflammatory cytokines in 12 hospitalized COVID-19 patients and 8 healthy controls (HC). Results In agreement with other studies, we found that inflammatory cytokines are elevated in hospitalized COVID-19 patients compared with HC [median (IQR), all units picograms per milliliter: IL-6 4.65 (3.32–9.16) vs 0.69 (0.55–0.89), p p p = 0.036; Hyal: 26.41 (16.4–35.1) vs 3.01 (1.66–4.61), p Conclusion We propose that GAC markers offer insights into the pathobiology of COVID-19, potentially guide therapeutic approaches, and could aid in early risk stratification that is particularly beneficial in phasic diseases such as COVID-19.
Published: 2021
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31. Prolonged postoperative ileus following right‐ versus left‐sided colectomy: A systematic review and meta‐analysis

Author: Sean Ho Beom Seo, Daniel A. Carson, Greg O'Grady, Ian P. Bissett, Chris Varghese, Sameer Bhat, and Cameron I. Wells
Subjects: Adult, medicine.medical_specialty, Colectomies, Ileus, business.industry, medicine.medical_treatment, Gastroenterology, Length of Stay, Cochrane Library, medicine.disease, Inflammatory bowel disease, Surgery, Ileostomy, Postoperative Complications, Elective Surgical Procedures, Meta-analysis, Humans, Medicine, Laparoscopy, business, Complication, Colectomy
Abstract: AIM Prolonged postoperative ileus (PPOI) is a common complication following colonic surgery, and is associated with longer hospital stay, greater risk of complications and substantial cost for patients and hospitals. Some reports have recently suggested that gastrointestinal (GI) recovery varies based on the side of resection (i.e., right-sided vs. left-sided colectomy). This systematic review and meta-analysis aimed to compare GI recovery by resection side. METHODS The MEDLINE, Embase, Cochrane Library and CENTRAL databases were systematically searched for articles reporting GI recovery outcomes in adults undergoing elective right- versus left-sided colectomy (excluding with ileostomy) of any surgical approach. The primary outcome was PPOI, and secondary outcomes included time to first passage of flatus, stool and tolerance of solid diet, and postoperative complications. Subgroup analyses of laparoscopic procedures and cohorts without inflammatory bowel disease and sensitivity analysis of adjusted multivariate results were also performed. RESULTS Nine studies were identified, of which seven were included in the meta-analysis, comprising 29 068 colectomies (14 581 right-sided; 14 487 left-sided). PPOI was heterogeneously defined and was significantly more likely following right-sided compared to left-sided colectomy regardless of the surgical approach (OR 1.78, 95% CI 1.32-2.39; P
Published: 2021
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32. Association between Intermittent Hypoxemia and Severe Bronchopulmonary Dysplasia in Preterm Infants

Author: Erik A. Jensen, Robin K. Whyte, Barbara Schmidt, Dirk Bassler, Nestor E. Vain, Robin S. Roberts, Prakesh Shah, Leanne Brown, Lisa Wenger, Samantha Frye, Francesca Imbesi, Edmond Kelly, Judy D’Ilario, Madan Roy, Joanne Dix, Beth Adams, Janice Cairnie, Patrice Gillie, Elizabeth V. Asztalos, Marilyn Hyndman, Maralyn Lacy, Denise Hohn, Laura Cooper Kruk, Soraya Abbasi, Toni Mancini, Emidio Sivieri, Kathleen Finnegan, Aida Bairam, Sylvie Bélanger, Marianne Deschenes, Annie Fraser, JoAnn Harrold, Jane Frank, Julie Barden, Michael Vincer, Sharon Stone, Yacov Rabi, Reg Sauve, Danielle Cyr, Heather Christianson, Deborah Anseeuw-Deeks, Dianne Creighton, Alfonso Solimano, Lindsay Colby, Arsalan Butt, Anne Synnes, Meredith Peterson, Aasma Chaudhary, Hallam Hurt, Danielle Foy, Kristina Ziolkowski, Marsha Gerdes, Judy Bernbaum, Abraham Peliowski, Manoj Kumar, Leonora Hendson, Melba Athaide, Jill Tomlinson, Christian F. Poets, Jutta Armbruster, Cecilia Garcia, Vanesa DiGruccio, Fernanda Tamanaha, Noemí Jacobi, Silvia Garcia, Norma Vivas, Cristina Osio, Shanthy Sridhar, Aruna Parekh, Rose McGovern, Shmuel Arnon, Michelle Meyer, Rachel Poller, Nabeel Ali, May Khairy, Isabelle Paquet, Larissa Perepolkin, Patricia Grier, Sadia Wali, Mary Seshia, Diane Moddemann, John Minski, Valerie Cook, Kim Kwiatkowski, Karen A. H. Penner, Debbie Williams, Laurentiu Givelichian, Koravangattu Sankaran, Cindy Thiel, David Bader, Bella Sandler, Aaron Chiu, Dayle Everatt, Naomi Granke, Agneta Golan, Esther Goldstein, Shlomith Dadoun, Riitta Vikevainen, Hanna Kallankari, Tuula Kaukola, Mikko Hallman, Keith Barrington, Julie Lavoie, William Fraser, Deborah J. Davis, George Wells, Lorrie Costantini, Wendy Yacura, Bronwyn Gent, and Harvey Nelson
Subjects: Male, Pulmonary and Respiratory Medicine, Canada, medicine.medical_specialty, Critical Care and Intensive Care Medicine, Hypoxemia, Internal medicine, medicine, Humans, Hypoxia, Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Newborn, medicine.diagnostic_test, business.industry, Extremely preterm, Infant, Newborn, Editorials, Hypoxia (medical), medicine.disease, Extremely Preterm Infant, Pathophysiology, Pulse oximetry, Bronchopulmonary dysplasia, Infant, Extremely Premature, Cardiology, Female, medicine.symptom, business, Severe Bronchopulmonary Dysplasia
Abstract: Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may pla...
Published: 2021
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33. Integrated analysis of genotype and phenotype reveals clonal evolution and cytogenetically driven disruption of myeloid cell maturation in myelodysplastic syndromes

Author: Nigar Zaidi, Richard Bennington, Haley R. Pugsley, Barbara K. Zehentner, Dongbin Xu, Timothy P. Singleton, Lisa Eidenschink Brodersen, Wayne Fritschle, Denise A. Wells, Andrew J. Menssen, Jevon Cutler, Luise Hartmann, and Michael R. Loken
Subjects: Pathology, medicine.medical_specialty, Histology, Myeloid, medicine.diagnostic_test, Myelodysplastic syndromes, Cell Biology, Biology, medicine.disease, Trisomy 8, Cell Maturation, Somatic evolution in cancer, Pathology and Forensic Medicine, Leukemia, medicine.anatomical_structure, hemic and lymphatic diseases, medicine, Clone (B-cell biology), Fluorescence in situ hybridization
Abstract: BACKGROUND Myelodysplastic syndromes (MDS) are a heterogenous collection of clonal bone marrow diseases characterized by cytopenias, abnormal karyotypes, molecular abnormalities, and dysplasia by flow cytometry and/or morphology. The progression of MDS to severe cytopenias and/or overt leukemia is associated with the accumulation of additional cytogenetic abnormalities, suggesting clonal evolution. The impact of these accumulated abnormalities on myeloid maturation and the severity of the disease is poorly understood. METHODS Bone marrow specimens from 16 patients with cytogenetic abnormalities were flow cytometrically sorted into three myeloid populations: progenitors, immature myeloid cells, and mature myeloid cells. Fluorescence in situ hybridization analysis was performed on each to determine the distribution of chromosomal abnormalities during myeloid maturation. RESULTS Our findings revealed three distinct distributions of cytogenetic abnormalities across myeloid maturation, each of which corresponded to specific cytogenetic abnormalities. Group 1 had continuous distribution across all maturational stages and contained patients with a single cytogenetic aberration associated with good-to-intermediate prognosis; Group 2 had accumulation of abnormalities in immature cells and contained patients with high-risk monosomy 7; and Group 3 had abnormalities defining the founding clone equally distributed across maturational stages while subclonal abnormalities were enriched in progenitor cells and contained patients with multiple, non-monosomy 7, abnormalities with evidence of clonal evolution. CONCLUSIONS Our findings demonstrate that low-risk abnormalities (e.g., del(20q) and trisomy 8) occurring in the founding clone display a markedly different disease etiology, with respect to myeloid maturation, than monosomy 7 or abnormalities acquired in subclones, which result in a disruption of myeloid cell maturation in MDS.
Published: 2021
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34. A dreaded delight: A longitudinal qualitative interview study of paternal childbirth fear during the transition to fatherhood

Author: Margareta Johansson, Michael B. Wells, and Li Thies-Lagergren
Subjects: Coping (psychology), interviews, longitudinal, media_common.quotation_subject, fathers, Reproduktionsmedicin och gynekologi, coping strategies, Developmental psychology, Obstetrics, Gynecology and Reproductive Medicine, Perception, Maternity and Midwifery, medicine, Childbirth, reasons for fear, reproductive and urinary physiology, media_common, Pregnancy, Qualitative interviews, Transition (fiction), Obstetrics and Gynecology, medicine.disease, Feeling, Pediatrics, Perinatology and Child Health, Thematic analysis, Psychology, Research Paper, childbirth fear
Abstract: INTRODUCTION: Childbirth is a life-changing event where fathers desire being involved. As fathers take a more active role, fear of childbirth can arise. The aim of this study was to explore fathers' experiences of childbirth fear during pregnancy and after the birth of their baby. METHODS: This was a qualitative longitudinal prospective study that included 14 interviews with seven fathers, one during the prenatal period, and one follow-up interview after childbirth. Data were analyzed using thematic analysis according to Braun and Clark. RESULTS: The main theme 'Being vulnerable during the transition to fatherhood' was based on the perception of childbirth as risky with threats toward the woman's and baby's health, not being able to give and receive enough support, unable to handle the unknown process of birth, and not being a good father. Helpful strategies for coping with fear were to talk about fear, to learn more about childbirth and techniques on how to handle fear, and to avoid dealing with fear. Fathers' fear of childbirth changed after the birth of their baby. Their thoughts of another childbirth did not evoke the same strong feelings of fear. Issues important for the reduction of childbirth fear were: receiving professional support, actively taking part in the childbirth process, and the partner having an uncomplicated birth. CONCLUSIONS: Fathers with childbirth fear regarded childbirth as risky, but they expressed helpful coping strategies. After the birth of their baby, they became less fearful. Quality of fear-reducing support to expectant fathers may influence how they cope with their transition into fatherhood.
Published: 2021
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35. Overview of Sport-Specific Injuries

Author: Matthew E. Wells, E’Stephan J. Garcia, John C. Dunn, and John P. Scanaliato
Subjects: biology, business.industry, Athletes, medicine, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, Medical emergency, medicine.disease, business, Everyday life, biology.organism_classification, Organ system, Variety (cybernetics)
Abstract: Athletes are at risk for a variety of injuries not typically sustained in everyday life. The team physician must be capable of not only identifying and treating injuries as they occur, but he or she must be armed with the knowledge to minimize the risk of injuries before they occur. This review serves to provide an overview of the various sport-specific injuries typically encountered by team physicians. Injuries are grouped by body part and/or organ system, when possible. We do not aim to cover in detail the various treatments for these injuries; rather, we hope that this article provides a comprehensive overview of sport-specific injury, and demonstrate the well-roundedness in skills that must be possessed by team physicians.
Published: 2021
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36. Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Author: Bacharach, J., Tatham, A., Ferguson, G., Belalcazar, S., Thieme, H., Goodkin, M. L., Chen, M. Y., Guo, Q., Liu, J., Robinson, M. R., Bejanian, M., Wirta, D. L., Alezzandrini, A., Bercovich, G., Deromedis, P., Furno Sola, F., Gentile, C., Lerner, S., Lupinacci, A., Zeolite, C., Birt, C., Crichton, A., Gagne, S., Giunta, M., Harasymowycz, P., Jinapriya, D., Nicolela, M., Nixon, D., Saurel, P., Yan, D., Yuen, D., Arango, S., Martinez, A., Parra Restrepo, J. C., Korda, V., Kadlecova, J., Svacinova, J., Khairy, H., El Ibiary, H., El Sanabary, Z., Bell, K., Greslechner, R., Koch, J., Lorenz, K., Oberacher-Velten, I., Schmickler, S., Schuart, C., Bandello, F., Cagini, C., Figus, M., Mastropasqua, L., Rossetti, L., Uva, M. G., Thayanithi, S., Wells, A., Husain, R., Koh, V., Lim, D., Tin, A., Gous, P., Venter, L., Kee, C., Kook, M., Park, K. -H., Eraslan, M., Kayikcioglu, O., Yildirim, N., Bourne, R., Choudhary, A., Cordeiro, F., Dubois, V., Kirwan, J., Lim, S., Martin, K., Nithy, A., Prabhu, A., Amir, A., Barnebey, H., Beck, A., Bergstrom, L., Borisuth, N., Branch, J. D., Briggs, J., Bylsma, S., Chang, P., Christie, W., Cotter, F., Depenbusch, M., Goldberg, D. F., Greiner, J., Gupta, S., Gutmark, R., Han, Y., Heersink, S., Kahook, M., Khouri, A., Kim, J., Kushnick, H., Lin, C., Luchs, J., Maharaj, A., Mansberger, S. L., Mares, F., Miller-Ellis, E., Modi, S., Paul, M., Pitha, I., Saltzmann, R., Sato, M., Savestsky, M., Segal, B., Segal, Z., Serle, J., Sherwood, M., Singh, I., Smith, S. E., Song, J., Sorenson, R., Tenkman, L., Tekwani, N., Tubbs, C., Tyson, F., Vizzeri, G., Vold, S., Vu, Q., Warren, K. S., and Wirta, D.
Subjects: Adult, Male, medicine.medical_specialty, Intraocular pressure, genetic structures, Corneal Touch, Ocular hypertension, Glaucoma, Timolol, Young Adult, Double-Blind Method, Ophthalmology, Clinical endpoint, Humans, Medicine, Pharmacology (medical), Original Research Article, Antihypertensive Agents, Intraocular Pressure, Aged, Aged, 80 and over, Drug Implants, Dose-Response Relationship, Drug, Bimatoprost, business.industry, Middle Aged, medicine.disease, eye diseases, Female, Ocular Hypertension, sense organs, Implant, Ophthalmic Solutions, business, Glaucoma, Open-Angle, medicine.drug
Abstract: Objective To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma. Clinicaltrials.gov Identifier NCT02250651. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01624-9.
Published: 2021
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37. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial

Author: Amy Ford, Calley Middleton, L. Campbell, Petra Jankowska, Gary Dougherty, Gillian Price, Aarti Gaba, Charlotte Poile, Sam Chan, Sarah Danson, Sean Ewings, Jason F. Lester, Gareth Griffiths, Paul Shaw, Mavis Nye, Mathilda Cominos, Dionysis Papadatos, Jay Naik, Jill Gardiner, Joanne Lord, Cathy J. Richards, Meenali Chitnis, Gerard G Hanna, Peter Wells-Jordan, Raffaele Califano, Lucy Johnson, Carol MacGregor, Dean A. Fennell, Andy Polychronis, Gairin Dancey, Kayleigh Hill, Angela Scott, Liz Darlison, Tom Geldhart, Nicola Steele, Judith Cave, Christian H. Ottensmeier, Lois Mullholand, and Peter W. Szlosarek
Subjects: Male, medicine.medical_specialty, Pleural Neoplasms, Population, Placebo, B7-H1 Antigen, Antineoplastic Agents, Immunological, Double-Blind Method, Recurrence, Internal medicine, medicine, Humans, Mesothelioma, education, Adverse effect, Immune Checkpoint Inhibitors, Peritoneal Neoplasms, Aged, education.field_of_study, business.industry, Mesothelioma, Malignant, Hazard ratio, Articles, medicine.disease, Progression-Free Survival, Peritoneal Malignant Mesothelioma, Survival Rate, Nivolumab, Oncology, Peritoneal mesothelioma, Female, business
Abstract: Background: no phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients.Methods: this was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450.Findings: between May 10, 2017, and March 30, 2020, 332 patients were recruited, of whom 221 (67%) were randomly assigned to the nivolumab group and 111 (33%) were assigned to the placebo group). Median follow-up was 11·6 months (IQR 7·2–16·8). Median progression-free survival was 3·0 months (95% CI 2·8–4·1) in the nivolumab group versus 1·8 months (1·4–2·6) in the placebo group (adjusted hazard ratio [HR] 0·67 [95% CI 0·53–0·85; p=0·0012). Median overall survival was 10·2 months (95% CI 8·5–12·1) in the nivolumab group versus 6·9 months (5·0–8·0) in the placebo group (adjusted HR 0·69 [95% CI 0·52–0·91]; p=0·0090). The most frequently reported grade 3 or worse treatment-related adverse events were diarrhoea (six [3%] of 221 in the nivolumab group vs two [2%] of 111 in the placebo group) and infusion-related reaction (six [3%] vs none). Serious adverse events occurred in 90 (41%) patients in the nivolumab group and 49 (44%) patients in the placebo group. There were no treatment-related deaths in either group.Interpretation: Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have progressed on first-line therapy.Funding: Stand up to Cancer–Cancer Research UK and Bristol Myers Squibb.
Published: 2021
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38. Defining Resilience to Smoking-related Lung Disease: A Modified Delphi Approach from SPIROMICS

Author: Anita L. Oh, Richard A. Mularski, Igor Barjaktarevic, R. Graham Barr, Russell P. Bowler, Alejandro P. Comellas, Christopher B. Cooper, Gerard J. Criner, MeiLan K. Han, Nadia N. Hansel, Eric A. Hoffman, Richard E. Kanner, Jerry A. Krishnan, Robert Paine, Trisha M. Parekh, Stephen P. Peters, Stephanie A. Christenson, Prescott G. Woodruff, Wayne H. Anderson, Mehrdad Arjomandi, Nirav Bhakta, Surya P. Bhatt, Russell Buhr, Jeffrey L. Curtis, M. Bradley Drummond, Victor Kim, Wassim Labaki, Allison Lambert, Stephen C. Lazarus, Alex Mackay, Wendy Moore, Sarah L. O'Beirne, Laura Paulin, Benjamin M. Smith, Donald P. Tashkin, and James Michael Wells
Subjects: Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, media_common.quotation_subject, Modified delphi, Pulmonary disease, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Forced Expiratory Volume, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Lung, media_common, COPD, medicine.diagnostic_test, business.industry, Smoking, Editorials, medicine.disease, respiratory tract diseases, 030228 respiratory system, Lung disease, Psychological resilience, Consensus development, business
Abstract: Rationale: Diagnosis of chronic obstructive pulmonary disease (COPD) relies on abnormal spirometry. However, spirometry may underestimate the effects of smoking, missing smokers with respiratory di...
Published: 2021
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39. Developing diagnostic assessment of breast lumpectomy tissues using radiomic and optical signatures

Author: Wendy A. Wells, Brian W. Pogue, Rebecca A. Zuurbier, Brady Hunt, Keith D. Paulsen, and Samuel S. Streeter
Subjects: Optical image, medicine.medical_specialty, Optical Phenomena, Science, Breast Neoplasms, Cancer detection, In Vitro Techniques, Mastectomy, Segmental, Malignancy, Multimodal Imaging, Article, Breast cancer, Humans, Medicine, Breast lumpectomy, Stochastic Processes, Multidisciplinary, business.industry, Optical Imaging, Imaging and sensing, Margins of Excision, X-Ray Microtomography, Translational research, medicine.disease, Domain imaging, Adipose Tissue, Feature (computer vision), Diagnostic assessment, Female, Radiology, business, Biomedical engineering
Abstract: High positive margin rates in oncologic breast-conserving surgery are a pressing clinical problem. Volumetric X-ray scanning is emerging as a powerful ex vivo specimen imaging technique for analyzing resection margins, but X-rays lack contrast between non-malignant and malignant fibrous tissues. In this study, combined micro-CT and wide-field optical image radiomics were developed to classify malignancy of breast cancer tissues, demonstrating that X-ray/optical radiomics improve malignancy classification. Ninety-two standardized features were extracted from co-registered micro-CT and optical spatial frequency domain imaging samples extracted from 54 breast tumors exhibiting seven tissue subtypes confirmed by microscopic histological analysis. Multimodal feature sets improved classification performance versus micro-CT alone when adipose samples were included (AUC = 0.88 vs. 0.90; p-value = 3.65e−11) and excluded, focusing the classification task on exclusively non-malignant fibrous versus malignant tissues (AUC = 0.78 vs. 0.85; p-value = 9.33e−14). Extending the radiomics approach to high-dimensional optical data—termed “optomics” in this study—offers a promising optical image analysis technique for cancer detection. Radiomic feature data and classification source code are publicly available.
Published: 2021

40. Serial decline in lung volume parameters on computed tomography (CT) predicts outcome in idiopathic pulmonary fibrosis (IPF)

Author: Rose Camoras, Joseph Jacob, Sujal R. Desai, Hasti Robbie, Cheng Fang, Athol U. Wells, Simon L.F. Walsh, Anand Devaraj, and Arjun Nair
Subjects: Vital capacity, medicine.medical_specialty, Lung, Proportional hazards model, business.industry, General Medicine, respiratory system, medicine.disease, respiratory tract diseases, FEV1/FVC ratio, Idiopathic pulmonary fibrosis, medicine.anatomical_structure, Fibrosis, medicine.artery, Ascending aorta, medicine, Radiology, Nuclear Medicine and imaging, Lung volumes, sense organs, Radiology, skin and connective tissue diseases, business
Abstract: In patients with IPF, this study aimed (i) to examine the relationship between serial change in CT parameters of lung volume and lung function, (ii) to identify the prognostic value of serial change in CT parameters of lung volume, and (iii) to define a threshold for serial change in CT markers of lung volume that optimally captures disease progression. Serial CTs were analysed for progressive volume loss or fibrosis progression in 81 IPF patients (66 males, median age = 67 years) with concurrent forced vital capacity (FVC) (median follow-up 12 months, range 6–23 months). Serial CT measurements of volume loss comprised oblique fissure posterior retraction distance (OFPRD), aortosternal distance (ASD), lung height corrected for body habitus (LH), and automated CT-derived total lung volumes (ALV) (measured using commercially available software). Fibrosis progression was scored visually. Serial changes in CT markers and FVC were compared using regression analysis, and evaluated against mortality using Cox proportional hazards. There were 58 deaths (72%, median survival = 17 months). Annual % change in ALV was most significantly related to annual % change in FVC (R2 = 0.26, p
Published: 2021
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41. Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas

Author: Funda Meric-Bernstam, Randy F. Sweis, F. Stephen Hodi, Wells A. Messersmith, Robert H.I. Andtbacka, Matthew Ingham, Nancy Lewis, Xinhui Chen, Marc Pelletier, Xueying Chen, Jincheng Wu, Thomas W. Dubensky, Sarah M. McWhirter, Thomas Müller, Nitya Nair, and Jason J. Luke
Subjects: Adult, Agonist, Cancer Research, medicine.medical_specialty, Lymphoma, Maximum Tolerated Dose, medicine.drug_class, Gastroenterology, Proinflammatory cytokine, Lesion, Pharmacokinetics, Neoplasms, Internal medicine, medicine, Humans, Adverse effect, Merkel cell carcinoma, business.industry, Neoplasms, Second Primary, medicine.disease, Sting, Oncology, Chills, Immunotherapy, medicine.symptom, business
Abstract: Purpose: This phase I study assessed the safety, pharmacokinetics (PKs), and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates the stimulator of IFN genes (STING) pathway, in patients with advanced/metastatic cancers. Patients and Methods: Patients (n = 47) received weekly i.t. injections of MIW815, 50 to 6,400 μg, on a 3-weeks-on/1-week-off schedule. Results: A maximum tolerated dose was not reached. Most common treatment-related adverse events were pyrexia (17%), chills, and injection-site pain (each 15%). MIW815 was rapidly absorbed from the injection site with dose-proportional PK, a rapid terminal plasma half-life (approximately 24 minutes), and high interindividual variability. One patient had a partial response (PR; Merkel cell carcinoma); two patients had unconfirmed PR (parotid cancer, myxofibrosarcoma). Lesion size was stable or decreased in 94% of evaluable, injected lesions. RNA expression and immune infiltration assessments in paired tumor biopsies did not reveal significant on-treatment changes. However, increases in inflammatory cytokines and peripheral blood T-cell clonal expansion suggested systemic immune activation. Conclusions: MIW815 was well tolerated in patients with advanced/metastatic cancers. Clinical activity of single-agent MIW815 was limited in this first-in-human study; however, evidence of systemic immune activation was seen.
Published: 2021
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42. Post‐operative ileus: definitions, mechanisms and controversies

Author: Sean Ho Beom Seo, Cameron I. Wells, Tony Milne, Ryash Vather, Ian P. Bissett, Greg O'Grady, and Stephen J Chapman
Subjects: Post operative ileus, medicine.medical_specialty, Ileus, business.industry, General Medicine, medicine.disease, digestive system diseases, Clinical trial, Postoperative Complications, Quality of life, Time course, Quality of Life, Paralysis, Animals, Humans, Medicine, Surgery, Postoperative Period, medicine.symptom, Distal colon, Gastrointestinal Transit, business, Intensive care medicine, Abdominal surgery
Abstract: Post-operative ileus (POI) is a syndrome of impaired gastrointestinal transit which occurs following abdominal surgery. There are few effective targeted therapies for ileus, and research has been limited by inconsistent definitions and an incomplete understanding of the underlying pathophysiology. Despite considerable effort, there remains no widely-adopted definition of ileus, and recent work has identified variation in outcome reporting is a major source of heterogeneity in clinical trials. Outcomes should be clearly-defined, clinically-relevant, and reflective of the underlying biology, impacts on hospital resources and quality of life. Further collaborative efforts will be needed to develop consensus definitions and a core outcome set for postoperative gastrointestinal recovery. Investigation into the pathophysiology of POI has been hindered by use of low-resolution techniques and difficulties linking cellular mechanisms to dysmotility patterns and clinical symptoms. Recent evidence has suggested the common assumption of post-operative GI paralysis is incorrect, and that the distal colon becomes hyperactive following surgery. The post-operative inflammatory response is important in the pathophysiology of ileus, but the time course of this in humans remains unclear, with the majority of evidence coming from animal models. Future work should investigate dysmotility patterns underlying ileus, and identify biomarkers which may be used to diagnose, monitor and stratify patients with ileus.
Published: 2021
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43. Ballroom Dance as a Form of Rehabilitation: A Systematic Review

Author: Feng Yang and Meredith Wells
Subjects: medicine.medical_specialty, Rehabilitation, Dance, business.industry, medicine.medical_treatment, MEDLINE, General Medicine, Ballroom, Disease, medicine.disease, law.invention, Randomized controlled trial, Quality of life, law, medicine, Physical therapy, Dementia, business
Abstract: Chronic health problems, such as neurological conditions or long-lasting diseases, impair patients’ physical and mental functions with a subsequent reduction in overall quality of life. The purpose of this systematic review was to summarize how ballroom dance is being investigated as a rehabilitative method in individuals with neurological or medical diseases. A systematic literature search was conducted in databases including MEDLINE, SPORTDiscus, and PubMed. Of 728 articles located and titles and abstracts screened, 12 studies were included in this review. Study groups included Parkinson’s disease (4 studies), multiple sclerosis (2), spinal cord injury (1), stroke (1), dementia (1), cancer (2), and diabetes (1). Ballroom dances utilized included a combination of smooth and rhythm dances. Results revealed that ballroom dance is effective in improving gait functions, balance, and quality of life among various populations living with chronic neurological or medical conditions. In addition, ballroom dance is safe and associated with a low attrition rate (7.7%). There is increasing evidence to support ballroom dance as a feasible and effective intervention for adults with chronic neurological disorders or medical diseases. Further large-scale, randomized controlled trials are needed to examine the mechanisms, effectiveness, retention, and safety of ballroom dance as a rehabilitative intervention.
Published: 2021
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44. Characterizing the willingness to undergo treatment in patients with alopecia areata

Author: Kristen M. Wells and Lauren O'Connor
Subjects: Autoimmune disease, medicine.medical_specialty, Disease onset, integumentary system, business.industry, Dermatology, General Medicine, Target population, Alopecia areata, medicine.disease, Hair loss, medicine.anatomical_structure, Disease severity, Scalp, medicine, In patient, skin and connective tissue diseases, business
Abstract: Alopecia areata is an autoimmune disease that results in partial or total balding of the scalp and/or body. Treatments available are minimally effective, have severe side effects, and are often painful. Given these burdens, patients may not feel undergoing treatment is worthwhile. The purpose of this study is to characterize the willingness of patients with alopecia areata to undergo treatment. We found that few patients are willing to undergo treatment at the risk of severe health side effects. The most acceptable form of treatment administration was topical and the least acceptable was injection at the site of hair loss. A majority of patients would only undergo treatment for hair growth that is cosmetically acceptable and the most important site of hair regrowth was the scalp. The willingness to undergo treatment differed significantly by gender, age, time since disease onset, and disease severity. This study offers insight into the preferences of patients with alopecia areata and characteristics that would make treatment widely acceptable. Institutions conducting research on treatment for alopecia areata can use the results of this study to better understand the needs of their target population.
Published: 2021
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45. Gastrointestinal Bleeding at CT Angiography and CT Enterography: Imaging Atlas and Glossary of Terms

Author: Don C. Yoo, Ashish Khandelwal, Seong Ho Park, Farnoosh Sokhandon, David J. Grand, Brian C. Allen, Olga R. Brook, Michael L. Wells, Avneesh Gupta, Jorge A. Soto, Lisa L. Strate, Alvaro Huete, David H. Bruining, Jeff L. Fidler, Flavius F. Guglielmo, Mark Anderson, Vijay Ramalingam, Martin L. Gunn, and Michael S. Gee
Subjects: medicine.medical_specialty, Gastrointestinal bleeding, medicine.diagnostic_test, Glossary, CT enterography, Computed Tomography Angiography, Gastrointestinal Diseases, business.industry, Angiography, MEDLINE, Multidisciplinary Collaboration, medicine.disease, Endoscopy, Gastrointestinal, medicine.anatomical_structure, Atlas (anatomy), medicine, Humans, Radiology, Nuclear Medicine and imaging, Radiology, Gastrointestinal Hemorrhage, Tomography, X-Ray Computed, business
Abstract: Gastrointestinal (GI) bleeding is a common potentially life-threatening medical condition frequently requiring multidisciplinary collaboration to reach the proper diagnosis and guide management. GI bleeding can be
Published: 2021
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46. Combining Stereotactic Body Radiotherapy and Microwave Ablation Appears Safe and Feasible for Renal Cell Carcinoma in an Early Series

Author: Paul M. Harari, Marci L. Alexander, John E. Bayouth, E. Jason Abel, J. Louis Hinshaw, Sara L. Best, John M. Floberg, Greg Cooley, Meghan G. Lubner, Poonam Yadav, Andrzej P. Wojcieszynski, Michael F. Bassetti, Grace C. Blitzer, Shane A. Wells, Timothy J. Ziemlewicz, and Fred T. Lee
Subjects: medicine.medical_specialty, Combination therapy, Stereotactic body radiation therapy, Nausea, Urology, medicine.medical_treatment, 030232 urology & nephrology, Radiosurgery, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, Humans, Medicine, Microwaves, Carcinoma, Renal Cell, business.industry, Microwave ablation, medicine.disease, Ablation, Kidney Neoplasms, Oncology, 030220 oncology & carcinogenesis, Radiology, medicine.symptom, business, Stereotactic body radiotherapy, Kidney cancer, Glomerular Filtration Rate
Abstract: Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) have potentially complementary advantages and limitations for treating inoperable renal cell carcinoma (RCC). Combining SBRT and MWA may optimize tumor control and toxicity for patients with larger (>5 cm) RCCs or those with vascular involvement. We retrospectively reviewed patients at our institution with RCC treated between 2014 – 2018 to identify patients treated with a combination of SBRT and MW ablation. Seven patients with RCC were treated with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, two with grade 1 hematuria and one with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR preceding and following SBRT and MW ablation was 69 mL/min/1.73m2 and 68 mL/min/1.73m2 (p=0.19) respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations.
Published: 2021
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47. Management of gastrointestinal bleeding: Society of Abdominal Radiology (SAR) Institutional Survey

Author: Lisa L. Strate, Vijay Ramalingam, Mark Anderson, Flavius F. Guglielmo, Jorge A. Soto, Alvaro Huete, Brian C. Allen, Olga R. Brook, Michael S. Gee, Don C. Yoo, David J. Grand, Jeff L. Fidler, Seong Ho Park, Michael L. Wells, Ashish Khandalwal, Martin L. Gunn, Farnoosh Sokhandon, Avneesh Gupta, and David H. Bruining
Subjects: Gastrointestinal bleeding, medicine.medical_specialty, Radiological and Ultrasound Technology, medicine.diagnostic_test, CT enterography, business.industry, Urology, Gastroenterology, Colonoscopy, Hepatology, medicine.disease, Occult, law.invention, Capsule endoscopy, law, Internal medicine, Angiography, medicine, Radiology, Nuclear Medicine and imaging, Radiology, business, Computed tomography angiography
Abstract: Despite guidelines developed to standardize the diagnosis and management of gastrointestinal (GI) bleeding, significant variability remains in recommendations and practice. The purpose of this survey was to obtain information on practice patterns for the evaluation of overt lower GI bleeding (LGIB) and suspected small bowel bleeding. A 34-question electronic survey was sent to all Society of Abdominal Radiology (SAR) members. Responses were received from 52 unique institutions (40 from the United States). Only 26 (50%) utilize LGIB management guidelines. 32 (62%) use CT angiography (CTA) for initial evaluation in unstable patients. In stable patients with suspected LGIB, CTA is the preferred initial exam at 21 (40%) versus colonoscopy at 24 (46%) institutions. CTA use increases after hours for both unstable (n = 32 vs. 35, 62% vs. 67%) and stable patients (n = 21 vs. 27, 40% vs 52%). CTA is required before conventional angiography for stable (n = 36, 69%) and unstable (n = 15, 29%) patients. 38 (73%) institutions obtain two post-contrast phases for CTA. 49 (94%) institutions perform CT enterography (CTE) for occult small bowel bleeding with capsule endoscopy (n = 26, 50%) and CTE (n = 21, 40%) being the initial test performed. 35 (67%) institutions perform multiphase CTE for occult small bowel bleeding. In summary, stable and unstable patients with overt lower GI are frequently imaged with CTA, while CTE is frequently performed for suspected occult small bowel bleeding.
Published: 2021
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48. Outcomes following out-of-hours acute cholecystectomy: A systematic review and meta-analysis

Author: Chris Varghese, Bathiya Ratnayake, Gregory O'Grady, Willam Xu, John A. Windsor, Cameron I. Wells, Ahmed W.H. Barazanchi, and Shameer Bhat
Subjects: medicine.medical_specialty, Evening, medicine.medical_treatment, Gallbladder disease, MEDLINE, Critical Care and Intensive Care Medicine, Patient Readmission, Sepsis, Postoperative Complications, After-Hours Care, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, Cholecystectomy, Hospital Mortality, Bile duct, business.industry, Odds ratio, Length of Stay, medicine.disease, Conversion to Open Surgery, medicine.anatomical_structure, Cholecystectomy, Laparoscopic, Meta-analysis, Surgery, business
Abstract: Cholecystectomy is one of the most commonly performed abdominal operations. Rising demands on acute operating theater availability and resource utilization in the daytime have led to acute cholecystectomy being performed out-of-hours (in the evenings, at night, or on weekends), although it remains unknown whether outcomes differ between out-of-hours and in-hours (during the daytime on weekdays) acute cholecystectomy. This systematic review and meta-analysis aimed to compare outcomes following out-of-hours versus in-hours acute cholecystectomy.The study protocol was prospectively registered on PROSPERO (ID: CRD42021226127). MEDLINE, EMBASE, and Scopus databases were systematically searched for studies comparing outcomes following out-of-hours and in-hours acute cholecystectomy in adults with any acute benign gallbladder disease. The outcomes of interest were rates of bile leakage, bile duct injury, overall postoperative complications, conversion to open cholecystectomy, specific intraoperative and postoperative complications, length of stay, readmission, and mortality. Subgroup (evening/night-time vs. daytime, weekend vs. weekday, acute surgical unit [ASU]-only, non-ASU, and laparoscopic-only) and sensitivity analyses of adjusted multivariate regression analysis results was also performed.Eleven studies were included. There were no differences between out-of-hours and in-hours acute cholecystectomy for rates of bile leakage, bile duct injury, overall postoperative complications, conversion to open cholecystectomy, operative duration, readmission, mortality, and postoperative length of stay. Higher rates of postoperative sepsis (odds ratio, 1.58; 95% confidence interval, 1.04-2.41; p = 0.03) and pneumonia (odds ratio, 1.55; 95% confidence interval, 1.06-2.26; p = 0.02) were observed following out-of-hours acute cholecystectomy on univariate meta-analysis, but not after the adjusted multivariate meta-analysis. Higher conversion rates were observed when out-of-hours cholecystectomy was performed in centers without an ASU.This systematic review and meta-analysis has not shown an increased risk in overall or specific complications associated with out-of-hours compared with in-hours acute cholecystectomy. However, future studies should assess the potential impact of structural hospital factors, such as an ASU, on outcomes following out-of-hours acute cholecystectomy.Systematic Review and Meta-Analysis Study, Level IV.
Published: 2021
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49. Effectiveness of a complex psychosocial intervention to reduce metabolic syndrome in psychiatric outpatients with severe/persistent mental illness

Author: Talia Emmanuel, Barna Konkolÿ Thege, Stephanie Hill, and Laurie Wells
Subjects: education.field_of_study, medicine.medical_specialty, Sleep hygiene, Population, Psychological intervention, Effectiveness, medicine.disease, Mental illness, Metabolic syndrome, Mental health, Article, Severe mental illness, Abdominal circumference, medicine, Psychosocial intervention, education, Psychiatry, Psychology, Body mass index, Psychosocial, General Psychology
Abstract: The prevalence of metabolic syndrome among individuals with severe mental illness is considerably higher than in the general population, contributing to the 15–20-year shorter life expectancy of this client population. The aim of this pilot study was to evaluate the effectiveness of a novel, complex psychosocial program to reduce metabolic syndrome. Members of both the intervention (n = 78) and control (n = 31) group were psychiatric outpatients with severe/persistent mental illness struggling with one or more symptoms of metabolic syndrome. Beyond the default elements of similar programs such as diet and exercise, the intervention covered medication use, sleep hygiene, stress management, as well as addressing spiritual needs, mindfulness, addictions, and self-care. Assessment of metabolic indicators were completed at baseline, at the end of the 11-week intervention, and 6 months post-intervention. The trajectory of change over time was significantly more favorable in the treatment than in the control group in terms of waist circumference (p = 0.013, η2 = 0.093) and a positive trend emerged in relation to blood glucose level (p = 0.082, η2 = 0.057). However, no statistically reliable difference was observed between the intervention and the control group regarding the other outcome variables (body mass index, systolic and diastolic blood pressure, serum triglyceride level, serum HDL cholesterol level, overall metabolic syndrome severity). These findings suggest that to produce more robust benefits, psychosocial interventions targeting the metabolic health of individuals with complex mental health needs should be either longer in duration if resources permit or narrower in focus (diet and exercise mainly) if resources are scarce. Supplementary Information The online version contains supplementary material available at 10.1007/s12144-021-02269-3.
Published: 2021
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50. Changing sex differences in undernutrition of African children: findings from Demographic and Health Surveys

Author: André Briend, Tanya Khara, Susan Thurstans, Mark Myatt, Michel Garenne, Andrew Seal, Carmel Dolan, Jonathan C. K. Wells, Tampere University, and Clinical Medicine
Subjects: Male, Thinness, 3123 Gynaecology and paediatrics, Sex differences, Prevalence, Faculty of Science, Humans, Medicine, Child, Wasting, Growth Disorders, Sex Characteristics, Sub-Saharan Africa, business.industry, Malnutrition, Infant, Newborn, Public Health, Environmental and Occupational Health, Infant, General Social Sciences, Undernutrition, Anthropometry, medicine.disease, Health Surveys, 3142 Public health care science, environmental and occupational health, Child, Preschool, Female, medicine.symptom, Underweight, business, Demography
Abstract: The study investigates sex differences in the prevalence of undernutrition in sub-Saharan Africa. Undernutrition was defined by Z-scores using the CDC-2000 growth charts. Some 128 Demographic and Health Surveys (DHS) were analysed, totalling 700,114 children under-five. The results revealed a higher susceptibility of boys to undernutrition. Male-to-female ratios of prevalence averaged 1.18 for stunting (height-for-age Z-score Z-score Z-score Z-scores
Published: 2021
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