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

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2,098 results on '"Sokol, A. A."'

1. Challenge of food allergy testing and avoidance in children with atopic dermatitis

Author: Pamela A. Frischmeyer-Guerrerio, Paula Mariam Mohyi, Stephanie Ann Kubala, and Kristin Sokol
Subjects: medicine.medical_specialty, Allergy, Eczema, Case Report, Immunoglobulin E, vitamin D deficiency, Dermatitis, Atopic, 03 medical and health sciences, 0302 clinical medicine, Food allergy, 030225 pediatrics, medicine, Humans, Intensive care medicine, Child, Asthma, biology, business.industry, digestive, oral, and skin physiology, General Medicine, Atopic dermatitis, Allergens, medicine.disease, Hypersensitivity reaction, 030228 respiratory system, biology.protein, business, Psychosocial, Food Hypersensitivity
Abstract: Atopic dermatitis (AD) is a common presenting complaint by children and their caretakers to their primary care providers. On testing, children with AD frequently exhibit positive food-specific IgE levels in the absence of immediate allergic reactions. Misinterpretation of these false positive tests can lead to unnecessary food avoidance, which can have tremendous psychosocial, economic and nutritional consequences and, in some cases, facilitate the development of an immediate hypersensitivity to the food. We present a child with persistent AD who underwent broad testing that led to unnecessary food avoidance resulting in Vitamin D deficiency, growth failure and the development of an IgE-mediated food allergy. This case underscores the need for caution by primary care clinicians in using food avoidance diets as a treatment for AD and the importance of limiting allergy testing to foods only when the clinical history indicates an immediate hypersensitivity reaction.
Published: 2023

2. Use and perceptions of menthol versus non-menthol cigarettes among pregnant women

Author: Nancy C. Jao, Laura R. Stroud, Katelyn Borba, Natasha A. Sokol, Lori A. J. Scott-Sheldon, and Chrystal Vergara-Lopez
Subjects: Adult, Male, Future studies, Maternal smoking, media_common.quotation_subject, Medicine (miscellaneous), Cigarette use, Intention, Article, Cigarette Smoking, chemistry.chemical_compound, Pregnancy, Perception, medicine, Humans, media_common, Smoke, business.industry, General Medicine, Tobacco Products, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Menthol, chemistry, Health education, Female, Pregnant Women, business, Demography
Abstract: BACKGROUND Menthol cigarette use among women who smoke cigarettes during pregnancy is high, but little is known about the factors that contribute to preference for menthol cigarette use during pregnancy. OBJECTIVE This study investigated preferences, perceptions, and intentions to use menthol vs. non-menthol cigarettes in a sample of pregnant women. METHODS Pregnant women (N = 124, Mage = 26.2 years, 50% minorities) completed a study investigating the impact of maternal smoking on biobehavioral markers of fetal risk. During the third trimester, participants self-reported preferences (liking, attractiveness, smoothness, interest), perceptions of harm (general, pregnancy-specific), and intentions to use menthol and non-menthol cigarettes. We examined differences in responses based on whether participants endorsed (1) cigarette use during pregnancy (yes/no) and (2) lifetime cigarette use (yes/no). RESULTS Sixty-two participants endorsed cigarette smoking during pregnancy (85.5% smoked menthol cigarettes), and 94 participants reported lifetime use. Overall, menthol cigarettes were perceived as more likeable and smoother vs. non-menthol (ps
Published: 2023

3. Pulmonary Embolism Response Team (PERT) - A New Paradigm for the Treatment of Pulmonary Embolism

Author: Robert T. Faillace, Amit Kakkar, Seth I. Sokol, and Jonathan Koslowsky
Subjects: Patient Care Team, Pharmacology, medicine.medical_specialty, business.industry, Psychological intervention, Catheter directed thrombolysis, medicine.disease, Pulmonary embolism, Risk Factors, Multidisciplinary approach, Drug Discovery, Risk stratification, Humans, Medicine, Thrombolytic Therapy, Pulmonary Embolism, business, Intensive care medicine, Cardiovascular mortality
Abstract: Pulmonary embolism (PE) is the third leading cause of cardiovascular mortality. Patients with PE can present with a wide array of symptoms, ranging from mild to life threatening. The mainstay of PE treatment is anticoagulation; however, many advanced options are available for more severe patients, including catheter- directed interventions, surgical treatments, and hemodynamic support. Although different risk scores and clinical guidelines exist, the primary treating teams are frequently left uncertain on the most suitable treatment for a specific complex patient. Pulmonary Embolism Response Teams (PERT), composed of multidisciplinary experts, have emerged and been implemented in many centers and are available 24 hours a day to help guide the primary team. PERTs have changed the way complex PE patients are managed. In centers with a PERT, teams are called upon very frequently, and there is a significant increase in the use of advanced treatments for PE, although there are differences between centers based upon the center's specific PERT protocol and available capabilities. As PE is an evolving area, and more studies are necessary, PERTs around the world can help advance the field and improve the treatment offered to PE patients.
Published: 2022
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4. Anxiety and temporal self-appraisal: How people with anxiety evaluate themselves over time

Author: Chynna Levin, Chayim Rosensweig, Yosef Sokol, and Mairav Linzer
Subjects: Depression, media_common.quotation_subject, Psychological intervention, Anxiety, medicine.disease, Anxiety Disorders, Causality, Self Concept, Diagnostic Self Evaluation, Psychiatry and Mental health, Clinical Psychology, Mood disorders, Perception, medicine, Humans, Self Report, medicine.symptom, Association (psychology), Psychology, Depression (differential diagnoses), Clinical psychology, media_common, Psychopathology
Abstract: Background Previous studies found that psychopathology is associated with distinct self-perceptions over time. Euthymic individuals report experiencing a self-enhancement bias, with self-appraisal increasing over time. In contrast, depressed individuals report viewing a personal decline from past to present and anticipated self-improvement from present to future. This study examined the association between the singular presence of anxiety and temporal self-appraisal. Methods Using the Depression Anxiety and Stress Scale, this study examined a depressed (n = 142), anxious (n = 95), comorbid depressed and anxious (n = 335), and euthymic group (non-depressed and non-anxious, n = 535), on a validated task of temporal self-appraisal. Results Anxiety has a unique association with temporal self-appraisal that differs from the other disorders examined in this study. Specifically, individuals with anxiety had a similar positive trend of self-view to the euthymic group; however, their overall trend was lower at each temporal point. Individuals with depression had a stable past-to-present self-view and an improving present-to-future self-view. Limitations The use of an online self-report sample without longitudinal assessment of variables, while sufficient for the intent of the present study, limits the potential extrapolation from this sample, as well as prevents the determination of the direction of causality. Conclusions While individuals with anxiety demonstrate a positive sense of improvement over time, their psychopathology is associated with a negative bias in their perception of their past, present, and future selves. These findings have important implications for clinicians regarding potential interventions and treatment for anxiety and depression.
Published: 2022
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5. Pharmacologic activation of hepatic farnesoid X receptor prevents parenteral nutrition–associated cholestasis in mice

Author: Michael W. Devereaux, Frederick J. Suchy, Angelo D'Alessandro, Ronald J. Sokol, Swati Ghosh, Colin T. Shearn, Karim C. El Kasmi, David J. Orlicky, Aimee L. Anderson, and Natarajan Balasubramaniyan
Subjects: Male, Parenteral Nutrition - Associated Cholestasis, Parenteral Nutrition, Lipoproteins, Interleukin-1beta, Gene Expression, Receptors, Cytoplasmic and Nuclear, Pharmacology, Bile Acids and Salts, Mice, Cholestasis, medicine, Animals, RNA, Messenger, ATP Binding Cassette Transporter, Subfamily G, Member 5, ABCB11, Liver X receptor, ATP Binding Cassette Transporter, Subfamily B, Member 11, Hepatology, Chemistry, Liver Diseases, Macrophages, FGF15, ATP Binding Cassette Transporter, Subfamily G, Member 8, Isoxazoles, Macrophage Activation, ABCB4, medicine.disease, Multidrug Resistance-Associated Protein 2, Mice, Inbred C57BL, Intestinal Diseases, medicine.anatomical_structure, Gene Expression Regulation, Hepatocyte, Hepatocytes, Farnesoid X receptor, Multidrug Resistance-Associated Proteins, Signal Transduction
Abstract: Parenteral nutrition (PN)-associated cholestasis (PNAC) complicates the care of patients with intestinal failure. In PNAC, phytosterol containing PN synergizes with intestinal injury and IL-1β derived from activated hepatic macrophages to suppress hepatocyte farnesoid X receptor (FXR) signaling and promote PNAC. We hypothesized that pharmacological activation of FXR would prevent PNAC in a mouse model.To induce PNAC, male C57BL/6 mice were subjected to intestinal injury (2% dextran sulfate sodium [DSS] for 4 days) followed by central venous catheterization and 14-day infusion of PN with or without the FXR agonist GW4064. Following sacrifice, hepatocellular injury, inflammation, and biliary and sterol transporter expression were determined. GW4064 (30 mg/kg/day) added to PN on days 4-14 prevented hepatic injury and cholestasis; reversed the suppressed mRNA expression of nuclear receptor subfamily 1, group H, member 4 (Nr1h4)/FXR, ATP-binding cassette subfamily B member 11 (Abcb11)/bile salt export pump, ATP-binding cassette subfamily C member 2 (Abcc2), ATP binding cassette subfamily B member 4(Abcb4), and ATP-binding cassette subfamily G members 5/8(Abcg5/8); and normalized serum bile acids. Chromatin immunoprecipitation of liver showed that GW4064 increased FXR binding to the Abcb11 promoter. Furthermore, GW4064 prevented DSS-PN-induced hepatic macrophage accumulation, hepatic expression of genes associated with macrophage recruitment and activation (ll-1b, C-C motif chemokine receptor 2, integrin subunit alpha M, lymphocyte antigen 6 complex locus C), and hepatic macrophage cytokine transcription in response to lipopolysaccharide in vitro. In primary mouse hepatocytes, GW4064 activated transcription of FXR canonical targets, irrespective of IL-1β exposure. Intestinal inflammation and ileal mRNAs (Nr1h4, Fgf15, and organic solute transporter alpha) were not different among groups, supporting a liver-specific effect of GW4064 in this model.GW4064 prevents PNAC in mice through restoration of hepatic FXR signaling, resulting in increased expression of canalicular bile and of sterol and phospholipid transporters and suppression of macrophage recruitment and activation. These data support augmenting FXR activity as a therapeutic strategy to alleviate or prevent PNAC.
Published: 2021
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6. Safety of sildenafil in extremely premature infants: a phase I trial

Author: Dan L. Stewart, Daniel Gonzalez, Namasivayam Ambalavanan, Andrew M. Atz, Wesley M. Jackson, Gregory M Sokol, Michael Cohen-Wolkowiez, Brenda B. Poindexter, Mary Mills, Chi D. Hornik, Karen Martz, Shawn K. Ahlfeld, Matthew M. Laughon, Christoph P. Hornik, Gratias Mundakel, and P. Brian Smith
Subjects: Mean arterial pressure, Sildenafil, Infant, Premature, Diseases, Enteral administration, Sildenafil Citrate, Article, chemistry.chemical_compound, Humans, Medicine, Adverse effect, Respiratory tract diseases, business.industry, Infant, Newborn, Obstetrics and Gynecology, Infant, Low Birth Weight, medicine.disease, respiratory tract diseases, Clinical trial, chemistry, Outcomes research, Infant, Extremely Premature, Anesthesia, Pediatrics, Perinatology and Child Health, Cohort, cardiovascular system, Population study, Elevated transaminases, Hypotension, business
Abstract: Objective To characterize the safety of sildenafil in premature infants. Study design A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. Results Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. Conclusion Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants. Clinical trial ClinicalTrials.gov Identifier: NCT01670136.
Published: 2021
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7. Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver

Author: Philip J. Rosenthal, Kathleen M. Loomes, Robert H. Squires, Saul J. Karpen, Simon Horslen, John C. Magee, Emily M. Fredericks, Wen Ye, Vicky L. Ng, Ronald J. Sokol, Binita M. Kamath, Kasper S. Wang, Estella M. Alonso, Jean P. Molleston, James E. Heubi, Daniel H. Leung, Kieran Hawthorne, and Lisa G. Sorensen
Subjects: Pediatrics, medicine.medical_specialty, Bilirubin, Cholestasis, Intrahepatic, Liver disease, chemistry.chemical_compound, Original Articles: Hepatology, Alagille syndrome, medicine, Humans, Child, alpha-1 antitrypsin deficiency, Cholestasis, Alpha 1-antitrypsin deficiency, Working memory, business.industry, Wechsler Scales, Gastroenterology, Progressive familial intrahepatic cholestasis, Wechsler Adult Intelligence Scale, medicine.disease, Alagille Syndrome, Malnutrition, chemistry, Child, Preschool, neurocognitive, Pediatrics, Perinatology and Child Health, progressive familial intrahepatic cholestasis, intelligence quotient, business
Abstract: Objective: To evaluate neurodevelopmental status among children with inherited cholestatic liver diseases with native liver and variables predictive of impairment. Methods: Participants with Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and alpha 1 antitrypsin deficiency (A1AT) enrolled in a longitudinal, multicenter study and completed the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV. Full Scale Intelligence Quotient (FSIQ) was analyzed continuously and categorically (>100, 85–99, 70–84, 1 standard deviation [SD] below average) was highest in ALGS (29%) versus 18.6% in PFIC and 12.8% in A1AT, and was greater than expected in ALGS based on normal distribution (29% vs 15.9%, P = 0.003). ALGS scored significantly lower than test norms in almost all Wechsler composites; A1AT scored lower on Working Memory and Processing Speed; PFIC was not different from test norms. Total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education were significantly associated with FSIQ. Conclusions: Patients with ALGS are at increased risk of lower FSIQ, whereas our data suggest A1AT and PFIC are not. A1AT and ALGS appear vulnerable to working memory and processing speed deficits suggestive of attention/executive function impairment. Malnutrition, liver disease severity, and sociodemographic factors appear related to FSIQ deficits, potentially identifying targets for early interventions.
Published: 2021
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8. Acute and Chronic Placental Abnormalities in a Multicenter Cohort of Newborn Infants with Hypoxic–Ischemic Encephalopathy

Author: Dennis E. Mayock, Amy M. Goodman, Rakesh Rao, Raymond W. Redline, Ellen M. Bendel-Stenzel, Mariana Baserga, Andrea L. Lampland, Taeun Chang, Krisa P. Van Meurs, Joern Hendrik Weitkamp, Tai-Wei Wu, Yvonne W. Wu, Bryan A. Comstock, Gregory M Sokol, Ulrike Mietzsch, Nathalie L. Maitre, Fernando F. Gonzalez, Brenda B. Poindexter, Toby D Yanowitz, John Flibotte, Kaashif A. Ahmad, Lina F. Chalak, Sandra E. Juul, David Riley, and Amit M. Mathur
Subjects: Male, medicine.medical_specialty, Placenta Diseases, Encephalopathy, Gestational Age, Gastroenterology, Hypoxic Ischemic Encephalopathy, Cohort Studies, Double-Blind Method, Hypothermia, Induced, Pregnancy, Risk Factors, Internal medicine, Placenta, Humans, Medicine, Erythropoietin, Asphyxia, Clinical pathology, business.industry, Infant, Newborn, medicine.disease, medicine.anatomical_structure, Acute Disease, Chronic Disease, Hypoxia-Ischemia, Brain, Pediatrics, Perinatology and Child Health, Cohort, Gestation, Female, medicine.symptom, business, Villitis of unknown etiology
Abstract: To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE.Infants born at ≥36 weeks of gestation (n = 500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system.Complete placental pathologic examination was available for 321 of 500 (64%) trial participants. Placental abnormalities were identified in 273 of 321 (85%) and were more common in infants ≥40 weeks of gestation (93% vs 81%, P = .01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (-15.9 vs -14.3, P = .049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs 38.0, P .001) and greater rates of clinically diagnosed chorioamnionitis (25% vs 2%, P .001) than those without acute abnormalities.Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.ClinicalTrials.gov: NCT02811263.
Published: 2021
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9. Caspase 8 sounds the alarm for allergic inflammation

Author: Caroline L. Sokol and Xueping Zhu
Subjects: Allergy, biology, business.industry, Immunology, Ripoptosome, Caspase 8, medicine.disease, Allergic inflammation, Interleukin 33, ALARM, medicine, biology.protein, Immunology and Allergy, business, Caspase
Published: 2022
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10. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C 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Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, 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Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, 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S.G., Ruzyllo W., Gosselin G., Maggioni A.P., White H.D., Bhargava B., Min J.K., John Mancini G.B., Berman D.S., Picard M.H., Kwong R.Y., Ali Z.A., Mark D.B., Spertus J.A., Krishnan M.N., Elghamaz A., Moorthy N., Hueb W.A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T.D., Szwed H., Doerr R., Keltai M., Selvanayagam J.B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N.O., Harrell F.E., Rockhold F.W., Broderick S., Bruce Ferguson T., Williams D.O., Harrington R.A., Stone G.W., Rosenberg Y, and ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, 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Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar 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George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona 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Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima 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Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020
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11. METHOD OF FORENSIC ASSESSMENT OF RISK FACTORS OF TREATMENT FAILURE OUTCOMES AS AN ELEMENT OF QUALITY MANAGEMENT OF MEDICAL CARE

Author: Kostyantin M. Sokol, Vyacheslav K. Sokol, Vira A. Kolesnichenko, and Vladyslav A Smiianov
Subjects: 030222 orthopedics, medicine.medical_specialty, Quality management, Osteosynthesis, business.industry, Osteomyelitis, 030208 emergency & critical care medicine, General Medicine, Knee Joint, medicine.disease, Medical care, Surgery, 03 medical and health sciences, Pseudarthrosis, 0302 clinical medicine, medicine, Displacement (orthopedic surgery), Contracture, medicine.symptom, business
Abstract: OBJECTIVE The aim: The aim of this research was to study causes of the development of adverse outcomes in isolated femоral diaphyseal fractures. PATIENTS AND METHODS Materials and methods: A retrospective analysis of the protocols of clinical and radiological examination of 21 patients was performed. Based on the initial expert assessment, these patients have not been established the severity of injuries due to the development of complications in the postoperative period. CONCLUSION Conclusions: Patient-dependent, implant-dependent, and surgery-dependent causes that caused a violation of the stability of osteosynthesis (95.2%) were identified. This led to a secondary displacement of bone fragments (71.4%), delayed fracture consolidation (61.9%), the formation of pseudarthrosis (38.1%), the development of post-traumatic osteomyelitis (14,3), migration of screws from the osseous plate (47.6%), and the development of post-traumatic contracture of the knee joint (81.0%).
Published: 2020
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12. Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study

Author: Mathurin Fumery, Jérôme Filippi, Vered Abitbol, Amélie Biron, David Laharie, Melanie Serrero, Romain Altwegg, Yoram Bouhnik, Laurent Peyrin‐Biroulet, Cyrielle Gilletta, Xavier Roblin, Guillaume Pineton de Chambrun, Lucine Vuitton, Anne Bourrier, Stephane Nancey, Jean‐Marc Gornet, Stephane Nahon, Guillaume Bouguen, Stephanie Viennot, Maria Nachury, Aurelien Amiot, Franck Brazier, Clara Yzet, Xavier Hebuterne, Guillaume Cadiot, Hedia Brixi, Pauline Rivière, Florian Poullenot, Xavier Treton, Carmen Stefanescu, Camille Zallot, Laurent Beaugerie, Philippe Seksik, Harry Sokol, Julien Kirchgesner, Gilles Boschetti, Bernard Flourié, Claire Gay, Pauline Danion, Chloe Venturin, Matthieu Allez, Clotilde Baudry, Benjamin Pariente, Pauline Wils, Charlotte Gagnière, Jenny Tannoury, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Bordeaux [Bordeaux], CHU Marseille, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Lille, CHI Créteil, GETAID, Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Adult, Male, medicine.medical_specialty, Pancolitis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Vedolizumab, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, Ustekinumab, Humans, Medicine, Pharmacology (medical), Adverse effect, Colectomy, Hepatology, business.industry, Remission Induction, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Ulcerative colitis, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Colitis, Ulcerative, 030211 gastroenterology & hepatology, medicine.symptom, business, medicine.drug, Cohort study
Abstract: International audience; Background Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. Aims To assess the real-world effectiveness and safety of ustekinumab in patients with UC. Methods From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score
Published: 2021
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13. Meaning and purpose in Huntington’s disease: a longitudinal study of its impact on quality of life

Author: David Cella, Danny Bega, Samuel Frank, Jane S. Paulsen, Benzi M. Kluger, Joshua Hauser, Jonathan P. Troost, Allison J. Applebaum, Noelle E. Carlozzi, Colin A. Depp, Nicholas R. Boileau, and Leonard L. Sokol
Subjects: Adult, Male, Longitudinal study, media_common.quotation_subject, Population, Neurosciences. Biological psychiatry. Neuropsychiatry, Anger, Quality of life, Huntington's disease, Humans, Medicine, Longitudinal Studies, Cognitive decline, RC346-429, education, Research Articles, Aged, media_common, education.field_of_study, business.industry, General Neuroscience, Cognition, Middle Aged, medicine.disease, Huntington Disease, Quality of Life, Anxiety, Female, Neurology. Diseases of the nervous system, Neurology (clinical), medicine.symptom, business, Research Article, RC321-571, Clinical psychology
Abstract: Objective Previous work in Huntington’s disease (HD) has shown that a sense of meaning and purpose (M&P) is positively associated with positive affect and well‐being (PAW); however, it was unknown whether HD‐validated patient‐reported outcomes (PROs) influence this association and how M&P impacts PROs in the future. Our study was designed to examine if HD‐validated PROs moderate the relationship between M&P and PAW and to evaluate if baseline M&P predicts 12‐ and 24‐month changes in HD‐validated PROs. Methods This was a longitudinal, multicenter study to develop several PROs (e.g., specific for the physical, emotional, cognitive, and social domains) for people with HD (HDQLIFE). The sample consisted of 322 people with HD (n = 50 prodromal, n = 171 early‐stage manifest, and n = 101 late‐stage manifest HD). A single, multivariate linear mixed‐effects model was performed with PAW as the outcome predicted by main effects for M&P and several moderators (i.e., an HD‐validated PRO) and interactions between M&P and a given PRO. Linear‐mixed models were also used to assess if baseline M&P predicted HD‐validated PROs at 12 and 24 months. Results Higher M&P was positively associated with higher PAW regardless of the magnitude of symptom burden, as represented by HD‐validated PROs, and independent of disease stage. In our primary analysis, baseline M&P predicted increased PAW and decreased depression, anxiety, anger, emotional/behavioral disruptions, and cognitive decline at 12 and 24 months across all disease stages. Interpretation These findings parallel those seen in the oncology population and have implications for adapting and developing psychotherapeutic and palliative HD interventions.
Published: 2021
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14. Targeting CD22 for the Treatment of B-Cell Malignancies

Author: Lubomir Sokol and Nikesh N. Shah
Subjects: medicine.drug_class, Immunology, lymphoma, Review, epratuzumab, acute lymphoblastic leukemia, inotuzumab ozogamicin, Monoclonal antibody, CD19, immune system diseases, hemic and lymphatic diseases, medicine, Immunology and Allergy, CD22, B cell, CD20, chimeric antigen receptor, biology, business.industry, medicine.disease, Chimeric antigen receptor, Lymphoma, bispecific antibody, medicine.anatomical_structure, biology.protein, Cancer research, business, Epratuzumab, medicine.drug
Abstract: Immunotherapeutic agents play an increasingly important role in the treatment of B-cell malignancies. CD19 and CD20 are common targets for lymphoid malignancies, though patients who relapse have few therapeutic options remaining. CD22 is a cell surface sialoglycoprotein uniquely present on B-cells and regulates B-cell function and proliferation. Thus, it is an appealing therapeutic target for autoimmune disorders and B-cell malignancies. A variety of therapies targeting CD22 have been developed, including monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, chimeric antigen receptor T cells, and bispecific antibodies. Here, we review the biology of CD22 and key therapies targeting CD22 in lymphoid malignancies.
Published: 2021
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15. A decision tree model for neuroimmune guidance of allergic immunity

Author: Caroline L. Sokol, Caroline Perner, and Cameron H. Flayer
Subjects: 0301 basic medicine, Damp, Allergy, animal diseases, Immunology, chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, Hypersensitivity, medicine, Humans, Immunology and Allergy, Innate immune system, Decision Trees, Cell Biology, Allergens, biochemical phenomena, metabolism, and nutrition, medicine.disease, Immunity, Innate, 030104 developmental biology, Neuroimmunology, Immune System, bacteria, Wound healing, Neuroscience, Function (biology), 030215 immunology
Abstract: The immune system defends the body from infectious and non-infectious threats. Distinct recognition strategies have evolved to generate antigen-specific immunity against pathogens or toxins versus antigen-independent tissue repair. Structural recognition, or the sensing of conserved motifs, guides the immune response to viruses, bacteria, fungi, and unicellular parasites. Functional recognition, which is sensing that is based on the activities of an input, guides antigen-independent tissue healing and antigen-specific Type 2 immunity to toxins, allergens, and helminth parasites. Damage-associated molecular patterns (DAMPs), released from damaged and dying cells, permit functional recognition by immune cells. However, the DAMP paradigm alone does not explain how functional recognition can lead to such disparate immune responses, namely wound healing and Type 2 immunity. Recent work established that sensory neurons release neuropeptides in response to a variety of toxins and allergens. These neuropeptides act on local innate immune cells, stimulating or inhibiting their activities. By integrating our knowledge on DAMP function with new information on the role of neuropeptides in innate immune activation in Type 2 immunity, we describe a decision tree model of functional recognition. In this model, neuropeptides complement or antagonize DAMPs to guide the development of antigen-specific Type 2 immunity through the activation of innate immune cells. We discuss why this decision tree system evolved and its implications to allergic diseases.
Published: 2021
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16. Comparative Genomic Analysis of Intrahepatic Cholangiocarcinoma: Biopsy Type, Ancestry, and Testing Patterns

Author: Jason K. Sicklick, Hanna Tukachinsky, Kimberly McGregor, Shumei Kato, Mason A. Israel, Halla Nimeiri, Geoffrey R. Oxnard, Jeffrey S. Ross, Karthikeyan Murugesan, Ethan Sokol, Razelle Kurzrock, Ole Gjoerup, and Natalie Danziger
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, IDH1, Biopsy, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Text mining, Internal medicine, medicine, Humans, Liquid biopsy, Intrahepatic Cholangiocarcinoma, medicine.diagnostic_test, business.industry, Genomics, medicine.disease, Primary tumor, Clinical trial, Bile Ducts, Intrahepatic, 030104 developmental biology, Bile Duct Neoplasms, 030220 oncology & carcinogenesis, Biomarker (medicine), Hepatobiliary, business
Abstract: BackgroundAt diagnosis, the majority of patients with intrahepatic cholangiocarcinoma (IHCC) present with advanced disease and a poor prognosis. Comprehensive genomic profiling (CGP) early in the disease course may increase access to targeted therapies and clinical trials; however, unresolved issues remain surrounding the optimal biopsy type to submit for CGP.Patients and MethodsMutational frequencies between primary tumor biopsies (Pbx), metastatic biopsies (Mbx), and liquid biopsies (Lbx) in 1,632 patients with IHCC were compared.ResultsPotentially actionable alterations were found in 52%, 34%, and 35% of patients in the Pbx, Mbx, and Lbx cohorts, respectively. In Pbx, Mbx, and Lbx, FGFR2 rearrangements were found in 9%, 6%, and 4%, and IDH1 mutations were identified in 16%, 5%, and 9% patients, respectively. Moreover, alterations in FGFR2 and IDH1 were significantly associated with distinct ancestries, including 2.1-fold enrichment for FGFR2 rearrangements in patients with African ancestry and 1.5-fold enrichment for IDH1 mutations in patients with admixed American (Hispanic) ancestry. Finally, the publication of biomarker-driven clinical trials in IHCC correlated with changing CGP testing patterns. Significant correlations between patient characteristics and IHCC trial disclosures were observed, including a significant decrease from time between biopsy and CGP testing, and more frequent testing of primary versus metastatic samples.ConclusionOverall, because of the high likelihood of identifying actionable genomic alterations, CGP should be considered for the majority of patients with inoperable IHCC, and Lbx and Mbx can be considered as part of the diagnostic suite.Implications for PracticeComprehensive genomic profiling (CGP) should be considered for all patients with intrahepatic cholangiocarcinoma (IHCC) or suspected IHCC, as actionable alterations were commonly found in multiple genes and a wide variety of FGFR2 fusion partners were identified. The disclosure of IHCC trial data correlated with increased use of CGP, an encouraging trend that moves new therapeutic options forward for rare cancers with a rare biomarker. Although tissue from the primary lesion may identify actionable alterations at higher rates, CGP of a liquid biopsy or metastatic site can be considered, particularly if the primary tissue block is exhausted.
Published: 2021
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17. Autoimmune liver damage in patients with primary Sjogren's syndrome associated with anticentromeric antibodies

Author: B. D. Chalcev, V. I. Vasiliev, S. G. Palshina, A. V. Torgashina, E. V. Sokol, J. I. Khvan, E. B. Rodionova, T. N. Safonova, and T. P. Nekrasova
Subjects: medicine.medical_specialty, Cirrhosis, systemic sclerosis, Immunology, Anti-centromere antibodies, Autoimmune hepatitis, Gastroenterology, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Cholestasis, Internal medicine, medicine, autoimmune cholangitis, Immunology and Allergy, Pharmacology (medical), 030203 arthritis & rheumatology, biology, business.industry, primary biliary cholangitis, primary sjogren's syndrome, Viral hepatitis b, medicine.disease, digestive system diseases, stomatognathic diseases, biology.protein, Cross syndrome, Medicine, 030211 gastroenterology & hepatology, anti-centromere antibodies, medicine.symptom, Antibody, business, biliary ducts epiteliitis
Abstract: Objective: to determine the frequency, spectrum and severity of liver affection in anti-centromere antibodies (ACA) positive patients with primary Sjogren's syndrome (pSS).Patients and methods. 119 ACA-positive patients with pSS were included in the study, 37 (31%) of them had signs of liver damage, 3 of these patients were excluded from the study (2 had cholelithiasis, 1 had viral hepatitis B). Signs of autoimmune liver damage were found in 34 (28.6%) patients, most of them were seropositive for antimitochondrial antibodies (AMA). The diagnosis of primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) was established according to the recommendations of the American Association for the Study of Liver Diseases, the Russian Gastroenterological Association and the Russian Society for the Study of the Liver. In 5 (14.7%) patients the cause of cholestasis remained unspecified.Results and discussion. AMA were found in 73.5% of patients, elevated serum IgM levels – in 57.6%. Clinically liver damage in most cases was characterized by an asymptomatic, slowly progressive course without a dramatic increase of symptoms over time. Liver cirrhosis was found in 14.7% of patients. According to clinical, laboratory and morphological manifestations, PBC was diagnosed in 21 patients, 4 of them also had a cross syndrome with AIH. AMA-negative PBC was found in 3 patients and isolated AIH – in 1. In most cases, histological stage I of PBC was detected. During follow-up, median of 7 years (range from 2 to 15 years), in 7 patients with stage I PBC and in 7 AMA-positive patients without functional liver disorders no clinical, laboratory or instrumental progression of liver damage was noted. In this regard, it was suggested that these patients have epitheliitis of the biliary ducts as manifestation of glandular affection in pSS, and not true PBC.Conclusion. Autoimmune liver lesions are detected in 28.6% of ACA-positive patients with pSS, most (41.2%) of them develop epitheliitis of the biliary ducts as pSS manifestation or a combination of pSS with PBC (with the same frequency), less often PBC / AIH cross syndrome is diagnosed. PBC / pSS-related epitheliitis of the biliary ducts in ACA-positive patients is characterized by a slowly progressive asymptomatic course in most cases and rarely leads to the development of liver cirrhosis.
Published: 2021

18. Comparative characteristics of the clinical and laboratory features of the primary Sjogren’s syndrome associated with anticentromere antibodies and the 'classic' subtype of the disease

Author: B. D. Chaltsev, V. I. Vasiliev, S. G. Palshina, A. V. Torgashina, E. V. Sokol, Yu. I. Khvan, E. B. Rodionova, and T. N. Safonova
Subjects: musculoskeletal diseases, medicine.medical_specialty, Paraproteinemia, systemic sclerosis, Immunology, Diseases of the musculoskeletal system, Gastroenterology, primary sjogren’s syndrome, Autoimmune thyroiditis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, stomatognathic system, Internal medicine, medicine, Immunology and Allergy, Rheumatoid factor, 030212 general & internal medicine, skin and connective tissue diseases, 030203 arthritis & rheumatology, medicine.diagnostic_test, business.industry, primary biliary cholangitis, Hypergammaglobulinemia, MALT lymphoma, anticentromere antibodies, medicine.disease, Cryoglobulinemia, eye diseases, Lymphoma, stomatognathic diseases, RC925-935, Liver biopsy, business, malt-lymphoma
Abstract: Objective: to compare clinical and laboratory manifestations in 2 groups of patients with primary Sjogren’s syndrome (pSS): with and without anticentromere antibodies (ACA); compare the incidence, clinical and laboratory characteristics of lymphomas in these two groups.Materials and methods. We examined 119 patients with ACA-positive pSS (pSS-ACA+). pSS was diagnosed based on Russian 2001 criteria, systemic sclerosis (SSc) – criteria ACR/EULAR 2013. To diagnose liver diseases, the level of transaminases, alkaline phosphatase and antimitochondrial antibodies (AMA) was determined, as well as liver biopsy. The diagnosis of primary biliary cholangitis (PBC) was established according to the recommendations of the American Association for the Study of Liver Diseases, the Russian Gastroenterological Association and the Russian Society for the Study of the Liver. Lymphomas were diagnosed according to histological, immunohistochemical and molecular studies of affected organs biopsies, according to the classification of the World Health Organization. A combination of pSS and SSc was diagnosed in 37 patients, and they were excluded from further analysis. We compared clinical and laboratory features in patients with pSS-ACA+ (n=82) and ACA-negative pSS (pSS-ACA–, n=64) and characterized lymphomas in the pSS-ACA+ (n = 14) and pSS-ACA– (n=10) groups.Results and discussion. In patients with pSS-ACA+, a later age of disease onset was revealed, the duration of the disease before lymphoma development did not differ. In patients with pSS-ACA+, we found a lower frequency of rheumatoid factor (RF), antibodies to Ro (anti-Ro) and La (anti-La), decreased C3-complement, hypergammaglobulinemia, increased IgG concentration, CRP, increased ESR, leukopenia and anemia. 51.2% of patients with pSS-ACA+ were seronegative for anti-Ro, anti-La and RF. Patients with pSS-ACA+ had a higher frequency of AMA and elevated IgM. The incidence of cryoglobulinemia and paraproteinemia did not differ. The frequency of recurrent parotitis in pSS-ACA+ was significantly lower, there were no differences in the frequency and severity of other signs of salivary and lacrimal gland damage. PBC and epitheliitis of the biliary ducts in patients with pSS-ACA+ were detected significantly more often. Damage to the peripheral nervous system, lungs, hypergammaglobulinemic purpura, arthralgia and autoimmune thyroiditis were significantly more often detected in the group of patients with pSS-ACA–. In the pSS-ACA+ group, Raynaud’s phenomenon was significantly more frequent, mainly with scleroderma-type capillaroscopic abnormalities. There was no difference in the frequency of other signs characteristic of SSc. MALT lymphomas were diagnosed in the study groups with the same frequency. Patients with lymphomas in the pSS-ACA+ group were characterized by significantly higher laboratory activity. All patients with lymphomas in both groups showed persistent parotid salivary gland enlargement. Lymphomas in both groups developed in patients with late stage salivary and lacrimal gland damage, systemic manifestations of pSS in both groups were rare.Conclusion. pSS-ACA+ is an independent subtype of pSS, which has a number of significant clinical and laboratory differences from the “classic” variant of the disease. ACA in pSS are associated with a low frequency of anti-Ro, anti-La, and RF, as well as an increased risk of PBC and limited SSc. MALT lymphomas in the pSS-ACA+ and pSS-ACA– groups developed with the same frequency and were associated with the progression of glandular damage, regardless of the presence of systemic manifestations.
Published: 2021

19. Advances in Neuroblastoma and Wilms Tumor

Author: Elizabeth Sokol and Amy L. Walz
Subjects: Loss of heterozygosity, business.industry, Neuroblastoma, Cancer research, Medicine, High risk neuroblastoma, Wilms' tumor, business, medicine.disease
Published: 2021
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20. Large granular lymphocytic leukemia – A retrospective study of 319 cases

Author: Haipeng Shao, Ling Zhang, Ning Dong, Lubomir Sokol, Qianxing Mo, Franco Castillo Tokumori, Todd C. Knepper, Yumeng Zhang, Ankita Tandon, and Leidy Isenalumhe
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Cyclophosphamide, Large granular lymphocytic leukemia, Antineoplastic Agents, Gastroenterology, Young Adult, Internal medicine, Humans, Medicine, Risk factor, Survival analysis, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Disease Management, Cancer, Retrospective cohort study, Hematology, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Leukemia, Large Granular Lymphocytic, Leukemia, Methotrexate, Treatment Outcome, Cyclosporine, Female, business, Immunosuppressive Agents, medicine.drug
Abstract: Large granular lymphocytic leukemia (LGLL) is a rare hematological malignancy that arises from cytotoxic T lymphocytes (T-LGLL) in 85% of cases and natural killer (NK) cells in the rest. A significant knowledge gap exists regarding the pathogenesis, treatment choices, and prognostic factors of LGLL. We report a cohort of 319 consecutive LGLL patients who presented to our cancer center between 2001 and 2020. A total of 295 patients with T-LGLL and 24 with chronic NK-cell lymphoproliferative disorder (CLPD-NK) were identified. The median age was 65 years (range, 17-90 years). Eighty-three patients (26.0%) had autoimmune diseases. A total of 119 patients (37.3%) had coexisting malignancies, 66 (20.7%) had solid tumors, and 59 (18.5%) had hematological malignancies. Most coexisting malignancies were diagnosed before the diagnosis of LGLL. Treatment was needed for 57% of patients. Methotrexate (MTX), cyclophosphamide (Cy), and cyclosporine A (CSA) were most used and had similar response rates between 61.5%-74.4%. Cy produced more complete responses (32.3%) compared to MTX and CSA (15.7% and 23.1%, respectively). Thrombocytopenia, splenomegaly, and female gender (after controlling for autoimmune diseases) were associated with decreased response rates to MTX, CSA, or Cy. Autoimmune diseases were associated with increased response rates. Thrombocytopenia was an independent risk factor for worse survival.
Published: 2021
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21. Postoperative complications and recurrence rates after rectal prolapse surgery versus combined rectal prolapse and pelvic organ prolapse surgery

Author: Kavita Mishra, Lisa Rogo-Gupta, Brooke Gurland, Leila Neshatian, Bertha Chen, Eric R. Sokol, Shannon L. Wallace, and Ekene Enemchukwu
Subjects: Pelvic organ, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, Urinary retention, Urology, Prolapse surgery, 030232 urology & nephrology, Obstetrics and Gynecology, Physical examination, medicine.disease, Surgery, Rectal prolapse, 03 medical and health sciences, 0302 clinical medicine, Bristol stool scale, Cohort, medicine, medicine.symptom, business, Cohort study
Abstract: Our primary objectives were to compare < 30-day postoperative complications and RP recurrence rates after RP-only surgery and combined surgery. Our secondary objectives were to determine preoperative predictors of < 30-day complications and RP recurrence. A prospective IRB-approved cohort study was performed at a single tertiary care center from 2017 to 2020. Female patients with symptomatic RP underwent either RP-only surgery or combined surgery based on the discretion of the colorectal and FPMRS surgeons. Primary outcome measures were < 30-day complications separated into Clavien-Dindo (CD) classes and rectal prolapse on physical examination. Seventy women had RP-only surgery and 45 had combined surgery with a mean follow-up time of 208 days. Sixty-eight percent underwent abdominal RP repair, and 32% underwent perineal RP repair. Twenty percent had one or more complications, 14% in the RP-only group and 29% in the combined surgery group (p = 0.06). On multivariate analysis, combined surgery patients had a 30% increased risk of complications compared to RP-only surgery patients (RR = 1.3). Most of these complications were minor (14/17, 82.4%) and categorized as CD I or II, including urinary retention and UTI. Twelve percent of this cohort had RP recurrence, 11% in the RP-only group and 13% in the combined surgery group (p = 0.76). Preoperative risk factors for RP recurrence included a primary complaint of rectal bleeding (RR 5.5) and reporting stools consistent with Bristol Stool Scale of 1 (RR 2.1). Patients undergoing combined RP + POP surgery had a higher risk of complications and equivalent RP recurrence rates compared to patients undergoing RP-only surgery.
Published: 2021
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22. Patients with dementia and atrial fibrillation less frequently receive direct oral anticoagulants (DOACs) and experience higher thrombotic and mortality risk

Author: Jelena Lucijanic, Tomislav Letilović, Irzal Hadžibegović, Ivana Jurin, Sanda Sokol Tomić, Ida Tješić-Drinković, Josip Pejić, Vedran Radonić, and Marko Lucijanic
Subjects: medicine.medical_specialty, Administration, Oral, Ventricular Function, Left, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Atrial Fibrillation, Humans, Medicine, Dementia, In patient, 030212 general & internal medicine, Retrospective Studies, business.industry, Warfarin, Anticoagulants, Stroke Volume, Thrombosis, Atrial fibrillation, General Medicine, dementia, atrial fibrillation, direct oral anticoagulants, thrombosis, warfarin, medicine.disease, Stroke, Case-Control Studies, 030220 oncology & carcinogenesis, cardiovascular system, Presentation (obstetrics), business, medicine.drug
Abstract: Objective: To investigate differences in clinical presentation, anticoagulation pattern and outcomes in patients with dementia and atrial fibrillation (AF).Methods: A total of 1217 hospitalized patients with non-valvular AF from two institutions were retrospectively evaluated. Diagnosis of dementia was established by a psychiatrist or a neurologist prior to or during hospitalization. Adequacy of warfarin anticoagulation was assessed during follow-up using at least 10 standardized international ratio values. In addition to unmatched comparison, nested case-control study was performed to further evaluate differences in clinical outcomes between patients with and without dementia.Results: A total of 162/1217 (13.3%) patients were diagnosed with dementia. Among other associations, patients with dementia were significantly older with higher number of comorbidities, had lower estimated glomerular filtration rate (eGFR) and lower left ventricular ejection fraction (LVEF), (P < 0.05 for all analyses). Patients with dementia were significantly less likely to receive direct oral anticoagulants (DOACs ; 27.2% vs 40.3% ; P = 0.001) and were significantly more likely to be inadequately anticoagulated with warfarin (38.9% vs 28.6% ; P = 0.008) than patients without dementia. After matching based on age, eGFR, LVEF, and CHA2DS2-VASC patients with dementia were significantly more likely to experience inferior overall survival (HR = 1.8 ; P = 0.001) and shorter time to thrombosis (HR = 2.3 ; P = 0.019).Conclusion: Our findings speak in support of increased thrombotic and mortality risks in patients with dementia, possibly due to inadequate anticoagulation and higher number of comorbidities.
Published: 2021
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23. Guideline for the management of long tunnelled external ventricular drains in chronic hydrocephalus

Author: Hamish Wallace, Drahoslav Sokol, Chandrasekaran Kaliaperumal, Jothy Kandasamy, Phillip Correia Copley, John Emelifeonwu, and Pasquale Gallo
Subjects: medicine.medical_specialty, Pilocytic astrocytoma, business.industry, Context (language use), Guideline, medicine.disease, Hydrocephalus, 03 medical and health sciences, Nursing care, 0302 clinical medicine, Quality of life (healthcare), Parental education, Multidisciplinary approach, 030220 oncology & carcinogenesis, Chronic Disease, Practice Guidelines as Topic, medicine, Drainage, Humans, Child, Intensive care medicine, business, 030217 neurology & neurosurgery, General Nursing
Abstract: This article reports on the journey of a child with an inoperable hypothalamic-origin pilocytic astrocytoma causing hydrocephalus, which was refractory to treatment with shunts, and required a new approach. With multidisciplinary support, excellent nursing care and parental education, the child's hydrocephalus was managed long term in the community with bilateral long-tunnelled external ventricular drains (LTEVDs). This article describes the patient's journey and highlights the treatment protocols that were created to achieve this feat. Despite the difficulties in initially setting up these protocols, they proved successful and thus the team managing the patient proposed that LTEVDs are a viable treatment option for children with hydrocephalus in the context of inoperable tumours to help maximise quality of life.
Published: 2021
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24. Linking MATTERS: Barriers and Facilitators to Implementing Emergency Department-Initiated Buprenorphine-Naloxone in Patients with Opioid Use Disorder and Linkage to Long-Term Care

Author: Ja Young Kim, Elizabeth Tammaro, Thomas J. Stopka, and Randi Sokol
Subjects: medicine.medical_specialty, Health (social science), Narcotic Antagonists, Medicine (miscellaneous), Buprenorphine/naloxone, medicine, Humans, In patient, Psychiatry, Addiction treatment, Linkage (software), business.industry, Public Health, Environmental and Occupational Health, Opioid use disorder, Emergency department, Opioid-Related Disorders, medicine.disease, Long-Term Care, humanities, Buprenorphine, Psychiatry and Mental health, Long-term care, Opioid, Buprenorphine, Naloxone Drug Combination, Emergency Service, Hospital, business, medicine.drug
Abstract: In March 2019, our health system launched a project called Linking MATTERS (Medication for Addiction Treatment linkage Through Emergency depaRtmentS) to initiate evidence-based treatment for opioid...
Published: 2021
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25. DElayed COloRectal cancer care during COVID-19 Pandemic (DECOR-19): Global perspective from an international survey

Author: Santoro, Giulio A., Grossi, Ugo, Murad-Regadas, Sthela, Nunoo-Mensah, Joseph W., Mellgren, Anders, Di Tanna, Gian Luca, Gallo, Gaetano, Tsang, Charles, Wexner, Steven D, LA TORRE, Filippo, Abary Ryan Rainiel, A, Philippines, Abdelwahab Khaled M, Egypt, Abellán Antonio M, Spain, Abraham Ned, Australia, Achkasov Sergey I, Russia, Adamina Michel, Switzerland, Adamo Vincenzo, Italy, Agapov Mikhail, Russia, Agarwal Amit, Usa, Aguado López Héctor, Spain, Aguilar Werner, Chile, AguilarMartínez María Del Mar AM, Spain, Aguilera Asuncion, Spain, Ahmed Jamil, Uk, Aiello Domenico, Italy, Akagi Tomonori, Japan, Akcakaya Adem, Turkey, Akhtar Khalid I, Pakistan, Akiba Ricardo, Brazil, Akrami Majid, Iran, Akyol Cihangir, Turkey, Alaamer Ohood H, Saudi Arabia, Alapati Kishore, India, Alasari Sami, Saudi Arabia, Albastaki Sara, Uae, Albergaria Diogo, Portugal, Alconchel Felipe, Spain, Alerta-Torre Andrea J, Philippines, Alex Ochsner, Switzerland, Alexander Herold, Germany, Alfaro Samuel, El Salvador, Ali Jehangir F, Pakistan, Aliyazicioglu Tolga, Turkey, Almgla Naser, South Africa, Alonsopoza Alfredo, Spain, Al-Radjid Jamiri, Philippines, Alselaim Nahar A, Saudi Arabia, Altaf Kiran K, Uk, Althebaity Rasha, Saudi Arabia, Altinel Yuksel, Turkey, Altiparmak Basak, Turkey, Altomare Donato F, Italy, Alvandipour Mina, Iran, Alvarez-Gallego Mario, Spain, Alyami Mohammad, Saudi Arabia, Amado Sandra, Portugal, Amato Antonio, Italy, Amodio Pietro M, Italy, Ana-Maria Mușină, Romania, Andrade Luis, Chile, Andreas Kohler, Switzerland, Angelini Giulio, Italy, Angenete Eva, Sweden, Annicchiarico Alfredo, Italy, Antelo Galarza Renan, Bolivia, Anwer Mariyah, Pakistan, Aparício David J, Portugal, Arciniega Jose A, Mexico, Arezzo Alberto, Italy, Argenio Giulio, Italy, Arenas Mara, Belgium, Arnaud Alves AA, France, Arredondo Jorge, Spain, Arslan Baha, Turkey, Arya Shobhit, Uk, Aselmann Heiko, Germany, Aumann Georg, Germany, Avanzolini Andrea, Italy, Avendano Rodolfo, Chile, Awedew Atalel F, Ethiopia, Ayantunde Abraham, Uk, Aycan Ilker, Turkey, Aytac Erman, Turkey, Azevedo Constança TM, Portugal, Ba Am, Iraq, Bader Fg, Germany, Baehrle Markus, Germany, Bagaglini Giulia, Italy, Balaban Vladimir, Russia, Balciscueta Zutoia, Spain, Balciscueta Izaskun, Spain, Baldazzi Gianandrea, Italy, Balik Emre, Turkey, Bandolon Robert, Philippines, Barberis Andrea, Italy, Barisic Goran I, Serbia, Barrera Alejandro, Chile, Barros Inês MSF, Portugal, Basaran Betul, Turkey, Basilio Pedro C, Brazil, Bech Flemming, Denmark, Behboo Roubik, Iran, Behboudi Behnam, Iran, Beitia Ivan E, Panama, Bellato Vittoria, Italy, Bellolio Felipe, Chile, Benli Sami, Turkey, Bernal Jc, Spain, Bernante Paolo, Italy, Berrospi Francisco E, Peru, Bertelson Noelle, Usa, Bevan Katharine, Uk, Bhama Anuradha, Usa, Bianco Francesco, Italy, Bievel Radulescu Raluca, Romania, Bintraiki Thamer, Saudi Arabia, Bisgin Tayfun, Turkey, Bislenghi Gabriele, Belgium, Blaslaina Juanluis, Spain, Bloom Itm, Uk, Boehm Gabriele, Germany, Bogoni Selene, Italy, Bohlooli Mehrdad, Iran, Bondurri Andrea, Italy, Boni Luigi, Italy, Bonomi Alessandro Michele, Italy, Booning Nitikun, Thailand, Boonpipattanapong Teeranut, Thailand, Bordeianou Liliana, Usa, Bossard Kerrie, Usa, Botelho Maria, Portugal, Boto Carlos, Portugal, Bottini Corrado, Italy, Bouchagier Konstantinos, Greece, Boutall Adam, South Africa, Bowers Dan, Usa, Bozbiyik Osman, Turkey, Brambilla Eduardo, Brazil, Brisinda Giuseppe, Italy, Brizzi Maria Pia, Italy, Brizzolari Marco, Italy, Brusciano Luigi, Italy, Bucci Luigi, Italy, Buchwald Pam, Sweden, Bugra Dursun, Turkey, Bui Andrew, Australia, Buldanlı Mehmet Zeki, Turkey, Bulut Orhan, Denmark, Cagigas Fernandez Carmen, Spain, Cai Yuankun, China, Calcerrada Alises Enrique, Spain, Caldes Pedro, Portugal, Calussi Marco, Italy, Calvo Espino Pablo, Spain, Campanelli Michela, Italy, Campbell Ken, Uk, Campennì Paola, Italy, Canda Arasemre, Turkey, Capolupo Gabriella T, Italy, Caravana Jorge, Portugal, Carballo Federico HE, Argentina, Carbone Fabio, Italy, Carcamo Leonardo C, Chile, Cardoso Paulo, Portugal, Cariati Maria, Italy, Caricato Marco, Italy, Carmona Maria, Spain, Carpelan Holmstrom Monika, Finland, Carrié Augusto J, Argentina, Carrino Francesco, Italy, Cartucho Daniel DF, Portugal, Carvalho Marcia, Portugal, Carvas João M, Portugal, Casagranda Biagio, Italy, Casimiro Carlos, Portugal, Castro Anyely, Dominican Republic, Catiwala-An Michael T, Philippines, Caushaj Philip F, Usa, Cavallo Debora, Italy, Cedermas Mariela, Argentina, Celayir Fevzi, Turkey, Celentano Valerio, Uk, Cengiz Fevzi, Turkey, Chaisomboon Nopdanai, Thailand, Chenghua Luo, China, Cherepenin Mikhail, Russia, Chessa Antonella, Italy, Chierici Andrea, France, Chok Aikyong, Singapore, Chouliaras Christos, Greece, Chowchankit Irin, Thailand, Christou Niki, France, Chun Hokyung, South Korea, Cillara Nicola, Italy, Cinza Margarida, Portugal, Cione Gianpiero, Italy, Cipe Gokhan, Turkey, Ciprian Duta, Romania, Cirocco William, Usa, Citgez Bulent, Turkey, Clark Jill E, Usa, Clementi Ilaria IC, Italy, Clerc Daniel, Switzerland, Clermonts Journal Pre-proof 39 Stefan HEM, Netherlands, Cobellis Luigi, Italy, Colak Tahsin, Turkey, Colao Garcia Laura, Spain, Colombo Francesco, Italy, Comba Andrea, Italy, Coret Franco Alba CFA, Spain, Correa Bonito Alba, Spain, Cosman Bard, Usa, Costa Susana GS, Portugal, Costa Marta RP, Portugal, Costa Pereira Joaquim, Portugal, Cózar Lozano Coral, Spain, Cravero Francesca, Italy, Creavin Ben, Ireland, Cross Katie LR, Uk, Cruz Arturo, Spain, Cui Junhui, China, Cunha Miguel F, Portugal, Curado Antonio, Portugal, D'Ugo Stefano, Italy, Dajti Irida, Albania, Dalessandro Antonio, France, Dal Monte Giorgio, Italy, Danelli Piergiorgio, Italy, Daniels Ian R, Uk, Dar Asif M, India, Davies Richard J, Uk, De Andrés Beatriz, Spain, De Angelis Marsilio, Italy, De Falco Nadia, Italy, De Luca Maurizio, Italy, De Luca Raffaele, Italy, De Nardi Paola, Italy, De Rosa Michele, Italy, De Silva Kaluthanthiri Patabanadi VR, Sri Lanka, De Simone Veronica, Italy, De Wilt Johannes HW, Netherlands, De-León-Rendón Jorge Luis, Mexico, Dean Phillip, Usa, Deangelis Nicola, France, Dedemadi Georgia, Greece, Delgadillo Xavier, Switzerland, Delgadillo Edgar, Switzerland, D’Elia Antonio, Italy, Delibegovic Samir, Bosnia and Herzegovina, Delis S, Greece, Della Porta Massimiliano, Italy, Del Rio Paolo, Italy, De Marano Gaetano, Italy, Demey Karel, Belgium, Demirli Atıcı Semra, Turkey, Denoya Paula I, Usa, Derebey Murat, Turkey, De Santis Mariangela, France, Devezas Vítor BS, Portugal, Dhaif Ali, Bahrain, Diaconescu Bogdan, Romania, Di Candido Francesca, Italy, Die Javier, Spain, Dieguez Beatriz, Spain, Dieter Hahnloser, Switzerland, Diez Alonso Manuel, Spain, Dimaren Ishmael, Philippines, Disimone Massimo, Italy, Doerner Johannes, Germany, Domingos Hugo VG, Portugal, Dominguez Rubén RD, Paraguay, Dorenbusch Michael, Usa, Doulias Triantafyllos A, Uk, Duff Sarah, Uk, Dulskas Audrius, Lithuania, Dunn Gary, Usa, Duque-Mallén Victoria, Spain, Dusek Tomas, Czech Republic, Dusitanond Navara, Thailand, Dzulkarnaen Zakaria Andee, Malaysia, Dworkin Michael, United Kingdom, Dybau Aleh, Belarus, Dziakova Jana, Spain, Dziki Lukasz, Poland, Dziki Adam, Poland, Efetov Sergey K, Russia, Eisa Mohamed, Egypt, Eisenstat Ted, Usa, El Sorogy Mohamed, Egypt, El-Hussuna Alaa, Denmark, Elfeki Hossam, Egypt, Elhussuna Alaa, Denmark, Eliasrabelo Fernanda, Brazil, Ellis Tyler, Usa, Elzalabany Tamer, Egypt, Emile Sameh H, Egypt, Emiroglu Mustafa, Turkey, Emmanuel Odet, France, Enomoto Masanobu, Japan, Epifani Angelo Gabriele, Italy, Erenler Ilknur, Turkey, Erkan Arman, Usa, Erol Timuçin, Turkey, Erturk Suphan, Turkey, Escalante Ricardo, Venezuela, Escartin Jorg, Spain, Escrevente Ricardo, Portugal, Espin-Basany Eloy, Spain, Estaire-Gomez Mercedes, Spain, Falaschi Federica, Italy, Falken Ylva, Sweden, Fantini Corrado, Italy, Fantozzi Mauricio, Argentina, Farid Asim, Usa, Farina Pablo, Argentina, Farmer Russ, Usa, Farmer Martin, Uk, Faul Eleanor M, Ireland, Favara Andrea, Italy, Febra Pedro, Portugal, Fenner Lyra Junior Humberto, Brazil, Fermani Claudio, Argentina, Fernandes Fábio FN, Portugal, Fernandes Miguel, Portugal, Ferracci Federica, Italy, Ferrara Francesco, Italy, Ferrari Giovanni, Italy, Ferrario Luca, Italy, Ferreira Rita, Portugal, Ferreira Carlos, Portugal, Ferris Jeff, Usa, Ferronetti Antonio, Italy, Fialho Guilherme L, Portugal, Fichera Alessandro, Usa, Figueiredo Odete, Portugal, Filipe Vieira Pedro JG, Portugal, Fiore Felicia, Italy, Folliero Cristina, Italy, Folstad Torbjorn, Norway, Forerotorres Alexander, Spain, Forgan Timothy R, South Africa, Franceschilli Marzia, Italy, Frizelle Frank, New Zealand, Froehner Junior Ilario, Brazil, Frois Miguel, Portugal, Frontali Alice, France, Fu Chuangang, China, Fulginiti Serena, Italy, Galiffa Giampaolo, Italy, Gallagher Hugh J, Uk, Gallardo Cristian, Chile, Galleano Raffaele, Italy, Gama Barbara, Portugal, Garcia Conde Maria, Spain, Garcia Granero Alvaro, Spain, Garcia Esther, Spain, García Sánchez Felipe, Spain, Garcia Septiem Javier, Spain, Garcia Walter, Argentina, Garcia-Urena Miguel Angel, Spain, Garmanova Tatiana N, Russia, Garofalo Thomas, Usa, Garoufalia Zoe, Greece, Garulli Gianluca, Italy, Gatti Matteo, Italy, Gecim Ethem, Turkey, Gellona Jose, Chile, Gercek Yuksel, Uk, Ghignone Federico, Italy, Gianchandani Moorjani Rajesh, Spain, Gianfrancisco James A, Usa, Giani Iacopo, Italy, Gibert Juan, Spain, Gilles Manceau, France, Gilmore Andrew, Australia, Gilsanz Carlos, Spain, Gilshtein Hayim, Usa, Girgin Behic, Turkey, Giria Joao, Portugal, Giuffrida Maria Carmela, Italy, Giuliani Antonio, Italy, Goi Gloria, Italy, Golovina Anastasiya, Russia, Gomez Rosado Juan Carlos, Spain, González Enrique, Spain, Granada Nemesio, Philippines, Grimme Frederike, Netherlands, Grobler Stephen, South Africa, Guaitoli Eleonora, Italy, Guerci Claudio, Italy, Guerra Daniel, Mexico, Guerreiro José MM, Portugal, Guido Jutten, Belgium, Gulcu Baris, Turkey, Gunay Emre, Turkey, Gundes Ebubekir, Turkey, Gurbuz Bulent, Turkey, Gurjar Shashank, Uk, Hainsworth Alison J, Uk, Hall Nigel, Uk, Hamed Hosam H, Egypt, Hammer Clare, Uk, Hannon Rob, Ireland, Harmston Christopher, New Zealand, Harran Nadine, South Africa, Hartendorp Paul, Usa, Hassan Iyad, Uae, Hassan Imran, Usa, Hawkins Alexander T, Usa, Hayssen Theresa, Usa, Hendren Samantha, Usa, Hernandez Garcia Miguel, Spain, Hershman Michael, Journal Pre-proof 40 UK, Hild Stefanie, Germany, Hilton Joanna, Uk, Hiranyakas Art, Thailand, Ho Ming, Australia, Hollington Paul, Australia, Holubar Stefan, Usa, Hompes Roel, Netherlands, Houcine Maghrebi, Tunisia, Hovsepyan Vardges, Armenia, Hul Rene, Netherlands, Hunt Louise E, Uk, Hyder Zargham, Uk, Ibrahim Aini F, Malaysia, Iglesias Gustavo, Brazil, Iesalnieks Igors, Germany, Ilkanich Andrei, Russia, Imanova Nargiz, Azerbaijan, Isik Arda, Turkey, Jayathilaka Buddika, Uk, Jimenez Virginia, Spain, Jimenez-Gomez Luis Miguel, Spain, Jitmungngan Romyen, Thailand, Joelsson Magnus, Sweden, Joshi Heman, Uk, Juloski Jovan T, Serbia, Juwid Abdallah E, Libya, Kanjanasilp Prapon, Thailand, Kannappa Lava, Uk, Kanno Danilo, Brazil, Kaplan Esin, Turkey, Kara Yasin, Turkey, Kartal Abdulcabbar, Turkey, Kawamura Junichiro, Japan, Kaya Tayfun, Turkey, Kazemi Nava Andrea, Italy, Kazachenko Ekaterina A, Russia, Kelkar Ashish, Uk, Kelly Michael E, Ireland, Keramati Mohammad Reza, Iran, Kerawala Asad, Pakistan, Khalil Mohammad I, Bangladesh, Khan Jim S, Uk, Khan Rbn, Uk, Khitaryan Alexander, Russia, Kinjo Tatsuya, Japan, Kirilova Tanya N, Bulgaria, Kirmizi Yasemin, Turkey, Klaristenfeld Daniel, Usa, Knapp Jens, Norway, Koc Mehmet A, Turkey, Kocián Petr, Czechia, Konishi Tsuyoshi, Japan, Konstantoudakis Georgios, Cyprus, Konsten Joop, Netherlands, Kontovounisios Christos, Uk, Korkmaztoker Melike, Turkey, Kørner, Hartwig, Norway, Krdzic Igor, D, Serbia, Krivokapic Zoran, Serbia, Kumar Sanjeev, India, Kumar Sandip, Malaysia, Kushtrim Shala, Germany, Kynaston James, Uk, Langmayr Johannes, Austria, La Torre Marco, Italy, La Torre Filippo, Italy, Labalde Maria, Spain, Lagopoulos Vasileios, Greece, Lal Roshan, Uk, Landaluce- Olavarria Aitor, Spain, Langone Antonio, Italy, Lapolla Pierfrancesco, Italy, Larach Sergio, Usa, Larach, Andres, Chile, Larsson, Peranders, Sweden, Lasala Alfred, Philippines, Lauretta Andrea, Italy, Leao Pedro, Portugal, Lee Pamela C, Usa, Lee Suk-Hwan, South Korea, Lee Wooyong, South Korea, Lefevre Jeremie H, France, Leite Julio, Portugal, Lemaire Julien, Belgium, Lemma Maria, Italy, Lemme Gustavo Nestor, Argentina, Lenna Giovanni, Italy, Leo Cosimo Alex, Uk, Leventoglu Sezai, Turkey, Licardie Eugenio, Spain, Lienert Mark, Germany, Lima Sergio, Brazil, Limbert Manuel CSB, Portugal, Lisi Giorgio, Italy, Litta Francesco, Italy, Littaua Dennis, Philippines, Liu Fanlong, China, Liyanage Chris, New Zealand, Llovera Antony, Cuba, Lo Oswens, China, Lo Dico Rea, France, Lobascio Pierluigi, Italy, Lohsiriwat Varut, Thailand, Lombana Luis, Colombia, Lopez Marc, Philippines, Lopez Jose, Mexico, Lopez Francisco, Chile, Lorber Julie, Usa, Losada Manuel, Spain, Lowenfeld Lea, Usa, Lucci Enrico, Italy, Luglio Gaetano, Italy, Lynch Craig, Australia, Luqman, Pakistan, Machairas Nikolaos, Uk, Maciel João MRP, Portugal, Madbouly Khaled, Egypt, Madhoun, Nisreen, Usa, Maffioli, Anna, Italy, Magbojos Christian Raymond S, Philippines, Magistro Carmelo CM, Italy, Magrino Thomas, Usa, Makhoul Rami, Usa, Mallmann Karen DP, Brazil, Manatakis Dimitrios K, Greece, Mancini Stefano, Italy, Manfredelli Simone, France, Mangione John, Usa, Manso Antonio, Portugal, Marakutsa Eugen V, Moldova, Marano Alessandra, Italy, Marchesi Federico, Italy, Marchiori Mauro, Brazil, Marfan Michael, Australia, Marianelli Raphael, Brazil, Mariani Nicolò M, Italy, Marimuthu Kalimuthu, Uk, Marinello Franco, Spain, Marinis Athanasios, Greece, Marino Marco V, Italy, Markides Georgios, Cyprus, Marquez Lucila, Spain, Marra Angelo A, Italy, Martín Navarro Fabian, Mexico, Martin-Martin Gonzalo P, Spain, Martinez Javier, Spain, Martinez-Iglesias Marta A, Uk, Martins Ruben AFP, Portugal, Martins Ana RG, Portugal, Mascali Davide DM, Italy, Massucco Paolo, Italy, Matas Fernando, Spain, Mathew Alexander, Usa, Matzel Klaus E, Germany, Maun Dipen, Usa, Maurus Christine F, Switzerland, McCormick Jim, Usa, McIntyre Robert, Uk, McKinley Aileen, Uk, McLemore Lisa, Usa, McNeil Jennifer, Usa, McNevin Shane, Usa, Medich David, Usa, Medina Cesar, Mexico, Medina Quintana Rita E, Spain, Melo Ingrid, Paraguay, Melstrom Kurt A, Usa, Mendoza-Moreno Fernando, Spain, Menna Maria Paola, Italy, Mentz Ricardo, Argentina, Merlini David A, Italy, Mihmanli Mehmet, Turkey, Mike Spencer, Usa, Millan Monica, Spain, Miller Jerad, Usa, Milone Marco, Italy, Minahi Ilyas, Uk, Minaya-Bravo Ana María, Spain, Mingoli Andrea, Italy, Minicozzi Annamaria, Uk, Miranda Pedro, Portugal, Miro Antonio, Italy, Miskovic Danilo, Uk, Mistrangelo Massimiliano, Italy, Mitra Rajarshi, Uae, Mittal Rohin, India, Mladenovikj Dragoslav P, North Macedonia, Moctezuma Velázquez Paulina, Mexico, Mohamed Kamil Nil Amri, Malaysia, Mohammed Mohammed MH, Egypt, Mohsen Yasser MA, Uk, Monami Benoit N, Belgium, Monroe Justin, Usa, Monroy Hermogenes DJ, Philippines, Montori Giulia, Italy, Montuori Mauro, Italy, Mora-Guzmán Ismael, Spain, Moraes Ana, Brazil, Morales Carlos, Usa, Morelli Luca, Italy, Moreno Almudena, Spain, Moretto Gianluigi, Italy, Morici Riccardo, Italy, Morini Andrea, Italy, Moro-Valdezate David, Spain, Moroni Eliana, Italy, Morton Dion, Uk, Moura Catarina, Portugal, Moysidis Moysis M, Greece, Mozo Ana S, Spain, Nacion Aeris Jane D, Philippines, Nada Mohamed, Journal Pre-proof 41 Egypt, Nagasaki Toshiya, Japan, Nakamoto Yoshihiko, Japan, Neary Peter, Ireland, Negoi Ionut, Romania, Neijenhuis Peter A, Niger, Ng Simon SM, China, Niazi Samiullah, Pakistan, Nikoupour Hamed, Iran, Nogueiro Jorge PM, Portugal, Noguera Jose, Spain, Nova Carlos, Portugal, Nunes Amadeu, Portugal, O'Riordain Micheal G, Ireland, Oke Olatunbosun A, Nigeria, Okkabaz Nuri, Turkey, Oliva Cristiano, Italy, Oliveira Olga, Portugal, Oliveira Manuel, Portugal, Oliveira Antonio, Portugal, Oliveira Lucia CC, Brazil, Olivier James B, Uk, Olivier Pittet, Switzerland, Omejc Mirko, Slovenia, Ong Loreto B, Philippines, Ong David, Malaysia, Onglao Mark, Philippines, Onody Peter, Hungary, Orefice Raffaele, Italy, Ortega David, Peru, Ozben Volkan, Turkey, Ozcan Onder, Turkey, Ozturk Ersin, Turkey, Pacheco Andre, Portugal, Paci Marco, France, Paczosa Marcin, Poland, Padmanabhan Anantha, Usa, Pai Ajit, India, Palmer Gabriella, Sweden, Pandey Diwakar, India, Panis Yves, France, Pantel, Haddon, Paonariang Krisada, Thailand, Papa Mario V, Italy, Papadopoulos Aristeidis, Greece, Papagni Vincenzo, Italy, Papp Andras, Sweden, Parello Angelo, Italy, Parente Alessandro, Uk, Parra Pedro, Spain, PascualMigueláñez Isabel, Spain, Pata Francesco, Italy, Patel Nikhil, Usa, Patel Reeya, Uk, Pattyn Paul RL, Belgium, Paul Bikram, Usa, Pavanello Maurizio, Italy, Pedro Luis E, Argentina, Pellino Gianluca, Spain, Peltrini Roberto, Italy, Peña Ros Emilio, Spain, Pennacchi Luca UC, Italy, Pereira André, A Portugal, Pereira Bela, Portugal, Perez Guillermo, Ecuador, Perez Horacio, Portugal, Perez Natalia, Spain, Perez Flecha Marina, Spain, Perinotti Roberto, Italy, Pernazza Graziano, Italy, Perra Teresa, Italy, Pertile Davide, Italy, Pessia Beatrice, Italy, Pessoa Joana, Brazil, Petagna Lorenzo, Italy, Peters Walter, Usa, Petit Mindy, Usa, Petracca Gabriele Luciano, Italy, Pezzolla Francesco, Italy, Philp Matthew, Usa, Pianim Nana, Usa, Picciariello Arcangelo, Italy, Piccinini Pablo E, Argentina, Piccinni Giuseppe, Italy, Piccolo Davide, Italy, Pigalarga, Rodolfo, Pikarsky Alon J, Israel, Pimentel Alice, Portugal, Pinchot Scott, Usa, Pinotti Enrico, Italy, Pinto Diogo, Portugal, Pirozzi Felice, Italy, Plastiras Aris, Greece, Platto Marco, Italy, Plerhoples Tim, Usa, Podda Mauro, Italy, Poggi Luis, Peru, Polastri Roberto, Italy, Porcu Alberto, Italy, Porter Michael, Usa, Poskus Eligijus, Lithuania, Potolicchio Analia I, Argentina, Poylin Vitaliy, Usa, Pozzo Mauro, Italy, Pramateftakis Manos, Greece, Pravosudov Igor V, Russia, Praxedes Vanessa P, Portugal, Primoromaguera Vicent, Spain, Progno Valerio C, Italy, Proud David M, Australia, Pucciarelli Salvatore, Italy, Qadir Abdul, Uk, Qayoom Hina, Pakistan, Quindos Patricia, Spain, Quintanilha Rui, Portugal, Quinteros Francisco A, Usa, Qureshi Nafees, Uk, Rachadell Juan J, Portugal, Ralf Schmidt, Germany, Raman Shankar, Usa, Ramos Diego, Spain, Ramos Jose, Portugal, Ramwell, Andrew, Randazzo, Valentina, Rattanarpichart Patsaporn, Thailand, Ratto Carlo, Italy, Rautio Tero, Finland, Raviolo Carla, Italy, Read Thomas, Usa, Real Joao, Portugal, Rega Daniela, Italy, Regadas Francisco, Brazil, Regenbogen Scott, Usa, Reia Marta, Portugal, Reina Angel, Spain, Rems Miran, Slovenia, Rencuzogullari Ahmet, Turkey, Renwick Andrew A, Uk, Reyes Juan C, Colombia, Reyes Jeryl Anne Silvia R, Philippines, Ribeiro Jr Ulysses, Brazil, Ridzuan Farouk, Singapore, Ripetti Valter, Italy, Ripoll Cristina, Mexico, Ripollés-Melchor Javier, Spain, Rizal Rizal, Indonesia, Rizk Mariam, Uk, Rizvi Irfan, Usa, Robinson Jonathan, Uk, Rodimov Sergei, Russia, Rodrigues João VL, Brazil, Rodriguez Javier, Mexico, Rodriguez Cristian, Argentina, Rodriguez Homero, Panama, Rodriguez Garcia Jaime, Mexico, Roig Jose, Spain, Rojanasakul Arun, Thailand, Rojas Julio, Chile, Romanelli Elena, France, Rosa Fausto, Italy, Rosato Guillermo, Argentina, Rosenberg Robert, Switzerland, Rosete Manuel, Portugal, Roslani April C, Malaysia, Rottoli Matteo, Italy, Roxas Manuel Francisco Roxas T, Philippines, Roxburgh Campbell S, Uk, Ruan Joseph, Usa, Rubbini Michele M, Italy, Rubio Eduardo, Spain, Ruddy Theresa, Usa, Rueda Camilo, Spain, Ruiztovar Jaime, Spain, Rusconi Andrea, Italy, Rutegård Martin, Sweden, Sá Milene RRM, Portugal, Saad Luiz Henrique Cury, Brazil, Sadien Iannish D, Uk, Sadowski Brian M, Usa, Saeed Mirza Faraz, Bahrain, Safiyeva Aynur K, Azerbaijan, Sagap Ismail, Malaysia, Sahnan Kapil, Uk, Sairafi Rami, Saudi Arabia, Saklami Avanish P, India, Salgado-Nesme Noel NSN, Mexico, Salman Nevriye, Turkey, Samalavicius Narimantas E, Lithuania, Sambucci Daniele, Italy, Sanchez Noel, Usa, Sanchez Robles Juan Carlos, Mexico, Sanmiguel Carlos, Spain, Santacruz Eduardo, Paraguay, Santoni Simone, Italy, Santos Pedro MD, Portugal, Santos Brian U, Argentina, Santos Carlos, Portugal, Sapienza Paolo, Italy, Saracoglu Ayten, Turkey, Saracoglu Kemal T, Turkey, Sardinas Carlos, Venezuela, Sari Ramazan, Turkey, Sarma Diwakar, Uk, Sartori Alberto A, Italy, Sasia Diego, Italy, Sbaih Mohammed H, Saudi Arabia, Scabini Stefano, Italy, Scaringi Stefano, Italy, Scheinin Tom M, Finland, Schiavo Marcello, Italy, Schizas Alexis, Uk, Sciaudone Guido, Italy, Scognamillo Fabrizio, Italy, Scott Kelley, Usa, Scow Jeffrey S, Usa, Sechi Raffaele, Italy, Seehra Harkiran, Uk, Segering Joerg, Germany, Selcuk Mehtap, Turkey, Journal Pre-proof 42 Selemane Carlos, Mozambique, Seltman Ann, Usa, Selvaggi Francesco, Italy, Sensi Bruno, Italy, SeowChoen Francis, Singapore, Sernagiotto Carlo, Italy, Serralta De Colsa Daniel, Spain, Serrano González Javier, Spain, Sert Ismail, Turkey, Serventi Alberto, Italy, Sforza Sergio, Italy, Shabbir Jamshed, Uk, Shabeeb Fadel, Uae, Shafik Ali, Egypt, Shalaby Mostafa, Egypt, Shanker Bethann, Usa, Shanmugam Venkatesh, Uk, Shariff Umar, Uk, Shehta Ahmed, Egypt, Shelton Andrew, Usa, Shintaro Akamoto, Japan, Shlyk Daria, Russia, Shukla Amit, Uk, Sibio Simone, Italy, Sietze Koopal, Netherlands, Sigurdardottir Johanna, Sweden, Silva Jorge, Mexico, Silva Anaisa, Portugal, Simianu Val, Usa, Singh Baljit, Uk, Siragusa Leandro, Italy, Sirikurnpiboon Siripong, Thailand, Sivrikoz Emre, Turkey, Sizonenko Nikolay, Russia, Slavchev Mihail T, Bulgaria, Sniuolis Pranas, Lithuania, Soares Duarte, Qatar, Sojar Valentin, Slovenia, Sokmen Selman, Turkey, Sokol Thomas, Usa, Soldatov Denis, Russia, Soncini Stefania, Italy, Sordo Ricardo, Mexico, Sosa María V, Spain, Sousa Xavier, Portugal, Sozutek Alper, Turkey, Spiezio Giovanni, Italy, Spinelli Antonino, Italy, Stahl Etienne, Mexico, Stanojevic Goran Z, Serbia, Steckel Brian, Usa, Stefan Neagu, Romania, Stefanescu Victor, Romania, Steinhagen Randolph, Usa, Stella Marco, Italy, Stephensen Bree D, Australia, Stevenson Andrew RL, Australia, Stitzenberg Karyn, Usa, Strombom Paul, Usa, Sturiale Alessandro, Italy, Suhail Anjum, Pakistan, Sungurtekin Ugur, Turkey, Sutton Jeffrey M, Usa, Suwannakij Chanchai, Thailand, Szczepkowski Marek, Poland, Sztipits Tamas, Hungary, Takashi Akiyoshi, Japan, Takkenberg Marijn, Netherlands, Tallon-Aguilar Luis, Spain, Tam Michael, Usa, Tamburini Andrea M, Italy, Tamini Nicolò, Italy, Tammaro Pasquale, Italy, Tan Kerkan, Singapore, Tan Teerasan, Thailand, Tanal Mert, Turkey, Tanda Cinzia, Italy, Tang Jinghua, China, Tapiolas Ingrid, Uk, Täreby Magnus, Sweden, Tariverdiev Andrey, Russia, Tayar Serkan, Turkey, Tejedor Patricia, Spain, Terrosu Giovanni, Italy, Testa Alessandro, Italy, Tewari Shirish, Uk, Thabet Waleed, Egypt, Thakur Sukesh, India, Thomas Ehmann, Germany, Thomas Kuruc, Germany, Tiesi Vincenzo, Italy, Tin Moemoetin, Myanmar, Tita Agustin C, Argentina, Titu Liviu V, Uk, Tkachenko Fedot, Ukraine, Tonello Paolo, Italy, Tooley Richard, Usa, Torres Juan, Spain, Troci Albert, Italy, Trompetto Mario, Italy, Troncoso Pereira Paula, Spain, Tropeano Francesca Paola FP, Italy, Trostchansky Ivan, Uruguay, Tsujinaka Shingo, Japan, Tufo Andrea, Italy, Tulina Inna, Russia, Turati Luca, Italy, Turchina Catalin, Sweden, Turina Matthias, Switzerland, Tutino Roberta, Italy, Tyler Km, Usa, Uemura Mamoru, Japan, Unal Ayse G, Turkey, Uraiqat Ahmad, Jordan, Uribe Sebastián, Chile, V Duke, Usa, Vailati Bruna, Brazil, Vaingurt Mariano, Argentina, Valente Michael, Usa, Van Dellen Jonathan, Uk, Van Ramshorst Gabrielle H, Belgium, Vannelli Alberto, Italy, Vanriel W, Belgium, Varabei Aliaksandr, Belarus, Varcada Massimo, Uk, Varela Cristopher L, Venezuela, Varma Madhulika G, Usa, Vasapollo Leoluca F, Italy, Venn Mary L, Uk, Vercillo Kristin, Usa, Vergara-Fernandez Omar, Mexico, Veronesi Paolo, Italy, Vicente Aline, Brazil, Victor Tomulescu, Romania, Vieiradesousa Paulo, Portugal, Vignali Andrea, Italy, Vigorita Vincenzo, Spain, Vilchis Jose, Mexico, Villaverde Kathia, Peru, Vindevoghel Koen, Belgium, Violante Tommaso, Italy, Vitoopinyoparb Kasidin, Thailand, Voutsarakis Athanasios, Uk, Wainstein Ricardo, Argentina, Wakefield Simon, Uk, Wallon Conny, Sweden, Wang Yongbing, China, Wang Xiaodong, China, Wang Xiaofeng, China, Warden Claire, South Africa, Wei Rockson, China, Wheeler Matthew, Usa, Willem Bemelman, Netherlands, Wilson Matthew, Usa, Winter Des C, Ireland, Wongwiwatseree Yongsun, Thailand, Woon Kyung Jeong, South Korea, Wright Danette B, Australia, Wu Jiong, China, Wuraola Funmilola O, Nigeria, Xenaki Sofia A, Greece, Xiaohua Jiang, China, Xiaoqiang Jia, China, Xue Yahong, China, Xynos Evangelos, Greece, Yamada Kazunosuke, Japan, Yanar Hakan, Turkey, Yang Bolin, China, Yanishev Alexey, Russia, Yildirim Ali C, Turkey, Yildiz Ufukmete, Turkey, Yildiz Alp, Turkey, Yilmaz Mehmet, Turkey, Younis Muhammad Umar MUY, Uae, Yousef Zeyad, Saudi Arabia, Yu Dongsheng, China, Zalucki James, Usa, Zaman Ahamaduz, Bangladesh, Zamora Aída T, Spain, Zampitis Nikolaos, Cyprus, Zanus Giacomo, Italy, Zapata Gonzalo H, Argentina, Zelic Marko, Croatia, Zenger Serkan, Turkey, Zheng Jianyong, China, Zigiotto Daniele, Italy, Zmora Oded, Israel, Zoikas Athanasios, Greece, Zorcolo Luigi, Italy, Zucchella Martino, Italy, Zuhdy, Mohammad, Santoro G.A., Grossi U., Murad-Regadas S., Nunoo-Mensah J.W., Mellgren A., Di Tanna G.L., Gallo G., Tsang C., Rottoli M., and Wexner S.D.
Subjects: Male, medicine.medical_specialty, Delayed Diagnosis, Internationality, Colorectal cancer, colorectal surgery - COVID-19 - delay - treatment - outcomes, MEDLINE, colorectal cancer, 030230 surgery, medicine.disease_cause, Article, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Pandemic, medicine, Humans, Practice Patterns, Physicians', Elective surgery, Personal protective equipment, SARS-CoV-2, COVID-19, delayed surgery, Coronavirus, Infection Control, business.industry, Outbreak, medicine.disease, 030220 oncology & carcinogenesis, Preparedness, Emergency medicine, Female, Surgery, Colorectal Neoplasms, business, Colorectal Surgery
Abstract: Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations.
Published: 2021
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26. Increased morbidity and mortality in elderly patients with lower extremity trauma and associated injuries: A review of 420,066 patients from the national trauma database

Author: Shima C. Sokol, Afshin Parsikia, John McNelis, Zachary T. Sharfman, Apostolos Dimitroulias, Milan K. Sen, Ta'ir N. Rocker, Mani Kahn, and Melvin E. Stone
Subjects: computer.software_genre, 03 medical and health sciences, 0302 clinical medicine, Trauma Centers, medicine, Humans, Elderly trauma, Aged, Retrospective Studies, General Environmental Science, Aged, 80 and over, 030222 orthopedics, Retrospective review, Database, business.industry, 030208 emergency & critical care medicine, medicine.disease, Polytrauma, Hospital care, Lower Extremity, Extremity fractures, Icd 9 codes, General Earth and Planetary Sciences, Morbidity, Lower extremity fracture, business, computer, Leg Injuries
Abstract: There is a paucity of research addressing the morbidity and mortality associated with polytrauma in elderly patients. This study aimed to compare the outcomes of elderly trauma patients with an isolated lower extremity fracture, to patients lower extremity fractures and associated musculoskeletal injuries.This study is a retrospective review from the National Trauma Database (NTDB) between 2008 and 2014. ICD 9 codes were used to identify patients 65 years and older with lower extremity fractures. Patients were categorize patients into three sub groups: patients with isolated lower extremity fractures (ILE), patients with two or more (multiple) lower extremity fractures (MLE) and, patients with at least one upper and at least one lower extremity fracture (ULE). Groups were stratified into patients age 65-80 and patients80 years of age.A total 420,066 patients were included in analysis with 356,120 ILE fracture patients, 27,958 MLE fracture patients, and 35,988 ULE fracture patients. The MLE group reported the highest dispatch to ACS level 1 trauma centers at 31.8% followed by the ULE group at 28.5% and the ILE group at 24.7% of patients (p0.001). The overall rate of complications was highest in the MLE group followed by the ULE and then the ILE group (41.4%, 40.3%, 36.1%, respectively p0.001). Motility rates in patients80 years old in the MLE group and ULE group were similar (1.483 vs 1.4432). However, in the 65-80 year group the odds of mortality was 1.260 in the MLE group and 1.450 in the ULE group (p0.001), such that the odds of mortality after sustaining a MLE fracture increases with age, whereas this effect was not seen in the ULE group.Patients who sustained MLE and ULE fractures, had increased mortality, complications and in hospital care requirements as compared to patients with isolated lower extremity injuries. These outcomes are comparable between ULE and MLE fracture patients over the age of 80 however patients 65-80 with ULE fractures had increased mortality as compared patients 65-80 with MLE fractures. Understanding the unique considerations and requirements of elderly trauma patients is vital to providing successful outcomes.
Published: 2021
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27. Appendectomy for Vague Symptoms and Equivocal Physical Findings on Physical Exam and Computed Tomography

Author: Meaghan Flatley, Brian K Sparkman, Eric M Balent, Joshua S Ritenour, Kyle K Sokol, and Sara B Placek
Subjects: Abdominal pain, medicine.medical_specialty, Population, Computed tomography, Disease, Pathognomonic, medicine, Appendectomy, Humans, education, Physical Examination, Retrospective Studies, education.field_of_study, medicine.diagnostic_test, business.industry, General Medicine, Appendicitis, medicine.disease, Vague symptoms, Laparoscopy, Physical exam, Radiology, medicine.symptom, Tomography, X-Ray Computed, business
Abstract: Background: Appendicitis is a common condition affecting 7-8% of the general population. With the improvement of noninvasive imaging, the diagnostic approach and treatment algorithm for patients with clear signs and symptoms suggestive of acute appendicitis are well agreed-upon. However, patients without pathognomonic signs and symptoms, but with equivocal imaging pose a diagnostic dilemma. These patients may still have acute appendicitis and could potentially benefit from laparoscopic appendectomy. This may be especially true in the subset of patients with appendicoliths. Methods: Our case series exams a group of patients with atypical symptoms who eventually underwent appendectomy and were followed after surgery for at least a month. This case series consists of eight patients with abdominal pain accompanied by a variety of other signs and symptoms in addition to laboratory results and imagining characteristics which were nondiagnostic. These patients had initial Alvarado scores ranging from 0-6. Results: All of these patients were subsequently taken to the operating room for diagnostic laparoscopy and laparoscopic appendectomy. Of these patients, six were known to have appendicoliths based on computed tomography obtained during initial diagnostic workup. Conclusions: All patients underwent a diagnostic laparoscopy and appendectomy. Four had appendicitis and four also had resolution of their symptoms. There exist atypical presentations of appendiceal disease. Patients with abdominal pain/tenderness, even without diagnostic laboratory results or imaging characteristics, may benefit from laparoscopic appendectomy.
Published: 2021
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28. Von Willebrand disease – comparison of two methods of vWF multimer analysis

Author: Ingrid Škorňová, Juraj Sokol, Peter Kubisz, Pavol Hollý, Jan Stasko, Tomas Simurda, Jana Žolková, Miroslava Dobrotova, and Ivana Plameňová
Subjects: business.industry, Immunology, Von Willebrand disease, Medicine, Hematology, business, medicine.disease
Published: 2021
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29. Longitudinal MRI brain findings in the R1349Q pathogenic variant of CACNA1A

Author: Chang Y. Ho, Laurence E. Walsh, Harrison L. Love, and Deborah K. Sokol
Subjects: Episodic ataxia, Pathology, medicine.medical_specialty, Ataxia, business.industry, R895-920, Case Report, medicine.disease, CACNA1A, Medical physics. Medical radiology. Nuclear medicine, Epilepsy, Migraine, Neuroimaging, medicine, Radiology, Nuclear Medicine and imaging, Cerebellar atrophy, Global developmental delay, medicine.symptom, business, Encephalomalacia, Hemiplegic Migraines, Episodic Ataxia
Abstract: Pathogenic CACNA1A gene variants are associated with a spectrum of disorders including migraine with or without hemiplegia, ataxia, epilepsy, and developmental disability. We present a case of a pathogenic variant (c.4046G>A, p.R1349Q) in the CACNA1A gene associated with a clinical phenotype of global developmental delay, left hemiparesis, epilepsy, and stroke-like episodes. Longitudinal neuroimaging demonstrates hemispheric encephalomalacia with mismatched perfusion and angiographic imaging, in addition to progressive cerebellar atrophy.
Published: 2021

30. Clinical characteristics and outcomes of black patients with mycosis fungoides and Sézary syndrome: a subgroup analysis of the phase III MAVORIC trial

Author: Neda Nikbakht, William T. Johnson, Kelsey Sokol, Pierluigi Porcu, and Saritha Kartan
Subjects: Cancer Research, medicine.medical_specialty, Skin Neoplasms, medicine.medical_treatment, Subgroup analysis, Article, 03 medical and health sciences, Mycosis Fungoides, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Humans, Sezary Syndrome, Mycosis fungoides, business.industry, Hematology, Immunotherapy, medicine.disease, Dermatology, Lymphoma, Black or African American, Oncology, 030220 oncology & carcinogenesis, Disease characteristics, Neoplasm Recurrence, Local, business, 030215 immunology, Lymphoid leukemia
Abstract: Treatment-specific responses and comprehensive disease characteristics are limited in black patients with cutaneous T-cell lymphoma (CTCL). These shortcomings prompted us to perform a subgroup analysis of black patients enrolled in the MAVORIC trial — an international, randomized, phase 3 trial comparing mogamulizumab vs. vorinostat in relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS). Ten percent (N=37) of the entire MAVORIC population (N=372) identified as black. Significant clinical differences in black patients when compared to non-black patients included a younger median age at enrollment (53 vs. 66 years; P
Published: 2021
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31. Use of a Comprehensive 66-Gene Cholestasis Sequencing Panel in 2171 Cholestatic Infants, Children, and Young Adults

Author: Ilia Ichetovkin, Philip J. Rosenthal, John J. Alexander, Richard J. Thompson, James E. Heubi, Saul J. Karpen, Shelley Dunn, Ronald J. Sokol, and Binita M. Kamath
Subjects: Pediatrics, medicine.medical_specialty, business.industry, Gastroenterology, ABCB4, medicine.disease, Chronic liver disease, DNA sequencing, Cholestasis, Pediatrics, Perinatology and Child Health, Alagille syndrome, medicine, Etiology, ABCB11, Young adult, business
Abstract: OBJECTIVES Cholestasis is caused by a wide variety of etiologies, often genetic in origin. Broad overlap in clinical presentations, particularly in newborns, renders prioritizing diagnostic investigations challenging. In this setting, a timely, comprehensive assessment using a multigene panel by a clinical diagnostic laboratory would likely prove useful. We summarize initial findings from a testing program designed to discover genetic causes of cholestasis. METHODS A neonatal/adult sequencing panel containing 66 genes (originally 57; nine added March 2017) relevant to cholestasis was used. A broad range of eligible patients were enrolled with current/history of cholestasis without an identified cause, or unexplained chronic liver disease. DNA sequencing utilized a custom-designed capture library, and variants were classified and reported as benign, likely benign, variant of unknown significance (VOUS), likely pathogenic (LP), or pathogenic (P), according to the clinical interpretation workflow at EGL Genetics (Tucker, GA). RESULTS A total of 2433 samples were submitted between February 2016 and December 2017; 2171 results were reported. Median turnaround time was 21 days. Results from the 2171 subjects (57%
Published: 2021
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32. Planar cell polarity pathway in kidney development, function and disease

Author: Sergei Y. Sokol and Elena Torban
Subjects: 0301 basic medicine, Cell, 030232 urology & nephrology, Kidney development, Organogenesis, Kidney, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, biology, business.industry, Cell Polarity, biology.organism_classification, medicine.disease, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Nephrology, Ureteric bud, Drosophila, Kidney Diseases, Kidney disorder, Drosophila melanogaster, business, Signal Transduction, Kidney disease
Abstract: Planar cell polarity (PCP) refers to the coordinated orientation of cells in tissue plane. Originally discovered and studied in Drosophila melanogaster, PCP is now widely recognized in vertebrates, where it has been implicated in organogenesis. Specific sets of PCP genes have been identified. The proteins encoded by these genes are organized into a dedicated signaling pathway, become asymmetrically distributed to opposite sides of each cell within a tissue plane and guide many processes that include changes in cell shape and polarity, collective cell movements or uniform distribution of cell appendages. A unifying characteristic of these changes is that they often involve actomyosin rearrangement. Mutations in PCP genes cause congenital malformations of multiple organs in many animals and, importantly, in humans. In the last decade, strong evidence has accumulated for a role of the PCP pathway in kidney development. It has been proposed that defective PCP signaling contributes to polycystic kidney disease and that specific PCP gene mutations lead to Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). In this review, we describe the origins, molecular constituents and cellular targets of PCP, with a special focus on the involvement of PCP molecules in normal kidney development and how their dysfunction leads to kidney disease.
Published: 2021
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33. Goal-Concordant Care in the Era of Advanced Stroke Therapies

Author: Michael J. Young, Hillary D. Lum, Joshua Hauser, Fan Z. Caprio, Moran Cerf, Leonard L. Sokol, and Jodi Forlizzi
Subjects: Advance care planning, medicine.medical_specialty, Palliative care, medicine.medical_treatment, Feature Editor: Craig D. Blinderman, Context (language use), withdrawal of interventions, Stroke care, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, 030502 gerontology, medicine, Humans, advance care planning, Intensive care medicine, Stroke, General Nursing, business.industry, Case Discussions in Palliative Medicine, goals of care, General Medicine, Thrombolysis, medicine.disease, stroke, Treatment Outcome, hospital transfers, Anesthesiology and Pain Medicine, Prima facie, thrombectomy, 030220 oncology & carcinogenesis, 0305 other medical science, business, Goals, Large vessel occlusion
Abstract: Stroke is a leading cause of disability and mortality worldwide. Recent advances in stroke care now enable patients with severe ischemic stroke owing to large vessel occlusion to safely undergo endovascular thrombectomy (EVT) up to 24 hours since their time of last known well, with the goal of improving functional outcomes by recanalization of the occluded vessel and reperfusion of downstream ischemic brain tissue. The objective of this analysis is to highlight clinical and ethical challenges related to ensuring goal-concordant care in this era of unprecedented advances in acute stroke care. Specifically, there is a salient challenge of whether advanced therapies such as EVT may be justifiably considered comfort focused, given their potential to preempt accumulated neurologic disability and suffering at the end of life. Through the lens of a patient case, we discuss key challenges, lessons learned, and suggestions for future care and research endeavors at the intersection of acute stroke care and palliative care principles. Although therapies such as thrombolysis and EVT may be considered aggressive prima facie, their potential to ameliorate additional disability and potential suffering at the end of life prompt close consideration of the proper role of these therapies on a case-by-case basis in the context of comfort-focused care. Modification to the workflow for EVT evaluations may facilitate goal-concordant care and timely resource allocation, especially for cases that involve hospital-to-hospital transfers for advanced stroke care.
Published: 2021
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34. Continuous Identity Cognitive Therapy: Feasibility and Acceptability of a Novel Intervention for Suicidal Symptoms

Author: Josephine Ridley, Lisa B. Dixon, Yosef Sokol, Marianne Goodman, Silvia C Hernandez, and Yulia Landa
Subjects: medicine.medical_treatment, 05 social sciences, Identity (social science), Experimental and Cognitive Psychology, Mental illness, medicine.disease, Acceptance and commitment therapy, 050105 experimental psychology, Meaningful life, 030227 psychiatry, Cognitive behavioral therapy, 03 medical and health sciences, Psychiatry and Mental health, Clinical Psychology, 0302 clinical medicine, Intervention (counseling), Cognitive therapy, medicine, 0501 psychology and cognitive sciences, Psychology, Suicide intervention, Clinical psychology
Abstract: We introduce continuous identity cognitive therapy (CI-CT), a novel suicide intervention. CI-CT was developed based on evidence that suicidal individuals have difficulty viewing and experiencing continuity with their perceived future self, and having meaningful and achievable personal goals. CI-CT integrates aspects of cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) with modality-specific techniques focusing on the individual's perceived present-to-future life story. The intervention guides the development of a meaningful life story with a vivid and positive future self. The results of an open-label pilot/feasibility trial (N = 17) for U.S. Veterans with a serious mental illness indicate that CI-CT is feasible, acceptable to Veterans, and may help with suicidality, depression, hopelessness, and future self-continuity. Reductions in clinical symptoms were associated with improvement in future self-continuity and were largely maintained at the 1-month follow-up. These results, along with high retention rates and positive Veteran feedback, support further exploration of the utility of CI-CT.
Published: 2021
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35. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II

Author: Dolores J. Lamb, Barbara Collura, Rebecca Z. Sokol, Cigdem Tanrikut, Jeffrey T. Oristaglio, Mark Sigman, Steven D. Spandorfer, Christopher J. De Jonge, Michael L. Eisenberg, Craig Niederberger, Armand Zini, Jonathan Treadwell, Peter N. Schlegel, John P. Mulhall, and Jay I. Sandlow
Subjects: Counseling, Selective Estrogen Receptor Modulators, Male, Infertility, medicine.medical_specialty, Sperm Retrieval, Urology, 030232 urology & nephrology, Fertilization in Vitro, Male infertility, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Pregnancy, Varicocele, medicine, Humans, Sperm Injections, Intracytoplasmic, Infertility, Male, Societies, Medical, Evidence-Based Medicine, business.industry, General surgery, Obstetrics and Gynecology, Guideline, medicine.disease, United States, Semen Analysis, Treatment Outcome, Reproductive Medicine, Dietary Supplements, Scrotum, Female, business
Abstract: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility.The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]).Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.
Published: 2021
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36. A PROSPECTIVE STUDY TO ANALYZE THE SPECIFICITY OF CHLAMYDIAL HEAT SHOCK PROTEIN (CHSP60) ANTIBODIES TO DIAGNOSE TUBAL INFERTILITY

Author: Vladyslav O Berestoviy, Inna V Sokol, Valentyna G Ginzburg, D. Govsieiev, and Ahmad A Mahmood
Subjects: Infertility, Gynecology, medicine.medical_specialty, animal structures, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, biology, business.industry, General Medicine, medicine.disease_cause, Immunofluorescence, medicine.disease, female genital diseases and pregnancy complications, 03 medical and health sciences, Titer, 0302 clinical medicine, Heat shock protein, medicine, biology.protein, 030212 general & internal medicine, Antibody, Chlamydia trachomatis, Prospective cohort study, business, Antibody screening
Abstract: Objective The aim: To investigate the utility of testing for chlamydial heat shock protein 60 (CHSP60) antibodies in the diagnosis of tubal infertility. Patients and methods Materials and methods: All the collected samples were assayed for IgM and IgG antibodies to chlamydia trachomatis and chlamydial heat shock protein 60 (CHSP60) by using immunofluorescence and enzyme-linked immunosorbent assay (ELISA) techniques, respectively. Results Results: There were no substantial differences between antibodies to C. trachomatis in females with tubal infertility (67%) and non-tubal infertility (48%). However, women with tubal infertility (45%) have more anti-CHSP60 antibodies than non-tubal infertility (9%). Antibody screening for C. trachomatis has only (63%) sensitivity and (54%) specificity for detecting tubal infertility. On the other hand, the CHSP60 antibody testing has (44%) sensitivity and 92% specificity for diagnosing tubal infertility. A positive microimmunofluorescence (MIF) titer was observed in 12 of 18 (67%) females with the tubal problem, 31 of 64 (48%) with non-tubal infertility (P=0.3, OR=2.2, 95% CI=0.71 to 8.01). The CHSP60 antibodies were found in 8 of 18 (45%) females with tubal problem & 6 of 64 (9%) women with non-tubal infertility, power factor alpha α P=0.004, OR=9.3, 95% CI=2.1 to 43.2, power= 1.002 for n= 0.05). Incorporating CHSP60 and C. trachomatis antibodies testing gives an excellent positive probability proportion of 10 to diagnose C. trachomatis associated tubal infertility. Conclusion Conclusions: CHSP60 antibody testing is a more specific evaluation than antibody testing for C. trachomatis for predicting chlamydia-associated tubal infertility. Using these tests at the first infertility examination may help the immediate diagnosis for non-interceptive tubal infertility.
Published: 2021
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37. Contrasting genomic profiles from metastatic sites, primary tumors, and liquid biopsies of advanced prostate cancer

Author: Ethan Sokol, Andrea Necchi, Jonathan Keith Killian, Hanna Tukachinsky, Joseph Jacob, Richard S.P. Huang, Petros Grivas, Alexa B. Schrock, Philippe E. Spiess, Jeffrey M. Venstrom, Douglas I. Lin, Jeffrey S. Ross, Gennady Bratslavsky, Ole Gjoerup, Vito Cucchiara, Russell Madison, Shakti H. Ramkissoon, Natalie Danziger, Ryon Graf, Geoffrey R. Oxnard, Brennan Decker, Necchi, A., Cucchiara, V., Grivas, P., Bratslavsky, G., Jacob, J., Spiess, P. E., Sokol, E. S., Killian, J. K., Lin, D., Ramkissoon, S., Huang, R. S. P., Madison, R. W., Venstrom, J. M., Schrock, A. B., Danziger, N., Decker, B., Gjoerup, O., Graf, R. P., Oxnard, G. R., Tukachinsky, H., and Ross, J. S.
Subjects: Male, Cancer Research, medicine.medical_treatment, TMPRSS2, Somatic evolution in cancer, Targeted therapy, Circulating Tumor DNA, Prostate cancer, medicine, Biomarkers, Tumor, PTEN, Humans, Lymph node, circulating tumor DNA, biology, comprehensive genomic profiling, business.industry, Liquid Biopsy, biomarkers, High-Throughput Nucleotide Sequencing, Prostatic Neoplasms, Genomics, prostate cancer, targeted therapy, medicine.disease, medicine.anatomical_structure, Oncology, Tumor progression, Mutation, biology.protein, Cancer research, Microsatellite Instability, business, Erg
Abstract: Background This study assessed the contrasting genomic profiles from the primary tumors (PTs), metastatic (MET) sites, and circulating tumor DNA (ctDNA) of patients with prostate cancer (PC). Methods A total of 1294 PC tissue specimens and 2462 ctDNA specimens underwent hybrid capture-based comprehensive genomic profiling (CGP). Specimens included tissue from PTs; MET biopsies from bone, liver (LIV), lung (LU), brain (BN), lymph node, and soft tissue sites; and ctDNA. Results Differences in alteration frequencies between PT, MET, and ctDNA specimens for selected genes were observed. TMPRSS2:ERG fusion frequencies were similar between PTs and MET sites (35% vs 33%) but varied among MET sites. Genomic alterations (GAs) in AR were lowest in PTs (2%) and highest in MET sites (from 24% in LU to 50% in LIV). BN had the highest genomic alterations/tumor (8) and enrichment for PTEN GAs. The BRCA2 GA frequency varied from 0% in BN to 15% in LIV. ERBB2 amplification was increased in MET sites in comparison with PTs. RB1 GAs were increased in LIV. Biomarkers potentially associated with an anti-PD(L)1 response included CDK12 GAs (16% in LU) and a microsatellite instability-high status (29% in BN). Analyses of ctDNA featured a broad spectrum of GAs similar to those detected across MET sites. Conclusions CGP of PTs, MET sites, and ctDNA in PC exhibited differences most likely associated with tumor progression, clonal evolution, and exposure to systemic therapies; ctDNA can also capture a broad range of potential therapeutic opportunities for patients with PC.
Published: 2021

38. Clinically Advanced Pheochromocytomas and Paragangliomas: A Comprehensive Genomic Profiling Study

Author: Joseph M. Jacob, Natalie Danziger, Nick Liu, Karel Pacak, Mehdi Mollapour, Andrea Necchi, Gennady Bratslavsky, Richard S.P. Huang, Hanan Goldberg, Jeffrey S. Ross, Ruben Pinkhasov, Tom S Sanford, Ethan Sokol, Oleg Shapiro, Shakti H. Ramkissoon, Michael Daneshvar, Jonathan Keith Killian, Eric Allan Severson, Bratslavsky, G., Sokol, E. S., Daneshvar, M., Necchi, A., Shapiro, O., Jacob, J., Liu, N., Sanford, T. S., Pinkhasov, R., Goldberg, H., Killian, J. K., Ramkissoon, S., Severson, E. A., Huang, R. S. P., Danziger, N., Mollapour, M., Ross, J. S., and Pacak, K.
Subjects: 0301 basic medicine, Cancer Research, SDHA, Germline, Article, Paraganglioma, Pheochromocytoma, 03 medical and health sciences, paraganglioma, 0302 clinical medicine, Germline mutation, medicine, PTEN, Comprehensive genomic profiling, Gene, RC254-282, biology, business.industry, comprehensive genomic profiling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Microsatellite instability, genomic alterations, medicine.disease, pheochromocytoma, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Genomic, biology.protein, Cancer research, Alterations pheochromocytoma, business
Abstract: Simple Summary Clinically advanced pheochromocytomas and paragangliomas are a rare form of endocrine malignancy which can occur in familial and sporadic clinical settings and feature a variety of genomic alterations. Comprehensive genomic profiling (CGP) was performed to characterize the genomic alterations (GA) in clinically advanced disease to enable the search for potential therapy targets. Although the GA/tumor is relatively low for clinically advanced disease, CGP can reveal important potential targets for therapy in the metastatic setting including RET, NF1 and FGFR1. Based on this data, further study of CGP as a method of developing precision therapies for clinically advanced disease appears warranted. Abstract Patients with clinically advanced paragangliomas (CA-Para) and pheochromocytomas (CA-Pheo) have limited surgical or systemic treatments. We used comprehensive genomic profiling (CGP) to compare genomic alterations (GA) in CA-Para and CA-Pheo to identify potential therapeutic targets. Eighty-three CA-Para and 45 CA-Pheo underwent hybrid-capture-based CGP using a targeted panel of 324 genes. Tumor mutational burden (TMB) and microsatellite instability (MSI) were determined. The GA/tumor frequencies were low for both tumor types (1.9 GA/tumor for CA-Para, 2.3 GA/tumor for CA-Pheo). The most frequent potentially targetable GA in CA-Para were in FGFR1 (7%, primarily amplifications), NF1, PTEN, NF2, and CDK4 (all 2%) and for CA-Pheo in RET (9%, primarily fusions), NF1 (11%) and FGFR1 (7%). Germline mutations in known cancer predisposition genes were predicted in 13 (30%) of CA-Pheo and 38 (45%) of CA-Para cases, predominantly involving SDHA/B genes. Both CA-Para and CA-Para had low median TMB, low PD-L1 expression levels and none had MSI high status. While similar GA frequency is seen in both CA-Para and CA-Para, germline GA were seen more frequently in CA-Para. Low PD-L1 expression levels and no MSI high status argue against strong potential for novel immune checkpoint inhibitors. However, several important potential therapeutic targets in both CA-Para and CA-Para are identified using CGP.
Published: 2021

39. Reperfusion Injury Following Catheter Directed Thrombolysis of Pulmonary Embolism

Author: Seth I. Sokol, Jincy Thankachen, Mark Guelfgaut, Amit Kakkar, and Ari B. Friedman
Subjects: medicine.medical_specialty, business.industry, Internal medicine, medicine, Catheter directed thrombolysis, Cardiology, General Earth and Planetary Sciences, medicine.disease, business, Reperfusion injury, General Environmental Science, Pulmonary embolism
Abstract: Catheter directed thrombolysis (CDT) is a growing field of intervention to treat pulmonary embolism (PE) and restore physiologic circulation. Reperfusion injury (RI) is a well-documented phenomenon seen post-thrombolysis. To date there are no reported cases of this phenomena following CDT. We present a patient with bilateral PE treated with CDT who subsequently developed RI.
Published: 2021
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40. ACTES 2019 - Abstracts Book; The 3rd Albanian Congress of Trauma and Emergency Surgery

Author: Agron Dogjani, Kastriot Haxhirexha, Hayato Kurihara, Carlos Mesquita, Antonio La Greca, Mauro Zago, Arben Gjata, Etmont Celiku, Xheladin Draçini, Arvin Dibra, Serhii Mistuk, Faton T. Hoxha, Teodor Pevec, Ridvan Alimehmeti, Artur Xhumari, Baris Saygili, Arsen Seferi, Artid Lame, Isuf Bajrami, Onder Murat Delialioglu, Simona Kalšek, Basri Lenjani, Gjergj Caushi, Arjan Mullahi, Adham Darweesh, Skender Veliu, Enver Fekaj, Haqif Gashi, Fadil Gradica, Fatmir Caushi, Ilir Skenduli, Petraq Mustaqe, Dorina Shtjefni, Ilir Alimehmeti, Kenan Ljuhar, Sadri Hulaj, Rezeart Dalipi, Besim Boci, Kenan Karavdić, Myzafer Kaci, Orjada Gashi, Ormir Shurdha, Fatmir Guni, Edmond Zaimi, Edmond Pistulli, Akgün Çelik, Elizana Petrela, Engin Göçmen, Erinda Kosturi, Parambath Arif Nelliylla, Alfred Aga, Flamur Vellku, Hassan Al-Thani, Edvin Selmani, Indrit Temali, Dorina Shqalshi, Alma Llukacaj, Ilir Hasmuca, Alan Andonovski, Esat Bardhoshi, Sadi Bexheti, Antonio Gavrilovski, Arben Beqiri, Alfred Ibrahimi, Lazar Todorovic, Majlinda Naco, Ayman Elmenyar, Hektor Sula, Ilir Hasani, Rudin Domi, Markus Konert, Husham Abdelrahman, Behar Tocilla, Marsida Krasniqi, Albert Lleshi, Admir Mustafa, Nehat Baftiu, Edmond Nuellari, Ismael Yousif Mahmood Alomar, Kenan Bayrakci, Skender Buci, Lutfi Zylbeari, Manushaqe Saraci, Agon Turkaj, Alma Cani, Katerina Kasa, Gezim Xhepa, Marjeta Bilaj, Vrenos Hodaj, Vladimir Filaj, Elona Markeci, Eriselda Taulla, Bledar Kruja, Albana Shahini, Ardiana Sinani, Gezim Galiqi, Nuhi Arslani, Arjana Strakosha, Sadık Yıldırım Özgeçmiş, Elona Hasalla, Anxhela Ahmataj, Sokol Isaraj, Gentian Zikaj, Nardi Kola, Rezarta Kapaj, Ferizat Dika- Haxhirexha, Sokol Xhepa, Albana Aleksi, Ilir Shani, Selim Birol, Astrit Xhemali, Viktor Marku, Hasan Vedat Ofluoğlu, Burak Koza, Dritan Todhe, Petrit Byberaj, Skender Brataj, Valentin Vejseli, Rezart Xhani, Herion Dredha, Arben Lloja, Matilda Imeraj, Denis Kosovrasti, Vilma Cadri, Arjeta Dedej, Henri Kolani, Gazmend Elezi, Ledian Fezollari, Alban Hysenaj, Leon Kaza, Zamira Shabani, Blerta Hamolli, Albana Kenga, Gentian Caco, Marsela Sopiqoti, Petrika Gjergo, Xhesika Xhetani, Aurela Kullolli, Natasha Merko, Arben Gjonej, Risida Gjonej, and Studim Hysa
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Abdominal Infection, Peritonitis, Retrospective cohort study, Emergency department, medicine.disease, University hospital, Surgery, Blunt, Abdominal trauma, medicine, General Materials Science, Embolization, business
Abstract: This event reflects the author's involvement in internationally recognized education and training models, as ATLS, ETC, and DSTC, and UEMS Boards of Emergency SurgeryDo different countries need very different things? I don’t think so, for the simple reason that in Europe and about the challenges we face, with regard to trauma and other medical and surgical emergencies, similarities are much greater than differences.• We all agree on the need for a trauma system “to assure that patients (…) seamlessly receive the proper care, in the proper locations, with proper interventions and, if necessary, transfer to a hospital able to provide the best and most appropriate care” (www.aast.org).• We all agree that teamwork is necessary for prehospital care, transportation, emergency room care, intensive care, surgery, and in/post-hospital rehabilitation.• We all agree on the need for trauma registries with, as much as possible, global follow-up of patient's course.• And finally, we all agree that it is necessary to educate, how to prevent and how to treat.This is also apparent from the recommendations of the European Trauma Course Organization (ETCO) about equipment and facilities: complete trauma team, trauma admission bay close to the ambulance entrance, enough space and adequate lighting, the adjacent operating room to allow emergency procedures, standardequipment for the initial management of major trauma, immediate availability of additional equipment as difficult airway equipment, X-ray, ultrasound machine, surgical instruments, readily available bloodproducts and massive transfusion equipment, co-located CT scanner to allow immediately imaging and access to angiography and interventional radiology, 24 hours a day within 30-60 minutes of request.
Published: 2019
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41. No pain, no gain: Sensory neurons heal a sunburn

Author: Caroline L. Sokol and Cameron H. Flayer
Subjects: Sensory Receptor Cells, Immunology, Sunburn, Sensory system, Inflammation, Biology, Bioinformatics, No pain, no gain, Article, Mice, medicine, Animals, Immunology and Allergy, Skin, Wound Healing, Macrophages, Tissue repair, medicine.disease, Fibrosis, Interleukin-10, Disease Models, Animal, Infectious Diseases, Tissue fibrosis, Cytokines, medicine.symptom, Wound healing, Signal Transduction
Abstract: Summary In a recent issue of Nature, Hoeffel et al. describe a novel pathway of sterile tissue repair utilizing a mouse model of sunburn. This wound healing pathway is coordinated by sensory neuron-derived TAFA4 that induces IL-10 production from Tim4+ dermal macrophages to prevent sustained inflammation and the emergence of tissue fibrosis.
Published: 2021
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42. Intraoperative random biopsies of strictureplasty sites can detect early small-bowel adenocarcinoma in patients with Crohn's disease

Author: Chloé Martineau, Jérémie H. Lefèvre, Najim Chafai, Lauren O'Connell, Magali Svrcek, Laurent Beaugerie, Lionel Arrive, Nicolas Benech, Anne Bourrier, Marine Camus, Edouard Chambenois, Ulriikka Chaput, Clotilde Debove, Xavier Dray, Jean-François Flejou, Nadia Hoyeau, Julien Kirchgesner, Cécilia Landman, Romain Leenhardt, Jérémie H. Lefevre, Philippe Marteau, Isabelle Nion-Larmurier, Yann Parc, Philippe Seksik, Laura Sirmai, Harry Sokol, and Dominique Wendum
Subjects: medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, medicine.medical_treatment, Gastroenterology, MEDLINE, Small bowel adenocarcinoma, medicine.disease, Internal medicine, Strictureplasty, Medicine, In patient, business
Published: 2021
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43. Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

Author: Haresh, Kirpalani, Edward F, Bell, Susan R, Hintz, Sylvia, Tan, Barbara, Schmidt, Aasma S, Chaudhary, Karen J, Johnson, Margaret M, Crawford, Jamie E, Newman, Betty R, Vohr, Waldemar A, Carlo, Carl T, D'Angio, Kathleen A, Kennedy, Robin K, Ohls, Brenda B, Poindexter, Kurt, Schibler, Robin K, Whyte, John A, Widness, John A F, Zupancic, Myra H, Wyckoff, William E, Truog, Michele C, Walsh, Valerie Y, Chock, Abbot R, Laptook, Gregory M, Sokol, Bradley A, Yoder, Ravi M, Patel, C Michael, Cotten, Melissa F, Carmen, Uday, Devaskar, Sanjay, Chawla, Ruth, Seabrook, Rosemary D, Higgins, Abhik, Das, and Marian, Willinger
Subjects: Pediatrics, medicine.medical_specialty, Anemia, Vision Disorders, MEDLINE, Infant, Premature, Diseases, 030204 cardiovascular system & hematology, law.invention, Hemoglobins, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Humans, 030212 general & internal medicine, Hearing Loss, Survival rate, Obstetrics, Extramural, business.industry, Cerebral Palsy, Cognitive delay, Infant, Newborn, General Medicine, medicine.disease, Survival Rate, Multicenter study, Infant, Extremely Low Birth Weight, Neurodevelopmental Disorders, Infant, Extremely Premature, Hemoglobin, Cognition Disorders, Erythrocyte Transfusion, business, Algorithms, Infant, Premature
Abstract: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).
Published: 2020
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44. FACT OF IDENTIFYING A NON-LIFE-THREATENING PEDESTRIAN INJURY DURING A FORENSIC MEDICAL EXAMINATION

Author: V.A. Kolesnichenko and V.K. Sokol
Subjects: medicine.medical_specialty, Pelvic girdle, business.industry, Medical record, medicine.disease, Surgery, Closed Fracture, Falling (accident), Blunt, Abdominal trauma, Concussion, Medicine, Tibia, medicine.symptom, business
Abstract: The forensic aspects of low-energy pedestrian injury have not been adequately studied yet. The objective of the study presented is to analyze forensic criteria for identifying the mechanism of injury in low-energy fractures of the lower extremities. The study material included 347 acts of forensic medical examinations of victims with fractures of the lower extremities performed in the Kharkiv Regional Bureau of Forensic Medical Examination for the period from February to June 2018. The selection of forensic medical evaluation reports was carried out at random. The methodology included retrospective analysis, descriptive statistics. The incidence of low-energy pedestrian injury was 0.9%. This type of road traffic injury was registered in people aged 78 – 88 as a result of an alleged collision with the back of a vehicle. The main difference between high- and low-energy fractures of the long bones of the lower extremities was the severity of concomitant injuries (given the fact that closed isolated fractures of the long bones of the lower extremities in our material were accompanied by injuries of the integumentary system (abrasions, bruises, etc.), those fractures were regarded as concomitant injury. In the first case, the action of kinetic energy of significant force led to the formation of multiple fractures of the upper (94; 27.1%) and lower (421; 121.3%) limbs, pelvic girdle (83; 23.9%); concomitant injuries were characterized by the presence of moderate brain concussion (54; 15.6%), non-penetrating blunt chest trauma (102; 29.4%) with rib fractures (48; 13.8%), non-penetrating blunt abdominal trauma (51; 14.7%); all the victims had bruised and lacerated wounds, multiple abrasions, subcutaneous hematomas of various localization. Low-energy trauma was characterized by the presence of isolated fractures of the proximal femur (n = 4) and tibia (n = 3) bones (Table 2). As a concomitant trauma, damage to the integumentary system was recorded in the form of abrasions and subcutaneous hematomas in the fractured area when falling from a height of one's own height (n = 3). In terms of the strength and speed of the impact of the traumatic force, the low-energy pedestrian injury was identical to the fall of the victim from his own height onto the lateral surface of the body with the formation of bodily injuries as closed fractures of the proximal femur. The cause and mechanism of these injuries have not been identified due to the late primary forensic medical evaluation, incomplete data in the medical records on the clinical signs of traumatic injuries to the skin of the victims during the initial examination, inconclusive results of forensic examinations of clothing and footwear, and uninformative data of a technical examination. During the forensic medical examination of a low-energy pedestrian injury, the identification of traumatic injuries of the skin on the side of the fall and on the contralateral side, the place of the first contact with the car, enables to establish the fact of collision and the duration of the damage.
Published: 2020
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45. Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer

Author: Prashanth Ashok Kumar, Ethan Sokol, Richard S.P. Huang, Shakti H. Ramkissoon, Eric Allan Severson, Jeffrey S. Ross, Abirami Sivapiragasam, Natalie Danziger, Lee A. Albacker, Jonathan Keith Killian, Kimberly McGregor, and Charlotte Brown
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_treatment, B7-H1 Antigen, 0302 clinical medicine, Neoplasm Metastasis, Precision Medicine, skin and connective tissue diseases, Immune Checkpoint Inhibitors, Original Research, Aged, 80 and over, biology, comprehensive genomic profiling, Middle Aged, Metastatic breast cancer, 030220 oncology & carcinogenesis, Immunohistochemistry, Mdm2, Female, immunotherapy, metastatic breast cancer, Databases, Nucleic Acid, Adult, medicine.medical_specialty, tumor mutational burden, Clinical Decision-Making, STK11, Breast Neoplasms, Young Adult, 03 medical and health sciences, Breast cancer, Predictive Value of Tests, PD-L1, Internal medicine, Biomarkers, Tumor, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, business.industry, Gene Expression Profiling, Clinical Cancer Research, biomarkers, Microsatellite instability, Immunotherapy, medicine.disease, 030104 developmental biology, Drug Resistance, Neoplasm, PD‐L1, Mutation, biology.protein, microsatellite instability, Transcriptome, business
Abstract: We examined a large dataset of female metastatic breast cancers (MBCs) profiled with comprehensive genomic profiling (CGP) to identify the prevalence and distribution of immunotherapy responsiveness‐associated biomarkers. DNA was extracted from 3831 consecutive MBCs: 1237 (ERpos/HER2 neg), 1953 ERneg/HER2 amp, and 641 triple‐negative breast cancer (TNBC). CGP was performed using the FoundationOne® or FoundationOne®CDx NGS assay. Tumor mutational burden (TMB) and microsatellite instability (MSI) were determined in a subset of cases. PD‐L1 expression in immunocytes in a subset of cases was determined by immunohistochemistry using the companion diagnostic VENTANA PD‐L1 SP142 Assay. The median age of the cohort was 54 years (range 20–89). Genomic alterations (GAs)/tumor were similar (range: 5.9–7.3). Markers of potential immune checkpoint inhibitor (ICPI) benefit included: CD274 (PD‐L1) amplification (1%–3%), BRAF GA (1%–4%), TMB of ≥10 mutations/Mb (8%–12%), MSI‐high (0.1%–0.4%), PBRM1 GA (1%), and positive PD‐L1 staining of immunocytes ranging from 13% in ERpos/HER2 neg and 33% in ERneg/HER2 amp to 47% in the TNBC group. Potential markers of ICPI resistance included inactivating STK11 GA (1%–2%) and MDM2 amplification (3%–6%). MTOR pathway targets were common with lowest frequency in TNBC. ERBB2 short variant mutations were most frequent ERpos/HER2 neg and absent in TNBC. BRCA1/2 GA were least frequent in ERneg/HER2 amp. The demonstrations of clinical benefit of immunotherapy in MBC support the need for development and utilization of biomarkers to guide the use of ICPIs for these patients. In addition to guiding therapy selection, CGP shows potential to identify GA linked to response and resistance to ICPI in MBC., Both our results and published literature suggest that in addition to guiding targeted therapy selection, comprehensive genomic profiling shows potential to identify genomic alterations linked to response and resistance to immune checkpoint inhibitor (ICPI) therapy in metastatic breast cancer (MBC). The demonstration of clinical benefit of immune checkpoint blockade in MBC supports the need for the development of biomarkers used to guide the use of ICPI drugs for these patients.
Published: 2020
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46. Serum TNF-α and IL-1β levels in patients with RNFL thinning in uveitis complicated by optic nerve inflammation

Author: O. Honchar, O. O. Sokol, H. S. Pereiaslova, M. M. Nikolaienko, D. O. Prykhodko, and M. Panchenko
Subjects: Ophthalmology, medicine.medical_specialty, business.industry, medicine, Optic nerve inflammation, In patient, business, medicine.disease, Uveitis
Published: 2020
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47. Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Origin: Retrospective Molecular Classification Considering the CUPISCO Study Design

Author: Holger Moch, Marlene Thomas, Andreas Beringer, Ethan Sokol, Alwin Krämer, Jeffrey S. Ross, Ferran Losa, Giulia Baciarello, Julia A. Elvin, Dexter X. Jin, Linda Mileshkin, Nhu Ngo, and University of Zurich
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Cancer Diagnostics and Molecular Pathology, Lung Neoplasms, medicine.medical_treatment, 610 Medicine & health, Targeted therapy, law.invention, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, 10049 Institute of Pathology and Molecular Pathology, Proto-Oncogene Proteins, ROS1, Carcinoma, Biomarkers, Tumor, Medicine, Unknown primary tumors, Genetic profiling, Humans, Molecular targeted therapy, Retrospective Studies, business.industry, Gene Expression Profiling, Microsatellite instability, Genomics, Protein-Tyrosine Kinases, medicine.disease, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Adenocarcinoma, Neoplasms, Unknown Primary, business
Abstract: Background Carcinoma of unknown primary origin (CUP) accounts for 2%–5% of newly diagnosed advanced malignancies, with chemotherapy as the standard of care. CUPISCO (NCT03498521) is an ongoing randomized trial using comprehensive genomic profiling (CGP) to assign patients with CUP to targeted or immunotherapy treatment arms based on genomic profiling. We performed a retrospective analysis of CUP cases referred for CGP to determine how many were potentially eligible for enrollment into an experimental CUPISCO arm. Materials and Methods Centrally reviewed adenocarcinoma and undifferentiated CUP specimens in the FoundationCore database were analyzed using the hybrid capture‐based FoundationOne CDx assay (mean coverage, >600×). Presence of genomic alterations, microsatellite instability (MSI), tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), and programmed death‐ligand 1 (PD‐L1) positivity were determined. Results A total of 96 of 303 patients (31.7%) could be matched to an experimental CUPISCO arm. Key genomic alterations included ERBB2 (7.3%), PIK3CA (6.3%), NF1 (5.6%), NF2 (4.6%), BRAF (4.3%), IDH1 (3.3%), PTEN, FGFR2, EGFR (3.6% each), MET (4.3%), CDK6 (3.0%), FBXW7, CDK4 (2.3% each), IDH2, RET, ROS1, NTRK (1.0% each), and ALK (0.7%). Median TMB was 3.75 mutations per megabase of DNA; 34 patients (11.6%) had a TMB ≥16 mutations per megabase. Three patients (1%) had high MSI, and 42 (14%) displayed high PD‐L1 expression (tumor proportion score ≥50%). gLOH could be assessed in 199 of 303 specimens; 19.6% had a score of >16%. Conclusions Thirty‐two percent of patients would have been eligible for targeted therapy in CUPISCO. Future studies, including additional biomarkers such as PD‐L1 positivity and gLOH, may identify a greater proportion potentially benefiting from CGP‐informed treatment. Clinical trial identification number. NCT03498521 Implications for Practice The findings of this retrospective analysis of carcinoma of unknown primary origin (CUP) cases validate the experimental treatment arms being used in the CUPISCO study (NCT03498521), an ongoing randomized trial using comprehensive genomic profiling to assign patients with CUP to targeted or immunotherapy treatment arms based on the presence of pathogenic genomic alterations. The findings also suggest that future studies including additional biomarkers and treatment arms, such as programmed death‐ligand 1 positivity and genomic loss of heterozygosity, may identify a greater proportion of patients with CUP potentially benefiting from comprehensive genomic profiling‐informed treatment., This article focuses on the ability of comprehensive genomic profiling to identify potentially targetable genetic alterations in cancers of unknown primary, based on the inclusion criteria for the CUPISCO clinical trial and aiming for more effective therapeutic options for patients.
Published: 2020

48. CYLD-mutant cylindroma-like basaloid carcinoma of the anus: a genetically and morphologically distinct class of HPV-related anal carcinoma

Author: Amanda Hemmerich, Mark C. Mochel, Shakti H. Ramkissoon, Jeffrey S. Ross, Radwa Sharaf, Brendan J. Gillespie, Julia A. Elvin, Brian M. Alexander, Ethan Sokol, Meagan Montesion, Erik A. Williams, Parth J. Patel, Kevin Jon Williams, Julie Y. Tse, James Corines, and Dean Pavlick
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Anal Carcinoma, DNA Mutational Analysis, Mutation, Missense, Alphapapillomavirus, medicine.disease_cause, Article, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Cylindroma, Cancer genomics, Biomarkers, Tumor, medicine, Humans, Missense mutation, Tumour virus infections, Genetic Predisposition to Disease, Hyaline, Aged, Retrospective Studies, Sequence Deletion, Aged, 80 and over, Mutation, business.industry, Papillomavirus Infections, Histology, Middle Aged, Anus Neoplasms, Cell Transformation, Viral, Anus, medicine.disease, Carcinoma, Adenoid Cystic, Deubiquitinating Enzyme CYLD, Phenotype, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Histopathology, RNA Splice Sites, business
Abstract: Rare reports of anal carcinoma (AC) describe histologic resemblance to cutaneous cylindroma, but mutations in the tumor suppressor CYLD, the gene responsible for familial and sporadic cylindromas, have not been systematically investigated in AC. Here, we investigate CYLD-mutant AC, focusing on molecular correlates of distinct histopathology. Comprehensive genomic profiling (hybrid-capture-based DNA sequencing) was performed on 574 ACs, of which 75 unique cases (13%) harbored a CYLD mutation. Clinical data, pathology reports, and histopathology were reviewed for each CYLD-mutant case. The spectrum of CYLD mutations included truncating (n = 50; 67%), homozygous deletion (n = 10; 13%), missense (n = 16; 21%), and splice-site (n = 3; 4%) events. Compared with CYLD-wildtype AC (n = 499), CYLD-mutant ACs were significantly enriched for females (88% vs. 67%, p = 0.0001), slightly younger (median age 59 vs. 61 years, p = 0.047), and included near-universal detection of high-risk HPV sequences (97% vs. 88%, p = 0.014), predominantly HPV16 (96%). The CYLD-mutant cohort also showed significantly lower tumor mutational burden (TMB; median 2.6 vs. 5.2 mut/Mb, p
Published: 2020
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49. Potentially serious consequences for the use of Bitrex as a deterrent for the intentional inhalation of computer duster sprays

Author: Seth A. Kolton, David Hayes, Brian E. Perron, Joseph M. Haroney, and Rebeccah L. Sokol
Subjects: Inhalation, business.industry, Biochemistry (medical), Pharmacology toxicology, Medicine, Medical law, Medical emergency, Toxicology, business, medicine.disease, Pathology and Forensic Medicine
Published: 2020
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50. Utility of flow cytometry and gene rearrangement analysis in tissue and blood of patients with suspected cutaneous T‑cell lymphoma

Author: Sophia Ma, Elizabeth M. Sagatys, Jane L. Messina, Anna Kim, Hailing Zhang, Pei‑Ling Chen, Lubomir Sokol, Lucia Seminario Vidal, Julie D. Gibbs, and Xiaohui Zhang
Subjects: Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Skin Neoplasms, Biopsy, Polymerase Chain Reaction, Sensitivity and Specificity, Flow cytometry, law.invention, Diagnosis, Differential, Young Adult, law, medicine, Humans, Early Detection of Cancer, Polymerase chain reaction, Aged, Skin, Aged, 80 and over, Gene Rearrangement, medicine.diagnostic_test, business.industry, Cutaneous T-cell lymphoma, High-Throughput Nucleotide Sequencing, Cancer, General Medicine, Middle Aged, Flow Cytometry, medicine.disease, Molecular medicine, Lymphoma, T-Cell, Cutaneous, Lymphoma, Oncology, Skin biopsy, Feasibility Studies, Immunohistochemistry, Female, business
Abstract: Cutaneous T‑cell lymphoma (CTCL) is difficult to diagnose at an early stage. Current diagnostic tools include clinical examination, histomorphologic analysis, immunohistochemistry, flow cytometry of peripheral blood and/or lesional tissue, and evaluation of T‑cell receptor (TCR) clonality by gene rearrangement analysis (TCRGR). Advances in genomic sequencing, including high‑throughput sequencing (HTS), can be used to identify specific clones of rearranged TCR genes. Even with all of these tools, CTCL can take as long as a decade to definitively diagnose, potentially delaying treatment options and causing patient anxiety. This study aimed to evaluate the performance of the various ancillary testing modalities used to diagnose early‑stage CTCL. In a subset of patients the performance of HTS was compared to flow cytometry and conventional TCRGR analysis via polymerase chain reaction (PCR). Fifty‑five patients, with a total of 68 skin biopsies and peripheral blood draws, were evaluated using flow cytometry, PCR‑TCRGR, and HTS‑TCRGR to determine the sensitivity and specificity of each ancillary test. In tissue biopsies, flow cytometry (64%), PCR (71%) and HTS (69%) shared similar sensitivities; flow cytometry had the highest specificity (93%), followed by HTS (86%) and PCR (76.9%). However, flow cytometry and PCR had insufficient DNA quantities in 29 and 15% of the specimens, respectively. Peripheral blood testing was less sensitive than tissue testing (flow cytometry 14%, PCR 41%, HTS 33%); in peripheral blood, HTS was the most specific test (flow cytometry, 70%; PCR, 62.5%; and HTS, 100%). HTS is a highly specific molecular test for identifying CTCL in peripheral blood and skin biopsy specimens; however, our findings suggest a need for a continued search for more sensitive tests for early‑stage CTCL.
Published: 2020
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