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1. Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

Author: Roseline Caume, M Scott Perry, Massimo Mastrangelo, Margarete Koch-Hogrebe, Pasquale Striano, Karen Müller-Schlüter, Petra Laššuthová, Monisa D. Wagner, Ingo Helbig, Stephan Lauxmann, Emmanuel Scalais, Marie-Cécile Nassogne, Silvia Masnada, Henrike O. Heyne, Konrad Platzer, Frederic Bilan, Chloe A Stutterd, Sonja Walsh, Katrine M Johannesen, Damien Lederer, Ngoc Minh Le, Christina Fenger, Daniel Tibussek, Lukas Sonnenberg, Andrea Berger, Yuanyuan Liu, Mikhail Abramov, Karen E. Wain, Sergey Korostelev, P Y Billie Au, Elena L. Dadali, An-Sofie Schoonjans, Cornelia Betzler, Artem Borovikov, Johanna Krüger, Maert Rannap, Sebastian Lebon, Nils A Koch, Nancy Eisenhauer, Judith Kroell-Seger, Julian Schubert, Marije Meuwissen, Caroline Lund, Mark Fitzgerald, Federico Zara, Siddharth Srivastava, Claudia M Bonardi, Pia Zacher, Haim Bassan, Arve Vøllo, Katherine B. Howell, Francesca Darra, Guido Rubboli, Stephen W. Scherer, Bénédicte Gérard, Stefano Sartori, Annapurna Poduri, Helene Verhelst, Katalin Sterbova, Mathilde Nizon, Marketa Vlckova, Christina E. Hoei-Hansen, Renzo Guerrini, Ilya V. Kanivets, Juliann M. Savatt, Johannes Rebstock, Jakob Christensen, Cecilia Altuzarra, Dennis Lal, Judith S. Verhoeven, Agathe Roubertie, Constanze Heine, Dagmar Wieczorek, Ingo Borggraefe, Aster V. E. Harder, Anne Destrée, Wen-Hann Tan, Tobias Brünger, Shoji Ichikawa, Laura Canafoglia, Mahmoud Koko, Sergey Kutsev, Sabine Grønborg, Patrizia Accorsi, Heather E. Olson, Bert van der Zwaag, Cathrine E Gjerulfsen, Patrick May, A. A. Sharkov, M. Mahdi Motazacker, Manuela Pendziwiat, Richard J. Leventer, Anna Jansen, Lucio Giordano, Holger Lerche, Carla Marini, Karl Martin Klein, Eva H. Brilstra, Ahmed Eltokhi, Ethan M. Goldberg, Walid Fazeli, Rikke S. Møller, Dorota Hoffman-Zacharska, Michael Alber, Susanne Ruf, Jennifer L. Howe, Phillis Lakeman, Josua Kegele, Katherine L. Helbig, Marga Buzatu, Alice W Ho, Jan Benda, Ilona Krey, Marion Gérard, Sara Matricardi, Thomas U. Mayer, Philippe Gelisse, Jong M. Rho, Johannes R. Lemke, Pierangelo Veggiotti, Tobias Loddenkemper, Gaetan Lesca, Ulrike B. S. Hedrich, Silvana Franceschetti, Elena Gardella, Irina Mishina, María Vaccarezza, Timo Roser, Public Health Sciences, Mental Health and Wellbeing research group, Neurogenetics, Neuroprotection & Neuromodulation, Pediatrics, Human Genetics, ANS - Complex Trait Genetics, ARD - Amsterdam Reproduction and Development, Human genetics, and Amsterdam Reproduction & Development (AR&D)
Subjects: medicine.medical_specialty, SCN8A, Gastroenterology, Epilepsy, Sodium channel blocker, Neurodevelopmental disorder, Seizures, Intellectual Disability, Internal medicine, medicine, Humans, Missense mutation, genetics, Generalized epilepsy, Genetic Association Studies, Benign familial infantile epilepsy, Generalized, business.industry, Infant, personalized medicine, Prognosis, medicine.disease, Phenotype, Settore MED/39 - Neuropsichiatria Infantile, NAV1.6 Voltage-Gated Sodium Channel, Mutation, epilepsy, Original Article, Epilepsy, Generalized, Human medicine, Neurology (clinical), Age of onset, business, Epileptic Syndromes, Sodium Channel Blockers
Abstract: We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1–3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1–3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1–3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life.
Published: 2022
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2. Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-naïve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study

Author: Robert E. Reiter, Andrew T. Lenis, Jeremie Calais, Taylor Y. Sadun, David W. Johnson, Cedric Lebacle, Patrick M Lec, Matthias Eiber, Johannes Czernin, Wolfgang P. Fendler, and Aydin Pooli
Subjects: Male, Urology, medicine.medical_treatment, 030232 urology & nephrology, Gallium Radioisotopes, urologic and male genital diseases, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, Positron Emission Tomography Computed Tomography, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Stage (cooking), Lymph node, Neoplasm Staging, Retrospective Studies, medicine.diagnostic_test, business.industry, Prostatectomy, Prostatic Neoplasms, Magnetic resonance imaging, Retrospective cohort study, Prostate-Specific Antigen, medicine.disease, Cross-Sectional Studies, medicine.anatomical_structure, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Surgery, Nuclear medicine, business
Abstract: Background The role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the initial staging of men with prostate cancer (PCa) has yet to be evaluated adequately. Objective To investigate the concordance of PSMA PET/CT with conventional imaging (CI) with cross-sectional abdominopelvic and/or radionuclide bone imaging in the initial staging of patients with treatment-naive PCa. Design, setting, and participants We performed a post hoc retrospective cohort study of patients enrolled in a prospective single-arm trial ( NCT03368547 ). We included patients with intermediate-risk (IR) and high-risk (HR) PCa who underwent PSMA PET/CT within 6 mo of CI. Patients with any treatment prior to PSMA PET/CT were excluded. Patient- and tumor-specific data, and imaging findings were obtained. Outcome measurements and statistical analysis Our primary outcome measurement was the concordance rate of PSMA PET/CT with CI for the identification of N, M1a, M1b, and M1c disease. Descriptive statistics were used. Results and limitations A total of 168 patients with treatment-naive IR and HR PCa met the inclusion criteria. HR disease accounted for 124/168 (73.8%) patients. The median prostate-specific antigen was 11.4 (6.8–24.6) ng/ml. The rates of nonconcordance between PSMA PET/CT and CI were 34/162 (21.0%), 5/70 (7.1%), 8/92 (8.7%), and 1/71 (1.4%) for N, M1a, M1b, and M1c disease, respectively. PSMA PET/CT assigned a higher stage in 37/168 (22.0%) patients and a lower stage in 12/170 (7.1%) patients. In a subset of 50 patients treated with radical prostatectomy and pelvic lymph node dissection, the prevalence of PSMA PET/CT–positive and that of CI-positive nodal disease were 14% and 4%, and the false negative rates were 30% and 32%, respectively. The principal limitations of this study include the heterogeneity in CI modalities and the 6-mo time frame between CI and PSMA PET. Conclusions PSMA PET/CT imaging may serve as a valuable tool in the initial staging of treatment-naive IR and HR PCa. Patient summary We evaluated how prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) compared with standard imaging (such as computed tomography, bone scan, and prostate magnetic resonance imaging) for initial staging of patients with prostate cancer. Our findings suggest that PSMA PET/CT may detect and rule out more metastatic lesions, which could prove valuable in guiding treatment.
Published: 2022
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3. Comparison of a Pure Plug-Based Versus a Primary Suture-Based Vascular Closure Device Strategy for Transfemoral Transcatheter Aortic Valve Replacement: The CHOICE-CLOSURE Randomized Clinical Trial

Author: Nicolas Majunke, Choice-Closure Investigators, Peter Boekstegers, Marcus Sandri, Ralf Müller, Sven Hohenstein, Holger Thiele, David Holzhey, Thilo Noack, Danilo Obradovic, Anne-Kathrin Funkat, Johannes Wilde, Philipp Hartung, Philipp Kiefer, Mohamed Abdel-Wahab, Mitsunobu Kitamura, Sergey Leontyev, Marc Vorpahl, Steffen Desch, Melchior Seyfarth, Oliver Dumpies, Michael A. Borger, and Johannes Rotta Detto Loria
Subjects: Male, medicine.medical_specialty, Percutaneous, medicine.medical_treatment, Hemorrhage, law.invention, Transcatheter Aortic Valve Replacement, Valve replacement, Suture (anatomy), Randomized controlled trial, law, Physiology (medical), medicine, Clinical endpoint, Humans, Vascular closure device, Aged, Aged, 80 and over, Peripheral Vascular Diseases, Hemostasis, Sutures, business.industry, Vascular disease, Aortic Valve Stenosis, medicine.disease, Surgery, Femoral Artery, Catheter, Treatment Outcome, Aortic Valve, Cardiology and Cardiovascular Medicine, business, Vascular Closure Devices
Abstract: Background: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. Methods: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site– or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site– or access-related bleeding, VCD failure, and time to hemostasis. Results: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07–2.44], P =0.029). Access site– or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91–2.73], P =0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40–1.82], P =0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32–180] versus 240 [174–316] seconds, P Conclusions: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site– or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04459208.
Published: 2022
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4. Oncological Long-term Outcome After Whole-gland High-intensity Focused Ultrasound for Prostate Cancer—21-yr Follow-up

Author: Florian Zeman, Stefan Denzinger, Johannes Bründl, Johannes Breyer, Maximilian Burger, Vera Osberghaus, Andreas Blana, Michael Gierth, Bernd Rosenhammer, and Roman Ganzer
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Urology, medicine.medical_treatment, Salvage treatment, 030232 urology & nephrology, Context (language use), medicine.disease, Focused ultrasound, High-intensity focused ultrasound, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, 030220 oncology & carcinogenesis, Biopsy, medicine, Statistical analysis, Radiology, business, Patient summary
Abstract: Background Owing to the morbidity of established radical treatment options for prostate cancer, alternative whole-gland and focal treatment strategies have emerged. High-intensity focused ultrasound (HIFU) is one of the most studied sources for tissue ablation and has been used since the 1990s. Objective To provide 21-yr oncological long-term follow-up data of an unselected series of patients who underwent whole-gland HIFU for nonmetastatic prostate cancer. Design, setting, and participants A total of 674 patients were treated between November 1997 and November 2012 in one university center. Outcome measurements and statistical analysis The oncological outcome was assessed by biopsy failure–free survival (BFFS), salvage treatment–free survival (STFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Multivariable Cox proportional hazard regression analyses were performed to estimate the prognostic relevance of clinical variables. Results and limitations In total, 560 patients were included into the evaluation and the median follow-up was 15.1 yr, with a range up to 21.4 yr. At 15 yr, CSS rates for low-, intermediate-, and high-risk patients were 95%, 89%, and 65%, respectively; MFS, STFS-1 (salvage treatment other than HIFU), STFS-2 (salvage treatment including repeat HIFU), and BFFS rates were 91%, 85%, and 58%; 77%, 63%, and 29%; 67%, 52%, and 28%; and 82%, 73%, and 47%, respectively. Preoperative high-risk category was an independent predictor of inferior OS, CSS, MFS, STFS, and BFFS. Conclusions Although whole-gland HIFU achieved good long-term cancer control in low- and intermediate-risk patients, high-risk patients should not be treated routinely by HIFU. Intermediate-risk patients achieve high CSS and MFS rates, but a relevant salvage treatment rate has to be reckoned with. Long-term data after whole-gland therapy might help derive implications for focal treatment sources and patient selection. Patient summary Long-term data after whole-gland high-intensity focused ultrasound (HIFU) therapy are crucial to prove its oncological efficacy, and may help derive implications for focal treatment strategies and patient selection. In this context, whole-gland HIFU achieved good long-term cancer control up to 21 yr in low- and intermediate-risk prostate cancer (PCa) patients. Owing to considerably inferior long-term cancer control, it should not routinely be used in high-risk PCa patients.
Published: 2022
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5. The effects of patients’ expectations on surgery outcome in total hip and knee arthroplasty

Author: Karolin Neubauer, Johannes A. C. Laferton, Thomas Munder, Lara Oeltjen, David Daniel Ebert, University of Zurich, Laferton, Johannes A C, and Clinical, Neuro- & Developmental Psychology
Subjects: medicine.medical_specialty, Prognostic factor, medicine.medical_treatment, Arthroplasty, Replacement, Hip, Osteoarthritis, Placebo, 03 medical and health sciences, 2738 Psychiatry and Mental Health, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, Arthroplasty, Replacement, Knee, Not evaluated, joint replacement surgery, Motivation, 030505 public health, business.industry, 10093 Institute of Psychology, 3203 Clinical Psychology, Random effects model, medicine.disease, Prognosis, Arthroplasty, meta-analysis, Psychiatry and Mental health, Clinical Psychology, osteoarthritis, Treatment Outcome, Patient Satisfaction, Meta-analysis, Surgery outcome, Physical therapy, arthroplasty, placebo effect, 0305 other medical science, business, 150 Psychology, Patients’ expectations
Abstract: Patients’ expectations are among the most frequently studied psychological prognostic factors in total knee and hip arthroplasty (TKA/THA). So far, however, evidence on the effect of patients’ preoperative expectations on surgery outcome is inconclusive. Heterogeneity of expectation constructs and the use of psychometrically not evaluated measurement instruments have constituted major obstacles for the integration of the current literature. Using a theory-based model of expectation constructs (Laferton, Kube, Salzmann, Auer, & Shedden-Mora, 2017), this meta-analysis set out to disentangle the conflicting results in the current literature. Systematic literature searches yielded k = 46 studies (N = 10,465) that reported associations of preoperative expectations with postoperative pain, functioning and disability, and satisfaction. Random effects meta-analysis revealed a robust small association (r = .16; 95% CI .13, .19) between patients’ positive preoperative expectations and better postoperative outcomes. This effect did not differ between THA and TKA, different outcome categories and different follow-up periods. Studies using psychometrically evaluated expectation measures reported significantly higher effects (r = .19; 95% CI .16, .22). Whether this effect varies among different expectation constructs remains unclear. High-quality studies using validated, multidimensional expectation measures are needed to further understand the role of different expectation constructs in THA and TKA surgery.
Published: 2022
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6. Musculoskeletal Ultrasound in Childhood Arthritis Limited Examination: A Comprehensive, Reliable, <scp>Time‐Efficient</scp> Assessment of Synovitis

Author: Amy Cassedy, Mekibib Altaye, Tracy V. Ting, Carra Musculoskeletal Ultrasound Workgroup, Edward J Oberle, Janet Figueroa, Johannes Roth, Courtney McCracken, Gurjit S. Kaeley, and Patricia Vega-Fernandez
Subjects: musculoskeletal diseases, Change over time, medicine.medical_specialty, business.industry, Intraclass correlation, Childhood arthritis, Ultrasound, Arthritis, medicine.disease, Time efficient, Rheumatology, Synovitis, medicine, Radiology, business, Pediatric ultrasound
Abstract: Objective To develop and initially validate a comprehensive pediatric musculoskeletal ultrasound (MSUS) joint-specific scoring system. To determine the minimum number of joints needed to identify active disease. Methods A semiquantitative scoring system was developed by consensus and initially validated by inter-rater reliability using intraclass correlation coefficients (ICC). Subsequently, newly diagnosed Juvenile Idiopathic Arthritis (JIA) patients with an active joint count >4 had a 42 joint MSUS performed at baseline and 3 months using this protocol. A minimum set of joints needed to identify all patients with synovitis on MSUS was obtained through a data reduction process. Spearman's correlation (rs) was calculated to determine the association between MSUS findings and clinical Juvenile Arthritis Disease Activity Score-10 (cJADAS-10). Standardized response means (SMR) were used to assess change over time. Results The final joint-specific scoring system revealed an excellent inter-rater reliability (ICC = 0.81-0.96) for all joints. Thirty patients were enrolled. Scanning 5 joints bilaterally: wrists, 2nd and 3rd MCPs, knees and ankles captured 100% of children with B-mode synovitis and had moderate correlation with cJADAS-10 at baseline (rs=0.45). Mean ultrasound scores at baseline and follow-up were 28.3 and 22.3 with SRM of 0.69 (p=0.002) for 42 joints and 36 and 27.7 with SRM of 0.76 (p=0.003) for the reduced joints, respectively. Conclusion A limited MSUS examination called MUSICAL (Musculoskeletal UltraSound In Childhood Arthritis Limited-examination) captures all patients with active synovitis and our new joint specific scoring system is highly reliable and sensitive to change.
Published: 2022
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7. A systematic review of the optimal drainage technique for septic hip arthritis in children

Author: Johannes H. J. M. Bessems, Cornelia Maria Donders, Christiaan J. A. van Bergen, Anne J. Spaans, and Orthopedics and Sports Medicine
Subjects: medicine.medical_specialty, medicine.medical_treatment, Arthroplasty, Replacement, Hip, Arthritis, 03 medical and health sciences, Arthroscopy, 0302 clinical medicine, medicine, Humans, Orthopedics and Sports Medicine, Drainage, Child, Retrospective Studies, Arthrotomy, 030222 orthopedics, Arthritis, Infectious, medicine.diagnostic_test, business.industry, Arthrocentesis, 030208 emergency & critical care medicine, medicine.disease, Surgery, Septic hip, Septic arthritis, Hip Joint, business
Abstract: Introduction: The hip is one of the most commonly affected joints in paediatric septic arthritis. Drainage can be performed using arthrocentesis (articular needle aspiration), arthroscopy or arthrotomy. The objective of this systematic review was to identify the most effective drainage technique for septic hip arthritis in the paediatric population. Materials and methods: The electronic MEDLINE, EMBASE and Cochrane databases were systematically searched for original articles that reported outcomes of arthrocentesis, arthroscopy or arthrotomy for septic arthritis of the paediatric hip. Outcome parameters were additional drainage procedures, clinical outcomes and radiological sequelae. The quality of each of the included studies was assessed with the Methodological Index for Non-randomized Studies (MINORS) score. Results: Out of 2428 articles, 19 studies with a total of 406 hip joints were included in the systematic review. Additional arthroscopy or arthrotomy was performed in 15% of the hips treated with arthrocentesis, in 14% after arthroscopy and in 3% after arthrotomy. Inferior clinical outcomes and more radiological sequelae were seen in patients treated with an arthrotomy. A meta-analysis could not be performed due to the diversity and low quality of the studies (MINORS median 4 [range 2–15]). Conclusions: This systematic review gives a comprehensive overview of the available literature on treatment for septic hip arthritis in children. Arthrocentesis and arthroscopic procedures may have a higher risk of additional drainage procedures in comparison with arthrotomy. However, arthrotomy might be associated with inferior outcomes in the longer term. The included studies are diverse and the scientific quality is generally low.
Published: 2022
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8. Changes in the classification of personality disorders: Comparing the DSM–5 Section II personality disorder model to the alternative model for personality disorders using structured clinical interviews

Author: Jan H. Kamphuis, Johannes Zimmermann, Laura C. Weekers, Joost Hutsebaut, and Medical and Clinical Psychology
Subjects: Personality Inventory, media_common.quotation_subject, AXIS II, PsycINFO, DSM-5, Schizotypal Personality Disorder, prevalence of PD, medicine, Narcissism, Humans, CRITERIA, Personality, AMPD, Section II PD, VALIDITY, Medical diagnosis, PSYCHOMETRIC EVALUATION, BORDERLINE, media_common, SEMISTRUCTURED INTERVIEW, convergence, Antisocial Personality Disorder, medicine.disease, Personality disorders, NARCISSISM, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Clinical Psychology, INTERRATER RELIABILITY, IV, Convergent validity, Structured interview, medicine.symptom, Psychology, TRAITS, Clinical psychology
Abstract: The current study examined the continuity of personality disorder (PD) diagnoses from Section II to Section III (alternative model for personality disorders [AMPD]) when using structured interviews. We investigated the continuity both in terms of stability of prevalence rates and in terms of convergent validity. A clinical sample of 189 participants were concurrently administered both Section II PD and AMPD interviews for diagnosing PD by 2 independent interviewers. Stability of prevalence between the models for specific PD diagnoses was generally supported. A higher prevalence of trait-specified PD in the AMPD model resulted in higher prevalence of PD in general when using the AMPD model compared with the Section II PD model. Correlations between matching criterion counts according to both models were generally high. Convergence between the Section II PD and AMPD model categorical diagnoses was adequate for the most frequently diagnosed and studied PDs (i.e., avoidant-, borderline-, and antisocial PD), but lower than previously found, likely due to the stringent test-retest design used in this study. Convergence between the models for narcissistic and obsessive-compulsive PD was low and could not be estimated for schizotypal PD. Future studies should investigate which of both models may prove to be most valid in terms of predicting current and future impairments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Published: 2022
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9. Skin diseases in hospitalized geriatrics

Author: Johannes M. Miocic, Franziska Schauer, Claudia Ansorge, and Geo-Energy
Subjects: medicine.medical_specialty, PEMPHIGUS VULGARIS/FOLIACEUS, Universities, Chronic venous insufficiency, Epidemiology, Geriatric patients, MELANOMA, Type 2 diabetes, Dermatology, DIAGNOSIS, Skin Diseases, Comorbidities, Angina, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Germany, Psoriasis, medicine, Humans, 030212 general & internal medicine, Medical diagnosis, Aged, Retrospective Studies, Geriatrics, RISK, Inpatients, business.industry, WOMEN, General Medicine, ASSOCIATION, medicine.disease, TRENDS, NMSC, Hospitalization, Diabetes Mellitus, Type 2, Cohort, S2K GUIDELINES, SQUAMOUS-CELL CARCINOMA, GENDER, business
Abstract: The demographic trend of an ageing society is mirrored in the rising number of hospitalized geriatric patients in Germany. However, there is still a wide gap of knowledge regarding the dermatological diseases, comorbidities and performed procedures within this growingly important group of patients. The study was conducted as a retrospective monocentric data analysis of all patients 65 years or older from the Department of Dermatology, Medical Center—University of Freiburg, Germany. In total, 10,009 individual hospitalisations were included from 2009 to 2017, and there was a notable increase of geriatric patients in the study period. This study illustrates the following: leading major diagnoses included malignant neoplasm of the head and neck, ulcerated and non-ulcerated inflammatory spectrum of chronic venous insufficiency, whereas angina pectoris, type 2 diabetes and cardiac diseases were noted most frequently as secondary diagnoses. Patients with venous diseases had considerably more often cardiopulmonary minor diagnoses, whereas endocrine diagnoses peaked in the cohort of patients with psoriasis and psychiatric and muscululoskeletal disorders in patients with bullous dieseases. Moh’s surgery, dressings and multimodal dermatological treatments were the most often encoded procedures.
Published: 2022

10. Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

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

Author: Michal D. Czerwinski, M. R. Vergeer, Abrahim Al-Mamgani, Peter P. Jansen, Cornelia G. Verhoef, Ellen M. Zwijnenburg, Johannes A. Langendijk, Johannes H.A.M. Kaanders, Frederik W.R. Wesseling, Radiotherapy, Radiotherapie, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Brachytherapy, All institutes and research themes of the Radboud University Medical Center, STAGE, SDG 3 - Good Health and Well-being, RADIATION-THERAPY, medicine, Humans, RECONSTRUCTION, Radiology, Nuclear Medicine and imaging, HEAD, External beam radiotherapy, Propensity Score, Head and neck cancer, Nose, Retrospective Studies, Radiotherapy, business.industry, Incidence (epidemiology), Prostatic Neoplasms, Cancer, Hematology, medicine.disease, Radiation therapy, medicine.anatomical_structure, Oncology, INTERVENTIONAL RADIOTHERAPY, CAVITY, INTERSTITIAL BRACHYTHERAPY, SQUAMOUS-CELL CARCINOMA, Radiology, Nasal vestibule, business, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Radiotherapy, Image-Guided
Abstract: Background and purpose: Primary radiotherapy is often preferred for early-stage cancer of the nasal vestibule (CNV), combining high disease control with preservation of nasal anatomy. However, due to practice variation and an absence of comparative trials, no consensus exists on preference for brachytherapy (BT) or external beam radiotherapy (EBRT). We compared these modalities in terms of disease control, nose preservation rates and toxicity. Materials and methods: Medical records of 225 patients with T1-T2 squamous cell carcinoma of the nasal vestibule treated with 3D image-guided primary radiotherapy between Jan 2010 and Dec 2016 in 6 Dutch institutions were reviewed retrospectively. Results: 153 of 225 patients were treated with BT, 65 with EBRT and 7 with other modalities. Median follow-up was 46 months. Overall 3-year local control (LC) and regional control (RC) were 87% and 89%. Five-year disease-specific survival (DSS) and overall survival (OS) were 94% and 82%. Three-year survival with preserved nose (SPN) was 76%. BT provided higher 3-year LC (95% vs 71%, p < 0.01) and SPN compared with EBRT (82% vs 61%, p < 0.01). Multivariable and propensity-score-matched cohort analyses confirmed better outcomes after BT. No difference was seen in DSS or OS. Five-year incidence of CTCAE 5.0 grade >2 toxicity was higher after BT (20% vs 3%, p = 0.03) and consisted mostly of radiation ulcers. 50% of all late toxicity recovered. Conclusion: In this largest-to-date multicenter analysis of T1-T2 CNV, BT achieved superior LC and SPN compared with EBRT. Grade 1-2 radiation ulcers occurred more frequently after brachytherapy, but were transient in half the cases. Considering these results, BT can be recommended as first-line treatment for T1-T2 CNV. (c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 164 (2021) 20-26 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Published: 2021
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12. Sekundäre Nutzung von hausärztlichen Routinedaten ist machbar – Bericht vom RADAR Projekt

Author: Ramin Yahyapour, Iris Demmer, Stephanie Heinemann, Roland Groh, Arne Blumentritt, Wolfgang Hoffmann, Thomas Bahls, Philipp Wieder, Johannes Pung, Johannes Drepper, Eva Hummers, Johannes Hauswaldt, Falk Schlegelmilch, Otto Rienhoff, and Valérie Kempter
Subjects: Privacy by Design, Computer science, business.industry, Medical record, Public Health, Environmental and Occupational Health, Health services research, Information repository, medicine.disease, 030210 environmental & occupational health, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Ambulatory care, Informed consent, General Data Protection Regulation, Health care, medicine, 030212 general & internal medicine, Medical emergency, business
Abstract: ZusammenfassungZiel der Studie „Real world“-Daten aus der ambulanten Gesundheitsversorgung sind in Deutschland nur schwer systematisch und longitudinal zu erlangen. Unsere Vision ist eine permanente Datenablage mit repräsentativen, de-identifizierten Patienten- und Versorgungsdaten, längsschnittlich, fortwährend aktualisiert und von verschiedenen Versorgern, mit der Möglichkeit zur Verknüpfung mit weiteren Daten, etwa aus Patientenbefragungen oder biologischer Forschung, zugänglich für andere Forscher. Wir berichten methodische Vorgehensweisen und Ergebnisse aus dem RADAR Projekt.Methodik Untersuchung des Rechtsrahmens, Entwicklung prototypischer technischer Abläufe und Lösungen, mit Machbarkeitsstudie zur Evaluation von technischer und inhaltlicher Funktionalität sowie Eignung für Fragestellungen der Versorgungsforschung.Ergebnisse Ab 2016 entwickelte ein interdisziplinäres Wissenschaftlerteam ein Datenschutzkonzept für Exporte von Versorgungsdaten aus elektronischen Praxisverwaltungssystemen. Eine technische und organisatorische Forschungsinfrastruktur im ambulanten Sektor wurden entwickelt und im Anwendungsfall „Orale Antikoagulation“ (OAK) umgesetzt. In 7 niedersächsischen Hausarztpraxen wurden 100 Patienten gewonnen und nach informierter Einwilligung ihre ausgewählten Behandlungsdaten, reduziert auf 40 relevante Datenfelder, über die Behandlungsdatentransfer-Schnittstelle extrahiert, unmittelbar vor Ort in identifizierende bzw. medizinische Daten getrennt und verschlüsselt zur Treuhandstelle (THS) bzw. an den Datenhalter übertragen. 75 Patienten, die die Einschlusskriterien erfüllten (mind. 1 Jahr Behandlung mit OAK), erhielten einen Lebensqualitäts-Fragebogen über die THS per Post. Von 66 Rücksendungen wurden 63 Fragebogenergebnisse mit den Behandlungsdaten in der Datenablage verknüpft.Schlussfolgerung Die rechtskonforme Machbarkeit der Gewinnung von pseudonymisierten hausärztlichen Routinedaten mit expliziter informierter Patienteneinwilligung und deren wissenschaftliche Nutzung einschließlich Re-Kontaktierung und Einbindung von Fragebogendaten konnte nachgewiesen werden. Die Schutzkonzepte Privacy by design und Datenminimierung (Artikel 25 mit Erwägungsgrund 78 DSGVO) wurden systematisch in das RADAR Projekt integriert und begründen wesentlich, dass der Machbarkeitsnachweis rechtskonformer Primärdatengewinnung und sekundärer Nutzung für Forschungszwecke gelang. Eine Nutzung hinreichend anonymisierter, aber noch sinnvoller hausärztlicher Gesundheitsdaten ohne individuelle Einwilligung ist im bestehenden Rechtsrahmen in Deutschland schwerlich umsetzbar.
Published: 2021
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13. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Author: Tim Niehues, Catherine Waruiru, Conleth Feighery, Uwe Schauer, Virginie Courteille, Kai Lehmberg, Ingo Müller, I. Esteves, Henner Morbach, Michael Borte, Patrick Hundsdoerfer, Klaus Schwarz, Ewelina Gowin, Alessandro Aiuti, Andreas Holbro, Federica Barzaghi, João Farela Neves, Dagmar Graf, Hannah Tamary, Veneta Milenova, Benedikt Boetticher, Eleonora Gambineri, Vera Goda, Alia Eldash, Jan-Christian Wasmuth, Fabio Candotti, Svetlana O. Sharapova, Markus Metzler, Juergen Brunner, Anna Hilfanova, Brindusa Ruxandra Capilna, Pere Soler-Palacín, Arnau Antolí, Horst von Bernuth, Vassilios Lougaris, Maria Carrabba, Bernd H. Belohradsky, Julian Thalhammer, Nathalie de Vergnes, Peter Olbrich, Peter Kopač, Leif G. Hanitsch, Alexandra Nieters, Filomeen Haerynck, Juliana Gabzdilova, Sezin Aydemir, Rabab El Hawary, Patrick F.K. Yong, Maria Giovanna Danieli, Alberto Tommasini, Sandra Steinmann, Ulrich Baumann, Figen Dogu, Elisabeth Förster-Waldl, Carolina Marasco, Donato Amodio, Lorenzo Lodi, Xavier Solanich, Caterina Cancrini, Brigita Sitkauskiene, Torsten Witte, Clementina Vanessa, Nima Rezaei, Jean-Christophe Goffard, Kirsten Wittke, Emmanouil Liatsis, Helen Baxendale, Susana L. Silva, Bodo Grimbacher, Henrike Ritterbusch, Evangelia Farmaki, Safa Meshaal, Sujal Ghosh, Larysa Kostyuchenko, David Edgar, Simone Cesaro, R Zeuner, Nerea Salmón Rodríguez, Isabella Quinti, Stephan Ehl, Pauline Brosselin, Joerg C. Henes, Pilar Llobet Agulló, Rosa Maria Dellepiane, Andrea Meinhardt, Marina Kojić, Georgios Sogkas, Stephan Borte, Catharina Schuetz, Suheyla Ocak, Karin Marschall, Lukas M. Gasteiger, Stefan Raffac, Sofia Tantou, Sadia Noorani, Matthaios Speletas, Philippe Randrianomenjanahary, Ursula Holzer, Ayca Kiykim, Johannes G. Liese, Angelo Vacca, Gisela Fecker, Ekrem Unal, Koen J. van Aerde, Alba Parra-Martínez, Kaan Boztug, Sophie Stiehler, Sybille Landwehr-Kenzel, Claudio Pignata, Jennifer Neubert, Janine Reichenbach, Shahnaz Parvin, Sarah Goddard, Andrea Schroll, Dirk Holzinger, Asghar Aghamohammadi, Hassan Abolhassani, Johannes Trück, Estela Paz-Artal, Shereen M. Reda, Anna Shcherbina, Maria Raptaki, Jaroslava Orosova, Beata Wolska-Kuśnierz, Tessa Kerre, Gerrit Ahrenstorf, Ben Zion Garty, Dirk Foell, Benjamin Becker, Ulrike F. Demel, Androniki Kapousouzi, Abraham Rutgers, Klaus Warnatz, Gemma Rocamora Blanch, Stephan Rusch, Luis M. Allende, Dalia Abd Elaziz, Safa Baris, Jorisvan Montfrans, Dominik T. Schneider, Raphael Scheible, Juana Gil-Herrera, Gerhard Kindle, Annarosa Soresina, Giovanna Fabio, Uwe Wintergerst, Emilia Faria, Maria Fasshauer, Silvia Ricci, Aisha Elmarsafy, Barbara Pietrucha, Carsten Speckmann, Nizar Mahlaoui, Ulrich Heininger, Isabelle Meyts, Matthew Buckland, Efimia Papadopoulou-Alataki, Robin Kobbe, A Herwadkar, Sebastian F. N. Bode, Ali Sobh, László Maródi, Baldassarre Martire, Chiara Azzari, Maximilian Heeg, Katja Masjosthusmann, Michael H. Albert, Matteo Chinello, Juan Luis Santos-Pérez, Aarnoud Huissoon, Tanya I. Coulter, Hendrik Schulze-Koops, Norbert Graf, Radwa Alkady, Jolanta Bernatoniene, Seraina Prader, Alenka Gagro, Joachim Roesler, Taco W. Kuijpers, Ewa Więsik-Szewczyk, Maria Elena Maccari, Conrad Ferdinand Lippert, Miriam González-Amores, Johannes Dirks, Daniel E Pleguezuelo, Christof M. Kramm, Anders Fasth, Volker Schuster, Olov Ekwall, Nikolaus Rieber, Javier Carbone, Petra Kaiser-Labusch, Diana Ernst, Lucia Augusta Baselli, Luis Ignacio Gonzalez-Granado, Maria Kanariou, Stefanie S. V. Henriet, Sigune Goldacker, Kerstin Felgentreff, Oana Joean, Fine Roosens, Fabian Hauck, Eva C. Schwaneck, Milos Jesenak, Manfred Hoenig, Lenka Kapustova, Christoph Boesecke, Alain Fischer, Sara Pereira da Silva, Julia Körholz, Ansgar Schulz, Carolynne Schwarze-Zander, Mikko Seppänen, Nermeen Galal, Nora Naumann-Bartsch, Tomaz Garcez, Peter Ciznar, Klara M. Posfay-Barbe, Zelimir Pavle Eric, Reinhold E. Schmidt, Hermann J. Girschick, Sabine Heine, Anika-Kerstin Biegner, Annick A. J. M. van de Ven, Stefan Schreiber, J. Merlijn van den Berg, Nurit Assia Batzir, Alexandra Jablonka, Kim Stol, Gregor Dückers, Antonios G.A. Kolios, Ioannis Kakkas, Christian Klemann, Marina N. Guseva, Sofia Grigoriadou, Elif Karakoc-Aydiner, Antonio Marzollo, Peter D. Arkwright, Urs C. Steiner, Sara Sebnem Kilic, Romina Dieli-Crimi, Gergely Kriván, Monika Sparber-Sauer, Marco Cazzaniga, Fulvio Porta, Paraskevi Maggina, Tomas Milota, Robbert G. M. Bredius, Martine Pergent, Klaus Tenbrock, Jana Pachlopnik Schmid, Florentia Dimitriou, Cathal Laurence Steele, Helen Bourne, Anna Bobcakova, Gerd Horneff, Judith Potjewijd, Marc Schmalzing, Tobias Ankermann, Paul Ryan, Oksana Boyarchuk, Necil Kutukculer, Carl Friedrich Classen, Zita Chovancová, Moira Thomas, Cinzia Milito, Michaela Bitzenhofer-Grüber, Faranaz Atschekzei, Eva Hlaváčková, Viviana Moschese, Julie Smet, Hans-Hartmut Peter, Carla Teixeira, Sabine M El-Helou, Suzanne de Kruijf Bazen, Helmut Wittkowski, Donate Jakoby, Marina Garcia-Prat, Esther de Vries, Richard Herriot, Sven Kracker, Alessandro Plebani, Lisa Göschl, Laura Hora Marques, Anna Sediva, Jiri Litzman, Mark M. Gompels, Renate Krüger, Şefika İlknur Kökçü Karadağ, Nadine Binder, Anna Szaflarska, Peter Jandus, Lisa Ibberson, Johann Greil, Ulf Schulze-Sturm, Mehtap Sirin, Aydan Ikinciogullari, Edyta Heropolitańska-Pliszka, Michael E. Weiss, Alla Skapenko, Lukas Wisgrill, Hana Alachkar, Uta Behrends, Silvia Sánchez-Ramón, Maria N. Hatzistilianou, Otilia Petrovicova, Darko Richter, Zoreh Nademi, Jürgen K. Rockstroh, Sohilla Lotfy, Markus G. Seidel, Timothy Ronan Leahy, Audra Blažienė, Translational Immunology Groningen (TRIGR), Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Inflammatory diseases, ARD - Amsterdam Reproduction and Development, University of Zurich, Ehl, Stephan, Thalhammer, J., Kindle, G., Nieters, A., Rusch, S., Seppanen, M. R. J., Fischer, A., Grimbacher, B., Edgar, D., Buckland, M., Mahlaoui, N., Ehl, S., Boztug, K., Brunner, J., Demel, U. F., Forster-Waldl, E., Gasteiger, L. M., Goschl, L., Kojic, M., Schroll, A., Seidel, M. G., Wintergerst, U., Wisgrill, L., Sharapova, S. O., Goffard, J. -C., Kerre, T., Meyts, I., Roosens, F., Smet, J., Haerynck, F., Eric, Z. P., Milenova, V., Gagro, A., Richter, D., Chovancova, Z., Hlavackova, E., Litzman, J., Milota, T., Sediva, A., Elaziz, D. A., Alkady, R. S., El Sayed El Hawary, R., Eldash, A. S., Galal, N., Lotfy, S., Meshaal, S. S., Reda, S. M., Sobh, A., Elmarsafy, A., Brosselin, P., Courteille, V., De Vergnes, N., Kracker, S., Pergent, M., Randrianomenjanahary, P., Ahrenstorf, G., Albert, M. H., Ankermann, T., Atschekzei, F., Baumann, U., Becker, B. C., Behrends, U., Belohradsky, B. H., Biegner, A. -K., Binder, N., Bode, S. F. N., Boesecke, C., Boetticher, B., Borte, M., Borte, S., Classen, C. F., Dirks, J., Duckers, G., El-Helou, S., Ernst, D., Fasshauer, M., Fecker, G., Felgentreff, K., Foell, D., Ghosh, S., Girschick, H. J., Goldacker, S., Graf, N., Graf, D., Greil, J., Hanitsch, L. G., Hauck, F., Heeg, M., Heine, S. I., Henes, J. C., Hoenig, M., Holzer, U., Holzinger, D., Horneff, G., Hundsdoerfer, P., Jablonka, A., Jakoby, D., Joean, O., Kaiser-Labusch, P., Klemann, C., Kobbe, R., Korholz, J., Kramm, C. M., Kruger, R., Landwehr-Kenzel, S., Lehmberg, K., Liese, J. G., Lippert, C. F., Maccari, M. E., Masjosthusmann, K., Meinhardt, A., Metzler, M., Morbach, H., Muller, I., Naumann-Bartsch, N., Neubert, J., Niehues, T., Peter, H. -H., Rieber, N., Ritterbusch, H., Rockstroh, J. K., Roesler, J., Schauer, U., Scheible, R., Schmalzing, M., Schmidt, R. E., Schneider, D. T., Schreiber, S., Schuetz, C., Schulz, A., Schulze-Koops, H., Schulze-Sturm, U., Schuster, V., Schwaneck, E. C., Schwarz, K., Schwarze-Zander, C., Sirin, M., Skapenko, A., Sogkas, G., Sparber-Sauer, M., Speckmann, C., Steinmann, S., Stiehler, S., Tenbrock, K., von Bernuth, H., Warnatz, K., Wasmuth, J. -C., Weiss, M., Witte, T., Wittke, K., Wittkowski, H., Zeuner, R. A., Farmaki, E., Hatzistilianou, M. N., Kakkas, I., Kanariou, M. G., Kapousouzi, A., Liatsis, E., Maggina, P., Papadopoulou-Alataki, E., Raptaki, M., Speletas, M., Tantou, S., Goda, V., Krivan, G., Marodi, L., Abolhassani, H., Aghamohammadi, A., Rezaei, N., Feighery, C., Leahy, T. R., Ryan, P., Batzir, N. A., Garty, B. Z., Tamary, H., Aiuti, A., Amodio, D., Azzari, C., Barzaghi, F., Baselli, L. A., Cancrini, C., Carrabba, M., Cazzaniga, M., Cesaro, S., Chinello, M., Danieli, M. G., Dellepiane, R. M., Fabio, G., Gambineri, E., Lodi, L., Lougaris, V., Marasco, C., Martire, B., Marzollo, A., Milito, C., Moschese, V., Pignata, C., Plebani, A., Porta, F., Quinti, I., Ricci, S., Soresina, A., Tommasini, A., Vacca, A., Vanessa, C., Blaziene, A., Sitkauskiene, B., Gowin, E., Heropolitanska-Pliszka, E., Pietrucha, B., Szaflarska, A., Wiesik-Szewczyk, E., Wolska-Kusnierz, B., Esteves, I., Faria, E., Marques, L. H., Neves, J. F., Silva, S. L., Teixeira, C., Pereira da Silva, S., Capilna, B. R., Guseva, M. N., Shcherbina, A., Bobcakova, A., Ciznar, P., Gabzdilova, J., Jesenak, M., Kapustova, L., Orosova, J., Petrovicova, O., Raffac, S., Kopac, P., Allende, L. M., Antoli, A., Blanch, G. R., Carbone, J., Dieli-Crimi, R., Garcia-Prat, M., Gil-Herrera, J., Gonzalez-Granado, L. I., Agullo, P. L., Olbrich, P., Parra-Martinez, A., Paz-Artal, E., Pleguezuelo, D. E., Rodriguez, N. S., Sanchez-Ramon, S., Santos-Perez, J. L., Solanich, X., Soler-Palacin, P., Gonzalez-Amores, M., Ekwall, O., Fasth, A., Bitzenhofer-Gruber, M., Candotti, F., Dimitriou, F., Heininger, U., Holbro, A., Jandus, P., Kolios, A. G. A., Marschall, K., Schmid, J. P., Posfay-Barbe, K. M., Prader, S., Reichenbach, J., Steiner, U. C., Truck, J., Bredius, R. G., de Kruijf- Bazen, S., de Vries, E., Henriet, S. S. V., Kuijpers, T. W., Potjewijd, J., Rutgers, A., Stol, K., van Aerde, K. J., Van den Berg, J. M., van de Ven, A. A. J. M., Montfrans, J., Aydemir, S., Baris, S., Dogu, F., Ikinciogullari, A., Karakoc-Aydiner, E., Kilic, S. S., Kiykim, A., Kokcu Karadag, S. I., Kutukculer, N., Ocak, S., Unal, E., Boyarchuk, O., Hilfanova, A., Kostyuchenko, L. V., Alachkar, H., Arkwright, P. D., Baxendale, H. E., Bernatoniene, J., Coulter, T. I., Garcez, T., Goddard, S., Gompels, M. M., Grigoriadou, S., Herriot, R., Herwadkar, A., Huissoon, A., Ibberson, L., Nademi, Z., Noorani, S., Parvin, S., Steele, C. L., Thomas, M., Waruiru, C., Yong, P. F. K., and Bourne, H.
Subjects: 0301 basic medicine, Male, Pediatrics, syndromic, Sex Factor, Disease, registry, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Primary Immunodeficiency Disease, inborn error of immunity, Immunology and Allergy, warning signs, Age Factor, Registries, Family history, presenting symptom, Child, Primary immunodeficiency, Granuloma, autoimmune, immune dysregulation, inflammatory, Adult, Autoimmune Diseases, Female, Humans, Infections, Lymphoproliferative Disorders, Middle Aged, Primary Immunodeficiency Diseases, Sex Factors, Age Factors, 10177 Dermatology Clinic, Infections/epidemiology, 3. Good health, Settore MED/02, Warning signs, Lymphoproliferative Disorder, 2723 Immunology and Allergy, Infection, Human, medicine.medical_specialty, Immunology, 610 Medicine & health, Malignancy, primary immunodeficiency, Autoimmune Disease, 03 medical and health sciences, Immunity, Autoimmune Diseases/epidemiology, medicine, 2403 Immunology, business.industry, warning sign, Common variable immunodeficiency, Granuloma/epidemiology, Immune dysregulation, medicine.disease, Primary Immunodeficiency Diseases/epidemiology, 030104 developmental biology, Lymphoproliferative Disorders/epidemiology, Cohort Studie, business, 030215 immunology
Abstract: BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.
Published: 2021

14. Case report: Flattening of the tectal plate in obstructive hydrocephalus with auto-ventriculostomy

Author: Johannes Schwab, Michael Städt, Markus Holtmannspötter, Heinz Voit-Höhne, and Florian Eff
Subjects: Ventriculostomy, Adult, medicine.medical_specialty, medicine.medical_treatment, Obstructive hydrocephalus, Case Reports, Flattening, 030218 nuclear medicine & medical imaging, Cerebral Ventricles, 03 medical and health sciences, Lateral ventricles, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Third Ventricle, business.industry, Cerebral Aqueduct, Tectal plate, General Medicine, medicine.disease, Magnetic Resonance Imaging, Hydrocephalus, Stenosis, sense organs, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery
Abstract: Background Obstructive hydrocephalus in adulthood can be caused by stenosis in the aqueductal area. Chronic changes lead to a dilatation of the lateral ventricles and ballooning of infratentorial recesses. In rare cases a rupture of the floor of the third ventricle (so-called spontaneous ventriculostomy) has been described in the literature. Case presentation: We present two cases of chronic obstructive hydrocephalus due to aqueductal stenosis in adult patients. Magnetic resonance imaging included phase-contrast-imaging and revealed significant flow through the floor of the third ventricle in keeping with spontaneous ventriculostomy. In addition to other typical changes associated with chronic hydrocephalus, a distinct flattening of the tectal plate could be identified in one case. Conclusion We present two cases of spontaneous ventriculostomy in patients with chronic hydrocephalus. To our knowledge, flattening of the tectal plate has not yet been described in the literature and may be caused by continuous cerebrospinal fluid-pulsation.
Published: 2023

15. Septic arthritis due to <scp> Neisseria gonorrhoea </scp> in Western Australia

Author: Helen Keen, David B. Preen, Warren Raymond, Charles A. Inderjeeth, and Johannes C. Nossent
Subjects: Male, medicine.medical_specialty, Gonococcal arthritis, Population, Gonorrhea, Interquartile range, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, education, Arthritis, Infectious, education.field_of_study, biology, business.industry, Incidence, Mortality rate, Western Australia, Middle Aged, medicine.disease, biology.organism_classification, Comorbidity, Neisseria gonorrhoeae, Female, Septic arthritis, Neisseria, business
Abstract: A high prevalence of gonococcal infections has been reported from remote parts of Western Australia, but the occurrence of disseminated infection leading to arthritis has not been studied.To investigate the frequency, risk factors and long-term outcome of gonococcal arthritis (GA) in Western Australia (WA).A population-based data linkage study of patients with a hospital-based diagnosis of GA in WA between 1990 and 2014. Demographics, standardised incidence rates per million and comorbidity accrued before (lookback 186 months, interquartile range (IQR) 86-267) and after the index hospital contact for GA (follow up 100 months, IQR 60-209) are presented as frequency (%), median (IQR) or rates /1000 months.In total, 98 patients were diagnosed with GA. The annual incidence of GA increased from 1.35 to 2.10 per million between 1990 and 2014, but the rate of GA complicating all gonococcal infections was stable around 0.25%. Female patients with GA (54%; n = 53/98) were younger (24 vs 38 years) and more frequently identified as indigenous (88% vs 49%) than male patients (46%; n = 45/98; P = 0.002). Female patients had higher rates of prior infections (15.5 vs 8.1 per 1000 months; P = 0.002) and diabetes mellitus (15.9% vs 2.5%; P = 0.03) and a longer hospital stay (10 vs 8 days; P = 0.02). GA recurrence rate during follow up was low (2%), but a broad range of comorbidities developed contributing to a 14% crude death rate.GA stably complicates 0.25% of gonococcal infections in WA with young indigenous females and middle-aged non-indigenous males most affected. Prior infectious disease and diabetes mellitus are potential risk factors for GA in females. GA recurs rarely, but its development reflects a high risk of morbidity and mortality over the following 10 years.
Published: 2022
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16. Short-term radiological results after spheroid-based autologous chondrocyte implantation in the knee are independent of defect localisation

Author: Christoph Brochhausen, Johannes Oppermann, David Grevenstein, Stavros Oikonomidis, Peer Eysel, Darius Schafigh, and Christian K. Spies
Subjects: Cartilage, Articular, Knee Joint, education, Biomedical Engineering, Biophysics, Health Informatics, Bioengineering, Articular cartilage, Osteoarthritis, Transplantation, Autologous, Biomaterials, Chondrocytes, medicine, Humans, Orthopedic Procedures, Maximum size, Autologous chondrocyte implantation, business.industry, Cartilage, Spheroid, medicine.disease, Treatment Outcome, medicine.anatomical_structure, Radiological weapon, Lateral femoral condyle, Nuclear medicine, business, Information Systems
Abstract: BACKGROUND: Lesions of articular cartilage represent a crucial risk factor for the early development of osteoarthritis. Autologous chondrocyte implantation (ACI) is a well-established procedure in therapy of those lesions in the knee. The aim of the presented study is to detect differences in short-term radiological outcome depending on defect localization (femoral condyle vs. retropatellar) after spheroid-based ACI. OBJECTIVE: This study aimed to demonstrate that radiological outcome after spheroid-based ACI in the knee is independent of defect localization. METHODS: MRI-scans after retropatellar ACI and ACI of the medial/lateral femoral condyle, with a preoperative Outerbridge grade of III or IV were evaluated regarding MOCART 2.0. RESULTS: The mean defect-size was 5.0 ± 1.8 cm2, with a minimum size of 2 cm2 and a maximum size of 9 cm2. Scans were performed 7.7 months (± 3.1 months) postoperatively. The mean MOCART 2.0 score was 78.5 ± 15.6. No statistically significant influence neither of the localization (p= 0.159), the gender (p= 0.124) nor defect size (< 5 cm2 vs. ⩾ 5 cm2; p= 0.201) could be observed. CONCLUSIONS: The presented data demonstrate good to excellent radiological short-term results after spheroid-based ACI. Data indicates, that at least radiological results are independent of gender, defect-size and defect-localization.
Published: 2022
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17. A data-driven disease progression model of fluid biomarkers in genetic frontotemporal dementia

Author: Ione O.C. Woollacott, Cristina Polito, Philip Van Damme, Mathieu Vandenbulcke, Rose Bruffaerts, Diana Duro, Chiara Fenoglio, David M. Cash, Maria Rosário Almeida, Sonja Schönecker, C. Ferreira, Sónia Afonso, Matthis Synofzik, Sara Prioni, Marta Cañada, Mikel Tainta, Miguel Tábuas-Pereira, Christin Andersson, Caroline Graff, Miguel Castelo-Branco, Enrico Premi, Håkan Thonberg, Fabrizio Tagliavini, Rachelle Shafei, Benjamin Bender, Ana Gorostidi, Maria João Leitão, Jennifer M. Nicholas, Elise G.P. Dopper, Silvana Archetti, Esther E. Bron, Ana Verdelho, Ron Keren, Isabel Santana, Christen Shoesmith, Pietro Tiraboschi, Sergi Borrego-Écija, Michela Pievani, Sandro Sorbi, Rick van Minkelen, Hans-Otto Karnath, Albert Lladó, Caroline V. Greaves, Jaume Olives, Alessandro Padovani, Miren Zulaica, Giuliano Binetti, Martin Rosser, Pedro Rosa-Neto, Vesna Jelic, Alexander Gerhard, Rosa Rademakers, Sandra E. Black, Wiro J. Niessen, Tobias Hoegen, Rhian S Convery, Janne M. Papma, Maria Carmela Tartaglia, Emily Todd, Adrian Danek, Rita Guerreiro, Robart Bartha, Linn Öijerstedt, Giuseppe Di Fede, Sebastien Ourselin, Núria Bargalló, James B. Rowe, Christopher C Butler, Giorgio G. Fumagalli, Valentina Bessi, Alberto Benussi, Nick C. Fox, Beatriz Santiago, Ekaterina Rogaeva, Alazne Gabilondo, Giacomina Rossi, Mircea Balasa, David L. Thomas, Benedetta Nacmias, Veronica Redaelli, Anna Antonell, Vikram Venkatraghavan, Jonathan D. Rohrer, Jackie M. Poos, Yolande A.L. Pijnenburg, Lieke H.H. Meeter, Carlo Wilke, Sandra V. Loosli, Elio Scarpini, Tobias Langheinrich, Alina Díez, Elisa Semler, Elizabeth Finger, Begoña Indakoetxea, Jessica L. Panman, Carolyn Timberlake, Gemma Lombardi, Luisa Benussi, Morris Freedman, Barbara Borroni, Ricardo Taipa, Johannes Levin, Thomas E. Cope, Paul M. Thompson, Giorgio Giaccone, Valentina Cantoni, Arabella Bouzigues, Jose Bras, Serge Gauthier, Andrea Arighi, Stefan Klein, Fermin Moreno, Markus Otto, Georgia Peakman, Emma L. van der Ende, David F. Tang-Wai, Sarah Anderl-Straub, Jason D. Warren, Alexandre de Mendonça, Camilla Ferrari, Elisabeth Wlasich, Catharina Prix, Michele Veldsman, Raquel Sánchez-Valle, Sara Mitchell, Carolina Maruta, Robert Laforce, Paola Caroppo, Jorge Villanua, Imogen J Swift, Harro Seelaar, Henrik Zetterberg, Simon Mead, Simon Ducharme, Myriam Barandiaran, Katrina M. Moore, John C. van Swieten, Gabriel Miltenberger, Mario Masellis, Timothy Rittman, Lize C. Jiskoot, Daniela Galimberti, Rik Vandenberghe, Carolin Heller, Stefano Gazzina, Aitana Sogorb-Esteve, Roberto Gasparotti, Martina Bocchetta, Neurology, Amsterdam Neuroscience - Neurodegeneration, Repositório da Universidade de Lisboa, Radiology & Nuclear Medicine, and Neurosurgery
Subjects: Oncology, medicine.medical_specialty, Medizin, tau Proteins, Disease, medicine.disease_cause, frontotemporal dementia, biomarker, disease progression model, event-based modelling, neurofilament light chain, Biomarkers, C9orf72 Protein, Complement C1q, Cross-Sectional Studies, Disease Progression, Glial Fibrillary Acidic Protein, Humans, Longitudinal Studies, Mutation, Frontotemporal Dementia, diagnosis [Frontotemporal Dementia], Settore BIO/13 - Biologia Applicata, C9orf72, Internal medicine, Medicine, ddc:610, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], business.industry, medicine.disease, Astrogliosis, genetics [tau Proteins], Cohort, Biomarker (medicine), Neurology (clinical), Sample collection, business, Frontotemporal dementia
Abstract: © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/ by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com, Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage frontotemporal dementia, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic frontotemporal dementia using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study. Two-hundred and seventy-five presymptomatic and 127 symptomatic carriers of mutations in GRN, C9orf72 or MAPT, as well as 247 non-carriers, were selected from the GENFI cohort based on availability of one or more of the aforementioned biomarkers. Nine presymptomatic carriers developed symptoms within 18 months of sample collection ('converters'). Sequences of biomarker abnormalities were modelled for the entire group using discriminative event-based modelling (DEBM) and for each genetic subgroup using co-initialized DEBM. These models estimate probabilistic biomarker abnormalities in a data-driven way and do not rely on previous diagnostic information or biomarker cut-off points. Using cross-validation, subjects were subsequently assigned a disease stage based on their position along the disease progression timeline. CSF NPTX2 was the first biomarker to become abnormal, followed by blood and CSF neurofilament light chain, blood phosphorylated neurofilament heavy chain, blood glial fibrillary acidic protein and finally CSF C3b and C1q. Biomarker orderings did not differ significantly between genetic subgroups, but more uncertainty was noted in the C9orf72 and MAPT groups than for GRN. Estimated disease stages could distinguish symptomatic from presymptomatic carriers and non-carriers with areas under the curve of 0.84 (95% confidence interval 0.80-0.89) and 0.90 (0.86-0.94) respectively. The areas under the curve to distinguish converters from non-converting presymptomatic carriers was 0.85 (0.75-0.95). Our data-driven model of genetic frontotemporal dementia revealed that NPTX2 and neurofilament light chain are the earliest to change among the selected biomarkers. Further research should investigate their utility as candidate selection tools for pharmaceutical trials. The model's ability to accurately estimate individual disease stages could improve patient stratification and track the efficacy of therapeutic interventions., This study was supported in the Netherlands by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813,733050103 and 733050513), the Bluefield Project to Cure Frontotemporal Dementia, the Dioraphte foundation (grant number 1402 1300), the European Joint Programme—Neurodegenerative Disease Research and the Netherlands Organisation for Health Research and Development (PreFrontALS: 733051042, RiMod-FTD: 733051024); V.V. and S.K. have received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 666992 (EuroPOND). E.B. was supported by the Hartstichting (PPP Allowance, 2018B011); in Belgium by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie; in the UK by the MRC UK GENFI grant (MR/M023664/1); J.D.R. is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH); I.J.S. is supported by the Alzheimer’s Association; J.B.R. is supported by the Wellcome Trust (103838); in Spain by the Fundació Marató de TV3 (20143810 to R.S.V.); in Germany by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198) and by grant 779357 ‘Solve-RD’ from the Horizon 2020 Research and Innovation Programme (to MS); in Sweden by grants from the Swedish FTD Initiative funded by the Schörling Foundation, grants from JPND PreFrontALS Swedish Research Council (VR) 529–2014-7504, Swedish Research Council (VR) 2015–02926, Swedish Research Council (VR) 2018–02754, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Swedish Demensfonden, Stohnes foundation, Gamla Tjänarinnor, Karolinska Institutet Doctoral Funding and StratNeuro. H.Z. is a Wallenberg Scholar.
Published: 2022
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18. Decision Aids for Shared Decision-making in Uro-oncology: A Systematic Review

Author: Britta Grüne, Anja K. Köther, Björn Büdenbender, Maximilian Lenhart, Johannes Huber, Georg W. Alpers, Maurice Stephan Michel, and Maximilian C. Kriegmair
Subjects: Male, musculoskeletal diseases, medicine.medical_specialty, Urology, 030232 urology & nephrology, Psychological intervention, MEDLINE, Context (language use), Decisional conflict, Cochrane Library, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Decision aids, Humans, Medicine, Bladder cancer, business.industry, Prostatic Neoplasms, medicine.disease, Checklist, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, Family medicine, Patient Participation, business, Decision Making, Shared
Abstract: Context Decision aids (DAs) aim to support patients in the process of shared decision-making for complex treatment decisions. To improve patient-centered care in uro-oncology, it is essential to evaluate the availability and quality of existing DAs. Objective To assess the quality of existing DAs for patients across the most prevalent uro-oncological entities. Evidence acquisition This study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. A systematic literature search (MedLine, Cochrane Library, Web of Science Core Collection, and CCMed) was conducted to identify DAs for treatment decisions for patients with prostate, renal, or bladder cancer. All studies reporting on the development or evaluation of DAs were included. The DAs were examined based on the International Patient Decision Aid Standards (IPDAS) and the evaluation studies were compared in accordance with Standards for Universal reporting of a patient Decision Aid Evaluations (SUNDAE). Evidence synthesis The literature search identified 1995 potentially relevant publications. Thirty-two studies reporting on 25 DAs met the inclusion criteria. Twenty-two DAs address prostate cancer, two renal tumor, and one bladder cancer. In the majority of DAs (n = 20), patients can enter individual data. A few (n = 6) DAs allow for personalization using a risk-adapted presentation of treatment options. The percentage of IPDAS criteria met in DAs ranged between 50% and 100% (median 87.5%), and the studies’ adherence to the SUNDAE checklist was between 62% and 96% (median 86.6%). Evaluation studies suggest that interventions are likely efficacious. However, a preliminary meta-analysis revealed no significant difference between "DA" and "usual care" for decisional conflict or decisional regret. Conclusions This review highlights that a number of well-developed DAs exist in urology. However, there is a need for specific instruments targeting kidney and bladder cancer. Personalization of tools and adherence to international standards of DAs should be further improved. Patient summary The majority of uro-oncological decision aids target prostate cancer, whereas fewer address kidney or bladder cancer. The quality of the existing instruments is high, but can be increased further to better address specific needs of individual patients.
Published: 2022
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19. Decreased Expression of Glial-Derived Neurotrophic Factor Receptors in Glaucomatous Human Retinas

Author: Markus H. Kuehn, Abhigna Akurathi, Erin A. Boese, Matthew M. Harper, Johannes Ledolter, and Randy H. Kardon
Subjects: Retinal Ganglion Cells, medicine.medical_specialty, Glial Cell Line-Derived Neurotrophic Factor Receptors, genetic structures, Receptor expression, Nerve fiber layer, Glaucoma, Ciliary neurotrophic factor, Retina, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Ophthalmology, medicine, Glial cell line-derived neurotrophic factor, Humans, Ciliary Neurotrophic Factor, Glial Cell Line-Derived Neurotrophic Factor, Receptor, biology, business.industry, Retinal, medicine.disease, eye diseases, Sensory Systems, medicine.anatomical_structure, chemistry, Retinal ganglion cell, biology.protein, sense organs, business, Ciliary Neurotrophic Factor Receptor alpha Subunit
Abstract: Purpose The purpose of this study was to examine the expression of glial derived neurotrophic factor (GDNF), the GDNF receptors GFRα1 and GFRα2, ciliary neurotrophic factor (CNTF), and the CNTF receptor CNTFRα in normal and glaucomatous human tissue. Methods Human retinas were collected from 8 donors that had been clinically diagnosed and treated for glaucoma, and also from 9 healthy control donors. Immunohistochemical analysis for each trophic factor and receptor was performed. The percent of each retinal section labeled with each antibody was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with measures of the subject's ocular histories. Results The percentage area immunopositive for GFRα2 was significantly decreased in the total retinal thickness containing all retinal layers and in the combined RGC complex + RNFL in glaucomatous eyes in both the peripapillary region and more peripheral retinal locations. We also observed a decrease in GFRα1 expression in the peripapillary RGC Complex + RNFL in glaucoma patients compared to healthy control patients. We also observed a relationship between GDNF and its receptors with several outcomes obtained from the medical record. No differences in CNTF or CNTFR labeling were observed. Conclusion Decreases in GDNF receptor expression in glaucomatous tissue may limit the potential for neuroprotective therapy by supplementation with GDNF.
Published: 2022
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20. Artificial Intelligence-Driven Video Analysis for Novel Outcome Measures After Smile Reanimation Surgery

Author: Zacharias Brugger, Jurij Kiefer, Steffen U. Eisenhardt, Verena K. Horner, Mark Fricke, Branislav Kollar, Johannes Zeller, Michael Gentz, and Laura Schneider
Subjects: medicine.medical_specialty, business.industry, Facial Paralysis, Outcome measures, medicine.disease, Smiling, Facial paralysis, stomatognathic diseases, Physical medicine and rehabilitation, Facial reanimation, Artificial Intelligence, Outcome Assessment, Health Care, Humans, Medicine, Surgery, business, Retrospective Studies
Abstract: Background: Since facial paralysis is a dynamic condition, the analysis of still photographs is not sufficient for measurement of facial reanimation outcomes. This study aimed at evaluating an arti...
Published: 2022
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21. Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study

Author: Waasila Jassat, Cheryl Cohen, Stefano Tempia, Maureen Masha, Susan Goldstein, Tendesayi Kufa, Pelagia Murangandi, Dana Savulescu, Sibongile Walaza, Jamy-Lee Bam, Mary-Ann Davies, Hans W Prozesky, Jonathan Naude, Ayanda T Mnguni, Charlene A Lawrence, Hlengani T Mathema, Jarrod Zamparini, John Black, Ruchika Mehta, Arifa Parker, Perpetual Chikobvu, Halima Dawood, Ntshengedzeni Muvhango, Riaan Strydom, Tsholofelo Adelekan, Bhekizizwe Mdlovu, Nirvasha Moodley, Eunice L Namavhandu, Paul Rheeder, Jacqueline Venturas, Nombulelo Magula, Lucille Blumberg, Shaina Abdullah, Fiona Abrahams, Vincentius Adams, Fhima Adnane, Sonia Adoni, Dieketso Melitta Adoons, Veronique Africa, D Aguinaga, Susan Akach, Prisha Alakram Khelawon, George Aldrich, Olatunde Alesinloye, Mathale Biniki Aletta, Mametja Alice, Tebogo Aphane, Moherndran Archary, Felicity Arends, Shireen Arends, Munonde Aser, T Asmal, Mohammed Asvat, Theunis Avenant, Muvhali Avhazwivhoni, Magnolia Azuike, Johanna Baartman, Dlava Babalwa, Johan Badenhorst, Miranda Badenhorst, Bianca Badripersad, Lalihla Badul, M Bagananeng, Mncedisi Bahle, Liezl Balfour, T C Baloyi, S Baloyi, Tinyiko Baloyi, Tshepo Mpho Baloyi, Thokozani Banda, Shimon Barit, Nicole Bartsch, Junaid Bayat, Siyabulela Bazana, Marlene Beetge, Nosindiso Bekapezulu, Rammala Belebele, Phala Bella, Zanenkululeko Belot, Lindi Gladys Bembe, Sonja Bensch, Gishma Beukes, Karla Bezuidenhout, Themba Bhembe, N A Bikisha, Ben Bilenge, Leesa Bishop, Baphamandla Biyela, Cyntheola Blaauw, Mark Blaylock, Nicola Bodley, Power Bogale, Sibongile Bokolo, Stefan Bolon, Mary Booysen, Eldereze Booysen, Lia Boretti, Paula Borges, Millicent Boshoga, Natasha Bosman, Lucinda Bosvark, Nicky Botes, Adele Botha, Chantall Botha, Jana Botha, Chantall botha, Mandlakayise Irvin Botha, Alet Botha, Janet Bradbury, Zandisile Breakfast, Maria Breed, Molele Brenda, Moshito Brice, Jolene Britz, Amanda Brown, T Buchanan, Thozama Bucwa, Crystelle Burger, Ziyanda Busakwe, Nosiviwe Bushula, Zinhle Buthelezi, Dumsile Buthelezi, Thubelihle Buthelezi, Mpumelelo Basil Buthelezi, Fundiswa Lidwina Buthelezi, Nadia Bux, Christoff Buys, Anneline Buys, Ernestina Caka, Armando Sanchez Canal, Sithole Caroline, Monrick Casper, Shannon Cawood, Oratile Cebisa, Nothando Cele, Sboniso Cele, Sthembile Goodness Cele, Mkhacani Chauke, Pinkie Chauke, Nevil Chelin, Xiaohui Chen, Venmalla Chetty, Kerisse Chetty, Christinah Cheu, Vindana Chibabhai, Takudzwa Chirima, Mantwa ChisaleMabotja, Charity Chivenge, Ngoasheng Choene, Mbali Nosisa Choko, Martin Choshi, Sabbir Chowdhury, Anastacia Christoforou, S L S Chuene, T S Chueu, Dale Cilliers, Vanessa Cilliers, Marcel Claassen, Jeané Cloete, Chantelle Coelho, Carol Coetzee, Hans Jurgens Coetzee, Christine Coetzee, Marelize Coetzee, Dane Coetzer, Sizwe Coka, M Colane, Herkulaas Combrink, Songezo Conjwa, Colleen Contrad, Faith Cornelissen, Leezelle Cronje, Christine Crouse, Tshidi Dabi, Ziyanda Dandala, Ziyaad Dangor, Gildenhuys Daniel, Ngwana Daniel, Alfred Daumas, Madelein Dauth, Mongalo David, Wayne Davids, Nozuko Daweti, Wandisa Dayile, B De Bruin, Karin De Klerk, Tanya De la Rosa, Marice de Nysschen, Marie De vos, Darien De Wet, Mohith Debising, Darshan Deenadayalu, Babalwa Dekeda, Mofokeng Desiree, Annelise Deysel, Abram Dhlamini, Makgethwa Dhlala Diala, Mathapelo Diale, Bella Diketane, Nosisa Dingani, Siyabonga Diniso, Lesego Diphatse, Anele Diya, Zihloniphile Dladla, Nompumelelo Dladla, Mlungisi Dladla, Patience Dladla, Baphilie Dlamini, Nonhlanhla Dlamini, Linda Dlamini, Nonzwakazi Dlamini, Wendy Dlamini, Ncomeka Dlamini, Siyabonga Dlamini, Nicodemus Dlamini, Lebohang Dlamini, Motshedise Dlamini, Babalwa Christine Dlava, Phikiwe Dlova, Lindiwe Dlozi, Maenetja Doreen, Vumile Doyi, Athini Doyi, Belinda Du Plessis, Johanna Aletta du Plessis, Eddie du Plessis, Nicolette du Plessis, Karin du Plessis, Briette du Toit, Narissa du Toit, Jabulile Dube, Athayanda Dubula, Msomi Duduzile, Sechaba Duiker, Unati Bongile Duma, Kholiwe Duma, Kella Dunne, Kholeka Dyantyi, Avile Dyantyi, Simphiwe Dyasi, Chauke Dyondzo, Phelisa Dyubhele, B J Dywili, Letitia Edwards, Madie Eksteen, Tersia Ellis, Tia Ellis, Glenda Emmerson, Theusia Enslin, Odimula Epule, Lana Erasmus, Mathonsi Erick, Lerato Etsane, Shimange Eunice, Zanele Fani, Mariette Ferreira, K L Finger-Motsepe, Fabion Floris, Tseko Fobo, Keresemetse Fokotsane, Duduzile Emmelda Fokwana, Genevieve Marion Fords, Juanita Fortein, Christine Fouche, Rulandi Fourie, Andrew Frean, Ludwig Fredericks, Wandile Funda, kabelo funjwa, Martha Futhane, Amanda Futuse, Dora Gabaediwe, Nonhlanhla Gabuza, Janycke Galant, Zanele Gama, Thobile Gano, Emma Cora Gardiner, Henri Gastrow, Kelly Gate, Ben Gaunt, Rikhotso Gavaza, Thapelo Gayi, Nkosinathi Gcakasi, Nomusa Gcobo, Leon Geffen, S Geldenhuys, Jenny George, Martha Gerber, Zolisa Getyengana, Nkululo Gigi, Radha Gihwala, Mitchell Gilliland, Zandile Gloria, Elitia Glover, Ellen Gokailemang, Suseth Goosen, Maria Gopane, Thandazile Gosa-Lufuta, Bernadett Gosnell, Sharleen Gouws, Christina Govender, Raksha Govender, Pearl Govender, Sally Govender, Roxanne Govender, K Govender, Savie Govender, Rashika Govinden, Luphumlo Gqabuza, Nomthandazo Gqaji, Maneo Gqetywa, Caroline Green, Nathan Green, Neera Green, Hendrik Grobler, Pamela Groenwald, Daniel Grootboom, Beatrice Gumede, Nomonde Gumede, Simphiwe Gumede, Slindile Gumede, Ntombikayise Gumede, Zenande Gumede, Thandiswa Gxotiwe, Makhubela H L, Nonhlanhla Hadebe, Skhumbuzo Hadebe, Christos Halkas, Ansie Hamer, Ebrahim Hamida, Juan Hammond, Sumayia Haniff, Annelise Hare, lorinda Hattingh, Thenjiwe Hendricks, Philip-George Henecke, Brends Henly-Smith, Glynis Herselman, Ansie Heymans, Chantel Heyns, Golekane Hlabahlaba, Lucky Hlabangwane, Simango Hlamarisa, Ntokozo Hlanzi, Hlengiwe Hlela, Katlego Hlokwe, Thembinkosi Hlongwa, Anele Hlongwana, Themba Hlubi, Tozama Hobo, Nare Nathaniel Hopane, Mariska House, Catharina Hudson, Marinda Huysamen, Jezreen Indheren, Samantha Ingle, Gavin Isaacs, T S Thekiso Isaacs, Maringa Itumeleng, Karien J van Rensburg, Saloshni Jackson, Neziswa Jacob, Burton Jacobs, Tshireletso Jacobs, Gugulethu Jacobs, Mesadi Jaftha, Zimkhitha Jaji, Sibusiso Jali, Gcobisa James, Gillian January, Andiswa Jeke, Laurent Jeremiah, L S Jeremiah, Mubeen Jhetam, Maureen John, Chuene John, Thandiwe Jola, Yolande Jonas, Anovick Jonas, Amilcar Juggernath, Eileen Kaba, Venetia Kabo, Disebo Kadi, Karabo Kaizer, Moshaya Peter Kambule, Lorraine Kapp, Tshepo Kau, Nchabeleng Keneth, O Kgabi, Tebogo Audrey Kgafela, Vincent Kgakgadi, Isabella Kgaswe, Tsholofelo Kgathlane, Vuyelwa Julia Kgetha, Mmaselloane Kgomojoo, B Kgoro, Christinah Kgosiemang, Gloria Kgosiencho, Stephen Khambula, Ariffa Khan, Refemetswe Khanare, Ncamsile Khanyase, Nokwethemba Khanyile, Fillip Kharatsi, Simangele Khawula, Themba Khohlakala, Letitia Khomo, Isabel Khoza, Sinethemba Khoza, Nombulelo Khukule, Busisiwe Khumalo, Tracy Khumalo, Zinhle khumalo, Vuyelwa Khumalo, Delisile Khumalo, Lebohang Khumalo, Boitumelo Khumalo, Thuli Khumalo, Gugu Khumalo, Bongiwe Khuzwayo, Thembhelihle Khuzwayo, Hennie Kidson, Jesne Kistan, Gugu Klaas, Marilyn Klassen, Josehine Koeberg, Marizel Koen, Simphiwe Koena, Ina Kok, Imraan Kola, Karabo Kolokoto, Ramachandra Konar, Dr Kotsedi, Jaline Kotze, Martins Koupis, Helen Kritzinger, Marlize Kruger, Henk Kruger, Tlangelani Kubayi, Thabisile Kubeka, Nonjabulo Kubheka, Melusi Kubheka, Sibusiso Clifford Kubheka, Erol Kubheka, Monica Kumalo, Thulani Kunene, Siphilile Candy Kunene, Yvette Kunneke, R P Kupa, Rachel Kutama, Nompumelelo Kwakwazi, Lwanele Kweyama, Maureen Labuschagne, Marina Labuschagne, Prabha Lakshman, Lungelo Lamani, Thembela Lamani, Naomi Langa, Khangelani Langeni, Aphelele Langeni, Nwabisa Hazel Langeni, Gena Langeveldt, Anchen Laubscher, Laetitia Le Roux, Magagane Leah, Collen Lebea, Sello Lebea, Viyella Phumla Cynthia Lebenya, Lorraine Lebogang, P K Leboho, Chantel Lee, Kelebogile Rejoice Lefakane, Zandile Legoabe, Patrick Lekala, Motsitsi Lekhoaba, Tanki Shadrack Lekunutu, Galaletsang Lerefolo, N Letebele, Tsepo Patric Lethoba, Emission Letlalo, Ofentse Letlhage, D S V Letshufi, Dineo Fiona Letsoalo, Seleka Jones Letsoalo, Pennelope Letsoalo, Getrude Letwaba, Sobekwa Linda, Katleho Lipholo, Sabata Litabe, Harsha Lochan, Linda Lomax, Francina Lombaard, Elmarie Loots, Ariana Lourens, Celeste Louw, Rianna Louw, Zikhona Lubambo, Msebenzi Moises Lubambo, Gregory Ludada, Michael Lukas, Thembela Lungu, Nomvume Lupindo, Emmah Lusenga, Happiness Luthuli, Zoleka Sylvia Luvuno, Gwangwa M H, Mustafa Maarman, Buyisiwe Mabaso, Cynthia Mabaso, Morena Mabitle, Grace Mabogoane, Kgakgamatso Mabone, Rueben Mabuza, Velaphi Mabuza, Mogantla Madiseng, Thobile Madlala, Mashooase Madolo, Thabiso Madonsela, Lesetsa Madubanya, Amukelani Maepa, Namhla Mafumana, Caroline Mafumo, Pumeza Magadla, Viscah Magale, Nompumelelo Magaqa, Oberholzer Magda, Rakgoale Magdeline, Tswai Maggie, Bongeka Maginxa, Cathrine Maite Magoba, Caroline Magongwa, Agretia Magubane, Agretia Ntombizodwa Magubane, R Magwai, D I Mahabane, Padmini Mahabeer, Elsie Mahadulula, Lungiswa Mahanjana, Amy Maharaj, Qedusiza Mahlambi, Yvonne Mahlangu, Lerato Mahlangu, Ntombifikile Mahlangu, Makhosazana Mahlangu, Mahlatsi Mahlangu, Penelope Mahlasela, Thosago Mahlatse, Regina Mahlobo, Dikhing Mahole, Adam Mahomed, Mapeu Debora Mahubane, Peter Mahume, Lehlogonolo Maifo, Vincent Maimane, Petunia Maimele, Phakoe Maine, Patricia Senyanyathi Mainongwane, Nomalungisa Majamani, Amahle Majozini, Noluthando Makalima, Nomfundo Makam, Khanyisa Makamba, R Makan, Mashiane Makarapa, Malesela Makgahlela, Mogoiwa David Makgisa, Makgoba Makgomo, M A Makgopa, Mabone Makhalema, Lindokuhle Lizo Makhanya, Philile Valentia Makhanya, Tolerance Makharaedzha, Nathi Makhathini, Elizabeth Makhesi, Cinile Makhubela, Nkululeko Freedom Makhunga, Nomalinge Makhupula, R R Makhura, Rangwato Makola, Zingisa Makuba, Asanda Makubalo, Lonwabo Makumsha, George Makuya, Levy Mmachuene Malaka, Themba Malangeni, M L Malatji, Pelonomi Malebana-Metsing, Malek Malek, Luthando Malevu, Juanita Malgas, Dimakatso Malgas, Paul Makgasane Malope, Monyeki Malose, Katekani Maluleke, Kato Mambane, Nthabiseng Mamorobela, Kukami Manamela, Tshepo Manana, Sathiel Maneto, Aron Kabelo Manganye, Pheto Mangena, Anna Mangoale, Tinotenda Florence Mangozho, Pariva Manickchund, Zandisile Mankayi, Arthur Manning, Kelebogile Manyaapelo Manyaapelo, Tabea Manyane, Zoliswa Manzana, Milton Manzini, Busisiwe Mapasa-Dube, Siboniso Maphumulo, Ntombifuthi Maphumulo, Sindy Maponya, Khomotso Mumsy Maponya, Napjadi Maponya, Lami Maqubela, Lizeka Maqubela, Vuyo Maqungo, Marisa Marais, Chantal Marais, Nondumiso Maramba, Annelize Mare, Madumetsa Maredi, Afikile Martins, Johanna Marule, Refilwe Marumo, N N Masakona, Kedibone Vincentia Masehla, Eric Maseko, Tshilidzi Maselesele, Mojalefa Maselo, M Maseloa, M E Masemola, Thembi Masemola, Bella Mashaba, James Mashangwane, Mantebele Mashao, Shalom Mashego, Lerato Mashele, Ester Mashiane, Joyce Mashibini, J Mashilo, Tumi Mashiloane, Charity Mashishi, Ngazibini Mashiyi, Khomola Mashudu, Aluwani Masindi, Caroline Maslo, Nduduzo Masondo, Dumisile Masuku, Cry Matamela, Mirriam Matandela, Nontokozo Mathabela, T Mathabi, Keitumetse Mathe, Mathabo Mathebula, Catherine Mathebula, Mdungazi Andres Mathebula, Nqobizwe Mathenjwa, Jane Mathibe, Lebohang Mathibela, Makwela Mathilda, Khakhu Mathiva, Mokgadi Alinah Mathobela, Fikile Pearl Mathonsi, K P Mathonsi, Katlego Mathosa, Noluvo Matiwane, Emma Matjeke, Bella Matjiane, Thabang Matjila, Chidi Matlala, Petlo Matome, Nolusindiso Matoti, C Matseliso, Dineo Matsemela, Phumeza Matsha, Gaalebale Prudence Matshediso, Motsumi Matshediso, Esther Matshela, Bongeka Mavuma, Pearl Mavundla, Nomthandazo Mavuso, Lovender Mawasha, Rebecca Mawelela, Nelisiwe Mazibuko, Phumlani Mazibuko, Lindiwe Mazubane, Bavumile Mbanjwa, Ayanda Mbasa, Nosimilo Mbatha, Zanele Mbatha, Rudolph Zenzele Mbatha, Gift Mbedzi, Tatenda Trevor Mbizi, Khumbulani Mbonambi, Nondumiso Mboniswa, Nomfanelo Mbonisweni, Jody Mbuilu, Siyabonga Mbulawa, Zama Mbutho, Natasha Mbuzi, Nonkululeko Mchunu, Cyprian Mchunu, Nokuzola Mchunu, Masesi Thandeka Mchunu, Vuyokazi Mciteka, Solly Mdaka, Neho Mdakane, Siyabonga Mdediswa, Melusi Mdima, Nozipho Mdima Masondo, Siviwe Mdindana, Ntombizikhona Mdleleni, Sibusiso Mdletshe, Gcobisa Precious Mdoda, Ntombi Mdolo, Anele Mdontsane, Ruchikas Mehta, Philile Rittah Memela, Masande Methuse, Keatlaretse Metshile, Pheliswa Metuse, Anton Meyer, Gavin Meyer, Cameron Meyer, Sisonke Mfazwe, Andiswa Mfecane, Bongeka Mfecane, Nelisiwe Mfeka, Busisiwe Mgaga, Thandiwe Portia Mgauli, Thembekile Mgedezi, Vuyokazi Mgedezi, Kalipile Mgevane, Bongni Mgiba, Babalwa Mgoduka, Patrick Mhlaba, Zeldah Mhlaba, Ntombizodwa Mhlanga, Vangile Mhlinza, Nokuthula Mhlongo, sibongiseni Mhlongo, Unamandla Mhlotshana, Mabaso Mikateko, Helena Minnie, Karen Mintoor, Bongi Miyeni, Mabelane M J, Rosy Mjethu, Gloria Mkhize, Mvuselelo Mkhize, Ntokozo Siyabonga Mkhize, Victoria Mkhize, Nomkhosi Mkhize, Nokuthula Mkhize, Mathini Mkhwanazi, Nolwandle Mkile, Kholofelo Mkise, Nokwandiso Mkiya, Pearl Mkongi, Mnonopheli Mkungeka, Hlomile Mlahleki, Nolukholo Mlibali, Sakhumzi Mlungwana, Jonas Mmachele, Mashatole Mmateka, Molebatsi Mmokwa, Thembisa Mmutlane, Zanele Olive Mndebele, Nonhlanhla Mngomezulu, Noluthando Millicent Mnguni, Pumza Mngunyana, Nomxolisi Mngunyana, Ntombebongo Mngxekeza, Zenzele Mnisi, Hlengiwe Precious Mnqayi, Phumzile Mnqayi, Thabiso Mntungwa, Siya Mnyaka, Ntombikayise Mnyakeni, Vuyani Mnyamana, Nomzingisi Mnyipika, Koena Moabelo, Mmakgoshi Alseria Moatshe, Jennifer Mochaki-Senoge, Sharon Moche, Tebello Mocwagae, Koeikantse Modibane, Tebogo godfrey Modimoeng, Obakeng Modisa, Itumeleng Modisane, Olebogeng Modise, Makaepeaa Flovia Modjadji, Sharon Modupe, Maja Moeketsi, Ntswaki Moeketsi, Kereditse Kingsley Moeng, Naledi Nthabiseng Mofamere, Samuel Mofokeng, Thabo Mofokeng, Jonas Mofomme, Vicky Mogakane, Lehlohonolo Mogale, Audrey Mogapi, Thomas Mogashoa, Mphaka James Mogatla, Kgaladi Mogoale, Dikeledi Maggie Mohajane, Nkuba Mohapi, Mthoamihla Mohatsela, Irene Mohlala, Daphney Mohlala, Mpho Mohlamonyane, Bonolo Millord Mohutsiwa, Selemela Moipone, Tshepang Moisi, Nelly Mojalefa, Vuyo Moji, Buhle Mokangwana, Matloa Mokgabo, Manaka Mokgaetji, Jane Mokgaotsi, Neo Theodore Mokgoro, Thalitha Mokhatla, Lerato Lovedalia Mokhele, Sheila Mokhema, Mamoya Mokoena, Mojalefa Mokoena, Lleka Mokome, Cynthia Mokone, Ipeleng Mokono, Thabiso Mokonyama, Josiah Mokori, Dolores Mokuena, Danny Mokumo, Oddy Mokwena, Kgaogelo Mokwena, Kgantshi Sam Mokwena, Lebogang Mokwene, Thato Elliott Molate, Ditoche Molebalwa, Boingotlo Molefe, Kgopa Stanley Molehe, Kgomotso Moleme, Sarah Moliane, Fanyana Moloi, Retshepile Joseph Molorane, Glenda Tsholanang Molotsi, Lerato Molukanele, Joy Monareng, Thapelo Moncho, Modiadie Monica, Refilwe Monnane, Andile Monqo, Neo Montewa, Kgalalelo Montsioa, Reitumetse Monyaki, Masekhobe Jeanett Monyane, Lipson Monyela, Yudeshan Moodley, Kriesen Moodley, Kaira Moodley, Boitumelo Donald Mooka, Prea Moonsamy, Simmi Moopanar, David Moore, Lineo Mophethe, Tshegohatso Moremedi, Kealeboga Moremong, Nthangeni Morgan, Egma Moripa, Lulamile Morris, Me. A.M. Mosala, Thabo Mosana, Alice Mosase, Yolanda Mose, Maponya Mosehlo, Mothusi Moseki, Mojalefa David Moshabe, D A Moshai, Mbulelo Moshani, Pelisa Moshani, Ledwaba Mosima, Ezrom Mosima, M P Mosoma, Lebohang Motaung, Mokete Motaung, Thozama Charmain Motaung Xhama, Purine Khethiwe Motha, Lerato Motimele, Boitumelo Motimeng, Shirley Motladiile, Otsile Motlhabane, Joshua Motlhamme, Mandla Motloba, Kagiso Motse, Sophia Motshegoa, Edward Moutlana, Irma Mouton, Zanele Moya, Nomonde Moyake, Maja M P, Jenny Mpete, Luamba Meltha Mpfuni, Seputule Mphahlele Mphahlele, Mashadi Mphake, Ephraim Letlhogonolo Mphanya, Mashudu Mphaphuli, Tebogo Chwene Mphela, MS Mpontshane, Thabile Mqotyana, Babalwa Mqungquthu, Noluthando Busane Msane, Malusi Mseleku, Sibusiso Msibi, Mancele Msibi, Thulisile Msibi, Siyabonga Linda Msibi, Clement Nhlanhla Msiza, Lungelo Msomi, Mandlenkosi Mtatambi, Thembisa Mthathambi, December Mthembu, Nhlahla Mthembu, Fezile Mbali Mthembu, Lungiswa Mthembu, Nompumelelo Petunia Mthethwa, Khulekani Mthimkhulu, Lungani Percival Mthuli, Ashley Mthunzi, Xolani Sydney Mtolo, Nomonde Precious Mtolo, Linda Mtshali, Neliswa Mtwa, Fezeka Mtyobile, Kanyisa Mtyobile, Mpfariseni Mudau, Magwabeni Muemeleli, Isaac Mulaudzi, Rebecca Mulaudzi, Mhlelekedzeni Mulaudzi, Dakalo Rejoyce Muligwe, Blessing Muponda, Mmbangiseni Stella Mushadi, M Mushid, Konanani Muthaphuli, J Muthavhine, Mpho Muthika, Samkelisiwe Mvelase, Vusi Mvelase, Laurent Kayumba Mwehu, Thabile Myaka, Magriet myburgh, Zimkhitha Mzamo, Fezeka Mzawuziwa, Mfundo Lunga Mzini, Oscar Mzizana, Ntokozo Mzobe, Thokozile Mzobe, Zamaswazi Mzobe, Mtimkulu Mzwandile, Fathima Naby, Keshnee Naicker, Pregashnie Naicker, Saroja Naicker, Pershen Naicker, Saiyen Virgil Naicker, Ria Naidoo, Sam Naidoo, Mergan Naidoo, Kamalambal Naidoo, Aroomugam Naidoo, Sivuyile Naku, Firdose Nakwa, Masoga Nancy, Rita Nathan, Maritsa Naude, Gcobisa Ncaza, Aviwe Ncaza, Relebohile Ncha, Yanelisa Ncoyini, Snothile Ncube, Mrs Ndaba, Vusumuzi Ndaba, Mmapula Ndaba, Siziwe Ndawonde, Ziphozihle Ndevu, Nonhlanhla Faith Ndhlovu, Simphiwe Ndima, Sindisiwe Ndlela, Thobsile P Ndlela, Nobuhle Ndlovu, Nwabisa Ndlovu, Virginia Dipuo Ndlovu, Sombekhaya Ndlumbini, Khululiwe Nduli, Priscilla Nontokozo Nduli, Michael Ndwambi, Jeremy Nel, Rina Nel, Lizelle Nel, Ntsundeni florah Nemanashi, Usinkhangwe Nyaphophi Nemudivhiso, Joyce Nemutavhanani Nemutavhanani, Jabu Nene, Xolani Nene, David Netshilonga, Rendani Netsianda, Charmaine Newton, Vuyo Leroy Ngalo, Ncumisa Ngani, Thabisa Monica Ngcakaza, Thamela Ngcobo, Trulove Nonhlanhla Ngcobo, Richards Ngcobo, Gcinile Ngcobo, Guguletu Ngcobo, Thozama Ngetu, Pinkie Ngewu, Tshepo Ngobeni, Providence Ngobeni, Khanyisile Ngobeni, Prudence Ngobeni, Thembisile Ngobese, Tracy Ngomane, Nolusindiso Ngondo, Nokukhanya Ngubane, Sithembiso Ngubane, Ntombizodwa Praxedise Nguse, Tholakele Ngwane, Elizabeth Ngwasheng, Siphamandla Ngwenya, Gugu Ngwenya, Nomthandazo Ngwenya, Themba Ngwenya, Eva Ngwenya, Zintlanu Ngxola, Tshegofatso Nhabe, Jabulile Nhlabathi, Ishmael Nhlangwana, Sithembile Nhlapo, Matlala Nick, Vicky Niemand, Carina Nienaber, Louise Nix, Chumisa Njikelana, Masiza Njomi, Lucia Nkabinde, M NKABINDE, Boitumelo Nkabiti, Gugu Nkabule, Mankopodi Nkadimeng, Nonkanyiso Nkanjeni, Palesa Portia Nkatlo, Bongani Nkewana, Audrey Nkhwashu, Ngokoana Nkoana, Mmathapelo Nkoane, M Nkogatse, Fezile Nkomo, Ntando Nkomo, Nontobeko Nkonyane, Sydney Nkosi, Ntombikayise Nkosi, Phumzile Nkosi, Ntombifuthi Nkosi, TINTSWALO NKOSI, ML Nkosi, Godfrey Nkosi, Amukelani Nkosi, Fikile Vinoliah Nkosi, Mbali Nkosi, Nomcebo Lucia Nkosi, Siphokazi Nkosi, Amanda Nkuhlu, Phumzile Nkumane, Malebo Nkuna, Wendy Nkwakwha, Sesi Noge, Elizabeth Nolte, Peko Nomawabo, Malibongwe Nombita, Nandipha Nophale, Jeanetta Nothnagel, Bongiwe Novokoza, Zanele Nqaphi, Thobekile Nqondo, Siphokazi Nqwelo, Nkoana N S, Sindiswa Ntabeni, Mr Ntabeni, mawethu Ntampula, Mthutuzeli Ntebe, Mokwabo Ntela, Hezekiah Ntimbane, Xolisa Ntintsilana, Patrick Ntleki, Zanele Ntobela, Bandile Ntombela, Zamaswazi Ntombela, Khonelihle Zandile Ntombela, Praisegod Samkelo Thobani Ntombela, Lindiwe Ntonintshi, Dipuo Ntseane, Thobeka Ntseane, Xolelwa Ntsham, Mbalenhle Ntshele, Amanda Ntshewula, Zinzi Ntsoko, Athini Ntsoto, Nomsa Ntuli, Nokwazi Ntuli, Nomvula Ntuli, Andrew Diffar Ntuli, Faith Ntuli, Margrit Nurnberger, Ntsikelelo Nxala, Sithandiwe Nxasane, Thanda Nxumalo, Xolani Nyathi, Nontobeko Nyawula, Nhlakanipho Nzama, Maila Nkuneng Obed, Florence Ogwal, Maureen Olifant, B Oliphant, Monota Olive, Kagisho Olyn, Raymond Omoighe, Phumeza One, Ratombo Oscar, Nkuna Owen, Mailula P, Nalini Padayachee, Vasaily Padayachy, Ntombizakhe Pakade, Mosiuoa Palime, Jane Palisa, Lesenyeho Parkies, Andy Parrish, Nilesh Patel, Anastasia Pather, Mkhombo Tsakani Patience, Marisa Patzke, Akhumzi Pawuli, Ntandokazi Pelako, Phaswana Sibasa Penrose, Litha Peppeta, Santosh Pershad, Makheda Pertunia, Nkuna Pertunia, Dane Perumal, Mongameli Peter, Justin Peters, Vatiswa Petlane, Harideen Petrus, Kgomotso Phahladira, Matebesi John Phakisa, R Phale, Livhuwani Phathela, Sekate Daniel Phillip, Beverly Phiri, Mapule Precious Phiri, Thapelo Phokane, Frank Phokoane, Moele Pholosho, Sekoro Phooko, Sekodi Geoffrey Phooko, Maponya Phutiane, Faiza Pillay, Melanie Pillay, Sayuri Pillay, C R Pillay, Zikhona Plaatjie, James Pootona, Samantha Potgieter, Marius Potgieter, Mulaudzi Mulatedzi Precious, Paul Janus Pretorius, Hans Prozesky, Mokhethi Pule, Jayshina Punwasi, Dot Putzier, Lutho Qankqiso, Siphokazi Qebedu, Phozisa Qhola, Ntombesithathu Qotoyi, Sipho Victor Qotso, Zanele Qwabe, Helena Rabie, Phoebe Rabothata, Christina Rachoene, Mteteleli Radana, Maria Radebe, Dr. Valentino Radebe, Nonkululeko Radebe, Ella Radinne, Sherly Raduvha, Shamintha Raghunath, Claudine Rajagopaul, Mary Rakgwale, Malumbete Michael Ralethe, Kenneth Ralimo, Motlalepule Ramafoko, Maduvhahafani Ramagoma, Charlotte Raman, Dr Ramavhuya, Molly Rambally, Nivasha Ramdeen, Tanusha Ramdin, Sharita Rameshwarnath, Yeishna Ramkillawan, null Ramotlou, Faith Rampedi, Vijayluxmi Rampersad, Avhashoni Ramuima, Noluthando Ranone, Mabohlale Portia Rapasa, Mpharoane rapelang, Nika Raphaely, Lesiba Rashokeng, Caroline Rashopola, Tebogo Ratau, M Ratau, Mpfariseni David Ratshili, Elmari Rautenbach, Rofhiwa Ravele, Johannes Reachable, Peta Mmalahla Rebecca, Kessendri Reddy, Andrew Redfern, Robertha Reed, Mumsy Rees, Dr Reji, Gary Reubenson, Veena Rewthinarain, Nkonayani Rhulani, Mufamadi Richard, J S Rikhotso, Shatimone Beverley Rikhotso, Lavhelani Ndivhaleni Robert, Noncedo Roto, Gideon Ruder, Kapil Rugnath, Lizette Ruiters, Mina Ruiters, Sue Russell, Lynn Ruwiza, Molokoane R Y, Mandy Saaiman, Emmanuel Sabela, Lerato Sadiq, Litha Saki, Hyppolite Salambwa, Menitha Samjowan, Nazlee Samodien, Rakgolele Samuel, Fakudze Sandile, Cekuse Sanelisiwe, Mandlankosi Sani, Simangele Sawuka, Lelani Schoeman, Magriet Scholts, Ronel Schroder, Mamotetekoane Sebalabala, Selwalenkwe Collet Sebati, Jacoline Seboko, Wilheminah Sebuthoma, Annah Segami, Ruth Segokotlo, MR Sehloho, Khutjo Seisa, Antony Sekgobela, Monica Sekhosana, John Sekonyela, Mpho Sekoto, Naledi Sekulisa, Mokgadi Vanessa Sekwadi, Lebogo Selaelo, Johannes Selatlha, Kgomotso Selekolo, William Selfridge, Lucy Semenya, Ivy Sengakane, Masabata Sengata, Petronella Sentle, Malebo Seoketsa, Pratheesha Seonandan, Thomas Mambushi Serumula, Nkululeko Setheni, Refiloe Setlale, Tumediso Setlhodi, Barbara Setlhodi, Robert Setloghele, Aarthi Sewpersad, Ryan Sewpersadh, Phumlile Shabalala, Owen Shabangu, Kungesihe Shabangu, Harriet Sbonangaye Shabangu, Thokozani Shabangu, Clifford Shadi, Hasifa Shaik, Tseliso Shale, Qedani Shandu, Nomvelo Shandu, Ntswaki Marcia Shange, Abongile Shenxane, A Sherriff, Sebenzile Shezi, Thenjiwe Shezi, Scally Shihangule, Cheyeza Shikwambana, Lungisani Shoba, Kamogelo shokane, Nora Sibande, Lydia Sibeko, Xolani Sibeko, Zanele Sibiya, Mncedisi Sibiya, Sphamandla Sibuta, Thembakazi Sifumba, Sipho Sigcau, Lutho Sigila, Kayakazi Sihentshe, Bongani Sihlangu, Daisy Sikhakhane, Shaun Nhlanhla Sikhakhane, Mbali Siko, Sipho Sikonje, Khumbulekile Simanga, Nomsa Simango, Thulisile Simela, Ntombikayise Simelane, Sashah Singh, Marjorie Singh, Ragani Singh, Shash Singh, Anita Singh, Hitekani Sithole, Senzekile Sithole, Ntokozo Danielle Sithole, Koketso Maxwell Sithole, Jonnie Situma, Annie Sivraman, Katekani Siwela, Nonqubela Siyewuyewu, Maweya Sizeka, Nonceba Siziba, Andrew Skhosana, Khanyisile Skhosana, Rorisang Skhosana, Tandiwe Skoko, Sunet Slabbert, Ntombela Smangaliso, Christine Smedley, Lydia Smit, Natassia Smit, Lizelle Smit, Michelle Smit, Fasie Smith, Lizzie Smith, Sunell Smith, Cassius Smith, Stefan Smuts, Ayanda Sofe, Khobane Solomon, L J Solomon, chauke Sombani, Richard Songca, Anga Sontamo, Supriya Soorju, Zubenathi Sopazi, Brian Soqasha, Bongiwe Sosibo, Ntsika Sotsaka, Mandy Soula, Simon Spoor, Sarah Stacey, Asanda Stali, Mutele Mmboniseni Stephina, Myra Steup, Sinoxolo Steven, AW Stevens, Vincent Stevens, Dewald Steyn, Bianca Steyn, Pat Stocks, Henk Stolk, Alida Stoltz, Renate Strehlau, Anneke Stroebel, Loraine Strydom, Jean-Marie Strydom, Anton Strydom, Ursula Strydom, Midhu Sunnyraj, Nwabisa Swana, Winnie Swanepoel, Suzan Swanepoel, Elsie Swartbooi, Estley Swartz Swartz, Casandra Syce, Shihambi T E, Joyce Tabane, N E Tabane, Mrs Tawana, Ntene Tebello, Siphosetu Wiseman Tembe, Samantha Terblanche, Ntombifuthi Thabede, Nkhumeleni Thabelo, Sibusiso Thabethe, Lekhanya Thabo George, Keorapetse Thare, Makofane Thebogo, Lerato Thekiso, Lloyd Theko, Celimphilo Zandi Themba, Danie Theron, Henda Theron, Ilze Theron, Thandiwe Thingathinga, M M Thlabadira, Dikeledi Thoka, Zanele Thokwana, Gustav Thom, Mamphot Joel Thubakgale, Theodora Thwala, P Thys, Monethi Tieho, Matodzi Timothy, Ndlovu Tintswalo, Babalwa Tivana, Molefi Tladi, Bongiwe Tokota, Simthandile Toni, Ariel Torres, Mande Toubkin, Marinda Tsatsi, Khanyisile Tshabalala, Nozibele Tshamase, Gontse Tshefu, Makgoga Tshegofatjo, Given Tshikomba, Thapelo Tshilo, Lerato Tshira, S T Tshirado, Maipfi Tshisikule, G Tsoke, N TSOKE, Alatha Tsoko, Mosele Tsotetsi, Sandeva Tsubella, Noxolo Tuswa, Maipato Tutse, Nomayenzeke Tutu, Sphephelo Twala, Nhlanhla Twala, Simphiwe Twala, John Ubisi, Tefo Unathi, A Van Aswegen, Marietjie van der Merwe, Trudie van der Merwe, Patience van der Plank, Elmarie van der Spuy, Linda Van Der Westhuizen, Adele Van Der Westhuizen, Talana van der Westhuizen, Mene van der Westhuyzen, Thea Van Dyk, Ingrid van Heerden, Ryno van Jaarsveld, M Van Lill, Heidi van Niekerk, Ben van Niekerk, Amanda van Rensburg, Judy van Schallwyk, Zeitschke Yarnrich Van Sensie, Magda van Vuuren, Cloete van Vuuren, Olga Funiswa Vandu, Mandisa Vane, Lucia VanZyl, Ebrahim Variava, Mariam Veerus, Nokhwezi Velapi, Sebina Veleko, Z Velezantsi, Retha Venter, Corlia Vergottini, Inga Vermeulen, Liabara Lufuluvhi Vidah, Bongani Vilakazi, Treasure N Vilakazi, Mbalenhle Precious Vilakazi, Karen Viljoen, Werner Viljoen, Zuretha Volschenk, Angelo Vos, Matlala V V, Jacques Walters, Kate Webb, John Welsh, D Wessels, Judy Wheller, Fundile White, Priscilla White, Carmen Whyte, Ansie Willemse, Sape William, Daniel Williams, Kamielah Williams, Mercia Williams, Anne Williamson, Cherade Wilson, Boipelo Wolff, Michelle Wray, Ntombizonke B Xaba, Thabang Jabulani Xaba, Thanks Xiniwe, Mtshali Xoliswa, Funokwakhe Xulu, Gibson Xulu, Sandlakazi Yam, NM Zakhura, Mashela Zareloa, Sive Zinto, Dyibeni Zinziswa, Lulamile Ziselo, Zakhele Zitha, Emmanuel Zitha, Anele Zokufa, Innocent Zondi, Sikhumbuzo Bernard Zondi, Sbuyi Zondi, Thulani Zondi, Wandiswa Zongola, Liesl Zühlke, Zandile Zulu, Lungelo Zulu, Thandeka Zulu, Slindili Zulu, Nkosinathi Zulu, Angel Zuma, Precious Zungu, Pamela Zungu, Melusi Zungu, Priscilla Zungu, Bongo Lihle Zwakala, Antonia Zwane, Promise Zwane, Muziwendoda Zwane, Hlengiwe Priscila Zwane, and Nomgcobo Zwane
Subjects: Male, Pediatrics, medicine.medical_specialty, Tuberculosis, Epidemiology, Immunology, HIV Infections, Comorbidity, Disease, Cohort Studies, South Africa, Risk Factors, Virology, Diabetes mellitus, Prevalence, Humans, Medicine, Hospital Mortality, Asthma, SARS-CoV-2, business.industry, Public health, COVID-19, Articles, Odds ratio, medicine.disease, Infectious Diseases, Anti-Retroviral Agents, Female, business, Cohort study
Abstract: Summary Background The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15–49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. Methods In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. Findings Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27–1·43), past tuberculosis (1·26, 1·15–1·38), current tuberculosis (1·42, 1·22–1·64), and both past and current tuberculosis (1·48, 1·32–1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22–1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals. Interpretation Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment. Funding South African National Government.
Published: 2021
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22. Comparison of the function and structural integrity of cryopreserved pulmonary homografts versus decellularized pulmonary homografts after 180 days implantation in the juvenile ovine model

Author: Christiaan Johannes Jordaan, Dreyer Bester, Francis E. Smit, Jacqueline Goedhals, Johannes Jacobus van den Heever, Lezelle Botes, Angelique Lewies, and Pascal M. Dohmen
Subjects: Cryopreservation, Pulmonary Valve, Transplantation, Pathology, medicine.medical_specialty, Sheep, Decellularization, business.industry, Cold ischaemia, Biomedical Engineering, Structural integrity, Cell Biology, Allografts, medicine.disease, Biomaterials, Extracellular matrix, Calcium content, Collagen network, medicine, Animals, Transplantation, Homologous, Collagen, business, Calcification
Abstract: Homograft availability and durability remain big challenges. Increasing the post-mortem ischaemic harvesting time beyond 24 h increases the potential donor pool. Cryopreservation, routinely used to preserve homografts, damages the extracellular matrix (ECM), contributing to valve degeneration. Decellularization might preserve the ECM, promoting host-cell infiltration and contributing towards better clinical outcomes. This study compared the performance of cryopreserved versus decellularized pulmonary homografts in the right ventricle outflow tract (RVOT) of a juvenile ovine model. Homografts (n = 10) were harvested from juvenile sheep, subjected to 48 h post-mortem cold ischaemia, cryopreserved or decellularized and implanted in the RVOT of juvenile sheep for 180 days. Valve performance was monitored echocardiographically. Explanted leaflet and wall tissue evaluated histologically, on electron microscopical appearance, mechanical properties and calcium content. In both groups the annulus diameter increased. Cryopreserved homografts developed significant (¾) pulmonary regurgitation, with trivial regurgitation (¼) in the decellularized group. Macroscopically, explanted cryopreserved valve leaflets retracted and thickened while decellularized leaflets remained thin and pliable with good coaptation. Cryopreserved leaflets and walls demonstrated loss of interstitial cells with collapsed collagen, and decellularized scaffolds extensive, uniform ingrowth of host-cells with an intact collagen network. Calcific deposits were shown only in leaflets and walls of cryopreserved explants. Young fibroblasts, with vacuoles and rough endoplasmic reticulum in the cytoplasm, repopulated the leaflets and walls of decellularized scaffolds. Young's modulus of wall tissue in both groups increased significantly. Cryopreserved valves deteriorate over time due to loss of cellularity and calcification, while decellularized scaffolds demonstrated host-cell repopulation, structural maintenance, tissue remodelling and growth potential.
Published: 2021
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23. <scp>COVID</scp> ‐19 Vaccine‐Associated Cerebral Venous Thrombosis in Germany

Author: Schulz, Jörg B, Berlit, Peter, Steinmetz, Helmuth, Thiele, Thomas, Kurth, Tobias, Group, German Society of Neurology SARS-CoV-2 Vaccination Study, Alonso, Angelika, Bartsch, Thorsten, Baumsteiger, Christoph, Bode, Felix, Cangür, Hakan, Daffertshofer, Michael, Diener, Hans-Christoph, Dafotakis, Manuel, Dieterich, Marianne, Fabian, Friederike, Fousse, Mathias, Godau, Jana, Grond, Martin, Günther, Albrecht, Gutschalk, Alexander, Hagemann, Georg, Hartmann, Corinna, Gerloff, Christian, Hilker-Roggendorf, Rüdiger, Höglinger, Günter, Ikenberg, Benno, Ismail, Fatme Seval, Jesse, Sarah, Kallmünzer, Bernd, Kern, Rolf, Klietz, Martin, Knauß, Samuel, Knier, Benjamin, Greinacher, Andreas, Limmroth, Volker, Mengel, Annerose, Meyne, Johannes, Morgenthaler, Martin, Müller, Matthias, Nagel, Simon, Niels, Ralf Dittrich, Onur, Oezguer A, Pelz, Johann, Plenge, Johannes, Klein, Christine, Poli, Sven, Roth, Christian, Röther, Joachim, Saß, Christian, Schönenberger, Silvia, Schubert, Roger, Simon, Ole, Agaplesion, Ina Specht, Sperfeld, Anne, Spreer, Annette, Petzold, Gabor C, Steinbrecher, Andreas, Steiner, Jochen, Stetefeld, Henning, Trendelenburg, George, Vatankhah, Nils Bijan, Wahl, Christoph Michael, Wartenberg, Katja, Witt, Karsten, Wittstock, Matthias, Wolf, Björn, Piccininni, Marco, Wolf, Joachim, Zimmermann, Julian, and Röhrig, Rainer
Subjects: Male, Pediatrics, Neurology, Medizin, etiology [Intracranial Thrombosis], BNT162 vaccine, epidemiology [Cerebral Hemorrhage], Rate ratio, etiology [Ischemic Stroke], Germany, Surveys and Questionnaires, epidemiology [Ischemic Stroke], epidemiology [Venous Thrombosis], Research Articles, etiology [Venous Thrombosis], Venous Thrombosis, Aged, 80 and over, education.field_of_study, Incidence, Incidence (epidemiology), Age Factors, Middle Aged, etiology [Cerebral Hemorrhage], Vaccination, Venous thrombosis, Female, Research Article, Adult, medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Population, epidemiology [Germany], Young Adult, Sex Factors, ChAdOx1 nCoV-19, medicine, adverse effects [COVID-19 Vaccines], Humans, ddc:610, education, BNT162 Vaccine, Cerebral Hemorrhage, Ischemic Stroke, Aged, epidemiology [Intracranial Thrombosis], business.industry, medicine.disease, Confidence interval, ChAdOx1 COVID-19 vaccine, Neurology (clinical), Intracranial Thrombosis, business
Abstract: OBJECTIVE We aimed to estimate the incidence of cerebral sinus and venous thrombosis (CVT) within 1 month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany. METHODS A web-based questionnaire was e-mailed to all departments of neurology. We requested a report of cases of CVT occurring within 1 month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of 9 German states. RESULTS A total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were younger than 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%) vaccination, and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within 1 month from first dose administration was 0.55 (95% confidence interval [CI] = 0.38-0.78) per 100,000 person-months (which corresponds to a risk of CVT within the first 31 days of 0.55 per 100,000 individuals) for all vaccines and 1.52 (95% CI = 1.00-2.21) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (95% CI = 3.46-34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (95% CI = 1.22-10.65) for females compared to non-females. In 26 of 45 patients with CVT (57.8%), VITT was graded highly probable. INTERPRETATION Given an incidence of 0.02 to 0.15 per 100,000 person-months for CVT in the general population, these findings point toward a higher risk for CVT after ChAdOx1 vaccination, especially for women. ANN NEUROL 2021;90:627-639.
Published: 2021
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24. Diagnostic performance of 18F-fluorodeoxyglucose-PET/MRI versus MRI alone in the diagnosis of pelvic recurrence of rectal cancer

Author: Michael Laniado, Jürgen Weitz, Heiner Nebelung, Ralf-Thorsten Hoffmann, Verena Plodeck, Jens-Peter Kühn, Christoph G Radosa, Sebastian Hoberück, Sophia Blum, Johannes Streitzig, Enrico Michler, Jörg Kotzerke, Ivan Platzek, Johannes Fritzmann, and Klaus Zöphel
Subjects: Male, medicine.medical_specialty, Colorectal cancer, Urology, Sensitivity and Specificity, Pelvis, Fluorodeoxyglucose PET, Recurrence, Fluorodeoxyglucose F18, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Rectal cancer, Recurrent Rectal Cancer, Retrospective Studies, Radiological and Ultrasound Technology, business.industry, Rectal Neoplasms, Gastroenterology, Hepatology, medicine.disease, Magnetic Resonance Imaging, Positron-Emission Tomography, Histopathology, Female, 18F-FDG-PET/MRI, Neoplasm Recurrence, Local, Radiopharmaceuticals, business, Nuclear medicine, MRI
Abstract: Purpose To compare the diagnostic performance of 18F-fluorodeoxyglucose-PET/MRI and MRI in the diagnosis of pelvic recurrence of rectal cancer. Methods All PET/MRIs of patients in the follow-up of rectal cancer performed between 2011 and 2018 at our institution were retrospectively reviewed. Recurrence was confirmed/excluded either by histopathology or imaging follow-up (> 4 months). Four groups of readers (groups 1/2: one radiologist each, groups 3/4: one radiologist/one nuclear medicine physician) independently interpreted MRI and PET/MRI. The likelihood of recurrence was scored on a 5-point-scale. Inter-reader agreement, sensitivity, specificity, PPV/NPV and accuracy were assessed. ROC curve analyses were performed. Results Fourty-one PET/MRIs of 40 patients (mean 61 years ± 10.9; 11 women, 29 men) were included. Sensitivity of PET/MRI in detecting recurrence was 94%, specificity 88%, PPV/NPV 97% and 78%, accuracy 93%. Sensitivity of MRI was 88%, specificity 75%, PPV/NPV 94% and 60%, accuracy 85%. ROC curve analyses showed an AUC of 0.97 for PET/MRI and 0.92 for MRI, but the difference was not statistically significant (p = 0.116). On MRI more cases were scored as equivocal (12% versus 5%). Inter-reader agreement was substantial for PET/MRI and MRI (0.723 and 0.656, respectively). Conclusion 18F-FDG-PET/MRI and MRI are accurate in the diagnosis of locally recurrent rectal cancer. Sensitivity, specificity, PPV, NPV and accuracy are comparable for both modalities, but PET/MRI increases readers’ confidence levels and reduces the number of equivocal cases. Graphic abstract
Published: 2021

25. The genetic landscape of intellectual disability and epilepsy in adults and the elderly: a systematic genetic work-up of 150 individuals

Author: Johannes Rebstock, Bernt Popp, Anne-Christin Teichmann, Malgorzata Kalita, Johannes R. Lemke, Tobias Bartolomaeus, Chiara Klöckner, Ilona Krey, Konrad Platzer, Mathias Stiller, Martin Finzel, Gudrun Körber, Susanne Horn, Frank Brandhoff, Pia Zacher, Thomas Mayer, Rami Abou Jamra, Julia Hentschel, Anja Heinze, Diana Le Duc, and Marina Nastainczyk-Wulf
Subjects: Adult, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Article, Fragile X Mental Retardation Protein, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Intellectual Disability, Exome Sequencing, Intellectual disability, medicine, Humans, Medical diagnosis, Genetics (clinical), Exome sequencing, Aged, business.industry, medicine.disease, FMR1, Work-up, Fragile X syndrome, 030104 developmental biology, Neurodevelopmental Disorders, Karyotyping, Nuchal cord, business, 030217 neurology & neurosurgery
Abstract: Purpose Genetic diagnostics of neurodevelopmental disorders with epilepsy (NDDE) are predominantly applied in children, thus limited information is available regarding adults or elderly. Methods We investigated 150 adult/elderly individuals with NDDE by conventional karyotyping, FMR1 testing, chromosomal microarray, panel sequencing, and for unresolved cases, also by exome sequencing (nsingle = 71, ntrios = 24). Results We identified (likely) pathogenic variants in 71 cases (47.3%) comprising fragile X syndrome (n = 1), disease-causing copy number (n = 23), and single-nucleotide variants (n = 49). Seven individuals displayed multiple independent genetic diagnoses. The diagnostic yield correlated with the severity of intellectual disability. Individuals with anecdotal evidence of exogenic early-life events (e.g., nuchal cord, complications at delivery) with alleged/unproven association to the disorder had a particularly high yield of 58.3%. Screening for disease-specific comorbidities was indicated in 45.1% and direct treatment consequences arose in 11.8% of diagnosed individuals. Conclusion Panel/exome sequencing displayed the highest yield and should be considered as first-tier diagnostics in NDDE. This high yield and the numerous indications for additional screening or treatment modifications arising from genetic diagnoses indicate a current medical undersupply of genetically undiagnosed adult/elderly individuals with NDDE. Moreover, knowledge of the course of elderly individuals will ultimately help in counseling newly diagnosed individuals with NDDE.
Published: 2021
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26. A physically active lifestyle is related to a lower level of skin autofluorescence in a large population with chronic-disease (LifeLines cohort)

Author: Jeroen K. de Vries, Johannes Zwerver, Andries J. Smit, Saskia van de Zande, Inge van den Akker-Scheek, SMART Movements (SMART), Public Health Research (PHR), and Groningen Kidney Center (GKC)
Subjects: Adult, Glycation End Products, Advanced, medicine.medical_specialty, Arbitrary unit, Population, Physical Therapy, Sports Therapy and Rehabilitation, EXERCISE, Health Promotion, 03 medical and health sciences, Skin autofluorescence, 0302 clinical medicine, Chronic disease population, Bayesian multivariate linear regression, Internal medicine, Diabetes mellitus, Medicine, Humans, Orthopedics and Sports Medicine, 030212 general & internal medicine, OXIDATIVE STRESS, education, Life Style, Aged, Skin, ACCUMULATION, education.field_of_study, business.industry, Physical activity, MORTALITY, Advanced glycation endproducts, General population, 030229 sport sciences, ASSOCIATION, Middle Aged, medicine.disease, Confidence interval, REFERENCE VALUES, Cross-Sectional Studies, MARKER, Cohort, Chronic Disease, RISK-FACTORS, Population study, HEALTH, business, GLYCATION END-PRODUCTS, Body mass index
Abstract: Background: Physical activity (PA) has substantial health benefits and is important in combatting chronic diseases, which have been associated with elevated levels of advanced glycation endproducts (AGEs). AGEs play a role in the aging process, and an association between PA and AGEs has been reported. We aimed to investigate the relationship between PA and AGE accumulation in a general population and in a population with chronic diseases.Methods: This large cross-sectional population study used data from adult participants in the LifeLines project, with participant information drawn from the LifeLines database as well data from patients with diabetes mellitus or renal and/or cardiovascular diseases. Tissue AGE accumulation was assessed non-invasively by skin-autofluorescence (SAF) using an AGE reader (DiagnOptics Technologies BV, Groningen, the Netherlands). PA was assessed using the short questionnaire to assess health-enhancing physical activity (SQUASH). Multivariate linear regression analyses were adjusted for age, body mass index, sex, and smoking status.Results: Data from 63,452 participants (general population n = 59,177, chronic disease n = 4275) were analyzed. The general population was significantly younger (43.58 +/- 11.77 years, mean +/- SD) and had significantly lower SAF (1.90 +/- 0.42 arbitrary units (AU)) compared to the population with chronic disease (age: 55.51 +/- 12.07 years; SAF: 2.27 +/- 0.51 AU). In the group with chronic disease, more hours of moderate to vigorous physical activities per week were associated with lower SAF (beta= -0.002, 95% confidence interval (95%CI): -0.002 to -0.001). For the general population, there was no association between hours of moderate to vigorous activity and SAF (beta= 3.2 x 10(-5), 95%CI: 0.000-0.001, p = 0.742). However, there was an association in the general population between total hours of PA per week and SAF (beta= 4.2 x 10(-4), 95%CI: 0.000-0.001, p < 0.001), but this association was not found in the chronic disease population (beta = -3.2 x 10(-4), 95%CI: -0.001 to 0.000, p = 0.347).Conclusion: Our study demonstrates that an inverse relationship exists between PA and AGE accumulation in the population with chronic disease. More hours of moderate to vigorous activity is associated with a significantly decreased SAF. More PA is associated with a lower SAF, even after adjusting for the established predictors (age, body mass index, smoking status, and sex). Our findings could help to promote health and prolong longevity.
Published: 2022
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27. Age Dependence of Liver Enzymes: An Analysis of Over 1,300,000 Consecutive Blood Samples

Author: David Petroff, Thomas Berg, Johannes Wiegand, Jan Kramer, Olaf Bätz, and Katrin Jedrysiak
Subjects: medicine.medical_specialty, Percentile, Hepatology, Triglyceride, business.industry, Cholesterol, Gastroenterology, Hepatitis B, medicine.disease, chemistry.chemical_compound, chemistry, Internal medicine, Liver enzyme, Cohort, Medicine, Glycated hemoglobin, Alanine aminotransferase, business
Abstract: Background & aims Upper levels of normal for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) generally take sex into account, but not age. This simplification may lead to misclassification and burden the patient and health system unnecessarily. Methods Consecutive blood samples were analyzed from a German laboratory. Subcohorts included samples from a prescribed routine check-up and a healthy cohort, defined as patients without increased GGT, triglyceride, cholesterol, glycated hemoglobin, or glucose levels, and without known hepatitis B. Results A total of 1,369,180 blood samples were analyzed from 601,779 participants (50.8% female; mean age, 58.5 y; SD, 18.0 y). There is an extreme age dependence in ALT values for men: increased values were seen in 20.0% (95% CI, 19.5%-20.4%) of patients in the age group of 25 to 34 years, but only 6.7% (95% CI, 6.4%-7.0%) for the ages of 65 to 74 years. The 95th percentile reaches values greater than 80 U/L instead of 50 U/L at the age of 35, and decrease to less than 50 U/L by the age of 75. The subpopulations of prescribed routine check-up and healthy individuals showed similar qualitative results. The age dependence is much weaker for ALT in women. The proportion of women with an increased aspartate aminotransferase level increases from approximately 6% to 12% at approximately age 50. The 95th percentile for GGT increases up to the age of 60 in men, and throughout life in women. Conclusions Current guidelines and reference values for ALT imply that subsequent diagnostics are needed for a large proportion of young men. Our data strongly suggest that age adaptation should be considered.
Published: 2022
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28. Low risk of contrast media-induced hypersensitivity reactions in all subtypes of systemic mastocytosis

Author: Wolf-Karsten Hofmann, Philipp Riffel, Georgia Metzgeroth, Mohamad Jawhar, Julia Riffel, Nicole Naumann, Alice Fabarius, Andreas Reiter, Knut Brockow, Johannes Lübke, Juliana Schwaab, Stefan O. Schoenberg, and Lukas Reiter
Subjects: Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Erythema, media_common.quotation_subject, Immunology, Contrast Media, Gastroenterology, Mastocytosis, Systemic, Internal medicine, medicine, Humans, Immunology and Allergy, Contrast (vision), Cumulative incidence, Systemic mastocytosis, Arthropod Venoms, Retrospective Studies, media_common, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Vomiting, Premedication, medicine.symptom, business, Mastocytosis
Abstract: Patients with systemic mastocytosis (SM) are at increased risk of hypersensitivity reactions (HRs). Although Hymenoptera venoms are the predominant triggers, cases of contrast media-induced HR (CMIHR) have also been reported and prophylactic premedication is often performed. However, data from larger series are limited and differences between indolent and advanced SM have not yet been investigated.To determine the incidence and severity of CMIHR in all subtypes of SM.We analyzed 162 adult patients with SM (indolent systemic mastocytosis [ISM], n = 65; advanced systemic mastocytosis [advSM], n = 97). First, the cumulative incidence of CMIHR was retrospectively assessed in the patient's history. Second, at our institution, patients underwent 332 contrast media (CM)-enhanced imaging including 80 computed tomography (CT) scans with iodine-based contrast agent and 252 magnetic resonance imaging (MRI) with a gadolinium-based contrast agent, and tolerance was assessed.Previous CMIHRs to CT (vomiting, n = 1, erythema, n = 1, cardiovascular shock, n = 1), and MRI (dyspnea, n = 1, cardiovascular shock, n = 1) had been reported by 4 out of 162 (2.5%) patients (ISM, n = 3; advSM, n = 1). In contrast, during or after 332 CM-enhanced CT or MRI examinations at our institution, no CMIHRs were reported. Premedication was solely given to 3 patients before CT scans, including 1 with previous CMIHR, who tolerated the imaging well.We conclude that: (1) there is a substantial discrepancy between the perception and prevalence of HRs to CM in SM; (2) reactions are scarce in ISM and even rarer in advSM; and (3) in SM patients without previous history of CM hypersensitivity, prophylactic premedication before CM-enhanced CT or MRI is dispensable.
Published: 2022
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29. Antihypertensive drugs demonstrate varying levels of hip fracture risk: A systematic review and meta-analysis

Author: Lukas P. E. Verweij, Stein J. Janssen, David W. G. Langerhuizen, Johannes C. van der Wouden, Gino M. M. J. Kerkhoffs, Graduate School, AMS - Amsterdam Movement Sciences, Orthopedic Surgery and Sports Medicine, AMS - Ageing & Vitality, AMS - Sports, AMS - Musculoskeletal Health, AMS - Tissue Function & Regeneration, APH - Personalized Medicine, APH - Quality of Care, General practice, and APH - Aging & Later Life
Subjects: Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Angiotensin-Converting Enzyme Inhibitors, law.invention, Randomized controlled trial, law, Internal medicine, medicine, Humans, Antihypertensive drug, Antihypertensive Agents, General Environmental Science, Antihypertensives drugs, Hip fracture, business.industry, Odds ratio, Calcium Channel Blockers, medicine.disease, Confidence interval, Meta-analysis, Hypertension, Hip fractures, Systematic review, General Earth and Planetary Sciences, Observational study, business, Cohort study
Abstract: Objective By aggregating the literature, we evaluated the association between use of specific antihypertensive drugs and the risk of hip fractures compared with nonuse. Study design and setting We systematically searched the Pubmed, Embase, and Cochrane databases from inception of each database until July 30, 2020 to identify articles including patients 18 years of age or older reporting on the association between antihypertensive drugs and the risk of hip fracture. Antihypertensive drugs were restricted to thiazides; beta-blockers; calcium-channel blockers; angiotensin-converting enzyme (ACE) inhibitors; and angiotensin receptor blockers. Nonusers encompass all patients that are not using the specific antihypertensive drug that has been reported. Unadjusted odds ratios with 95% confidence intervals (CIs) of the association between antihypertensive drug use and hip fractures were reported. Meta-analysis was performed when a minimum of five studies were identified for each antihypertensive drug class. Quality assessment was done using ROBINS-I tool. The GRADE approach was used to evaluate the certainty of the evidence. Results Of 962 citations, 22 observational studies were included; 9 studies had a cohort design and 13 studies were case-control studies. No randomized controlled trials were identified. We found very low certainty of evidence that both thiazides (pooled odds ratio: 0.85, 95% CI 0.73 to 0.99, p = 0.04) as well as beta-blockers (pooled odds ratio: 0.88, 95% CI 0.79 to 0.98, p = 0.02) were associated with a reduced hip fracture risk as compared to specific nonuse. One study, reporting on angiotensin receptor blockers, also suggested a protective effect for hip fractures, whereas we found conflicting findings in four studies for calcium-channel blockers and in two studies for ACE inhibitors. Conclusion Among 22 observational studies, we found very low certainty of evidence that, compared to specific nonuse of antihypertensive drugs, use of thiazides, beta-blockers, and angiotensin receptor blockers were associated with a reduced protective hip fracture risk, while conflicting findings for calcium-channel blockers and ACE inhibitors were found. Given the low quality of included studies, further research –randomized controlled trials– are needed to definitively assess the causal relationship between specific antihypertensive drug classes and (relatively infrequent) hip fractures.
Published: 2022
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30. Combined cCTA and TAVR Planning for Ruling Out Significant CAD

Author: Matthias Horn, Matthias Gutberlet, Christoph Panknin, Christian Lücke, David Holzhey, Steffen Desch, Sebastian Ebel, Johannes Wilde, Christian Krieghoff, Mohamed Abdel-Wahab, Konrad Pawelka, Philipp Lauten, Patrick Seitz, Michael A. Borger, Katharina Renatus, Philipp Kiefer, Linda Heiser, Sebastian Gottschling, Holger Thiele, Thilo Noack, Robin Gohmann, and Nicolas Majunke
Subjects: Coronary angiography, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Computed tomography, Diagnostic accuracy, Coronary ct angiography, Fractional flow reserve, medicine.disease, Coronary artery disease, medicine, Radiology, Nuclear Medicine and imaging, Radiology, Cardiology and Cardiovascular Medicine, business
Abstract: Objectives To analyze the ability of machine-learning (ML)-based computed tomography (CT)-derived fractional flow reserve (CT-FFR) to further improve the diagnostic performance of coronary...
Published: 2022
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31. Pregnancy outcomes in women with Budd-Chiari syndrome or portal vein thrombosis A multicentre retrospective cohort study

Author: Eva N. Hamulyák, Luuk J. J. Scheres, Jack R van Duuren, Saskia Middeldorp, Johannes J. Duvekot, Stefanie E Damhuis, Sanne J. Gordijn, Sarwa Darwish Murad, Mandy N Lauw, Jenneke Leentjens, Barbara A. Hutten, Hanke M. G. Wiegers, Wessel Ganzevoort, Gastroenterology & Hepatology, Obstetrics & Gynecology, Hematology, Graduate School, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, Amsterdam Reproduction & Development (AR&D), Obstetrics and Gynaecology, Epidemiology and Data Science, ACS - Diabetes & metabolism, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, and APH - Quality of Care
Subjects: Adult, medicine.medical_specialty, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Population, Pregnancy Complications, Cardiovascular, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Budd-Chiari Syndrome, SDG 3 - Good Health and Well-being, Pregnancy, medicine, Humans, education, Contraindication, thrombosis, Retrospective Studies, Venous Thrombosis, education.field_of_study, Obstetrics, business.industry, Portal Vein, Obstetrics and Gynecology, Retrospective cohort study, medicine.disease, Delivery, Obstetric, Thrombosis, Portal vein thrombosis, counselling, Portal hypertension, Female, Live birth, business, Budd–Chiari Syndrome – portal vein thrombosis, Live Birth
Abstract: Contains fulltext : 248726.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To evaluate current practice and outcomes of pregnancy in women previously diagnosed with Budd-Chiari syndrome and/or portal vein thrombosis, with and without concomitant portal hypertension. DESIGN AND SETTING: Multicentre retrospective cohort study between 2008 and 2021. POPULATION: Women who conceived in the predefined period after the diagnosis of Budd-Chiari syndrome and/or portal vein thrombosis. METHODS AND MAIN OUTCOME MEASURES: We collected data on diagnosis and clinical features. The primary outcomes were maternal mortality and live birth rate. Secondary outcomes included maternal, neonatal and obstetric complications. RESULTS: Forty-five women (12 Budd-Chiari syndrome, 33 portal vein thrombosis; 76 pregnancies) were included. Underlying prothrombotic disorders were present in 23 of the 45 women (51%). Thirty-eight women (84%) received low-molecular-weight heparin during pregnancy. Of 45 first pregnancies, 11 (24%) ended in pregnancy loss and 34 (76%) resulted in live birth of which 27 were at term (79% of live births and 60% of pregnancies). No maternal deaths were observed; one woman developed pulmonary embolism during pregnancy and two women (4%) had variceal bleeding requiring intervention. CONCLUSIONS: The high number of term live births (79%) and lower than expected risk of pregnancy-related maternal and neonatal morbidity in our cohort suggest that Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy. Individualised, nuanced counselling and a multidisciplinary pregnancy surveillance approach are essential in this patient population. TWEETABLE ABSTRACT: Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy.
Published: 2022
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32. Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin

Author: Irwin Goldstein, Silvia Diviccaro, Silvia Giatti, Audrey S. Bahrick, Barbara D'Avanzo, Caroline F. Pukall, David Healy, Heiko Graf, Angelo Barbato, David Edmund Johannes Linden, Amy M. Pearlman, Barbara M. Chubak, Michał Lew-Starowicz, Mohit Khera, Stuart Shipko, Fiammetta Cosci, Omar Walid Muquebil Ali Al Shaban Rodríguez, Joanna Le Noury, Michael S. Irwig, Arianna Patacchini, Paddy K.C. Janssen, Rudy Schreiber, Celine Lüning, Maarten Bak, Jalesh N. Panicker, Dee Mangin, Ahad Waraich, Manoj Therayil Kumar, Barbora Vašečková, Rachel Rubin, Yacov Reisman, Emmanuele A. Jannini, Wayne J.G. Hellstrom, Roberto Cosimo Melcangi, Sanjana Raj, Rocco Salvatore Calabrò, Antonei B. Csoka, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: DA KFT Medische Staf (9), Clinical Pharmacy, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Section Psychopharmacology, and RS: FPN NPPP II
Subjects: Male, Adolescent, Serotonin reuptake inhibitor, Irritability, Asexuality, Arousal, Persistent genital arousal disorder, DOUBLE-BLIND, PERSISTENT, selective serotonin reuptake inhibitors, medicine, Humans, Child, business.industry, Health Policy, Public Health, Environmental and Occupational Health, isotretinoin, General Medicine, GENITAL AROUSAL DISORDER, medicine.disease, EFFICACY, Antidepressive Agents, finasteride, Sexual Dysfunction, Physiological, Sexual desire, Post-SSRI sexual dysfunction, Sexual dysfunction, Erectile dysfunction, PREMATURE EJACULATION, CITALOPRAM, antidepressants, SAFETY, medicine.symptom, business, Clinical psychology
Abstract: BACKGROUND: A set of enduring conditions have been reported in the literature involving persistent sexual dysfunction after discontinuation of serotonin reuptake inhibiting antidepressants, 5 alpha-reductase inhibitors and isotretinoin.OBJECTIVE: To develop diagnostic criteria for post-SSRI sexual dysfunction (PSSD), persistent genital arousal disorder (PGAD) following serotonin reuptake inhibitors, post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction (PRSD).METHODS: The original draft was designed using data from two published case series (Hogan et al., 2014 and Healy et al., 2018), which represent the largest public collections of data on these enduring conditions. It was further developed with the involvement of a multidisciplinary panel of experts.RESULTS: A set of criteria were agreed upon for each of the above conditions. Features of PSSD, PFS and PRSD commonly include decreased genital and orgasmic sensation, decreased sexual desire and erectile dysfunction. Ancillary non-sexual symptoms vary depending on the specific condition but can include emotional blunting and cognitive impairment. PGAD presents with an almost mirror image of unwanted sensations of genital arousal or irritability in the absence of sexual desire. A new term, post-SSRI asexuality, is introduced to describe a dampening of sexual interest and pleasure resulting from a pre-natal or pre-teen exposure to a serotonin reuptake inhibitor.CONCLUSIONS: These criteria will help in both clinical and research settings. As with all criteria, they will likely need modification in the light of developments.
Published: 2022

33. Multifaceted pathomolecular mechanism of a VWF large deletion involved in the pathogenesis of severe VWD

Author: Ulrich Budde, Muhammad Ahmer Jamil, Orla Rawley, N. Marquardt, Hamideh Yadegari, David Lillicrap, Johannes Oldenburg, Jens Müller, and Osman El-Maarri
Subjects: Weibel-Palade Bodies, biology, Angiogenesis, Cellular differentiation, Endothelial Cells, Blood vessel morphogenesis, Hematology, medicine.disease, Cell biology, Endothelial stem cell, P-Selectin, Phenotype, Von Willebrand factor, hemic and lymphatic diseases, von Willebrand Factor, Von Willebrand disease, medicine, biology.protein, Humans, Interleukin 8, Cell adhesion
Abstract: An in-frame heterozygous large deletion of exons 4 through 34 of the von Willebrand factor (VWF) gene was identified in a type 3 von Willebrand disease (VWD) index patient (IP), as the only VWF variant. The IP exhibited severe bleeding episodes despite prophylaxis treatment, with a short VWF half-life after infusion of VWF/factor VIII concentrates. Transcript analysis confirmed transcription of normal VWF messenger RNA besides an aberrant deleted transcript. The IP endothelial colony-forming cells (ECFCs) exhibited a defect in the VWF multimers and Weibel-Palade bodies (WPBs) biogenesis, although demonstrating normal VWF secretion compared with healthy cells. Immunostaining of IP-ECFCs revealed subcellular mislocalization of WPBs pro-inflammatory cargos angiopoietin-2 (Ang2, nuclear accumulation) and P-selectin. Besides, the RNA-sequencing (RNA-seq) analysis showed upregulation of pro-inflammatory and proangiogenic genes, P-selectin, interleukin 8 (IL-8), IL-6, and GROα, copackaged with VWF into WPBs. Further, whole-transcriptome RNA-seq and subsequent gene ontology (GO) enrichment analysis indicated the most enriched GO-biological process terms among the differentially expressed genes in IP-ECFCs were regulation of cell differentiation, cell adhesion, leukocyte adhesion to vascular endothelial, blood vessel morphogenesis, and angiogenesis, which resemble downstream signaling pathways associated with inflammatory stimuli and Ang2 priming. Accordingly, our functional experiments exhibited an increased endothelial cell adhesiveness and interruption in endothelial cell–cell junctions of the IP-ECFCs. In conclusion, the deleted VWF has a dominant-negative impact on multimer assembly and the biogenesis of WPBs, leading to altered trafficking of their pro-inflammatory cargos uniquely, which, in turn, causes changes in cellular signaling pathways, phenotype, and function of the endothelial cells.
Published: 2022
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34. Preoperative glans & penile dimensions in different hypospadias grades

Author: Johannes Wirmer, Michael Sennert, and Ahmed T. Hadidi
Subjects: medicine.medical_specialty, Under anaesthesia, business.industry, Urology, medicine.disease, Perineal hypospadias, Surgery, medicine.anatomical_structure, Urethra, Hypospadias, Pediatrics, Perinatology and Child Health, medicine, Penile curvature, Glans, Who classification, business, Penis
Abstract: Summary Purpose To report glans and penile dimensions in 1023 consecutive boys with hypospadias. Patients & methods Boys admitted for hypospadias surgery between 2016 and 2018 were included in this study. Age ranged between 6 and 36 months. Boys who underwent previous surgery, received hormone therapy or older than 36 months were excluded. The hypospadias was classified according to ICD and WHO classification into glanular (Grade I), distal (Grade II), proximal (Grade III) and perineal (Grade IV). The flaccid penile length (PL), the dorsal glans length (DGL), the ventral glans length (VGL) and the glans width (GW) were measured in the operating room under anaesthesia just before operative correction. Small (GW) in this study was defined as less than 14 mm. Results 1023 boys were included. 273 had glandular, 468 distal, 194 proximal and 88 perineal hypospadias. The mean glans width was 14 mm with a range of 8 to 20 mm. The mean glans width for glanular hypospadias was 14.0 mm (range 9–19 mm), 14.0 mm (range 10–20 mm) for distal hypospadias (p > 0.05), 13.1 mm (range 9–19 mm) for proximal hypospadias (p 0.2), but there was a difference when compared to patients older than 25 months (p Conclusions A small glans is found in about a third of distal, two thirds in proximal and more than 90% of perineal hypospadias. Download : Download high-res image (211KB) Download : Download full-size image Summary Figure . A 9 month old child with proximal hypospadias and 50° penile curvature; A. the Glans Width (GW) was 9 mm. B. The Dorsal Glans Length (DGL) was 9 mm. C. The Ventral Glans Length (VGL) was 4 mm. D. The flaccid Penile Length (PL)was 18 mm.
Published: 2022
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35. Identifying the Best Candidates for Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as the Primary Staging Approach Among Men with High-risk Prostate Cancer and Negative Conventional Imaging

Author: Michael L. Steinberg, Kathleen Nguyen, Vinayak Muralidhar, Neil R. Parikh, Vincent Lok, Ting Martin Ma, Ida Sonni, Andrei Gafita, Pan Thin, David Elashoff, Johannes Czernin, Ricky Savjani, Matthew Rettig, Jesus E. Juarez, Jie Deng, Tristan Grogan, David Shabsovich, Amar U. Kishan, Patrick A. Kupelian, David D. Yang, Jeremie Calais, Nicholas G. Nickols, Carissa Chu, Felix Y. Feng, Wesley R Armstrong, and Robert E. Reiter
Subjects: Male, Aging, Staging, Prostate biopsy, Positron emission tomography/computed tomography, 030232 urology & nephrology, Prostate-specific membrane antigen, Nomogram, Metastasis, Prostate cancer, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Prospective Studies, Lymph node, Cancer, screening and diagnosis, Clinical Trials as Topic, medicine.diagnostic_test, Prostate, Percent positive core, Detection, medicine.anatomical_structure, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Biomedical Imaging, Overall upstaging, Radiology, 4.2 Evaluation of markers and technologies, Conventional imaging, Gleason grade, Urologic Diseases, medicine.medical_specialty, Urology, Article, 03 medical and health sciences, Clinical Research, medicine, Humans, Radiology, Nuclear Medicine and imaging, business.industry, Prevention, Prostatic Neoplasms, Odds ratio, medicine.disease, Nomograms, Surgery, business
Abstract: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.1%, 8.9%, and 23.9% of patients experienced nodal, metastatic, and overall upstaging, respectively, without histologic confirmation. On multivariable analysis, Gleason grade group (GG) and percent positive core (PPC) on systematic biopsy significantly predict overall upstaging (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.33-3.45; p = 0.002; and OR 1.03, 95% CI 1.01-1.04; p
Published: 2022
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36. Less loop diuretic use in patients on sacubitril/valsartan undergoing remote pulmonary artery pressure monitoring

Author: Jasper J. Brugts, Folkert W. Asselbergs, Johannes Brachmann, Michael Böhm, Lutz Hilker, Marie-Elena Brett, Friedrich Koehler, Amr Abdin, Christiane E. Angermann, Jan Wintrich, Stephan Rosenkranz, Philip B. Adamson, Qian Zhou, Stefan D. Anker, David M. Leistner, Birgit Assmus, Georg Ertl, AiJia Wang, and Cardiology
Subjects: medicine.medical_specialty, medicine.drug_class, Population, Tetrazoles, Heart failure, Pulmonary Artery, Ventricular Function, Left, Sacubitril, Loop diuretics, Angiotensin Receptor Antagonists, Sodium Potassium Chloride Symporter Inhibitors, Internal medicine, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, education, education.field_of_study, Ejection fraction, business.industry, Aminobutyrates, Biphenyl Compounds, Hemodynamic Monitoring, Furosemide, Stroke Volume, Original Articles, Monitor, Loop diuretic, medicine.disease, Pulmonary artery pressure, Valsartan, RC666-701, Cardiology, Original Article, Drug therapy, Cardiology and Cardiovascular Medicine, business, Sacubitril, Valsartan, medicine.drug
Abstract: Aims: Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). Methods and results: The MEMS-HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS-HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2] vs. non-users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2, P = 0.0002, P Conclusions: In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes.
Published: 2022
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37. NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options

Author: Peter R. Galle, Simon Johannes Gairing, Lukas Müller, and Friedrich Foerster
Subjects: Oncology, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Disease, Type 2 diabetes, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, medicine, Humans, neoplasms, Hepatology, business.industry, Liver Neoplasms, Fatty liver, medicine.disease, digestive system diseases, Liver Transplantation, Clinical trial, Treatment Outcome, Liver, Hepatocellular carcinoma, Disease Progression, Metabolic syndrome, Steatohepatitis, business
Abstract: In light of a global rise in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) represent an increasingly important underlying aetiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation are characterised by several unique features: in contrast to virally driven HCC, up to 50% of NAFLD-HCC occurs in patients without cirrhosis and annual HCC incidence is comparatively low, complicating current surveillance strategies. On average, patients are older and are more frequently diagnosed at an advanced stage. While locoregional treatments are probably equally effective regardless of HCC aetiology, the picture is less clear for systemic therapy. Tyrosine kinase inhibitors are probably equally effective, while there have been initial signals that immune checkpoint inhibitors may be less effective in NAFLD-HCC than in viral HCC. Current international clinical practice guidelines for HCC do not consider aetiology, as there are insufficient data to draw specific conclusions or to recommend aetiology-specific modifications to the current management of patients with HCC. However, in light of the growing relevance of NAFLD-HCC, future clinical trials should assess whether HCC aetiology - and NAFLD/NASH in particular - influence the safety and efficacy of a given treatment.
Published: 2022
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38. Early motor outcomes in infants with critical congenital heart disease are related to neonatal brain development and brain injury

Author: Janjaap van der Net, Manon J.N.L. Benders, Nicolaas J. G. Jansen, Johannes M.P.J. Breur, Raymond Stegeman, Nathalie H.P. Claessens, Maaike C. A. Sprong, Felix Haas, Linda S. de Vries, and Floris Groenendaal
Subjects: Heart Defects, Congenital, Male, medicine.medical_specialty, Developmental Disabilities, Gross motor skill, Pyramidal Tracts, Cerebral palsy, White matter, Child Development, Developmental Neuroscience, Interquartile range, Cerebellum, Internal medicine, PRETERM INFANTS, Humans, Medicine, Prospective Studies, Gray Matter, Critical congenital heart disease, Ischemic Stroke, Cerebral Cortex, medicine.diagnostic_test, business.industry, Cerebral Palsy, Infant, Newborn, Infant, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, White Matter, Cardiac surgery, medicine.anatomical_structure, Motor Skills, Brain Injuries, Pediatrics, Perinatology and Child Health, Corticospinal tract, Cardiology, Female, Neurology (clinical), business
Abstract: Aim To assess the relationship between neonatal brain development and injury with early motor outcomes in infants with critical congenital heart disease (CCHD). Method Neonatal brain magnetic resonance imaging was performed after open-heart surgery with cardiopulmonary bypass. Cortical grey matter (CGM), unmyelinated white matter, and cerebellar volumes, as well as white matter motor tract fractional anisotropy and mean diffusivity were assessed. White matter injury (WMI) and arterial ischaemic stroke (AIS) with corticospinal tract (CST) involvement were scored. Associations with motor outcomes at 3, 9, and 18 months were corrected for repeated cardiac surgery. Results Fifty-one infants (31 males, 20 females) were included prospectively. Median age at neonatal surgery and postoperative brain magnetic resonance imaging was 7 days (interquartile range [IQR] 5-11d) and 15 days (IQR 12-21d) respectively. Smaller CGM and cerebellar volumes were associated with lower fine motor scores at 9 months (CGM regression coefficient=0.51, 95% confidence interval [CI]=0.15-0.86; cerebellum regression coefficient=3.08, 95% CI=1.07-5.09) and 18 months (cerebellum regression coefficient=2.08, 95% CI=0.47-5.12). The fractional anisotropy and mean diffusivity of white matter motor tracts were not related with motor scores. WMI was related to lower gross motor scores at 9 months (mean difference -0.8SD, 95% CI=-1.5 to -0.2). AIS with CST involvement increased the risk of gross motor problems and muscle tone abnormalities. Cerebral palsy (n=3) was preceded by severe ischaemic brain injury. Interpretation Neonatal brain development and injury are associated with fewer favourable early motor outcomes in infants with CCHD.
Published: 2022
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39. Slowly resorbable biosynthetic mesh

Author: G. W. M. Tetteroo, Alastair Windsor, René H. Fortelny, Johannes Jeekel, Tim Tollens, Francesco Gossetti, Janusz Lange, Andreas Koch, T. S. de Vries Reilingh, H. L. van Westreenen, Lars N. Jorgensen, Marc Miserez, M. M. J. van Rooijen, Bertrand Dousset, Guido Woeste, Ferdinand Köckerling, Frederik Berrevoet, Guillaume Piessen, Surgery, and Neurosciences
Subjects: medicine.medical_specialty, Incisional hernia, medicine.medical_treatment, 030230 surgery, Hernia surgery, Biosynthetic mesh, 03 medical and health sciences, SUTURE, 0302 clinical medicine, Quality of life, QUALITY-OF-LIFE, POLY-4-HYDROXYBUTYRATE MESH, Surgical site, medicine, Clinical endpoint, Medicine and Health Sciences, INCISIONAL HERNIA, COMPLICATIONS, OUTCOMES, Science & Technology, business.industry, Significant difference, medicine.disease, Hernia repair, Surgery, Hernia recurrence, 030220 oncology & carcinogenesis, business, Life Sciences & Biomedicine, Abdominal surgery
Abstract: Introduction Information on the long-term performance of biosynthetic meshes is scarce. This study analyses the performance of biosynthetic mesh (Phasix™) over 24 months. Methods A prospective, international European multi-center trial is described. Adult patients with a Ventral Hernia Working Group (VHWG) grade 3 incisional hernia larger than 10 cm2, scheduled for elective repair, were included. Biosynthetic mesh was placed in sublay position. Short-term outcomes included 3-month surgical site occurrences (SSO), and long-term outcomes comprised hernia recurrence, reoperation, and quality of life assessments until 24 months. Results Eighty-four patients were treated with biosynthetic mesh. Twenty-two patients (26.2%) developed 34 SSOs, of which 32 occurred within 3 months (primary endpoint). Eight patients (11.0%) developed a hernia recurrence. In 13 patients (15.5%), 14 reoperations took place, of which 6 were performed for hernia recurrence (42.9%), 3 for mesh infection (21.4%), and in 7 of which the mesh was explanted (50%). Compared to baseline, quality of life outcomes showed no significant difference after 24 months. Despite theoretical resorption, 10.7% of patients reported presence of mesh sensation in daily life 24 months after surgery. Conclusion After 2 years of follow-up, hernia repair with biosynthetic mesh shows manageable SSO rates and favorable recurrence rates in VHWG grade 3 patients. No statistically significant improvement in quality of life or reduction of pain was observed. Few patients report lasting presence of mesh sensation. Results of biosynthetic mesh after longer periods of follow-up on recurrences and remodeling will provide further valuable information to make clear recommendations. Trial registration Registered on clinicaltrials.gov (NCT02720042), March 25, 2016.
Published: 2022
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40. Disc Hemorrhages Are Associated With Localized Three-Dimensional Neuroretinal Rim Thickness Progression in Open-Angle Glaucoma

Author: Janice Kim, Michele Zemplenyi, Teresa C. Chen, Milica A. Margeta, Johannes F. de Boer, Fei Yu, Courtney L. Ondeck, Kitiya Ratanawongphaibul, Anne L. Coleman, Edem Tsikata, Ophthalmology, Amsterdam Neuroscience - Systems & Network Neuroscience, VU University medical center, Physics and Astronomy, Amsterdam Neuroscience - Brain Imaging, Biophotonics and Medical Imaging, and LaserLaB - Biophotonics and Microscopy
Subjects: Retinal Ganglion Cells, medicine.medical_specialty, Open angle glaucoma, genetic structures, Optic Disk, Nerve fiber layer, Glaucoma, Hemorrhage, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nerve Fibers, Optical coherence tomography, Ophthalmology, medicine, Humans, Longitudinal Studies, Prospective Studies, Prospective cohort study, Intraocular Pressure, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, business.industry, Retinal, medicine.disease, eye diseases, medicine.anatomical_structure, chemistry, 030221 ophthalmology & optometry, Optic nerve, sense organs, business, Glaucoma, Open-Angle, Tomography, Optical Coherence, Optic disc
Abstract: Purpose To evaluate the relationship between the occurrence of optic disc hemorrhages (DH) and glaucoma progression as determined by multiple glaucoma testing modalities. Design A prospective cohort study. Methods A longitudinal study of 124 open angle glaucoma patients who had yearly disc photography (DP), visual fields (VFs), spectral-domain optical coherence tomography (SD-OCT) retinal nerve fiber layer (RNFL) thickness scans, and optic nerve volume scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany), all performed on the same day over a 5-year period. The minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter, was calculated from optic nerve volume scans. Patients were classified as glaucoma progressors or non-glaucoma progressors using event-based analysis. Results Out of 124 open angle glaucoma patients, 19 (15.3%) had one or more DHs on yearly DPs. Presence of a DH was associated with localized 3D neuroretinal rim thickness progression (superior MDB progression; OR 3.96, P = 0.04), but not with global or inferior MDB progression (P = 0.14 and 0.81 respectively), DP progression (P = 0.08), VF progression (P = 0.45), or RNFL global, inferior or superior progression (P = 0.17, 0.26 and 0.76 respectively). In the majority of patients with MDB progression (14/17, or 82%), the progression was noted before or concurrently with the first instance of DH. Conclusions Glaucoma progression detected by high-density 3D SD-OCT neuroretinal rim measurements preceded DH occurrence in the majority of patients. These findings support the hypothesis that DHs are indicators of ongoing glaucoma progression rather than discrete events that cause subsequent progression.
Published: 2022
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41. Oral hygiene in patients with motor neuron disease requires attention

Author: Johannes J. de Soet, Berthe A M Makizodila, Johanna H E van de Wijdeven, Maurits K. A. van Selms, C.M.C. Volgenant, Academic Centre for Dentistry Amsterdam, Preventive Dentistry, and Oral Kinesiology
Subjects: medicine.medical_specialty, Neuromuscular disease, Cross-sectional study, business.industry, Amyotrophic Lateral Sclerosis, Treatment team, Disease, Oral health, medicine.disease, Oral Hygiene, Oral hygiene, stomatognathic diseases, Quality of life (healthcare), Cross-Sectional Studies, Family medicine, medicine, Quality of Life, Humans, In patient, Motor Neuron Disease, business, General Dentistry
Abstract: Aims: Motor Neuron Disease (MND) is a progressive neurodegenerative neuromuscular disease, which can progressively impair arm-hand function. Needs and barriers of MND patients and their caregivers in performing oral hygiene were studied. Methods: An online survey was sent to 706 MND patients. The questions of the survey included self-reliance, self-reported oral health, and oral hygiene. The oral health-related quality of life (GOHAI-NL) and the subjective well-being (ALSAQ-5) were also measured. Results: A total of 259 patients responded (36.7%), of which 71.9% stated not to be informed about the importance of maintaining good oral health by their MND treatment team. Moreover, 40.4% would like to receive help concerning oral hygiene from a dental professional. 19.8% were not satisfied about oral care as conducted by themselves or their caregivers. Patients who do not ask for support with their daily oral care had a significantly worse oral health-related quality of life compared to patients who do ask for support. Conclusions: The support for daily oral hygiene of MND patients and their barriers to requesting support needs more attention from both MND-treatment teams and general dental professionals.
Published: 2022
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42. Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor–Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies

Author: Scott R. Solomon, Richard J. O'Reilly, Sergio Giralt, Raquel Palencia, Lori Muffly, Leyla Shune, Miguel-Angel Perales, Brent R. Logan, Mary M. Horowitz, Marcelo C. Pasquini, Nancy L. Geller, Richard J. Jones, Leo Luznik, Adam Mendizabal, Sumithira Vasu, Juan Wu, Johannes Schetelig, Steven M. Devine, Helen E. Heslop, Lynn O'Donnell, Eneida R. Nemecek, Mark R. Litzow, Robert J. Soiffer, and Vincent T. Ho
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Time Factors, Transplantation Conditioning, Adolescent, Calcineurin Inhibitors, Graft vs Host Disease, Disease, Disease-Free Survival, Tacrolimus, Young Adult, Recurrence, Germany, Internal medicine, medicine, Humans, Cyclophosphamide, Aged, Hematopoietic cell, business.industry, Hematopoietic Stem Cell Transplantation, ORIGINAL REPORTS, Middle Aged, Myeloablative Agonists, medicine.disease, United States, Calcineurin, Transplantation, Methotrexate, Graft-versus-host disease, Hematologic Neoplasms, Chronic Disease, Drug Therapy, Combination, Female, business, Immunosuppressive Agents
Abstract: PURPOSE Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD). METHODS This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS). RESULTS Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037). CONCLUSION CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.
Published: 2022
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43. Diaphragm-Based Position Verification to Improve Daily Target Dose Coverage in Proton and Photon Radiation Therapy Treatment of Distal Esophageal Cancer

Author: Lydia A. den Otter, Cássia O. Ribeiro, Johannes A. Langendijk, Erik W Korevaar, Christina T. Muijs, S. Visser, Nanna M. Sijtsema, Stefan Both, Antje Knopf, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Organs at Risk, Cancer Research, INTERPLAY, Proton, Esophageal Neoplasms, IMPACT, Photon radiation therapy, Diaphragm, ANATOMICAL CHANGES, Position (vector), SETUP, Proton Therapy, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Proton therapy, Radiation, business.industry, Radiotherapy Planning, Computer-Assisted, Radiotherapy Dosage, Esophageal cancer, QUANTIFICATION, musculoskeletal system, medicine.disease, Intensity (physics), Diaphragm (structural system), ROBUSTNESS EVALUATION, Target dose, FIDUCIAL MARKERS, Oncology, RESPIRATORY MOTION, Radiotherapy, Intensity-Modulated, Protons, business, Nuclear medicine, TUMOR MOTION, RADIOTHERAPY
Abstract: Purpose: In modern conformal radiation therapy of distal esophageal cancer, target coverage can be affected by variations in the diaphragm position. We investigated if daily position verification (PV) extended by a diaphragm position correction would optimize target dose coverage for esophageal cancer treatment.Methods and Materials: For 15 esophageal cancer patients, intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans were computed. Displacements of the target volume were correlated with diaphragm displacements using repeated 4-dimensional computed tomography images to determine the correction needed to account for diaphragm variations. Afterwards, target coverage was evaluated for 3 PV approaches based on: (1) bony anatomy (PV_B), (2) bony anatomy corrected for the diaphragm position (PV_BD) and (3) target volume (PV_T).Results: The cranial-caudal mean target displacement was congruent with almost half of the diaphragm displacement (y = 0.459x), which was used for the diaphragm correction in PV_BD. Target dose coverage using PV_B was adequate for most patients with diaphragm displacements up till 10 mm (>= 94% of the dose in 98% of the volume [D-98%]). For larger displacements, the target coverage was better maintained by PV_T and PV_BD. Overall, PV_BD accounted best for target displacements, especially in combination with tissue density variations (D-98%: IMPT 94% +/- 5%, VMAT 96% +/- 5%). Diaphragm displacements of more than 10 mm were observed in 22% of the cases.Conclusions: PV_B was sufficient to achieve adequate target dose coverage in case of small deviations in diaphragm position. However, large deviations of the diaphragm were best mitigated by PV_BD. To detect the cases where target dose coverage could be compromised due to diaphragm position variations, we recommend monitoring of the diaphragm position before treatment through online imaging. (C) 2021 Elsevier Inc. All rights reserved.
Published: 2022
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44. Risk-stratification of HPV-positive women with low-grade cytology by FAM19A4/miR124-2 methylation and HPV genotyping

Author: Dick, Stèfanie, Vink, Frederique J., Heideman, Daniëlle A. M., Lissenberg-Witte, Birgit I., Meijer, Chris J. L. M., Berkhof, Johannes, Pathology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Epidemiology and Data Science, AII - Cancer immunology, and APH - Methodology
Subjects: Adult, Cancer Research, medicine.medical_specialty, Genotype, Referral, Hpv genotyping, Dyskaryosis, Cytodiagnosis, Uterine Cervical Neoplasms, Alphapapillomavirus, Article, Risk Factors, Cytology, Humans, Medicine, Genotyping, Colposcopy, DNA methylation, Molecular medicine, medicine.diagnostic_test, business.industry, Obstetrics, HPV Positive, Papillomavirus Infections, Diagnostic markers, Methylation, Middle Aged, Uterine Cervical Dysplasia, medicine.disease, female genital diseases and pregnancy complications, MicroRNAs, Oncology, Cervical cancer, Cytokines, Female, business
Abstract: Background The introduction of primary HPV screening has doubled the number of colposcopy referrals because of the direct referral of HPV-positive women with a borderline or mild dyskaryosis (BMD) cytology (ASC-US/LSIL) triage test. Further risk-stratification is warranted to improve the efficiency of HPV-based screening. Methods This study evaluated the discriminative power of FAM19A4/miR124-2 methylation, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping in HPV-positive women with BMD (n = 294) in two Dutch screening trials. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated. Results Methylation analysis discriminated well, yielding a CIN3+ risk of 33.1% after a positive result and a CIN3+ risk of 9.8% after a negative result. HPV16/18 and HPV16/18/31/33/45 genotyping resulted in a 27.6% and 24.6% CIN3+ risk after a positive result, and a 13.2% and 9.1% CIN3+ risk after a negative result. Colposcopy referral percentages were 41.2%, 43.2%, and 66.3% for FAM19A4/miR124-2 methylation, HPV16/18 and HPV16/18/31/33/45 genotyping, respectively. The CIN3+ risk after a negative result could be lowered to 2.8% by combining methylation and extended genotyping, at the expense of a higher referral percentage of 75.5%. Conclusion The use of FAM19A4/miR124-2 methylation and/or HPV genotyping in HPV-positive women with BMD can lead to a substantial reduction in the number of direct colposcopy referrals.
Published: 2022
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45. Risk factors for failure of ileal pouch-anal anastomosis in patients with refractory ulcerative colitis

Author: Johannes C. Lauscher, Jörn Gröne, Claudia Seifarth, Jan Paul Frese, Martin E. Kreis, and Frank Konietschke
Subjects: Adult, Male, medicine.medical_specialty, Prednisolone, medicine.medical_treatment, Anti-Inflammatory Agents, Colonic Pouches, Anastomosis, Body Mass Index, Sex Factors, Refractory, Risk Factors, medicine, Humans, Mesentery, In patient, Treatment Failure, Retrospective Studies, Proctocolectomy, business.industry, Proctocolectomy, Restorative, Age Factors, Perioperative, Middle Aged, medicine.disease, Ulcerative colitis, Surgery, Ileal Pouch Anal Anastomosis, stomatognathic diseases, Case-Control Studies, Colitis, Ulcerative, Female, business, Body mass index
Abstract: Background Proctocolectomy with ileal pouch-anal anastomosis is the standard surgical procedure for ulcerative colitis refractory to medical treatment. In a few cases, ileal pouch-anal anastomosis cannot be completed due to intraoperative technical problems. The aim of this single-center study was to identify risk factors for a technically failed ileal pouch-anal anastomosis. Methods In total, 391 patients with ulcerative colitis who received ileal pouch-anal anastomosis were identified. Clinical and perioperative data from patients with successful ileal pouch-anal anastomosis (IPAA+) were compared to data from failed ileal pouch-anal anastomosis (IPAA-). Definition of failed ileal pouch-anal anastomosis was intraoperative failure to perform ileal pouch-anal anastomosis. Risk factors for failed ileal pouch-anal anastomosis were assessed by logistic regression. Cut-off values were calculated on the basis of receiver operating characteristic curves and the Youden Index. Results The rate of failed ileal pouch-anal anastomosis was 26 of 391 (6.6%). In 22 of 26 cases (84.6%), there was an insufficient length of the small intestinal mesentery. Patients with failed ileal pouch-anal anastomosis were more often male (80.8% vs 54.5%, P = .009), older (47.1 ± 14.1 vs 39.2 ± 12.8 years, P = .007), had a higher body mass index 27.2 ± 4.5 vs 23.7 ± 4.3 kg/m2, P Conclusion Technical failure of ileal pouch-anal anastomosis is elevated in patients with higher body mass index, with refractory ulcerative colitis, and/or extended immunosuppressive medication. Three-staged ileal pouch-anal anastomosis and optimizing preoperative conditions may help to elevate the rate of successful ileoanal pouch construction in these patients.
Published: 2022
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46. Emerging and New Treatment Options for Knee Osteoarthritis

Author: T.L.Th.A. Jansen, Abu Bakar Siddiq, Johannes J. Rasker, Danny Clegg, and Psychology, Health & Technology
Subjects: musculoskeletal diseases, medicine.medical_specialty, Statin, medicine.drug_class, medicine.medical_treatment, Pain, Arthritis, Osteoarthritis, Injections, Intra-Articular, Rheumatology, Quality of life, Weight loss, Internal medicine, medicine, Humans, business.industry, Cartilage, Osteoarthritis, Knee, Bisphosphonate, medicine.disease, n/a OA procedure, Treatment Outcome, medicine.anatomical_structure, Platelet-rich plasma, Quality of Life, medicine.symptom, business
Abstract: Osteoarthritis (OA) is the most prevalent type of arthritis worldwide, resulting in pain and often chronic disability and a significant burden on healthcare systems globally. Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee OA has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. Due to a better understanding of osteoarthritis, innovative new treatment options have been developed. In this narrative review, we focus on emerging OA knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), metformin, lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC), exosomes, interleukin-1 blockers, gene-based therapy, and bisphosphonate.
Published: 2022
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47. Acute heart failure and iron deficiency: a prospective, multicentre, observational study

Author: Claudia C R Klaarwater, Cees Th.B.M. van Deursen, Dirk Hendrikus van Dalen, Mireille E Emans, Rémond Hendrick, Hans-Peter Brunner-La Rocca, Mireille H A Spanjers, Johannes A. Kragten, Clara E E van Ofwegen-Hanekamp, MUMC+: MA Alg Ond Onderz Cardiologie (9), MUMC+: MA Maag Darm Lever (9), Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: Carim - H02 Cardiomyopathy
Subjects: medicine.medical_specialty, Acute decompensated heart failure, Worsening heart failure, Comorbidity, DIAGNOSIS, Gastroenterology, Interquartile range, Internal medicine, medicine, Functional iron deficiency, Humans, Diseases of the circulatory (Cardiovascular) system, Prospective Studies, ANEMIA, Heart Failure, Anemia, Iron-Deficiency, biology, Transferrin saturation, business.industry, Iron deficiency, Iron Deficiencies, Original Articles, medicine.disease, PREVALENCE, Ferritin, Iron availability disorder, Heart failure, RC666-701, Ferritins, biology.protein, Original Article, Observational study, Cardiology and Cardiovascular Medicine, business
Abstract: Aims The prevalence and the natural course of iron deficiency (ID) in acute heart failure (AHF) are still unclear. We investigated the prevalence of ID in unselected patients admitted with AHF on admission, at discharge and up to 3 months thereafter. Methods and results In this prospective, multicentre, observational study, 742 patients admitted with AHF were enrolled. The main study outcome was the percentage of patients with ID (ferritin
Published: 2022

48. CXCR4 PET/MRI for follow-up of gastric mucosa–associated lymphoid tissue lymphoma after first-line Helicobacter pylori eradication

Author: Hans-Juergen Wester, Alexander Haug, Marcus Hacker, Markus Raderer, Asha Leisser, Stefan Schmitl, Ingrid Simonitsch-Klupp, Wolfgang Lamm, Johannes Rohrbeck, Marius E. Mayerhoefer, Michael Weber, Lukas Nics, and Barbara Kiesewetter
Subjects: Male, Receptors, CXCR4, medicine.medical_specialty, Immunology, Gallium Radioisotopes, Peptides, Cyclic, Biochemistry, Gastroenterology, CXCR4, Helicobacter Infections, Coordination Complexes, Stomach Neoplasms, hemic and lymphatic diseases, Internal medicine, medicine, Gastric mucosa, Humans, Prospective Studies, Prospective cohort study, Aged, Helicobacter pylori, medicine.diagnostic_test, business.industry, Esophagogastroduodenoscopy, MALT lymphoma, Lymphoma, B-Cell, Marginal Zone, Cell Biology, Hematology, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Anti-Bacterial Agents, Lymphoma, Lymphatic system, medicine.anatomical_structure, Positron-Emission Tomography, Immunohistochemistry, business, Follow-Up Studies
Abstract: Posttreatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G protein–coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate positron emission tomography (PET) with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow up biopsies for assessment of residual disease (noncomplete remission [CR]) after first-line Helicobacter pylori eradication. Forty-six post–H pylori eradication [68Ga]Pentixafor–PET/magnetic resonance imaging (MRI) examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor–PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard and showed CR in 6 cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive values of [68Ga]Pentixafor–PET for detection of residual gastric MALT lymphoma at follow-up were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r = 0.51 and r = 0.52 (P = .008 and P = .006). In summary, CXCR4 imaging with [68Ga]Pentixafor–PET may represent a promising test for assessment of residual gastric MALT lymphomas after H pylori eradication.
Published: 2022
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49. CEBPA mutations in 4708 patients with acute myeloid leukemia

Author: Christoph Schliemann, Sylvia Herold, Friedrich Stölzel, Claudia D. Baldus, Sebastian Scholl, Richard Noppeney, Michael Kramer, Martin Bornhäuser, Martin Kaufmann, Julia Annabell Georgi, Tim H. Brümmendorf, Uwe Platzbecker, Hubert Serve, Carsten Müller-Tidow, Bjoern Steffen, Wolfgang E. Berdel, Stefan W. Krause, Sebastian Stasik, Malte von Bonin, Ralph Naumann, Andreas Petzold, Kerstin Schäfer-Eckart, Andreas Neubauer, Gerhard Ehninger, Mathias Hänel, Alwin Krämer, Roger Mulet-Lazaro, Hermann Einsele, Utz Krug, Markus Schaich, Andreas Hochhaus, Johannes Schetelig, Peter J. M. Valk, Christian Thiede, Christoph Röllig, Andreas Burchert, Franziska Taube, Jan Moritz Middeke, Katja Sockel, Ulrich Kaiser, and Hematology
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Immunology, Medizin, Favorable prognosis, Biochemistry, Transactivation, Internal medicine, CEBPA, medicine, Basic Leucine Zipper, Humans, Differential impact, Aged, Retrospective Studies, business.industry, Myeloid leukemia, Cell Biology, Hematology, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Leukemia, Leukemia, Myeloid, Acute, Basic-Leucine Zipper Transcription Factors, Mutation, CCAAT-Enhancer-Binding Proteins, Female, business, Protein Binding
Abstract: Biallelic mutations of the CEBPA gene (CEBPAbi) define a distinct entity associated with favorable prognosis; however, the role of monoallelic mutations (CEBPAsm) is poorly understood. We retrospectively analyzed 4708 adults with acute myeloid leukemia (AML) who had been recruited into the Study Alliance Leukemia trials, to investigate the prognostic impact of CEBPAsm. CEBPA mutations were identified in 240 patients (5.1%): 131 CEBPAbi and 109 CEBPAsm (60 affecting the N-terminal transactivation domains [CEBPAsmTAD] and 49 the C-terminal DNA-binding or basic leucine zipper region [CEBPAsmbZIP]). Interestingly, patients carrying CEBPAbi or CEBPAsmbZIP shared several clinical factors: they were significantly younger (median, 46 and 50 years, respectively) and had higher white blood cell (WBC) counts at diagnosis (median, 23.7 × 109/L and 35.7 × 109/L) than patients with CEBPAsmTAD (median age, 63 years, median WBC 13.1 × 109/L; P < .001). Co-mutations were similar in both groups: GATA2 mutations (35.1% CEBPAbi; 36.7% CEBPAsmbZIP vs 6.7% CEBPAsmTAD; P < .001) or NPM1 mutations (3.1% CEBPAbi; 8.2% CEBPAsmbZIP vs 38.3% CEBPAsmTAD; P < .001). CEBPAbi and CEBPAsmbZIP, but not CEBPAsmTAD were associated with significantly improved overall (OS; median 103 and 63 vs 13 months) and event-free survival (EFS; median, 20.7 and 17.1 months vs 5.7 months), in univariate and multivariable analyses. Additional analyses revealed that the clinical and molecular features as well as the favorable survival were confined to patients with in-frame mutations in bZIP (CEBPAbZIP-inf). When patients were classified according to CEBPAbZIP-inf and CEBPAother (including CEBPAsmTAD and non-CEBPAbZIP-inf), only patients bearing CEBPAbZIP-inf showed superior complete remission rates and the longest median OS and EFS, arguing for a previously undefined prognostic role of this type of mutation.
Published: 2022
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50. A modified Camel and Cactus Test detects presymptomatic semantic impairment in genetic frontotemporal dementia within the GENFI cohort

Author: Moore, Katrina, Convery, Rhian, Bocchetta, Martina, Neason, Mollie, Cash, David M., Greaves, Caroline, Russell, Lucy L., Clarke, Mica T. M., Peakman, Georgia, van Swieten, John, Jiskoot, Lize, Moreno, Fermin, Barandiaran, Myriam, Sanchez-Valle, Raquel, Borroni, Barbara, Laforce, Robert, Dore, Marie-Claire, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Finger, Elizabeth, Synofzik, Matthis, Karnath, Hans-Otto, Vandenberghe, Rik, de Mendonca, Alexandre, Maruta, Carolina, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alex, Levin, Johannes, Danek, Adrian, Otto, Markus, Warren, Jason D., Rohrer, Jonathan D., Rossor, Martin N., Fox, Nick C., Woollacott, Ione O. C., Shafei, Rachelle, Heller, Carolin, Guerreiro, Rita, Bras, Jose, Thomas, David L., Nicholas, Jennifer, Mead, Simon, Meeter, Lieke, Panman, Jessica, Papma, Janne, van Minkelen, Rick, Pijnenburg, Yolande, Indakoetxea, Begona, Gabilondo, Alazne, Tainta, Mikel, de Arriba, Maria, Gorostidi, Ana, Zulaica, Miren, Villanua, Jorge, Diaz, Zigor, Borrego-Ecija, Sergi, Olives, Jaume, Llado, Albert, Balasa, Mircea, Antonell, Anna, Bargallo, Nuria, Premi, Enrico, Cosseddu, Maura, Gazzina, Stefano, Padovani, Alessandro, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wa, David, Oijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Thonberg, Hakan, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Bender, Benjamin, Bruffaerts, Rose, Van Damme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B., Miltenberger, Gabriel, Verdelho, Ana, Afonso, Sonia, Taipa, Ricardo, Caroppo, Paola, Di Fede, Giuseppe, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitao, Maria Joao, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Veldsman, Michele, Flanagan, Toby, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Semler, Elisa, Anderl-Straub, Sarah, Neurology, Clinical Psychology, Clinical Genetics, Moore, Katrina [0000-0002-4458-8390], Convery, Rhian [0000-0002-9477-1812], Bocchetta, Martina [0000-0003-1814-5024], Neason, Mollie [0000-0001-9419-7171], Greaves, Caroline [0000-0002-6446-1960], Russell, Lucy L [0000-0001-5023-5893], Clarke, Mica TM [0000-0003-0570-4296], Peakman, Georgia [0000-0002-3319-138X], Galimberti, Daniela [0000-0002-9284-5953], Otto, Markus [0000-0003-4273-4267], Rohrer, Jonathan D [0000-0002-6155-8417], and Apollo - University of Cambridge Repository
Subjects: Oncology, Cactaceae, medicine.medical_specialty, Camelus, Semantic dementia, Temporal lobe, Atrophy, Progranulins, ddc:150, complications [Frontotemporal Dementia], C9orf72, Internal medicine, Developmental and Educational Psychology, medicine, MAPT, progranulin, Semantic memory, Animals, Humans, genetics, genetics [Frontotemporal Dementia], semantic knowledge, C9orf72 Protein, Cognition, medicine.disease, Semantics, Neuropsychology and Physiological Psychology, Frontal lobe, Frontotemporal Dementia, Psychology, Frontotemporal dementia
Abstract: Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes MAPT, C9orf72, and GRN. We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 MAPT mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 GRN mutation carriers (33 symptomatic, 132 presymptomatic), and 164 C9orf72 mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = −0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: MAPT mean 22.3 (standard deviation 8.0), GRN 24.4 (7.2), C9orf72 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late MAPT and late C9orf72 mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic MAPT mutation group (rho > 0.80). In the C9orf72 group, mCCT score correlated with both bilateral temporal lobe volume (rho > 0.31) and bilateral frontal lobe volume (rho > 0.29), whilst in the GRN group mCCT score correlated only with left frontal lobe volume (rho = 0.48). This study provides evidence for presymptomatic impaired semantic knowledge in genetic FTD. The different neuroanatomical associations of the mCCT score may represent distinct cognitive processes causing deficits in different groups: loss of core semantic knowledge associated with temporal lobe atrophy (particularly in the MAPT group), and impaired executive control of semantic information associated with frontal lobe atrophy. Further studies will be helpful to address the longitudinal change in mCCT performance and the exact time at which presymptomatic impairment occurs.
Published: 2022
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