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Background: It has been suggested that fellowship training can reduce patient morbidity and mortality related to the learning curve. There are limited data comparing the outcomes before and after b...

Background Adherence to direct oral anticoagulants (DOACs) remains a concern among non‐valvular atrial fibrillation (AF) patients. We aimed to assess patterns of adherence with DOACs and examine their association with ischemic stroke and systemic embolism (SE). Methods This retrospective cohort study includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed non‐valvular AF between January 2014 and March 2019, who initiated DOACs within 90 days of AF diagnosis and used DOACs exclusively. Adherence was assessed using the proportion of days covered (PDC) over the first year of treatment, and high adherence was defined as PDC ≥80%. Regression models were used to identify predictors of high adherence to DOACs and to examine the association between adherence and stroke or SE. Results Overall 15,255 patients were included in this study. The proportion of highly adherent (PDC ≥80%) DOACs users was around 75% and decreased slightly over the years. On multivariable analyses, the likelihood of high adherence to DOACs increased with age and across higher socioeconomic classes, and was more likely among females, Jews, statins users, and patients with CHA2DS2‐VASc score ≥2. Risk of stroke and SE was lower among highly adherent DOACs users; adjusted HR 0.56 (95% CI, 0.45–0.71), compared to users with PDC

BACKGROUND & AIMS There is a lack of convenient, sensitive, non-invasive strategies for screening and surveillance for colorectal neoplasia. An assay combining the results of circulating gastrointestinal epithelial cells (CEC) and somatic mutations of cell-free DNA adjusting for age/sex using a unique algorithm is evaluated in patients requiring colonoscopy. METHODS A prospective single-site 458-subject study (asymptomatic: 43% screening/43% surveillance, enriched with 65 symptomatic subjects) undergoing colonoscopy was conducted. The test analyzed CEC and somatic mutations. The probability of advanced neoplasia (advanced adenoma (AA) and CRC) was determined by logistic regression methods adjusted for expected CRC incidence rate, prior history of AA, patient age and sex on a training subset. A linear predictor was developed to generate a score scaled from 0-100. The test performance was evaluated on an independent set of subjects using pre-specified algorithms and cutpoint. RESULTS Based on a pre-defined clinical threshold and predictive model derived from the training set (n=232), analysis of an independent asymptomatic validation set (n=194) yielded 89% (Lower exact one-sided 95% CI: 80%) specificity and 100% (95% CI: 37%)/78% (95% CI: 61%) sensitivity for detection of CRC/AA. In a secondary analysis, excluding surveillance subjects, the 97-subject screening cohort yielded 91% (95% CI: 79%) specificity and CRC/AA sensitivity at 100% (95% CI:37%)/83% (95% CI: 56%, 87% for advanced neoplasia 95% CI: 64%). Significant associations, (p CONCLUSIONS A multimodal blood test that included CEC and somatic mutations with adjustment for age and sex demonstrated high sensitivity for the diagnosis of advanced colorectal neoplasia. The resulting score captures prognostic information for CRC progression of index adenoma size and number and has the potential to enable stratification of patients for screening or post- polypectomy surveillance colonoscopy.

We report a case of huge carcinosarcoma of lung initially presenting as an intra-abdominal mass: treatment with enucleation of the firm sarcomatous component followed by pulmonary resection. A 65-year-old man with mild mental retardation who smoked one pack of cigarettes per day until 1-month before he was admitted to our hospital complaining of a progressively poorer appetite, vomiting and an abdominal mass at the left upper quadrant region. Physical examination revealed a palpable mass over the left upper abdomen with percussion dullness of the lower hemithorax. Chest radiograph revealed a homogeneous mass lesion in the left lower lung field with obliteration of the costophrenic angle. Computed tomography scans of the chest disclosed a huge mass over the left lower thorax and upper abdomen with compression of the heart and shift of the esophagus and descending aorta to the midline. Sono-guided aspiration biopsy cytology revealed squamous cell carcinoma. Surgical intervention with enucleation of the very firm sarcomatous component with fragmentation followed by radical lobectomy. Chemotherapy was planned as adjuvant therapy in the postoperative period, but the patient's family declined it. The patient is currently survived without tumor recurrence 14 months after surgery. Our case revealed a huge tumor not only mediastinal compression but also initial presenting abdominal symptoms. Initially, from the symptoms and nonbiopsy study, we were unable to determine exactly if it was an intrathoracic tumor or an intra-abdominal tumor. This case highlights the importance of remaining clinically vigilant to differentiate an unusual tumor mass, and preoperative tissue proof is warranted.

Background: Auricular keloids belong to the most perplexing medical conditions, which have significant psychosocial impact on the patient’s body image and quality of life. Summary: The article is purposed to provide dermatologists and plastic surgeons with the best proven practice using intralesional cryosurgery for the treatment of the different auricular keloid types in order to obtain superior clinical results by minimizing the probability of recurrence. In the past 20 years, the authors have developed novel procedures in order to increase the effectiveness of intralesional cryosurgery on auricular keloids, including hydrodissection, warm gauze technique, and excision of dangling skin. Long-lasting clinical results with a low recurrence rate and a satisfactory aesthetic outcome are achieved with no deformation of the ear framework.

AML can be associated with autoimmune or inflammatory phenomena (AIP) occurring prior, concomitantly, or after its diagnosis. Trisomy 8 is one of the most common cytogenetic abnormalities associated with AML. We describe three patients with AML, trisomy 8, and associated AIP and review the known literature on this association. All of our patients had major symptomatic relief when treated with leukemia-directed therapy and corticosteroids. AIP in AML may be an underdiagnosed phenomenon, particularly in patients with trisomy 8.

Endoscopic findings in early esophageal cancer are often subtle and require careful inspection and meticulous endoscopic examination. When dysplasia is suspected, we recommend performing 1 or 2 targeted biopsies of the abnormal area and review with a pathologist specialized in evaluating gastrointestinal diseases. In the case of adenocarcinoma, after resection of any visible cancer, residual Barrett's can be treated by ablation. Endoscopic resection can offer the opportunity for patients to avoid surgery. Further studies are needed to evaluate the optimal management of circumferential and near-circumferential lesions as well as tools and techniques to facilitate the performance of endoscopic submucosal dissection and endoscopic mucosal resection.

While perforations, postoperative fistulas, and leaks have traditionally led to surgical or interventional radiology consultation for management, the introduction of the over-the-scope clip has allowed increased therapeutic possibilities for endoscopists. While primarily limited to case reports and series, the over-the-scope clip successfully manages gastrointestinal bleeding, perforations, as well as postoperative leaks and fistulas. Retrospective studies have demonstrated a relatively high success rate and a low complication rate. Given the similarity to variceal banding equipment, the learning curve with the over-the-scope clip is rapid. However, given the higher risk of procedures involving the use of the over-the-scope clip, it is essential to obtain the scope in a stable position and grasp sufficient tissue with the cap using a grasping tool and/or suction. From our experience, while closure may be successful in lesions sized up to 3 cm, successful outcomes are obtained for lesions sized

Purpose Apparent diffusion coefficient (ADC) values in the developing fetus provide valuable information on the diagnosis and prognosis of prenatal brain pathologies. Normative ADC data has been previously established in 1.5 T MR scanners but lacking in 3.0 T scanners. Our objective was to measure ADC values in various brain areas in a cohort of normal singleton fetuses scanned in a 3.0 T MR scanner. Methods DWI (diffusion-weighted imaging) was performed in 47 singleton fetuses with normal or questionably abnormal results on sonography followed by normal structural MR imaging. ADC values were measured in cerebral lobes (frontal, parietal, temporal lobes), basal ganglia, and pons. Regression analysis was used to examine gestational age-related changes in regional ADC. Results Median gestational age was 30.1 weeks (range, 26-34 weeks). There was a significant effect of region on ADC values, whereby ADC values were highest in cerebral lobes (parietal > frontal > temporal lobes), compared with basal ganglia. The lowest values were found in the pons. On regression analysis, there was a decrease in ADC values in basal ganglia and pons with increasing gestational age. ADC values in frontal, parietal, and temporal lobes were stable in our cohort. Conclusion Regional brain ADC values in 3.0 T scanners are comparable with previously reported values in 1.5 T scanners, with similar changes over gestational age. Using 3.0 T scanners is increasing worldwide. For fetal imaging, establishing normal ADC values is critical as DWI enables a sensitive and quantitative technique to evaluate normal and abnormal brain development.

Introduction: Skin biopsies can be used to evaluate physiological effects of aging targeted intervention at the tissue/cellular levels. Recent clinical trials have shown that hyperbaric oxygen therapy (HBOT) can target aging hallmarks, including telomere shortening, senescent cells clearance and angiogenesis. The aim of this study was to evaluate the effects of HBOT on the skin of a normal, non-pathological, aging population. Methods: The study was performed as a prospective clinical trial. After signing informed consent and undergoing baseline evaluations, the subjects were assigned to a three-month control period followed by three months of HBOT daily sessions. Skin biopsies were taken at baseline, after three months of no intervention (control) and 1-2 weeks following the last HBOT session. Trichrome, Orecin, lipofuscin and CD31 staining were used to evaluate collagen fibers, elastic fibers, senescent cells and blood vessels, respectively. Results: Out of the cohort of 70 participants in the normal aging population study, thirteen male patients (age 68.07±2.5y) gave consent for repeated skin biopsies. Following HBOT, there was a significant increase in collagen density (p

Background COVID-19, the novel coronavirus, has caused a global pandemic affecting millions of people around the world. Risk factors for critical disease in adults are advanced age and underlying medical comorbidities, including cancer. Data are sparse on the effect of COVID-19 infection on pediatric patients with cancer during their active antineoplastic therapy. The optimal management of antineoplastic treatment during COVID-19 infection in this unique population is controversial. Aim To describe the severity and clinical course of COVID-19 infection in pediatric patients with cancer during active antineoplastic treatment and to study their course of treatment. Methods Clinical and laboratory data were collected from medical files of patients diagnosed with COVID-19, confirmed by polymerase chain reaction (PCR), who received active antineoplastic treatment between March 2020 and May 2021 in a large tertiary pediatric medical center. Results Eighteen patients with diverse pediatric cancers are described. They were infected with COVID-19 at different stages of their antineoplastic treatment regimen. Eight had an asymptomatic COVID-19 infection, nine had mild symptoms, and one had severe disease. All of them recovered from COVID-19 infection. Two patients experienced delays in their antineoplastic treatment; none of the other patients had delays or interruptions, including patients who were symptomatic for COVID-19. Conclusion In pediatric patients with cancer who test positive for COVID-19, yet are asymptomatic or have mild symptoms, the continuance of antineoplastic therapy may be considered.

Purpose To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. Methods Injection index is defined as the mean anti-vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: ≥9, low: Results Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04-12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. Conclusion Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.

The growing human population is currently facing an unprecedented challenge on global food production and sustainability. Despite recognizing poultry as one of the most successful and rapidly growing food industries to address this challenge; poultry health and safety remain major issues that entail immediate attention. Bacterial diseases including colibacillosis, salmonellosis, and necrotic enteritis have become increasingly prevalent during poultry production. Likewise, outbreaks caused by consumption of undercooked poultry products contaminated with zoonotic bacterial pathogens such as Salmonella, Campylobacter and Listeria, are a serious public health concern. With antimicrobial resistance problem and restricted use of antibiotics in food producing animals, bacteriophages are increasingly recognized as an attractive natural antibacterial alternative. Bacteriophages have recently shown promising results to treat diseases in poultry, reduce contamination of carcasses, and enhance the safety of poultry products. Omics technologies have been successfully employed to accurately characterize bacteriophages and their genes/proteins important for interaction with bacterial hosts. In this review, the potential of using lytic bacteriophages to mitigate the risk of major poultry-associated bacterial pathogens are explored. This study also explores challenges associated with the adoption of this technology by industries. Furthermore, the impact of omics approaches on studying bacteriophages, their host interaction and applications is discussed.

Background: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI. Methods: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments. Results: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P =0.02; odds ratio, 0.58 (95% CI, 0.37–0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment. Conclusions: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897). Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02610283.

BACKGROUND: Temporal lobe T2 hyperintensity has been described in association with prenatal cytomegalovirus (CMV) infection on fetal MRI. However, these findings are often perplexing with high inter-observer variability. Our objective was to evaluate temporal lobe T2 signal quantitatively in prenatal CMV infection. METHODS: In this retrospective study, 119 fetuses, of which 51 fetuses with suspected CMV exposure (29–36 weeks of gestation) based on maternal seroconversion and age-matched 68 normal controls, were included. Mean and maximal temporal lobe T2 signal were evaluated quantitatively by measuring the T2 signal in the temporal lobes relative to the amniotic fluid’s signal. Intra-observer, inter-observer variability and diagnostic performance were assessed. The occurrence of neonatal sensorineural hearing loss (SNHL) was recorded. RESULTS: Relative temporal lobe T2 signal did not change along with the examined gestational age. Of our suspected CMV cohort, 29 fetuses were positive for fetal CMV infection on polymerase chain reaction (PCR) analysis. There were no statistically significant differences in the relative mean or maximal temporal lobes T2 signal between CMV positive, CMV negative fetuses, or normal controls. No correlation was found between neonatal SNHL and temporal lobe T2 signal. CONCLUSIONS: When temporal lobe T2 signal is analyzed quantitatively, CMV infected fetuses do not present an increased signal than age-matched controls. Thus, reported subjective temporal T2 hyperintensities should be interpreted carefully and should have a limited effect on pregnancy management, especially as an isolated finding. Our study illustrates the importance of quantitative imaging in diagnostic neuroradiology.

Background We recently reported that autologous fecal microbiota transplantation (aFMT), derived from the time of maximal weight-loss and administrated in the regain-phase, might preserve weight loss and glycemic control in moderately obese subjects, and is associated with specific microbiome signatures. Here, we sought to explore the global effect of aFMT on adipokines, inflammatory markers and blood cholesterol and on the overall gut microbiome preservation. Methods In the DIRECT-PLUS weight-loss trial, abdominally obese participants were randomized to three distinct weight-loss diets. Following the expected weight loss phase (0–6 m), 90 participants were randomized to receive their personal frozen fecal microbiota or placebo oral capsules (ten 1 g-capsules over ten sessions-total=100 g) during the expected weight regain phase (8–14 m). Results Of the 90 participants (age=52 yr; 0–6 m weight loss=-8.3 kg), 95.6% ingested at least 80/100 oral aFMT/placebo capsules over 6 months. Overall, the gut microbiome community structure was associated with plasma levels of leptin, cholesterol and interleukin-6 at baseline and after 6 m, whereas 6 m (weight loss phase) changes in specific microbiome species associated with the dynamic of leptin and inflammatory biomarkers. Following the 8–14 m aFMT administration phase, aFMT maintained decreased levels of leptin (ΔaFMT=-3.54 ng/mL vs. Δplacebo=-0.82 ng/mL;P = 0.04), C-reactive-protein (ΔaFMT=-1.45 mg/L vs. Δplacebo=-0.66 mg/L;P = 0.009), Interleukin-6 (ΔaFMT=-0.03pg/mL vs. Δplacebo=1.11pg/mL;P = 0.03) and total cholesterol (ΔaFMT=2.2 mg/dl vs. Δplacebo=13.1 mg/dl;P = 0.04) achieved in the weight loss phase. Overall, aFMT induced a significant preservatory effect on personal gut microbiome global composition (P = 0.03;Jensen-Shannon distance), as compared to placebo. Conclusions aFMT treatment in the regain phase might retain weight-loss induced metabolic benefits. These findings may suggest a novel aFMT treatment approach for personal metabolic attainment preservation.

Acute chorioamnionitis complicates 1-2% of all pregnancies and might increase the prevalence of endometritis that can cause Asherman syndrome or adhesions, but little is known about the direct effects of chorioamnionitis on future fertility. We aimed to evaluate the effect of chorioamnionitis on future fertility and obstetrics complications in patients diagnosed with chorioamnionitis during their pregnancy. We performed an observational, case-control retrospective study of pregnant women aged 18-40 years old, hospitalized with a diagnosis of chorioamnionitis between January 2013 and December 2017. The control group consisted of patients with similar demographic/obstetrics characteristics, matched with a ratio of 1:2 without chorioamnionitis. The prevalence of post gestational diagnostic hysteroscopy was significantly higher in the study group as compared to the control group (22.9% versus 9.0%, respectively

This article queries how learning analytics systems can support content-specific group formation to develop students’ thinking about a specific mathematical concept. Automated group formation requires identifying personal characteristics, designing tasks to probe students’ perceptions, and grouping them to increase individual learning chances. Designers of automated group formation recommendation modules (GFRMs) rarely consider content-specific objectives. We draw on theories on conceptual learning in mathematics and dialogic thinking to emphasize the role of a dialogic gap between students’ voices to enhance individual learning. In an experiment, fifty 8th and 9th grade students solved three mathematical tasks in a pre-intervention-post-set-up: individually, then in dyads, and then individually again. We used a learning analytics system to collect fine-grained content-specific data on students’ responses based on four pre-defined aspects of the parabola concept. We compared students’ answers with those of their peers in order to identify interpersonal relations. The experiment results indicate that students’ thinking about the parabola concept was the most successfully developed when every group member had a different perception of this concept. We illustrate the learning trajectories of four students and elaborate on the learning sequence of one of these students in particular. This article suggests that the centrality of a dialogic gap in developing personal learning is probably content independent. We thus call for software engineers to think about GFRMs that can support content-specific learning and instruction.

Third trimester amniocentesis is often performed when indications arise after 24 weeks of gestation—typically to investigate new sonographic findings, and might be related to pre-term birth. Scarcity of data exists concerning the risks of third-trimester amniocentesis in twin pregnancies. A retrospective cohort study of all twin gestations that underwent amniocentesis in a tertiary hospital between 2007 and 2016. Outcomes and procedure-related complications were compared between third-trimester (≥ 24 weeks) and mid-trimester amniocentesis (16–23 weeks). Primary outcome was defined as membrane rupture within four weeks of procedure. Logistic regression analysis was utilized to adjust results to potential confounders. Overall, 185 eligible women were included, of them, 28 (15.1%) underwent third-trimester amniocentesis and 157 (84.9%) underwent mid-trimester amniocentesis. Women in the third-trimester amniocentesis group were younger and presented higher frequencies of intra-uterine growth restriction (31.5 vs. 35.3, p

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by multiorgan hamartomas, including cerebral lesions, with seizures as a common presentation. Most TSC patients will also experience neurocognitive comorbidities. Our objective was to use machine learning techniques incorporating clinical and imaging data to predict the occurrence of major neurocognitive disorders and seizures in TSC patients. A cohort of TSC patients were enrolled in this retrospective study. Clinical data included genetic, demographic, and seizure characteristics. Imaging parameters included the number, characteristics, and location of cortical tubers and the presence of subependymal nodules, SEGAs, and cerebellar tubers. A random forest machine learning scheme was used to predict seizures and neurodevelopmental delay or intellectual developmental disability. Prediction ability was assessed by the area-under-the-curve of receiver-operating-characteristics (AUC-ROC) of ten-fold cross-validation training set and an independent validation set. The study population included 77 patients, 55% male (17.1 ± 11.7 years old). The model achieved AUC-ROC of 0.72 ± 0.1 and 0.68 in the training and internal validation datasets, respectively, for predicting neurocognitive comorbidity. Performance was limited in predicting seizures (AUC-ROC of 0.54 ± 0.19 and 0.71 in the training and internal validation datasets, respectively). The integration of seizure characteristics into the model improved the prediction of neurocognitive comorbidity with AUC-ROC of 0.84 ± 0.07 and 0.75 in the training and internal validation datasets, respectively. This proof of concept study shows that it is possible to achieve a reasonable prediction of major neurocognitive morbidity in TSC patients using structural brain imaging and machine learning techniques. These tools can help clinicians identify subgroups of TSC patients with an increased risk of developing neurocognitive comorbidities.

Vascular dysfunction is entwined with aging and in the pathogenesis of Alzheimer's disease (AD) and contributes to reduced cerebral blood flow (CBF) and consequently, hypoxia. Hyperbaric oxygen therapy (HBOT) is in clinical use for a wide range of medical conditions. In the current study, we exposed 5XFAD mice, a well-studied AD model that presents impaired cognitive abilities, to HBOT and then investigated the therapeutical effects using two-photon live animal imaging, behavioral tasks, and biochemical and histological analysis. HBOT increased arteriolar luminal diameter and elevated CBF, thus contributing to reduced hypoxia. Furthermore, HBOT reduced amyloid burden by reducing the volume of pre-existing plaques and attenuating the formation of new ones. This was associated with changes in amyloid precursor protein processing, elevated degradation and clearance of Aß protein and improved behavior of 5XFAD mice. Hence, our findings are consistent with the effects of HBOT being mediated partially through a persistent structural change in blood vessels that reduces brain hypoxia. Motivated by these findings, we exposed elderly patients with significant memory loss at baseline to HBOT and observed an increase in CBF and improvement in cognitive performances. This study demonstrates HBOT efficacy in hypoxia-related neurological conditions, particularly in AD and aging.

Scarring of the face following chemical peeling is an uncommon and devastating complication. This case report describes the successful treatment of bulky mature keloids on both cheeks following deep chemical peeling by using a combined approach of intralesional cryosurgery followed by pulsed dye and ablative fractional CO2 laser therapy. Level of evidence: Level V, therapeutic study.

Background Anatomical location and extent of disease are main factors that affect inflammatory bowel disease (IBD) course and prognosis. No explanation is available for segmental intestinal involvement in either Crohn’s disease (CD) or ulcerative colitis (UC), or for selective segmental response to therapy or disease complications. Therefore, studying the cellular composition of different intestinal segments may provide pathophysiological insights into these phenomena. Methods We compared location-specific cell composition and function by Cytometry Time-of-Flight (CyTOF), gene expression and single-cell (sc) RNAseq data obtained from 3 independent cohorts of healthy donors and IBD patients during remission and flare-ups. Using CyTOF data (n = 38 biopsies), we built a high-resolution screening of immune cell behaviour along the intestine. We validated the findings with gene expression data of 370 samples, and expanded screening resolution by computational methodologies. We then tested a specific pathway in scRNAseq data (n = 10 paired biopsies from 5 patients) and validated its significance by cell-specific Significance Analysis of Microarrays (csSAM). Results We found a location along the intestine to be a dominant feature determining immune and non-immune cell composition. We observed that inflammation reduced anatomic segregation beyond cell infiltration, and decreased the ability to cope with oxidative stress. An upregulated IL-6 pathway in T regulatory cells in UC patients was recognised as sigmoid-specific compared with known inflammatory IL-6 roles in macrophages, as seen in the right colon. This observation may be linked to colonic perforations associated with anti-IL-6R treatment. Suppressor of cytokine signalling 3 (SOCS3) may control IL-6 location-specific action. Conclusion Our study displays a unique and comprehensive cell map of IBD in a location-specific context, providing potential explanations to unexplained clinical phenomena. These observations may allow to tailor therapies to affected areas with improved therapeutic index and efficacy.

Corporate Social Responsibility (CSR) initiatives play an important starring role in changing the livelihoods of community members close to casinos around Gauteng. In addition, a contested industry such as gaming needs to ensure CSR initiatives are in place and communicated. The specific objective was to develop a CSR conceptual framework with guidelines for implementation in the casino industry using an Exploratory Factor Analysis (EFA). The study used quantitative research approach which involved eight casinos in Gauteng province, South Africa. Accidental sampling was used with a sample size of 385 with adjacent community members. Structured questionnaires were used as data collection instrument. The results indicated that social aspects and involvement, business and socio-environment, financial contribution, community basic services and food and nutrition are the basic initiatives to be incorporated in casino’s strategies and communicated to different stakeholders in order to improve community satisfaction, ideal public relations and gaining competitive advantage. Findings offer valuable cognizance in helping community members, Gauteng Gambling Board, CSR managers in casinos, employees and other interested stakeholders to review and evaluate the casinos’ CSR policies and implementation strategies.

An “unplanned excision” refers to soft tissue sarcomas excised without planning imaging studies and a diagnostic biopsy, resulting in the presence of residual disease and usually necessitating a re-excision procedure. We aimed to assess the impact of previous unplanned excisions on the intra-operative pathologic assessment at the time of re-excision, in terms of need to perform repeat assessments and the accuracy to predict margin status of the final pathologic specimen. Data was collected for all patients with extremity soft tissue sarcoma who had undergone wide local excision limb salvage surgery or amputation between 2012 and 2017. Intra-operative pathologic assessment with frozen sections was performed in all cases and was classified as negative, negative but close (

ObjectiveAnti-drug antibodies (ADA) to anti-tumour necrosis factor (anti-TNF) therapy drive treatment loss of response. An association between intestinal microbial composition and response to anti-TNF therapy was noted. We therefore aimed to assess the implications of antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD).DesignWe analysed data from the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all patients with IBD in Israel. We included all patients treated with anti-TNF who had available ADA levels. Survival analysis with drug use as time varying covariates were used to assess the association between antibiotic use and ADA development. Next, specific pathogen and germ-free C57BL mice were treated with respective antibiotics and challenged with infliximab. ADA were assessed after 14 days.ResultsAmong 1946 eligible patients, with a median follow-up of 651 days from initiation of therapy, 363 had positive ADA. Cox proportional hazard model demonstrated an increased risk of ADA development in patients who used cephalosporins (HR=1.97, 95% CI 1.58 to 2.44), or penicillins with β-lactamase inhibitors (penicillin-BLI, HR=1.4, 95% CI 1.13 to 1.74), whereas a reduced risk was noted in patients treated with macrolides (HR=0.38, 95% CI 0.16 to 0.86) or fluoroquinolones (HR=0.20, 95% CI 0.12 to 0.35). In mice exposed to infliximab, significantly increased ADA production was observed in cephalosporin as compared with macrolide pretreated mice. Germ-free mice produced no ADA.ConclusionADA production is associated with the microbial composition. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillin-BLIs, or by treatment with fluoroquinolones or macrolides.

Objectives There are multiple etiologies of heterotopic ossification )HO) and limited information regarding the outcome of HO complicating specific injuries in children. The aim of this study was to examine the characteristics and long term results of treatment of HO in pediatric patients with severe traumatic brain injury (TBI). Patients and methods The files of all patients treated at a pediatric rehabilitation center with severe TBI during the study period were retrospectively examined. Patients diagnosed with HO during the rehabilitation period were examined in the clinic. Results Of 75 patient with TBI, HO was diagnosed in six patients at an average of four months after the injury. No difference was found between patients with or without HO, regarding age, gender, GCS, length of stay in rehabilitation facility or ventilation during this period. In all the six patients diagnosed with HO, the involved side was the spastic and paraparetic limb, 4 in the elbow, 1 knee and 1 hip joint. Symptoms resolved in five patients with NSAIDS treatment. One patient required surgical excision of the elbow HO, due to a progressive ulnar neuropathy. Conclusion Severe TBI in children may be complicated by HO of the spastic and paraparetic limb at a rate of 8%, the majority in the elbow joint. The rate and manifestations of the HO are less severe than in adults. Although treatment and timing of excision of HO is controversial, a peripheral neuropathy may be an indication for early excision of the HO mass. [Hand Microsurg 2021; 10(2.000): 80-87]

Bicuspid aortic valve (BAV) is the most common valvular congenital heart disease, with a prevalence of 0.5 to 2% in the general population. Patients with BAV are at risk for developing cardiovascular complications, some of which are life-threatening. BAV has a wide spectrum of clinical presentations, ranging from silent malformation to severe and even fatal cardiac events. Despite the significant burden on both the patients and the health systems, data are limited regarding pathophysiology, risk factors, and genetics. Family studies indicate that BAV is highly heritable, with autosomal dominant inheritance, incomplete penetrance, variable expressivity, and male predominance. Owing to its complex genetic model, including high genetic heterogenicity, only a few genes were identified in association with BAV, while the majority of BAV genetics remains obscure. Here, we review the different forms of BAV and the current data regarding its genetics. Given the clear heritably of BAV with the potential high impact on clinical outcome, the clinical value and cost effectiveness of cascade screening are discussed.

Late onset neutropenia (LON) after rituximab is a previously described complication. We aimed to assess and characterize LON after obinutuzumab, a novel anti-CD20 antibody, in the real-world setting and compare it to LON after rituximab therapy. We retrospectively analyzed 330 consecutive patients with lymphoproliferative neoplasms (rituximab-treated n = 283; obinutuzumab-treated n = 47). LON occurred in 23% patients with similar incidence in rituximab (n = 66, 23%) or obinutuzumab (n = 10, 21%) groups (p = 0.853). Patients treated for CLL and post-transplantation lymphoproliferative disease (PTLD) were at higher risk to develop LON (multivariate analysis: HR for CLL - 6.62 CI 95% 1.33-32.92; HR for PTLD 15.82 CI 95% 2.04-122.4). Febrile neutropenia was uncommon during LON and occurred in 15 patients (4.5%; rituximab (n = 14) and obinutuzumab (n = 1).These data suggest that LON after obinutuzumab treatment is as common as with rituximab. The similarities in LON after rituximab and obinutuzumab argue for a possible class effect for anti-CD20 monoclonal antibodies.

BACKGROUND Minimally-invasive endoscopic strip-craniectomy (or suturectomy) for the repair of craniosynostosis combined with postoperative cranial orthotic molding has been widely adopted in the past 2 decades, proving itself as a safe and effective procedure. Over time the authors transitioned from performing an endoscopic strip-craniectomy, to performing the same surgery without the endoscope. The authors here describe our technique and compare its results to those published in the literature for endoscopic suturectomies. METHODS A retrospective chart review was performed for patients with nonsyndromic craniosynostosis who underwent minimally-invasive nonendoscopic suturectomy between 2019 and 2020 at our institution. RESULTS Thirteen patients (11 males; 2 females) were operated including 5 Metopic, 5 Sagittal, 2 coronal, and 1 lambdoid craniosynostosis. The average age at surgery was 4.35 months. The average length of surgery was 71 minutes. Averaged intraoperative estimated blood loss was 31.54 mL. Eleven patients received a blood transfusion (most before performing the skin incision) with a mean amount of 94.62 mL of blood transfused during surgery. The mean hemoglobin at discharge was 10.38 mg/dL. There was only 1 intraoperative mild complication. The mean intrahospital length of stay was 1.77 days with no postoperative complications noted. All patients initiated remodeling orthotic treatment following surgery. Long-term follow-up scans were available for 8 patients (5 metopic, 2 sagittal, and 1 lambdoid) with an average follow-up of 9 months. In all cases, there was a significant improvement in the skull width at the synostosis location as well as in the skull proportions and symmetry. The above outcomes are similar to those published in the literature for endoscope-assisted strip-craniectomies. CONCLUSIONS Suturectomies assisted with cranial orthosis remodeling for the treatment of all types of nonsyndromic craniosynostosis can be performed without an endoscope while maintaining minimal-invasiveness, good surgical results, and low complication rates.

Background/aim Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk. Materials and methods MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples. Results MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index. Conclusion Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of disease than age-matched non-pregnant women, the risk of feto-placental infection is low. Using a cohort of 66 COVID-19-positive women in late pregnancy, we correlated clinical parameters with disease severity, placental histopathology, and the expression of viral entry and Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None of the demographic parameters or placental histopathological characteristics were associated with disease severity. The fetal-maternal transfer ratio for IgG against the N or S viral proteins was commonly less than one, as recently reported. We found that the expression level of placentalACE2,but notTMPRSS2orFurin,was higher in women with severe COVID-19. Placental expression of IFITM1 and IFITM3, which have been implicated in antiviral response, was higher in participants with severe disease. We also showed that IFITM3 protein expression, which localized to early and late endosomes, was enhanced in severe COVID-19. Our data suggest an association between disease severity and placental SARS-CoV-2 processing and antiviral pathways, implying a role for these proteins in placental response to SARS-CoV-2.

Robert N Jamison,1 Robert R Edwards,1 Samantha Curran,1 Limeng Wan,1 Edgar L Ross,1 Christopher J Gilligan,1 Shai N Gozani2 1Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School, Brigham & Women’s Hospital, Chestnut Hill, MA, USA; 2NeuroMetrix, Inc., Woburn, MA, USACorrespondence: Shai N GozaniNeuroMetrix, Inc., 4b Gill St., Woburn, MA, 01801, USATel +1 781 314 2789Fax +1 781 890 1556Email gozani@neurometrix.comPurpose: Fibromyalgia is a chronic condition characterized by widespread pain and interference with daily activities. The aim of this study is to assess the benefit of transcutaneous electrical nerve stimulation (TENS) for persons diagnosed with fibromyalgia.Patients and Methods: Adults meeting diagnostic criteria for fibromyalgia were randomized in a double-blind trial to receive either an active (n=62) or sham (n=57) wearable TENS device for 3-months. Subjects were classified as having lower or higher pain sensitivity by Quantitative Sensory Testing (QST). Patient Global Impression of Change (PGIC, primary outcome) and secondary efficacy measures including Fibromyalgia Impact Questionnaire (FIQR), Brief Pain Inventory (BPI) and painDETECT questionnaire (PDQ) were assessed at baseline, 6-weeks and 3-months. Treatment effects were determined by a mixed model for repeated measures (MMRM) analysis of the intention-to-treat (ITT) population (N=119). A pre-specified subgroup analysis of pain sensitivity was conducted using an interaction term in the model.Results: No differences were found between active and sham treatment on PGIC scores at 3-months (0.34, 95% CI [− 0.37, 1.04], p=0.351) in the ITT population. However, in subjects with higher pain sensitivity (n=60), PGIC was significantly greater for active treatment compared to sham (1.19, 95% CI [0.24, 2.13], p=0.014). FIQR total score (− 7.47, 95% CI [− 12.46, − 2.48], p=0.003), FIQR pain item (− 0.62, 95% CI [− 1.17, − 0.06], p=0.029), BPI Interference (− 0.70, 95% CI [− 1.30, − 0.11], p=0.021) and PDQ (− 1.69, 95% CI [− 3.20, − 0.18], p=0.028) exhibited significant improvements for active treatment compared to sham in the ITT population. Analgesics use was stable and comparable in both groups.Conclusion: This study demonstrated modest treatment effects of reduced disease impact, pain and functional impairment from wearable TENS in individuals with fibromyalgia. Subjects with higher pain sensitivity exhibited larger treatment effects than those with lower pain sensitivity. Wearable TENS may be a safe treatment option for people with fibromyalgia.Clinicaltrials.gov Registration: NCT03714425.Keywords: fibromyalgia, wearable, transcutaneous electrical nerve stimulation, neuromodulation, non-pharmacological treatment, clinical trial

The European pharmaceutical industry uses the alleged efficacy of self-regulation to question the need for transparency laws similar to the US Physician Payment Sunshine Act. We conducted a comparative analysis of 20 large companies’ payment disclosures in seven European countries in 2017–2019. The data was extracted as part of eurosfordocs.eu, a novel transparency project that scrapes and integrates publicly available databases and disclosures. Our analysis of EUR 735 million showed marked differences in country payment patterns. For example, payment totals per registered doctor were substantially larger in Spain and lowest in Sweden. There were significant country and company differences in individualized data completeness. Only 19% of totals were reported with recipient names in Germany, compared to Ireland (59%), the United Kingdom (60%), Italy (67%), Switzerland (73%), Sweden (79%) and Spain (100%), with little or no improvement over time. Payment data in Spain was particularly difficult to extract. Thus, in no country did self-regulation generate comprehensive individualized data allowing for building an accurate picture of financial relationships between the industry and healthcare professionals. We conclude that the cultures and policies of countries and companies create structural problems of data inaccessibility and incompleteness within the self-regulatory framework. Therefore, this study supports calls for a Europe-wide “Sunshine Act” to achieve real transparency of drug company payments.

To investigate the effect of the COVID-19 pandemic on healthcare utilization related to labor and delivery and to assess the effect of the COVID-19 pandemic on intra-partum and delivery complications.This retrospective study was performed at a university-affiliated, tertiary medical center. It included women admitted to the delivery room from 1 March 2020 to 23 July 2020 during the first wave of the COVID-19 pandemic. They were compared against women who were admitted to the delivery room during the same time period in 2019. The outcomes of 2701 deliveries during the pre-pandemic period were compared to those of 2668 deliveries during the pandemic period. Main outcomes were pregnancy and delivery outcomes.The mean number of emergency department visits before admission for delivery was higher in the pre-pandemic period than in the pandemic period (2.3 ± 1.5 and 2.1 ± 1.3 visits, respectively;In our study population, in the presence of public and accessible obstetric medicine, the first wave of the COVID-19 pandemic did not affect pregnancy or early delivery outcomes.

Endometriosis is a gynaecological disease in which cell tissue that lines inside of the uterine cavity (the endometrium) flourishes outside of the uterus. This leads to inflammation in the surrounding tissue and causes the main symptoms of endometriosis: chronic pain, digestive problems, fertility complications, and fatigue. This paper describes a group intervention for women suffering from endometriosis, which was conducted at a hospital Center for Endometriosis. Using a narrative therapy approach, we designed and implemented a group-work process focused on addressing the quality of life (QoL) and well-being of women with endometriosis. Intervention design: 23 patients from the Center for Endometriosis, Sheba Medical Center, were anonymously surveyed to ensure that the group work would address the needs of potential participants. The results of the survey indicated that the group intervention should focus on participants’ QoL and well-being, addressing low self-perception, feelings of loneliness and lack of control over their condition, and the effects of coping with chronic pain on their daily lives. In order to achieve these goals, a series of interim targets were set, for example, the creation of a sense of belonging among group members, participants’ awareness of unique outcomes in their narratives, identification of strengths and capabilities. Our group intervention protocol was based on a model for group work with women who have experienced sexual assault. The model was adapted and tailored to the experiences of women with endometriosis. Participants noted significantly reduced feelings of loneliness. They gained an enhanced ability to cope with the disease and identified strengths and skills that helped increase their sense of control over their condition. Consequently, they noticed a change in their self-perception and their perception of their condition. Based on the encouraging results, we recommend conducting similar group interventions for endometriosis patients as an additional tool for improving their quality of life and well-being.

PURPOSE To evaluate whether ethnicity affects the risk of full mutation expansion among females heterozygous for FMR1 premutation. METHODS Women who carry the FMR1 premutation alelle of Jewish origin who underwent fragile X prenatal diagnosis between 2011 and 2018 in two medical centers in Israel were included. The heterozygote women and fetuses were analyzed for the number of CGG repeats and AGG interruptions. RESULTS Seven hundred sixty-six subjects were included. Parental ethnicity was fully concordant in 592 cases (Jewish, Ashkenazi, and non-Ashkenazi). Ashkenazi compared with non-Ashkenazi heterozygotes have a significantly higher mean number of CGG repeats (68 ± 8.7, 64 ± 6.4 respectively, P = 0.03) and a lower mean number of AGG interruptions (0.89 ± 0.83, 1.60 ± 1.18 respectively, p = 0.0001). Overall, 56/198 (28.2%) fetuses of Ashkenazi heterozygotes had an expansion to a full mutation compared with 6/98 among the non-Ashkenazi (6.1%) (p = 0.001). Multivariate analysis demonstrated that, in addition to CGG repeats and AGG interruptions (which contributed 68.3% of variance), ethnicity is an independent risk factor for a full mutation expansion (odds ratio [OR] = 2.04, p

Background Substance misuse is a global public health problem. In addition to social and economic concerns, consumption of tobacco and alcohol is associated with susceptibility to cardiovascular, respiratory, and infectious diseases, cancers, and risk of transition to substance use disorders. African data suggest regional differences in the prevalence and patterns of substance use, but a number of key questions remain. This cross-sectional population-based study of middle-aged adults aims to examine prevalence and socio-demographic correlates of substance use in four sub-Saharan African countries, in rural and urban settings. Methods Participants aged between 40 and 60 years were recruited from six research centres as part of the Africa Wits-INDEPTH partnership for Genomic Research study. Data on patterns of tobacco and alcohol consumption was captured, and the latter further assessed using the CAGE (cut-annoyed-guilty-eye) questionnaire. Results Data from 10,703 participants suggested that more men (68.4%) than women (33.3%) were current substance users. The prevalence of current smoking was significantly higher in men than in women (34.5% vs 2.1%, p Conclusions Regional variation in the patterns and prevalence of substance use was observed across study sites, and in rural and urban settings. The high levels of substance use recorded in this study are of concern due to the increased risk of associated morbidities. Further longitudinal data will be valuable in determining trends in substance misuse in Africa.

AIMS Oral anticoagulants (OACs) are considered the mainstay in preventing stroke in atrial fibrillation (AF). OAC treatment remains suboptimal among AF patients, even after the introduction of direct oral anticoagulants (DOACs). We aimed to assess trends overtime and current implementation of OAC treatment guidelines in AF, using a large dataset of real world data from Israel. METHODS This is a retrospective cohort study that includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed nonvalvular AF between January 2014 and December 2019 with CHA2 DS2 -VASc score ≥2. OAC treatment rates were calculated and multivariate regression models were used to identify predictors of OACs initiation. RESULTS Overall, 46 531 patients were included in the study. The 3-months cumulative OAC treatment rates increased consistently over the years: 46.9% (95% confidence interval, 46.1-47.7%), 54.9% (54.1-55.6%) and 61.7% (60.9-62.4%) during 2014-2015, 2016-2017 and 2018-2019, respectively. DOACs constituted 51.3% of prescribed OACs in 2014-2015 and increased to 95.1% during 2018-2019. On multivariate analyses, the likelihood of OACs initiation among AF patients increased across the years and across higher socioeconomic classes, and was more likely among females, Jews, statins users and patients previously screened for colorectal cancer, but less likely among smokers and patients with impaired renal function. The likelihood of treatment increased with higher CHA2 DS2 -VASc score and decreased with higher HAS-BLED score. CONCLUSION Despite the increasing OAC treatment rates among high-risk AF patients, mainly attributed to the expanding DOAC use, OAC treatment scope is still far from optimal.

BACKGROUND AND AIMS In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF. METHODS For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA-), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays. RESULTS At baseline, participants (92% men; body mass index = 30.2 kg/m2 ) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P

COVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents. Supplementary Information The online version contains supplementary material available at 10.1186/s40246-021-00326-3.

LAY SUMMARY As the COVID-19 pandemic continues to grow in many areas of the world, the virus may increasingly infect military service members and their families. Most service members who contract COVID-19 develop a mild disease course that requires primarily supportive care and steps to limit the spread of infection to others. However, increasing evidence suggests that heart, lung, and coagulation disorders and psychological sequelae may occur even among generally healthy young adult COVID-19 patients. These potential manifestations of the disease are a cause for concern for Israeli Air Force pilot cadets and aircrew personnel, particularly in high-performance aircraft, because they may lead to decreased performance during flight and potentially to sudden incapacitation. In this article, the authors describe the Israeli Aeromedical Center’s recommendations to flight surgeons on the medical workup required before military aviators return to flight duties after recovery from COVID-19.

Background We tested whether CHA2DS2-VASc and/or HAS-BLED scores better predict ischemic stroke and major bleeding, respectively, than their individual components in maintenance hemodialysis (MHD) patients with atrial fibrillation (AF). Methods A retrospective cohort study of a clinical database containing the medical records of 268 MHD patients with non-valvular AF (167 women, mean age 73.4 ± 10.2 years). During the median follow-up of 21.0 (interquartile range, 5.0–44.0) months, 46 (17.2%) ischemic strokes and 24 (9.0%) major bleeding events were reported. Results Although CHA2DS2-VASc predicted ischemic stroke risk in the study population (adjusted HR 1.74 with 95% CI 1.23–2.46 for each unit of increase in CHA2DS2-VASc score, and HR of 5.57 with 95% CI 1.88–16.49 for CHA2DS2-VASc score ≥ 6), prior ischemic strokes/transient ischemic attacks (TIAs) were non-inferior in both univariate and multivariate analyses (adjusted HR 8.65 with 95% CI 2.82–26.49). The ROC AUC was larger for the prior ischemic stroke/TIA than for CHA2DS2-VASc. Furthermore, the CHA2DS2-VASc score did not predict future ischemic stroke risks in study participants who did not previously experience ischemic strokes/TIAs (adjusted HR 1.41, 95% CI: 0.84–2.36). The HAS-BLED score and its components did not have predictive abilities in discriminating bleeding risk in the study population. Conclusions Previous ischemic strokes are non-inferior for predicting of future ischemic strokes than the complete CHA2DS2-VASc score in MHD patients. CHA2DS2VASc scores are less predictive in MHD patients without histories of CVA/TIA. HAS-BLED scores do not predict major bleeding in MHD patients. These findings should redesign approaches to ischemic stroke risk stratification in MHD patients if future large-scale epidemiological studies confirm them.