Citations

Background and Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans. Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts. Results: In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the HNF1A gene that reached genome-wide significance ( P =4.62×10 −8 ) and an additional 29 variants with suggestive evidence of association ( P <1×10 −6 ), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction P value of 2.08×10 −3 (0.05/24 unique loci), we were able to validate associations at the HNF1A locus in both SiGN ( P =8.18×10 −4 ) and METASTROKE ( P =1.72×10 −3 ) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the HNF1A gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the SFXN4 and TMEM108 genes represent potential novel ischemic stroke loci. Conclusions: These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.

Background and objectives It is unclear whether the presence of albuminuria modifies the effects of intensive systolic BP control on risk of eGFR decline, cardiovascular events, or mortality. Design, setting, participants, & measurements The Systolic Blood Pressure Intervention Trial randomized nondiabetic adults ≥50 years of age at high cardiovascular risk to a systolic BP target of <120 or <140 mm Hg, measured by automated office BP. We compared the absolute risk differences and hazard ratios of ≥40% eGFR decline, the Systolic Blood Pressure Intervention Trial primary cardiovascular composite outcome, and all-cause death in those with or without baseline albuminuria (urine albumin-creatinine ratio ≥30 mg/g). Results Over a median follow-up of 3.1 years, 69 of 1723 (4%) participants with baseline albuminuria developed ≥40% eGFR decline compared with 61 of 7162 (1%) participants without albuminuria. Incidence rates of ≥40% eGFR decline were higher in participants with albuminuria (intensive, 1.74 per 100 person-years; standard, 1.17 per 100 person-years) than in participants without albuminuria (intensive, 0.48 per 100 person-years; standard, 0.11 per 100 person-years). Although effects of intensive BP lowering on ≥40% eGFR decline varied by albuminuria on the relative scale (hazard ratio, 1.48; 95% confidence interval, 0.91 to 2.39 for albumin-creatinine ratio ≥30 mg/g; hazard ratio, 4.55; 95% confidence interval, 2.37 to 8.75 for albumin-creatinine ratio <30 mg/g; P value for interaction <0.001), the absolute increase in ≥40% eGFR decline did not differ by baseline albuminuria (incidence difference, 0.38 events per 100 person-years for albumin-creatinine ratio ≥30 mg/g; incidence difference, 0.58 events per 100 person-years for albumin-creatinine ratio <30 mg/g; P value for interaction =0.60). Albuminuria did not significantly modify the beneficial effects of intensive systolic BP lowering on cardiovascular events or mortality evaluated on relative or absolute scales. Conclusions Albuminuria did not modify the absolute benefits and risks of intensive systolic BP lowering.

Abstract Background Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as “food‐induced immediate response of the esophagus” (FIRE), observed in EoE patients. Methods Food‐induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE. Results Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P < .01) and in those with high allergic comorbidity. Food‐induced immediate response of the esophagus symptoms included narrowing, burning, choking, and pressure in the esophagus appearing within 5 minutes of ingesting a provoking food that lasted less than 2 hours. Symptom severity rated a median 7 points on a visual analogue scale from 1 to 10. Fresh fruits/vegetables and wine were the most frequent triggers. Endoscopic food removal was significantly more commonly reported in male patients with vs without FIRE (44.3% vs 27.6%; P = .03). Conclusions Food‐induced immediate response of the esophagus is a novel syndrome frequently reported in EoE patients, characterized by an intense, unpleasant/painful sensation occurring rapidly and reproducibly in 40% of surveyed EoE patients after esophageal contact with specific foods.

Abstract Introduction. Commonly prescribed medications are associated with various gastrointestinal (GI) side effects but few data are available on prescription medication use and polypharmacy in a gastroenterology outpatient practice. We aimed to examine the prevalence of polypharmacy, defined as the simultaneous use of 5 or more medications. Methods. A descriptive correlational study of consecutive outpatient consultations in 988 patients referred to a tertiary gastroenterology practice. Main outcome measurements were frequency of prescription medication use and polypharmacy. Results. The most common GI symptoms were abdominal pain (72%), nausea (57%), and constipation (53%). The frequency of polypharmacy was 10%. Eighty percent of patients took at least one medication and 60% took two or more. The most frequently used medication classes were proton pump inhibitors (43%), followed by benzodiazepines (30%), selective serotonin-reuptake or norepinephrine-reuptake inhibitors (28%), non-steroidal anti-inflammatory drugs (27%), and opioids (21%). Conclusion. There was a higher use of prescription medicine including antidepressants, and a lower frequency of polypharmacy in our study cohort compared to the general population. The use of medications may have contributed to the symptoms leading to our study’s population GI consultation.

PURPOSE The cancer research community is constantly evolving to better understand tumor biology, disease etiology, risk stratification, and pathways to novel treatments. Yet the clinical cancer genomics field has been hindered by redundant efforts to meaningfully collect and interpret disparate data types from multiple high-throughput modalities and integrate into clinical care processes. Bespoke data models, knowledgebases, and one-off customized resources for data analysis often lack adequate governance and quality control needed for these resources to be clinical grade. Many informatics efforts focused on genomic interpretation resources for neoplasms are underway to support data collection, deposition, curation, harmonization, integration, and analytics to support case review and treatment planning. METHODS In this review, we evaluate and summarize the landscape of available tools, resources, and evidence used in the evaluation of somatic and germline tumor variants within the context of molecular tumor boards. RESULTS Molecular tumor boards (MTBs) are collaborative efforts of multidisciplinary cancer experts equipped with genomic interpretation resources to aid in the delivery of accurate and timely clinical interpretations of complex genomic results for each patient, within an institution or hospital network. Virtual MTBs (VMTBs) provide an online forum for collaborative governance, provenance, and information sharing between experts outside a given hospital network with the potential to enhance MTB discussions. Knowledge sharing in VMTBs and communication with guideline-developing organizations can lead to progress evidenced by data harmonization across resources, crowd-sourced and expert-curated genomic assertions, and a more informed and explainable usage of artificial intelligence. CONCLUSION Advances in cancer genomics interpretation aid in better patient and disease classification, more streamlined identification of relevant literature, and a more thorough review of available treatments and predicted patient outcomes.

Object Spinal arthropathy is associated with hereditary hemochromatosis and has been linked to calcium pyrophosphate dehydrate crystal deposition (CPPD) which resembles ankylosing spondylitis on radiograph, yet lacks clinical findings of inflammatory spinal arthritis. The aim of our study was to assess the use of spinal surgery and its outcomes in the US inpatient population with hereditary hemochromatosis from 2012 to 2016 by using the US Nationwide Inpatient Sample (NIS) database. Methods The observational retrospective cohort study uses the NIS 2012 to 2016. All patients with hereditary hemochromatosis were included using International Classification of Diseases 9th and 10th revisions, Clinical Modification codes. The cohort was stratified according to having undergone spinal surgery and substratified by the type of surgery. The primary outcome was determining the use of spinal surgery in patients with hereditary hemochromatosis. Secondary outcomes were determining length of hospital stay and total hospital charges and costs. Results A total of 39 780 patients with hereditary hemochromatosis were identified and propensity matched to nonhereditary hemochromatosis controls. The mean patient age was 61 years, and 65% were females. For the primary outcome patients with hereditary hemochromatosis underwent significantly more spinal fusion surgery compared to patients without hereditary hemochromatosis odds of 2.13 (P = 0.05). While there was no difference in mean LOS, or costs, patients with hereditary hemochromatosis had higher hospital charges. Conclusion Hereditary hemochromatosis is associated with higher odds of spinal fusion. It is a major complication not improved by phlebotomy, and there are currently no therapies to prevent this joint disease.

Aims Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310.

Literature on postoperative urinary retention (POUR) after colorectal resections is limited. The aim of our study was to evaluate the incidence of and risk factors for POUR after elective colorectal resections in men ≥55 years without genitourinary issues. A retrospective review of elective colorectal resections (June 1, 2014 to June 1, 2015) in men ≥55 years without genitourinary conditions was performed at our institution. Patient demographics, American Society of Anesthesiologist score, body mass index (BMI), surgical history, type of disease, extent of resection, surgical approach, operating room (OR) time, volume of OR fluids administered, and intra- and postoperative urine output were included for analysis. Seventy patients were identified. Nine (12.9%) experienced POUR. Patients with POUR experienced longer OR time (324 vs 239 minutes; P = 0.048) and had a lower median BMI (23.8 vs 28 kg/m 2 ; P = 0.038). There were no significant differences in regards to age, comorbidities, diagnosis, type of resection, surgical approach, intravenous fluids administered operatively, or postoperative urine output. The incidence of POUR in male patients at least 55 years of age after elective colorectal resection in our institution was 12.9 per cent. Longer operative time and lower BMI were associated with a higher incidence of POUR.