Prevalence of H. pylori and gastric intestinal metaplasia in BRCA1 and BRCA2 carriers.

BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer (GC), however the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of GC risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of GC in this population. 100 unselected BRCA1/2 carriers undergoing endoscopic ultrasound from 3/2022-3/2023 underwent concomitant upper endoscopy with non-targeted gastric antrum and body biopsies. The study population (70% women; mean age: 60.1) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no GCs were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to the general population, however identification of H. pylori or GIM may help inform future GC risk management strategies in BRCA1/2 carriers.

Gastric Cancer Risk and Pathogenesis in BRCA1 and BRCA2 Carriers.

Carriers of a pathogenic germline variant (PV) in BRCA1 or BRCA2 are at increased risk for a number of malignancies, including breast, ovarian, pancreatic, and prostate cancer. In this review, we discuss emerging evidence that BRCA2 PV carriers, and likely also BRCA1 PV carriers, are also at increased risk for gastric cancer (GC), highlighting that GC may be part of the BRCA1/2 cancer risk spectrum. While the pathogenesis of GC among BRCA1/2 PV carriers remains unclear, increasing evidence reveals that GCs are often enriched with mutations in homologous recombination-associated genes such as BRCA1/2, and that GC prognosis and response to certain therapies can depend on BRCA1/2 expression. Given the strength of data published to date, a risk management strategy for GC among BRCA1/2 PV carriers is needed, and herein we also propose a potential strategy for GC risk management in this population. Moving forward, further study is clearly warranted to define the mechanistic relationship between BRCA1/2 PVs and development of GC as well as to determine how GC risk management should be factored into the clinical care of BRCA1/2 carriers.

Interventions to Decrease Unplanned Healthcare Utilization and Improve Quality of Care in Adults With Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) care and outcomes exhibit substantial variability, suggesting quality gaps. We aimed to identify interventions to narrow these gaps. METHODS: We performed a systematic review of Medline, Embase, and Web of Science through May 2021 to find manuscripts and abstracts reporting quality improvement (QI) interventions in IBD. We included studies with interventions that addressed acute care utilization, vaccination, or Crohn's and Colitis Foundation quality indicators for care processes, including pre-therapy testing, tobacco cessation, colorectal cancer surveillance, Clostridium difficile infection screening in flares, sigmoidoscopy in patients hospitalized with ulcerative colitis, and use of steroid-sparing therapy. The primary objective was to identify successful QI interventions. Risk of bias assessment was conducted using the Joanna Briggs Institute critical appraisal checklist. RESULTS: Twenty-three manuscripts and 23 meeting abstracts met inclusion criteria. Influenza and pneumococcal vaccination were the most studied indicators (24 references), followed by emergency room and/or hospital utilization, tobacco cessation, and pre-therapy testing (17, 11, and 10 references, respectively). Electronic medical record-based interventions were the most frequent, whereas other initiatives used strategies that included changes to care structure or delivery, vaccination protocols, or physician and patient education. Successful interventions matched the complexity of the metric to the intervention including making changes to care structure or delivery, empowered non-physician staff, and used electronic medical record changes to prompt clinicians. CONCLUSIONS: The quality of IBD care can be improved with diverse interventions that range from simple to complex. However, these interventions are not universally successful. Clinicians should emulate successful interventions and design new initiatives to narrow gaps in care quality.

STAT: Mobile app helps clinicians manage inpatient emergencies.

In response to the unprecedented surge of patients with COVID-19, Massachusetts General Hospital created both repurposed and de-novo COVID-19 inpatient general medicine and intensive care units. The clinicians staffing these new services included those who typically worked in these care settings (e.g., medicine residents, hospitalists, intensivists), as well as others who typically practice in other care environments (e.g., re-deployed outpatient internists, medical subspecialists, and other physician specialties). These surge clinicians did not have extensive experience managing low frequency, high acuity emergencies, such as those that might result from COVID-19. Physician-innovators, in collaboration with key hospital stakeholders, developed a comprehensive strategy to design, develop, and distribute a digital health solution to address this problem. MGH STAT is an intuitive mobile application that empowers clinicians to respond to medical emergencies by providing immediate access to up-to-date clinical guidelines, consultants, and code-running tools at the point-of-care. 100% of surveyed physicians found STAT to be easy to use and would recommend it to others. Approximately 1100 clinicians have downloaded the app, and it continues to enjoy consistent use over a year after the initial COVID-19 surge. These results suggest that STAT has helped clinicians manage life threatening emergencies during and after the pandemic, although formal studies are necessary to evaluate its direct impact on patient care.

Success of Direct-Acting, Antiviral-Based Therapy for Chronic Hepatitis C Is Not Affected by Type 2 Diabetes.

Chronic hepatitis C virus (HCV) is a risk factor for type 2 diabetes. In the era of interferon-based HCV therapy, type 2 diabetes was associated with decreased likelihood of sustained virologic response (SVR). Preliminary studies suggest that type 2 diabetes may not reduce the efficacy of regimens involving direct-acting antiviral (DAA) medications. We aimed to determine whether preexisting type 2 diabetes is associated with a reduced rate of SVR achieved 12 weeks after treatment of HCV with DAA-based regimens.

Zinc Deficiency and the Recurrence of Clostridium difficile Infection after Fecal Microbiota Transplant: A Retrospective Cohort Study.

BACKGROUND: Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT. METHODS: We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013-9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency. RESULTS: Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66 µg/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR = 11.327, 95% CI = 2.162-59.336, p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR = 0.102, 95% CI = 0.015-0.704, p=0.021). CONCLUSION: Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.

Increased risk of venous thromboembolism in hospitalized patients with cirrhosis due to non-alcoholic steatohepatitis.

OBJECTIVE: Patients with cirrhosis are at increased risk for venous thromboembolism (VTE) and portal vein thrombosis (PVT). Cirrhosis due to non-alcoholic steatohepatitis (NASH) appears to be particularly prothrombotic. We investigated hospitalized patients with NASH cirrhosis to determine if they are at increased risk for VTE. METHODS: Data on adult hospitalized patients with cirrhosis and VTE (deep vein thrombosis and/or pulmonary embolism) between November 1, 2010 and December 31, 2015 were obtained. Cases with VTE were matched by age, gender, and model for end stage liver disease (MELD) score to corresponding controls without VTE. RESULTS: Two hundred and ninety subjects (145 matched pairs) with mean age of 58.4 ± 11.8 years and MELD score of 16.0 ± 7.2 were included. Baseline characteristics were similar between cases and controls. Independent adjusted risk factors for VTE included NASH (OR: 2.46, 95% CI: 1.07-5.65, p = 0.034), prior VTE (OR: 7.12, 95% CI: 1.99-25.5, p = 0.003), and presence of PVT (OR: 2.18, 95% CI: 1.03-4.58, p = 0.041). Thrombocytopenia was associated with decreased risk (OR: 0.49, 95% CI: 0.26-0.95, p = 0.035). CONCLUSIONS: NASH is an independent risk factor for VTE among cirrhosis patients and provides further evidence that NASH is a hypercoagulable state. While all hospitalized patients with cirrhosis at risk for VTE should be considered for medical thromboprophylaxis, those with NASH cirrhosis are at particularly increased risk and therefore a high index of suspicion for VTE should be maintained even in the presence of thromboprophylaxis.

Innovation and entrepreneurship programs in US medical education: a landscape review and thematic analysis.

BACKGROUND: Training in innovation and entrepreneurship (I&E) in medical education has become increasingly prevalent among medical schools to train students in complex problem solving and solution design. OBJECTIVE: We aim to characterize I&E education in US allopathic medical schools to provide insight into the features and objectives of this growing field. DESIGN: I&E programs were identified in 2016 via structured searches of 158 US allopathic medical school websites. Program characteristics were identified from public program resources and structured phone interviews with program directors. Curricular themes were identified via thematic analysis of program resources, and themes referenced by >50% of programs were analyzed. RESULTS: Thirteen programs were identified. Programs had a median age of four years, and contained a median of 13 students. Programs were led by faculty from diverse professional backgrounds, and all awarded formal recognition to graduates. Nine programs spanned all four years of medical school and ten programs required a capstone project. Thematic analysis revealed seven educational themes (innovation, entrepreneurship, technology, leadership, healthcare systems, business of medicine, and enhanced adaptability) and two teaching method themes (active learning, interdisciplinary teaching) referenced by >50% of programs. CONCLUSIONS: The landscape of medical school I&E programs is rapidly expanding to address newfound skills needed by physicians due to ongoing changes in healthcare, but programs remain relatively few and small compared to class size. This landscape analysis is the first review of I&E in medical education and may contribute to development of a formal educational framework or competency model for current or future programs. ABBREVIATIONS: AAMC: American Association of Medical Colleges; AMA: American Medical Association; I&E: Innovation and entrepreneurship.

Automated analysis of investigational near-infrared fluorescence lymphatic imaging in humans.

ALFIA (Automated Lymphatic Function Imaging Analysis), an algorithm providing quantitative analysis of investigational near-infrared fluorescence lymphatic images, is described. Images from nine human subjects were analyzed for apparent lymphatic propagation velocities and propulsion periods using manual analysis and ALFIA. While lymphatic propulsion was more easily detected using ALFIA than with manual analysis, statistical analyses indicate no significant difference in the apparent lymphatic velocities although ALFIA tended to calculate longer propulsion periods. With the base ALFIA algorithms validated, further automation can now proceed to provide a clinically relevant analytic tool for quantitatively assessing lymphatic function in humans.