Chronic wounds affect 12–15% of patients with diabetes and are associated with a drastic decrease in their quality of life. Here we demonstrate that purified mature naïve B220+/CD19+/IgM+/IgD+ B cells improve healing of acute and diabetic murine wounds after a single topical application. B cell treatment significantly accelerated acute wound closure by 2–3 days in wild-type mice and 5–6 days in obese diabetic mice. The treatment led to full closure in 43% of chronic diabetic wounds, as compared to only 5% in saline-treated controls. Applying equivalent numbers of T cells or disrupted B cells failed to reproduce these effects, indicating that live B cells mediated pro-healing responses. Topically-applied B cell treatment was associated with significantly reduced scar size, increased collagen deposition and maturation, enhanced angiogenesis and increased nerve growth into and under the healing wound. β-III tubulin+ nerve endings in scars of wounds treated acutely with B cells showed increased relative expression of growth-associated protein 43. The improved healing associated with B cell treatment was supported by significantly increased fibroblast proliferation and decreased apoptosis in the wound bed and edges, altered kinetics of neutrophil infiltration, as well as an increase in TGF-β and a significant reduction in MMP2 expression in wound granulation tissue. Our findings indicate that the timeline and efficacy of wound healing can be experimentally manipulated through the direct application of mature, naive B cells, which effectively modify the balance of mature immune cell populations within the wound microenvironment and accelerate the healing process.

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BackgroundThe long-term natural history of microscopic colitis (MC) (collagenous colitis (CC), lymphocytic colitis (LC)), traditionally considered relapsing but non-progressive diseases, is poorly defined. Whether persistent histologic inflammation in such diseases is associated with an increased risk of colorectal neoplasia (CRN) or extracolonic cancers has not been robustly established.MethodsThis retrospective cohort included diagnosed with MC at a referral center. Rates of CRN and extracolonic cancer were compared to patients undergoing screening colonoscopy (n = 306) and to the United States population using data from the Surveillance, Epidemiology, and End-Results (SEER) program. Standardized incidence ratios (SIR) and 95% confidence intervals were calculated and multivariable regression models used to identify the effect of MC diagnosis and severity on cancer risk.ResultsOur study included 221 patients with microscopic colitis (112 CC, 109 LC) among whom 77% were women. Compared to the colonoscopy control population, MC was associated with similar odds of tubular adenoma (Odds ratio (OR) 1.07, 95% CI 0.69–1.66) or villous adenoma (OR 1.26, 95% CI 0.17–9.42). Compared to patients with a single episode of MC, those with 2 or more episodes had similar risk of colon cancer (OR 0.83, 95% CI 0.20–3.39) or tubular adenoma (OR 1.49 95% CI 0.83–2.67). We also identified no statistical increase in the rates of cancer in the MC population compared to US-SEER data.ConclusionMicroscopic colitis was not associated with increased risk of CRN and extracolonic cancers when compared to controls undergoing colonoscopy or the US SEER population.

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Background: Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis. Methods: Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDE R), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs). Results: Among 549 participants with a mean age of 61 years enrolled in GIDER, we confirmed diverticulosis in 245 (44.6%). The prevalence of diverticulosis appeared to decrease with higher consumption of fruit and vegetables (P trend = 0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60-1.17) with five to seven servings per week and 0.62 (95% CI, 0.44-0.89) with greater than one serving per day. Similarly, compared to participants with less than five servings per week of fruit, the multivariable-adjusted PR of diverticulosis was 0.60 (95% CI, 0.41-0.87) with greater than one serving per day. These associations were not modified by age, BMI, smoking, or red meat intake (All P interaction > 0.055). Conclusion: In a colonoscopy-based longitudinal cohort study, we show that higher consumption of fruit and vegetables is associated with lower risk of prevalent diverticulosis.

Background Exposure to pregnant women with cardiovascular disease (CVD) during cardiology fellowship training is limited and without a standard curriculum in the United States. The authors sought to evaluate a dedicated curriculum to teach management of CVD in pregnancy to improve general cardiology fellowship training. Methods The authors developed a dedicated CVD in pregnancy curriculum for the general cardiology fellows at a large academic medical center in the fall of 2019. Fellows’ knowledge was assessed via a board-style examination and exposure and attitudes related to the care of pregnant women with CVD were evaluated with a needs assessment questionnaire before and after the curriculum. Results Of the 17 fellows who participated in the curriculum, 12 completed the needs assessment pre-curriculum and 9 post-curriculum. The mean (SD) number of pregnant women with CVD cared for by each fellow in the inpatient and outpatient settings were 0.75 (1.29) and 0.56 (0.73), respectively. After the curriculum, all fellows reported awareness of available resources to treat pregnant women with CVD, while a majority disagreed that they receive regular exposure to pregnant patients with CVD in their training. The authors observed significant increases in fellows’ confidence in their knowledge of normal cardiovascular physiology of pregnancy, physical exam skills, and ability to care for pregnant women with valvular disease and arrhythmias from pre to post-curriculum. A total of 15 fellows completed the board-style exam pre-curriculum and 15 post-curriculum. Fellows’ performance on the board-style examination improved slightly from before to after the curriculum (64.0 to 75.3% correct, p = 0.02). Conclusions A dedicated curriculum improved cardiology fellows’ knowledge to recognize and treat CVD in pregnancy and improved confidence in caring for this unique patient population.

Background: Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis. Methods: Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDER), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs).Results: Among 549 participants with a mean age of 61 years enrolled in GIDER, we confirmed diverticulosis in 245 (44.6%). The prevalence of diverticulosis appeared to decrease with higher consumption of fruit and vegetables (P trend =0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60-1.17) with five to seven servings per week and 0.62 (95% CI, 0.44-0.89) with greater than one serving per day. Similarly, compared to participants with less than five servings per week of fruit, the multivariable-adjusted PR of diverticulosis was 0.60 (95% CI, 0.41-0.87) with greater than one serving per day. These associations were not modified by age, BMI, smoking, or red meat intake (All P interaction >0.055). Conclusion: In a colonoscopy-based longitudinal cohort study, we show that higher consumption of fruit and vegetables is associated with lower risk of prevalent diverticulosis. Key Words : Diverticulosis, Diet, Fruit and Vegetables, and Epidemiology

Background Hypertension in pregnancy is a leading cause of maternal morbidity and mortality in the United States. Although the Dietary Approaches to Stop Hypertension (DASH) diet is recommended for all adults with hypertension, rates of DASH adherence and anti-hypertensive medications use in women of child-bearing age is unknown. Objectives To determine DASH adherence and anti-hypertensive medication use in women of child-bearing age. Methods In the National Health and Nutrition Examination Surveys from 2001-2016, we estimated DASH adherence among women of child-bearing age (20-50 years). We derived a DASH score (0-9) based on 9 nutrients, with DASH adherence defined as DASH score ≥4.5. Hypertension was defined by blood pressure (BP) ≥130/80 mm Hg or anti-hypertensive medication use. DASH scores were compared across BP categories and anti-hypertensive medication use was categorized. Results Of the 7782 women, the mean age (SE) was 32.8 (0.2) years, 21.4% were non-Hispanic Black, and 20.3% had hypertension. The mean DASH score was 2.11 (0.06) for women with self-reported hypertension and 2.40 (0.03) for women with normal BP (P<0.001). DASH adherence was prevalent in 6.5% of women with self-reported hypertension compared to 10.1% of women with normal BP (P<0.05). Self-reported hypertension is predominantly managed with medications (84.8%), while DASH-adherence has not improved in these women from 2001-2016. Moreover, 39.5% of US women of child-bearing age are taking medications contraindicated in pregnancy. Conclusions Given the benefits of optimized BP during pregnancy, this study highlights the critical need to improve DASH adherence and guide prescribing among women of child-bearing age.