Pericardial Tamponade in a Patient with Inactive Ulcerative Colitis

Cardiac tamponade is a rare extraintestinal manifestation of ulcerative colitis. We present a case report of tamponade occurring four years after curative proctocolectomy and in the absence of any medical therapy for ulcerative colitis. Options for medical management of this condition are also discussed

Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection

Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1–infected individuals to a mean of 49.4 ± SD 12.9% of CD8+ T cells expressing Tim-3 in HIV-1–infected chronic progressors versus 28.5 ± 6.8% in HIV-1–uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1–infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4+ T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1–specific CD8+ T cells. Tim-3–expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1–specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1–associated T cell dysfunction

Physical Activity In Renal Disease (PAIRED) and the effect on hypertension: study protocol for a randomized controlled trial

Abstract Background The prevalence of hypertension among people with chronic kidney disease is high with over 60% of people not attaining recommended targets despite taking multiple medications. Given the health and economic implications of hypertension, additional strategies are needed. Exercise is an effective strategy for reducing blood pressure in the general population; however, it is not known whether exercise would have a comparable benefit in people with moderate to advanced chronic kidney disease and hypertension. Methods This is a parallel-arm trial of adults with hypertension (systolic blood pressure greater than 130 mmHg) and an estimated glomerular filtration rate of 15–45 ml/min 1.73 m2. A total of 160 participants will be randomized, with stratification for estimated glomerular filtration rate, to a 24-week, aerobic-based exercise intervention or enhanced usual care. The primary outcome is the difference in 24-h ambulatory systolic blood pressure after 8 weeks of exercise training. Secondary outcomes at 8 and 24 weeks include: other measurements of blood pressure, aortic stiffness (pulse-wave velocity), change in the Defined Daily Dose of anti-hypertensive drugs, medication adherence, markers of cardiovascular risk, physical fitness (cardiopulmonary exercise testing), 7-day accelerometry, quality of life, and adverse events. The effect of exercise on renal function will be evaluated in an exploratory analysis. The intervention is a thrice-weekly, moderate-intensity aerobic exercise supplemented with isometric resistance exercise delivered in two phases. Phase 1: supervised, facility-based, weekly and home-based sessions (8 weeks). Phase 2: home-based sessions (16 weeks). Discussion To our knowledge, this study is the first trial designed to provide a precise estimate of the effect of exercise on blood pressure in people with moderate to severe CKD and hypertension. The findings from this study should address a significant knowledge gap in hypertension management in CKD and inform the design of a larger study on the effect of exercise on CKD progression. Trial registration ClinicalTrials.gov, ID: NCT03551119. Registered on 11 June 2018

Angiotensin receptor blockers and risk of myocardial infarction: systematic review

Objective To evaluate the effect of angiotensin receptor blockers on the risk of myocardial infarction in patients at risk for cardiovascular events. Design Systematic review of controlled trials of angiotensin receptor blockers. Data sources Medline, Embase, Cochrane central register of controlled trials, hand search, and contact with investigators. Selection of studies Predefined criteria were used to select controlled clinical trials comparing use of angiotensin receptor blockers with angiotensin converting enzyme (ACE) inhibitors or placebo in patients at risk for cardiovascular events. Data were extracted for patients' characteristics, interventions, quality of trials, and rates of myocardial infarction. Results 19 studies with 31 569 patients were included in the analysis. Two studies investigated the use of angiotensin receptor blockers in hypertensive patients, four studies in patients with diabetes and nephropathy, 10 studies in patients with heart failure, and three in patients with recent myocardial infarction or ischaemic syndrome. 11 studies of 21 062 patients allowed for comparison between angiotensin receptor blockers and placebo; nine studies of 10 625 patients allowed for comparison between angiotensin receptor blockers and ACE inhibitors. Use of angiotensin receptor blockers was not associated with increased risk of myocardial infarction compared with placebo (odds ratio 0.94, 95% confidence interval 0.75 to 1.16) nor with increased risk of myocardial infarction compared with ACE inhibitors (1.01, 0.87 to 1.16). Conclusions Treatment with angiotensin receptor blockers was not associated with a significantly increased risk of myocardial infarction. The 95% confidence intervals do, however, not exclude an increase of up to 16% in the risk of myocardial infarction or a reduction in risk of up to 25%. Until further information specifically dealing with this issue is available from large prospective trials, our findings may alleviate recent concerns over the safety of this class of medications

The effect of exercise on blood pressure in chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES:Management of hypertension in chronic kidney disease (CKD) remains a major challenge. We conducted a systematic review to assess whether exercise is an effective strategy for lowering blood pressure in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS:We searched MEDLINE, EMBASE, the Cochrane Library, CINAHL and Web of Science for randomized controlled trials (RCTs) that examined the effect of exercise on blood pressure in adults with non-dialysis CKD, stages 3-5. Outcomes were non-ambulatory systolic blood pressure (primary), other blood pressure parameters, 24-hour ambulatory blood pressure, pulse-wave velocity, and flow-mediated dilatation. Results were summarized using random effects models. RESULTS:Twelve studies with 505 participants were included. Ten trials (335 participants) reporting non-ambulatory systolic blood pressure were meta-analysed. All included studies were a high risk of bias. Using the last available time point, exercise was not associated with an effect on systolic blood pressure (mean difference, MD -4.33 mmHg, 95% confidence interval, CI -9.04, 0.38). The MD after 12-16 and 24-26 weeks of exercise was significant (-4.93 mmHg, 95% CI -8.83, -1.03 and -10.94 mmHg, 95% CI -15.83, -6.05, respectively) but not at 48-52 weeks (1.07 mmHg, 95% CI -6.62, 8.77). Overall, exercise did not have an effect on 24-hour ambulatory blood pressure (-5.40 mmHg, 95% CI -12.67, 1.87) or after 48-52 weeks (-7.50 mmHg 95% CI -20.21, 5.21) while an effect was seen at 24 weeks (-18.00 mmHg, 95% CI -29.92, -6.08). Exercise did not have a significant effect on measures of arterial stiffness or endothelial function. CONCLUSION:Limited evidence from shorter term studies suggests that exercise is a potential strategy to lower blood pressure in CKD. However, to recommend exercise for blood pressure control in this population, high quality, longer term studies specifically designed to evaluate hypertension are needed

Clinical and Immunologic Features of an Atypical Intracranial Mycobacterium avium Complex (MAC) Infection Compared with Those of Pulmonary MAC Infections▿

Members of the Mycobacterium avium complex (MAC) may cause chronic pulmonary infections in otherwise healthy elderly persons but rarely invade parts of the body outside of the lungs in immunocompetent hosts. We present a case of an isolated intracranial MAC infection in an apparently immunocompetent individual and review previous reports. We studied the T-cell and monocyte responses in healthy volunteers, individuals with a pulmonary MAC infection, and one individual with an isolated intracranial MAC infection. Genomic DNA from the individual with the brain MAC infection was studied for gamma interferon (IFN-γ) receptor mutations. Individuals with localized pulmonary MAC infections showed increased activation of monocytes and enhanced monocyte and T-cell tumor necrosis factor alpha (TNF-α) production in response to lipopolysaccharide and MAC antigens but defects in T-cell IFN-γ secretion. The individual with an intracranial MAC infection showed a lack of monocyte activation and deficiencies in both monocyte and T-cell TNF-α production and monocyte interleukin-12 (IL-12) production but had preserved T-cell IFN-γ production. Mutations or deletions in the IFN-γ receptor were not detected in the individual with the intracranial MAC infection. Our data suggest that distinct immune defects characterize two different manifestations of MAC infection. A relative defect in IFN-γ production in response to MAC may predispose an individual to localized but partially controlled lung disease, whereas defects leading to reduced IL-12 and TNF-α production may allow the dissemination of MAC. Further studies delineating the potential role of TNF-α in limiting the spread of MAC outside the lung are warranted