SGLT2 inhibitors in hypertension: Role beyond diabetes and heart failure.

Type 2 Diabetes Mellitus (T2DM) is a pandemic that affects millions of patients worldwide. Diabetes affects multiple organ systems leading to comorbidities including hypertension. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) recently have been approved for the treatment of T2DM and heart failure with reduced and preserved ejection fraction. Retrospective analyses of clinical trials have noted SGLT2 inhibitors to have a promising effect on blood pressure. Moreover, the observed blood pressure reduction is not just an acute effect of treatment initiation but has been shown to have a long-term impact on both systolic and diastolic blood pressure. The mechanism of action leading to the blood pressure reduction is still unclear; however, proposed mechanisms are related to the natriuretic effect, modification of the renin-angiotensin-aldosterone system, and/or the reduction in the sympathetic nervous system, SGLT2i should be considered as second-line medication in those patients with diabetes or heart disease and concomitant hypertension. This article reviews the pharmacology, side effect profile, and clinical trials surrounding the use of SGLT2i for the treatment of hypertension.

Implementation of Spaced Repetition by First-Year Medical Students: a Retrospective Comparison Based on Summative Exam Performance.

Many medical students use spaced repetition as a study strategy to improve knowledge retention, and there has been growing interest from medical students in using flashcard software, such as Anki, to implement spaced repetition. Previous studies have provided insights into the relationship between medical students' use of spaced repetition and exam performance, but most of these studies have relied on self-reports. Novel insights about how medical students use spaced repetition can be gleaned from research that takes advantage of the ability of digital interfaces to log detailed data about how students use software. This study is unique in its use of data extracted from students' digital Anki data files, and those data are used to compare study patterns over the first year of medical school. Implementation of spaced repetition was compared between two groups of students who were retrospectively grouped based on average performance on three exams throughout the first year of medical school. Results indicate that students in the higher scoring group studied more total flashcards and implemented spaced repetition via Anki earlier in the year compared to the lower scoring group. These findings raise the possibility that implementing spaced repetition as a study strategy early in medical school may be related to improved knowledge retention and exam performance. Additional research should be performed at more sites to further examine the relationship between spaced repetition implementation and exam performance.

Protease-Activated Receptor Antagonist for Reducing Cardiovascular Events - A Review on Vorapaxar.

Acute Coronary Syndrome (ACS) is a term that describes pathologies related to myocardial ischemia, and is comprised of unstable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction. Urgent management of ACS is typically necessary to prevent future morbidity and mortality. Current medical recommendations of ACS management involve use of dual antiplatelet therapy, typically with aspirin and clopidogrel. However, newer therapies are being designed and researched to improve outcomes for patients with ACS. Vorapaxar is a novel antiplatelet therapy that inhibits thrombin-mediated platelet aggregation to prevent recurrence of ischemic events. It has been Food and Drug Administration approved for reduction of thrombotic cardiovascular events in patients with a history of MI or peripheral arterial disease with concomitant use of clopidogrel and/or aspirin, based upon the findings of the TRA 2°P-TIMI 50 trial. However, Vorapaxar was also found to have a significantly increased risk of bleeding, which must be considered when administering this drug. Based upon further subgroup analysis of both the TRA 2°P-TIMI 50 trial and TRACER trial, Vorapaxar was found to be potentially beneficial in patients with peripheral artery disease, coronary artery bypass grafting, and ischemic stroke. There are current trials in progress that are further evaluating the use of Vorapaxar in those conditions, and future research and trials are necessary to fully determine the utility of this drug.

Next-Day Discharge vs Early Discharge After Transcatheter Aortic Valve Replacement: Systematic Review and Meta-Analysis.

With the growing utilization of transcatheter aortic valve replacement (TAVR) as an alternative option to surgical valve replacement (SAVR) in patients considered to be suboptimal for surgery, there is a need to explore the possibility of next day discharge (NDD) and its potential outcomes. The aim of our study is to compare outcomes and complications following NDD vs the standard early discharge (ED) (less than 3 days). A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. Studies comparing same-day or next-day discharge vs discharge within the next three days were included in our analysis. 6 studies with 2,672 patients were identified. The risk of bleeding and vascular complications was significantly lower in patients with NDD compared to ED (OR 0.10, P < 0.00001 and OR 0.22, P = 0.002 respectively). The incidence of permanent pacemaker (PPM) implants was significantly lower in patients who had NDD compared to ED (OR 0.21, P = 0.0005). The incidence of 30 day mortality, stroke, AKI and readmission rates was not different between the two groups. NDD after TAVR allows for reduction in hospital stay and can mitigate hospital costs without an increased risk of complications. Our analysis shows that complication rate is comparable to ED, NDD is a reasonable option for certain patients with severe aortic stenosis who undergo TAVR. Further studies are needed to elucidate whether higher risk patients who would benefit from an extended inpatient monitoring post TAVR.

Granzyme B PET Imaging as a Predictive Biomarker of Immunotherapy Response.

While cancer immunotherapy can produce dramatic responses, only a minority of patients respond to treatment. Reliable response biomarkers are needed to identify responders, and conventional imaging modalities have not proved adequate. Here, we provide a preclinical proof of concept for the use of granzyme B, a downstream effector of tumoral cytotoxic T cells, as an early biomarker for tumors responding to immunotherapy. We designed novel PET imaging probes for the murine and human granzyme B isoforms that specifically and quantitatively bind granzyme B. Immunotherapy-treated mice were imaged prior to therapy-induced tumor volume reduction. Imaging distinguished treated responders from nonresponders with excellent predictive ability. To assess the clinical value of a granzyme B imaging paradigm, biopsy specimens from melanoma patients on checkpoint inhibitor therapy were analyzed. A marked differential in granzyme B expression was observed between treated responders and nonresponders. Additionally, our human probe was able to specifically detect granzyme B expression in human samples, providing a clear candidate for clinical application. Overall, our results suggest granzyme B PET imaging can serve as a quantitatively useful predictive biomarker for efficacious responses to cancer immunotherapy. Cancer Res; 77(9); 2318-27. ©2017 AACR.

Glomerular Pathology in Dent Disease and Its Association with Kidney Function.

BACKGROUND AND OBJECTIVES: Dent disease is a rare X-linked disorder characterized by low molecular weight proteinuria and often considered a renal tubular disease. However, glomerulosclerosis was recently reported in several patients. Thus, Dent disease renal histopathologic features were characterized and assessed, and their association with kidney function was assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical renal pathology reports and slides (where available) were collected from 30 boys and men in eight countries who had undergone clinical renal biopsy between 1995 and 2014. RESULTS: Median (25th, 75th percentiles) age at biopsy was 7.5 (5, 19) years with an eGFR of 69 (44, 94) ml/min per 1.73 m2 and a 24-hour urine protein of 2000 (1325, 2936) mg. A repeat biopsy for steroid-resistant proteinuria was performed in 13% (four of 30) of the patients. Prominent histologic findings included focal global glomerulosclerosis in 83% (25 of 30; affecting 16%±19% glomeruli), mild segmental foot process effacement in 57% (13 of 23), focal interstitial fibrosis in 60% (18 of 30), interstitial lymphocytic infiltration in 53% (16 of 30), and tubular damage in 70% (21 of 30). Higher percentages of globally sclerotic glomeruli, foot process effacement, and interstitial inflammation were associated with lower eGFR at biopsy, whereas foot process effacement was associated with steeper annual eGFR decline. CONCLUSIONS: These associations suggest a potential role for glomerular pathology, specifically involving the podocyte, in disease progression, which deserves further study. Furthermore, Dent disease should be suspected in boys and men who have unexplained proteinuria with focal global glomerulosclerosis and segmental foot process effacement on renal biopsy.