With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose
In recent years, the drug class of SGLT2 inhibitors has attracted a lot of attention given the demonstrated effects on reducing cardiovascular death in certain patient populations. This study was designed to determine the impact of sotagliflozin (SGLT-1 and SGLT-2 inhibitor) on days alive and out of the hospital (DAOH) compared to placebo. It was a prespecified analysis of data from the SOLOIST-WHF trial, a multicenter randomized control trial that initially showed decrease in cardiovascular death, hospitalizations for heart failure, and other poor outcomes in patients taking sotagliflozin when compared to placebo.
The study enrolled 1222 patients with Type 2 Diabetes and either HFrEF or HFpEF who had a recent hospitalization for heart failure requiring IV diuresis. The study found that for patients in the sotagliflozin group, the DAOH rate was 3% higher (p = 0.027) compared to placebo. Of note, this finding was largely driven by a decrease in the rate of days dead rather than by a decrease in the rate of days hospitalized for any cause. This is important to note given that patients who were at the highest risk of hospitalization were also at the highest risk of death. When examined separately, their findings showed only a 0.3-day difference in days in the hospital between the sotagliflozin and placebo groups. They did report that more patients in the placebo group were hospitalized more than once compared to the sotagliflozin group.
There are a few clear limitations to this study. The median follow-up time was about 9 months, as the study was stopped early due to COVID. They also report only a minority of hospitalizations were explicitly for heart failure; 60% of hospitalizations in the study were without a specified primary reason in the study data. By the end of the study, the majority of patients were alive and had not required repeat hospitalization, which impacts the utility of this particular study outcome. While measuring DAOH is a potentially interesting metric, its development specifically for this study limits generalizability and sidesteps other metrics of quality of life. Notably, this study enrolled around 80% patients with HFrEF. If clinical gains are sustained when considering the HFpEF group independently, this represents a potential new therapeutic option for the treatment of heart failure with preserved ejection fraction.
In comparison to Troponin I assays in the evaluation of potential acute coronary syndrome (ACS), which are adjusted for gender, high-sensitivity Troponin T (HsTnT) values are interpreted without any such adjustments for gender and age (cutoff is based on the 99th percentile of a health population, with a normal value of up to 14ng/L) despite the fact that these patient characteristics may impact the significance of the result.
This was a prospective, observational study of 1611 consecutive patients presenting to an emergency department with symptoms concerning for ACS. Baseline HsTnT measurements were obtained and used to assign a diagnosis of Type-1 MI, Type-2 MI, acute myocardial injury, or chronic myocardial injury based on the Fourth Universal Definition of Myocardial Infarction. Patients were categorized by age (young, [<65 years], old [65-79 years], or very old [80 years or older]. The primary outcome was late, all-cause mortality (at 6 months, 1 year, and 5 years).
They found large variations in baseline HsTnT levels based on gender and age groups; 73% of younger patients had initial levels < or equal to 14. The elderly and very elderly had significantly higher rates of elevated baseline troponin compared to younger patients, only 27% of whom had elevated baseline troponin, indicating age likely needs to be taken into account when analyzing troponin levels. Among very old people (i.e., those 80 years or older), elevated troponin was generally due to myocardial injury, whereas Type I MI was more frequent in younger patients. Mortality at 5 year follow up was significantly higher in very elderly men and women, but the majority of these deaths were due to noncardiac causes. Of note women had lower baseline HsTnT levels than men across all age groups, suggesting adjustment by gender for HsTnT level may be useful in aiding interpretation.
This study is limited in that it was a single-center prospective observational study, with several noted systemic inefficiencies leading to variation in timing for HsTnT readings, EKGs and other diagnostic tests. As with any laboratory test, the use of HsTnT in emergent clinical situations must include clinical context and follow a trend in order to guide decision making. This study begins to provide big-picture context with which to view elevated HsTnT, which can be used to develop more precise triage algorithms to more efficiently and effectively risk stratify patients and follow up accordingly.
Initial Phase 3 studies of the SARS-CoV-2 vaccines excluded pregnant women, though pregnant women are at risk for severe complications of COVID, including ICU admission and the need for mechanical ventilation. This retrospective cohort study was designed to measure the efficacy of the Pfizer-BioNTech SARS-CoV-2 Vaccine in pregnant women, as well as evaluate its safety. During the study period, 7,530 pregnant women in a large health system in Israel who received vaccination were matched with unvaccinated women by various factors including age, gestational age (up to 5 weeks difference), parity, residential area, and receipt of influenza vaccination.
The primary endpoint of the study was COVID infection 28 days or more after beginning the vaccination series. After 28 days, 10 vaccinated patients and 46 unvaccinated patients were diagnosed with COVID, a statistically significant (p < 0.001) hazard ratio of 0.22 in vaccinated patients (translating to 78% vaccine effectiveness). Notably, for patients with COVID, symptom rates were similar, though the study does not comment on severity. COVID-related hospitalizations were 0.2% in the vaccinated group and 0.3% in the unvaccinated group.
Secondary outcomes in the study included rates of preeclampsia, stillbirth, maternal death, preterm birth and infant weight, all of which were similar between the vaccinated and unvaccinated groups. While limited as an observational study, this study demonstrates the value of COVID vaccination in pregnancy without evident excess risk. Further prospective studies could provide even more data to help optimize vaccination rates in an at-risk population.
Calcitonin gene-related peptide (CGRP) provides a potential target for migraine prophylaxis, as it is present in increased levels during migraines and has been shown to precipitate migraine-like headaches. This study was a phase 3, multicenter, double-blind randomized trial seeking to elucidate the efficacy and safety of Atogepant (a CGRP receptor antagonist). The primary endpoint was a decrease in baseline migraine days per month. The target patient population was individuals with 4-14 migraine days a month. They studied once daily medication dosing (of either 10, 30, or 60 mg) for prevention of migraines. They found a significant decrease in miragine days with -2.5 days for placebo compared with -3.7 to -4.2 days for the trial drug, with increasing dose effect. Mild adverse effects such as constipation and nausea were common and proportional to dose, but with few severe effects. Notably, this study excluded patients with migraines who had already failed multiple preventive therapies, and compared to placebo rather than standard of care, limiting its applicability for patients already on preventive therapy.
C. Auris is a notoriously resistant fungal pathogen that can cause invasive disease with high mortality. This single-center cross-sectional study investigated Candida Auris colonization and potential effectiveness of control measures at a ventilator-capable skilled nursing facility. They found that routine swab screening (inguinal and axillary creases) was only 61.9% sensitive for colonization. By adding swabbing sites, they could increase overall sensitivity; however, it took 4 sites – nares, palms, toe webs, and inguinal crease – to reach 89% sensitivity, and 6 sites to approach 100%. In addition, CHG, a bisbiguanide antiseptic that has in vitro efficacy against C Auris and is used for bathing, rarely reaches effective concentration on the skin to decrease C Auris colonization. Overall, it seems that the utility of widespread screening is limited by both low sensitivity of swabbing methods and low efficacy of known treatment options.
With the constantly evolving nature of the COVID pandemic, computer modeling offers a fast, adaptive way to pre-emptively investigate dynamic scenarios. The safe opening of schools is an essential topic, as much as it is a complex one. This study (while pre-Delta variant) models the effectiveness of various containment strategies – symptomatic isolation, classroom quarantine, and weekly screening, with different levels of uptake (low, medium, high mitigation) from elementary and high schools. According to the study models, in-school transmission is much less likely in elementary schools as compared to high schools, particularly when children are assumed to be less infection-susceptible and less likely to be infectious. In-school spread is best mitigated by weekly screening, which circumvents factors that are more difficult to regulate, such as consistency with masking, distancing, and quarantine. Regardless, a key takeaway is that population Rt(effective reproduction number) < 1 – which implies self-limited disease spread – can be maintained while schools are open, provided adequate population-wide vaccination and mitigation efforts are in place.
Dr. Christopher Chornay is a Neurology prelim resident at NYU Langone Health
Peer reviewed by Neha Nagpal, MD, chief resident at NYU Langone Health
Image courtesy of Wikimedia Commons, source: [[File:Adventist Kids.jpg|Adventist_Kids]], Author: Benjamin Korankye
 Szarek M, Bhatt DL, Steg PG, et al. Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure : A Randomized Trial. Ann Intern Med. 2021;174(8):1065-1072. doi:10.7326/M21-0651
 Etaher A, Chew DP, Frost S, et al. Prognostic Implications of High-Sensitivity Troponin T Levels Among Patients Attending Emergency Departments and Evaluated for an Acute Coronary Syndrome. Am J Med. 2021;134(8):1019-1028.e1. doi:10.1016/j.amjmed.2021.03.005
 Goldshtein I, Nevo D, Steinberg DM, et al. Association Between BNT162b2 Vaccination and Incidence of SARS-CoV-2 Infection in Pregnant Women. JAMA. 2021;326(8):728-735. doi:10.1001/jama.2021.11035
 Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021;385(8):695-706. doi:10.1056/NEJMoa2035908
 Proctor DM, Dangana T, Sexton DJ, et al. Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility. Nat Med. 2021;27(8):1401-1409. doi:10.1038/s41591-021-01383-w
 Bilinski A, Salomon JA, Giardina J, Ciaranello A, Fitzpatrick MC. Passing the Test: A Model-Based Analysis of Safe School-Reopening Strategies [published correction appears in Ann Intern Med. 2021 Aug;174(8):1195]. Ann Intern Med. 2021;174(8):1090-1100. doi:10.7326/M21-0600