End-stage liver disease is a common cause of non-AIDS-related mortality in HIV patients, despite effective anti-retroviral therapies (ARTs). HIV-1 infection causes gut CD4 depletion and is thought to contribute to increased gut permeability, bacterial translocation, and immune activation. Microbial products drain from the gut into the liver via the portal vein where Kupffer cells (KCs), the resident liver macrophage, clear translocated microbial products. As bacterial translocation is implicated in fibrogenesis in HIV patients through unclear mechanisms, we tested the hypothesis that HIV infection of KCs alters their response to LPS in a TLR4-dependent manner. We showed that HIV-1 productively infected KCs, enhanced cell-surface TLR4 and CD14 expression, and increased IL-6 and TNF-α expression, which was blocked by a small molecule TLR4 inhibitor. Our study demonstrated that HIV infection sensitizes KCs to the proinflammatory effects of LPS in a TLR4-dependent manner. These findings suggest that HIV-1-infected KCs and their dysregulated innate immune response to LPS may play a role in hepatic inflammation and fibrosis and represent a novel target for therapy.
Cardiovascular involvement is common in COVID-19 patients and is associated with increased mortality, especially in patients with pre-existing cardiac comorbidities. Elevated levels of troponin have been noted to predict worse prognosis for COVID-19 patients, regardless the physiology of insult. We report a case of a 65-year old man who was admitted for acute hypoxemic respiratory failure due to COVID-19 disease that rapidly decompensated and required mechanical ventilation. He responded well with medical treatment and was successfully extubated. Interestingly, his serum troponin T levels remained negative (<0.01 ng/mL) until day 10, when it was noted to be elevated despite him being completely asymptomatic. Echocardiogram revealed new left ventricular wall motion abnormalities suggestive of reverse Takotsubo cardiomyopathy. Unfortunately, he suffered from a pulseless electrical arrest less than 24 hours later and eventually expired. This case shows that a policy of trending troponin levels may be valuable as a screening tool for critically ill COVID-19 patients and may be beneficial for early silent validation of cardiovascular involvement in these patients, who could otherwise be asymptomatic yet presage adverse clinical events. Moreover, using troponin as a screening tool may lead to decreased utilization of echocardiography and reduce the exposure of COVID-19 to healthcare workers.
The pandemic of coronavirus disease 2019 (COVID-19) secondary to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has bestowed an unprecedented challenge upon us, resulting in an international public health emergency. COVID-19 has already resulted in > 1,600,000 deaths worldwide and the fear of a global economic collapse. SARS-CoV-2 is notorious for causing acute respiratory distress syndrome, however emerging literature suggests various dreaded cardiac manifestations associated with high mortality. The mechanism of myocardial damage in COVID-19 is unclear but thought to be multifactorial and mainly driven by the host's immune response (cytokine storm), hypoxemia and direct myocardial injury by the virus. Cardiac manifestations from COVID-19 include but are not limited to, acute myocardial injury, cardiac arrhythmias, congestive heart failure and acute coronary syndrome. Cardiac imaging is paramount to appropriately diagnose and manage the cardiac manifestations of COVID-19. Herein, we present cardiac imaging findings of COVID-19 patients with biomarker and imaging confirmed myocarditis to provide insight regarding the variable manifestations of COVID-19 myocarditis via Cardiac MRI (CMR) coupled with CMR-edema education along with recommendations on how to incorporate advanced CMR into the clinicians' COVID-19 armamentarium.
Adenoma detection rate (ADR) is a quality marker of colonoscopy and operator performance. Prior studies evaluating the effect of an extended workday on the ADR reported variable outcomes that remain controversial. Given the variable results of prior studies and the potential legal implications of reduced ADR in the afternoon, we aimed to further evaluate this parameter and its effect on ADR. We performed a systematic review of the PubMed, CINAHL and Scopus electronic databases. Studies were included if they reported ADR in patients undergoing colonoscopy in the morning session and the afternoon session. Afternoon sessions included both sessions following a morning shift and half-day block shifts. Subgroup analyses were performed for ADR comparing morning and afternoon colonoscopies in a continuous workday, advanced ADRs (AADRs) and polyp detection rates (PDRs) were also compared. Thirteen articles with 17 341 (61.2%) performed in the morning session and 10 994 (38.8%) performed in the afternoon session were included in this study. There was no statistical significance in the ADR or AADR between morning and afternoon sessions, respectively [relative risk (RR) 1.06, 95% confidence interval (CI) 0.99–1.14] and (RR 1.19, 95% CI 0.95–1.5). Afternoon procedures had a significantly higher PDR than morning procedures (RR 0.93, 95% CI 0.88–0.98). ADR was not significantly influenced in the afternoon session when operators continued to perform procedures throughout the day or on a half-day block schedule.
Introduction
The safety of renin–angiotensin–aldosterone system inhibitors (RAASi) among COVID-19 patients has been controversial since the onset of the pandemic.
Methods
Digital databases were queried to study the safety of RAASi in COVID-19. The primary outcome of interest was mortality. The secondary outcome was seropositivity improvement/viral clearance, clinical manifestation progression, and progression to intensive care units. A random-effect model was used to compute an unadjusted odds ratio (OR).
Results
A total of 49 observational studies were included in the analysis consisting of 83,269 COVID-19 patients (RAASi n = 34,691; non-RAASi n = 48,578). The mean age of the sample was 64, and 56% were males. We found that RAASi was associated with similar mortality outcomes as compared to non-RAASi groups (OR 1.07; 95% CI 0.99–1.15; p > 0.05). RAASi was associated with seropositivity improvement including negative RT-PCR or antibodies, (OR 0.96; 95% CI 0.93–0.99; p < 0.05). There was no association between RAASi versus control with progression to ICU admission (OR 0.99; 95% CI 0.79–1.23; p > 0.05) or higher odds of worsening of clinical manifestations (OR 1.04; 95% CI 0.97–1.11; p > 0.05). Metaregression analysis did not change our outcomes for effect modifiers including age, sex, comorbidities, RAASi type, or study type on outcomes.
Conclusions
COVID-19 is not a contraindication to hold or discontinue RAASi as they are not associated with higher mortality or worsening symptoms. Continuation of RAASi might be associated with favorable outcomes in COVID-19, including seropositivity/viral clearance.
Supplementary Information
The online version contains supplementary material available at 10.1007/s40292-021-00462-w.
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