Ischemic and Bleeding Outcomes of Potent P2Y12 Inhibitor Antiplatelet Agents Versus Clopidogrel in Elderly Patients With Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials.

BACKGROUND: The role of P2Y12 inhibition in acute coronary syndrome (ACS) has been well described in literature. However, the agent of choice is less clear among elderly patients (>65 years) who are at increased risk of bleeding. This meta-analysis was designed to investigate the efficacy and safety of potent P2Y12 inhibitors vs. clopidogrel in this population. METHODS AND RESULTS: PubMed, Cochrane Central Register of Clinical Trials, EMBASE, and ClinicalTrial.gov (inception through February 25, 2021) were searched for randomized studies comparing potent oral P2Y12 inhibitors to clopidogrel in elderly population presenting with ACS. Study endpoints included major adverse cardiac events (MACE), major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) were computed and p<0.05 was considered significant. Eight randomized studies with a total 10,081 patients were included in the final analysis. At mean follow up of 26 months, there were no significant differences between potent oral P2Y12 inhibitors and clopidogrel in MACE (HR 0.97, 95% CI [0.82-1.15]; p=0.73), all-cause mortality (HR 0.91, 95% CI [0.75-1.10]; p=1.00), MI (HR 0.95, 95% CI [0.78-1.17]; p=0.64), and stroke (HR 1.24, 95% CI [0.82-1.86]; p=0.31). However, potent oral P2Y12 inhibitors were associated with a reduction in cardiovascular mortality (HR 0.82, 95% CI [0.68-0.98]; p=0.03), and an increase in major bleeding events (HR 1.32, 95% CI [1.09-1.59]; p<0.01). CONCLUSION: In comparison with clopidogrel, the use of potent oral P2Y12 inhibitors in elderly patients with ACS, is associated with a reduction in the risk of cardiovascular mortality with increased risk of bleeding events and no significant change in MACE outcomes.

An Unusual Association between Neurofibromatosis Type 1 and Diffuse B Cell Lymphoma.

Neurofibromatosis type 1 (NF-1) is known to be associated with increased risk of malignancy by at least fourfold. Malignant lymphomas are rare in adults with NF-1. Hereby, we present a 75-year-old male with NF-1 complaining of weakness, nausea, and vomiting associated with abdominal pain. Three months prior to presentation, he had suffered a motor vehicle accident (MVA) resulting in multiple rib fractures that was seen in chest X-ray. For the following three months, he had intermittent chest pain, but it was attributed to the recent rib fracture. During this admission, the severity of chest pain worsened and the associated vomiting inclined further investigation; including CT imaging and bone biopsy, it was revealed to be a rare case of diffuse B cell lymphoma in a patient with NF-1. However, we believe the recent MVA caused an anchoring bias in making a prompt diagnosis. In addition, the appearance of the neurofibroma, resulted in suboptimal physical examination, and hence, there was a delay in reaching the diagnosis. We will discuss here the presentation of this case, to highlight the rare association and to increase awareness of when encountering a challenging diagnosis.

Remdesivir for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The nucleotide analogue prodrug remdesivir was among the first antiviral therapies to be tested in randomized controlled trials (RCTs) for COVID-19. We performed a meta-analysis to understand efficacy and safety. METHODS: We searched PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov databases (from January 1, 2020 to November 5, 2020). We included RCTs comparing the efficacy and safety of remdesivir to control/placebo in COVID-19. Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. RESULTS: A total of 4 RCTs with 7334 patients with COVID-19 were included. At a follow-up of 28-29 days from randomization, very low certainty evidence showed that use of remdesivir compared with control group (placebo and/or standard of care) was not associated with a significant decrease in time to clinical improvement (standardized mean difference -0.80 day; [CI, -2.12, 0.53]). However, moderate certainty of evidence showed that remdesivir was associated with higher rates of recovered patients (risk difference [RD] 0.07 [0.05, 0.08]) and discharged patients (RD 0.07 [0.03, 0.11]) and lower rates of developing serious adverse events (RD -0.05 [-0.10, -0.01]) compared with control. Moderate and very low certainty of evidence showed there was no significant difference in deaths at 28-29 days follow-up (RD -0.01 [-0.03, 0.01]) and developing any adverse events (RD 0.01 [-0.17, 0.19]) between both groups, respectively. CONCLUSION: Patients given remdesivir are more likely to demonstrate recovery and were associated with higher rates of hospital discharge, but not with significant reduction in mean time to clinical improvement or mortality.

Squamous Cell Carcinoma of the Tonsil Causing Small Bowel Perforation in the Setting of Metastasis and Treatment With Programmed Death-1 Inhibitors: A Case Report.

Metastasis of extra-intestinal carcinoma to the gastrointestinal tract (GIT) is a rare event, most commonly occurring with malignant melanoma. Anti-PD-1 (programmed death-1) immunotherapeutic agents are immune checkpoint inhibitors with proven benefit across multiple cancer types, including squamous cell carcinoma of the head and neck (SCCHN). Here we describe a case of small bowel perforation attributed to a primary SCCHN metastasizing to the GIT in the setting of treatment with PD-1 inhibitors.

Effects of Febuxostat on Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To investigate the association between using febuxostat and cardiovascular events. METHODS: Systematic search of randomized controlled trials was performed using PubMed/MEDLINE, Cochrane review, and EMBASE databases through April 17, 2019. Meta-analysis was performed using random effect model and estimates were reported as risk difference (RD) with 95% CIs. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The main outcomes of interest were cardiovascular mortality and all-cause mortality. RESULTS: A total of 15 randomized controlled trials (16,070 participants) were included. The mean ± SD age was 58.1±11.7 years. At the median follow-up of 6.4 months, use of febuxostat was not associated with statistically significant risk of cardiovascular mortality (RD, 0.12%; 95% CI, -0.25% to 0.49%; I 2 =48%; low certainty evidence), all-cause mortality (RD, 0.20%; 95% CI, -0.28% to 0.68%; I 2  =60%; very low certainty evidence), major adverse cardiovascular events (RD, 0.40%; 95% CI, -0.34% to 1.13%; I 2 =26%; low certainty evidence), myocardial infarction (RD, -0.06%; 95% CI, -0.29% to 0.17%; I 2  =0%; moderate certainty evidence), stroke (RD, 0.10%; 95% CI, -0.15% to 0.35%; I 2 =0%; moderate certainty evidence), or new-onset hypertension (RD, 1.58%; 95% CI, -0.63% to 3.78%; I 2 =58%; very low certainty evidence). These findings were consistent in patients with existing cardiovascular disease. CONCLUSION: This meta-analysis suggested that use of febuxostat was not associated with higher risk of mortality or adverse cardiovascular outcomes in patients with gout and hyperuricemia. The results were limited by low to moderate certainty of evidence.

Progression of valvular calcification and risk of incident stroke: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Prevalent valvular calcification (VC) is associated with stroke but little is known about associations of VC progression with stroke. METHODS: Progression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors. RESULTS: We studied 5,539 MESA participants free of baseline CVD and atrial fibrillation. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 83% had no progression of VC; 15%, progression at one site (AVC or MAC), and 3%, progression at both sites. Over a median of 12 years, 211 total and 167 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p > 0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratio (95% CI) 1.59 (1.11, 2.28)] and ischemic stroke [1.64 (1.10, 2.45)]. Results remained significant after further adjustment for baseline coronary artery calcification. After excluding participants with interim atrial fibrillation and coronary heart disease, findings were no longer statistically significant in fully-adjusted models. There was no interaction by age, sex, or race/ethnicity. There was no association with AVC progression and stroke. CONCLUSIONS: Progression of MAC but not AVC over 2.4 years is associated with increased risk of total and ischemic stroke.

Complete Revascularization in Patients With STEMI and Multi-Vessel Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Percutaneous coronary intervention (PCI) is the treatment of choice for ST-elevation myocardial infarction (STEMI). However, efficacy of complete vs culprit only revascularization in patients with STEMI and multivessel disease remains unclear. METHODS: We searched PubMed/MEDLINE, and Cochrane library. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), repeat revascularization, stroke, major bleeding, and contrast induced nephropathy. Estimates were calculated as random effects hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: Twelve trials with 7592 patients were included. There was a significantly lower risk of MACE [HR 0.61; 95% CI (0.43-0.60); p = 0.0009; I2 = 72%], cardiovascular mortality [HR 0.74; 95% CI (0.56-0.99); p = 0.04; I2 = 2%], and repeat revascularization [HR 0.43; 95% CI (0.31-0.59); p < 0.00001; I2 = 67%] in patients treated with complete compared with culprit-only revascularization. There was no statistically significant difference in MI [HR 0.77; 95% CI (0.52-1.12); p = 0.17; I2 = 49%], all-cause mortality [HR 0.86; 95% CI (0.65-1.13); p = 0.28; I2 = 14%], heart failure [HR 0.82 95% CI (0.51-1.32); p = 0.42; I2 = 26%], major bleeding [HR 1.07; 95% CI (0.66-1.75); p = 0.78; I2 = 25%], stroke [HR 0.67; 95% CI (0.24-1.89); p = 0.45; I2 = 54%], or contrast induced nephropathy, although higher contrast volumes were used in the complete revascularization group [HR 1.22; 95% CI (0.78-1.92); p = 0.39; I2 = 0%]. CONCLUSION: Complete revascularization was associated with a significantly lower risk of MACE, cardiovascular mortality, and repeat revascularization compared with culprit-only revascularization. These results suggest complete revascularization with PCI following STEMI and multivessel disease should be considered.