Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors.

BACKGROUND: We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. MATERIALS AND METHODS: We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. RESULTS: A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. CONCLUSIONS: Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

Two gaps too many, three clues too few? Do elevated osmolal and anion gaps with crystalluria always mean ethylene glycol poisoning?

A 60-year-old African-American man with a medical history significant for heavy alcohol abuse, hypertension, delirium tremens, nephrolithiasis and seizure disorder was brought to the hospital with altered mental status. He was found to have high anion gap metabolic acidosis with significantly elevated lactate along with an elevated osmolal gap and calcium oxalate crystals in his urine. With this combination of findings, ethylene glycol poisoning was high in the differential. This case report describes why ethylene glycol poisoning was not the diagnosis in this patient despite the presence of these three classic laboratory findings, therefore emphasising the fact that these findings should not be taken at face value because they can be seen collectively in a patient yet each have a different cause.

Drug-eluting stent placement versus coronary artery bypass surgery for unprotected left main coronary artery disease: A meta-analysis of randomized controlled trials.

BACKGROUND: Coronary artery bypass grafting (CABG) is the standard of care for treating left main coronary lesions. However, recently published randomized controlled trials (RCT) have shown conflicting results. We sought to compare clinical outcomes of percutaneous coronary intervention (PCI) with drug-eluting stent placement to CABG using a meta-analysis of randomized controlled trials. METHODS: A systemic search of Pubmed, Scopus, Cochrane library, and Clinicaltrials.gov was performed for randomized controlled trials comparing PCI with CABG in patients with left main stenosis. Data were analyzed using random effect models and Mantel-Haenszel methods. The primary outcome was major adverse cardiovascular and cerebral events (MACCE). The secondary outcomes were myocardial infarction, stroke, cardiac, and all-cause mortality. A subgroup analysis based on SYNTAX score was also performed. RESULTS: A total of 4595 patients (2297 in the PCI group and 2298 in the CABG group) from five RCTs were included in the analysis. There were significant differences in MACCE (odds ratio [OR] 1.36, confidence interval [CI] 95%, 1.18-1.58, p-value: < 0.0001) and repeat revascularization (OR 1.85, CI 95%, 1.53-2.23, p-value: < 0.00001) favoring CABG. There were no significant differences in the incidence of myocardial infarction, stroke, or cardiac and all-cause mortality. Based on SYNTAX score, CABG was superior in terms of MACCE only in the subgroup with SYNTAX score of 33 or more. CONCLUSIONS: CABG results in fewer MACCE and need for repeat revascularization than PCI in patients with unprotected left main disease.