Cancer immunotherapy seeks to up regulate immune activators and down regulate immune suppressing agents to induce the body’s own immune system to confront malignancy. Nivolumab, a monoclonal antibody to PD1 (immune checkpoint inhibitor), has been tried in highly immunogenic malignancies such as metastatic melanoma. In this randomized, placebo-controlled trial of patients with advanced squamous cell non-small-cell lung cancer (NSCLC) that has progressed on first-line chemotherapy, 272 patients were randomized to either nivolumab or docetaxel (standard cytotoxic chemotherapy). There was a statistically significant increase in median overall survival (9.2 months with nivolumab vs. 6.0 months with docetaxel, HR 0.59, 95% CI 0.44-0.79, p < 0.001). There was a statistically significant increase in response rate (20% vs. 9%, p = 0.008), and less severe treatment-related adverse events (7% vs. 55%). The expression of PD-1 ligand on pathology review was not correlated or predictive of benefit with nivolumab. This trial shows nivolumab as an effective second-line agent for squamous cell NSCLC.
The optimal duration of anticoagulation after symptomatic pulmonary embolism is unclear as there is limited randomized, placebo-controlled trial evidence of different anticoagulation durations. For a first episode of an unprovoked pulmonary embolism, patients are often put on at least 6 months of anticoagulation, however the need of further anticoagulation is unclear. In this randomized, double-blind study, 371 patients at 14 French centers after a first episode of symptomatic, unprovoked pulmonary embolism were randomized to either 6 or 24 months of warfarin. At 18 months, 1.6% of patients who underwent anticoagulation for 24 months had either recurrent venous thromboembolism vs. 13.4% of patients who underwent anticoagulation for only 6 months (HR 0.15, 95% CI 0.05 – 0.43, p < 0.001). There was no statistically significant increase in major bleeding. After follow-up for 42 months, there was no statistically significant difference in a composite outcome of major bleeding or recurrent venous thromboembolism (20.8% vs. 24.0%, HR 0.75, 95% CI 0.47 – 1.18), suggesting the benefit was not maintained after discontinuation of anticoagulation and patients remain at high risk for recurrent venous thromboembolism. While on therapy, the benefits appear to outweigh the risks of anticoagulation, however even after 2 years patients remain at high risk for recurrent venous thromboembolism.
Coronary artery calcification (CAC) is associated with increased risk for myocardial infarction and all-cause mortality in short term follow-up, however the relationship with more long-term mortality is unknown. In this observational cohort study, investigators recruited 9715 asymptomatic patients that underwent coronary artery calcification scoring and followed for a median of 14.6 years for all-cause mortality. The CAC score was found to be highly predictive of all-cause mortality with a range from 3% to 28% depending on strata. The investigators found a 3.7 fold increase in all-cause mortality between patients with a high CAC score (>1000) compared to patients with a low CAC score (1 to 10). This study was performed at one institution, however had a large sample with long term follow-up that suggest the utility of characterizing coronary artery calcification to predict all-cause mortality.
Maternal obesity has been associated with poor pregnancy outcomes including macrosomia, increased rates of premature births, and even decreased life expectancy in adult offspring. There is concern that even in non-diabetic obese women, hyperglycemia and insulin resistance during pregnancy leads to adverse outcomes. In this randomized, placebo-controlled trial, 449 obese adult women (BMI > 30) without diabetes were randomized to either daily oral metformin 500mg or placebo and followed for pregnancy outcomes. There was no statistically significant difference in birth weight at delivery or a combined primary outcome of miscarriage, termination of pregnancy, stillbirth or neonatal death ( OR 3.6, 95% CI 0.74 – 17.50, p = 0.11). Metformin did not appear to improve pregnancy outcomes in obese women without diabetes.
Hypertension can both cause and be preceded by cardiac abnormalities as chronic subclinical myocardial damage can cause left ventricular hypertrophy (LVH) or early heart failure. With new high-sensitivity cardiac troponin-T (hs-cTNT) assays, chronic subclinical myocardial damage can be more readily assessed. In this observational study of 6,516 healthy participants without hypertension or prior history of cardiovascular disease, high-sensitivity cardiac troponin-T markers were obtained and followed for 6 years. Patients with higher hs-cTNT levels were more likely to be diagnosed with hypertension (HR 1.31 for patients with hs-cTNT > 14ng/L vs. <5ng/L, p-trend < 0.001) and also strongly associated with LVH by electrocardiography (HR 5.19 31 for patients with hs-cTNT > 14ng/L vs. <5ng/L, 95% CI 1.49-18.08). The investigators suggest that patients with elevated hs-cTNT even without history of hypertension or cardiovascular disease could potentially benefit for more aggressive lifestyle modification strategies.
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