Introduction:In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALKpositive NSCLC, brigatinib exhibited superior progressionfree survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results.

BACKGROUNDPatients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. METHODSIn this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTSA total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). CONCLUSIONSIn patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.)A BS TR AC T

Aggressive tumor biology might be the main factor contributing to positive microscopic resection margin after gastrectomy. Positive resection margin had a definite unfavorable impact on the OS of gastric cancer patients undergoing gastrectomy. When GC patients underwent gastrectomy with positive resection margin, positive nodal metastasis determined the worst OS, and distant metastasis was the most common site of recurrence.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868.

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Objective Neurotensin is a peptide whose receptor (SORT1) is linked to cardiovascular disease (CVD) development. We hypothesized concentrations of pro-neurotensin (pro-NT; stable pro-fragment of neurotensin) would predict incident CV events in community-based subjects. Approach and Results Blood samples from 3439 participants in the Framingham Heart Study (FHS) Offspring cohort (mean age 59.2 years, 47.1% male) were tested for pro-NT. Primary outcome of interest was incident hard CVD (myocardial infarction, stroke, and CV death); interaction between pro-NT concentration with sex, low density lipoprotein (LDL) concentrations or SORT1 single-nucleotide polymorphisms (SNP) was sought. At baseline, those in the highest log-pro-NT quartile were younger and heavier (P<0.001); across pro-NT quartiles, more prevalent hard CVD (from 3% to 7%; P<0.001) and diabetes mellitus (from 6% to 14; P<0.001) was present. In age and sex-adjusted models, log-pro-NT concentrations predicted incident hard CVD (hazard ratio [HR] = 1.24 per standard deviation [SD] change in log-pro-NT; 95% confidence intervals [CI] = 1.11–1.39; P<0.001), a finding that remained upon adjustment for standard CVD risk factors (HR 1.13; 95% CI = 1.01–1.27; P = 0.03). Elevated log-pro-NT concentrations were associated with shorter time to first event (P=0.02). We found no effect modification by sex, LDL concentration, or SORT1 SNPs. Concentrations of pro-NT were modestly associated with left ventricular mass and coronary artery calcium in these subjects. Conclusions Higher concentrations of pro-NT are associated with a greater risk of incident CV events in the community. This association did not vary according to sex, baseline LDL, or SORT1 genotype.

Hypoalbuminemia is a common finding and independent predictor for unfavorable prognosis. The prognostic value of albumin measurement for short‐term VTE prediction in hospitalized patients remains unclear. In the APEX trial (http://ClinicalTrials.gov identifier: NCT01583218), medical inpatients were randomized to receive either extended‐duration betrixaban or shorter‐duration enoxaparin and followed for 77 days. Baseline albumin concentrations were obtained in 7266 subjects with evaluable VTE endpoints. The association of baseline albumin to VTE was assessed, with adjustment for patient characteristics, thromboprophylaxis, and biomarkers for fibrinolysis and inflammation (ie, D‐dimer and C‐reactive protein [CRP]). VTE risk refinement was evaluated by incorporation of albumin to well‐validated risk assessment models. A stepwise increase in the risk of VTE (P < .0001) was observed with lower levels of albumin. Patients at the bottom albumin quartile (<35 g/L) had a two‐fold greater odds for developing VTE compared with the top quartile (≥42 g/L) (OR = 2.119 [95% CI, 1.592‐2.820]; adjusted OR = 2.079 [1.485‐2.911]). The odds for VTE increased by 1.368 (95% CI, 1.240‐1.509) times per SD decrement of albumin (5.24 g/L). Compared with the propensity score‐matched pairs of patients with albumin ≥35 g/L, patients with albumin <35 g/L had a greater risk of VTE (OR = 1.623 [1.260‐2.090]; adjusted OR = 1.658 [1.209‐2.272]). Albumin measurement also refined VTE risk discrimination and reclassification after inclusion in the risk assessment models. In conclusion, acutely ill hospitalized patients with low serum albumin had an increased VTE risk through 77 days. VTE risk assessment models for medical inpatients should consider incorporation of baseline albumin measurement.