is a new culprit gene for IPAH ranking second to BMPR2. The rare deleterious mutations in BMP9, which lead to the reduction in BMP9 secretion and impairment in BMP9 function, account for 6.7% of IPAH cases.

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PURPOSE We evaluated the efficacy and safety of pembrolizumab in patients from Asia with previously treated advanced hepatocellular carcinoma (HCC). METHODS In a double-blind, phase III trial, 453 patients with advanced HCC and progression during or after treatment with or intolerance to sorafenib or oxaliplatin-based chemotherapy were randomly assigned in a 2:1 ratio to receive pembrolizumab (200 mg) or placebo once every 3 weeks for ≤ 35 cycles plus best supportive care. The primary end point was overall survival (one-sided significance threshold, P = .0193 [final analysis]). Secondary end points included progression-free survival (PFS) and objective response rate (ORR; one-sided significance threshold, P = .0134 and .0091, respectively [second interim analysis]; RECIST version 1.1, by blinded independent central review). RESULTS Median overall survival was longer in the pembrolizumab group than in the placebo group (14.6 v 13.0 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = .0180). Median PFS was also longer in the pembrolizumab group than in the placebo group (2.6 v 2.3 months; hazard ratio for progression or death, 0.74; 95% CI, 0.60 to 0.92; P = .0032). ORR was greater in the pembrolizumab group (12.7% [95% CI, 9.1 to 17.0]) than in the placebo group (1.3% [95% CI, 0.2 to 4.6]; P < .0001). Treatment-related adverse events occurred in 66.9% of patients (grade 3, 12.0%; grade 4, 1.3%; grade 5, 1.0%) in the pembrolizumab group and 49.7% of patients (grade 3, 5.9%; grade 4, 0%; grade 5, 0%) in the placebo group. CONCLUSION In patients from Asia with previously treated advanced HCC, pembrolizumab significantly prolonged overall survival and PFS, and ORR was greater versus placebo.

BackgroundvAcute pulmonary embolism (PE) is a life threatening disease. The treatment options depend on the severity of the disease and the mortality varies widely depending on the severity of the condition. It is important to identify patients who are at high risk of mortality. The aim of the present study was to explore the prognostic alues of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) for 30-day mortality in patients with acute PE.MethodsThe study included 321 patients admitted to our university hospital between January 2013 and May 2015 with the diagnosis of acute PE. Multivariable risk models were developed to assess the predictive values of the NLR and PLR for 30-day mortality. Discrimination was evaluated using receiver operating characteristic (ROC) curves.ResultsTwo hundred forty-eight patients met our selection criteria. Twenty of them died within 30 days of hospital admission. NLR was found to be an independent predicator after other confounding factors were adjusted in the model. For 1 unit of increase of NLR, the risk of 30-day mortality rose about 13  % (OR = 1.13,95 % CI: 1.04–1.23). The area under ROC for NLR is 0.79 (95 %CI: 0.703–0.880). PLR was associated with 30-day mortality in univariate analysis but the predicative ability diminished with inclusion of other predicators in multivariable model.ConclusionsNLR is readily available predicator for short-term mortality. It could be a useful indicator for identifying high risk population and guiding clinical management of acute PE.

Following the demonstration of 50 BMPR2 mutations, including 25 novel mutation sites, in 305 Chinese IPAH and HPAH patients, 15 we analyzed their phenotype-genotype relationship. The aim was to investigate the influence of BMPR2 mutations on the clinical trait and whether this influence is associated with sex.Background-BMPR2 mutations predispose to idiopathic and heritable pulmonary arterial hypertension (IPAH and HPAH).The influence of BMPR2 mutations on clinical outcome is not concordant in different ethnic groups. Although the BMPR2 mutation spectrum and mutation rate in Chinese PAH patients has been reported previously, the influence of genotype on phenotype and whether this influence is associated with sex have not been investigated. Methods and Results-We analyzed data from 305 PAH patients considered as either idiopathic or heritable who underwent genetic counseling in Shanghai Pulmonary Hospital. The clinical, functional, and hemodynamic characteristics of BMPR2 mutation carriers and noncarriers were compared. The more severe hemodynamic compromise at diagnosis in BMPR2 mutation carriers versus noncarriers is concordant with other ethnic groups. In the Chinese PAH cohort, BMPR2 mutations were associated with a higher risk of mortality after adjustment for age and sex (hazard ratio, 1.971; 95% confidence interval, 1.121-3.466; P=0.018). The overall survival difference between mutation carriers and noncarriers was more obvious in male patients, which was reflected by a higher mortality risk of male mutation carriers than that of male noncarriers after adjustment for age at diagnosis (hazard ratio, 3.702; 95% confidence interval, 1.416-9.679; P=0.008). In females, this trend did not reach statistical significance. Conclusions-BMPR2 mutations influence phenotype more obviously in male PAH patients. The pathogenesis of female PAH patients is more complicated, and the influence of BMPR2 mutations may be modified by other unknown factors, making disparities in the prognosis between female mutation carriers and noncarriers less evident. (Circ Cardiovasc Genet. 2012;5:511-518.)