Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus). Next-generation sequencing was performed using panels comprised of 46–200 genes. Recurrence-free and overall survival was compared across gene mutational status in both univariate and multivariate analyses. 342 patients were identified, 245 of which had endometrioid histology. For grade 1–2, stage I–II endometrioid endometrial cancer patients, age (HR 1.07, 95% CI 1.03–1.10), CTNNB1 mutation (HR 5.97, 95% CI 2.69–13.21), and TP53 mutation (HR 4.07, 95% CI 1.57–10.54) were associated with worse recurrence-free survival on multivariate analysis. When considering endometrioid tumors of all grades and stages, CTNNB1 mutant tumors were associated with significantly higher rates of grade 1–2 disease, lower rates of deep myometrial invasion, and lower rates of lymphatic/vascular space invasion. When both TP53 and CTNNB1 mutations were considered, presence of either TP53 mutation or CTNNB1 mutation remained a statistically significant predictor of recurrence-free survival on multivariate analysis and was associated with a more precise confidence interval (HR 4.69, 95% CI 2.38–9.24). Thus, mutational analysis of a 2 gene panel of CTNNB1 and TP53 can help to identify a subset of low grade, early stage endometrial cancer patients who are at high risk of recurrence.

Rectal cancer patients who underwent surgery at high-volume hospitals were less likely to have a permanent colostomy and had better survival rates than those treated in low-volume hospitals. Identifying processes of care that contribute to these differences may improve patients' outcomes in all hospitals.

As there are millions of cancer deaths every year, it is of great value to identify applicable prognostic biomarkers. As an important alarm, the prognostic role of high mobility group box 1 (HMGB1) in cancer remains controversial. We aim to assess the association of HMGB1 expression with prognosis in cancer patients. Systematic literature searches of PubMed, Embase and Web of Science databases were performed for eligible studies of HMGB1 as prognostic factor in cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the influence of HMGB1 expression on overall survival (OS) and progression-free survival (PFS) in cancer patients. 18 studies involving 11 different tumor types were included in meta-analysis. HMGB1 overexpression was significantly associated with poorer OS (HR: 1.99; 95% CI, 1.71-2.31) and PFS (HR: 2.26; 95% CI, 1.65-3.10) irrespective of cancer types including gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, nasopharyngeal carcinoma, head and neck squamous-cell carcinoma, esophageal cancer, malignant pleural mesothelioma, bladder cancer, prostate cancer, and cervical carcinoma. Subgroup analyses indicated geographical area and size of studies did not affect the prognostic effects of HMGB1 for OS. Morever, HMGB1 overexpression had a consistent correlation with poorer OS when detected by immunohistochemistry in tissues and enzyme-linked immunosorbent assay in serum, whereas the correlation did not exist by quantitative real-time reverse-transcription polymerase chain reaction in tissues. HMGB1 overexpression is associated with poorer prognosis in patients with various types of cancer, suggesting that it is a prognostic factor and potential biomarker for survival in cancer.

POEMS syndrome is a rare clonal plasma cell disease. Patients with POEMS syndrome are at risk of developing pulmonary hypertension, but the data on its incidence and impact on outcome are limited. We reviewed records of 154 POEMS syndrome patients with complete duplex echocardiography data for estimation of pulmonary artery systolic pressure (sPAP) at the time of diagnosis. Forty-two (27%) of 154 patients with pulmonary hypertension (estimated sPAP ≥50mmHg) were identified. Median age was 46 years (range 31-71 years). Patients with pulmonary hypertension were more likely to have peripheral edema (P=0.04), ascites (P=0.02), pleural effusion (P=0.005), and have longer time from onset to diagnosis (P=0.004) when compared with those without pulmonary hypertension. Restrictive abnormalities and decreased diffusion capacity of carbon monoxide were observed in 83% and 96% patients with pulmonary hypertension, compared with 50% and 72% in patients without pulmonary hypertension, respectively. Reversibility of pulmonary hypertension was observed after treatment of POEMS syndrome. After median follow of 32 months, survival of patients with pulmonary hypertension was worse than those without (median overall survival 54 months vs. median not reached, P=0.021). In conclusion, pulmonary hypertension is a common feature of POEMS syndrome, and is associated with signs of extravascular volume overload. Although active treatment of POEMS syndrome can reverse pulmonary hypertension, survival of these patients is worse than those without pulmonary hypertension.

Patients with PA-HVOD had different characteristics than those with HSCT-HVOD. Anticoagulation and TIPS treatment may be effective for patients with PA-HVOD.

Here, we sought to explore the underlying role of interleukin (IL)-8 in neutrophil extracellular traps (NETs) formation during atherosclerosis (AS). The concentration of pro-inflammatory cytokines IL-8, IL-6 and IL-1β was determined by enzyme-linked immunosorbent assay (ELISA). NETs formation was evaluated by immunofluorescence and myeloperoxidase (MPO)-DNA complex ELISA. The mRNA levels of IL-8 and Toll-like receptor 9 (TLR9) were measured by quantitative real-time PCR (qRT-PCR). The phosphorylation levels of NF-κB p65 were detected by western blotting. The hematoxylin and eosin (H&E) staining of atherosclerotic lesion areas was performed in ApoE-deficiency mice. Results showed that patients with AS showed higher serum levels of IL-8, a pro-inflammatory cytokine and NETs. IL-8 interacted with its receptor CXC chemokine receptor 2 (CXCR2) on neutrophils, leading to the formation of NETs via Src and extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPK) signaling to aggravate AS progression in vivo. PMA-induced NETosis directly upregulated the TLR9/NF-κB pathway in macrophages and subsequently initiated the release of IL-8. Our data reveal a neutrophil-macrophage interaction in AS progression, and indicate that NETs represent as a novel therapeutic target in treatment of AS and other cardiovascular diseases (CVD).

BackgroundCarotid atherosclerosis (CA) is a reflector of generalized atherosclerosis that is associated with systemic vascular disease. Data are limited on the epidemiology of carotid lesions in a large, nationally representative population sample. We aimed to evaluate the prevalence of CA detected by carotid ultrasonography and related risk factors based on a national survey in China.Methods and ResultsA total of 107 095 residents aged ≥40 years from the China National Stroke Prevention Project underwent carotid ultrasound examination. Participants with carotid endarterectomy or carotid stenting and those with stroke or coronary heart disease were excluded. Data from 84 880 participants were included in the analysis. CA was defined as increased intima–media thickness (IMT) ≥1 mm or presence of plaques. Of the 84 880 participants, 46.4% were men, and the mean age was 60.7±10.3 years. The standardized prevalence of CA was 36.2% overall, increased with age, and was higher in men than in women. Prevalence of CA was higher among participants living in rural areas than in urban areas. Approximately 26.5% of participants had increased IMT, and 13.9% presented plaques. There was an age‐related increase in participants with increased IMT, plaque presence, and stenosis. In multiple logistic regression analysis, older age, male sex, residence in rural areas, smoking, alcohol consumption, physical inactivity, obesity, hypertension, diabetes mellitus, and dyslipidemia were associated with CA.Conclusions CA was highly prevalent in a middle‐aged and older Chinese population. This result shows the potential clinical importance of focusing on primary prevention of atherosclerosis progression.

Purpose Utilizing cell-based approaches to identify genetic markers predictive of patients’ risk for poor response prior to chemotherapy. Experimental Design We performed genome-wide association studies (GWASs) to identify SNPs associated with cellular sensitivity to carboplatin through their effects on mRNA expression using International HapMap lymphoblastoid cell lines (LCLs) and replicated them in additional LCLs. SNPs passing both stages of the cell-based study were tested for association with progression free survival (PFS) in patients. Phase-1 validation was based on 377 ovarian cancer patients receiving at least 4-cycle of carboplatin and paclitaxel from the Australian Ovarian Cancer Study (AOCS). Positive associations were then assessed in the phase-2 validation analysis of 1,326 patients from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas. Results In the initial GWAS, 342 SNPs were associated with carboplatin-induced cytotoxicity, of which 18 unique SNPs were retained after assessing their association with gene expression. One SNP (rs1649942) was replicated in an independent LCL set (p-valueBonferroni adjusted=9×10−3). It was found to be significantly associated with decreased PFS in phase-1 AOCS patients (Pper-allele=2×10−2), with a stronger effect in the subset of women with optimally debulked tumours (Pper-allele=4×10−3). rs1649942 was also associated with poorer overall survival in women with optimally debulked tumours (Pper-allele=9×10−3). However, this SNP was not significant in the phase-2 validation with patients from numerous cohorts. Conclusion This study demonstrates the potential of cell-based, genome-wide approaches to identify germ-line predictors of treatment outcome and highlights the need for extensive validation in patients to assess their clinical effect.