Citations

SNF'ing out antitumor immunity Immune checkpoint inhibitors induce durable tumor regressions in some, but not all, cancer patients. Understanding the mechanisms that determine tumor sensitivity to these drugs could potentially expand the number of patients who benefit (see the Perspective by Ghorani and Quezada). Pan et al. discovered that tumor cells in which a specific SWI/SNF chromatin remodeling complex had been experimentally inactivated were more sensitive to T cell–mediated killing. The cells were more responsive to interferon-γ, leading to increased secretion of cytokines that promote antitumor immunity. Miao et al. examined the genomic features of tumors from patients with metastatic renal cell carcinoma who had been treated with immune checkpoint inhibitors. Tumors harboring inactivating mutations in PBRM1 , which encodes a subunit of the same SWI/SNF complex, were more likely to respond to the drugs. Science , this issue p. 770 , p. 801 ; see also p. 745

Objective. Keeping in mind the rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the need to establish noninvasive tests for its detection, the aim of our study was to investigate whether platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) can predict the presence of liver fibrosis in this group of patients. Methods. In 98 patients with NAFLD and 60 healthy volunteers, complete blood counts with automated differential counts were performed and values of PC, PDW, MPV, and PCT were analyzed. Results. Patients with NAFLD had lower PC and higher MPV, PCT, and PDW compared to the controls (P < 0.05). When NAFLD group was stratified according to severity of liver fibrosis, there was a statistically significant difference in the average values of PDW and PC between the groups (P < 0.05). Conclusion. Patients with NAFLD have significantly higher values of PCT, PDW, and MPV when compared to the healthy controls. Further studies are needed to establish their potential use for prediction of the degree of liver steatosis and fibrosis in NAFLD patients.

Celiac disease (CD) is a systemic, chronic autoimmune disease that occurs in genetically predisposed individuals following dietary gluten exposure. CD can present with a wide range of gastrointestinal and extraintestinal manifestations and requires lifelong adherence to a gluten-free diet [GFD]. Venous thromboembolism (VTE) as a presentation of celiac disease is unusual and rarely reported. We present a case of a 46-year-old man who was admitted for shortness of breath and pleuritic chest pain and was found to have iron deficiency anemia, deep venous thrombosis, and bilateral pulmonary emboli (PE). After work-up for his anemia, the patient was diagnosed with CD. Comprehensive investigation for inherited or acquired prothrombotic disorders was negative. It is becoming increasingly recognized that CD is associated with an increased risk for VTE. PE, however, as a presentation of CD is exceedingly rare and to the best of our knowledge this is the third case report of such an occurrence and the only case report of a patient from North America. It is important to recognize that the first symptoms or signs of celiac disease might be extraintestinal. Furthermore, VTE as a presentation of CD is rare but life-threatening.

Abstract Purpose: We hypothesized that mutations in homologous recombination repair (HRR) genes beyond BRCA1 and BRCA2 improve outcomes for ovarian carcinoma patients treated with platinum therapy and would impact the relative benefit of adding prolonged bevacizumab. Experimental Design: We sequenced DNA from blood and/or neoplasm from 1,195 women enrolled in GOG-0218, a randomized phase III trial in advanced ovarian carcinoma of bevacizumab added to carboplatin and paclitaxel. Defects in HRR were defined as damaging mutations in 16 genes. Proportional hazards models were used to estimate relative hazards for progression-free survival (PFS) and overall survival (OS). Results: Of 1,195 women with ovarian carcinoma, HRR mutations were identified in 307 (25.7%). Adjusted hazards for progression and death compared with those without mutations were lower for women with non-BRCA HRR mutations [HR = 0.73; 95% confidence interval (CI), 0.57–0.94; P = 0.01 for PFS; HR = 0.67; 95% CI, 0.50–0.90; P = 0.007 for OS] and BRCA1 mutations (HR = 0.80; 95% CI, 0.66–0.97; P = 0.02 for PFS; HR = 0.74; 95% CI, 0.59–0.94; P = 0.01 for OS) and were lowest for BRCA2 mutations (HR = 0.52; 95% CI, 0.40–0.67; P &lt; 0.0001 for PFS; HR = 0.36; 95% CI, 0.25–0.53; P &lt; 0.0001 for OS). A test of interaction showed no difference in the effect of bevacizumab on PFS between cases with and without mutations. Conclusions: HRR mutations, including non-BRCA genes, significantly prolong PFS and OS in ovarian carcinoma and should be stratified for in clinical trials. The benefit of adding bevacizumab was not significantly modified by mutation status. Clin Cancer Res; 24(4); 777–83. ©2017 AACR.

AbstractBackgroundThere are sparse clinical data on the procedural trends, outcomes and readmission rates following FDA approval and expansion of Transcatheter mitral valve repair/MitraClip®. Whether a complex new technology can be disseminated safely and quickly is controversial.MethodsThe study cohort was derived from the National Readmission Data (NRD) 2013–14. MitraClip® was identified using appropriate International Classification of Diseases, 9th Revision, Clinical Modification (ICD‐9‐CM) codes. The primary outcome was a composite of in‐hospital mortality + procedural complications. Secondary outcome included 30‐day readmissions. Hierarchical two level logistic models were used to evaluate study outcomes.ResultsOur analysis included 2003 MitraClip® procedures. Overall in‐hospital mortality was 3.9%. As expected, there was a significant increase in procedural volume post‐FDA approval. Importantly, a corresponding downward trend in mortality and procedural complications was observed. Significant predictors of in‐hospital mortality and procedural complications included the use of vasopressors (P <0.001) and hemodynamic support (P < 0.001). Higher hospital volume (≥10 MitraClips/year) was associated with lower in‐hospital mortality and complications (P = 0.02). There were 304 (15.1%) 30‐day readmissions, with heart failure being the most common cause of readmission. Elective procedures had lower in‐hospital mortality (P < 0.001) and lower readmission rates (P = 0.011) compared with nonelective procedures.ConclusionA significant increase in MitraClip® procedural volumes occurred post‐FDA approval. Overall morbidity and mortality were low and trended downwards. Hospital procedure volume ≥10 cases were associated with lower mortality and overall complication rates. These data suggest a successful roll out of a very complex novel structural heart procedure.

Policy and financial pressures have driven up use of observation stays for patients in traditional Medicare and the Veterans’ Affairs Healthcare System. Using claims data (2004-2014) from OptumLabs™ Data Warehouse, we examined whether people in private Medicare Advantage (MA) and commercial plans experienced similar changes. We found that use of observation increased rapidly for patients in MA plans—even though MA plans were not subject to the same pressures as government-run programs. In contrast, use of observation remained constant for people in commercial plans—except for enrollees 65 and older, for whom it increased somewhat. Privately insured patients returning to the hospital after an inpatient stay were increasingly likely to be placed under observation. Our results suggest that observation is rapidly replacing inpatient admissions and readmissions for many older patients in MA and commercial plans, while younger patients continue to be admitted as inpatients at relatively constant rates.

Objective Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions These data suggest several plausible genetic links between DLBCL and SLE.

Portal vein thrombosis (PVT) is an uncommon condition usually associated with hypercoagulable states or liver cirrhosis. PVT due to sports-related injuries is rarely reported and, to the best of our knowledge, only two cases have been reported thus far. Brazilian jiu-jitsu (BJJ) is a form of martial arts and is considered very safe with minimal risk for injury. It has growing popularity worldwide. Here, we report the first case of PVT secondary to abdominal trauma related to the practice of (BJJ) in an otherwise healthy 32-year-old man with no other traditional risk factors for PVT.