No abstract

No abstract

ObjectivesMET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC.MethodsTwo independent investigators applied parallel search strategies with the terms “MET AND lung cancer”, “MET AND NSCLC”, “MET gene copy number AND prognosis” in PubMed through January 2014. We selected the studies that investigated the association of MET gene copy number with survival, in patients who received surgery.ResultsAmong 1096 titles that were identified in the initial search, we retrieved 9 studies on retrospective cohorts with adequate retrievable data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Out of those, 6 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. We calculated the I2 statistic to assess heterogeneity (I2 = 72%). MET gene copy number predicted worse overall survival when all studies were combined in a random effects model (HR = 1.78, 95% CI 1.22–2.60). When only the studies that had at least 50% of adenocarcinoma patients in their populations were included, the effect was significant (five studies, HR 1.55, 95% CI 1.23–1.94). This was not true when we included only the studies with no more than 50% of the patients having adenocarcinoma histology (four studies HR 2.18, 95% CI 0.97–4.90).ConclusionsHigher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC. This prognostic impact may be adenocarcinoma histology specific.

Non-Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non-Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non-Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin-resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy.

Guidelines advocate universal, prompt treatment of hepatitis C (HCV) infection in HIV/HCV co-infected patients, but barriers to uptake of HCV direct-acting antivirals (DAAs) remain unclear in this population. This retrospective study investigated the care cascade from HCV diagnosis to sustained virologic response (SVR) at an urban infectious disease clinic in Saint Louis, Missouri during the first 18 months of interferon-free DAA availability in the United States. Of 1949 HIV patients seen in clinic, 91.9% were screened for HCV and 5.4% (n = 106) had chronic HCV infection with follow-up. Of these 106 co-infected patients, 100 underwent fibrosis testing, 55 were offered DAAs, 38 completed treatment, and 37 achieved SVR. Delayed DAA treatment was associated with no insurance, substance abuse, poor HIV control, and younger age. Providers delayed DAA treatment most commonly for substance abuse, psychiatric disease, and uncontrolled HIV. Mean time to insurance decision from initial prescription was 20.9 ± 29.6 days and mean time to final decision was 29.9 ± 40.1 days. DAAs are highly successful in co-infected patients in this early period but insurance delays and misconceptions from the interferon era can ultimately limit uptake. Addressing these factors in a comprehensive treatment model may bridge disparities and improve real-world SVRs.