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BackgroundIpilimumab (IPI) and BRAF inhibitors (BRAFi) improve survival in melanoma, but not all patients will benefit and toxicity can be significant. Pretreatment neutrophil to lymphocyte ratio (NLR) has been associated with outcome in IPI-treated patients, but has not been studied during treatment or in BRAFi-treated patients.MethodsUsing a prospectively maintained database, patients with unresectable stage III or IV melanoma treated with IPI or a BRAFi (vemurafenib or dabrafenib as monotherapy) from 2006 to 2011 were identified. NLR was calculated before treatment and at 3-week intervals after treatment initiation until 9 weeks. Baseline NLR was tested for association with overall survival (OS), progression free survival (PFS), and clinical response to treatment. On-treatment NLRs were tested for association with the same outcomes using landmark survival analyses and time-dependent Cox regression models. The association of relative change of NLR from baseline with outcomes was also examined. A multivariate model tested the association of NLR and OS/PFS with additional clinical factors.ResultsThere were 197 IPI patients and 65 BRAFi patients. In multivariable analysis adjusting for M stage, and disease type (in OS)/gender (in PFS), an NLR value of 5 or above at every timepoint was associated with worse OS (HR 2.03–3.37, p < 0.001), PFS (HR 1.81–2.51, p < 0.001), and response to therapy (OR 3.92–9.18, p < 0.007), in the IPI cohort. In addition, a > 30% increase in NLR above baseline at any timepoint was associated with a worse OS and PFS (HR 1.81 and 1.66, p < 0.004). In BRAFi patients, NLR was not consistently associated with outcomes.ConclusionsA high NLR, whether measured prior to or during treatment with IPI, is associated with worse OS, PFS, and clinical response in patients with advanced melanoma. An increasing NLR from baseline during treatment was correlated with worse OS and PFS in IPI-treated patients. In comparison, as NLR was not associated with outcomes in BRAFi patients, NLR may have a uniquely predictive value in patients treated with immunotherapy.

Recurrence is highly associated with DSD and events occur as late as 16 years after initial presentation, including in patients with initially considered benign tumors. Patients with large (≥ 8 cm) tumors in the chest or abdominal/retroperitoneal cavity are at greatest risk.

I COUGH, a standardized postoperative care program emphasizing patient education, early mobilization, and pulmonary interventions, reduced the incidence of postoperative pneumonia and unplanned intubation among our patients.

Clostridium difficile is the principal pathogen associated with hospital-acquired acute diarrheal disease. We have evaluated the performances of six approaches for diagnosis of C. difficile-associated diarrhea (CDAD). Consecutive stool specimens (n ‫؍‬ 200) from 133 patients were examined by cytotoxin assay, by culture of C. difficile on cycloserine-cefoxitin-fructose agar, and by toxin detection using four rapid immunoassay systems (Oxoid Toxin A test, ImmunoCard Toxin A test, TechLab Tox A/B II test, and Premier Toxins A&B test). A diagnosis of CDAD was established for 35 (27%) patients (representing 29% of specimens). The adjusted sensitivity and specificity of the methods were, respectively, 98 and 99% for the cytotoxin assay, 54 and 99% for ImmunoCard, 50 and 98% for Oxoid, 79 and 98% for TechLab, 80 and 98% for Premier, and 57 and 100% for culture. The TechLab and Premier assays are acceptable tests for diagnosis of CDAD but are not equivalent to the cytotoxin assay.Nosocomial infection with Clostridium difficile increases morbidity and mortality among hospitalized patients and places a significant economic burden on health services (3,7,18). Early diagnosis is associated with better prognosis (12); therefore; rapid laboratory diagnosis is highly desirable.The diagnosis of C. difficile-associated diarrhea (CDAD) is usually based on clinical features and detection of C. difficile toxin. Tissue culture assay is considered the "gold standard" for the demonstration of C. difficile toxins in specimens of feces. The technical complexity, slow turnaround time (24 to 48 h), and lack of standardization of the cytotoxin assay are significant limiting factors (11). As a result, a number of commercial products for rapid immunological detection of toxin have been developed. Some products are based on detection of only C. difficile toxin A, while others detect both toxin A and toxin B. The practical importance of detection of both toxins is unclear (4, 7). The impetus to detect both toxins may be supported if the suggestion that toxin A Ϫ B ϩ strains of C. difficile are emerging as significant pathogens is validated (1, 13).In this study, four rapid immunoassays were evaluated for the detection of C. difficile toxins in stool specimens and their performances were compared with that of the cytotoxin assay. The rapid assays consisted of two microwell-based enzyme immunoassays that detected both toxin A and toxin B and two chromatographic cassette-based immunoassays that detected toxin A only. The performances of six assay methods (the four immunoassays, the cytotoxin assay, and bacteriological culture) were evaluated with reference to clinical and biological criteria for diagnosis of CDAD. MATERIALS AND METHODSTwo hundred consecutive stool specimens (from 133 adult patients) received in the laboratory for routine investigation of C. difficile infection were included in the study. Stool specimens were cultured on the day of receipt. The study included specimens that were transported by routine road transport at room temper...

Background-Genetic risk for Alzheimer's disease (AD) may be conferred by the susceptibility polymorphism apolipoprotein E (APOE), where the ε4 allele increases the risk of developing lateonset Alzheimer's disease but is not a definitive predictor of the disease, or by autosomal dominant mutations (e.g., the presenilins), which almost inevitably result in early-onset familial Alzheimer's disease. The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients.Methods-Data were compared from two separate protocols. The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study is a randomized, multi-site clinical trial that evaluated the impact of susceptibility testing for Alzheimer's disease with APOE in 101 adult children of Alzheimer's disease patients. A separate study, conducted at the University of Washington, assessed the impact of deterministic genetic testing by disclosing presenilin-1, presenilin-2, or TAU genotype to 22 individuals at risk for familial Alzheimer's disease or frontotemporal dementia. In both protocols, participants received genetic counseling and completed the Impact of Event Scale (IES), a measure of test-specific distress. Scores were analyzed at the time point closest to one year postdisclosure at which IES data were available. The role of genetic test result (positive vs. negative) and type of genetic testing (deterministic vs. susceptibility) in predicting log-transformed IES scores was assessed with linear regression, controlling for age, gender, and time from disclosure.Corresponding Author: Robert C. Green, MD, MPH, Professor of Neurology, Genetics and Epidemiology, Boston University Schools of Medicine and Public Health, 715 Albany Street, L-320, Boston, MA 02118, Tel: 617-638-5362, Fax: 617-638-4275, Email: rcgreen@bu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The authors have no conflicts of interest to disclose. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResults-Subjects from the REVEAL Study who learned that they were positive for the susceptibility gene APOE ε4+ experienced similar, low levels of test-specific distress compared to those who received positive results of deterministic testing in the University of Washington study (p= 0.78). APOE ε4+ individuals in the susceptibility protocol experienced more test-specific distress than those who tested ε4− in the same study (p= 0.04); however, among those receiving deterministic te...

Objective: To identify predictors of desmoid progression during observation.Summary Background Data: Untreated desmoids can grow, remain stable, or regress, but reliable predictors of behavior have not been identified.Methods: Primary or recurrent desmoid patients were identified retrospectively from an institutional database. In those managed with active observation who underwent serial MRIs with T2-weighted sequences, baseline tumor size was recorded, and two radiologists independently estimated the percentage of tumor volume showing hyperintense T2 signal at baseline. Associations of clinical or radiographic characteristics with progression-free survival (PFS; by RECIST) were evaluated by Cox regression and Kaplan-Meier statistics.Results: Among 160 patients with desmoids, 72 were managed with observation, and 37 of these had serial MRI available for review. Among these 37 patients, median age was 35 years and median tumor size was 4.7 cm; all tumors were extra-abdominal (41% in abdominal wall). While PFS was not associated with size, site, or age, it was strongly associated with hyperintense T2 signal in ≥90% vs <90% of baseline tumor volume (as defined by the "test" radiologist; hazard

Objective: To understand the role of racial residential segregation on Black-White disparities in breast cancer presentation, treatment, and outcomes. Summary of Background Data: Racial disparities in breast cancer treatment and outcomes are well documented. Black individuals present at advanced stage, are less likely to receive appropriate surgical and adjuvant treatment, and have lower overall and stage-specific survival relative to White individuals. Methods: Using data from the Surveillance, Epidemiology, and End Results program, we performed a retrospective cohort study of Black and White patients diagnosed with invasive breast cancer from 2005 to 2015 within the 100 most populous participating counties. The racial index of dissimilarity was used as a validated measure of residential segregation. Multivariable regression was performed, predicting advanced stage at diagnosis (stage III/IV), surgery for localized disease (stage I/II), and overall stage-specific survival. Results: After adjusting for age at diagnosis, estrogen/progesterone receptor status, and region, Black patients have a 49% greater risk (relative risk [RR] 1.49 95% confidence interval [CI] 1.27, 1.74) of presenting at advanced stage with increasing segregation, while there was no observed difference in Whites (RR 1.04, 95% CI 0.93, 1.16). Black patients were 3% less likely to undergo surgical resection for localized disease (RR 0.97, 95% CI 0.95, 0.99) with increasing segregation, while Whites saw no significant difference. Black patients had a 29% increased hazard of death (RR 1.29, 95% CI 1.04, 1.60) with increasing segregation; there was no significant difference among White patients. Conclusions: Our data suggest that residential racial segregation has a significant association with Black-White racial disparities in breast cancer. These findings illustrate the importance of addressing structural racism and residential segregation in efforts to reduce Black-White breast cancer disparities.