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BACKGROUNDBody weight is associated with colorectal cancer (CRC) risk and survival, but to the authors' knowledge, the impact of long‐term postdiagnostic weight change is unclear. Herein, the authors investigated whether weight change over the 5 years after a diagnosis of CRC is associated with survival.METHODSCRC cases diagnosed from 1997 to 2008 were identified through 4 population‐based cancer registry sites. Participants enrolled within 2 years of diagnosis and reported their height and weight 2 years prior. Follow‐up questionnaires were administered approximately 5 years after diagnosis. Associations between change in weight (in kg) or body mass index (BMI) with overall and CRC‐specific survival were estimated using Cox regression analysis adjusted for age, sex, American Joint Committee on Cancer stage of disease, baseline BMI, nonsteroidal anti‐inflammatory drug use, smoking, time between diagnosis and enrollment, and study site.RESULTSAt the 5‐year postdiagnostic survey, 2049 participants reported higher (53%; median plus 5 kg), unchanged (12%), or lower (35%; median ‐4 kg) weight. Over a median of 5.1 years of subsequent follow‐up (range, 0.3‐9.9 years), 344 participants died (91 of CRC). Long‐term weight loss (per 5 kg) was found to be associated with poorer overall survival (hazard ratio, 1.13; 95% confidence interval, 1.07‐1.21) and CRC‐specific survival (hazard ratio, 1.25; 95% confidence interval, 1.13‐1.39). Significantly lower survival was similarly observed for relative weight loss (>5% vs ≤5% change), BMI reduction (per 1 unit), or BMI category change (overweight to normal vs remaining overweight).CONCLUSIONSWeight loss 5 years after a diagnosis of CRC was found to be significantly associated with decreased long‐term survival, suggesting the importance of avoiding weight loss in survivors of CRC. Future research should attempt to further evaluate this association, accounting for whether this weight change was intentional or represents a marker of declining health. Cancer 2017;123:4701‐4708. © 2017 American Cancer Society.

Background: Veterans with posttraumatic stress disorder (PTSD) who seek mental health care in the Veterans Health Administration frequently discontinue treatment prematurely. Early discontinuation of mental health treatment is more common among Veterans with PTSD who are of minority race or ethnicity. Objectives: To determine whether retention in individual therapy or pharmacotherapy among Veterans with PTSD are associated with patients’ ratings of their mental health providers, and if those associations differ depending on Veteran race or ethnicity. Research Design: Latino, African American, and white Veterans (n=2452) who participated in a prospective national cohort study of Veterans with PTSD at the beginning of an episode of care were surveyed immediately following Veterans’ PTSD diagnoses and 6 months later. Pharmacy and mental health service utilization were abstracted from Veterans Health Administration administrative databases for 6 months postdiagnosis. Retention in treatments were modeled using logistic regression among Veterans who initiated individual therapy or pharmacotherapy. Demographics, treatment need, treatment-related beliefs, treatment process measures, and ratings of mental health providers were considered as predictors. Results: Ratings of mental health providers, more than treatment beliefs, were associated with treatment retention. Among African American Veterans, retention in pharmacotherapy was reduced if the provider was perceived as not having helped manage medication side-effects (odds ratio, 0.36; confidence interval, 0.16–0.80). All Latino Veterans but one (99% or n=64) who rated their therapist as not caring discontinued individual psychotherapy. Conclusions: Ratings of mental health providers were associated with treatment retention. The salience of specific provider behaviors to treatment retention varied by Veteran race or ethnicity.

Objective: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. Study Selection: Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. Data Sources: Fifteen studies described hospital-based cohorts (n = 17,065), whereas one was a large insurance-based database (n = 683,421). Individual-level patient data were incorporated from all selected studies. Data Extraction: Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. Data Synthesis: Use of aspirin was associated with a 7% (95% CI, 2–12%; p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity (I 2 = 61.6%). Conclusions: These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.

ABSTRACT Microbiota-modulating strategies, including probiotic administration, have been tested for the treatment of chronic gastrointestinal diseases despite limited information regarding their mechanisms of action. We previously demonstrated that patients with active celiac disease have decreased duodenal expression of elafin, a human serine protease inhibitor, and supplementation of elafin by a recombinant Lactococcus lactis strain prevents gliadin-induced immunopathology in the NOD/DQ8 mouse model of gluten sensitivity. The commensal probiotic strain Bifidobacterium longum NCC2705 produces a serine protease inhibitor (Srp) that exhibits immune-modulating properties. Here, we demonstrate that B. longum NCC2705, but not a srp knockout mutant, attenuates gliadin-induced immunopathology and impacts intestinal microbial composition in NOD/DQ8 mice. Our results highlight the beneficial effects of a serine protease inhibitor produced by commensal B. longum strains. IMPORTANCE Probiotic therapies have been widely used to treat gastrointestinal disorders with variable success and poor mechanistic insight. Delivery of specific anti-inflammatory molecules has been limited to the use of genetically modified organisms, which has raised some public and regulatory concerns. By examining a specific microbial product naturally expressed by a commensal bacterial strain, we provide insight into a mechanistic basis for the use of B. longum NCC2705 to help treat gluten-related disorders.

Abstract Background: Patients (pts) with CLL/SLL who use unmutated IGHV (u-CLL) have a less favorable outcome with standard chemotherapy than pts who use mutated IGHV (m-CLL). Ibrutinib (ibr) inhibits B-cell receptor signaling through Bruton’s tyrosine kinase and has robust clinical activity against CLL. This integrated analysis of 3 phase 3 studies examined the impact of IGHV status on ibr- and comparator (comp)-treated pts. Methods: Pooled data from 3 studies of ibr (420 mg/d) in CLL/SLL pts (RESONATE: relapsed/refractory [R/R] pts, ibr vs ≤ 24 weeks ofatumumab; RESONATE-2: treatment-naïve [TN] pts ≥ 65 yrs of age [no del17p], ibr vs ≤ 12 cycles chlorambucil; HELIOS: R/R pts [no del17p], ≤ 6 cycles bendamustine-rituximab with ibr vs placebo) were analyzed by IGHV status. Analyses included Kaplan-Meier method (overall survival [OS]; progression-free survival [PFS]); log-rank test (group comparisons); and Cox multivariate analysis (prognostic factors; Table). Results: For 491 ibr- (366 u-CLL, 125 m-CLL) and 494 comp-treated (351 u-CLL, 143 m-CLL) pts with IGHV data, baseline characteristics were similar for u-CLL vs m-CLL, except for the proportions of pts who were TN (17 vs 31%), had bulky disease (60 vs 37%), or had CLL cells with del11q (32 vs 16%). Median follow up was 21.4 mos for ibr and 20.6 mos for comp. PFS and OS were similar for u-CLL and m-CLL ibr-treated pts; u-CLL had poorer outcomes than m-CLL in comp-treated pts, which remained after adjustment for prognostic factors (Table). Ibr treatment was more effective than comp regardless of IGHV status. Incidence of adverse events (AEs) was similar between groups. For ibr vs comp pts (u-CLL/m-CLL): serious AEs: 49% (50%/47%) vs 36.5% (37%/35%); AEs that led to discontinuation: 12% (11%/15%) vs 13% (13%/14%); death within 30 days of last dose: 5% (6%/3%) vs 5% (6%/2%). Conclusions: U-CLL was an adverse predictor of outcome for comp-treated, but not for ibr-treated pts. Table.Efficacy Outcomes in Ibr- and Comparator-Treated Patients by IGHV Mutation StatusIbrutinib (N=491)Comparator (N =494)u-CLL (n=717)m-CLL (n=268)u-CLL(n=366): m-CLL(n=125)u-CLL(n=351): m-CLL(n=143)Ibr(n=366): Comp(n=351)Ibr (n=125): Comp (n=143)PFS24-month rate HR78%:81%10%:32%78%:10%81%:32%0.93a1.99a0.12b0.21bp = 0.78p < 0.0001p < 0.0001p <0.0001Adjusted HRc1.02a1.94a0.11b0.17bp = 0.93p < 0.0001p < 0.0001p < 0.0001OS24-month rate HR88%:89%78%:87%88%:78%89%:87%0.95a1.96a0.49b0.85b,ep = 0.86p = 0.02p < 0.01p = 0.66Adjusted HRc1.21a2.10a0.49bNAp =0.57p = 0.01p < 0.001Response ratesu-CLLm-CLLu-CLLm-CLLIbrCompIbrCompORR, %d8990475189479051p = 0.96p = 0.36p < 0.0001p < 0.0001CR, %d221546224156p = 0.10p = 0.44p < 0.0001p = 0.01CI, confidence interval; CR, complete response; HR, hazard ratio; ORR, overall response rate; NA, not applicable. aHR < 1 favors unmutated. bHR < 1 favors ibrutinib. cMultivariate Cox model adjusted for age, sex, current Rai stage, baseline ECOG performance status score, del11q, del17p, number of prior therapies, and cytopenias. dp value is from a Cochran-Mantel-Haenszel chi-square test. eInsufficient number of events prevents meaningful analysis, only 13 and 16 events observed in ibr and comp groups, respectively, and 46 (32%) pts in comp arm crossed over to ibr arm; interpret results with caution. Citation Format: Thomas J. Kipps, Graeme Fraser, Steven Coutre, Jennifer R. Brown, Jacqueline C. Barrientos, Paul M. Barr, John C. Byrd, Susan M. O'Brien, Marie-Sarah Dilhuydy, Stephen Devereux, Ulrich Jaeger, Carol Moreno, Paula Cramer, Stephan Stilgenbauer, Asher A. Chanan-Khan, Michelle Mahler, Mariya Salman, Mei Cheng, Anil Londhe, Joi Ninomoto, Angela Howes, Danelle James, Michael Hallek. Unmutated IGHV is not an adverse predictor of outcome to therapy with ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT158. doi:10.1158/1538-7445.AM2017-CT158

Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.