Background Evidence regarding all-cause and cause-specific mortality in inflammatory bowel disease (IBD) is conflicting, and debate exists over appropriate study design to examine these important outcomes. We conducted a comprehensive meta-analysis of all-cause and cause-specific mortality in both Crohn’s disease (CD) and ulcerative colitis (UC), and additionally examined various effects of study design on this outcome. Methods A systematic search of PubMed and EMBASE was conducted to identify studies examining mortality rates relative to the general population. Pooled summary standardized mortality ratios (SMR) were calculated using random effect models. Results Overall, 35 original articles fulfilled the inclusion and exclusion criteria, reporting all-cause mortality SMRs varying from 0.44 to 7.14 for UC and 0.71 to 3.20 for CD. The all-cause mortality summary SMR for inception cohort and population cohort UC studies was 1.19 (95% confidence interval, 1.06–1.35). The all-cause mortality summary SMR for inception cohort and population cohort CD studies was 1.38 (95% confidence interval, 1.23–1.55). Mortality from colorectal cancer, pulmonary disease, and nonalcoholic liver disease was increased, whereas mortality from cardiovascular disease was decreased. Conclusions Patients with UC and CD have higher rates of death from all causes, colorectal-cancer, pulmonary disease, and nonalcoholic liver disease.

It is one of the major aims in cancer research to improve our understanding of the underlying mechanisms which initiate and maintain tumor growth and to translate these findings into novel clinical diagnostic and therapeutic concepts with the ultimate goal to improve patient care. One of the greater success stories in this respect has been Waldenström’s Macroglobulinemia (WM), which is an incurable B-cell neoplasm characterized by serum monoclonal immunoglobulin M (IgM) and clonal lymphoplasmacytic cells infiltrating the bone marrow. Recent years have succeeded to describe the molecular landscape of WM in detail, highlighting two recurrently mutated genes, the MYD88 and the CXCR4 genes: MYD88 with an almost constant and recurrent point mutation present in over 90% of patients and CXCR4 with over 40 different mutations in the coding region affecting up to 40% of patients. Intriguingly, both mutations are activating mutations leading in the case of CXCR4 to an indelible activation and perpetual signaling of the chemokine receptor. These data have shed light on the essential role of CXCR4 in this disease and have paved the way to use these findings for predicting treatment response to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and novel therapeutic approaches in WM, which might be transferable to other related CXCR4 positive diseases. Well known for its central role in cancer progression and distribution, CXCR4 is highlighted in this review with regard to its biology, prognostic and predictive relevance and therapeutic implications in WM.

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BACKGROUND AND AIMS: Vaporized nicotine products (VNPs) can vary in important characteristics including size, shape, flavor, and nicotine yield. We examined whether complex interactions among these characteristics could affect smokers' VNP perceptions and usage patterns. DESIGN: A within-subject randomized crossover trial.

Rationale: There is limited understanding regarding how various e-cigarette flavorings may influence the behavior of non-regular e-cigarette users who are regular cigarette smokers.Objectives: To assess differences in nicotine delivery, puffing topography, subjective effects, and user satisfaction from different flavored e-liquids.Methods: Eighteen daily smokers (average age 44.1±7.0; 9 males; average CPD 13.0±5.8) smoked their tobacco cigarettes during an initial visit and returned five times to try an e-cigarette (eGo type) refilled with a nicotine solution (24 mg/ml) of five different flavors: cherry, tobacco, espresso, menthol, and vanilla (randomized order). Assessments at each visit included puffing topography, blood samples for nicotine analysis, and subjective reports of nicotine effects and flavor satisfaction. Results:Vaping different flavors resulted in different levels of plasma nicotine. The flavor producing the highest plasma nicotine concentration (C max ) was cherry (median 21.2 ng/ml), which was not significantly different than nicotine delivery from a combustible cigarette (29.2 ng/ml, p>.05). Vanilla e-liquid produced the lowest C max (9.7 ng/ml), and participants tended to puff less frequently on vanilla compared to tobacco flavor (p=.013). Flavors did not differ significantly in the speed of nicotine delivery (T max ). During controlled use, puff duration for all flavors was significantly longer than a combustible cigarette (p<0.05). After controlling for