Citations

Sepsis in patients with cirrhosis is associated with high mortality. An impaired immune response accounts for the increased infection risk observed in these patients. Hemodynamic and systemic changes suggestive of sepsis may be observed in patients with cirrhosis in the absence of infection; therefore, diagnosis and treatment of sepsis may be delayed. The optimal management of the critically ill patient with sepsis and cirrhosis has not been well established and is generally extrapolated from consensus guidelines and expert recommendations made for management of patients without cirrhosis with sepsis. Despite the lack of strong evidence, we propose a contemporary pragmatic approach to sepsis management in patients with cirrhosis, including the choice of fluids, vasopressors, and antibiotics.

As a follow‐up to genome‐wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well‐known ovarian cancer risk factors and their interactions with 28 genome‐wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case–control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10−4). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46–0.60) compared to 0.71 (95%CI = 0.66–0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1–5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene–environment analysis in ovarian cancer.

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.

AbstractBackgroundThe study aims were to model acute pain intensity and opioid consumption trajectories up to 72 hr after open hepatic resection, identify predictors of trajectory membership and examine the association between trajectory memberships and 6‐month pain and psychological outcomes. This is a long‐term analysis of a published randomized controlled trial on the impact of medial open transversus abdominis plane catheters on post‐operative outcomes.MethodsA total of 152 patients (89 males; mean age 63.0 [range: 54–72]) completed questionnaires on pain and related characteristics pre‐operatively and 6 months post‐operatively. Total opioid use was recorded several times over a 72‐hr period while self‐reported pain intensity scores were collected multiple times until hospital discharge. Analyses were carried out using growth mixture modelling, logistic regression and general linear models.ResultsBoth pain intensity and opioid consumption showed that a four‐trajectory model best fits the data. Patients in the lowest opioid consumption trajectory were more likely to be classified in the constant mild pain intensity trajectory. Age and baseline levels of anxiety significantly predicted opioid trajectory membership while baseline depressive symptoms significantly predicted pain intensity trajectory membership. Patients in the two highest opioid consumption trajectories reported significantly higher levels of pain catastrophizing at 6 months compared to patients in the other 3 trajectories (all p < 0.05).ConclusionHigh consumption of opioids after surgery is associated with higher levels of pain catastrophizing 6 months later. Identification of patients within these trajectories may lead to the development of early interventions targeted to high risk individuals.SignificanceDifferences in initial levels of opioid consumption and rates of change in opioid consumption shortly after surgery can help predict long‐term psychological responses to pain. Identifying key characteristics associated with initial opioid consumption can lead to the development of cost‐effective early interventions targeted to high risk individuals.

Abstract Background Mild asymptomatic left ventricular systolic dysfunction (ALVSD) may be associated with incident heart failure (HF). However, this gray zone group needs incremental risk refinement. We hypothesized that diastolic dysfunction (DD) may refine HF and death risk prediction in mild ALVSD. Methods and results Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, N-terminal pro B-type natriuretic peptide, and echocardiogram. Based on left ventricular ejection fraction (LVEF) and DD, subjects were classified as: control group (normal LVEF, n = 459, 76%), mild ALVSD (LVEF ≥40%/&lt;53%) without DD (n = 89, 15%) and with DD (n = 54, 9%). Subjects with LVEF &lt;40% or without full echocardiographic data were excluded from the analysis (n = 21). Mean age of the population was 69 ±7 years, 56% were men, mostly hypertensive, mean LVEF was 61%. During a median follow-up of 5.7 years, 88 subjects (15%) experienced HF/death events (59 HF events and 29 deaths). Compared to the control group, mild ALVSD was associated with a higher risk of incident HF/death (hazard ratio 1.80, 95% confidence interval 1.10–2.93, adjusted P = 0.019) according to the Cox proportional hazards model. However, this higher risk was present only in subjects with combined DD (P = 0.005) and not in those without it (P = 0.30). Results were consistent even considering the individual components of the primary outcome. Conclusion In a high-risk population, an echocardiographic exam is normally performed to assess systolic dysfunction. Our data underline the importance of also relying on DD to risk stratify mild ALVSD. Mild ALVSD might be a predictor of adverse events mainly in subjects with combined DD, though further studies are needed to confirm these results.

AbstractObjectiveWhile prior Epstein–Barr virus (EBV) infection has been consistently associated with subsequent risk of developing multiple sclerosis (MS), the association with other common herpesviruses has been more controversial. Our objectives were to determine whether remote infection with EBV and other common herpesviruses affect the susceptibility to pediatric MS and if there are interactions between genetic and demographic factors and viral infections.MethodsCases with pediatric‐onset MS or clinically isolated syndrome within 4 years of disease onset, and controls were recruited from 16 American pediatric MS centers. Logistic regression models adjusted for potential confounders assessed the association between case status and serological evidence for past infection with EBV, cytomegalovirus (CMV), Herpes Simplex viruses‐1 (HSV‐1) and ‐2. We determined the heterogeneity of the effect of viral infection on the risk of having MS according to race, ethnicity and HLA‐DRB1:1501 status.ResultsA total of 356 pediatric cases and 493 controls were recruited. In multivariable models, EBV‐viral capsid antigen (VCA) seropositivity was associated with increased odds of having MS by 7.4 times (95% CI: 4.5–12.0, P < 0.001). Seropositivity for HSV‐1 was also associated with increased odds of having MS (OR 1.54, 95% CI: 1.06–2.25, P = 0.025) but this increase was seen only in Whites (OR = 2.18, 95% CI 1.35–3.52, P < 0.001) and those negative for HLA‐DRB1*1501 (OR = 1.89, 95% CI 1.17–3.03, P = 0.009). The effect of remote EBV infection on the risk of pediatric MS depended on race and HLA‐DRB1*15:01 status.InterpretationEBV seropositivity is strongly associated with pediatric MS, as is HSV‐1 seropositivity in subjects negative for HLA‐DRB1*15:01. Our report of interactions between select viral exposures, and age, race and DRB1 status suggests a complex effect of environmental and genetic risk factors on MS development.