Holm Beatty (bloodyarn75)

22 vs. 0.65, P less then 0.0001). Moreover, serum from patients with cirrhosis decreases the ability of healthy control neutrophils to kill C. albicans (from 60% to 41%, P less then 0.003). Circulating concentration of the inflammatory cytokines tumor necrosis factor α, interleukin-6, and interleukin-8 were found to be significantly elevated in patients with cirrhosis compared to healthy controls. Following pretreatment with granulocyte-colony stimulating factor and granulocyte-macrophage colony-stimulating factor, neutrophil function was restored to almost that of healthy controls. Conclusion Our data establish profound neutrophil dysfunction against, and altered swarming to, C. albicans in patients with cirrhosis. This dysfunction can be partially reversed with cytokine augmentation ex vivo.Disturbed sleep is common among patients with cirrhosis. The extent to which this is associated with the different stages of compensated cirrhosis is unknown. This study examines whether the presence of portosystemic collaterals, an indicator of clinically significant portal hypertension, is associated with sleep disturbance in compensated cirrhosis. We conducted a cross-sectional study among patients with compensated cirrhosis, comparing sleep characteristics, sleep quality, and excessive daytime sleepiness between 21 patients without and 21 patients with portosystemic collaterals. Patients were assessed with wrist actigraphy, Pittsburgh Sleep Quality Index, and the Epworth Sleepiness Scale. Collateral presence was determined by imaging and esophagogastroduodenoscopy. Differences in sleep characteristics were analyzed using t tests and computed effect sizes. Multivariable linear regression analysis was used to evaluate the association between collaterals and sleep disturbance while controlling for possible confounders. The group of patients with collaterals had greater beta-blocker and tobacco use, lower albumin, and higher international normalized ratio compared to the group without collaterals. Patients with collaterals had more sleep fragmentation (Cohen's d = -0.86), lower sleep efficiency (Cohen's d = 0.59), and lower total sleep time (Cohen's d = 0.75) than patients without collaterals. The presence of collaterals was independently associated with greater sleep fragmentation (P = 0.046) and greater daytime sleepiness (P = 0.030). Conclusion Patients with compensated cirrhosis complicated by portosystemic collaterals experienced more sleep disturbance than those without collaterals.Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease with no approved treatments. C-C chemokine receptor types 2 and 5 (CCR2/CCR5) play an important role in inflammation and fibrosis and are potential therapeutic targets for PSC. We evaluated the efficacy and safety of cenicriviroc (CVC), a dual antagonist of CCR2 and CCR5, for the treatment of PSC. This was a single-arm, open-label, exploratory study of CVC in adults with a clinical diagnosis of PSC, serum alkaline phosphatase (ALP) ≥1.5 times the upper limit of normal (ULN), with or without inflammatory bowel disease, across eight sites in the United States and Canada. The primary endpoint was percent change in ALP over 24 weeks; key secondary efficacy endpoints were proportion of participants who achieved ALP normalization and overall response (decrease to less then 1.5 times the ULN or 50% decrease). Of the 24 participants, 20 completed the study. The mean age was 43 years, 50% were female, and the mean body mass index was 25 kg/m2. From a median ALP baseline of 369 U/L (range 173, 1,377 U/L), a median absolute reduction of 49.5 U/L (range -460, 416 U/L) was achieved at week 24, corresponding to a median reduction of 18.0% (range -46%, 89%). No participant achieved ALP normalization or a 50% decrease; 2 participants (10%) achieved a reduction in ALP to less then 1.5 times the ULN, and 4 had ≥25% increase. Twenty participants (83.3%) reported at least one adverse event; most were mil