Effect of Renal Function Impairment on the Mortality of Cirrhotic Patients With Hepatic Encephalopathy: A Population-Based 3-Year Follow-Up Study

[[abstract]]Kidney is an important organ to clear neurotoxic substance in circulation. However, it is still unknown about the effect of renal function impairment (RFI) on the mortality of cirrhotic patients with hepatic encephalopathy (HE). We used the Taiwan National Health Insurance Database to identify 4932 cirrhotic patients with HE, hospitalized between January 1, 2007 and December 31, 2007. The enrolled patients were followed up individually for 3 years to identify their 3-year mortalities. There were 411 (8.3%) patients with RFI and 4521 (91.7%) patients without RFI. The adjusted hazard ratio (HR) of RFI for 3-year mortality was 2.03 (95% CI, 1.82–2.27). In RFI group, there were 157 (38.2%) patients with acute renal failure (ARF), 61 (14.8%) with hepatorenal syndrome (HRS), 93 (22.6%) with chronic kidney disease (CKD), and 100 (24.3%) with end-stage renal disease (ESRD). Compared with the non-RFI group, the adjusted HR of ARF for 3-year mortality was 2.57 (95% CI, 2.17–3.06), CKD 1.93 (95% CI, 1.55–2.40), ESRD 1.26 (95% CI, 1.01–1.57), and HRS 3.58 (95% CI, 2.78–4.63). Among ESRD patients, there were 99 patients receiving hemodialysis regularly. Compared with the CKD group, the adjusted HR of ESRD with hemodialysis for 3-year mortality was 0.664 (95% CI, 0.466–0.945). RFI increased the 3-year mortality of cirrhotic patients with HE, especially ARF and HRS. HE patients with ESRD receiving hemodialysis had better 3-year survival rate than those with CKD.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]IN

P4T-DOTA - a lanthanide chelating tag combining a sterically highly overcrowded backbone with a reductively stable linker

Herein we report a DOTA-based lanthanide chelating tag (LCT) with rigidified backbone and a reduction-stable linker. The newly developed tag induces strong pseudocontact shifts suitable for paramagnetic protein nuclear magnetic resonance spectroscopy and the obtained anisotropic susceptibility parameters are in the range of the best performing LCTs

EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on Dietary reference values for water

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) deals with the setting of dietary reference values for water for specific age groups. Adequate Intakes (AI) have been defined derived from a combination of observed intakes in population groups with desirable osmolarity values of urine and desirable water volumes per energy unit consumed. The reference values for total water intake include water from drinking water, beverages of all kind, and from food moisture and only apply to conditions of moderate environmental temperature and moderate physical activity levels (PAL 1.6). AIs for infants in the first half of the first year of life are estimated to be 100-190 mL/kg per day. For infants 6-12 months of age a total water intake of 800-1000 mL/day is considered adequate. For the second year of life an adequate total water intake of 1100-1200 mL/day is defined by interpolation, as intake data are not available. AIs of water for children are estimated to be 1300 mL/day for boys and girls 2-3 years of age; 1600 mL/day for boys and girls 4-8 years of age; 2100 mL/day for boys 9-13 years of age; 1900 mL/day for girls 9-13 years of age. Adolescents of 14 years and older are considered as adults with respect to adequate water intake. Available data for adults permit the definition of AIs as 2.0 L/day (P 95 3.1 L) for females and 2.5 L/day (P95 4.0 L) for males. The same AIs as for adults are defined for the elderly. For pregnant women the same water intake as in non-pregnant women plus an increase in proportion to the increase in energy intake (300 mL/day) is proposed. For lactating women adequate water intakes of about 700 mL/day above the AIs of non-lactating women of the same age are derive

Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis

Background Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disaccharides and no differences between lactulose versus lactitol. Objectives To assess the beneficial and harmful effects of i) non-absorbable disaccharides versus placebo/no intervention and ii) lactulose versus lactitol in people with cirrhosis and hepatic encephalopathy. Search methods We carried out electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 10), MEDLINE, EMBASE, and Science Citation Index Expanded to 19 October 2015; manual searches of meetings and conference proceedings; checks of bibliographies; and correspondence with investigators and pharmaceutical companies. Selection criteria We included RCTs, irrespective of publication status, language, or blinding. Data collection and analysis Two review authors, working independently, retrieved data from published reports and correspondence with investigators. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We presented the results of meta-analyses as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the quality of the evidence using 'Grading of Recommendations Assessment Development and Evaluation' (GRADE) and bias control using the Cochrane Hepato-Biliary Group domains. Our analyses included regression analyses of publication bias and other small study effects, Trial Sequential Analyses to detect type 1 and type 2 errors, and subgroup and sensitivity analyses. Main results We included 38 RCTs with a total of 1828 participants. Eight RCTs had a low risk of bias in the assessment of mortality. All trials had a high risk of bias in the assessment of the remaining outcomes. Random-effects meta-analysis showed a beneficial effect of non-absorbable disaccharides versus placebo/no intervention on mortality when including all RCTs with extractable data (RR 0.59, 95% CI 0.40 to 0.87; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence) and in the eight RCTs with a low risk of bias (RR 0.63, 95% CI 0.41 to 0.97; 705 participants). The Trial Sequential Analysis with the relative risk reduction (RRR) reduced to 30% confirmed the findings when including all RCTs, but not when including only RCTs with a low risk of bias or when we reduced the RRR to 22%. Compared with placebo/no intervention, the non-absorbable disaccharides were associated with beneficial effects on hepatic encephalopathy (RR 0.58, 95% CI 0.50 to 0.69; 1415 participants; 22 RCTs; I2 = 32%; moderate quality evidence). Additional analyses showed that non-absorbable disaccharides can help to reduce serious adverse events associated with the underlying liver disease including liver failure, hepatorenal syndrome, and variceal bleeding (RR 0.47, 95% CI 0.36 to 0.60; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence). We confirmed the results in Trial Sequential Analysis. Tests for subgroup differences showed no statistical differences between RCTs evaluating prevention, overt, or minimal hepatic encephalopathy. The evaluation of secondary outcomes showed a potential beneficial effect of the non-absorbable disaccharides on quality of life, but we were not able to include the data in an overall meta-analysis (very low quality evidence). Non-absorbable disaccharides were associated with non-serious (mainly gastrointestinal) adverse events (very low quality evidence). None of the RCTs comparing lactulose versus lactitol evaluated quality of life. The review found no differences between lactulose and lactitol for the remaining outcomes (very low quality evidence). Authors' conclusions This review includes a large number of RCTs evaluating the prevention or treatment of hepatic encephalopathy. The analyses found evidence that non-absorbable disaccharides may be associated with a beneficial effect on clinically relevant outcomes compared with placebo/no intervention. Plain language summary Are non-absorbable disaccharides associated with beneficial or harmful effects in people with cirrhosis and hepatic encephalopathy? Background Cirrhosis is a chronic disorder of the liver. People with cirrhosis may develop hepatic encephalopathy, a condition that results in poor brain functioning. Hepatic encephalopathy may be clinically obvious (overt) with changes including poor concentration, tremor, and alterations in consciousness. Others have no obvious clinical changes (minimal) but, when tested, some aspects of brain function such as attention and the ability to perform complex tasks are impaired. The reason why people develop hepatic encephalopathy is complex. The accumulation of ammonia plays a key role. The non-absorbable disaccharides, lactulose and lactitol, are indigestible sugars that reduce the levels of ammonia in the blood. Review question We investigated the use of non-absorbable disaccharides for the prevention and treatment of hepatic encephalopathy in people with cirrhosis by reviewing randomised clinical trials (RCTs). Search date The search date was October 2015. Study funding sources Seven RCTs received financial support and 11 RCTs received lactitol or inactive placebo free of charge from a pharmaceutical company. Study characteristics We included 29 RCTs comparing non-absorbable disaccharides with inactive placebo or no intervention and nine RCTs comparing lactulose with lactitol. Seven of the included RCTs evaluated the prevention of hepatic encephalopathy and 31 evaluated the treatment of hepatic encephalopathy. Sixteen of the treatment RCTs included people with overt hepatic encephalopathy while 15 included people with minimal hepatic encephalopathy. The duration of treatment varied depending on the type of hepatic encephalopathy from five days to one year. Key results People who received non-absorbable disaccharides were less likely to die than people given a placebo or no treatment. They were also less likely to develop serious complications of their liver disease such as liver failure, bleeding, and infections. The non-absorbable disaccharides were also effective in preventing the development of hepatic encephalopathy and increased the number of participants who recovered from hepatic encephalopathy. There was some evidence from a small number of trials that lactulose has a beneficial effect on the quality of life, but we were unable to include the data in an overall analysis. The non-absorbable disaccharides were associated with adverse events including diarrhoea, nausea, bloating, and flatulence. None of the RCTs comparing lactulose versus lactitol reported quality of life. The analyses showed no differences between the two interventions for the remaining outcomes. Quality of the evidence In the comparison of non-absorbable disaccharides versus placebo/no intervention, we found moderate quality evidence of benefit for the outcomes of death, hepatic encephalopathy, and serious complications. The evidence for the remaining outcomes was of very low quality

Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT)

PurposeWe have previously shown that 6 weeks of reduced-exertion high-intensity interval training (REHIT) improves V˙O2V˙O2 max in sedentary men and women and insulin sensitivity in men. Here, we present two studies examining the acute physiological and molecular responses to REHIT.MethodsIn Study 1, five men and six women (age: 26 ± 7 year, BMI: 23 ± 3 kg m−2, V˙O2V˙O2 max: 51 ± 11 ml kg−1 min−1) performed a single 10-min REHIT cycling session (60 W and two 20-s ‘all-out’ sprints), with vastus lateralis biopsies taken before and 0, 30, and 180 min post-exercise for analysis of glycogen content, phosphorylation of AMPK, p38 MAPK and ACC, and gene expression of PGC1α and GLUT4. In Study 2, eight men (21 ± 2 year; 25 ± 4 kg·m−2; 39 ± 10 ml kg−1 min−1) performed three trials (REHIT, 30-min cycling at 50 % of V˙O2V˙O2 max, and a resting control condition) in a randomised cross-over design. Expired air, venous blood samples, and subjective measures of appetite and fatigue were collected before and 0, 15, 30, and 90 min post-exercise.ResultsAcutely, REHIT was associated with a decrease in muscle glycogen, increased ACC phosphorylation, and activation of PGC1α. When compared to aerobic exercise, changes in V˙O2V˙O2 , RER, plasma volume, and plasma lactate and ghrelin were significantly more pronounced with REHIT, whereas plasma glucose, NEFAs, PYY, and measures of appetite were unaffected.ConclusionsCollectively, these data demonstrate that REHIT is associated with a pronounced disturbance of physiological homeostasis and associated activation of signalling pathways, which together may help explain previously observed adaptations once considered exclusive to aerobic exercise

Tick species from cattle in the Adama Region of Ethiopia and pathogens detected

Ticks will diminish productivity among farm animals and transmit zoonotic diseases. We conducted a study to identify tick species infesting slaughter bulls from Adama City and to screen them for tick-borne pathogens. In 2016, 291 ticks were collected from 37 bulls in Adama, which were ready for slaughter. Ticks were identified morphologically. Total genomic DNA was extracted from ticks and used to test for Rickettsia spp. with real-time PCR. Species identification was done by phylogenetic analysis using sequencing that targeted the 23S-5S intergenic spacer region and ompA genes. Four tick species from two genera, Amblyomma and Rhipicephalus, were identified. Amblyomma cohaerens was the dominant species (n = 241, 82.8%), followed by Amblyomma variegatum (n = 22, 7.5%), Rhipicephalus pulchellus (n = 19, 6.5%), and Rhipicephalus decoloratus (n = 9, 3.0%). Among all ticks, 32 (11%) were positive for Rickettsia spp. and 15 (5.2%) of these were identified as R. africae comprising at least two genetic clades, occurring in A. variegatum (n = 10) and A. cohaerens (n = 5). The remainder of Rickettsia-positive samples could not be amplified due to low DNA yield. Furthermore, another 15 (5.2%) samples carried other pathogenic bacteria: Ehrlichia ruminantium (n = 9; 3.1%) in A. cohaerens, Ehrlichia sp. (n = 3; 1%) in Rh. pulchellus and A. cohaerens, Anaplasma sp. (n = 1; 0.5%) in A. cohaerens, and Neoehrlichia mikurensis (n = 2; 0.7%) in A. cohaerens. All ticks were negative for Bartonella spp., Babesia spp., Theileria spp., and Hepatozoon spp. We reported for the first time E. ruminatium, N. mikurensis, Ehrlichia sp., and Anaplasma sp. in A. cohaerens. Medically and veterinarily important pathogens were mostly detected from A. variegatum and A. cohaerens. These data are relevant for a One-health approach for monitoring and prevention of tick-borne disease transmission

In-vivo kinetics of inhaled 5-Aminolevulinic acid-Induced Protoporphyrin IX fluorescence in bronchial tissue

BACKGROUND: In the diagnosis of early-stage lung cancer photosensitizer-enhanced fluorescence bronchoscopy with inhaled 5-aminolevolinic acid (5-ALA) increases sensitivity when compared to white-light bronchoscopy. This investigation was to evaluate the in vivo tissue pharmacokinetics of inhaled 5-ALA within the bronchial mucosa in order to define the time optimum for its application prior to bronchoscopy. METHODS: Patients with known or suspected bronchial carcinoma were randomized to receive 200 mg 5-ALA via inhalation 1, 2, 3, 4 or 6 hours before flexible fluorescence bronchoscopy was performed. Macroscopically suspicious areas as well as areas with visually detected porphyrin fluorescence and normal control sites were measured spectroscopically. Biopsies for histopathology were obtained from suspicious areas as well as from adjacent normal areas. RESULTS: Fluorescence bronchoscopy performed in 19 patients reveals a sensitivity for malignant and premalignant changes (moderate dysplasia) which is almost twice as high as that of white-light bronchoscopy, whereas specificity is reduced. This is due to false-positive inflammatory lesions which also frequently show increased porphyrin fluorescence. Malignant and premalignant alterations produced fluorescence values that are up to 5 times higher than those of normal tissue. According to the pharmacokinetics of porphyrin fluorescence measured by spectroscopy, the optimum time range for 5-ALA application is 80–270 min prior to fluorescence bronchoscopy, with an optimum at 160 min. CONCLUSION: According to our results we propose inhalation of 5-ALA 160 min prior to fluorescence bronchoscopy, suggesting that this time difference provides the best tumor/normal tissue fluorescence ratio

Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection

BACKGROUND: Type I interferon (IFN-I) predisposes to bacterial superinfections, an important problem during viral infection or treatment with interferon-alpha (IFN-alpha). IFN-I-induced neutropenia is one reason for the impaired bacterial control; however there is evidence that more frequent bacterial infections during IFN-alpha-treatment occur independently of neutropenia. METHODS: We analyzed in a mouse model, whether Pseudomonas aeruginosa control is influenced by co-infection with the lymphocytic choriomeningitis virus (LCMV). Bacterial titers, numbers of neutrophils and the gene-expression of liver-lysozyme-2 were determined during a 24 hours systemic infection with P. aeruginosa in wild-type and Ifnar(-/-) mice under the influence of LCMV or poly(I:C). RESULTS: Virus-induced IFN-I impaired the control of Pseudomonas aeruginosa. This was associated with neutropenia and loss of lysozyme-2-expression in the liver, which had captured P. aeruginosa. A lower release of IFN-I by poly(I:C)-injection also impaired the bacterial control in the liver and reduced the expression of liver-lysozyme-2. Low concentration of IFN-I after infection with a virulent strain of P. aeruginosa alone impaired the bacterial control and reduced lysozyme-2-expression in the liver as well. CONCLUSION: We found that during systemic infection with P. aeruginosa Kupffer cells quickly controlled the bacteria in cooperation with neutrophils. Upon LCMV-infection this cooperation was disturbed

Near fatal posterior reversible encephalopathy syndrome complicating chronic liver failure and treated by induced hypothermia and dialysis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Posterior reversible encephalopathy syndrome is a clinico-neuroradiological entity characterized by headache, vomiting, altered mental status, blurred vision and seizures with neuroimaging studies demonstrating white-gray matter edema involving predominantly the posterior region of the brain.</p> <p>Case presentation</p> <p>We report a 47-year-old Caucasian man with liver cirrhosis who developed posterior reversible encephalopathy syndrome following an upper gastrointestinal hemorrhage and who was managed with induced hypothermia for control of intracranial hypertension and continuous veno-venous hemodiafiltration for severe hyperammonemia.</p> <p>Conclusion</p> <p>We believe this is the first documented case report of posterior reversible encephalopathy syndrome associated with cirrhosis as well as the first report of the use of induced hypothermia and continuous veno-venous hemodiafiltration in this setting.</p