The Effect of Infections on the Mortality of Cirrhotic Patients with Hepatic Encephalopathy

[[abstract]]Cirrhotic patients are prone to having infections, which may aggravate hepatic encephalopathy (HE). However, the effect of infections on mortality in HE cirrhotic patients is not well described. The National Health Insurance Database, derived from the Taiwan National Health Insurance Programme, was used to identify 4150 adult HE cirrhotic patients hospitalized between 1 January 2004 and 31 December 2004. Nine hundred and eighty-five patients (23.7%) had one or more co-existing infections during their hospitalization. After Cox proportional hazard regression modelling adjusted by the patients' gender, age, and medical comorbidity disorders, the hazard ratios (HRs) in HE patients with infections for 30-day, 30- to 90-day, and 90-day to 1-year mortalities were 1.66 [95% confidence interval (CI) 1.42-1.94], 1.51 (95% CI 1.23-1.85) and 1.34 (95% CI 1.13-1.58), respectively. Compared to the non-infection group, the HRs of pneumonia, spontaneous bacterial peritonitis, urinary tract infection, sepsis without specific focus (SWSF), cellulitis, and biliary tract infection were 2.11, 1.48, 1.06, 2.21, 1.06, and 0.78, respectively, for 30-day mortality; 1.82, 1.22, 0.93, 2.24, 0.31, and 2.82, respectively, for 30- to 90-day mortality; and 2.03, 0.82, 1.24, 1.64, 1.14, and 0.60, respectively, for 90-day to 1-year mortality for HE cirrhotic patients. We conclude that infections increase the mortality of HE cirrhotic patients, especially pneumonia and SWSF.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

Outcomes in culture positive and culture negative ascitic fluid infection in patients with viral cirrhosis: cohort study

<p>Abstract</p> <p>Background</p> <p>Ascitic fluid infection (AFI) in cirrhotic patients has a high morbidity and mortality. It has two variants namely, spontaneous bacterial peritonitis (SBP) and culture negative neutrocytic ascites (CNNA). The aim of this study was to determine the outcome in cirrhotic patients with culture positive (SBP) and culture negative neutrocytic ascites.</p> <p>Methods</p> <p>We analyzed 675 consecutive hepatitis B and/or C related cirrhosis patients with ascites admitted in our hospital from November 2005 to December 2007. Of these, 187 patients had AFI; clinical and laboratory parameters of these patients including causes of cirrhosis, Child Turcotte Pugh (CTP) score were recorded.</p> <p>Results</p> <p>Out of 187 patients with AFI, 44 (23.5%) had SBP while 143 (76.4%) had CNNA. Hepatitis C virus (HCV) infection was the most common cause of cirrhosis in 139 (74.3%) patients. Patients with SBP had high CTP score as compared to CNNA (12.52 ± 1.45 vs. 11.44 ± 1.66); p < 0.001. Platelets count was low in patients with SBP (101 ± 53 × 10⁹/L) as compared to CNNA (132 ± 91 × 10⁹/L), p = 0.005. We found a high creatinine (mg/dl) (1.95 ± 1.0 vs. 1.44 ± 0.85), (p = 0.003) and high prothrombin time (PT) in seconds (24.8 ± 6.6 vs. 22.4 ± 7.2) (p = 0.04) in SBP as compared to CNNA. More patients with SBP (14/44; 31.8%) had blood culture positivity as compare to CNNA (14/143; 9.8%), p = 0.002. Escherichia. Coli was the commonest organism in blood culture in 15/28 (53.5%) patients. SBP group had a higher mortality (11/44; 25%) as compared to CNNA (12/143; 8.4%), p = 0.003. On multiple logistic regression analysis, creatinine >1.1 mg/dl and positive blood culture were the independent predictors of mortality in patients with SBP.</p> <p>Conclusion</p> <p>Patients with SBP have a higher mortality than CNNA. Independent predictors of mortality in SBP are raised serum creatinine and a positive blood culture.</p

Bespoken Nanoceria : An Effective Treatment in Experimental Hepatocellular Carcinoma

Despite the availability of new-generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer-related deaths worldwide. Cerium oxide nanoparticles (CeONPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti-inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeONPs as therapeutic agents in HCC. HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeONPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeONPs on tumor progression and animal survival was investigated. Hepatic tissue MS-based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeONPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeONPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeONPs decreased phosphatidylcholine-derived arachidonic acid and reverted the HCC-induced increase of linoleic acid in several lipid components. Furthermore, CeONPs reduced serum alpha-protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated. These data indicate that CeONPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC

A colanic acid operon deletion mutation enhances induction of early antibody responses by live attenuated salmonella vaccine strains

Colanic acid (CA) is a common exopolysaccharide produced by many genera in the Enterobacteriaceae. It is critical for biofilm formation on HEp-2 cells and on chicken intestinal tissue by Salmonella. In this study, we generated different CA synthesis gene mutants and evaluated the immune responses induced by these mutants. One of these mutations, Δ(wza-wcaM)8, which deleted the whole operon for CA synthesis, was introduced into two Salmonella vaccine strains attenuated by auxotrophic traits or by the regulated delayed attenuation strategy (RDAS). The mice immunized with the auxotrophic Salmonella vaccine strain with the deletion mutation Δ(wza-wcaM)8 developed higher vaginal IgA titers against the heterologous protective antigen and higher levels of antigen-specific IgA secretion cells in lungs. In Salmonella vaccine strains with RDAS, the strain with the Δ(wza-wcaM)8 mutation resulted in higher levels of protective antigen production during in vitro growth. Mice immunized with this strain developed higher serum IgG and mucosal IgA antibody responses at 2 weeks. This strain also resulted in better gamma interferon (IFN-γ) responses than the strain without this deletion at doses of 10(8) and 10(9) CFU. Thus, the mutation Δ(wza-wcaM)8 will be included in various recombinant attenuated Salmonella vaccine (RASV) strains with RDAS derived from Salmonella enterica serovar Paratyphi A and Salmonella enterica serovar Typhi to induce protective immunity against bacterial pathogens

eCLIPs bifurcation remodeling system for treatment of wide neck bifurcation aneurysms with extremely low dome-to-neck and aspect ratios: a multicenter experience

In our case series, 24 patients treated at 12 international centers were taken from a larger prospective voluntary post-marketing registry of 65 patients treated with the eCLIPs device and coiling. Those who had WNBAs at either the carotid or basilar terminus with a DTN ratio Wide necked bifurcation aneurysms (WNBA) are among the most difficult aneurysms to treat. Very low dome-to-neck (DTN) and aspect ratios provide an even greater challenge in the management of WNBAs. We present the safety and efficacy profile for endovascular clip system (eCLIPs) device in the treatment of this subset of WNBAs with very unfavorable morphologies.Our series of patients with aneurysms having adverse DTN and aspect ratios demonstrated that the eCLIPs device has a safety and efficacy profile comparable with currently available devices in the treatment of WNBAs.The eCLIPs device was successfully deployed in 23 cases (96%). One patient (4.2%) died due to guidewire perforation distal to the implant site. No other complications were documented. After a mean follow-up of 15.8 months (range 3-40 months), good radiologic outcomes (modified Raymond-Roy classification (MRRC) scores of 1 or 2) were documented in 20 of 21 patients (95%) with follow-up data. The lone patient with an MRRC score of 3 showed coiled compaction after incomplete neck coverage with the device.</div

The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury

Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood. Therefore, we lack efficient therapeutic strategies to treat this pathology. Here we show that APAP interferes with the formation of mitochondrial respiratory supercomplexes via the mitochondrial negative regulator MCJ, and leads to decreased production of ATP and increased generation of ROS. In vivo treatment with an inhibitor of MCJ expression protects liver from acetaminophen-induced liver injury at a time when N-acetylcysteine, the standard therapy, has no efficacy. We also show elevated levels of MCJ in the liver of patients with acetaminophen overdose. We suggest that MCJ may represent a therapeutic target to prevent and rescue liver injury caused by acetaminophen

Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study

AbstractThere are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2–63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made