Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

Effectiveness and economic evaluation of rhTPO and rhIL-11 in the treatment of cancer therapy induced thrombocytopenia based on real-world research.

Objective: Based on real-world research, we aimed to evaluate the effectiveness and economy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin 11 (rhIL-11) in the treatment of cancer therapy induced thrombocytopenia (CTIT). Methods: We retrospectively collected clinical data of patients with CTIT who were treated with rhTPO or rhIL-11 in a single cancer hospital from January 2020 to December 2021. Propensity score matching (PSM) was applied to eliminate confounding factors. The measurements of effectiveness analysis were the platelet compliance rate, days of medication, days of compliance, highest platelet count after medication, platelet count elevation before and after medication, and the lowest platelet count after next-cycle cancer therapy. The economic evaluation was performed according to the results of the effectiveness evaluation. At the same time, patients were stratified according to type of tumor and grade of thrombocytopenia for subgroup analysis. Results: A total of 262 patients were collected and 174 patients were enrolled after PSM, 87 in the rhTPO group and 87 in the rhIL-11 group. In all patients, there were no significant differences in the platelet compliance rate, mean days of medication, median days of compliance, median highest platelet count after medication, and the median platelet count elevation before and after medication between the two groups (p > 0.05), but the median lowest platelet count after next-cycle cancer therapy in the rhTPO group was lower than that in the rhIL-11 group (p = 0.014). The subgroup analysis showed that the rhTPO group had longer mean days of medication than the rhIL-11 group in patients with hematological malignancies (p = 0.042), and a lower median lowest platelet count after next-cycle cancer therapy in patients with grade I/II thrombocytopenia than rhIL-11 group (p = 0.022), with no significant difference in other outcome indicators (p > 0.05). As there was no statistically significant difference in platelet compliance rate between the two groups, the cost-minimization analysis showed that the rhIL-11 group had lower treatment costs than the rhTPO group. Conclusion: RhTPO and rhIL-11 showed similar effectiveness in the treatment of CTIT, but rhIL-11 was more advantageous in economic cost.

Polymyxin B-Associated Nephrotoxicity and Its Predictors: A Retrospective Study in Carbapenem-Resistant Gram-Negative Bacterial Infections.

Polymyxin B (PMB), a kind of polymyxin, was widely used in carbapenem-resistant Gram-negative bacterial (CR-GNB) infections. However, adverse reactions such as nephrotoxicity and neurotoxicity limit its use in clinical practice. The aim of this study was to explore PMB associated with nephrotoxicity and its predictors. Patients who received PMB intravenous drip for more than 72 h were eligible for the study. Characteristics of patients, concomitant nephrotoxic agents, underlying disease, and antimicrobial susceptibility were submitted for descriptive analysis. Univariate analysis and binary logistic regression were used to assess the factors leading to acute kidney injury (AKI). AKI was assessed with serum creatinine variations according to the classification of risk (stage R), injury (stage I), failure (stage F), loss, and end-stage of kidney disease. Among 234 patients with CR-GNB infections who used PMB in our study, 67 (28.63%) patients developed AKI, including 31 (14.25%) patients in stage R, 15 (6.41%) patients in stage I, and 21 (8.97%) patients in stage F. The incident rate of PMB-related nephrotoxicity in patients with normal renal function was 32.82% (43/131). The higher risk factors of AKI include males [odds ratio (OR) = 3.237; 95% confidence interval (95%CI) = 1.426-7.350], digestive system diseases [OR = 2.481 (1.127-5.463)], using furosemide (>20 mg/day) [OR = 2.473 (1.102-5.551)], and baseline serum creatinine [OR = 0.994 (0.990-0.999)]. Nonparametric tests of K-independent samples showed that baseline serum creatinine and the PMB maintenance dose were associated with the severity of nephrotoxicity (both p < 0.05). Male, digestive system diseases, using furosemide (>20 mg/day), and high baseline serum creatinine were the independent risk factors of PMB-associated AKI development. The maintenance dose of PMB may be related to the severity of AKI. These risk factors should be taken into consideration when initiating PMB-based therapy. The serum creatinine value should be closely monitored when using PMB.

Polymyxin B-Based Regimens for Patients Infected with Carbapenem-Resistant Gram-Negative Bacteria: Clinical and Microbiological Efficacy, Mortality, and Safety.

Background: The increasing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) represents a global healthcare crisis. This study explored the efficacy and safety of Polymyxin B (PMB)-based regimens and factors influencing their effectiveness. Methods: Patients with CR-GNB infections treated with PMB for more than three days were enrolled in this retrospective study from 1st June 2018 to 30th April 2020. Data were collected on patient characteristics, bacterial culture, and drug-sensitivity test results; anti-infection treatment regimens, particularly details of PMB use; and adverse drug reactions. Clinical and microbiological efficacy, mortality, and safety of PMB-based regimens in CR-GNB infected patients were evaluated. Univariate analysis and multivariate logistic regression analyses were used to assess factors influencing efficacy and mortality. Results: A total of 373 CR-GNB strains were cultured from 268 patients. About 41.04% of patients used PMB loading dose of 1.01 (0.84-1.69) mg/kg. Maintenance dose was 0.85 (0.82-1.00) mg/kg q12h. The clinical efficacy rate was 36.57% (98/268), the total bacterial clearance rate of PMB was 39.42%, and the all-cause mortality rate was 33.96%. The adverse drug reaction rate was 19.58%, among which the incidence of renal toxicity was highest (8.21%). Multivariate logistic regression analysis showed that clinical efficacy, bacterial clearance rate, and all-cause mortality were associated with patient-related facts, including mechanical ventilation use, underlying diseases (such as respiratory disease), the type and site of CR-GNB infection, and PMB administration timing and loading dose. Conclusion: PMB is a relatively safe and effective antibiotic drug for treatment of critically ill patients with CR-GNB infection; however, PMB use should be subject to guidelines recommendations for early administration, loading administration, and adequate administration, which could help to improve the clinical efficacy, microbiological efficacy, and mortality.

Super-enhancers: a new frontier for epigenetic modifiers in cancer chemoresistance.

Although new developments of surgery, chemotherapy, radiotherapy, and immunotherapy treatments for cancer have improved patient survival, the emergence of chemoresistance in cancer has significant impacts on treatment effects. The development of chemoresistance involves several polygenic, progressive mechanisms at the molecular and cellular levels, as well as both genetic and epigenetic heterogeneities. Chemotherapeutics induce epigenetic reprogramming in cancer cells, converting a transient transcriptional state into a stably resistant one. Super-enhancers (SEs) are central to the maintenance of identity of cancer cells and promote SE-driven-oncogenic transcriptions to which cancer cells become highly addicted. This dependence on SE-driven transcription to maintain chemoresistance offers an Achilles' heel for chemoresistance. Indeed, the inhibition of SE components dampens oncogenic transcription and inhibits tumor growth to ultimately achieve combined sensitization and reverse the effects of drug resistance. No reviews have been published on SE-related mechanisms in the cancer chemoresistance. In this review, we investigated the structure, function, and regulation of chemoresistance-related SEs and their contributions to the chemotherapy via regulation of the formation of cancer stem cells, cellular plasticity, the microenvironment, genes associated with chemoresistance, noncoding RNAs, and tumor immunity. The discovery of these mechanisms may aid in the development of new drugs to improve the sensitivity and specificity of cancer cells to chemotherapy drugs.

Clinical Analysis of Metagenomic Next-Generation Sequencing Confirmed Chlamydia psittaci Pneumonia: A Case Series and Literature Review.

INTRODUCTION: Chlamydia psittaci infection is a zoonotic infectious disease, which mainly inhaled through the lungs when exposed to the secretions of poultry that carry pathogenic bacteria. The traditional respiratory specimens or serological antibody testing is slow, and the false-negative rate is high. Metagenomic next-generation sequencing (mNGS) gives a promising rapid diagnosis tool. METHODS: We retrospectively summarized the clinical characteristics of five C. psittaci pneumonia patients diagnosed by mNGS, conducted a literature review summarizing the clinical characteristics of patients with C. psittaci pneumonia reported since 2010. RESULTS: Five C. psittaci pneumonia patients confirmed by mNGS aged from 36 to 66 years with three males. About 60% of patients had a history of contact with avian or poultry. All patients had a high fever over 38.5 °C, cough, hypodynamia, hypoxemia, and dyspnea on admission. Two patients had invasive ventilator support and extracorporeal membrane oxygenation support. Inflammatory index levels on admission and follow-up were all higher than normal values. Doxycycline or moxifloxacin and their combination therapy were used in patients. Four patients improved and were discharged, and one patient died due to multiple organ failures and disseminated intravascular coagulation. We summarized 19 articles including 69 C. psittaci pneumonia patients and patients in 11 publications were identified by mNGS, and most patients are treated with tetracycline and quinolone with good outcomes. CONCLUSION: mNGS is a promising rapid diagnosis tool, which may increase the detection rate and shorten the diagnosis time of C. psittaci pneumonia. Further case-control studies are needed to confirm.

A Comparative Study of the Microbiological Efficacy of Polymyxin B on Different Carbapenem-Resistant Gram-Negative Bacteria Infections.

Objective: The emergence of carbapenem-resistant gram-negative bacteria (CR-GNB) has brought great challenges to clinical anti-infection treatment around the world. Polymyxins are often considered as the last line of defense in the treatment of CR-GNB infections. In this study, we explored the microbiological efficacy of Polymyxin B (PMB) on different CR-GNB infections as well as the factors influencing microbiological efficacy. Methods: CR-GNB infected patients with PMB-based regimens were enrolled. Clinical and microbiological data were collected from the medical electronic record system of the Second Xiangya hospital. The efficacy of PMB on different CR-GNB was evaluated by the clearance rate at 7-days and within the course of treatment, as well as the 30-day mortality rate. Results: A total of 294 CR-GNB infected patients were enrolled: 154 CR-Acinetobacter baumannii (CRAB), 55 CR-Klebsiella pneumoniae (CRKP), and 85 CR-Pseudomonas aeruginosa (CRPA). The CRAB group had the highest 7-day bacterial clearance rate [(CRAB: 39.0%) vs. (CRKP: 29.4%) vs. (CRPA: 14.5%), P = 0.003] and total bacterial clearance rate [(CRAB: 49.0%) vs. (CRKP: 39.8%) vs. (CRPA: 18.2%), P < 0.001] among the three groups, while the bacterial clearance rate of the CRPA group was the lowest. Multivariate logistic regression showed that the differences among the three groups were multiple CR-GNB infections (P = 0.004), respiratory infections (P = 0.001), PMB resistance (P < 0.001), and the combination of tigecycline (P < 0.001). Binary logistic regression showed that multiple CR-GNB infection [(7-day bacterial clearance: P = 0.004) & (total bacterial clearance: P = 0.011)] and bacterial species [(7-day bacterial clearance: P < 0.001) & (total bacterial clearance: P < 0.001)] were independent risk factors for microbiological efficacy. Conclusion: PMB exhibited differential microbiological efficacy on different types of CR-GNB infections; it had the best effect on CRAB, followed by CRKP and CRPA. Multiple CR-GNB infections and bacterial species were independent risk factors for microbiological efficacy.

Association between gene variants and the recurrence of atrial fibrillation: An updated meta-analysis.

BACKGROUND: Studies showed the controversial results about the effect of common genetic polymorphisms on the atrial fibrillation (AF) recurrence. We performed the systematic review and meta-analysis to qualify the association between common genetic polymorphisms and AF recurrence. METHODS: Articles were systematically retrieved PubMed, Web of Science, EMBASE, Wanfang, and CNKI database and 9 studies including 3204 patients were enrolled in our meta-analysis. RESULTS: Results showed that the associations were significant under rs2200733 3 genetic models (TT vs CC: odds ratio [OR] [confidence interval [CI]] = 1.336 [1.061-1.683], P = .014; CT vs CC: OR [CI] = 0.759 [0.614-0.937], P = .01; TT vs CT + CC: OR [CI] = 2.308 [1.440-3.700], P = .001). The association was significant under rs10033464 genetic model (TT vs GG: OR [CI] = 1.517 [1.165-1.976], P = .002). CONCLUSIONS: Rs13376333 on chromosome 1q21 (in KCNN3), rs7193343 and rs2106261 on chromosome 16q22 (in ZFHX3) were not associated with AF recurrence in our meta-analysis. In total, our meta-analysis found that rs2200733 and rs10033464 on chromosome 4q25 (near PITX2) were associated with the risk of AF recurrence.

[Long-term prognosis and quality of life of survivors with hepatitis B virus-related acute-on-chronic liver failure].

OBJECTIVE: To explore the long-term prognosis and health-related quality of life of patients surviving hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: The clinical data were collected from patients with HBV-ACLF, who were hospitalized in our department between November, 2011 and October, 2016 and survived for more than 90 days. The patients were followed for occurrence of newly diagnosed cirrhosis, decompensation events, hepatocellular carcinoma and death. The quality of life of the patients was evaluated using SF-36 score, and the patients with chronic hepatitis B (CHB) and cirrhosis treated during the same period served as controls. RESULTS: A total of 223 ACLF survivors were included in this study. According to the presence of cirrhosis on admission, the enrolled patients were divided into chronic hepatitis B-related ACLF (CHB-ACLF) group (n=130) and liver cirrhosis ACLF (CIR-ACLF) group (n=93). The 12-, 24- and 50-month survival rates in CHB-ACLF group were 97%, 95.7% and 93.9%, respectively, significantly higher than the rates in CIR-ACLF group (91%, 86% and 74%, respectively; P=0.007). In patients with CHB-ACLF, the 12-, 24- and 36-month progression rates of cirrhosis were 37.9%, 58.4% and 68.7% respectively. Multivariate Cox regression identified the peak value of serum creatinine (HR=1.015, P=0.026) and INR (HR=2.032, P=0.006) within 28 days as independent risk factors and serum sodium at baseline (HR=0.84, P=0.035) as an independent protective factor of occurrence of cirrhosis. The score of mental health on SF-36 in ACLF group was significantly lower than the national norms, and the scores for general health and body pain of ACLF patients were significantly higher than those in patients with CHB or cirrhosis. CONCLUSION: The long-term prognosis of ACLF survivors with and without cirrhosis can be different. Acute attacks are associated with an increased rate of cirrhosis progression in CHB patients who recovered from ACLF, possibly in relation with the severity of extra-hepatic organ injuries. The physical and social functions of long-term survivors of ACLF do not significantly decline, but their psychological status can be affected.

Development of a method for identification and accurate quantitation of aroma compounds in Chinese Daohuaxiang liquors based on SPME using a sol-gel fibre.

Aroma compositions of Chinese Daohuaxiang liquors, including five kinds of commercial liquors and three kinds of base liquors, were extracted by solid phase microextraction using a sol-gel divinylbenzene/hydroxy-terminated silicone oil fibre. The effectiveness of the fibre was evaluated in comparison with commercial fibres and liquid-liquid extraction. After identification by GC-MS and GC-O, the compounds were accurately quantified by GC-FID using internal standards. Wide linear ranges, low limits of detection, satisfactory precision and recoveries were achieved. A total of 57 volatile compounds were detected and 28 of them were quantified. Most of them were common in these liquors but differed in terms of their relative amounts. Thirteen out of the 28 compounds had odour activity values greater than 1 in all of the liquors, and are suggested to be the key aroma-contributing substances of Daohuaxiang liquors. Besides, the differences among different aroma types and kinds of Daohuaxiang liquors were also discussed.

Magnetic solid phase extraction based on magnetite/reduced graphene oxide nanoparticles for determination of trace isocarbophos residues in different matrices.

A simple one-step solvothermal method was applied for the preparation of magnetite/reduced graphene oxide (MRGO), and the synthetic nanocomposites with a magnetic particle size of ∼8nm were used as an adsorbent for magnetic solid phase extraction of isocarbophos (ICP) in different sample matrices prior to gas chromatography (GC) detection. The identity of the nanomaterial was confirmed using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. It was shown that Fe3O4 nanoparticles with a uniform size were homogeneously anchored on RGO nanosheets. Increased oxidation degrees of graphite oxide, big particle sizes and large loading amounts of Fe3O4 on the surface of RGO led to a decrease of adsorption capacity of MRGO to ICP. The adsorption behavior of this adsorbent was better fitted by the pseudo-second-order kinetic model. Several parameters affecting the extraction efficiency were investigated and optimized, including adsorbent dosage, extraction time, ionic strength and desorption conditions. And then, a rapid and effective method based on MRGO combined with GC was developed for the determination of ICP in aqueous samples. A linear range from 0.05 to 50ngmL(-1) was obtained with a high correlation coefficient (R(2)) of 0.9995, and the limit of detection was found to be 0.0044ngmL(-1). This method was successfully applied to the analysis of ICP in five kinds of samples, including apple, rice, lake water, cowpea and cabbage. The recoveries in different sample matrices were in the range from 81.00% to 108.51% with relative standard deviations less than 9.72%. It can be concluded that the proposed analytical method is highly-efficient, sensitive, precise, accurate and practicable.

Prevention of postsurgical cauterization-induced peritoneal adhesions by biodegradable and thermosensitive micelles.

Postsurgical peritoneal adhesion is a major concern in clinical practice which causes significant morbidity and mortality. In this study, we investigated the efficacy of biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) micelles in preventing postsurgical cauterization-induced peritoneal adhesion. The biodegradable PEG-PCL-PEG copolymer could form nano-sized micelles in water, which instantly turned into a non-flowing gel at body temperature due to micellar aggregation. Moreover, a novel sidewall and cecum cauterization rat model was developed and the micelles were assigned for adhesion prevention tests. The PEG-PCL-PEG micelles could be administered by an ordinary syringe and provided unrestricted coverage of the cauterized peritoneum. The micelles instantly formed a gel in situ at body temperature and the formed gel could adhere to the cauterized sites as a durable barrier during critical time of adhesion formation. All rats from the control group (n = 10) developed score 5 adhesion, whereas, eight out of ten rats in the micelle-treated group showed no adhesion at all. Besides, cauterization-induced adhesion formation, adhesiveness and degradation of micelles, remesothelization of peritoneum, and restoration of cauterized tissue were investigated in detail. Our results thus indicated that, it was feasible to use biodegradable and injectable thermosensitive PEG-PCL-PEG micelles for prevention of peritoneal adhesions after surgery.