The burden and predictors of 30-day unplanned readmission in patients with acute liver failure: a national representative database study.

BACKGROUND: Liver diseases were significant source of early readmission burden. This study aimed to evaluate the 30-day unplanned readmission rates, causes of readmissions, readmission costs, and predictors of readmission in patients with acute liver failure (ALF). METHODS: Patients admitted for ALF from 2019 National Readmission Database were enrolled. Weighted multivariable logistic regression models were applied and based on Directed Acyclic Graphs. Incidence, causes, cost, and predictors of 30-day unplanned readmissions were identified. RESULTS: A total of 3,281 patients with ALF were enrolled, of whom 600 (18.3%) were readmitted within 30 days. The mean time from discharge to early readmission was 12.6 days. The average hospital cost and charge of readmission were $19,629 and $86,228, respectively. The readmissions were mainly due to liver-related events (26.6%), followed by infection (20.9%). The predictive factors independently associated with readmissions were age, male sex (OR 1.227, 95% CI 1.023-1.472; P = 0.028), renal failure (OR 1.401, 95% CI 1.139-1.723; P = 0.001), diabetes with chronic complications (OR 1.327, 95% CI 1.053-1.672; P = 0.017), complicated hypertension (OR 1.436, 95% CI 1.111-1.857; P = 0.006), peritoneal drainage (OR 1.600, 95% CI 1.092-2.345; P = 0.016), etc. CONCLUSIONS: Patients with ALF are at relatively high risk of early readmission, which imposes a heavy medical and economic burden on society. We need to increase the emphasis placed on early readmission of patients with ALF and establish clinical strategies for their management.

ATP-Responsive Manganese-Based Bacterial Materials Synergistically Activate the cGAS-STING Pathway for Tumor Immunotherapy.

Stimulating the cyclic guanosine monophophate(GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway is a crucial strategy by which bacteria activate the tumor immune system. However, the limited stimulation capability poses significant challenges in advancing bacterial immunotherapy. Here, an adenosine 5'-triphosphate (ATP)-responsive manganese (Mn)-based bacterial material (E. coli@PDMC-PEG (polyethylene glycol)) is engineered successfully, which exhibits an exceptional ability to synergistically activate the cGAS-STING pathway. In the tumor microenvironment, which is characterized by elevated ATP levels, this biohybrid material degrades, resulting in the release of divalent manganese ions (Mn2+) and subsequent bacteria exposure. This combination synergistically activates the cGAS-STING pathway, as Mn2+ enhances the sensitivity of cGAS to the extracellular DNA (eDNA) secreted by the bacteria. The results of the in vivo experiments demonstrate that the biohybrid materials E. coli@PDMC-PEG and VNP20009@PDMC-PEG effectively inhibit the growth of subcutaneous melanoma in mice and in situ liver cancer in rabbits. Valuable insights for the development of bacteria-based tumor immunotherapy are provided here.

The clinical courses of HBV-related acute-on-chronic liver failure and a multi-state model to predict disease evolution.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a highly dynamic syndrome. The objective of this study was to delineate the clinical course of patients with HBV-ACLF and to develop a model to estimate the temporal evolution of disease severity. METHODS: We enrolled eligible patients from 2 large, multicenter prospective cohorts. The ACLF grade, organ failures, and outcomes were assessed at multiple time points (days 1/4/7/14/21/28). Probabilities for ACLF transitions between these disease states and to death within 28 days were calculated using a multi-state model that used baseline information and updated ACLF status. The model was validated in independent patients. RESULTS: Among all the 445 patients with HBV-ACLF, 76 represented disease progression, 195 had a stable or fluctuating course, 8 with improvement, and the remaining 166 with resolution within 28-day follow-up. New coagulation (63.64%) or renal failure (45.45%) was frequently observed during early progression. Patients with disease progression had a higher incidence of new episodes of ascites [10 (13.16%) vs. 22 (5.96%), p = 0.027] and HE [13(17.11%) vs. 21 (5.69%), p = 0.001], and a significant increase in white blood cell count. The multi-state model represented dynamic areas under the receiver operating characteristic curves ranging from 0.71 to 0.84 for predicting all ACLF states and death at 4, 7, 14, 21, and 28 days post-enrollment and from 0.73 to 0.94 for predicting death alone, performing better than traditional prognostic scores. CONCLUSIONS: HBV-ACLF is a highly dynamic syndrome with reversibility. The multi-state model is a tool to estimate the temporal evolution of disease severity, which may inform clinical decisions on treatment.

Citrullinemia type II accompanied by mental derangement combined with multidrug resistance 3 decrease, case report.

Background: Here we report a rare case of citrullinemia type II (CTLN2) accompanied by mental derangement with a deficiency of multidrug resistance 3 (MDR3) in the liver. Case presentation: The clinical data of a 17-year-old girl were collected. Liver puncture was performed, and hepatic expression of MDR3 was determined by immunohistochemistry. Serum amino acids of the patient and her parents wwere determined by a chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). Genetic mutations of ABCB4 and SLC25A13 were screened by whole-exome sequencing. Immunohistochemical analysis showed a remarkably lower expression of MDR3. Mutation in ABCB4 gene was not found and whole-exome sequencing revealed the SLC25A13 mutation 852-855 del. Elevated serum levels of citrulline, homocitrulline, and homoarginine in the patient and her mother were found. Conclusions: We reported a rare case of CTLN2 combined with MDR3 deficiency, without mutation of ABCB4. The link between MDR3 down-expression and CTLN2 warrants further investigation. Meanwhile, clinicians need to further rule out the possibility of CTLN2 if MDR3 decreases in adolescent patients with mental disorders and abnormal liver function.

The burden of liver cirrhosis and underlying etiologies: results from the Global Burden of Disease Study 2019.

BACKGROUND: Liver cirrhosis is a major health concern. Herein, we aimed to estimate the incidence, prevalence, and mortality of liver cirrhosis caused by specific etiologies for 204 countries and territories. MATERIALS AND METHODS: The data were retrieved from the Global Burden of Disease Study 2019. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized death rate, and estimated annual percentage changes were used to estimate the trends in incidence, prevalence, and mortality of liver cirrhosis by sex, region, country, and etiology between 2009 and 2019. RESULTS: From 2009 to 2019, the incident cases of liver cirrhosis increased by 16.7%, from 1.8 million (95% uncertainty interval: 1.5-2.1) to 2.1 million (1.7-2.5), and the prevalent cases increased from 1378.3 million (1275.1-1498.8) to 1691.0 million (1560.9-1845.5). Liver cirrhosis contributed to nearly 1.5 million (1.4-1.6) deaths in 2019, nearly 0.2 million more than in 2009. However, the age-standardized death rate fell from 20.71 (19.79-21.65) per 100,000 population in 2009 to 18.00 (16.80-19.31) per 100,000 population in 2019. In terms of sex, males showed higher ASIR, ASPR, and age-standardized death rate than females. Among the etiologies, the ASIR and ASPR of NAFLD increased markedly, and there was also a modest increase in ASIR and ASPR for HCV and alcohol use. In contrast, the ASIR and ASPR of HBV decreased considerably. CONCLUSIONS: Our finding suggests an increasing burden of liver cirrhosis worldwide but a declining attributed death. A high prevalence and still rising trend of NAFLD and alcohol use-etiology were found in patients with cirrhosis globally, although variation was found between regions/countries. These data indicate that efforts to reduce the associated burden need to be improved.

Hepatitis E virus superinfection impairs long-term outcome in hospitalized patients with hepatitis B virus-related decompensated liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis. PATIENTS AND METHODS: A retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed. RESULTS: After a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p< 0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40-4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87-17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM. CONCLUSIONS: Elder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.

Vaccination with SARS-CoV-2 inactivated vaccines reduced the risk of anxiety and depression in a population majored by health care workers during the recent omicron variant outbreak.

Background: The mental health status of the population majored by health care workers in China during the omicron variant outbreak remains unknown. Furthermore, the effect of COVID-19-inactivated vaccines on mental health is yet to be investigated. Methods: A cross-sectional, online survey study was conducted from 12-20 April, 2022. The prevalence of symptoms of depression and anxiety were evaluated using the Hospital Anxiety and Depression Scale. Results: Responses from a total of 1,387 participants were analyzed, 39.7% of which reported symptoms of mental health illness. The incidence of anxiety (30.4% vs. 48.4%, p < 0.001) and depression (27.1% vs. 46.3%, p < 0.001) decreased with COVID-19 inactivated vaccination. From multivariate analysis, living in Shanghai (anxiety: Odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.14-2.19, p = 0.006; depression: OR: 1.61, 95% CI: 1.16-2.25, p = 0.005), with a mental illness (anxiety: OR: 8.97, 95% CI: 1.01-79.56, p = 0.049; depression: OR: 9.32, 95% CI: 1.06-82.30, p = 0.045) increased the incidence of anxiety and depression. Elderly participants (anxiety: OR: 0.986, 95% CI: 0.975-0.997, p = 0.012; depression: OR: 0.976, 95% CI: 0.965-0.987, p < 0.001) who had been vaccinated against COVID-19 (anxiety: OR: 0.49, 95% CI: 0.32-0.75, p = 0.001; depression: OR: 0.45, 95% CI: 0.29-0.69, p < 0.001) had decreased incidences of anxiety and depression. Conclusion: Our findings increase the awareness of the high incidence of mental health illness symptoms during the omicron variant outbreak despite previous experiences with the COVID-19 pandemic, and vaccination is suggested to reduce the risk of anxiety and depression.

Prognosis prediction performs better in patients with non-cirrhosis hepatitis B virus-related acute-on-chronic liver failure than those with cirrhosis.

Background: The accurate prediction of the outcome of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is impeded by population heterogeneity. The study aimed to assess the impact of underlying cirrhosis on the performance of clinical prediction models (CPMs). Methods: Using data from two multicenter, prospective cohorts of patients with HBV-ACLF, the discrimination, calibration, and clinical benefit were assessed for CPMs predicting 28-day and 90-day outcomes in patients with cirrhosis and those without, respectively. Results: A total of 919 patients with HBV-ACLF were identified by Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria, including 675 with cirrhosis and 244 without. COSSH-ACLF IIs, COSSH-ACLFs, Chronic Liver Failure-Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLFs), Tongji Prognostic Predictor Model score (TPPMs), Model for End-Stage Liver Disease score (MELDs), and MELD-Sodium score (MELD-Nas) were all strong predictors of short-term mortality in patients with HBV-ACLF. In contrast to a high model discriminative capacity in ACLF without cirrhosis, each prognostic model represents a marked decline of C-index, net reclassification index (NRI), and integrated discrimination improvement (IDI) in predicting either 28-day or 90-day prognosis of patients with cirrhosis. The hazard analysis identified largely overlapping risk factors of poor outcomes in both subgroups, while serum bilirubin was specifically associated with short-term mortality in patients with cirrhosis and blood urea nitrogen in patients without cirrhosis. A subgroup analysis in patients with cirrhosis showed a decline of discrimination of CPMS in those with ascites or infections compared to that in those without. Conclusion: Predicting the short-term outcome of HBV-ACLF by CPMs is optimal in patients without cirrhosis but limited in those with cirrhosis, at least partially due to the complicated ascites or infections.

One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C.

BACKGROUND: Entecavir (ETV) is a potent and selective nucleotide analog with significant activity against hepatitis B virus (HBV). ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV (Baraclude) when used in Chinese patients with chronic hepatitis B (CHB) in phase III clinical trials (Clinical Trials.gov number, NCT01926288) at weeks 48, 96, and 144. AIM: To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C. METHODS: In this double-blind study, we randomly assigned patients to receive 0.5 mg/d ETV (Group A) or ETV maleate (Group B) (ratio, 1:1), each with a placebo tablet for 48 wk. Then, all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49. The primary efficacy endpoint was the reduction in HBV DNA levels from baseline. Secondary endpoints included the proportion of patients with undetectable HBV DNA (< 20 IU/mL), serologic response, serum alanine aminotransferase (ALT) normalization and development of resistance mutations. RESULTS: Two hundred eighteen patients who were hepatitis B e antigen (HBeAg) positive and 57 who were HBeAg negative were analyzed and predominantly presented with genotype B (49.82%) or C (48.73%). For the HBeAg-positive CHB patients, the mean HBV DNA level decrease (6.61 Log10 IU/mL vs 6.69 Log10 IU/mL, P > 0.05), viral suppression with HBV DNA < 20 IU/mL (83.33% vs 79.17%, P > 0.05) and HBeAg seroconversion (28.77% vs 20.00%, P > 0.05) occurred similarly between Groups A and B at week 192. However, there was a significant difference in the proportion of patients with normal ALT levels (91.14% vs 78.38%, P < 0.05). For the HBeAg-negative CHB patients, no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline (6.05 Log10 IU/mL vs 6.03 Log10 IU/mL, P > 0.05), percentages of patients who achieved undetectable HBV DNA (100% vs 100%, P > 0.05) and rates of ALT normalization (95.65% vs 100.00%, P > 0.05). Safety and adverse event profiles were similar between Groups A and B. Two HBeAg-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV. CONCLUSION: Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.

Acute decompensation events differentially impact the risk of nosocomial infections and short-term outcomes in patients with cirrhosis.

Aims: This research aimed to evaluate the influence of acute decompensation (AD) events upon admission on the subsequent risk of nosocomial infections (NIs) and the synergy between AD and the following NIs on the short-term outcome. Methods: A total of 419 hospitalized individuals with cirrhosis and AD participated in the current study. Various AD events at admission and outcomes in patients with or without NIs were compared. The logistic regression and Cox proportional hazards models were designed for NIs development and liver transplant (LT)-free mortality at 28 and 90 days, respectively. Results: During hospitalization, 91 patients developed NIs. Notably, a higher proportion of patients with NIs had jaundice (52.7 vs. 30.5%; p < 0.001) and bacterial infections (37.4 vs. 20.7%; p = 0.001) at admission compared to patients without NIs, while a lower proportion suffered gastrointestinal hemorrhage (16.5 vs. 36.6%; p < 0.001). Multivariate analysis revealed that jaundice was independently linked with the development of NIs (OR, 2.732; 95% CI: 1.104-6.762). The 28-day (16.5 vs. 7.3%; p = 0.008) and 90-day (27.5 vs. 15.9%; p = 0.011) LT-free mortality rates of patients with NIs were significantly higher than those without NIs. According to the Cox proportional hazards model, jaundice remained an independent risk factor for 90-day death (HR, 5.775; 95% CI: 1.217-27.397). The connection between total bilirubin and 90-day mortality was nonlinear, and a 6 mg/mL threshold was proposed. Conclusion: The types of AD events differentially predispose to risk of NIs. Presenting jaundice at admission is independently associated with NIs occurrence and increased 90-day mortality of patients with NIs. Antibiotic prophylaxis may benefit this specific subset of patients.

240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.

Ketogenic Diets and Hepatocellular Carcinoma.

The ketogenic diet (KD) is a low-carbohydrate, high-fat diet regarded as a potential intervention for cancers owing to its effects on tumor metabolism and behavior. Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, and its management is worth investigating because of the high fatality rate. Additionally, as the liver is the glucose and lipid metabolism center where ketone bodies are produced, the application of KD to combat HCC is promising. Prior studies have reported that KD could reduce the energy supply and affect the proliferation and differentiation of cancer cells by lowering the blood glucose and insulin levels. Furthermore, KD can increase the expression of hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in hepatocytes and regulate lipid metabolism to inhibit the progression of HCC. In addition, ß-hydroxybutyrate can induce histone hyperacetylation and reduce the expression of inflammatory factors to alleviate damage to hepatocytes. However, there are few relevant studies at present, and the specific effects and safety of KD on HCC warrant further research. Optimizing the composition of KD and combining it with other therapies to enhance its anti-cancer effects warrant further exploration.

Delayed Clearance of Viral RNA in Sputum for Severity COVID-19 Patients with Initial High Viral Load.

Aim: To analyze the possible risk factors of delayed virus clearance in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods: Retrospective analysis of patients with COVID-19 admitted to the isolation wards from our hospital from 19th Jan 2020 to 18th March 2020. We were collected patient's data including demographic, epidemiologic, and clinical information, as well as laboratory and radiologic findings. The possible confounding risk factors for prolonged viral RNA shedding of COVID-19 during hospitalization were explored by univariate analysis and any variables with a p value less than 0.05 after univariate analysis were included in a subsequent multivariate logistic regression model analysis. Results: The 104 patients included 30 mild patients and 74 severe or critically ill patients. The median duration of viral RNA positivity in sputum was 11 days, and the longest duration of viral RNA positivity was 49 days after admission. Multivariate analysis shown that the used with darunavir/cobicistat treatment (odds ratio [OR]: 4.25, 95% confidence interval [CI]: 1.25-14.42, p = 0.020), duration of fever (OR: 1.15, 95% CI: 1.03-1.30, p = 0.015) and time to radiological improvement (OR: 1.14, 95% CI: 1.01-1.30, p = 0.033) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Then adjusted in the multivariate binary logistic regression analysis model in severe COVID-19 and found that critical COVID-19 patients (OR: 13.25, 95% CI: 1.45-12.07, p = 0.022), lower virus cycle threshold (CT) values of RT-PCR (OR: 0.96, 95% CI: 0.93-0.99, p = 0.004) and used with darunavir/cobicistat treatment (OR: 8.44, 95% CI: 2.21-32.28, p = 0.022) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Conclude: Clearance of viral RNA in sputum was delayed in severe COVID-19 patients, especially with lower virus CT value. And antivirals with darunavir/cobicistat has little advantage in eliminating SARS-CoV-2.

Drug delivery strategy in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high rates of recurrence and death. Surgical resection and ablation therapy have limited efficacy for patients with advanced HCC and poor liver function, so pharmacotherapy is the first-line option for those patients. Traditional antitumor drugs have the disadvantages of poor biological distribution and pharmacokinetics, poor target selectivity, high resistance, and high toxicity to nontargeted tissues. Recently, the development of nanotechnology has significantly improved drug delivery to tumor sites by changing the physical and biological characteristics of drugs and nanocarriers to improve their pharmacokinetics and biological distribution and to selectively accumulate cytotoxic agents at tumor sites. Here, we systematically review the tumor microenvironment of HCC and the recent application of nanotechnology in HCC. Video Abstract.

Omicron COVID-19 variant outcomes and vaccination in non-severe and non-critical patients at admission.

The clinical data of patients infected with the Omicron variant virus in Zhejiang Province from January to 14 May 2022 were collected retrospectively. We analyzed the differences in symptoms, clinical categories of COVID-19, length of hospital stay, and time for clearance of Omicron variant viral RNA in the sputum among the groups receiving a different number of vaccine doses. The analysis showed that as the number of vaccine doses increased, the frequency of clinical symptoms, such as fever and fatigue, decreased and the frequency of patients with moderate infections gradually decreased. At the same time, the length of hospital stay was significantly shortened. Based on the multivariate analysis, one vaccine dose [odds ratio (OR): 0.21, 95% confidence interval (CI): 0.08-0.56, p = 0.002], two vaccine doses (OR: 0.54, 95% CI: 0.33-0.88, p = 0.013), and three vaccine doses (OR: 0.40, 95% CI: 0.24-0.64, p < 0.001) shortened the length of hospitalization than those with no vaccination. The persistence of the virus in the sputum was significantly shortened with one vaccine dose (OR: 0.36, 95% CI: 0.15-0.89, p = 0.027), two vaccine doses (OR: 0.46, 95% CI: 0.27-0.78, p = 0.004), and three vaccine doses (OR: 0.38, 95% CI: 0.22-0.64, p < 0.001) than those with no vaccination. Therefore, we concluded that vaccination was an effective way to protect people against infection with the Omicron variant. Indeed, on the premise of the current routine recommendation of vaccination, three vaccines were necessary for people to be protected against the Omicron variant.

A Predictive Nomogram for Predicting Improved Clinical Outcome Probability in Patients with COVID-19 in Zhejiang Province, China.

The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019 (COVID-19). Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected. Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients. The least absolute shrinkage and selection operator (LASSO) logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients. The concordance index (C-index) was used to assess the discrimination of the model, and internal validation was performed through bootstrap resampling. A novel predictive nomogram was constructed by incorporating these features. Of the 104 patients included in the study (median age 55 years), 75 (72.1%) had improved short-term outcomes, while 29 (27.9%) showed no signs of improvement. There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes. After a multi-step screening process, prognostic factors were selected and incorporated into the nomogram construction, including immunoglobulin A (IgA), C-reactive protein (CRP), creatine kinase (CK), acute physiology and chronic health evaluation II (APACHE II), and interaction between CK and APACHE II. The C-index of our model was 0.962 (95% confidence interval (CI), 0.931-0.993) and still reached a high value of 0.948 through bootstrapping validation. A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve. The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient, which may facilitate personalized counselling and treatment.

Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected Patients Through Single-Cell Transcriptome Sequencing.

Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

Tenofovir disoproxil fumarate for multiple nucleos(t)ide analogues treatment failure hepatitis B: Is monotherapy enough?

BACKGROUND AND AIM: Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs). METHODS: Patients included were aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA > 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA < 20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed. RESULTS: Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log10 IU/mL), with 77.0% patients (95% confidence interval: 71.1, 82.9) achieving serum HBV DNA < 20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (hepatitis B e antigen [HBeAg]-positive at baseline) experienced HBeAg loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced more than one adverse event (AE). Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug-related AEs; 9.4% patients experienced serious AEs (none were TDF-related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly. CONCLUSIONS: Tenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.

Proton Pump Inhibitor Therapy Does Not Affect Prognosis of Cirrhosis Patients With Acute Decompensation and Acute-on-Chronic Liver Failure: A Single-Center Prospective Study.

Background: The aim of this study was to investigate the impact of proton pump inhibitor (PPI) therapy on complications and prognosis in cirrhosis patients with and without acute-on-chronic liver failure (ACLF). Materials and Methods: Cirrhosis patients with acute decompensation (AD) (n = 489) admitted in our center were enrolled in this prospective observational cohort study. According to treatment received, patients were identified as users or nonusers of PPI. Clinical and laboratory data, complications during hospitalization, and overall survival were recorded in all the patients. Results: Of the 489 patients, 299 (61.1%) patients received PPI therapy. The logistic regression analysis showed that age, albumin, history of previous hepatic encephalopathy (HE), and the chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score were independent risk factors for HE in patients with decompensated cirrhosis [odds ratio (OR) = 1.07, 95% CI: 1.03-1.12, p = 0.001; OR = 1.13, 95% CI: 1.04-1.24, p = 0.006; OR = 242.52, 95% CI: 40.17-1464.11, p < 0.001; and OR = 2.89, 95% CI: 2.11-3.96, p < 0.001, respectively]. Previous severe liver injury and previous bacterial infections were independent risk factors for spontaneous bacterial peritonitis (SBP) in patients with decompensated cirrhosis (OR = 3.43, 95% CI: 1.16-10.17, p = 0.026 and OR = 6.47, 95% CI: 2.29-18.29, p < 0.001, respectively). The multivariate Cox proportional hazards regression model showed that the type and dose of the PPI used were not related to 28-day and 90-day mortality in cirrhosis patients with AD or ACLF. Conclusion: PPI use does not appear to increase mortality or the risk of HE and SBP in the hospitalized cirrhosis patients with and without ACLF.