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Bioscience Trends Jun 2024Liver transplantation (LT) has been an established treatment for end-staged liver disease for acute, chronic, metabolic diseases and liver cancer. Advanced surgical...
Liver transplantation (LT) has been an established treatment for end-staged liver disease for acute, chronic, metabolic diseases and liver cancer. Advanced surgical techniques, refined indications and contraindications for LT, improvements of donor selection, prognostic scorings system and immunosuppressive regimens have contributed to the improved outcomes of liver transplantation. The etiologies of cirrhosis have been shifting from viral hepatitis to metabolic associated fatty liver disease. New indications include peripheral or mass forming bile duct cancer, metastases from bowel cancers or neuroendocrine tumors. Resection and partial liver segments 2-3 transplantation with delayed total hepatectomy has been performed to the limited cases, which was the explored technique of auxiliary partial orthotopic LT. Minimally invasive donor hepatectomy (laparoscopic or robotic) has been increasingly done. In this review are described the recent pressing topics in LT.
PubMed: 38945855
DOI: 10.5582/bst.2024.01176 -
Chinese Medical Journal Jun 2024Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that...
BACKGROUND
Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that the vagus nerve exerts anti-inflammatory activity in many inflammatory diseases. Here, we aimed to identify the key molecule mediating the inflammatory process in ACLF and reveal the neuroimmune communication arising from the vagus nerve and immunological disorders of ACLF.
METHODS
Proteomic analysis was performed and validated in ACLF model mice or patients, and intervention animal experiments were conducted using neutralizing antibodies. PNU-282987 (acetylcholine receptor agonist) and vagotomy were applied for perturbing vagus nerve activity. Single-cell RNA sequencing (scRNA-seq), flow cytometry, immunohistochemical and immunofluorescence staining, and CRISPR/Cas9 technology were used for in vivo or in vitro mechanistic studies.
RESULTS
The unbiased proteomics identified C-X-C motif chemokine ligand 9 (CXCL9) as the greatest differential protein in the livers of mice with ACLF and its relation to the systematic inflammation and mortality were confirmed in patients with ACLF. Interventions on CXCL9 and its receptor C-X-C chemokine receptor 3 (CXCR3) improved liver injury and decreased mortality of ACLF mice, which were related to the suppressing of hepatic immune cells' accumulation and activation. Vagus nerve stimulation attenuated while vagotomy aggravated the expression of CXCL9 and the severity of ACLF. Blocking CXCL9 and CXCR3 ameliorated liver inflammation and increased ACLF-associated mortality in ACLF mice with vagotomy. scRNA-seq revealed that hepatic macrophages served as the major source of CXCL9 in ACLF and were validated by immunofluorescence staining and flow cytometry analysis. Notably, the expression of CXCL9 in macrophages was modulated by vagus nerve-mediated cholinergic signaling.
CONCLUSIONS
Our novel findings highlighted that the neuroimmune communication of the vagus nerve-macrophage-CXCL9 axis contributed to ACLF development. These results provided evidence for neuromodulation as a promising approach for preventing and treating ACLF.
PubMed: 38945689
DOI: 10.1097/CM9.0000000000003104 -
Journal of Gastrointestinal and Liver... Jun 2024Chronic liver diseases belong to the most common diseases worldwide and are associated with increased morbidity and mortality. Although more than one in three adults are...
BACKGROUND AND AIMS
Chronic liver diseases belong to the most common diseases worldwide and are associated with increased morbidity and mortality. Although more than one in three adults are estimated to have metabolic dysfunction-associated steatotic liver disease (MASLD), awareness of this condition is low amongst the general public, health care professionals and policy makers. However, meaningful knowledge transfer is essential for raising awareness and improving prevention and treatment. This study set out to investigate the use of the major internet search engine to understand how knowledge transfer has evolved by analyzing liver-related searches trends.
METHODS
We investigated Google search trends by measuring the number of hits relating to liver diseases between 2004 and 2021 in seven languages and European countries but also worldwide. All analyses were performed in R using the R Google trends package gtrendsR.
RESULTS
We found that interest in MASLD [formerly non-alcoholic fatty liver disease (NAFLD)] has generally increased over time, but that interest in metabolic associated steatohepatitis (MASH) - the most severe form of MASLD - has decreased. Interest in viral hepatitis C has decreased, whereas the number of queries regarding viral hepatitis B have been stable but dominated by interest in vaccination for it. Recent medical developments (in viral hepatitis) did not lead to a noticeable change in overall search behavior. Users preferred searching using their native language and less complex medical terms and acronyms (e.g., fatty liver instead of NAFLD).
CONCLUSIONS
In the last two decades, Google search trends have followed the general development in the field of hepatology. Searches were dominated by non-experts and are not being rapidly influenced by novel scientific developments. Also, users preferred search terms in their native languages rather than English and tended to avoid complex medical search terms. Awareness and communication strategies around MASLD should consider these preferences when addressing the general public.
Topics: Humans; Europe; Search Engine; Liver Diseases; Internet; Non-alcoholic Fatty Liver Disease; Information Seeking Behavior; Consumer Health Information
PubMed: 38944876
DOI: 10.15403/jgld-5477 -
Journal of Gastrointestinal and Liver... Jun 2024Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral...
BACKGROUND AND AIMS
Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown.
MATERIALS
We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
RESULTS
The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
CONCLUSIONS
We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
Topics: Humans; Membrane Proteins; Polymorphism, Single Nucleotide; Lipase; Female; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Middle Aged; 17-Hydroxysteroid Dehydrogenases; Genetic Predisposition to Disease; Case-Control Studies; Hepatitis B, Chronic; Prognosis; Adult; Turkey; Risk Factors; Prospective Studies; Phenotype; Genetic Association Studies; Acyltransferases; Phospholipases A2, Calcium-Independent
PubMed: 38944871
DOI: 10.15403/jgld-5474 -
Mymensingh Medical Journal : MMJ Jul 2024Objective of the study was the effect of Covid-19 infection on pregnancy and neonatal outcomes. This prospective cohort study was conducted in Combined Military Hospital... (Comparative Study)
Comparative Study
Objective of the study was the effect of Covid-19 infection on pregnancy and neonatal outcomes. This prospective cohort study was conducted in Combined Military Hospital (CMH) Bogura, Obstetrics and Gynaecology department from June 2020 to October 2020. We have collected and analyzed data of 29 pregnant ladies positive for Covid-19. Control group was Covid-19 negative pregnant patients. Nasopharyngeal swab was taken for real time polymerase chain reaction for detection of Covid-19. We observed symptoms, compared any complication in mother and fetus, mode of termination, and duration of hospital stay. Only six patients were asymptomatic (10.3%). Fifteen (25.9%) had fever, six (6) had weakness (10.3%), 5(8.6%) had sore throat, 3(5.2%) had nausea and 5(8.6%) presented with loss of smell. Among twenty-nine patients, 5(8.6%) delivered normally, 24(41.4%) were delivered through caesarean section which was significantly higher than control group (p value <0.001). No mother became critical or expired, neonatal death was also absent. Mean duration of hospital stay was 14.13±6.192 days in case and 5.18±4.99 in control which was significantly (p value <0.001) higher. Breast feeding was significantly higher in control group (p value <0.001). This study shows feto-maternal outcome of Covid-19 pregnancy is almost same as those of normal pregnancy.
Topics: Humans; Pregnancy; Female; COVID-19; Pregnancy Complications, Infectious; Adult; Prospective Studies; Pregnancy Outcome; Bangladesh; Infant, Newborn; SARS-CoV-2; Length of Stay; Cesarean Section; Young Adult
PubMed: 38944726
DOI: No ID Found -
Mymensingh Medical Journal : MMJ Jul 2024Major causes of acute insult in Hepatitis B virus related acute on chronic liver failure in the Asian region are reactivation of Hepatitis B virus and super infection... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Major causes of acute insult in Hepatitis B virus related acute on chronic liver failure in the Asian region are reactivation of Hepatitis B virus and super infection with hepatitis A and E virus (ACLF). Anti viral therapy should be started as soon as possible in the ACLF patients at presentation while waiting for confirmation by HBV DNA level. This randomized controlled trial was carried out at the Department of Hepatology, BSMMU, Bangladesh from September 2019 to august 2020 with Hepatitis B virus related ACLF patient. This trial was conducted among twenty seven HBV acute on chronic liver failure patient to compare Child Turcotte pugh (CTP) score, Model for end stage liver disease (MELD) score, Asia Pacific Association for study of Liver (APASL) ACLF Research consortium (AARC) score, survival of the patients and HBV DNA level at 3 months with antiviral therapy between tenofovir alafenamide (25mg) and entecavir (0.5mg) group. CTP score, MELD score and AARC score were significantly (p<0.05) decline from baseline to all subsequent follow-up at 1st (at 7 days), 2nd (at 14 days), 3rd (at 30 days) and 4th (at 90 days) in each group but non significant (p>0.05) difference occurred between two group. All twenty seven patients had detectable HBV DNA level at pre-treatment and all survived patients became undectable at 4th, 90 days follow-up. Total 10 patients (37.07%) were survived at 90 days follow-up, out of them seven patients (70.0%) were in tenofovir alafenamide group and three patients (30.0%) were in entecavir group which was statistically significant (p<0.05) in between two group. Hepatic encephalopathy and hepatorenal syndrome were most common causes of death in both groups. Both drugs tenofovir alafenamide and entecavir significantly improves liver functions but the former one is superior regarding survival.
Topics: Humans; Tenofovir; Guanine; Antiviral Agents; Male; Acute-On-Chronic Liver Failure; Female; Adult; Middle Aged; Treatment Outcome; Alanine; Hepatitis B; Hepatitis B virus
PubMed: 38944709
DOI: No ID Found -
Nature Communications Jun 2024Evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and...
Evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S subunit, which folds as a spring-loaded fusion machinery. We describe a strategy for prefusion-stabilization and high yield recombinant production of SARS-CoV-2 S trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S subunits. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S trimer elicits broadly reactive sarbecovirus antibodies and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines.
Topics: Animals; Mice; Antibodies, Neutralizing; Antibodies, Viral; Spike Glycoprotein, Coronavirus; SARS-CoV-2; Humans; COVID-19; Female; COVID-19 Vaccines; Mice, Inbred BALB C
PubMed: 38944664
DOI: 10.1038/s41467-024-49656-5 -
Nature Communications Jun 2024One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and... (Randomized Controlled Trial)
Randomized Controlled Trial
One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial (ISRCTN43622374). Biomarkers were assayed using ELISA and Luminex. Associations between baseline values and all-cause 24-week mortality were analysed using Cox models, and for cause-specific mortality used Fine & Gray models, including prophylaxis randomisation, viral load, CD4, WHO stage, age, BMI, and site as covariates; and weighted according to inverse probability of selection into the substudy. Higher baseline CRP, IFN-γ, IL-6 and IP-10 were associated with higher all-cause mortality; and higher IL-23, IL-2 and RANTES with lower all-cause mortality. Associations varied by cause of death: tuberculosis-associated mortality was most strongly associated with higher CRP and sST2, and cryptococcosis-associated mortality with higher IL-4 and lower IL-8. Changes in I-FABP (p = 0.002), faecal alpha-1 antitrypsin (p = 0.01) and faecal myeloperoxidase (p = 0.005) between baseline and 4 weeks post-ART were greater in those receiving enhanced versus cotrimoxazole prophylaxis. Our findings highlight how the immune milieu shapes outcomes following ART initiation, and how adjunctive antimicrobials can modulate the gut environment in advanced HIV.
Topics: Humans; HIV Infections; Biomarkers; Africa South of the Sahara; Male; Female; Adult; Adolescent; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Young Adult; Anti-HIV Agents; Child
PubMed: 38944653
DOI: 10.1038/s41467-024-49317-7 -
NPJ Biofilms and Microbiomes Jun 2024Gut metaproteomics can provide direct evidence of microbial functions actively expressed in the colonic environments, contributing to clarify the role of the gut... (Meta-Analysis)
Meta-Analysis
Gut metaproteomics can provide direct evidence of microbial functions actively expressed in the colonic environments, contributing to clarify the role of the gut microbiota in human physiology. In this study, we re-analyzed 10 fecal metaproteomics datasets of healthy individuals from different continents and countries, with the aim of identifying stable and variable gut microbial functions and defining the contribution of specific bacterial taxa to the main metabolic pathways. The "core" metaproteome included 182 microbial functions and 83 pathways that were identified in all individuals analyzed. Several enzymes involved in glucose and pyruvate metabolism, along with glutamate dehydrogenase, acetate kinase, elongation factors G and Tu and DnaK, were the proteins with the lowest abundance variability in the cohorts under study. On the contrary, proteins involved in chemotaxis, response to stress and cell adhesion were among the most variable functions. Random-effect meta-analysis of correlation trends between taxa, functions and pathways revealed key ecological and molecular associations within the gut microbiota. The contribution of specific bacterial taxa to the main biological processes was also investigated, finding that Faecalibacterium is the most stable genus and the top contributor to anti-inflammatory butyrate production in the healthy gut microbiota. Active production of other mucosal immunomodulators facilitating host tolerance was observed, including Roseburia flagellin and lipopolysaccharide biosynthetic enzymes expressed by members of Bacteroidota. Our study provides a detailed picture of the healthy human gut microbiota, contributing to unveil its functional mechanisms and its relationship with nutrition, immunity, and environmental stressors.
Topics: Humans; Gastrointestinal Microbiome; Proteomics; Bacteria; Feces; Bacterial Proteins; Healthy Volunteers; Proteome; Metabolic Networks and Pathways
PubMed: 38944645
DOI: 10.1038/s41522-024-00526-4 -
Advances in Pediatrics Aug 2024Respiratory syncytial virus (RSV) is a common viral pathogen that accounts about 33 million cases of acute lower respiratory tract infection (LRTI) worldwide in children... (Review)
Review
Respiratory syncytial virus (RSV) is a common viral pathogen that accounts about 33 million cases of acute lower respiratory tract infection (LRTI) worldwide in children under the age of 5 years each year. High-risk populations, particularly preterm infants, those with underlying chronic lung disease, congenital heart disease, or compromised immune systems, are afflicted most significantly. RSV infection is characterized by significant amount of mucus and submucosal edema in the respiratory tract, leading to congestion and, oftentimes, significant respiratory distress. Antigen- and PCR-based testing are used to diagnose RSV infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Infant; Cost of Illness; Child, Preschool; Infant, Newborn; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Antiviral Agents; Risk Factors; Global Health
PubMed: 38944477
DOI: 10.1016/j.yapd.2024.02.003