BACKGROUND AND OBJECTIVE

Evidence regarding the impact of performing endoscopy within 12 hours of variceal bleeding (VB) on outcomes is inconclusive, and there is a lack of local data on this topic. This study aimed to determine if the timing of endoscopy is associated with clinical outcomes.

This was a single-center retrospective cohort study which included adult cirrhotic patients admitted for VB from January 2016 to September 2022. The primary outcomes were in-hospital and 6-week mortality. Secondary outcomes included 5-day rebleeding, length of hospital stay (LOS), and blood transfusion requirements (BTR). The relationships between timing of endoscopy and outcomes were evaluated using regression analysis.

In 140 patients, 5.7% underwent urgent endoscopy (?12 hours). The overall median door-to-endoscopy time (DET) was 39.4 hours (IQR 20.0-73.4). The overall in-hospital mortality, 6-week mortality, and 5-day rebleeding rates were 12.9%, 11.4%, and 8.6%, respectively, without significant variability at different DET (p >0.05). Prolonged LOS was evident when endoscopy was delayed to >12 hours from admission (3.5 [IQR 2.25-5.75] vs 6 days [IQR 4-9.75], p = 0.021), while BTR was greater starting at endoscopies performed at >24 hours from admission (1 [0-2] vs 2 units [1-3], p = 0.000). Delayed endoscopy was significantly correlated with LOS (Beta 0.316, SE 0.011, p = 0.000) and BTR (Beta 0.214, SE 0.469, p = 0.003), but not with mortality and early rebleeding.

Timing of endoscopy may be independent of mortality and early rebleeding. Timely endoscopy may shorten hospitalization and decrease need for blood transfusion. Other factors affecting clinical outcomes may be at play.

Schistosomiasis, a snail-borne disease caused by infection with a trematode parasite of the genus Schistosoma, is one of the most neglected tropical diseases in the world. One of its rare complications is hepatosplenic schistosomiasis which ultimately leads to fibrosis and presinusoidal portal hypertension.

We report a case of a 13-year-old Filipino male from Quezon City with previous one year residence in the endemic island of Leyte, presenting with melena. Diagnostic work-up revealed hepatosplenomegaly and periportal fibrosis with multiple hepatic nodules on ultrasound, positive Schistosoma japonicum eggs on Kato-Katz stool examination technique, and findings of esophageal varices on upper endoscopy. The patient was managed with praziquantel, propranolol, and endoscopic rubber band ligation of the esophageal varices, with note of resolution of bleeding, and improvement on sonographic liver findings.

The degree of liver fibrosis from schistosomiasis is affected by poorly understood mechanisms which affect its severity, progression, and complications, regardless of biosocial factors including egg burden and duration of parasite exposure. This is the first case report on a Filipino adolescent to document significant interval improvement, within four weeks of treatment, of the characteristic fibrotic pattern in hepatosplenic schistosomiasis. Hepatosplenic schistosomiasis is still often missed out as the diagnosis in patients who consult with common symptoms, and high index of suspicion is recommended for those with history of residence in endemic areas. Likewise, treatment focusing on parasite eradication can aid in promptly addressing the resulting fibrosis and its complications.

BACKGROUND

Non-Alcoholic Fatty Liver Disease (NAFLD) is common in Type 2 Diabetes Mellitus (T2DM). The FIB-4 index is one of the most-studied non-invasive biomarkers that combines age and laboratory parameters (platelet count, alanine-and aspartate- aminotransferase) to evaluate underlying hepatic fibrosis. This study aims to determine the diagnostic value of Fibrosis-4 (FIB-4) index scoring in screening for non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus, which is a high-risk population in development of advance fibrosis.

A single center, analytical cross-sectional study was conducted among adult T2DM patients with and without NAFLD seen at the Out-Patient Department (OPD) and those with NAFLD enrolled under the Liver Disease Databank of the Liver Disease and Transplant Center in collaboration with Research and Biotechnology Division at St. Luke’s Medical Center, Quezon City. Medical history was obtained by reviewing charts of eligible patients using data collection form. Liver ultrasound was used as the reference standard in the diagnosis of NAFLD. The FIB-4 index was calculated with this formula: age (years) x AST (U/L)/(platelets (10^9/L) x ALT (U/L)^1/2.

A total of 305 adult patients with type 2 diabetes mellitus were included in the study. The prevalence of non-alcoholic fatty liver disease based on ultrasound among diabetic patients is 76.07%. The median age (p = 0.0204), AST (p < 0.00001), ALT (p < 0.00001) were significantly higher in patients with NAFLD than those without. Platelet count (p = 0.0002) was significantly lower in patients with NAFLD than those without. The proportion of patients with low platelet count, high AST and high ALT were significantly higher in patients with NALFD than those without. In this study, the FIB-4 index cutoff score for screening of NAFLD is ≥0.76, which has an accuracy of 66.23%, sensitivity of 75%, specificity of 38.3%, PPV of 79.46% and NPV of 32.56% in detecting fatty liver.

A FIB-4 index value of ≥0.76 has an acceptable sensitivity for screening NAFLD even in the absence of fibrosis among patients with T2DM. However, due to its low specificity, additional tests to establish NAFLD diagnosis may be required.

BACKGROUND

Hepatitis B virus causes life-threatening chronic liver infection and increases the risk of death from cirrhosis and liver cancer. A three-dose series of universal HBV vaccination initiated from birth is effective against the disease. It is unclear if catch-up vaccination is also effective in those with incomplete or no HBV vaccination.

To review the evidence on the effect of HBV catch-up vaccination on children and adults to decrease HBV-related morbidity.

We searched MEDLINE, Cochrane CENTRAL, ChinaXiv, MedRXIV, BioRXIV, Google Scholar, and ongoing and completed trials on USA: https://clinicaltrials.gov/; China: http://www.chictr.org.cn/searchprojen.aspx, and WHO: https://www.who.int/clinical-trials-registry-platform. The last search date was 30 June 2023. We considered experimental or observational studies, meta-analysis/systematic reviews, completed trials and preprints that investigated the efficacy of catch-up HBV immunization in decreasing morbidity from hepatitis B infection including acute and chronic hepatitis B infection, liver cirrhosis, and hepatocellular carcinoma. There was no age and language restriction. Two reviewers independently rated the quality of included studies using Newcastle – Ottawa Quality Assessment Scale for cohort and crosssectional studies. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was used to determine the certainty of evidence. Data was presented as number (%) for categorical values. Differences between the unvaccinated and vaccinated group was described as relative risk or odds ratio for categorical variables. Data was pooled using Review Manager 5.4.

A total of four observational studies were included, one of which had data in children and adults [two (one with data in adults) studies in children; 3 in adults]. The cross-sectional study was assessed as good quality; and the three cohorts as fair to good. In children, a high certainty evidence study showed that catch up vaccination in 9 to 18 years old decreased risk of HBsAg positivity [RR: 0.09 (0.004, 0.21)], reduced HBV DNA detection [RR: 0.084 (0.026, 0.273)], and increased antiHBs seroconversion [RR: 2.08 (1.84, 2.33)]. The quality of evidence was deemed high based on a large treatment effect. Another low certainty evidence study in Italy showed that HBV mass immunization in 0-10 years old decreased the prevalence of HBsAg anti-HBc and increased anti-HBs seroconversion after vaccination.

In adults, three low certainty evidence studies were included. Two studies showed decreased incidence of acute hepatitis B [OR: 0.08 (0.05, 0.12), I2 = 33%]. Another study demonstrated a decreased prevalence of hepatocellular carcinoma with HBV vaccination with the incidence ratio of vaccinated with chronically infected at 0.04 (0.02, 0.07) showing a large magnitude of benefit for vaccination against HCC when chronic HBV infection is prevented. The studies were deemed to have low quality due to issue of directness and study design.

HBV catch-up vaccination in adults is effective in decreasing the prevalence of acute hepatitis B and hepatocellular carcinoma. It likewise decreased the prevalence of HBsAg and anti-HBc, and provided anti-HBs protection in 0 to 18 years.

BACKGROUND AND OBJECTIVE

Evidence regarding the impact of performing endoscopy within 12 hours of variceal bleeding (VB) on outcomes is inconclusive, and there is a lack of local data on this topic. This study aimed to determine if the timing of endoscopy is associated with clinical outcomes.

This was a single-center retrospective cohort study which included adult cirrhotic patients admitted for VB from January 2016 to September 2022. The primary outcomes were in-hospital and 6-week mortality. Secondary outcomes included 5-day rebleeding, length of hospital stay (LOS), and blood transfusion requirements (BTR). The relationships between timing of endoscopy and outcomes were evaluated using regression analysis.

In 140 patients, 5.7% underwent urgent endoscopy (?12 hours). The overall median door-to-endoscopy time (DET) was 39.4 hours (IQR 20.0-73.4). The overall in-hospital mortality, 6-week mortality, and 5-day rebleeding rates were 12.9%, 11.4%, and 8.6%, respectively, without significant variability at different DET (p >0.05). Prolonged LOS was evident when endoscopy was delayed to >12 hours from admission (3.5 [IQR 2.25-5.75] vs 6 days [IQR 4-9.75], p = 0.021), while BTR was greater starting at endoscopies performed at >24 hours from admission (1 [0-2] vs 2 units [1-3], p = 0.000). Delayed endoscopy was significantly correlated with LOS (Beta 0.316, SE 0.011, p = 0.000) and BTR (Beta 0.214, SE 0.469, p = 0.003), but not with mortality and early rebleeding.

Timing of endoscopy may be independent of mortality and early rebleeding. Timely endoscopy may shorten hospitalization and decrease need for blood transfusion. Other factors affecting clinical outcomes may be at play.

OBJECTIVE: To observe the effects of moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) on the circular RNA of exon 2-5 of the Pan3 gene (circPAN3), forkhead box O3 (FOXO3), and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in rats with chronic heart failure (CHF), and explore the potential mechanisms of moxibustion in alleviating myocardial fibrosis. METHODS: Ten rats of 60 male SPF-grade SD rats were randomly assigned into a normal group. The remaining rats underwent left anterior descending coronary artery (LAD) ligation to establish the CHF model. Forty successfully modeled rats were randomly divided into a model group, a moxibustion group, a rapamycin (RAPA) group, and a moxibustion+RAPA group, with 10 rats in each group. The moxibustion group received mild moxibustion at bilateral "Feishu" (BL13) and "Xinshu" (BL15), 30 min per session. The RAPA group received intraperitoneal injection of the autophagy activator RAPA (1 mg/kg). The moxibustion+RAPA group first received RAPA injection, followed by mild moxibustion at bilateral "Feishu" (BL13) and "Xinshu" (BL15). All interventions were administered once daily for 4 consecutive weeks. After the intervention, cardiac ultrasound was used to measure ejection fraction (EF) and left ventricular fractional shortening (FS). Serum placental growth factor (PLGF) level was determined by ELISA. Myocardial tissue morphology and collagen volume were assessed using hematoxylin-eosin (HE) staining and Masson's trichrome staining. The expression levels of circPAN3, FOXO3, and BNIP3 mRNA in myocardial tissue were detected by real-time PCR, while FOXO3 and BNIP3 protein expression levels were analyzed by Western blot. RESULTS: Compared with the normal group, the model group exhibited myocardial cell disorder, severe fibrosis, and increased collagen volume (P<0.01), along with significantly decreased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and the serum PLGF level, as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue were increased (P<0.01). Compared with the model group, the moxibustion group showed reduced myocardial fibrosis, decreased collagen volume (P<0.01), increased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and decreased serum PLGF level as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue (P<0.01). Compared with the model group, the RAPA group showed further deterioration in these parameters (P<0.01). Compared with the RAPA group, the moxibustion+RAPA group exhibited alleviation of myocardial fibrosis, reduced collagen volume (P<0.01), increased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and decreased serum PLGF level as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue (P<0.01). CONCLUSION Moxibustion could alleviate myocardial fibrosis in CHF rats, possibly through upregulation of myocardial circPAN3 expression, downregulation of FOXO3 and BNIP3 expression, and inhibition of excessive myocardial autophagy.
Animals ; Moxibustion ; Heart Failure/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Myocardium/pathology* ; RNA, Circular/metabolism* ; Membrane Proteins/metabolism* ; Forkhead Box Protein O3/metabolism* ; Acupuncture Points ; Humans ; Fibrosis/genetics* ; Chronic Disease/therapy* ; Mitochondrial Proteins

Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP) + fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune-stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.
Humans ; Fibrosis/metabolism* ; Inflammatory Bowel Diseases/pathology* ; Animals ; Transforming Growth Factor beta/metabolism* ; Intestines/pathology*

This article reviews the role of different types of T lymphocyte subpopulations in pathological cardiac fibrosis remodeling. T helper 17 (Th17) cells are implicated in promoting the development of pathological cardiac fibrosis remodeling, while regulatory T (Treg) cells exert an immunosuppressive functions as negative regulators, attributing to their interleukin-10 (IL-10) secretion and functional phenotype. Th1 and Th2 cells are involved in different stages of the inflammatory response in pathological cardiac fibrosis remodeling, and their influence varies according to the pathological mechanisms of different cardiac diseases. In addition, CD8⁺ T cells regulate the activation and polarization of macrophages, promote the secretion of granzyme B, induce cardiomyocyte apoptosis, and aggravate cardiac fibrosis post-myocardial infarction. Considering the limitation of cytokine modulation in clinical therapy of heart failure, targeting T-cell co-stimulatory molecules emerges as a promising strategy for treating pathologic cardiac remodeling. Future research will explore chimeric antigen receptor modified T cells (CAR-T cells) technology and targeted regulation of Treg cells quantity and phenotype, for both of which have the potential to become effective methods for treating heart disease.
Humans ; Fibrosis ; T-Lymphocytes, Regulatory/immunology* ; Ventricular Remodeling/immunology* ; Myocardium/immunology* ; Animals ; Th17 Cells/immunology* ; Interleukin-10/metabolism* ; Th1 Cells/immunology* ; Th2 Cells/immunology*

Persistent inflammation plays a pivotal role in the initiation and progression of renal fibrosis. Activation of the pattern recognition receptor retinoic acid-inducible gene-I (RIG-I) is implicated in the initiation of inflammation. This study aimed to investigate the upstream mechanisms that regulates the activation of RIG-I and its downstream signaling pathway. Eight-week-old male C57BL/6 mice were used to establish unilateral ureteral obstruction (UUO)-induced renal fibrosis model, and the renal tissue samples were collected 14 days later for analysis. Transforming growth factor-β (TGF-β)-treated mouse renal tubular epithelial cells were used in in vitro studies. The results demonstrated that, compared to the control group, UUO kidney exhibited significant fibrosis, which was accompanied by the increases of RIG-I, p-NF-κB p65 and inflammatory cytokines, such as TNF-α and IL-1β. Additionally, the protein level of the E3 ubiquitin ligase RNF125 was significantly downregulated and predominantly localized in the renal tubular epithelial cells. Similarly, the treatment of tubular cells with TGF-β induced the increases in RIG-I, p-NF-κB p65 and inflammatory cytokines while decreasing RNF125. Co-immunoprecipitation (Co-IP) assays confirmed that RNF125 was able to interact with RIG-I. Overexpression of RNF125 promoted the ubiquitination of RIG-I, and accelerated its degradation via the ubiquitin-proteasome pathway. Overexpression of RNF125 in UUO kidneys and in vitro tubular cells effectively mitigated the inflammatory response and renal fibrosis. In summary, our results demonstrated that the decrease in RNF125 under pathological conditions led to reduction in RIG-I ubiquitination and degradation, activation of the downstream NF-κB signaling pathway and increase in inflammatory cytokine production, which promoted the progression of renal fibrosis.
Animals ; Fibrosis ; Male ; Ubiquitination ; Mice ; Mice, Inbred C57BL ; DEAD Box Protein 58 ; Ubiquitin-Protein Ligases/physiology* ; Inflammation/metabolism* ; Ureteral Obstruction/complications* ; Kidney/pathology* ; Signal Transduction ; Transforming Growth Factor beta/pharmacology*

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*