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Reliable in vitro models with human-derived cells that recapitulate in vivo-like physiologies are required for drug discovery and development to reduce the gap between the results of cell-based drug testing, animal testing, and human clinical trials. Liver organoid models have emerged as novel tools for hepatotoxicity evaluation, liver disease modeling, and drug screening. Liver organoids can be generated from biopsies of liver tissues or pluripotent stem cells and can be applied to various liver diseases, including metabolic associated fatty liver disease, infectious liver disease, genetic liver disease, and liver cancer. This review focuses on recent studies on organoids to model human liver diseases and discusses the advantages and limitations of current liver organoids for translational applications. [ABSTRACT FROM AUTHOR]

Drugs targeting the ER-resident innate immune receptor Stimulator of Interferon Genes (STING) are in development for treatments of cancer and inflammatory diseases. Accurate determination of STING receptor levels in normal and disease tissue is an essential component of modeling pharmacology and drug-target disposition. Using metabolic labeling with deuterium oxide paired with high resolution mass spectrometry, we report the protein fractional synthesis rates and turnover of STING in wild-type (C57BL/6) and inflamed mice carrying the Trex1 D18N mutation (Trex1D18N) as a STING-dependent model of human Acardi-Goutiéres syndrome. Remarkably, STING protein half-life is tissue specific with the shortest half-life of 4 days in colon and lymph node and longest half-life of 24 days in skeletal muscle. Despite the relative increase in STING protein abundance in the inflamed Trex1D18N mouse, the overall kinetics of protein degradation and resynthesis was similar between Trex1D18N and WT mice. The extent of tissue specific interferon stimulated gene transcription, a hallmark of SLE linked pathophysiology, correlates with the extend of increased STING levels in Trex1D18N tissues and appears inversely proportional to the turnover rate of STING. Understanding STING's fractional protein synthesis rate and half-life provides a valuable component of quantitative modeling of drug pharmacology, dose frequency and targeting tissues of STING directed therapies. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C (CHC) is the most common cause of infection related deaths in USA according to Central Disease Control and Prevention (CDC) report in 2016. Hepatitis C is a blood borne virus and is common in chronic kidney disease (CKD) and in hemodialysis (HD) dependent patients. A majority of patients with CHC could remain asymptomatic and are still undiagnosed. Early detection of CHC and linkage of infected patients to care for evaluation and treatment is the standard of care as emphasized by Kidney Disease Improving Global Outcome (KDIGO) and American Association for the Study of Liver Disease- Infectious Disease Society of America (AASLD-IDSA) practice guidelines. Historically, the management of hepatitis C virus (HCV)-infected CKD patients, including those on dialysis and in the peri-transplant setting, was a challenge. However, the evolution of various liver assessment tools, HCV tests, therapies and treatment strategies in the recent years has catalyzed a paradigm change in this area. This review provides an update on evaluating methodology, diagnostic tests and the various assessment tools for liver fibrosis pertaining to the CKD/HD patient infected with HCV. [ABSTRACT FROM AUTHOR]

Heart failure is a leading cause of mortality worldwide, necessitating the development of novel therapeutic and lifestyle interventions. Recent studies highlight a potential role of time‐restricted feeding (TRF) in the prevention and treatment of cardiac diseases. Here, it is found that TRF protected against heart failure at different stages in mice. Metabolomic profiling revealed that TRF upregulated most circulating amino acids, and amino acid supplementation protected against heart failure. In contrast, TRF showed a mild effect on cardiac amino acid profile, but increased cardiac amino acid utilization and activated the cardiac urea cycle through upregulating argininosuccinate lyase (ASL) expression. Cardiac‐specific ASL knockout abolished the cardioprotective effects afforded by TRF. Circulating amino acids also protected against heart failure through activation of the urea cycle. Additionally, TRF upregulated cardiac ASL expression through transcription factor Yin Yang 1, and urea cycle‐derived NO contributes to TRF‐afforded cardioprotection. Furthermore, arteriovenous gradients of circulating metabolites across the human hearts were measured, and found that amino acid utilization and urea cycle activity were impaired in patients with decreased cardiac function. These results suggest that TRF is a promising intervention for heart failure, and highlight the importance of urea cycle in regulation of cardiac function. [ABSTRACT FROM AUTHOR]

Evolutionary medicine emerged in the late twentieth century, integrating principles of natural selection and adaptation with the health sciences. Today, with a rapidly widening gap between the biology of Homo sapiens and its environment, maladaptation or maladaptive disorders can be detected in almost all diseases, including liver dysfunction. However, in hepatology, as in most medical specialties, evolutionary considerations are neglected because the majority of the medical community is not familiar with evolutionary principles. The aim of this brief review is to highlight an evolutionary approach that may facilitate understanding various liver diseases. [ABSTRACT FROM AUTHOR]

Zavegepant is a calcitonin gene‐related peptide receptor antagonist for acute migraine treatment. This Phase I, open‐label, fixed‐sequence study evaluated the effects of itraconazole (a strong cytochrome P450 3A4 [CYP3A4] and P‐glycoprotein [P‐gp] inhibitor) on the pharmacokinetics of intranasal/oral zavegepant and the effects of rifampin (a strong inducer of CYP3A4 and P‐gp; and an inhibitor of organic anion transporting polypeptide 1B3 [OATP1B3]) on oral zavegepant in healthy participants. In the intranasal/oral zavegepant–itraconazole cohort, participants received a single 10‐mg dose of zavegepant nasal spray on Day 1, followed by oral zavegepant (50 mg) on Day 3. Itraconazole 200 mg once daily was administered from Days 4 to 12. On Day 7 zavegepant nasal spray and on Day 11 oral zavegepant were coadministered with itraconazole. In the oral zavegepant–rifampin cohort, participants received oral zavegepant (100 mg) on Day 1, rifampin 600 mg once daily on Days 2–10, and rifampin with zavegepant on Day 11. No significant change in zavegepant exposure was observed following coadministration of itraconazole with zavegepant nasal spray. For oral zavegepant coadministered with itraconazole, the area under the curve from 0 to infinity (AUC0−inf) and the maximum observed concentration (Cmax) of oral zavegepant increased by 59% and 77%, respectively. For oral zavegepant coadministered with rifampin, the AUC0−inf and Cmax of oral zavegepant increased by approximately 2.3‐ and 2.2‐fold, respectively. These results suggest that OATP1B3 and intestinal P‐gp are the more prominent pathways, as opposed to CYP3A4, for a zavegepant drug–drug interaction. Coadministration of OATP1B3 inhibitors with zavegepant nasal spray should be avoided. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is the prevailing primary glomerulonephritis globally and is the key factor contributing to the onset of chronic kidney disease and eventual progression to end-stage renal disease. This study aims to explore the mutated gene in a familial case of IgAN, especially COL4A3. Methods: Family lineages diagnosed with familial IgAN at the Longyan First Hospital of Fujian Medical University were selected for this study, followed by comprehensive whole exome sequencing. After obtaining the sequencing data, bioinformatics analyses were conducted to discern potential mutated genes. These findings within the familial lineages were validated using Sanger sequencing to identify IgAN-associated mutated genes, based on literature references and in accordance with the genetic variation classification criteria determined by the American College of Medical Genetics and Genomics. Results: Whole exome sequencing analysis of familial IgAN family lineages led to the identification of a total of 212,187 single nucleotide variant/insertion-deletion mutation sites, annotated using ANNOVAR. These sites were screened targeting four mutated genes, revealing three mutations of undetermined significance along with a single disease-causing mutation: a heterozygous disease-causing mutation within COL4A3 (p.G1167R). This mutation manifested across seven family members within the group, encompassing both family members diagnosed with kidney disease and those serving as normal carriers. Notably, one additional family member with IgAN within the familial lineage exhibited an absence of the pathogenic mutation. Conclusion: This study identified four mutated genes that may be involved in the onset and progression of IgAN, further revealing the complex multigenic inheritance characteristics of IgAN. The underlying mechanisms of the disease require further investigation. Additionally, we discovered potential mutations associated with known genetic kidney diseases, such as COL4A3 mutations. Therefore, we recommend comprehensive genetic screening in familial cases of IgAN to improve disease diagnosis and facilitate genetic counseling. [ABSTRACT FROM AUTHOR]

According to the World Health Organization (WHO), the incidence of HCV remains high (around 1.5 million new patients every year), and 80% of patients with acute infection will progress to chronic hepatitis and develop cirrhosis and even liver cancer. Furthermore, some extrahepatic pathologies may be correlated with HCV (such as mixed cryoglobulinemia, porphyria cutanea tarda, lichen planus, glomerulonephritis, Sjogren's syndrome, Hodgkin and non-Hodgkin cell lymphoma, and others). In view of these secondary complications, together with the substantial risk of liver damage, the objective of this review was to research and suggest, based on the scientific evidence, the appropriate clinical use of drugs with direct antiviral action (AAD) according to the criteria of international medical organizations. This is to maximize the clinical benefits for patients and to facilitate access to DAA therapy for all patients with chronic hepatitis C. According to the WHO, no vaccine is currently available, and therapies using new antivirals and their combinations are now an effective and safer solution for patients than they have been in the past with the use of interferons. This study aims to analyse the history and knowledge of the pathogenic biomolecular mechanisms and current therapies for HCV. [ABSTRACT FROM AUTHOR]

Background: Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear. Methods: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNTNT5E- mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured. Results: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A. Conclusion: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background: Despite curative treatment options since 2014, only 12% of individuals in Washington State diagnosed with Hepatitis C (HCV) received treatment in 2018. Washington State agencies launched an elimination plan in 2019 to promote access to and delivery of HCV screening and treatment. The purpose of this study is to evaluate provider and health system barriers to successful implementation of HCV screening and treatment across Washington State. Methods: This is a cross-sectional online survey of 547 physicians, nurse practitioners, physician assistants, and clinical pharmacists who provide care to adult patients in Washington State conducted in 2022. Providers were eligible if they worked in a primary care, infectious disease, gastroenterology, or community health settings. Questions assessed HCV screening and treating practices, implementation barriers, provider knowledge, observed stigma, and willingness to co-manage HCV and substance use disorder. Chi-squared or fishers exact tests compared characteristics of those who did and did not screen or treat. Results: Provider adoption of screening for HCV was high across the state (96%), with minimal barriers identified. Fewer providers reported treating HCV themselves (28%); most (71%) referred their patients to another provider. Barriers identified by those not treating HCV included knowledge deficit (64%) and lack of organizational support (24%). The barrier most identified in those treating HCV was a lack of treating clinicians (18%). There were few (< 10%) reports of observed stigma in settings of HCV treatment. Most clinicians (95%) were willing to prescribe medication for substance use disorders to those that were using drugs including alcohol. Conclusion: Despite widespread screening efforts, there remain barriers to implementing HCV treatment in Washington State. Lack of treating clinicians and clinician knowledge deficit were the most frequently identified barriers to treating HCV. To achieve elimination of HCV by 2030, there is a need to grow and educate the clinician workforce treating HCV. [ABSTRACT FROM AUTHOR]

Background: Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with substance use disorders (SUDs) among rural Veterans. Methods: We implemented a clinic-based intervention which used motivational interviewing (MI) techniques to promote medication adherence and treatment completion with 12 weeks of DAA treatment among rural Veterans with chronic HCV and SUDs. Patients received an MI session with a licensed psychologist at baseline and at each two-week follow-up visit during DAA treatment. Patients received $25 per study visit completed. Patients were to attend a laboratory visit 12 weeks after treatment completion to assess for sustained virologic response (SVR). Results: Of the 20 participants who enrolled, 75% (n = 15) completed the planned 12-week course of treatment. Average adherence by pill count was 92% (SD = 3%). Overall SVR was 95% (19/20). Conclusions: We demonstrated that a clinic-based intervention which incorporated frequent follow up visits and MI techniques was feasible and acceptable to a sample of predominantly rural Veterans with chronic HCV and SUDs. Clinical trial registration: Registered at ClinicalTrials.gov (NCT 02823457) on July 1, 2016. https://clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Introduction: Splenomegaly is the enlargement of spleen. Splenomegaly is a sign seen in various disease processes in infants and children. So, an attempt was made in the present study to know the various etiological factors and clinical features and clinical outcome of splenomegaly in the cases admitted in Prathima institute of medical sciences, Nagunoor, Karimnagar Aim and objectives: 1. To establish the possible etiology of Splenomegaly in children by clinical and laboratory methods Material and methods: 100 children from 3 months to 18years, with varying grades of Splenomegaly of different etiologies, admitted to paediatric wards of Prathima Institute of Medical Sciences, Karimnagar were studied in this observational study between Decembers 2015 to November 2017. Detailed study of each case including history, thorough physical examination and necessary investigations were done to reach the diagnosis. Results: Male preponderance was seen in present study. Maximum incidence of Splenomegaly was seen between 3 months to 6 years age group (62%). Majority of the cases had moderate Splenomegaly (62%). Fever was the most common presenting feature associated with Splenomegaly. Hepatomegaly was the most common association with Splenomegaly. Infections (42%) were the most common cause of Splenomegaly, followed by hematologic (25%) causes. Conclusions: Infections was the most common cause of Splenomegaly in present study. Male preponderance was seen; majority of cases had moderate Splenomegaly and belonged to preschool age group. [ABSTRACT FROM AUTHOR]

Background and aim: Limited data are available regarding pre‐liver transplantation (LT) bacteremia in adults with end‐stage liver disease. In this study, we investigated the risk factors independently associated with pre‐LT bacteremia and their effects on clinical outcomes of LT. Methods: This retrospective study performed between 2010 and 2021 included 1287 LT recipients. The study population was categorized into patients with pre‐LT bacteremia and those without pre‐LT infection. Pre‐LT bacteremia was defined as bacteremia detected within 90 days before LT. Results: Among 1287 LT recipients, 92 (7.1%) developed pre‐LT bacteremia. The mean interval between bacteremia and LT was 28.3 ± 19.5 days. Of these 92 patients, seven (7.6%) patients died after LT. Of the 99 microorganisms isolated in this study, gram‐negative bacteria were the most common microbes (72.7%). Bacteremia was mainly attributed to spontaneous bacterial peritonitis. The most common pathogen isolated was Escherichia coli (25.2%), followed by Klebsiella pneumoniae (18.2%), and Staphylococcus aureus (15.1%). Multivariate analysis showed that massive ascites (adjusted odds ratio [OR] 1.67, 95% confidence Interval [CI] 1.048–2.687) and a prolonged international normalized ratio for prothrombin time (adjusted OR 1.13, 95% CI 1.074–1.257) were independent risk factors for pre‐LT bacteremia in patients with end‐stage liver disease. Intensive care unit and in‐hospital stay were significantly longer, and in‐hospital mortality was significantly higher among LT recipients with pre‐LT bacteremia than among those without pre‐LT infection. Conclusions: This study highlights predictors of pre‐LT bacteremia in patients with end‐stage liver disease. Pre‐LT bacteremia increases the post‐transplantation mortality risk. [ABSTRACT FROM AUTHOR]

Background and Aims: Biallelic variants in the sorbitol dehydrogenase (SORD) gene have been identified as the genetic cause of autosomal recessive (AR) peripheral neuropathy (PN) manifesting as Charcot–Marie–Tooth disease type 2 (CMT2) or distal hereditary motor neuropathy (dHMN). We aim to observe the genetic and clinical spectrum of a cohort of patients with SORD‐related PN (SORD‐PN). Methods: A total of 107 patients with AR or sporadic CMT2/dHMN underwent molecular diagnosis by whole‐exome sequencing and subsequent Sanger sequencing validation. Available phenotypic data for SORD‐PN were collected and analyzed. Results: Eleven (10.28%) of 107 patients were identified as SORD‐PN, including four with CMT2 and seven with dHMN. The SORD variant c.210 T > G;p.His70Gln in F‐d3 was firstly reported and subsequent analysis showed that it resulted in loss of SORD enzyme function. Evidence of subclinical muscle involvement was frequently detected in patients with SORD‐PN, including mildly to moderately elevated serum creatine kinase (CK) levels in 10 patients, myogenic electrophysiological changes in one patient, and muscle edema in five patients undergoing lower extremity MRI. Fasting serum sorbitol level was 88‐fold higher in SORD‐PN patients (9.69 ± 1.07 mg/L) than in healthy heterozygous subjects (0.11 ± 0.01 mg/L) and 138‐fold higher than in healthy controls (0.07 ± 0.02 mg/L). Interpretation: The novel SORD variant c.210 T > G;p.His70Gln and evidence of subclinical muscle involvement were identified, which expanded the genetic and clinical spectrum of SORD‐PN. Subclinical muscle involvement might be a common but easily overlooked clinical feature. The serum CK and fasting serum sorbitol levels were expected to be sensitive biomarkers confirmed by follow‐up cohort study. [ABSTRACT FROM AUTHOR]

Purpose: To provide a detailed overview of the fundamentals of saliva constituents and production. The review outlines the clinical manifestations as a consequence of salivary gland dysfunction and management strategies for patients with salivary gland dysfunction. Prosthodontic implications of saliva and salivary gland dysfunction are presented. Materials and methods: English‐language literature relating to saliva constituents, physiologic saliva production, clinical manifestations secondary to salivary gland dysfunction, salivary biomarkers, and management strategies were retrieved via electronic search. Relevant articles were summarized for this manuscript with a view toward providing pragmatic information. Results: Saliva is produced by three pairs of major and minor salivary glands. The major salivary glands, namely, the parotid, submandibular, and sublingual glands, contribute approximately 90% of saliva production. Saliva contains serous and mucinous secretions produced by different types of cells within salivary glands. Parasympathetic and sympathetic fibers innervate the major salivary glands, and upon stimulation, the parasympathetic innervation increases serous secretions, while the sympathetic innervation increases protein secretion. Stimulated saliva is mainly derived from the parotid glands which are composed of serous acini, while unstimulated saliva is mainly derived from the submandibular glands which are composed of mixed seromucous acini. As major salivary glands contribute the most to salivary flow, local or systemic factors influencing those glands can disrupt saliva production resulting in clinically significant oral manifestations. Conclusion: This review provides a fundamental overview of saliva production. In addition, the review highlights the various clinical manifestations secondary to salivary gland dysfunction, explores salivary biomarkers for screening of systemic diseases, discusses management strategies for patients with salivary gland dysfunction, and outlines the prosthodontic implications of saliva and salivary gland dysfunction. [ABSTRACT FROM AUTHOR]

Background: Early detection and monitoring of anemia are important in CKD patients, which significantly increases the effectiveness of clinical treatment, reduce treatment cost and improve quality of life patients. Differential diagnosis of anemia based on conventional erythrocyte indices is limited, therefore it requires to be combined with other indices to determine iron deficiency. Reticulocyte hemoglobin equivalent (RETHe) is an alternative indicator of iron deficiency that is not affected by inflammation, and has been proposed as an additional marker for iron deficiency screening. Objective: To determine the correlation between RET-He and erythrocyte indices (MCV, MCH, MCHC) in predialytic CKD patients. Method: Cross-sectional retrospective study of predialytic CKD patient data in Prof. Ngoerah General Hospital, that were tested for RET-He and erythrocyte indices in January - March 2022. Data was collected from laboratory information system (LIS) and medical record. RET-He was measured with lightscatter flow cytometry method and erythrocyte indices was calculated. Result: Sixty and three (63) study subjects were consisted of 37 men (58,7%) and 26 women (41,3%), with average of age was 60,68±10,52 years. The mean value of RET-He, MCV, MCH and MCHC was 30,55±2,86 pg, 89,08±7,78 fL, 28,76±2,72 pg, and 30,55±2,86 g/dL. Result of data analysis showed positive correlation between RET-He and MCV (r = 0,659), MCH (r = 0,734), and also between RET-He and MCHC (r = 0,383), with p < 0,05. Conclusion: There was a significant positive correlation between RET-He with erythrocyte indices in predialytic CKD patients. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is highly prevalent in United States prisons and jails. In prisons and jails, rates of infection are ten to twenty times greater than national levels. And, more than thirty percent of all people living with HCV in the United States will spend time in prisons and jails in any given year. Rates are especially high among people who inject drugs (PWID), a population whose members are also likely to move between carceral settings and the community. Thus, addressing HCV among incarcerated populations would have a significant effect on the virus's transmission both in and out of confinement and is a crucial part of any HCV elimination strategy. Safe and effective HCV treatment is available. Direct-acting antivirals (DAAs) offered in an eight to twelve week course of oral treatment cure HCV in more than ninety percent of cases. Widespread testing and treatment in prisons and widespread testing and treatment or linkage to community care in jails are essential public health approaches. But testing and treatment in confinement lags behind medical guidance and public health recommendations. People incarcerated in prisons and detained in jails are entitled to adequate health care, and the U.S. Constitution prohibits deliberate indifference to their serious medical needs. In recent years, lawsuits filed by people with HCV in carceral facilities across the country have alleged violations of federal law for failure to provide DAA treatment. Although litigation results have been mixed, settlement agreements in states across the country have expanded HCV testing and broadened access to DAA treatment. These settlement agreements reflect a growing understanding that widespread testing and treatment is cost-effective, avoid the harmful health consequences of disease progression, and meaningfully reduce community transmission. This paper recommends model policies for prisons and jails to expand HCV testing and DAA treatment. The policy recommendations draw from relevant settlement agreements and current medical guidelines, supplemented by input from public health experts, medical professionals, and advocates. The paper proceeds as follows: • Part I describes the HCV epidemic in United States prisons and jails, the recent sea change in treatment protocols, and relevant clinical guidance and public health recommendations. • Part II sets out the legal landscape, including governing federal law and judicial decisions interpreting that law in this context, and describes settlement agreements in class action lawsuits addressing DAA access. • Finally, Part III offers model policies for prisons and jails to expand testing and treatment and to support successful outcomes for people with HCV in their custody. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long‐term risk in the era of direct‐acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon‐based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow‐up. We used extended landmark modelling, with time‐varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time‐to‐event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval‐years of follow‐up. SVR from DAA or IFN‐based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08–0.20; and aHR 0.45, 95% CI 0.31–0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17–0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17–4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six‐variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval‐based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring. [ABSTRACT FROM AUTHOR]

To explore the value of 1.5T magnetic resonance (MR) fat saturation-T2-weighted imaging (FS-T2WI) and apparent diffusion coefficient (ADC) imaging texture features in distinguishing the renal changes of patients with stage III type 2 diabetic kidney disease (DKD) from healthy people.Methods: This study collected 55 patients with stage III DKD (39 males and 16 females) and 33 healthy controls (13 males and 20 females) from December 2021 to June 2022 in the China-Japan Union Hospital of Jilin University. All subjects were randomly divided in a ratio of 6:4 to extract and screen the FS-T2WI and ADC texture features of the right kidney of the subjects. The area under the curve (AUC) was used to assess the diagnostic accuracy of each model.Results: There were significant differences between urea, creatinine and sex (p< 0.05) of the two groups in the training and test set, and no significant difference in age and body mass index (BMI). We extracted 1409 imaging features from the original ADC sequence and selected them by wavelet and Laplace-Gaussian filter and LASSO algorithm, and using the same methods of FS-T2WI. Finally, FS-T2WI and ADC models were selected to construct the united model, including 3 first-order features and 8 texture features. The AUC values of the training set of FS-T2WI, ADC, FS-T2WI+ADC combined logistic regression model were 0.96, 0.91, 0.98; the AUC values of the test set were 0.91, 0.89 and 0.93, and the specificity and accuracy values of the united model were 0.90 and 0.89, respectively.Conclusion: FS-T2WI and ADC imaging features based on 1.5 T MR had diagnostic value in the early diagnosis of DKD stage III, and the combined model of FS-T2WI and ADC had high diagnostic efficiency. [ABSTRACT FROM AUTHOR]

Background: Oral cancer (OC), which happens to be one of the leading causes of death in the Indian population, is caused primarily by tobacco use, although other factors are also responsible. Serum vitamin B12 is important in maintaining the immune system and also repairing the damaged deoxyribonucleic acid (DNA) of cells. The aim of our study was to evaluate the serum B12 levels in patients with OC and look for any association between the two. Methods: One hundred subjects were selected for the study and divided into two groups: group A having OC (including cases of oral squamous cell carcinoma (OSCC), verrucous carcinoma and oropharyngeal carcinoma; 50 patients) and group B had age‑ and gender‑matched healthy controls (50 healthy volunteers). Patients diagnosed clinically and histopathologically confirmed as OC were selected for the study. All the patients were subjected to haematological investigation to assess serum vitamin B12. Results: Males subjects in the 4th and 5th decades of life were predominantly affected. Serum vitamin B12 was significantly increased in OC patients when compared with controls, which was statistically significant. The mean serum vitamin B12 was slightly higher in males than in females, which was statistically non‑significant. Conclusion: Our study found increased vitamin B12 levels in OC patients, and it was statistically significant. [ABSTRACT FROM AUTHOR]

Background Cholangiocarcinoma (CCA), a fatal bile duct cancer, has a high incidence in Western Siberia, Russian Federation. In addition, Opisthorchis felineus , a bile duct–dwelling trematode liver fluke is highly endemic. Closely related species have been shown to be cancerogenic agents in Asia. We therefore examined the association between O felineus infection and CCA in Western Siberia. Methods We conducted a hospital-based, individually matched case-control study between January 2017 and August 2020 in Tomsk Oblast and Khanty-Mansiysk Autonomous Okrug, Yugra, Russian Federation. Histologically confirmed CCA patients (cases) were compared with matched age, sex, and place of residence hospital controls. The examination of study participants included the diagnosis of current and past O felineus infection, abdominal ultrasonographical assessment, physical examination, and interview on exposures to potential risk factors. Results We identified 40 patients with CCA and 160 controls. Exposures to O felineus infection was strongly associated with CCA (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4–10.8; P =.008). Also, cases reported more often that they were currently or in the past were infected by O felineus compared with controls (OR, 4.03; 95% CI, 1.7–9.5; P =.001). Furthermore, cases reported river fish consumption and fishing habits significantly more often than controls (OR, 5.5; 95% CI, 1.5–19.8; P =.009 and OR, 3.3; 95% CI, 1.4–7.7; P =.005). Conclusions The study results revealed a strong significantly increased risk for CCA development in O felineus –infected individuals. Elaboration of the guidelines on screening programs for early CCA diagnosis, prevention, and treatment is socially important in endemic regions. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection remains a major cause of morbidity and mortality in early-stage post-liver transplantation (LT). Methods: We retrospectively analyzed the demographic and clinical infections characteristics of all LT recipients in our hospital between January 2019 and December 2021. Results: Among the 272 LT recipients who received LT between January 2019 and December 2021, sixty-two patients had at least one infection within 3-months post-LT, with a prevalence of 22.8% (62/272). The prevalence of CRKP infections was 7.0% (19/272), and the 3-months post-LT mortality was 19.4% (12/62). The risk factors independently related to 3-monthsmortality were age (Odds ratio (OR)= 1.126, 95% Confidence interval (CI): 1.009~1.257; P=0.034), mechanical ventilation (MV) (OR=1.206, 95% CI: 1.039~1.401; P =0.014), and CRKP infection (OR=18.240, 95% CI: 2.206~150.842; P =0.007). In CRKP infection, the length of ICU stay (OR=1.067, 95% CI: 1.015~1.122; P=0.011), pre-operation infection (POI) (OR=6.733, 95% CI: 1.160~39.088; P=0.034), and hepatocellular carcinoma (HCC) (OR=26.772, 95% CI: 1.747~410.187; P=0.018) were the independent risk factors. With COX multivariate regression analysis, the 3-months survival rate of CRKP infected patients was significantly lower than that without CRKP infection post-LT. Conclusions: CRKP infection is closely correlated with poor prognosis in 3-months post-LT. [ABSTRACT FROM AUTHOR]

Catheter-related infections (CRIs) include catheter-associated urinary tract infections (CAUTIs) and central line-associated bloodstream infections (CLABSIs), and they are associated with high morbidity, mortality, and healthcare costs. The diagnosis of a CRI is made difficult by its non-specific symptoms. We aimed to investigate the factors influencing the plasma concentration of galectin-3 in catheter-bearing patients and to explore its potential usefulness as an index for CRIs. Circulating the concentrations of galectin-3, we measured the chemokine (C-C) motif ligand 2, procalcitonin, and C-reactive protein in 110 patients with a central catheter, in 165 patients with a urinary catheter, and in 72 control subjects. Catheter-bearing patients had higher concentrations (p < 0.001) of galectin-3 than the control group [central catheter: 19.1 (14.0–23.4) µg/L; urinary catheter: 17.1 (12.7–25.4) µg/L; control group: 6.1 (5.0–8.7) µg/L]. We identified chronic kidney disease as an independent determinant of galectin-3 concentrations in patients with a central catheter, and serum creatinine, cardiovascular disease, and number of days that the catheter was indwelling were identified as determinants in urinary catheter patients. We found that measuring galectin-3 concentrations in urinary catheter patients with a CRI was more accurate for diagnosis than the other parameters. We conclude that the measurement of galectin-3 concentration may be useful for assessing the inflammatory status of catheter-bearing patients and may contribute to the diagnosis of CRIs in those with a urinary catheter. [ABSTRACT FROM AUTHOR]

Aim: Heart failure (HF), a progressive disease, is accompanied by chronic inflammation and changes in osmolality. The neutrophil-to-lymphocyte ratio (NLR) demonstrates a systemic inflammatory response in most diseases; however, the relationship between plasma osmolality and the systemic inflammatory response in HF patients is not yet clear. Therefore, we aimed to investigate the possible associations of NLR with plasma osmolality levels in patients with HF. Materials and Methods: The present study included 189 consecutive patients with chronic HF with an ejection fraction (EF) of <40%. They were classified into four groups based on admission plasma osmolality quartiles: hypo-osmolar (first quartile), normohypo-osmolar (second quartile), normo-hyperosmolar (third quartile), and hyperosmolar (fourth quartile). We evaluated the relationship between NLR, plasma osmolality, type-B natriuretic peptide (BNP), and the New York Heart Association (NYHA) functional class. Results: The hyperosmolar group had an increased NLR (p = 0.007). The presence of NYHA class 3-4 functional capacity, high-sensitivity C-reactive protein, and high osmolality were independent predictors of increased NLR. In correlation analysis, osmolality was significantly positively correlated with NLR (r = 0.201, p = 0.011). Conclusion: Higher NLR values may be associated with increased plasma osmolality, which may indicate an increased inflammatory status in the HF phenomenon. [ABSTRACT FROM AUTHOR]

Objectives: Long-term therapy with low-dose methotrexate (MTX) is widely used in treatment of rheumatic diseases, in children. The purpose of this study was to evaluate liver elasticity in patients with juvenile idiopathic arthritis (JIA) who received MTX and compare the results with control group. Methods: Liver elasticity was evaluated with shear wave elastography (SWE) technique in 25 patients aged 3-17 years who were followed up with JIA and received MTX and compared with 25 healthy controls of the same age and weight. Factors that had an effect on liver elasticity were examined. Results: The mean SWE value of patients was 2.64 ± 2.13 m/s and 24.10 ± 18.50 kPa, whereas 1.83 ± 0.16 m/s and 10.09 ± 1.83 kPa in control group. There was a significant difference in liver elasticity in the patient and control groups. When the patients were evaluated as Group 1 (< 1000 mg) and Group 2 (≥1000 mg) according to the cumulative MTX dose, no significant difference was obtained. There was positive correlation between liver elasticity and weekly MTX dose and age. Conclusions: Our study revealed that liver elasticity significantly decreased in patients who received MTX when compared with the control group. The elastography technique will be understood better over time and used safely in many areas. [ABSTRACT FROM AUTHOR]

Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-β1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes of RA pathway inhibition induced the expression and production of PEX-associated matrix components by disease-relevant cell culture models in vitro. Conversely, RA signaling pathway activation by natural and synthetic retinoids was able to suppress PEX-associated matrix production and formation of microfibrillar networks via antagonization of Smad-dependent TGF-β1 signaling. The findings indicate that deficient RA signaling in conjunction with hyperactivated TGF-β1/Smad signaling is a driver of PEX-associated fibrosis, and that restoration of RA signaling may be a promising strategy for anti-fibrotic intervention in patients with PEX syndrome and glaucoma. [ABSTRACT FROM AUTHOR]

Introduction: MDRO-colonization has been shown to impair survival in patients with hematological malignancies and solid tumors as well as in patients with liver disease. Despite the increasing spread of multidrug-resistant organisms (MDRO), its impact on patients with hepatocellular carcinoma (HCC) has not been studied. We conducted this retrospective study to analyze the impact of MDRO-colonization on overall prognosis in HCC patients. Materials and methods: All patients with confirmed HCC diagnosed between January 2008 and December 2017 at the University Hospital Frankfurt were included in this study. HCC patients with a positive MDRO screening before or within the first 90 days after diagnosis of HCC were defined as colonized HCC patients, HCC patients with a negative MDRO screening were defined as noncolonized HCC patients. Results: 59 (6%) colonized and 895 (94%) noncolonized HCC patients were included. Enterobacterales with extended-spectrum β-lactamase-like phenotype with or without resistance to fluoroquinolones (ESBL/ ± FQ) were the most frequently found MDRO with 59%, followed by vancomycin-resistant Enterococcus faecium with 37%. Colonized HCC patients had more severe cirrhosis and more advanced HCC stage compared to noncolonized HCC patients. Colonized HCC patients showed an impaired survival with a median OS of 189 days (6.3 months) compared to a median OS of 1001 days (33.4 months) in noncolonized HCC patients. MDRO-colonization was identified as an independent risk factor associated with survival in multivariate analysis. Conclusion: MDRO-colonization is an independent risk factor for survival in patients with HCC highlighting the importance of regular MDRO screening, isolation measures as well as interdisciplinary antibiotic steward-ship programs to guide responsible use of antibiotic agents. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to explore the value of MRI texture features based on T1WI, T2-FS and diffusion-weighted imaging (DWI) in differentiation of renal changes in patients with stage III type 2 diabetic nephropathy (DN) and normal subjects. Materials and Methods: A retrospective analysis was performed to analyze 44 healthy volunteers (group A) and 40 patients with stage III type 2 diabetic nephropathy (group B) with microalbuminuria. Urinary albumin to creatinine ratio (ACR) <30 mg/g, estimated glomerular filtration rate (eGFR) in the range of 60–120 ml/(min 1.73 m2), and randomly divided into primary cohort and test cohort. Conventional MRI and DWI of kidney were performed using 1.5 T magnetic resonance imaging (MRI). The outline of the renal parenchyma was manually labeled in fat-suppressed T2-weighted imaging (FS-T2WI), and PyRadiomics was used to extract radiomics features. The radiomics features were then selected by the least absolute shrinkage and selection operator (LASSO) method. Results: There was a significant difference in sex and body mass index (BMI) (P <0.05) in the primary cohort, with no significant difference in age. In the final results, the wavelet and Laplacian–Gaussian filtering are used to extract 1,892 image features from the original T1WI image, and the LASSO algorithm is used for selection. One first-order feature and six texture features are selected through 10 cross-validations. In the mass, 1,638 imaging extracts features from the original T2WI image.1 first-order feature and 5 texture features were selected. A total of 1,241 imaging features were extracted from the original ADC images, and 5 texture features were selected. Using LASSO-Logistic regression analysis, 10 features were selected for modeling, and a combined diagnosis model of diabetic nephropathy based on texture features was established. The average unit cost in the logistic regression model was 0.98, the 95% confidence interval for the predictive efficacy was 0.9486–1.0, specificity 0.97 and precision 0.93, particularly. ROC curves also revealed that the model could distinguish with high sensitivity of at least 92%. Conclusion: In consequence, the texture features based on MR have broad application prospects in the early detection of DN as a relatively simple and noninvasive tool without contrast media administration. [ABSTRACT FROM AUTHOR]

The article discusses the U.S. Sixth Circuit case Atkins v. Parker which deals with the alleged liability of a chief medical director (CMD) for deliberate indifference to the needs of inmates with chronic hepatitis C. Topics noted include the analysis of violation of Eighth Amendment for failure of CMD to provide direct-acting antivirals to every infected inmate, a brief background on hepatitis C virus (HCV), the changes in 2016 HCV guidance in Tennessee, and the HCV litigation in other courts.

Environmental chemicals such as inorganic arsenic (iAs) significantly contribute to redox toxicity in the human body by enhancing oxidative stress. Imbalanced oxidative stress rapidly interferes with gut homeostasis and affects variety of cellular processes such as proliferation, apoptosis, and maintenance of intestinal barrier integrity. It has been shown that gut microbiota are essential to protect against iAs3+-induced toxicity. However, the effect of microbial metabolites on iAs3+-induced toxicity and loss of gut barrier integrity has not been investigated. The objectives of the study are to investigate impact of iAs on gut barrier function and determine benefits of gut microbial metabolite, urolithin A (UroA) against iAs3+-induced adversaries on gut epithelium. We have utilized both colon epithelial cells and in a human intestinal 3D organoid model system to investigate iAs3+-induced cell toxicity, oxidative stress, and gut barrier dysfunction in the presence or absence of UroA. Here, we report that treatment with UroA attenuated iAs3+-induced cell toxicity, apoptosis, and oxidative stress in colon epithelial cells. Moreover, our data suggest that UroA significantly reduces iAs3+-induced gut barrier permeability and inflammatory markers in both colon epithelial cells and in a human intestinal 3D organoid model system. Mechanistically, UroA protected against iAs3+-induced disruption of tight junctional proteins in intestinal epithelial cells through blockade of oxidative stress and markers of inflammation. Taken together, our studies for the first time suggest that microbial metabolites such as UroA can potentially be used to protect against environmental hazards by reducing intestinal oxidative stress and by enhancing gut barrier function. Highlights: The gut microbial metabolite Urolithin A (UroA) enhances cell viability during inorganic arsenic (iAs3+) exposure and prevents arsenite-induced cell death in colon epithelial cells. UroA reduced iAs3+-induced oxidative stress in intestinal epithelial cells. UroA alleviated iAs3+-induced barrier dysfunction in both colon epithelial cell monolayers and a human 3D small intestinal tissue model. The protective effect of UroA is associated with enhanced accumulation of tight junctional proteins including Zonula occludens-1, Occludin, and Claudin-4 to repair iAs3+-induced intestinal barrier damage. [ABSTRACT FROM AUTHOR]

Psoriatic patients with latent tuberculosis infection and properly treated active tuberculosis need careful management when prescribing modern biological drugs. Although data and guidelines regarding tumour necrosis factor-α inhibitors advise caution and initiation of prophylactic therapy in patients with latent tuberculosis infection, the same indications do not seem to find equal force for interleukin (IL)-23 and IL-17 inhibitors. In order to evaluate the risk of reactivation in patients with latent tuberculosis infection or properly treated active tuberculosis, an observational retrospective study was conducted on the population referred to our centre at Dermatologic Clinic of University of Turin, Italy. In the last 10 years at the clinic 19 psoriatic patients were found to be at risk of tuberculosis reactivation: 10 patients were QuantiFERON-TB-positive at baseline, 2 became positive during treatment, 6 reported prior tuberculous infection, and 1 was QuantiFERON-TB-negative at baseline and developed disseminated tuberculosis during treatment with anti-tumour necrosis factor-α. Overall, 10.5% of this group of patients developed active tuberculosis; however, stratifying by biologic therapy, zero cases were observed among patients treated with anti-IL-17, -23, or -12/23 over a relatively long followup (48.1 months) A review of the available literature following our experience confirms the increased risk of tuberculosis reactivation with tumour necrosis factor-α inhibitors. Concerning anti-IL-23 and IL-17 drugs, available data showed high safety in patients at risk of tuberculosis reactivation. Screening of patients who should be taking IL-17 and IL-23 inhibitors is recommended for public health purposes. In case of a positive result with these therapies, consulting with an infectious diseases specialist is suggested in order to weigh up the risks and benefits of prophylactic treatment. [ABSTRACT FROM AUTHOR]

Background: Thrombocytopenia is a common hematological abnormality during gestation. Pregnant women with severe thrombocytopenia may be associated with a higher risk of excessive bleeding during or after delivery. Therefore, the main aim of this study was to assess the magnitude and associated factors of thrombocytopenia among pregnant women attending antenatal care services at Dessie comprehensive and specialized hospital, Northeast Ethiopia. Methods: An institution-based cross-sectional study was conducted from February to March 2021. Using a systematic random sampling technique, a total of 294 pregnant women were enrolled in the study. Structured interviewer-administered questionnaires were used to collect socio-demographic and clinical data of study participants. Four ml of venous blood were collected from each pregnant woman and a complete blood count was determined using DIRUI BF 6500 automated hematology analyzer. Data were entered into Epidata version 4.6.0 and then exported into SPSS version 24.0. Multivariate logistic regression was used to assess the association between dependent and independent variables. P-value < 0.05 was considered to be statistically significant. Results: A total of 294 pregnant women who visited antenatal care services at Dessie comprehensive specialized hospital were included. The mean (±SD) age of the study participants was 29.7 (±6.1) years. The prevalence of thrombocytopenia among pregnant women was 9.9% (95% CI: 6.5, 13.6). A mild type of thrombocytopenia is the major type and accounted for 72.4% whereas moderate thrombocytopenia and severe thrombocytopenia accounted for 17.2% and 10.4% respectively among pregnant women. Multivariate logistic regression showed that urban residents (AOR: 0.206,95% CI, 0.055-0.748), gestational ages within the first trimester (AOR: 0.183, 95% CI, 0.057-0.593) and gestational ages within the second trimester (AOR = 0.264, 95% CI, 0.092-0.752) were significantly associated and independent predictors of thrombocytopenia in pregnant women. Conclusion: In this study, the prevalence of thrombocytopenia was 9.9% and the mild type of thrombocytopenia (72.4%) was higher than the other type of thrombocytopenia among pregnant women. In multivariate logistic regression analysis, residence and gestational age (trimester) were significantly associated with thrombocytopenia. Therefore, the platelet count should be routinely determined during the antenatal care visit for proper diagnosis and to minimize bleeding during and or after childbirth. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to explore the immunological characteristics and cytokine profile of the initial stage of type 1 diabetes. Patients and Methods: In total, 123 age- and sex-matched subjects with newly diagnosed classic type 1 diabetes mellitus (T1ADM), fulminant type 1 diabetes mellitus (FT1DM), and normal glucose tolerance (NGT) were enrolled. Serum cytokine levels were measured using Milliplex MAP multifactor detection. Results: There was a significant increase in the levels of transforming growth factor β (TGFβ 1) and TGFβ 2 and decrease in programmed death-1 (PD-1), PD ligand 1 (PD-L1), pro-inflammatory cytokines, and anti-inflammatory cytokines in type 1 diabetes patients compared with the NGT subjects (all P < 0.05). There was no significant difference in C-reactive protein (CRP) and blood routine indicators between the two groups. Type 1 diabetes was further divided into T1ADM and FT1DM subgroups. FT1DM patients had much higher CRP levels than T1ADM patients (4.90 [0.95– 26.05] mg/L vs 0.39 [0.20– 0.74] mg/L, P < 0.01). Blood routine results showed that the number of leukocytes was significantly increased in FT1DM compared with that in T1ADM (9.2 [5.1– 18.8] × 109 cells/L vs 5.4 [4.5– 6.7] × 109 cells/L, P < 0.01). In FT1DM patients, neutrophil% was increased, and lymphocyte% was declined significantly, compared with that in T1ADM patients (neutrophil%: 80.2 [59.2– 85.2]% vs 59.5 [54.8– 64.0]%; lymphocyte%: 18.3 [10.1– 32.3]% vs 32.6 [26.8– 35.9]%; both P < 0.01). However, there was no difference between FT1DM and T1ADM in cytokine profile except for the decrease in CTLA-4 in T1ADM (P < 0.05). Conclusion: Compared with T1ADM, CRP and leukocytes' levels were increased significantly in FT1DM, with an increase in neutrophil% and decline in lymphocyte%, suggesting that FT1DM may have more abrupt onset and occur as a more serious subtype of type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Introduction: Telehealth technologies for rural patients are increasingly being used to deliver care within the Department of Veterans Affairs (VA), and treatment of hepatitis C virus (HCV) is no exception. However, data evaluating outcomes with telehealth compared with specialty clinics in the era of direct-acting antiviral (DAA) agents is sparse.Methods: In a retrospective analysis, we compared treatment outcomes for patients receiving DAAs followed solely in a telehepatology clinic (telehealth) versus an in-person specialty care clinic (standard of care) at the VA Eastern Colorado Health Care System. Patients with decompensated cirrhosis (CTP-B or CTP-C) were excluded from the study as they were exclusively followed via standard of care. Provider overlap occurred between clinics and consisted of physician specialists (hepatology and infectious diseases), physician assistants and clinical pharmacists.Results: From 1 January 2014 to 31 December 2017, we treated 764 veterans for HCV infection. Standard of care was provided to 629 patients representing 654 treatment courses, and telehealth was provided to 135 patients representing 138 treatment courses. Sustained virologic response rates were not significantly different between the two clinics when looking at total treatment courses (93% telehepatology vs 89% specialty care, p = 0.203) and individual patients treated (95% telehepatology vs 93% specialty care, p = 0.377).Discussion: Hepatitis C treatment utilizing telehealth technologies to improve access to care does not negatively impact treatment outcomes when compared with specialty care clinics in the era of DAAs. [ABSTRACT FROM AUTHOR]

Background: There are no national data on hepatitis C virus awareness and burden among pregnant women to justify its routine screening. Objectives: To investigate awareness, seroprevalence and risk factors for hepatitis C virus infection among pregnant women in Nigeria. Methods: A total of 159 pregnant women from antenatal clinics across six geopolitical zones in Nigeria consented to anti-hepatitis C virus testing which was confirmed using polymerase chain reaction technique. Confirmed hepatitis C virus positive women were further tested for hepatitis B and HIV. Participants were evaluated for risk factors for hepatitis C virus. Odds ratios, adjusted odds ratios, and their 95% confidence intervals (CIs) were determined, and p-values of <0.05 were considered significant. Results: Of 159 participants, 77 (48.4%; 95% confidence interval = 38.2%–60.5%) were aware of hepatitis C virus infection and awareness of hepatitis C virus was associated with young age (odds ratio = 2.21; 95% confidence interval = 1.16–4.21), high educational level (odds ratio = 3.29; 95% confidence interval = 1.63–6.64), and participants' occupation (odds ratio = 0.51; 95% confidence interval = 0.26–0.99). In multivariable logistic regression, adjusted for confounders, the association between awareness of hepatitis C virus and participants' young age (adjusted odds ratio = 1.60; 95% confidence interval = 1.09–2.35; p = 0.018) and high educational level (adjusted odds ratio = 1.48; 95% confidence interval = 1.17–1.86; p = 0.001) remained significant. Hepatitis C virus seroprevalence was found to be 1.3% (95% confidence interval = 0.2%–4.5%). All (100.0%, 95% confidence interval = 12.1%–100.0%) the hepatitis C virus-positive participants and 99 (63.1%, 95% confidence interval = 51.3%–76.8%) hepatitis C virus-negative participants had identifiable hepatitis C virus risk factors. Dual seropositivity of anti-hepatitis C virus/anti-HIV and anti-hepatitis C virus/hepatitis B surface antigen each accounted for 0.6%. The most identified risk factors were multiple sexual partners (15.7%), shared needles (13.8%), and blood transfusion (11.3%). There was no significant association between the risk factors and hepatitis C virus positive status. Conclusion: Awareness of hepatitis C virus infection among pregnant women in Nigeria is low and those aware are positively influenced by young age and high educational level. The prevalence of hepatitis C virus infection is high and provides preliminary evidence to justify antenatal routine screening. [ABSTRACT FROM AUTHOR]

Background: Activation of the transforming growth factor beta (TGF-β) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is a dipeptide that can inhibit TGF-β synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-β levels among patients with diabetic nephropathy.Methods: We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30-299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-β level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-β.Results: The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-β and renal function measurements. Urinary TGF-β significantly decreased with carnosine supplement (- 17.8% of the baseline values), whereas it tended to increase with placebo (+ 16.9% of the baseline values) (between-group difference P < 0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects.Conclusions: These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-β level that serves as a marker of renal injury in diabetic nephropathy.Trial Registration: Thai Clinical Trials, TCTR20200724002 . Retrospectively Registered 24 July 2020. [ABSTRACT FROM AUTHOR]

Regular physical activity seems to have a positive effect on the microbiota composition of the elderly, but little is known about the added possible benefits of strenuous endurance training. To gain insight into the physiology of the elderly and to identify biomarkers associated with endurance training, we combined different omics approaches. We aimed to investigate the gut microbiome, plasma composition, body composition, cardiorespiratory fitness, and muscle strength of lifetime elderly endurance athletes (LA) age 63.5 (95% CI 61.4, 65.7), height 177.2 (95% CI 174.4, 180.1) cm, weight 77.8 (95% CI 75.1, 80.5) kg, VO2max 42.4 (95% CI 39.8, 45.0) ml.kg–1.min–1 (n = 13) and healthy controls age 64.9 (95% CI 62.1, 67.7), height 174.9 (95% CI 171.2, 178.6) cm, weight 83.4 (95% CI 77.1, 89.7) kg, VO2max 28.9 (95% CI 23.9, 33.9), ml.kg–1.min–1 (n = 9). Microbiome analysis was performed on collected stool samples further subjected to 16S rRNA gene analysis. NMR-spectroscopic analysis was applied to determine and compare selected blood plasma metabolites mostly linked to energy metabolism. The machine learning (ML) analysis discriminated subjects from the LA and CTRL groups using the joint predictors Bacteroides 1.8E + 00 (95% CI 1.1, 2.5)%, 3.8E + 00 (95% CI 2.7, 4.8)% (p = 0.002); Prevotella 1.3 (95% CI 0.28, 2.4)%, 0.1 (95% CI 0.07, 0.3)% (p = 0.02); Intestinimonas 1.3E-02 (95% CI 9.3E-03, 1.7E-02)%, 5.9E-03 (95% CI 3.9E-03, 7.9E-03)% (p = 0.002), Subdoligranulum 7.9E-02 (95% CI 2.5E-02, 1.3E-02)%, 3.2E-02 (95% CI 1.8E-02, 4.6E-02)% (p = 0.02); and the ratio of Bacteroides to Prevotella 133 (95% CI -86.2, 352), 732 (95% CI 385, 1079.3) (p = 0.03), leading to an ROC curve with AUC of 0.94. Further, random forest ML analysis identified VO2max, BMI, and the Bacteroides to Prevotella ratio as appropriate, joint predictors for discriminating between subjects from the LA and CTRL groups. Although lifelong endurance training does not bring any significant benefit regarding overall gut microbiota diversity, strenuous athletic training is associated with higher cardiorespiratory fitness, lower body fat, and some favorable gut microbiota composition, all factors associated with slowing the rate of biological aging. [ABSTRACT FROM AUTHOR]

Context: Postoperative hyperthermia, which may lead to cognitive decline, is a common complication of cardiovascular surgery with cardiopulmonary bypass (CPB).Aims: The aim of this study was to examine the effectiveness of perioperative intravenous acetaminophen on body temperature in adult patients after cardiovascular surgery with CPB.Settings and Design: This was a single-center retrospective study focusing on adult patients who underwent elective cardiovascular surgery with CPB at a university hospital in Japan.Subjects and Methods: Patients were divided into two groups based on whether they received acetaminophen perioperatively. In the acetaminophen group, 15 mg/kg intravenous acetaminophen solution was infused at 30 min after discontinuation of CPB and every 6 h after intensive care unit (ICU) admission.Statistical Analysis Used: The primary outcome was the maximum axillary temperature within 12 h after ICU admission. The effects of acetaminophen on postoperative body temperature were estimated by the standardization and inverse probability weighting using propensity scores.Results: A total of 201 patients were included in the final analysis (acetaminophen group, n = 101; non-acetaminophen group, n = 100). The maximum axillary temperature within 12 h after ICU admission was 37.20 ± 0.54°C in the acetaminophen group and 37.78 ± 0.59°C in the non-acetaminophen group. Acetaminophen lowered the standardized mean of primary endpoint (-0.54°C, 95% confidence interval, -0.69 to -0.38) compared to non-acetaminophen.Conclusions: Perioperative intravenous acetaminophen inhibited body temperature elevation after cardiovascular surgery with CPB, compared with the non-acetaminophen group. [ABSTRACT FROM AUTHOR]

Liver involvement in sickle cell disease (SCD) is often referred to as sickle cell hepatopathy (SCH) and is a complication of SCD which may be associated with significant mortality. This review is based on a round-table workshop between paediatric and adult hepatologists and haematologists and review of the literature. The discussion was prompted by the lack of substantial data and guidance in managing these sometimes very challenging cases. This review provides a structured approach for the diagnosis and management of SCH in children and young adults. The term SCH describes any hepatobiliary dysfunction in the context of SCD. Diagnosis and management of biliary complications, acute hepatic crisis, acute hepatic sequestration and other manifestations of SCH are discussed, as well as the role of liver transplantation and haemopoietic stem cell transplantation in the management of SCH. [ABSTRACT FROM AUTHOR]

Background: Direct-acting antivirals (DAAs) are current standard of HCV treatment (Rx). However, data remain lacking on real-world safety, patterns of biochemical, virologic responses, and sustained virologic response (SVR12) rate in geriatric patients. Aims: The present study assessed clinical presentation, safety, SVR12 rate, dynamic changes in HCV RNA, ALT, and AFP in geriatric patients (age ≥ 65 year old, G1) versus non-geriatric patients (G2) with chronic hepatitis C and received DAA treatment. Methods: This was a single-center, retrospective study on 183 patients with DAA Rx and 12-week post-Rx follow-up. Results: There were no significant differences in patterns of biochemical and virologic responses between the two groups. Undetectable HCV RNA rates were 67.2% versus 75.7% (p = 0.22) and 77.3% versus 84.3% (p = 0.24) at Rx week 2 and Rx week 4, respectively. The SVR12 rate was comparable in 2 groups, 94.1% (G1) versus 95.7% (G2, p = 0.64). ALT normalization rates were 91.2% versus 91.3% (p = 0.98), 92.6% versus 93.9% (p = 0.74), and 97.1% versus 97.4% (p = 0.89) at Rx week 2, post-Rx week12, and post-Rx week 24, respectively. AFP normalization was lower in G1 with 89.7% versus 95.7% (p = 0.12), 77.9% versus 87.8% (p = 0.08), and 79.4% versus 92.2% (p = 0.01), at Rx week 2, and post-Rx week 12, and post-Rx week 24, respectively. Both groups showed similar side effects profile including fatigue 11.8% versus 12.2% (p = 0.93) and headache 11.8% versus 13.9% (p = 0.68). Conclusion: Based on our real-world data, geriatric patients had excellent and comparable treatment outcomes with non-geriatric patients in safety and SVR12 rates to different DAA regimens. [ABSTRACT FROM AUTHOR]

Objective: Investigation of functional magnetic resonance (MR) imaging role in early diagnosis of diabetic nephropathy (DN) in patients with diabetes mellitus (DM) type 2, by quantification of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values. Material and methods: 10 healthy volunteers and 91 DM type 2 patients were scanned using diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) sequences. Patients were divided into four groups based on the estimated glomerular filtration value (eGFR). ADC and FA values, calculated in six regions of interest in each kidney (cortex and medulla), were compared to eGFR and laboratory parameters of renal function. Results: ADC values of DM patients were higher in the cortex than in the medulla (p < 0.01), while FA values were higher in the medulla (p = 0.284). Creatinine, cystatin C negatively correlated with ADC (cortex, medulla, parenchyma). Medullary FA were lower in DM patients and positively correlated with the eGFR (p = 0.049). Tractography showed disturbed structure in patients with impaired renal function. Discussion: Medullary FA value is a more sensitive parameter than parenchymal ADC in the early detection of renal damage in DM patients. ADC and FA values are significant in the diagnosis of DN; further research is needed for the update and refinement of the established recommendations. [ABSTRACT FROM AUTHOR]

Background: The impact of albumin-to-alkaline phosphatase ratio (AAPR) on prognosis in cancer patients remains uncertain, despite having multiple relevant studies in publication.Methods: We systemically compiled literatures from 3 databases (Cochrane Library, PubMed, and Web of Science) updated to May 24th, 2020. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed and synthesized using STATA 14, values were then pooled and utilized in order to assess the overall impact of AAPR on patient's prognosis.Results: In total, 18 studies involving 25 cohorts with 7019 cases were incorporated. Pooled results originated from both univariate and multivariate analyses (HR = 2.14, 95%CI:1.83-2.51, random-effects model; HR = 1.93, 95%CI:1.75-2.12, fixed-effects model; respectively) suggested that decreased AAPR had adverse effect on overall survival (OS). Similarly, pooled results from both univariate and multivariate analysis of fixed-effects model, evinced that decreased AAPR also had adverse effect on disease-free survival (DFS) (HR = 1.81, 95%CI:1.60-2.04, I2 = 29.5%, P = 0.174; HR = 1.69, 95%CI:1.45-1.97, I2 = 13.0%, P = 0.330; respectively), progression-free survival (PFS) (HR = 1.71, 95%CI:1.31-2.22, I2 = 0.0%, P = 0.754; HR = 1.90, 95%CI:1.16-3.12, I2 = 0.0%, P = 0.339; respectively), and cancer-specific survival (CSS) (HR = 2.22, 95%CI:1.67-2.95, I2 = 5.6%, P = 0.347; HR = 1.88, 95%CI:1.38-2.57, I2 = 26.4%, P = 0.244; respectively). Admittedly, heterogeneity and publication bias existed, but stratification of univariate meta-analytic results, as well as adjusted meta-analytic results via trim and fill method, all showed that AAPR still significantly correlated with poor OS despite of confounding factors.Conclusions: In summary, decreased AAPR had adverse effect on prognosis in cancer patients. As an inexpensive and convenient ratio derived from liver function test, AAPR might become a promising indicator of prognosis in human cancers. [ABSTRACT FROM AUTHOR]