Dietary selenium intake in relation to non-alcoholic fatty liver disease assessed by fatty liver index and hepatic steatosis index; a cross-sectional study on the baseline data of prospective PERSIAN Kavar cohort study.

BACKGROUND: There is limited and conflicting evidence on the association between selenium and non-alcoholic fatty liver disease (NAFLD). Therefore, the present population-based cross-sectional study aimed to explore the relationship between dietary selenium intake and the risk of NAFLD. METHODS: A total of 3026 subjects from the PERSIAN (Prospective Epidemiological Research Studies in IrAN) Kavar cohort study were included in the analysis. The daily selenium intake was evaluated using a semi-quantitative food frequency questionnaire, and energy-adjusted quintiles of selenium intake (µg/day) were calculated. NAFLD was defined as the fatty liver index (FLI) ≥ 60 or the hepatic steatosis index (HSI) > 36. The association between dietary selenium intake and NAFLD was evaluated using logistic regression analysis. RESULTS: The prevalence rates of NAFLD were 56.4% and 51.9%, based on the FLI and HSI markers, respectively. The odds ratios (ORs) for FLI-defined NAFLD were 1.31 (95% confidence interval (CI): 1.01-1.70) and 1.50 (95% CI: 1.13-1.99) for the fourth and fifth quintiles of selenium intake, respectively, after adjustment for sociodemographic variables, smoking status, alcohol drinking, physical activity, and dietary factors (P trend = 0.002). There was also a similar association between selenium intakes and HSI-defined NAFLD (OR = 1.34 (95% CI: 1.03-1.75) for the fourth quintile and OR = 1.50 (95% CI: 1.12-2.01) for the fifth quintile of selenium intake) (P trend = 0.006). CONCLUSION: In this large sample study, we observed a weak positive association between dietary selenium intake and NAFLD risk.

Quality of diet and odds of metabolic syndrome in Iranian adults: Baseline results from the PERSIAN Kavar cohort study (PKCS).

BACKGROUND AND AIMS: Metabolic Syndrome (MetS) is a major risk factor for cardiovascular diseases and type 2 diabetes mellitus. Diet quality has been associated with multiple chronic diseases. We aimed to investigate the association between the quality of diet and the odds of being diagnosed with MetS. METHODS AND RESULTS: This study was conducted cross-sectionally on baseline data of 2225 individuals from the PERSIAN Kavar Cohort Study (PKCS). The quality of diet was measured based on the Diet Quality Index - International (DQI-I), using Food Frequency Questionnaires. The association between DQI-I and MetS and its components was measured via logistic regression models in crude and adjusted models. We did not observe any association between DQI-I and MetS in the overall population. However, after adjustment for potential confounders, we found that male participants with higher DQI-I scores had a lower risk of MetS [adjusted odds ratio (OR) 95% confidence interval CI) = 0.62 (0.42-0.93)]. Moreover, analogous trends were observed with respect to some components of MetS, including elevated triglyceride (TG) [crude OR (95% CI) = 0.89 (0.70-0.98); adjusted OR = 0.82 (0.65-0.93)], lowered high-density lipoprotein cholesterol (HDL-c) [crude OR (95% CI) = 0.79 (0.57-0.99); adjusted OR = 0.76 (0.55-0.97)], and abnormal glucose homeostasis [crude OR (95% CI) = 0.80 (0.55-0.94); adjusted OR = 0.73 (0.51-0.91)] only in male participants, both before and after adjustment for potential confounders. CONCLUSION: In this study, we showed that higher adherence to a high-quality diet was associated with a lower chance of developing MetS in men. Biological gender might be responsible for the observed discrepancies.

A systematic review and meta-analysis of the global epidemiology of pediatric traumatic spinal cord injuries.

Despite being relatively rare, pediatric traumatic spinal cord injury (TSCI) is a debilitating event with high morbidity and long-term damage and dependency. This study aims to provide insight on the epidemiological characteristics of pediatric TSCI worldwide. The studies were included if they provided data for the pediatric population with the diagnosis of TSCI. Information sources included PubMed, Embase, Web of Science, and Scopus. All databases were searched from 1990 to April 2023. The quality of included studies was evaluated by Joanna Briggs Institute Critical Appraisal Tools. The results of the meta-analysis were presented as forest plots. PROSPERO Registration code: CRD42020189757. We identified 87 studies from 18 developed and 11 developing countries. Of the 87 studies evaluated, 52 studies were considered medium quality, 27 studies were considered high quality, and 8 studies were considered low quality. In developed countries, the proportion of TSCIs occurring in patients aged 0-15 years was 3% (95% CI: 2.2%; 3.9%), while in developing countries, it was 4.5% (95% CI: 2.8%; 6.4%). In developed countries, the pooled incidence of pediatric TSCI was 4.3/millions of children aged 0-15/year (95% CI: 3.1; 6.0/millions children aged 0-15/year) and boys comprised 67% (95% CI: 63%; 70%) of cases. The most prevalent level of injury was cervical (50% [95% CI: 41%; 58%]). The frequency of SCI Without Obvious Radiological Abnormality (SCIWORA) was 35% (95% CI: 18%; 54%) among children 0-17 years. The most common etiology in developed countries was transport injuries (50% [95% CI: 42%; 57%]), while in developing countries falls were the leading cause (31% [95% CI: 20%; 42%]). The most important limitation of our study was the heterogeneity of studies in reporting age subgroups that hindered us from age-specific analyses.   Conclusion: Our study provided accurate estimates for the epidemiology of pediatric TSCI. We observed a higher proportion of pediatric TSCI cases in developing countries compared to developed countries. Furthermore, we identified distinct epidemiological characteristics of pediatric TSCI when compared to adult cases and variations between developing and developed countries. Recognizing these unique features allows for the implementation of cost-effective preventive strategies aimed at reducing the incidence and burden of TSCI in children. What is Known: • Pediatric Traumatic Spinal Cord Injury (TSCI) can have profound physical and social consequences for affected children, their families, and society as a whole. • Epidemiological insights are vital for they provide the data and understanding needed to the identification of vulnerable populations, aiding in the development of targeted prevention strategies and effective resource allocation. What is New: • The estimated incidence of pediatric TSCI in developed countries is 4.3 cases per million children aged 0-15. The proportion of pediatric TSCI cases in relation to all-age TSCI cases is 3% in developed countries and 4.5% in developing countries. • The etiology of TSCI in pediatric cases differs between developing and developed countries. In developed countries, transport injuries are the most prevalent cause of pediatric TSCI, while falls are the least common cause. Conversely, in developing countries, falls are the leading cause of pediatric TSCI.

Influence of Garlic on the Glycemic Control and Lipid Profile in Animals with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Nonalcoholic fatty liver disease is the hepatic sign of metabolic syndrome. Here, we aimed to assess the effects of garlic and its major components on fasting plasma glucose, fasting insulin, and lipid profile levels in animal models of nonalcoholic fatty liver disease. A systematic search in PubMed, Scopus, ProQuest, and Web of Science was performed. After the screening process and data extraction, the pooled effect sizes were estimated using a random-effect model and stated as standardized mean differences and a 95% confidence interval. Out of 839 reports, 22 articles were included in the present study. The pooled results revealed that garlic and its components significantly decreased fasting plasma glucose (standardized mean difference: - 0.77, 95% confidence interval: - 1.42 to - 0.12, I2 : 58.85%), fasting insulin (standardized mean difference: - 1.88, 95% confidence interval: - 3.07 to - 0.69, I2 : 70.42%), serum triglyceride (standardized mean difference: - 1.01, 95% confidence interval: - 1.43 to - 0.59, I2 : 61.41%), cholesterol (standardized mean difference: - 1.00, 95% confidence interval: - 1.39 to - 0.60, I2 : 52.12%), and low-density lipoprotein cholesterol (standardized mean difference: - 0.98, 95% CI: - 1.63 to - 0.32, I2 : 71.58%) and increased high-density lipoprotein cholesterol (standardized mean difference: 1.05, 95% confidence interval: 0.52 to 1.58, I2 : 59.39%) levels. The type of animal, nonalcoholic fatty liver disease induction model, kind and duration of intervention, study model, and risk of bias were detected as possible sources of heterogeneity across studies. We conclude that garlic and its major components have a favorable impact on glycemic control and lipid profile in diet-induced nonalcoholic fatty liver disease animal models.

Association of plant-based dietary patterns with metabolic syndrome: baseline results from the Persian Kavar cohort study (PKCS).

Plant-based diets (PBDs) have gained a positive reputation among experts as a solution to combat the epidemic of MetS. A total of 2225 healthy Iranian individuals aged 35-70 years were considered eligible to be included in this cross-sectional investigation. Various dietary, anthropometric, and biochemical assessments were conducted using standard, valid methods/tools. Relevant PBD scores were calculated using three a posteriori indices, including the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). Our findings showed that women with the highest adherence to hPDI had a lower chance of MetS. Also, participants in the top tertiles of hPDI were more likely to have a lower risk of low serum HDL-c and abnormal glucose homeostasis. Additionally, a significant increasing trend was observed for low serum HDL-c across tertiles of uPDI. Our observations suggest that healthful-rich plant foods may have a protective effect against MetS, especially in women.

Indirect Spinal Canal Decompression Using Ligamentotaxis Compared With Direct Posterior Canal Decompression in Thoracolumbar Burst Fractures: A Prospective Randomized Study.

Background: There is still no standard of care to manage thoracolumbar burst fractures. With all the recent advances, posterior approaches are still one of the mainstays of treatment. On the other hand, while spinal canal decompression in neurological impaired patients is an important goal of treatment, its technique remains controversial.This study compared the effects of direct laminectomy decompression against ligamentotaxis/indirect canal decompression on neurological and radiographic improvements. Methods: A prospective double-blind randomized clinical trial was conducted on 60 thoracolumbar burst-fracture patients meeting our inclusion and exclusion criteria. They were randomized into 2 treatment arms: (1) direct decompression using laminectomy and (2) indirect decompression using ligamentotaxis/distraction. Each patient was observed for 6 months, and their neurological and radiographical data were collected prospectively. Statistical analysis was done by the Student t test, Friedman test, Mann Whitney-U test, Wilcoxon ranked test, and 1-way analysis of variance. Results: Among 60 patients enrolled in our study, each treatment arm had an improvement in Frankel scores but there was no difference between the groups at any given time. After 6 months of surgery, local sagittal kyphosis improved in both groups (from 32.2 to 7.43 and 29.93 to 8.77 for the indirect and direct groups, respectively), as well as anterior vertebral height ratio (from 57.73 to 70.7 and 62.17 to 66.27 for the indirect and direct group, respectively) and posterior vertebral height ratio (from 61.17 to 74.87 and 64 to 67.5 for the indirect and direct group, respectively). For between-group comparisons after 6 months, there was a significant difference only for posterior vertebral height ratio (P = 0.040). Conclusion: Posterior approaches with ligamentotaxis have shown to be safe and may present the same outcome as direct decompression techniques using wide laminectomy.

Comparing Therapeutic versus Prophylactic Enoxaparin Therapy in Severe COVID-19 Patients: A Randomized Clinical Trial.

Background: Coronavirus disease 2019 (COVID-19) has been associated with a hypercoagulopathy state; however, the efficacy of different anticoagulant regimens in preventing thrombotic events is not clear. We aimed to compare therapeutic versus prophylactic enoxaparin therapy in severe COVID-19 patients. Methods: In this single-center, open-label, randomized controlled trial, adult patients with severe COVID-19 presentations and an increased D-dimer level of more than 4 times the normal upper limit were randomly assigned to receive either prophylactic or therapeutic dose of enoxaparin. All patients were observed for at least 4 months regarding the overall survival as the primary outcome. Hospitalization duration, the need for intensive care unit (ICU) admission, the need for mechanical ventilation, and major adverse events (MAEs) were also analyzed as the secondary outcomes. Survival analysis was done via Kaplan-Meier curves and the Log-rank test. Cox regression was used, adjusting for baseline variables. Results: Overall, 237 patients (152 men and 85 women) were randomized to either arm (121 to prophylactic and 116 to therapeutic groups). The mortality rate was 27 (22.3%) and 52 (44.8%) in prophylactic and therapeutic arms, respectively. Prophylactic enoxaparin was associated with better survival in the log-rank test (P < 0.001; HR, 0.42). Additionally, a significantly lower rate of ICU admission, a lower rate of MAEs, and shorter hospitalization were observed in the prophylactic arm (P < 0.001, P = 0.009, and P = 0.028, respectively). Conclusion: The results of the current study were in favor of anticoagulant treatment with prophylactic doses of enoxaparin. Still, due to the limitations of this paper, we suggest that these findings be treated cautiously.

Comparison of laboratory-based and non-laboratory-based WHO cardiovascular disease risk charts: a population-based study.

BACKGROUND: Determining the risk of Cardiovascular Disease (CVD) is a necessity for timely preventive interventions in high-risk groups. However, laboratory testing may be impractical in countries with limited resources. This study aimed at comparison and assessment of the agreement between laboratory-based and non-laboratory-based WHO risk charts models. METHODS: This study was performed using the baseline data of 8138 participants in the pars cohort study who had no history of CVD and stroke. The updated 2019 WHO model was used to determine the 10-year fatal and non-fatal CVD risks. In general, there are two types of new WHO risk prediction models for CVD. The scores were determined based on age, sex, smoking status, diabetes, Systolic Blood Pressure (SBP), and total cholesterol for the laboratory-based model and age, sex, smoking status, SBP, and Body Mass Index (BMI) for the non-laboratory-based model. The agreement of these two models was determined via kappa statistics for the classified risk (low: < 10%, moderate: 10-< 20%, high: ≥ 20%). Correlation coefficients (r) and scatter plots was used for correlation between scores. RESULTS: The results revealed very strong correlation coefficients for all sex and age groups (r = 0.84 for males < 60 years old, 0.93 for males ≥ 60 years old, 0.85 for females < 60 years old, and 0.88 for females ≥ 60 years old). In the laboratory-based model, low, moderate, and high risks were 76.10%, 18.17%, and 5.73%, respectively. These measures were respectively obtained as 77.00%, 18.08%, and 4.92% in the non-laboratory-based model. Based on risk classification, the agreement was substantial for males < 60 years old and for both males and females aged ≥ 60 years (kappa values: 0.79 for males < 60 years old, 0.65 for males ≥ 60 years old, and 0.66 for females ≥ 60 years old) and moderate for females < 60 years old (kappa = 0.46). CONCLUSIONS: The non-laboratory-based risk prediction model, which is simple, inexpensive, and non-invasive, classifies individuals almost identically to the laboratory-based model. Therefore, in countries with limited resources, these two models can be used interchangeably.

Rectus Sheath Hematoma in COVID-19 Patients as a Mortal Complication: A Retrospective Report.

Background: Rectus sheath hematoma is a rare self-limited presentation that has become a concern in hospitalized COVID-19 patients receiving anticoagulant therapies. Method: A retrospective multicentric study was conducted in referral hospitals affiliated with the Tehran University of Medical Science, Tehran, Iran, between June and August 2021. Patients with a confirmed diagnosis of COVID-19 that were complicated with rectus sheath hematoma during hospitalization were included. Median (lower quartile to upper quartile) was used to report the distribution of the results. Result: This study was conducted on nine patients with confirmed COVID-19 pneumonia, including eight females and one male. The severity of viral pneumonia was above average in eight patients. The median age and median body mass index were 65 (55.5 to 78) years and 29.38 (23.97 to 31.71) kg/m2. The duration of anticoagulant therapy was 10 (6 to 14) days, and the median length of hospital stay was 20 (10 to 23.5) days. Rectus sheath hematoma occurred after a median reduction of 4 (2.7 to 6.6) units in blood hemoglobin. Although 66.7% received ICU care and all of them were under full observation in well-equipped hospitals, the mortality rate was 55.6%. Conclusion: In summary, increased levels of inflammatory markers such as lactic acid dehydrogenase along with an abrupt decrease in blood hemoglobin in COVID-19 patients should be considered as predisposing factors for rectus sheath hematoma, especially in patients with moderate to severe COVID-19 pneumonia under anticoagulant therapy. This complication had been considered a self-limited condition; however, it seems to be fatal in patients with COVID-19 pneumonia. Further studies in larger sample sizes should be conducted to find out suitable management for this complication.

Socioeconomic inequalities in prevalence, awareness, treatment and control of hypertension: evidence from the PERSIAN cohort study.

BACKGROUND: Elevated blood pressure is associated with cardiovascular disease, stroke and chronic kidney disease. In this study, we examined the socioeconomic inequality and its related factors in prevalence, Awareness, Treatment and Control (ATC) of hypertension (HTN) in Iran. METHOD: The study used data from the recruitment phase of The Prospective Epidemiological Research Studies in IrAN (PERSIAN). A sample of 162,842 adults aged > = 35 years was analyzed. HTN was defined according to the Joint National Committee)JNC-7(. socioeconomic inequality was measured using concentration index (Cn) and curve. RESULTS: The mean age of participants was 49.38(SD = ± 9.14) years and 44.74% of the them were men. The prevalence of HTN in the total population was 22.3%(95% CI: 20.6%; 24.1%), and 18.8%(95% CI: 16.8%; 20.9%) and 25.2%(95% CI: 24.2%; 27.7%) in men and women, respectively. The percentage of awareness treatment and control among individuals with HTN were 77.5%(95% CI: 73.3%; 81.8%), 82.2%(95% CI: 70.2%; 81.6%) and 75.9%(95% CI: 70.2%; 81.6%), respectively. The Cn for prevalence of HTN was -0.084. Two factors, age (58.46%) and wealth (32.40%), contributed most to the socioeconomic inequality in the prevalence of HTN. CONCLUSION: The prevalence of HTN was higher among low-SES individuals, who also showed higher levels of awareness. However, treatment and control of HTN were more concentrated among those who had higher levels of SES, indicating that people at a higher risk of adverse event related to HTN (the low SES individuals) are not benefiting from the advantage of treatment and control of HTN. Such a gap between diagnosis (prevalence) and control (treatment and control) of HTN needs to be addressed by public health policymakers.

Translation and validation of the Persian version of Godin Leisure-Time Exercise Questionnaire in patients with multiple sclerosis.

STUDY DESIGN: Psychometric study. OBJECTIVE: The purpose of this study is to translate, culturally adapt and evaluate the validity and reliability of the Persian (Farsi) version of GLTEQ in patients with multiple sclerosis. METHODS: This study had three phases, including translation of the questionnaire into Persian and making cultural adaptation, evaluation of pre-final version of questionnaire's comprehensibility in a pilot study, and investigation of reliability and validity of the final version of the translated questionnaire. Content validity, and convergent validity (correlations among the Persian version of GLTEQ and Global physical activity questionnaire (GPAQ), and international physical activity questionnaire (IPAQ)) and after all test-retest reliability were studied. RESULTS: The subjects were 87 MS patients. The Persian version demonstrated moderate to good convergent validity; the correlation coefficient between the Persian version and GPAQ was r=0.64 (p<0.001), and between the Persian version and IPAQ was r=0.59 (p<0.001). The test-retest reliability was strong (Intra-class Correlation (ICC) value ranged between 0.908 and 0.992). Besides, its face validity and content validity were acceptable. CONCLUSIONS: The Persian version of GLTEQ is a valid and reliable instrument to assess physical activity in patients with MS. This questionnaire can be a step toward standardization of physical activity measurement in patients with MS. Also, in research, it provides the possibilities to carry on a comparative study across cultures using the same outcome measure.

Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver transplantation: a cross-sectional study.

BACKGROUND: Genetic abnormalities might have important role in pathogenesis of hepatic steatosis after liver transplantation. We aimed to investigate association between genetic variations in transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, proprotein convertase subtilisin/kexin type 9 (PCSK9) rs505151 and proprotein convertase subtilisin/kexin type 7 (PCSK7) rs2277287 with hepatic steatosis in liver transplant recipients. METHODS: In a cross-sectional study, adult (> 18 years) liver transplant recipients who were referred for their routine post-transplant follow-up between June 2018 and September 2018 were included in the study. Hepatic steatosis in transplant recipients was assessed by controlled attenuation parameter (CAP). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to study TM6SF2 rs58542926, PCSK7 rs2277287 and PCSK9 rs505151 genotypes. RESULTS: 107 liver transplant recipients were included. There was no association between different genotypes of PCSK9 rs505151 and PCSK7 rs2277287 with hepatic steatosis in liver transplant recipients (P value > 0.05). The presence of TT genotype of TM6SF2 rs58542926 was higher in patients with hepatic steatosis measured by CAP after liver transplantation. In patients with moderate and severe hepatic steatosis (grade 2 and 3 steatosis), AG + GG genotypes of PCSK9 rs505151 were more prevalent than AA genotype (OR 8.667; 95% CI 1.841-40.879; P value = 0.004) compared to patients with mild steatosis (grade 1). In multivariate regression model, AG + GG genotypes of PCSK9 rs505151 were associated with moderate and severe steatosis in liver transplant recipients (OR 5.747; 95% CI 1.086-30.303; P value = 0.040). CONCLUSIONS: Genetic variations in TM6SF2 rs58542926 and PCSK9 rs505151 might be associated with hepatic steatosis in liver transplant recipients.

The Effect of hsa-miR-451b Knockdown on Biological Functions of Gastric Cancer Stem-Like Cells.

Numerous researches have extensively studied factors such as microRNAs that lead to cancer. Thus, the current study's purpose is to investigate the biological consequences of hsa-miR-451b inhibition on the properties and functions of gastric cancer stem-like cells. First, gastric cancer stem-like cells were transfected by hsa-miR-451b inhibitor then we used real-time RT-PCR to evaluate its effect on the expression of hsa-miR-451b and two of its direct target genes, Stemness markers such as KLF4, SOX2, CD44, OCT3/4 and NANOG genes and finally Akt, PI3K, Bcl-2, Bax, CASP3 and PCNA genes involved in apoptosis. Here, we conducted a DNA Laddering assay to investigate apoptosis. The level of the MMP-2 and -9 Activities and Migration were examined by Zymography and Transwell invasion assay. HUVEC cells were used to investigate angiogenesis. The outcomes revealed that the level of the MMP-2 and -9 Activities, migration and angiogenesis decreased, but apoptosis was induced by inhibiting hsa-miR-451b. Evaluating KREMEN1 and CASK expression showed that the former increased, and the latter dropped under hsa-miR-451b inhibition. Also, upregulation of the KLF4 and SOX2 and downregulation of the CD44, OCT3/4, and NANOG decreased Self-renewal ability of gastric cancer stem cells under hsa-miR-451b inhibition. Even, under hsa-miR-451b inhibition, downregulation of Akt, PI3K, Bcl-2 and PCNA as well as upregulation of Bax and CASP3 revealed a movement towards apoptosis in MKN-45 stem-like cells. In summary, hsa-miR-451b is an oncomir in the carcinogenesis of gastric cancer stem-like cells and may be suggested as an appropriate therapeutic target for future gastric cancer treatment.

Biofluid Biomarkers in Traumatic Brain Injury: A Systematic Scoping Review.

Emerging evidence suggests that biofluid-based biomarkers have diagnostic and prognostic potential in traumatic brain injuries (TBI). However, owing to the lack of a conceptual framework or comprehensive review, it is difficult to visualize the breadth of materials that might be available. We conducted a systematic scoping review to map and categorize the evidence regarding biofluid-based biochemical markers of TBI. A comprehensive search was undertaken in January 2019. Of 25,354 records identified through the literature search, 1036 original human studies were included. Five hundred forty biofluid biomarkers were extracted from included studies and classified into 19 distinct categories. Three categories of biomarkers including cytokines, coagulation tests, and nerve tissue proteins were investigated more than others and assessed in almost half of the studies (560, 515, and 502 from 1036 studies, respectively). S100 beta as the most common biomarker for TBI was tested in 21.2% of studies (220 articles). Cortisol was the only biomarker measured in blood, cerebrospinal fluid, urine, and saliva. The most common sampling time was at admission and within 24 h of injury. The included studies focused mainly on biomarkers from blood and central nervous system sources, the adult population, and severe and blunt injuries. The most common outcome measures used in studies were changes in biomarker concentration level, Glasgow coma scale, Glasgow outcome scale, brain computed tomography scan, and mortality rate. Biofluid biomarkers could be clinically helpful in the diagnosis and prognosis of TBI. However, there was no single definitive biomarker with accurate characteristics. The present categorization would be a road map to investigate the biomarkers of the brain injury cascade separately and detect the most representative biomarker of each category. Also, this comprehensive categorization could provide a guiding framework to design combined panels of multiple biomarkers.

Viral metagenomic analysis of fecal samples reveals an enteric virome signature in irritable bowel syndrome.

BACKGROUND: Changes in the enteric microbiota have been suggested to contribute to gastrointestinal diseases, including irritable bowel syndrome. Most of the published work is on bacterial dysbiosis with meager data on the role of the virome in irritable bowel syndrome and other gastrointestinal diseases. In the current study, we therefore aimed to investigate the viral community composition of the gut and test for potential dysbiosis linked to irritable bowel syndrome. RESULTS: A metagenomics analysis on fecal samples of 50 individuals - 30 of whom met the Rome IV criteria for IBS and 20 healthy controls- was conducted. There was a noticeable alteration in viral taxa observed in association with irritable bowel syndrome when compared to healthy individuals - where some eukaryotic viral taxa noticeably prevail over others. We observed a significant decrease in the diversity and abundance of enteric virome particularly in eukaryotic viruses of Megavirales in patients with irritable bowel syndrome. CONCLUSIONS: These findings shed light on a new hypothesis that the alteration of the viral taxa contributes to the pathogenesis of irritable bowel syndrome and related symptoms, and therefore, pave the way for developing a new diagnostic biomarker or anti-viral drugs for the treatment of irritable bowel syndrome.

The combination of sofosbuvir and daclatasvir is effective and safe in treating patients with hepatitis C and severe renal impairment.

BACKGROUND AND AIM: Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir-containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir-based treatment in patients with severe renal impairment, including those on hemodialysis. METHOD: We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m2 from 13 centers in Iran. Patients were treated for 12 weeks with a single daily pill containing 400-mg sofosbuvir and 60-mg daclatasvir. Patients with cirrhosis were treated for 24 weeks. Response to treatment was evaluated 12 weeks after end of treatment (sustained viral response [SVR]). ClinicalTrials.gov identifier: NCT03063879. RESULTS: A total of 103 patients were enrolled from 13 centers. Seventy-five patients were on hemodialysis. Thirty-nine had cirrhosis and eight were decompensated. Fifty-three were Genotype 1, and 27 Genotype 3. Twenty-seven patients had history of previous failed interferon-based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow-up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed. CONCLUSIONS: The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.

Effects of partial internal biliary diversion on long-term outcomes in patients with progressive familial intrahepatic cholestasis: experience in 44 patients.

PURPOSE: Progressive familial intrahepatic cholestasis (PFIC) is a hereditary disease characterized by cholestasis, which may cause jaundice, severe pruritus, and cirrhosis in the later stages. By the invention of biliary diversion methods, these patients were prevented from undergoing liver transplant. Using biliary diversion techniques, the entero-hepatic cycle was interrupted. This lowers the bile acid pool and resolves the pruritus. Herein, we report 44 cases of PFIC who underwent partial internal biliary diversion (PIBD) and long-term follow-up of these children. This comprises the largest case series of PIBD. METHODS: All patients were diagnosed by liver biopsy as PFIC before the operation. All underwent cholecysto colic bypass by jejunal interposition due to severe pruritus unresponsive to medication. Laboratory blood tests, sonography, and physical exam were done before and after the operation once every 3 months. Besides, a questionnaire was designed to ask the patients about the symptoms after the operation, and a pruritus score was measured using the 5D-itch scale. RESULTS: 44 children (25 boys, 19 girls), between 1.75 and 27.5 years (at the time of this study) were followed for a median period of 54 months. Age at operation ranged from 2 months to 18 years, with a median of 29 months. Of these children, 14 were lost to follow up. Results showed a significant decrease in pruritus and sleep disturbance after the surgery (p < 0.001). Also, jaundice decreased from 82.1 before to 7.1% following the surgery. 50% of the patients became medication-free at follow-up. CONCLUSION: PIBD is a safe procedure which helps non-cirrhotic children preserve their liver function. Therefore, PIBD prevents them from undergoing liver transplant. Effective results were achieved in terms of severe pruritus and jaundice, and children were able to regain their sleep patterns. It also avoided external stoma, which is more convenient from the patient's point of view.

New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial).

Hepatitis C virus (HCV) infection induces autophagy, but the virus assimilates the autophagic response into its own life cycle. Chloroquine (CQ) is an autophagy inhibitor that is clinically used to treat malaria. The aims of this pilot clinical trial were to evaluate the therapeutic potential and short-term safety of CQ in patients with chronic HCV genotype 1, who were unresponsive to a combination of pegylated interferon alpha and ribavirin. Ten non-responders to previous antiviral treatment(s) were randomized to receive either CQ (150 mg daily for 8 weeks) or placebo, and were followed for 4 weeks after CQ therapy. HCV RNA load and plasma alanine transaminase (ALT) levels were measured at baseline, week 4 (initial response), week 8 (end-of-treatment response), and at the end of 12 weeks. A significant decrease in HCV RNA after the treatments (week 8) was observed in all patients in the CQ group (P = 0.04). However, HCV RNA levels increased within 4 weeks after discontinuation of CQ treatment although they were still lower than baseline. In addition, the ALT normalized during treatment in the CQ group. However, this response was also lost after treatment cessation. This study provides preliminary evidence that CQ is possibly a safe treatment option for HCV non-responders.

Thyroid diseases in children and adults with celiac disease: A cross-sectional study.

Background: There are few reports evaluating different factors, including the severity of duodenal histopathological findings and serological levels of celiac disease (CD), in increasing the probability of thyroid diseases (TD) in adults and children with CD, so, we designed this research. Methods: CD was defined as Marsh type 2 or higher in duodenal histopathology and serological levels of anti-transglutaminase antibodies (anti-tTG) equal to or greater than 18 IU/ml. To assess the likelihood of TD in CD patients, logistic regression analysis was employed. Results: 538 patients were included in this study. Of these, 354 (65.8%) were females and 184 (34.2%) were males. 370 (68.8%) patients were children. Overall, 57 (10.6%) patients had TD, of which 49 (9.1%) had hypothyroidism and 8 (1.5%) had hyperthyroidism. Adults had a significantly higher probability of developing TD than children (OR 1.9; 95% CI 1.1-3.4; P = 0.03). The odds of developing TD were also significantly higher in patients with family marriage in parents (OR 2.3; 95% CI 1.1-4.7; P = 0.03). Other variables such as gastrointestinal symptoms, anti-tTG levels, and severity of Marsh classification did not exhibit a substantial rise in the likelihood of TD development. Conclusion: The study findings indicated that the likelihood of developing TD in CD patients can be linked to advancing age and having family marriage in parents, while there was no significant association observed with anti-tTG levels, severity of histological damage, and gastrointestinal symptoms.