Gamma-glutamyl Transpeptidase Research Articles

Reference intervals for 23 common biochemical parameters during pregnancy and the first six postpartum months.

The concentration of many biochemical parameters changes significantly during pregnancy and the postpartum period, causing a need for specific reference values for biochemical parameters in these life periods. We have collected blood samples in pregnancy week 18, 28 and 36 and six weeks, four months and six months postpartum from 139 healthy women. Blood samples from 59 healthy never-pregnant women were included as controls. Serum samples were analyzed for 23 common biochemical parameters and reference intervals for pregnancy and postpartum periods were computed with the non-parametric method in accordance with recommendations from IFCC and CLSI. The dynamics of different biochemical parameters during and after pregnancy vary considerably between parameters. Some analytes like serum amylase and HDL cholesterol do not differ from never-pregnant values. Of the 23 parameters, serum alkaline phosphatase, chloride, gamma-glutamyl transferase and sodium and urea which were still significantly changed at six months postpartum compared to never-pregnant women. The physiological changes related to pregnancy and lactation have profound effects on biochemical parameters, denoting the use of specific reference intervals for both pregnancy and the postpartum period.

Acute Coronary Syndrome After Aneurysmal Subarachnoid Hemorrhage: Incidence, Risk Factors and Impact on the Outcome

Background and Objectives: Development of acute coronary syndrome (ACS) after aneurysmal subarachnoid hemorrhage (aSAH) strongly affects further neuro-intensive care management. We aimed to analyze the incidence, risk factors and clinical impact of ACS in aSAH patients. Materials and Methods: This retrospective analysis included 855 aSAH cases treated between 01/2003 and 06/2016. The occurrence of ACS during 3 weeks of aSAH was documented. Patients’ demographic, clinical, radiographic and laboratory characteristics at admission were collected as potential ACS predictors. The association between ACS and the aSAH outcome was analyzed as the occurrence of cerebral infarcts in the computed tomography scans and unfavorable outcome (modified Rankin scale > 3) at 6 months after aSAH. Univariable and multivariable analyses were performed. Results: ACS was documented in 28 cases (3.3%) in the final cohort (mean age: 54.9 years; 67.8% females). In the multivariable analysis, there was a significant association between ACS, an unfavorable outcome (adjusted odds ratio [aOR] = 3.43, p = 0.027) and a borderline significance with cerebral infarcts (aOR = 2.5, p = 0.066). The final prediction model for ACS occurrence included five independent predictors (age > 55 years [1 point], serum sodium < 142 mmol/L [3 points], blood sugar ≥ 170 mg/dL [2 points], serum creatine kinase ≥ 255 U/L [3 points] and gamma-glutamyl transferase ≥ 36 U/L [1 point]) and showed high diagnostic accuracy for ACS prediction (AUC = 0.879). Depending on the cumulative score value, the risk of ACS in the cohort varied between 0% (0 points) and 66.7% (10 points). Conclusions: ACS is a rare, but clinically very relevant, complication of aSAH. The development of ACS can reliably be predicted by the presented prediction model, which enables the early identification of aSAH individuals at high risk for ACS. External validation of the prediction model is mandatory.

Efficacy of Screening and Brief Intervention for Alcohol Misuse in Opioid Agonist Maintenance Treatment: A Randomized Clinical Trial

ABSTRACT Alcohol misuse is common in persons on opioid agonist maintenance treatment (OAMT). We tested the efficacy of screening and brief intervention (SBI) for harmful/hazardous alcohol use in buprenorphine/naloxone (BNX)-assisted OAMT. It was a double-blind, parallel-group, randomized trial, where 150 participants with alcohol misuse (Alcohol Use Disorder Identification Test – AUDIT 8–19) on BNX were allocated equally to receive either a single session SBI or screening and brief advice (control). Participants were followed up at three months. The primary outcome was the change in AUDIT; other outcomes were risk transition, change in the frequency of heavy drinking, days of abstinence from alcohol, Gamma-glutamyl transferase (GGT) levels, non-prescription opioid use, and adherence to BNX. Follow-up data was gathered from 138 participants. SBI participants had a higher reduction in AUDIT scores at the follow-up (F = 129. 173, df = 1, p < .001, ηp 2 =.469). A higher proportion of participants transitioned to a low-risk category in the SBI group. The SBI group showed a higher reduction in heavy drinking and days of alcohol abstinence. Although the proportion of persons with normal serum GGT increased in both groups, the difference was not significant at the follow-up. The SBI group performed better in non-prescription opioid use and BNX adherence.

Predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma: nomograms based on deep learning analysis of gadoxetic acid-enhanced MRI.

This study aimed to develop nomograms for predicting post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC), using deep learning analysis of Gadoxetic acid-enhanced hepatobiliary (HBP) MRI. This retrospective study analyzed patients who underwent gadoxetic acid-enhanced MRI and hepatectomy for HCC between 2016 and 2020 at two referral centers. Using a deep learning algorithm, volumes and signal intensities of whole non-tumor liver, expected remnant liver, and spleen were measured on HBP images. Two multivariable logistic regression models were formulated to predict PHLF, defined and graded by the International Study Group of Liver Surgery: one based on whole non-tumor liver measurements (whole liver model) and the other on expected remnant liver measurements (remnant liver model). The models were presented as nomograms and a web-based calculator. Discrimination performance was evaluated using the area under the receiver operating curve (AUC), with internal validation through 1000-fold bootstrapping. The study included 1760 patients (1395 male; mean age ± standard deviation, 60 ± 10 years), with 137 (7.8%) developing PHLF. Nomogram predictors included sex, gamma-glutamyl transpeptidase, prothrombin time international normalized ratio, platelets, extent of liver resection, and MRI variables derived from the liver volume, liver-to-spleen signal intensity ratio, and spleen volume. The whole liver and the remnant liver nomograms demonstrated strong predictive performance for PHLF (optimism-corrected AUC of 0.78 and 0.81, respectively) and symptomatic (grades B and C) PHLF (optimism-corrected AUC of 0.81 and 0.84, respectively). Nomograms based on deep learning analysis of gadoxetic acid-enhanced HBP images accurately stratify the risk of PHLF. Question Can PHLF be predicted by integrating clinical and MRI-derived volume and functional variables through deep learning analysis of gadoxetic acid-enhanced MRI? Findings Whole liver and remnant liver nomograms demonstrated strong predictive performance for PHLF with the optimism-corrected area under the curve of 0.78 and 0.81, respectively. Clinical relevance These nomograms can effectively stratify the risk of PHLF, providing a valuable tool for treatment decisions regarding hepatectomy for HCC.

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Abstract 4135517: Echocardiographic Biomarkers Enhance Mortality Predictions in Cirrhosis Patients

Introduction: Cirrhosis, a late-stage liver disease, is associated with numerous systemic complications, making long-term mortality prediction challenging. Traditional models like Child-Pugh and MELD are primarily designed for short-term (3-month) mortality. This study evaluates the impact of incorporating echocardiographic (echo) variables in predicting long-term mortality in cirrhosis patients. Methods: A retrospective cohort study was conducted using data from 60 patients with clinically diagnosed cirrhosis from Hippokration Hospital, Greece, spanning 2018 to 2022. Patients were followed for up to 52 months. Exclusion criteria included pre-existing cardiovascular diseases and significant co-morbidities. Patients were categorized into survived to end of study (n=31) and died during study (n=29) groups. Outcomes were analyzed using multivariate logistic regression and Cox proportional hazards models, and include parameters for age, blood pressure, lab-based biomarkers (potassium, pro-brain natriuretic peptide, hemoglobin, platelet count, aspartate transaminase, gamma-glutamyl transferase, uric acid), and echo/ecg measurements (QT interval, left ventricular (LV) ejection fraction, LV global longitudinal strain (GLS), left atrial GLS, annulus velocities, and E/A ratio). Results: The multivariate logistic regression model (MELD+) that included echo variables showed a 10% improvement in area under the curve (AUC: 0.901) compared to the MELD model alone (AUC: 0.817). MELD+ improved risk classification accuracy by nearly 10% with a conservative threshold. The Cox proportional hazards model with MELD+ also demonstrated superior performance (AUC: 0.923; C-index: 0.875; Brier Score: 0.097) compared to the MELD model alone (AUC: 0.892; C-index: 0.831; Brier Score: 0.134). The MELD+ model showed less variation in hazard ratio confidence intervals, indicating more consistent risk estimation. Conclusion: Incorporating echocardiographic measurements enhances the accuracy of long-term mortality predictions in cirrhosis patients. These findings suggest that cardiac imaging should be considered in risk assessments for cirrhosis patients, particularly for predicting survival beyond three months.

Loncastuximab tesirine in previously treated diffuse large B-cell lymphoma: A plain language summary of the LOTIS-2 study.

This article provides a plain-language summary of the results of a clinical trial called the LOTIS-2 study.The LOTIS-2 study included 145 participants with an aggressive type (one that forms, grows, or spreads quickly) of non-Hodgkin lymphoma called diffuse large B-cell lymphoma (a type of blood cancer), or DLBCL for short, whose disease came back or did not respond after 2 or more previous treatments. The LOTIS-2 study was conducted from August 2018 to September 2022.Participants received loncastuximab tesirine, also referred to as Lonca, for up to 1year, or longer if the treatment was working, and their health was monitored. The primary purpose of the LOTIS-2 study was to find out if participants' lymphoma shrank partially or completely after receiving Lonca. A total of 145 participants who were treated with Lonca lived a median (meaning the middle value in a set of numbers) of 9.5months after starting Lonca treatment. The lymphoma shrank partially or completely in nearly half of participants and shrank completely in 1 in 4 participants. Among participants whose disease either shrank partially or completely in response to Lonca treatment, responses happened relatively quickly, with a median time to response (the time between starting treatment and when the participant's lymphoma either partially or completely shrank) of 41days. In these participants, the lymphoma did not grow or come back for a median of 13.4months. Researchers estimated that 83% of participants whose disease shrank completely remained disease free for at least 1year.Nearly all participants had a side effect from Lonca treatment. The most common side effects were abnormal liver tests (increased gamma-glutamyl transferase), decreased white blood cells (neutropenia), and decreased platelets (thrombocytopenia). One in 4 participants had their treatment stopped due to side effects. The most common side effects that resulted in participants needing to stop Lonca treatment were abnormal liver tests (increased gamma-glutamyl transferase), swelling in the arms or legs (peripheral edema), swelling in an individual spot (localized edema), and fluid around the lungs (pleural effusion). These results show that Lonca is a treatment option with controllable side effects for many patients with DLBCL whose disease did not respond or came back after 2 or more previous treatments. For participants whose lymphoma completely shrank while taking Lonca, those responses to treatment occurred quickly and lasted for over a year.

Exploring Risk Factors of Type 2 Diabetes Mellitus Using Decision Tree and Random Forest Models: Baseline Data From Kharameh Cohort Study

Background and aims: Identifying subjects that are at risk of type 2 diabetes mellitus (T2DM) and predicting the associated risk factors are highly important. Thus, this study aimed to explore the risk factors and find the prediction model for T2DM using decision trees (DTs) and random forest (RF) models. Methods: This cross-sectional study is a part of the Kharameh Cohort Study. Kharameh Cohort is a part of the Fars Cohort, which started in 2014 with 10663 people aged 40–70. In this study, the risk factors of T2DM were explored using two data mining methods. Accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were applied to evaluate the models. The data were statistically analyzed using R software. Results: The DT modeling showed that age, triglycerides (TG), physical activity, systolic blood pressure, low-density lipoproteins (LDL), and body mass index (BMI) were the most associated factors in D2MT, while applying RF revealed that fasting blood sugar, cholesterol, creatinine, TG, gamma-glutamyl transferase physical activity, BMI, and LDL were the most effective on T2DM. The RF model was superior to the DT based on the applied criteria. Sensitivity, specificity, accuracy, and AUC for the RF were 73.4, 70.10, 73.5, and 79.1. These findings for the DT were 63.8, 69.7, 62.8, and 66.8, respectively. Conclusion: Based on the inferences, a strong association was found between several risk factors and the risk of T2DM. Therefore, predictive analytics using the RF model can be applied to identify the risk factors of other chronic diseases.

Rare carcinoma of the ampulla of Vater with mixed histologies: A case report

The current case is about a 62-year-old female presented with persistent fever for 10 days and yellowing of the skin for 5 days at our outpatient clinic. Laboratory tests revealed elevated levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and &amp;gamma;-glutamyl transpeptidase. Abdominal computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography revealed a mass in the ampulla of Vater, as well as dilatation of the intra- and extra-hepatic bile and pancreatic ducts. The patient underwent pancreaticoduodenectomy under general anesthesia. Post-operative pathological and immunohistochemical results confirmed a tumor located in the ampulla, measuring 1.5 &amp;times; 1 &amp;times; 1 cm. The main component of the tumor was a moderately differentiated pancreaticobiliary adenocarcinoma (ADC), combined with squamous cell carcinoma (SCC) as well as small cell neuroendocrine carcinoma (SCNEC). The cancer tissue infiltrated the entire intestinal wall, with no invasion of microvessels, lymphatic vessels, or nerves observed. Until 46 months later, there was no tumor recurrence or distant metastasis. We present an uncommon case of ADC of the ampulla of Vater combined with SCC and SCNEC. Carcinoma of the ampulla of Vater may have mixed histological components; therefore, in cases of ampullary carcinoma, appropriate specimen collection is necessary, and further studies with more focus on histological origins are required.

Association between ethylene oxide exposure and osteoarthritis risk mediated by oxidative stress: evidence from NHANES 2013-2020.

Ethylene oxide is extensively used for sterilizing medical equipment, and its carcinogenicity has been well documented. Furthermore, the onset of multiple diseases, including diabetes and hypertension, has been demonstrated to be associated with exposure to this compound. However, its association with osteoarthritis risk remains elusive. The study analyzed data from the National Health and Nutrition Examination Survey from 2013-2020, which included 6088 American adults, among whom 763 (12.5%) were diagnosed with osteoarthritis. We utilized a weighted generalized linear model to assess the correlation between ethylene oxide exposure levels and osteoarthritis risk. This study used mediation analysis to assess the functions of indicators of oxidative stress (γ-glutamyl transferase) and inflammation (alkaline phosphatase, white blood cell count, neutrophil count, and lymphocyte count) as mediators of how ethylene oxide affects osteoarthritis. The analysis revealed that elevated levels of ethylene oxide were correlated with a higher risk of osteoarthritis, even when controlling for other variables. The odds of developing osteoarthritis were 1.86 times higher in the fourth quartile than in the first quartile (95% confidence interval: 1.20-2.88, P = 0.0097, P for trend = 0.0087). Subgroup analyses indicated consistency across different cohorts. Mediation analysis revealed that oxidative stress (γ-glutamyl transferase), not inflammation, was the mediator linking ethylene oxide levels to the risk of osteoarthritis. This finding in a sample of American adults revealed a direct relationship between exposure to ethylene oxide and increased osteoarthritis risk. Oxidative stress has been suggested as a possible biological explanation for osteoarthritis caused by ethylene oxide.

The relationship between fixed dental prostheses, blood lead levels, and liver function: Mediating effects and gender differences

Metal alloys, pure titanium, metal-ceramics, and ceramic materials are used for fixed dental prostheses, which contained lead and potentially involved hepatotoxicity. To investigate the connection between fixed dental prostheses, blood lead levels, and liver function. A cross-sectional study enrolled 3624 American adults were conducted. Multivariate linear regression models and smooth curve fittings were used to describe correlations between the number of fixed dental prostheses, blood lead levels, and four liver function markers. Mediation analysis suggested an intermediary association of blood lead levels between prosthesis count and liver function. Here, number of fixed dental prostheses was significantly positive correlated with blood lead levels (p < 0.0001), but specifically negative correlated with alanine aminotransferase, lactate dehydrogenase, and gamma glutamyl transferase levels in males. Moreover, mediation analysis confirmed a mediating role for blood lead levels in the association between the number of prostheses and alanine aminotransferase levels in males only, with a mediation effect rate of 74.27% (p = 0.0020). An increased count of fixed prostheses is associated with changes in liver function markers in a gender-dependent manner, with blood lead levels serving as a potential mediator in males.

Identifying causal relationships between 35 blood and urine biomarkers and urologic cancers: MR-meta combined with Bayesian colocalization Mendelian randomization analysis

BackgroundBlood and urine biomarkers have been associated with urologic tumors, but their causal relationship with urologic tumors is unclear.MethodsWe performed a bidirectional Mendelian randomization (MR) analysis of the association between 35 blood and urine biomarkers and urological tumors in our discovery cohort. A Bayesian weighting approach was used to validate the positive results identified in the discovery cohort, and steiger filtering analysis was used to distinguish causality from reverse causality. Bayesian colocalization analysis was used to analyze which single nucleotide polymorphisms (SNPs) specifically co-located between the positive blood and urine biomarkers and the disease phenotypes were driven, and MR-positive results from the discovery cohort and the validation cohort were combined using the MR-meta method.ResultsSeveral blood and urine biomarkers were found to be significantly and causally associated with urologic cancers. Notably, calcium (OR: 1.34, 95%CI 1.10–1.63, P = 0.0040) and sex hormone-binding globulin (SHBG) (OR: 0.81, 95%CI 0.70–0.95, P = 0.0092) were associated with bladder cancer; gamma glutamyl transferase (GGT) (OR: 0.91, 95%CI 0.83–0.99, P = 0.0209), lipoprotein A (Lp(a)) (OR: 1.12, 95%CI 1.01–1.24, P = 0.0399), and insulinlike growth factor 1 (IGF 1) (OR: 1.10, 95%CI 1.01–1.20, P = 0.0220) were linked to prostate cancer (PCa); non albumin protein (OR: 0.78, 95%CI 0.65–0.93, P = 0.0065) and total protein (OR: 0.80, 95%CI 0.64–0.99, P = 0.0380) were linked to renal cancer; and apolipoprotein A (Apo-A) (OR: 0.56, 95%CI 0.32–0.98, P = 0.0426) and urate (OR:1.89, 95%CI 1.03–3.47, P = 0.0399) were associated with renal pelvis cancer. These associations were validated in an independent cohort, with GGT, IGF 1, and Lp(a) being consistently linked to PCa.ConclusionThis study identified significant biomarkers associated with urological cancers in blood and urine. These include GGT, IGF 1, and Lp(a), which are strong biomarkers for PCa. In addition, the findings of this study provide evidence for a handful of risk and protective factors for the development of urologic cancers.

Critical risk factors analysis of infection-associated hemophagocytic lymphohistiocytosis in children.

To analyze the critical factors of infection-associated Hemophagocytic lymphohistiocytosis (HLH) in children, so as to provide theoretical basis for clinicians to evaluate the disease condition, formulate treatment plan and improve prognosis.This study is a retrospective analysis. 60 cases of children with infection-associated HLH were divided into critical and non-critical groups based on the presence of multiple organ dysfunction syndrome (MODS), and the clinical characteristics and laboratory data of the two groups of children were analyzed. A multifactor logistic regression analysis model was used to assess the independent risk factors affecting critical illness in children with infection-associated HLH, and the Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the predictive value of risk factors for critical illness in children with infection-associated HLH. Children in the critical group with HLH had a younger age at onset. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), D-dimer (DD), and triglycerides (TG) were significantly higher in the critical group, while albumin (ALB) was significantly lower, showing statistical significance (P < 0.05). Multifactorial logistic regression analysis of age, ALB, and TG showed that younger age and lower ALB were associated with a higher risk of MODS in children with infection-associated HLH, with age and ALB being independent risk factors for critical illness. ALB predicted the ROC area under the curve for critical children with infection-associated HLH was 0.765 (95% CI: 0.643-0.888, P = 0.011), with the optimal cut-off value being 32.50g/L (sensitivity = 68.3%, specificity = 84.2%); age predicted the ROC area under the curve for critical children with infection-associated HLH was 0.711 (95% CI: 0.570-0.851, P = 0.009), with the optimal cut-off value being 1.50 years (sensitivity = 70.7%, specificity = 68.4%). This study suggests that younger patients and those with hypoalbuminemia among infection-related HLH patients are more likely to develop MODS. In the future, verification will be required through large-scale, multi-center studies.

Associations between glycemic status and the ratio of γ-glutamyl transferase to HDL-C in middle-aged women.

The ratio of γ-glutamyl transferase to HDL-C (GGT/HDL-C) has been proposed as a discriminator of metabolic syndrome. The purpose of this study was to elucidate the relationship between GGT/HDL-C and glycemic status in women. The subjects were 18,218 middle-aged women who had received annual health checkups in their workplaces. They were divided by habitual alcohol intake into nondrinkers, occasional drinkers, regular light drinkers, and regular heavy drinkers. In overall subjects, hemoglobin A1c level and prevalence of diabetes tended to be higher in subjects with higher GGT/HDL-C, and GGT/HDL-C tended to be higher with an increase of alcohol intake. The odds ratio for hyperglycemia in subjects with vs. subjects without high GGT/HDL-C tended to be lower with an increase of alcohol intake, and the association between high GGT/HDL-C and hyperglycemia was significantly weaker in regular heavy drinkers than in nondrinkers. In middle-aged women, there were positive associations of GGT/HDL-C with alcohol intake and glycemic status, and the association between GGT/HDL-C and glycemic status tended to be weaker with an increase of alcohol intake. Thus, alcohol use should be taken into account when GGT/HDL-C is used as a discriminator of diabetes.

Maternal and Cord Blood Levels of Metals and Fetal Liver Function

Exposure to metals during pregnancy has been associated with adverse birth outcomes, but its impact on fetal liver function remains poorly understood. This study for the first time aimed to investigate the association between maternal and umbilical cord blood Metals levels and umbilical liver enzymes. A comprehensive analysis was conducted on 450 mother-newborn pairs in 2022, measuring 13 Metals in serum samples from pregnant women during the third trimester and umbilical cord blood samples. Regression analyses were utilized to examine the relationship between levels of maternal and umbilical cord blood Metals and the levels of gamma-glutamyl transferase (GGT), umbilical alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). G-comp analyses evaluated the combined effect of metals exposure on umbilical liver enzymes. Elevated levels of certain Metals in cord blood and maternal samples were positively linked with increased umbilical GGT, ALP, ALT, and AST levels. Notably, zinc (Zn) levels in cord blood exhibited an inverse correlation with umbilical liver enzyme levels. Furthermore, g-comp analyses revealed significant positive associations between exposure to metals mixtures and umbilical liver enzyme levels. An increase of one quartile in the mixture of maternal and umbilical Metals was linked with 99.45 U/L (95% CI:37.72, 161.19, p < 0.01), 2.79 (95% CI: 0.92, 4.65, p < 0.01), and 87.17 (95% CI: 53.96, 120.38, p < 0.01) increase in ALP, ALT and GGT levels. Further examination of the weight of Metals revealed As, Cd, Ni, Pb, Hg and Cr with the highest positive effects and Zn with the highest negative effect in the mixture effect on the umbilical liver enzyme. In summary, our results underscore the potential influence of prenatal heavy metal exposure on fetal liver function.

Allometric fat mass index and alanine aminotransferase attenuate the associations of platelet parameters with lung cancer risk

We have previously shown that body mass index attenuates a positive association of platelet count (PLT) and inverse of mean platelet volume (MPV) with lung cancer risk in men. It is unclear whether fat mass, lean mass, or liver function tests (LFTs) show similar attenuations. Using bioelectrical impedance measurements (UK Biobank cohort) and multivariable Cox proportional hazards models, we examined the associations of allometric fat-mass index (AFI, fat mass adjusted for height), allometric lean-mass index (ALI, fat-free mass adjusted for height and fat mass), and LFTs with lung cancer risk and their multiplicative and additive interactions with platelet parameters. Based on 1573 lung cancer cases in men and 1473 in women with body composition measurements (1541 in men; 1428 in women with biomarker measurements), AFI in women, ALI in both sexes, alanine aminotransferase (ALT) and total bilirubin in men were inversely associated, while gamma-glutamyl transferase in men and alkaline phosphatase in both sexes were positively associated with lung cancer risk. Only AFI and ALT interacted inversely with PLT and positively with MPV in men. The attenuation of the associations of platelet parameters with lung cancer risk by high-AFI and high-ALT in men suggests that adiposity-related factors hinder lung-cancer-related platelet associations.

Clinical and Epidemiological Features of Pediatric COVID-19: A Retrospective Study.

There is a demand for additional data regarding the impact of coronavirus disease 2019 (COVID-19) on the pediatric population. This study sought to determine the clinical and epidemiological features of pediatric COVID-19 in Iran. A retrospective study was performed to assess medical records of children with COVID-19 admitted to Abuzar Hospital in Ahvaz (Iran). Their clinical and demographic data were recorded. In this study, 600 medical records of pediatric COVID-19 patients were evaluated. Over 50% of them were boys. Mild, moderate, and severe manifestations of COVID-19 were identified in 250, 200, and 150 children, respectively. Patients with severe or moderate COVID-19 had substantially higher levels of various inflammatory markers (C-reactive protein (CRP), fibrinogen, and d-dimer), alanine transaminase (ALT), creatine kinase (CPK), blood urea nitrogen (BUN), neutrophils, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine (Cr), bilirubin, and gamma-glutamyl transferase (GGT) compared to children with mild COVID-19 (p < 0.001); they also had lower levels of lymphocytes, hemoglobin (Hb), and vitamin D than patients with mild COVID-19 (p < 0.001). In addition, children with severe or moderate COVID-19 had a notably higher incidence of fever or dry cough and longer hospital stays than those with mild COVID-19 (p < 0.001). The prevalence of malnutrition and anemia in patients was 50.6% and 31.5%, respectively. A significant proportion of children who were underweight and stunted experienced moderate to severe COVID-19. Furthermore, there was a considerably higher prevalence of malnutrition, anemia, and vitamin D insufficiency, or deficiency in children with moderate-to-severe COVID-19 compared to patients with mild COVID-19 (p < 0.001). The outcomes of this study revealed a significantly higher prevalence of malnutrition, anemia, vitamin D insufficiency or deficiency, elevated liver and kidney function test results, and increased inflammatory markers in children with moderate to severe COVID-19 compared to those with mild COVID-19.

Curcumin on Human Health: A Comprehensive SystematicReview and Meta-Analysis of 103 RandomizedControlled Trials.

The aim of this meta-analysis was to determine the effect of curcumin on a range of health outcomes. PubMed, EMBASE, Scopus, and Web of Science were searched from inception until September 2023. Randomized clinical trials (RCTs) that compared the effect of Curcuma longa L. with placebo were considered eligible. The risk of bias and overall certainty of evidence were assessed using the Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development, and Evaluation (GRADE), respectively. We meta-analyzed the effect sizes across eligible studies using the random-effects model. In total, 103 RCTs on 42 outcomes were included, incorporating a total population of 7216 participants. Overall, 23 out of 42 (55%) outcomes reported statistically significant effect sizes. The credibility of the evidence was rated as high for fasting blood sugar (FBS), C-reactive protein (CRP), high-density lipoprotein (HDL), and weight. The remaining outcomes presented moderate (waist circumference [WC], hip circumference [HC], body mass index [BMI], insulin, Homeostatic Model Assessment for Insulin Resistance [HOMA-IR], quantitative insulin-sensitivity check index [QUICKI], leptin, gamma-glutamyl transferase [GGT], glutathione [GSH], and superoxide dismutase [SOD]), low (14 outcomes), or very low (14 outcomes) evidence. In conclusion, curcumin supplementation can modify FBS and some glycemic indices, lipid parameters, as well as inflammatory and oxidative parameters. This updated summary of the accumulated evidence may help inform clinicians and future guidelines regarding medical and scientific interest in curcumin. However, due to limitations in the methodological quality of the included studies, well-designed and long-term RCTs with large sample sizes are needed. Trial registration: PROSPERO: CRD42021251969.

The Efficacy of a Combination of Milk Thistle, Artichoke, and Green Tea in the Treatment of Biliary Sludge: An Interventional Prospective Open Study

Background: In Western countries, 10–20% of adults have gallstones, of which about 1–3% of patients are symptomatic for biliary colic. The treatment with ursodeoxycholic acid is debated. Silymarin is emerging nowadays as a natural substance with choleretic and beneficial properties, useful in the case of gallbladder sludge. Aim: The aim of our study was to evaluate the efficacy of supplementation with a mix of natural compounds (milk thistle 150 mg, artichoke 150 mg, and green tea 150 mg) in patients affected by biliary sludge in reducing biliary colic and biliary sludge and improving lipid profiles after 3 months of treatment compared to a control group. Patients and Methods: This was an interventional open study on 65 consecutive adult patients (23 M/42 F; mean age 61.0 ± 18.7 years) affected by biliary sludge without indication for surgery, admitted to the Internal Medicine Department of San Carlo di Nancy Hospital Rome. Forty patients were treated with milk thistle 150 mg, artichoke 150 mg, and green tea 150 mg, 2 capsules/day for three months, and followed up for abdominal ultrasound, the frequency of occurrence of biliary colic, and blood tests. Twenty-five control group patients were followed up for abdominal ultrasound, the frequency of occurrence of biliary colic, and blood tests after 3 months. Results: In Group A, we observed a disappearance of biliary sludge in 32.4% (12/37) of patients compared to 8.7% in the control group (p &lt; 0.05). In 32.4% of treated patients, we report a reduction in biliary sludge. There were no side effects during treatment. In both groups, we registered a significant reduction in transaminases and gamma-glutamyl transferase (γ-GT) (p &lt; 0.05). No significant modification of the lipid profile was observed. Conclusions: The treatment with a mix of natural compounds (milk thistle, artichoke, and green tea) in patients affected by symptomatic biliary colic resulted in efficacy and safety in reducing biliary sludge, biliary colic, and transaminases levels after three months of treatment. The limitations of this study include a small number of patients and the absence of long-term follow up after the end of treatment.

Role of Obeticholic Acid, a Farnesoid X Receptor Agonist, in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Background. Obeticholic acid (OCA) has emerged as a promising drug in the management of nonalcoholic fatty liver disease (NAFLD). This meta-analysis aimed to analyse the therapeutic effect of OCA on NAFLD. Methods. Randomized controlled trials (RCTs) involving patients with NAFLD receiving OCA in the intervention arm and placebo in the control arm were searched throughout the electronic databases. The primary outcomes were changes in non-invasive markers of hepatic fibrosis and liver histology. The secondary outcomes included changes in liver enzymes, metabolic parameters from baseline and adverse events (AEs). Results. Four RCTs involving 1,278 subjects met the inclusion criteria. Over 6 weeks to 18 months of clinical use, OCA outperformed placebo in resolving definite nonalcoholic steatohepatitis (odds ratio [OR] 1.60, 95% confidence interval [CI] [1.04-2.48], p=0.03) and improving fibrosis (OR 2.23, 95% CI [1.56-3.20], p<0.0001), hepatocellular ballooning (OR 1.83, 95% CI [1.35-2.47], p<0.0001) and lobular inflammation (OR 1.62, 95% CI [1.13-2.32], p=0.009). OCA did not improve the enhanced liver fibrosis score and steatosis better than placebo, and demonstrated superior efficacy compared with the placebo in reducing serum alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase levels. Although a favourable effect of OCA over placebo was seen in body-weight reduction, the OCA use was associated with adverse changes in lipid parameters. Except for the greater risk of pruritus and constipation, the AE profile was comparable between the OCA and placebo groups. Conclusions. OCA has a favourable efficacy in improving liver histology and liver enzymes. However, the worsening of lipid parameters and other AEs with the OCA use warrants further investigation.