[Association of metal/metalloids exposure with abnormal liver function among occupational population in a mining area of Hunan Province:a prospective study].

OBJECTIVE: To investigate the association of metals/metalloids exposure with risk of liver disfunction among occupational population in Hunan Province, and to explore the potential dose-response relationship. METHODS: In 2017, a mining area in Hunan Province was chosen as the research site, and eligible workers were recruited as study subjects. General demographic characteristics, levels of 23 metals/metalloids in plasma and urine, and liver function index(total bilirubin(TBIL), alanine amino transferase(ALT), globulin(GLB) and γ-glutamyl transferase(GGT)) were obtained by questionnaire, physical examination and laboratory tests. Participants were followed up in 2018, 2019 and 2020 respectively. Cox proportional risk model was used to evaluate the relationship between metal/metalloids exposure and risk of liver disfunction, and dose-response relationship curves were plotted by using the restricted cubic spline function. RESULTS: A total of 891 employees were recruited in the study, 576(65.0%)were aged ≤45 years, 832(93.4%) were male and 530(59.5%) worked as smelters. After adjusting various factors such as age, gender, BMI, type of work, education, smoking, alcohol consumption, diet, stress, medical history, exercise and tea consumption, positive correlations were found between plasma tungsten(HR=4.90, 95%CI 1.17-20.48) and urinary barium(HR=1.07, 95%CI 1.02-1.12) levels with abnormally elevated TBIL levels. Additionally, a significant association was observed between plasma thallium and the risk of elevated ALT levels(HR=11.15, 95%CI 1.97-63.29). CONCLUSION: Plasma tungsten and thallium, along with barium found in urine, are risk factors for the development of abnormally elevated liver function indices in occupational groups.

Eribulin, Child-Pugh score, and liver-function tests: lessons from pivotal breast cancer studies 301 and 305.

BACKGROUND: The recommended starting dose of eribulin in patients with hepatic impairment is based on the Child-Pugh score, largely informed by a pharmacokinetic study of 18 patients. In the pivotal studies of eribulin in metastatic breast cancer (Study 301 and Study 305 [EMBRACE]), entry criteria and dose modifications were based on liver-function test (LFT) results rather than Child-Pugh score. In populations such as patients with metastatic breast cancer, in which metastatic infiltration is the predominant cause of hepatic impairment, using Child-Pugh score may be problematic; in clinical practice, it has been more common for oncologists to make dosing decisions based on LFTs. To address this, the effects of abnormal baseline LFT results on eribulin efficacy and safety were investigated. METHODS: In this pooled post hoc analysis, 1062 patients who were randomized to receive eribulin in Studies 301 and 305 were divided into 4 groups: (A) no elevated LFT results (no liver impairment); (B) increased levels of aspartate aminotransferase and/or alanine aminotransferase; (C) decreased albumin and/or increased levels of aspartate aminotransferase and/or alanine aminotransferase but not increased bilirubin; and (D) increased bilirubin. Patients were subcategorized by presence of liver metastasis. Drug exposure, dose intensity, and treatment-emergent adverse events (TEAEs) were analyzed. RESULTS: Eribulin mesylate mean dosage was 0.82 (group A)-0.65 mg/m2/week (group D). Group D had shorter treatment, more dose reductions/delays, more TEAEs leading to dose modifications, and numerically lower objective response rates and clinical benefit rates versus groups A-C. TEAE rates leading to dose modification were similar between group D (45.5%) and groups A-C (range, 43.5-54.9%) in the absence of liver metastases, but higher in group D (91.3%) compared with groups A-C (range, 41.7-54.3%) if liver metastases were present. CONCLUSIONS: Mild elevations in bilirubin levels were associated with increased toxicity and a greater requirement for dose modifications. Based both on these study data and existing recommendations, we propose a novel scheme to guide initial dose selection in patients with metastatic breast cancer and hepatic impairment that is based on LFTs rather than Child-Pugh score.

FeasibilitystudyofMRIDEAL-IQsequenceinevaluatingliverfunctionofpatientswithlivercirrhosis / 实用放射学杂志

Objective ToinvestigatethefeasibilityofassessingliverfunctiongradingbyIDEAL-IQsequenceon1.5T MR.Methods The patientswhowereclinicallydiagnosedaslivecirrhosisandunderwent1.5T MRIDEAL-IQsequenceinourhospitalfrom February 2016toDecember2017wereanalyzedretrospectively.TheyweredividedintoA,BandCgradesaccordingtotheChild-Pughgrading standardofliverfunction.Finally,therewere30patientsinChild-PughA,25patientsinChild-PughBand16patientsinChild-Pugh C.ThefatratiomapsandR2?relaxationratemapswereusedtomeasuretheliverfatcontentandironcontentbythetwoobservers onAW4.6workstation,respectively.ThemeanvaluesofthefatfractionsandtheR2?valuesweremeasuredandcomparedbyusing K ruskal-W allis H testamongthethreegroups.Then,thegroupAandBwerecombinedtoestablishthepredictivemodelindiagnosingthegroup Cbyusingthe L o g istic regressionanalysis,whichcombinedthefatfractionandR2?value.TheROCcurvewasdrawntoobtainedtheAUC,and calculatedthesensitivityandthespecificitywiththeoptimalthreshold.Results Thereweregoodconsistencyofmeasurementdata betweenthetwoobserves(ICC>0.8).ThefatfractionandR2?valueincreasedwiththedecreaseoftheliverfunction.Thefatfractionsofthe Child-PughA,BandCgroupwere(3.58±0.91)%,(3.64±1.20)%,(6.87±3.91)%,respectively.TheR2?valuesoftheChild-Pugh A,BandCgroupswere(33.31±11.80)Hz,(38.00±13.31)Hz,(58.98±44.54)Hz,respectively.TheAUCofwhichcombinedfat fractionandR2?valuediagnosingChild-PughCwas0.843.Thesensitivityandthespecificitywere81.8% and81.3%,respectively. Conclusion The1.5T MRIDEAL-IQsequencecanbeusedtoevaluatetheliverreserveunctionoflivercirrhosispatientsaccording ffatfractionandR2?value,especiallyfortheChild-PughCcirrhosis patientswithhighsensitivityandspecificity.

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1-Risk Myelodysplastic Syndrome-A Small, Investigative Study.

BACKGROUND: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. AIM: To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. METHOD: Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. RESULTS: 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. DISCUSSION: In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis.

Safety of dronedarone in routine clinical care.

OBJECTIVES: The aim of this study was to examine mortality and liver disease among patients exposed to dronedarone. BACKGROUND: There has been concern about the safety of dronedarone, especially for patients with heart failure and permanent atrial fibrillation (AF). There have also been suspicions about liver toxicity. METHODS: All 174,995 patients with a diagnosis of AF during 2010 to 2012 were identified in the Swedish Patient Register. Of these, 4,856 patients had received dronedarone according to the Swedish Drug Register, and 170,139 patients who had not were used as a control population. Mean follow-up was 1.6 years, with a minimal follow-up of 6 months. RESULTS: Patients prescribed dronedarone were younger (age 65.5 years vs. 75.7 years, p < 0.0001) and healthier than control patients. The annual mortality rate among patients who received dronedarone was 1.3% compared with 14.0% in the control population. There were no sudden cardiac deaths and no deaths related to liver failure among patients who received treatment with dronedarone. After propensity score matching and adjustment for cofactors, patients who received dronedarone had lower mortality than other AF patients (hazard ratio [HR]: 0.41; 95% confidence interval [CI]: 0.33 to 0.51). Dronedarone patients with heart failure had lower mortality than other heart failure patients (HR: 0.40; 95% CI: 0.30 to 0.53). They also had lower mortality than expected from the general population (standardized mortality ratio: 0.67; 95% CI: 0.55 to 0.78), which indicates the selection of low-risk patients. The risk of liver disease was not increased (HR: 0.57; 95% CI: 0.34 to 0.92). CONCLUSIONS: Dronedarone, as prescribed to AF patients in Sweden, has not exposed patients to increased risks of death or liver disease.

Glicemia, proteinograma e perfil de alguns componentes bioquímicos séricos de cabritos da raça Bôer / Glycemic, protein profile and serum biochemical profile in Bôer goat kids

Os cabritos recém-nascidos sofrem diversas adaptações à vida extrauterina que afetam diferentes funções orgânicas, pois precisam produzir calor, iniciar a atividade muscular e buscar alimento. Todos estes eventos levam a modificações em diversos constituintes sanguíneos, como proteínas e parâmetros bioquímicos séricos. Outros estudos demonstraram estas variações, mas sem se estender além do período neonatal até a fase de animais jovens. Objetivou-se testar a hipótese de que ocorre variação doproteinograma, dos componentes bioquímicos e da glicemia de cabritos desde o nascimento até 75 dias de vida em função da adaptação à vida extrauterina. Para atingir estes objetivos, foram colhidas amostras de sangue de 25 cabritos nascidos de partos normais, independentemente do sexo. As variáveis séricas proteína total (PT), albumina, α-globulina, β-globulina, γ-globulina, onde se incluem a imunoglobulina G (IgG), aspartatoaminotransferase (AST), fosfatase alcalina (FA), gamaglutamiltransferase (GGT), creatinina, ureia, e glicemia foram determinadas nos momentos zero (logo após o nascimento), dois, sete, 15, 30 e 75 dias pós-parto. Observaram-se diferenças significativas em todas as variáveis entre os momentos, mas somente a concentração de creatinina foi maior que aquelas dos demais momentos, nos tempos zero e de dois dias pós-nascimento, devido, provavelmente, à imaturidade da função renal em animais neonatos. Os constituintes sanguíneos dos cabritos tiveram variações no período avaliado, relacionados a causas fisiológicas e nutricionais.

The newborn goat kids suffer several adjustments to life outside the uterus that affect different body functions that they need to produce heat, muscle activity and start searching for food. All these events lead to changes in several blood constituents such as proteins and serum biochemical parameters. Other studies have shown these variations, but not extend beyond the neonatal period to phase in young animals. The aim was to test the hypothesis that there is variation of the protein profile, and biochemical components of blood glucose in goat kids from birth to 75 days of life in terms of adaptation to extra uterine life. To achieve these objectives have been collected blood samples from 25 goats born by normal delivery, regardless of their sex. The variables serum total protein (TP), albumin, α-globulin, β-globulin, γ-globulin, which includes the immunoglobulin G (IgG), aspartate (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), creatinine and urea, and glucose were determined at times zero (immediately after birth), two, seven, 15, 30 and 75 days old. We observed significant differences in all variables between times, but only the creatinine concentration was higher than those of other moments in time zero and two days old, probably due to immaturity of renal function in newborn animals. The blood constituents of the kids had variations in the study period, related to physiological and nutritional causes.

Evaluation of Clinical Effect of Serum FT_3,FT_4 in Patients With Liver Cirrhosis / 中国医师杂志

Objective To study the relationship between changes of contents of serum free-triiodothyronine(FT 3),Free-thyroxine(FT 4) and liver cirrhosis,and analyse it's clinical significanec.Methods The concentration of serum FT 3 and FT 4 were determined by radioimmunoassay in 69 patients with liver cirrhosis,compared with liver function classification(Child-Pugh).Results Contents of serum FT 3,FT 4 in cirrhosis patients were markedly lower than that of controls(P