Correlation of Serum Bilirubin with Clinical and Pathological Characteristics of Patients with IgA Nephropathy.

OBJECTIVE: To investigate the correlations of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) with various clinical indicators and pathological features of patients with IgA nephropathy (IgAN). METHODS: Patients diagnosed with IgAN were included and divided into low and high TBIL/DBIL/IBIL groups. Correlation analysis was performed to assess the relationships between the bilirubin indices and other clinical and pathological variables. Logistic regression was applied to identify the independent risk factors of mesangial cell proliferation (corresponding to M1 in the Oxford classification of IgAN). RESULTS: Totally 192 patients with IgAN were included, and the patient clinical indicators were compared between the different bilirubin subgroups. Compared to the groups with higher TBIL, DBIL, and IBIL levels, groups with lower values of these bilirubin indices exhibited a higher 24-hour urine protein (24hUP) concentration but a lower proportion of males as well as reduced total protein, albumin, haemoglobin, and glutamic-pyruvic transaminase levels (p < 0.05). Moreover, the low-DBIL group displayed higher total cholesterol, triglyceride, and low-density lipoprotein (LDL) concentrations (p < 0.05) than those in the high DBIL group. Spearman analysis further revealed that TBIL, DBIL, and IBIL were negatively correlated with 24hUP and positively correlated with haemoglobin, total protein, and albumin (p < 0.05). Additionally, DBIL exhibited negative correlations with total cholesterol, triglyceride, and LDL (p < 0.05). From a pathological perspective, M1 incidence was higher in the low TBIL and IBIL groups (both p < 0.05). Furthermore, the high IBIL group showed a lower occurrence of cellular/fibrocellular crescents (C1 (in at least one glomerulus) and C2 (in >25% of glomeruli) in the Oxford classification, p < 0.05). Lastly, the multivariate regression model suggested that IBIL was an independent protective factor for M1 (odds ratio = 0.563, 95% confidence interval = 0.344-0.921, p = 0.022). CONCLUSIONS: Patients with IgAN accompanied by low values of bilirubin indices exhibit worsened disease-related clinical indicators (24hUP, total protein, albumin, and haemoglobin levels). Reduced TBIL and IBIL concentrations are indicative of severe renal pathology, with IBIL being a protective factor against M1.

Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: insights from NHANES data (2009-2018).

BACKGROUND: Bilirubin is known for its multifaceted attributes, including antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic properties. The systemic immune-inflammation index (SII) is a recent marker that reflects the balance between inflammation and immune response. Despite the wealth of information available on bilirubin's diverse functionalities, the potential correlation between the total bilirubin (TB) levels and SII has not been investigated so far. METHODS: Leveraging data from the National Health and Nutrition Examination Survey spanning 2009-2018, the TB levels were categorized using tertiles. Employing the chi-squared test with Rao and Scott's second-order correction and Spearman's rank correlation analysis, the association between TB and SII was examined. The potential nonlinearities between TB and SII were evaluated using restricted cubic spline (RCS) analysis. Weighted linear regression, adjusted for covariates, was used to explore the correlation between TB and SII, with further subgroup analyses. RESULTS: A total of 16,858 participants were included, and the findings revealed significant SII variations across TB tertiles (p < 0.001). The third tertile (Q3) exhibited the lowest SII level at 495.73 (295.00) 1000 cells/µL. Spearman rank correlation disclosed the negative association between TB and SII. RCS analysis exposed the lack of statistically significant variations in the nonlinear relationship (p > 0.05), thereby providing support for a linear relationship. Weighted linear regression analysis underscored the negative correlation between TB and SII (ß 95% CI - 3.9 [- 5.0 to - 2.9], p < 0.001). The increase in the TB levels is associated with a significant linear trend toward decreasing SII. After controlling for relative covariates, this negative correlation increased (p < 0.001). Subgroup analysis confirmed the significant negative TB-SII association. CONCLUSION: A notable negative correlation between TB and SII implies the potential protective effects of bilirubin in inflammation-related diseases.

Comparing animal well-being between bile duct ligation models.

A prevailing animal model currently used to study severe human diseases like obstructive cholestasis, primary biliary or sclerosing cholangitis, biliary atresia, and acute liver injury is the common bile duct ligation (cBDL). Modifications of this model include ligation of the left hepatic bile duct (pBDL) or ligation of the left bile duct with the corresponding left hepatic artery (pBDL+pAL). Both modifications induce cholestasis only in the left liver lobe. After induction of total or partial cholestasis in mice, the well-being of these animals was evaluated by assessing burrowing behavior, body weight, and a distress score. To compare the pathological features of these animal models, plasma levels of liver enzymes, bile acids, bilirubin, and within the liver tissue, necrosis, fibrosis, inflammation, as well as expression of genes involved in the synthesis or transport of bile acids were assessed. The survival rate of the animals and their well-being was comparable between pBDL+pAL and pBDL. However, surgical intervention by pBDL+pAL caused confluent necrosis and collagen depositions at the edge of necrotic tissue, whereas pBDL caused focal necrosis and fibrosis in between portal areas. Interestingly, pBDL animals had a higher survival rate and their well-being was significantly improved compared to cBDL animals. On day 14 after cBDL liver aspartate, as well as alanine aminotransferase, alkaline phosphatase, glutamate dehydrogenase, bile acids, and bilirubin were significantly elevated, but only glutamate dehydrogenase activity was increased after pBDL. Thus, pBDL may be primarily used to evaluate local features such as inflammation and fibrosis or regulation of genes involved in bile acid synthesis or transport but does not allow to study all systemic features of cholestasis. The pBDL model also has the advantage that fewer mice are needed, because of its high survival rate, and that the well-being of the animals is improved compared to the cBDL animal model.

Assessing causal associations of blood counts and biochemical indicators with pulmonary arterial hypertension: a Mendelian randomization study and results from national health and nutrition examination survey 2003-2018.

Background: Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH). Methods: A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 to verify the relationship. Results: The MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P<0.001), platelet crit(OR=1.87, 95% CI1.17-7.65, P=0.022), direct bilirubin (DBIL)(OR=1.71, 95%CI 1.18-2.47,P=0.004), insulin-like growth factor (IGF-1)(OR=0.51, 95% CI 0.27-0.96, P=0.038), Lipoprotein A (Lp(a))(OR=0.66, 95% CI 0.45-0.98, P=0.037) and total bilirubin (TBIL)(OR=0.51, 95% CI 0.27-0.96, P=0.038) were significantly associated with PAH. In NHANES, multivariate logistic regression analyses revealed a significant positive correlation between platelet count and volume and the risk of PAH, and a significant negative correlation between total bilirubin and PAH. Conclusion: Our study reveals a causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension. These findings offer novel insights into the etiology and pathological mechanisms of PAH, and emphasizes the important value of these markers as potential targets for the prevention and treatment of PAH.

Correlation between serum bilirubin, blood uric acid, and C-reactive protein and the severity of chronic obstructive pulmonary disease.

OBJECTIVE: To explore the correlation between serum bilirubin, blood uric acid, and C-reactive protein (CRP) and the severity of chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD who were admitted to our hospital between March 2020 and March 2023 were retrospectively studied. Based on whether their condition progressed to the acute exacerbation stage, they were divided into an exacerbation group (100 cases) and a stability group (100 cases). The clinical data from both groups were analysed to assess the correlations between serum bilirubin, blood uric acid, CRP, and the severity of COPD. RESULTS: Univariate analysis indicated significant differences in the neutrophil-to-lymphocyte ratio (t = 5.678, P < 0.05), α-hydroxybutyrate dehydrogenase (t = 5.862, P < 0.05), total bilirubin (t = 4.341, P < 0.05), direct bilirubin (t = 5.342, P < 0.05), indirect bilirubin (t = 5.452, P < 0.05), blood uric acid (t = 4.698, P < 0.05), and CRP (t = 4.892, P < 0.05) between the two groups. Multivariate analysis revealed that total bilirubin, blood uric acid, and CRP were positively correlated with exacerbations of COPD (regression coefficients were 0.413, 0.354, and 0.356, respectively; P < 0.05). The evaluation of predictive value showed that the combined predictive value of these three indicators was the highest, with an AUC of 0.823 (95% CI: 0.754-0.911). CONCLUSION: Serum bilirubin, blood uric acid, and CRP levels are elevated in patients with acute exacerbations of COPD (AECOPD), showing good consistency in predicting the occurrence of AECOPD. The combined diagnostic value of these three indicators is greater than that of any single indicator, providing a reference for the early clinical prediction of AECOPD.

Analysis of gut microecological characteristics and differences between children with biliary atresia and non-biliary atresia in infantile cholestasis.

Introduction: In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles. Methods: Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators. Results: Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA. Conclusion: The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.

Bilothorax: A Case Report and Systematic Literature Review of the Rare Entity.

Background: Bilothorax is defined as the presence of bile in the pleural space. It is a rare condition, and diagnosis is confirmed with a pleural fluid-to-serum bilirubin ratio of >1. Methods: The PubMed, Embase, Google Scholar, and CINAHL databases were searched using predetermined Boolean parameters. The systematic literature review was done per PRISMA guidelines. Retrospective studies, case series, case reports, and conference abstracts were included. The patients with reported pleural fluid analyses were pooled for fluid parameter data analysis. Results: Of 838 articles identified through the inclusion criteria and removing 105 duplicates, 732 articles were screened with abstracts, and 285 were screened for full article review. After this, 123 studies qualified for further detailed review, and of these, 115 were pooled for data analysis. The mean pleural fluid and serum bilirubin levels were 72 mg/dL and 61 mg/dL, respectively, with a mean pleural fluid-to-serum bilirubin ratio of 3.47. In most cases, the bilothorax was reported as a subacute or remote complication of hepatobiliary surgery or procedure, and traumatic injury to the chest or abdomen was the second most common cause. Tube thoracostomy was the main treatment modality (73.83%), followed by serial thoracentesis. Fifty-two patients (51.30%) had associated bronchopleural fistulas. The mortality was considerable, with 18/115 (15.65%) reported death. Most of the patients with mortality had advanced hepatobiliary cancer and were noted to die of complications not related to bilothorax. Conclusion: Bilothorax should be suspected in patients presenting with pleural effusion following surgical manipulation of hepatobiliary structures or a traumatic injury to the chest. This review is registered with CRD42023438426.

The role of bilirubin as a biomarker of rheumatic diseases: a systematic review and meta-analysis.

The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I2 = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I2 = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I2 = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.

The Effect of Tub Bathing on the Skin and Bilirubin Levels of Babies Receiving Tunnel and Light-Emitting Diode Phototherapies: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of tub bathing on the skin and bilirubin levels of newborns receiving tunnel and light-emitting diode phototherapy. METHODS: In this randomized controlled trial, hospitalized newborns diagnosed with hyperbilirubinemia treated with a tunnel or light-emitting diode device were randomly assigned to either the experimental (bath) or control (no bath) groups using a computer program. The skin integrity moisture balance of all groups was recorded using the Newborn Skin Condition Score at 6, 12, and 24 hours after phototherapy, and their total serum bilirubin measurements were evaluated. RESULTS: A statistically significant difference was observed in the babies' total serum bilirubin levels; this decrease was the highest in the experimental groups. Further, the skin integrity-moisture balance was higher in the experimental groups than in the control groups; it was highest in the tunnel-experimental group and lowest in the tunnel control group. CONCLUSIONS: These results show that bathing is effective in reducing total bilirubin levels. This study adds to the evidence on skin integrity and moisture balance in newborns who were bathed during phototherapy.

Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). METHODS: All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. RESULTS: Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. CONCLUSION: TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.

Dynamic whole-transcriptome landscape of acute bilirubin encephalopathy in newborns.

Hyperbilirubinemia in newborns may progress to acute bilirubin encephalopathy (ABE), posing short- and long-term health risks. Despite extensive research identifying numerous mRNAs, lncRNAs, circRNAs, and miRNAs associated with brain injury, their roles in neonatal bilirubin-induced brain injury remain elusive. This study employed whole-transcriptome sequencing to ascertain the differentially expressed (DE) RNA profiles in a newborn ABE rat model, followed by bioinformatic analysis. A time-series competing endogenous RNA (ceRNA) regulatory network was established, and the expression trends of 9 arbitrarily chosen RNAs were verified through quantitative real-time polymerase chain reaction(qRT-PCR). In comparison with the control group, we identified 595, 888, and 1448 DE mRNAs; 22, 37, and 37 DE miRNAs; 1945, 1869, and 1997 DE lncRNAs; and 31, 28, and 36 DE circRNAs at 6 h, 12 h, and 24 h, respectively. Predominantly, these DERNAs contribute to biological functions and pathways associated with inflammation, immunity, metabolism, cell death, and neurodevelopmental regulation. Moreover, we constructed ceRNA networks of DE lncRNA/circRNA-DE miRNA-DE mRNA based on time series. The qRT-PCR expression trends for the selected 9 RNAs were generally similar to the RNA-seq outcomes. This investigation uniquely delineated the temporal expression patterns of mRNA and non-coding RNA in ABE, establishing ceRNA networks and identifying potential molecular mechanisms underlying bilirubin-induced hippocampal damage. Nonetheless, further studies are warranted to corroborate these findings in humans.

Machine learning-based model for predicting tumor recurrence after interventional therapy in HBV-related hepatocellular carcinoma patients with low preoperative platelet-albumin-bilirubin score.

Introduction: This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment. Methods: We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance. Results: The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Conclusion: Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.

Preventive effect of prenatal maternal oral probiotic supplementation on neonatal jaundice (POPS Study): A protocol for the randomised double-blind placebo-controlled clinical trial.

INTRODUCTION: Neonatal jaundice is a common and life-threatening health problem in neonates due to overaccumulation of circulating unconjugated bilirubin. Gut flora has a potential influence on bilirubin metabolism. The infant gut microbiome is commonly copied from the maternal gut. During pregnancy, due to changes in dietary habits, hormones and body weight, maternal gut dysbiosis is common, which can be stabilised by probiotics supplementation. However, whether probiotic supplements can reach the baby through the mother and reduce the incidence of neonatal jaundice has not been studied yet. Therefore, we aim to evaluate the effect of prenatal maternal probiotic supplementation on the incidence of neonatal jaundice. METHODS AND ANALYSIS: This is a randomised double-blind placebo-controlled clinical trial among 94 pregnant women (47 in each group) in a tertiary hospital in Hong Kong. Voluntary eligible participants will be recruited between 28 and 35 weeks of gestation. Computer-generated randomisation and allocation to either the intervention or control group will be carried out. Participants will take either one sachet of Vivomixx (450 billion colony-forming units per sachet) or a placebo per day until 1 week post partum. Neither the study participants nor researchers will know the randomisation and allocation. The intervention will be initiated at 36 weeks of gestation. Neonatal bilirubin level will be measured to determine the primary outcome (hyperbilirubinaemia) while the metagenomic microbiome profile of breast milk and maternal and infant stool samples as well as pregnancy outcomes will be secondary outcomes. Binary logistic and linear regressions will be carried out to assess the association of the microbiome data with different clinical outcomes. ETHICS AND DISSEMINATION: Ethics approval is obtained from the Joint CUHK-NTEC Clinical Research Ethics Committee, Hong Kong (CREC Ref: 2023.100-T). Findings will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT06087874.

Can direct bilirubin-to-lymphocyte ratio predict surgery for pediatric adhesive small bowel obstruction?

OBJECTIVE: Estimating which patients might require surgical intervention is crucial. Patients with complete bowel obstructions exhibit disrupted enterohepatic cycles of bile and bacteremia due to bacterial translocation. The goal of this study was to develop a prediction index using laboratory inflammatory data to identify patients who may need surgery. MATERIALS AND METHODS: The patients were divided into two groups based on their management strategy: Non-operative management (Group 1) and surgical management (Group 2). RESULTS: The indirect bilirubin, direct bilirubin, and total bilirubin were significantly higher in Group 2 than in Group 1 (p = 0.001, p < 0.001, and p < 0.001, respectively). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-NLR (PNLR), and direct bilirubin-to-lymphocyte ratio (DBR) were significantly higher in Group 2 compared to Group 1 (p = 0.041, p = 0.020, and p < 0.001, respectively). In group 2, 78% have viable bowels. Resection was performed in 40% of cases, with 12% mortality and a 10-day average hospital stay. DLR performs the best overall accuracy (72%), demonstrating a well-balanced sensitivity (62%) and specificity (81%). CONCLUSIONS: This study suggested that DBR is a more accurate predictive index for surgical intervention in pediatric adhesive small bowel obstruction patients compared to NLR and PNLR, providing valuable guidance for treatment strategies.

OBJETIVO: Desarrollar un índice de predicción utilizando datos inflamatorios de laboratorio para identificar qué pacientes podrían necesitar cirugía. MÉTODO: Los pacientes se dividieron en dos grupos según su estrategia de manejo: no quirúrgico (grupo 1) o quirúrgico (grupo 2). RESULTADOS: Las bilirrubinas indirecta, directa y total fueron significativamente más altas en el grupo 2 que en el grupo 1 (p = 0.001, p < 0.001 y p < 0.001, respectivamente). Las relaciones neutrófilos-linfocitos, plaquetas-neutrófilos-linfocitos y bilirrubina directa-linfocitos fueron significativamente más altas en el grupo 2 que en el grupo 1 (p = 0.041, p = 0.020 y p < 0.001, respectivamente). En el grupo 2, el 78% tenían intestino viable. Se realizó resección en el 40% de los casos, con un 12% de mortalidad y una estancia hospitalaria promedio de 10 días. La relación bilirrubina directa-linfocitos tuvo la mejor precisión general (72%), demostrando una sensibilidad bien equilibrada (62%) y una buena especificidad (81%). CONCLUSIONES: Este estudio sugiere que la relación bilirrubina directa-linfocitos es un índice predictivo más preciso para la intervención quirúrgica en pacientes pediátricos con obstrucción adhesiva de intestino delgado en comparación con la de neutrófilos-linfocitos y la de plaquetas-neutrófilos-linfocitos, proporcionando una valiosa orientación para las estrategias de tratamiento.

The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. METHOD: Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. RESULT: Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034). CONCLUSIONS: Growth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

Hyaluronic Acid-Bilirubin Nanoparticles as a Tumor Microenvironment Reactive Oxygen Species-Responsive Nanomedicine for Targeted Cancer Therapy.

Introduction: The tumor microenvironment (TME) has attracted considerable attention as a potential therapeutic target for cancer. High levels of reactive oxygen species (ROS) in the TME may act as a stimulus for drug release. In this study, we have developed ROS-responsive hyaluronic acid-bilirubin nanoparticles (HABN) loaded with doxorubicin (DOX@HABN) for the specific delivery and release of DOX in tumor tissue. The hyaluronic acid shell of the nanoparticles acts as an active targeting ligand that can specifically bind to CD44-overexpressing tumors. The bilirubin core has intrinsic anti-cancer activity and ROS-responsive solubility change properties. Methods & Results: DOX@HABN showed the HA shell-mediated targeting ability, ROS-responsive disruption leading to ROS-mediated drug release, and synergistic anti-cancer activity against ROS-overproducing CD44-overexpressing HeLa cells. Additionally, intravenously administered HABN-Cy5.5 showed remarkable tumor-targeting ability in HeLa tumor-bearing mice with limited distribution in major organs. Finally, intravenous injection of DOX@HABN into HeLa tumor-bearing mice showed synergistic anti-tumor efficacy without noticeable side effects. Conclusion: These findings suggest that DOX@HABN has significant potential as a cancer-targeting and TME ROS-responsive nanomedicine for targeted cancer treatment.

Spicy Recipe for At-Home Diagnostics: Smart Salivary Sensors for Point-of-Care Diagnosis of Jaundice.

Even though significant advances have been made, there is still a lack of reliable sensors capable of noninvasively monitoring bilirubin and diagnosing jaundice as the most common neonatal disease, particularly at the point-of-care (POC) where blood sampling from infants is accompanied by serious challenges and concerns. Herein, for the first time, using an easy-to-fabricate/use assay, we demonstrate the capability of curcumin embedded within paper for noninvasive optical monitoring of bilirubin in saliva. The highly selective sensing of the developed sensor toward bilirubin is attributed to bilirubin photoisomerization under blue light exposure, which can selectively restore the bilirubin-induced quenched fluorescence of curcumin. We also fabricated an IoT-enabled hand-held optoelectronic reader to measure and quantify the fluorescence and color signals of our sensor. Clinical analysis on the saliva of 18 jaundiced infants by using our developed smart salivary sensor proved that it is amenable to be widely exploited in POC applications for bilirubin monitoring as there are good correlations between its results with those of reference methods in saliva and blood. Meeting all WHO's REASSURED criteria by our developed sensor makes it a highly promising sensor for smart noninvasive diagnosis and therapeutic monitoring of jaundice, hepatitis, and other bilirubin-induced neurologic diseases at the POC.

Prognostic and immunotherapeutic implications of bilirubin metabolism-associated genes in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a major subtype of non-small-cell lung cancer and accompanies high mortality rates. While the role of bilirubin metabolism in cancer is recognized, its specific impact on LUAD and patient response to immunotherapy needs to be elucidated. This study aimed to develop a prognostic signature of bilirubin metabolism-associated genes (BMAGs) to predict outcomes and efficacy of immunotherapy in LUAD. We analysed gene expression data from The Cancer Genome Atlas (TCGA) to identify survival-related BMAGs and construct a prognostic model in LUAD. The prognostic efficacy of our model was corroborated by employing TCGA-LUAD and five Gene Expression Omnibus datasets, effectively stratifying patients into risk-defined cohorts with marked disparities in survival. The BMAG signature was indeed an independent prognostic determinant, outperforming established clinical parameters. The low-risk group exhibited a more favourable response to immunotherapy, highlighted by increased immune checkpoint expression and immune cell infiltration. Further, somatic mutation profiling differentiated the molecular landscapes of the risk categories. Our screening further identified potential drug candidates preferentially targeting the high-risk group. Our analysis of critical BMAGs showed the tumour-suppressive role of FBP1, highlighting its suppression in LUAD and its inhibitory effects on tumour proliferation, migration and invasion, in addition to its involvement in cell cycle and apoptosis regulation. These findings introduce a potent BMAG-based prognostic indicator and offer valuable insights for prognostication and tailored immunotherapy in LUAD.

DGPRI, a new liver fibrosis assessment index, predicts recurrence of AFP-negative hepatocellular carcinoma after hepatic resection: a single-center retrospective study.

Although patients with alpha-fetoprotein-negative hepatocellular carcinoma (AFPNHCC) have a favorable prognosis, a high risk of postoperative recurrence remains. We developed and validated a novel liver fibrosis assessment index, the direct bilirubin-gamma-glutamyl transpeptidase-to-platelet ratio (DGPRI). DGPRI was calculated for each of the 378 patients with AFPNHCC who underwent hepatic resection. The patients were divided into high- and low-score groups using the optimal cutoff value. The Lasso-Cox method was used to identify the characteristics of postoperative recurrence, followed by multivariate Cox regression analysis to determine the independent risk factors associated with recurrence. A nomogram model incorporating the DGPRI was developed and validated. High DGPRI was identified as an independent risk factor (hazard ratio = 2.086) for postoperative recurrence in patients with AFPNHCC. DGPRI exhibited better predictive ability for recurrence 1-5 years after surgery than direct bilirubin and the gamma-glutamyl transpeptidase-to-platelet ratio. The DGPRI-nomogram model demonstrated good predictive ability, with a C-index of 0.674 (95% CI 0.621-0.727). The calibration curves and clinical decision analysis demonstrated its clinical utility. The DGPRI nomogram model performed better than the TNM and BCLC staging systems for predicting recurrence-free survival. DGPRI is a novel and effective predictor of postoperative recurrence in patients with AFPNHCC and provides a superior assessment of preoperative liver fibrosis.

Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4.

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor alpha (PPARα), and stress sensor, activating transcription factor 4 (ATF4). When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep) and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.