Association of Neonatal Jaundice with Gut Dysbiosis Characterized by Decreased Bifidobacteriales

Neonatal jaundice, caused by excess serum bilirubin levels, is a common condition in neonates. Imbalance in the gut microbiota is believed to play a role in the development of neonatal jaundice. Thus, we aimed to reveal the gut microbiota characteristics in neonates with jaundice. 16S rRNA gene sequencing was performed on stool samples collected on day 4 from 26 neonates with jaundice (serum total bilirubin > 15.0 mg/dL) and 17 neonates without jaundice (total serum bilirubin < 10.0 mg/dL). All neonates were born full term, with normal weight, by vaginal delivery, and were breastfed. Neonates who were administered antibiotics, had serum direct bilirubin levels above 1 mg/dL, or had conditions possibly leading to hemolytic anemia were excluded. The median serum bilirubin was 16.0 mg/dL (interquartile range: 15.5–16.8) and 7.4 mg/dL (interquartile range: 6.8–8.3) for the jaundice and non-jaundice groups, respectively. There was no difference in the alpha diversity indices. Meanwhile, in the jaundice group, linear discriminant analysis effect size revealed that Bifidobacteriales were decreased at the order level, while Enterococcaceae were increased and Bifidobacteriaceae were decreased at the family level. Bifidobacteriaceae may act preventatively because of their suppressive effect on beta-glucuronidase, leading to accelerated deconjugation of conjugated bilirubin in the intestine. In summary, neonates with jaundice had dysbiosis characterized by a decreased abundance of Bifidobacteriales.

Serum uric acid and total bilirubin as putative biomarkers of resistance in Prodromal Parkinson’s disease: Longitudinal data from the PPMI study

BackgroundThe role of blood uric acid and more recently bilirubin as biomarkers in symptomatic motor PD has been increasingly established in the literature.ObjectiveOur present study assessed the role of serum uric acid and total bilirubin as putative biomarkers in a prodromal PD cohort followed longitudinally.MethodsLongitudinal 5-year serum uric acid and total bilirubin measurement data of 65 Prodromal PD patients (including REM Sleep Behavior disorder (RBD), N=39 and Hyposmia, N=26) with an abnormal DATSCAN imaging were downloaded from the Parkinson’s Progression Markers Initiative (PPMI) database. This cohort was compared with 423 de novo sporadic PD patients and 196 healthy controls enrolled in the same study.ResultsAfter adjusting for age, sex and Body Mass Index (BMI), baseline and 5-year longitudinal serum uric acid levels were higher in the Prodromal cohort and RBD subgroup as compared to the motor PD cohort. This was also true for longitudinal measurements in the Hyposmic subgroup. In contrast, baseline and longitudinal serum total bilirubin did not differ between each prodromal group and the PD cohort.ConclusionsOur results are indicative of a role of serum uric acid (but probably not of total bilirubin) as a marker of neuroprotection, in a certain subgroup of premotor patients exhibiting exclusively non motor features (hyposmia or RBD). It is possible that an inherent antioxidant resistance of a subset of RBD or hyposmia patients with high serum uric acid level delayed or precluded the emergence of a motor PD phenotype as opposed to the PD cohort.

Associations between serum total bilirubin, obesity and type 2 diabetes

Background This study aims to examine the cross-sectional association between serum total bilirubin (STB) and type 2 diabetes (T2D) risk in the general population, and whether obesity could moderate this association. Methods We used data from the 1999–2018 National Health and Nutrition Examination Surveys (NHANES), including a total of 38,641 US adult participants who were 18 years or older. The STB was classified as the low, moderate, and high groups according to tertiles. Results We found that participants with lower STB had a significantly higher risk of T2D than those with moderate (OR = 0.81; 95% CI 0.74, 0.89; P < 0.001) and high (OR = 0.65; 95% CI 0.59, 0.73; P < 0.001) STB. Also, a significant interaction between body mass index (BMI) and STB on T2D was observed (P < 0.001). Stratified analysis showed that low STB was associated with a 20% and 27% decrease of T2D risk for moderate and high STB groups in obese patients, however, these effect estimates were smaller in the population with lower BMI (< 30 kg/m2). Similar associations of STB with glycohemoglobin and insulin resistance were observed. Conclusion This study suggests that STB is associated with an elevated risk of T2D. More importantly, we reported for the first time that BMI may moderate the association between bilirubin and T2D.

Expectant management of prolonged hemolysis following complete transcatheter coil closure of a patent ductus arteriosus after previous pulmonary artery banding: a case report

Background Transcatheter coil occlusion has been the treatment of choice for closure of small patent ductus arteriosus (PDA). In spite of its safety, complications such as hemolysis still occasionally occur. And the hemolysis almost always occurs following partial transcatheter closure of PDA; hence, it occurs extremely rarely following complete transcatheter closure of PDA without residual ductal flow. Case presentation Here, we describe a male newborn who developed prolonged hemolysis following complete transcatheter coil closure of his PDA after previous palliative pulmonary artery banding. Over the following days, we corrected his refractory anemia by repeated blood transfusion with packed red blood cells and frequently monitored his hemoglobin, serum total bilirubin, and serum lactate dehydrogenase. We speculated that the high-velocity pulmonary blood flow jet coming into contact with the extruded part of the coil led to red blood cell mechanical injury, thereby resulting in the hemolysis. We adopted expectant management in expectation of the endothelialization of the coil with a resultant reduction in the hemolysis. The hemolysis, as expected, was reduced gradually until it spontaneously resolved 81 days after coil implantation. Conclusions This case reminds us that hemolysis can still potentially occur following complete transcatheter coil closure of PDA. It also highlights the importance of preventing coils from extruding into the pulmonary artery in patients after previous pulmonary artery banding.

A High Urinary Urobilinogen / Serum Total Bilirubin Ratio Reported in Abdominal Pain Patients Can Indicate Acute Hepatic Porphyria

Background: Due to its variable symptoms and nonspecific laboratory test results during routine examinations, acute hepatic porphyria (AHP) has always been a diagnostic dilemma for physicians. Correct diagnosis mainly depends on the elevated urinary porphobilinogen (PBG) level, which is not a routine test performed in the emergency department. Therefore, identifying a more convenient indicator during routine examinations is important to improve the diagnosis of AHP.Methods: In this retrospective study, we enrolled 12 AHP patients and 100 patients with abdominal pain of other causes as the control groups in Qilu hospital of Shandong University between 2015 and 2021. The clinical manifestations and laboratory result data including urinary urobilinogen/serum total bilirubin ratio were compared between these two groups. The diagnostic performance of urinary urobilinogen/serum total bilirubin ratio was measured as sensitivity, specificity, and accuracy. The cut-off for optimal clinical performance was determined by the receiver operator characteristic (ROC) curve. Results were considered significant at a P < 0.05.Results: Compared with the control groups, AHP patients showed a significantly higher urinary urobilinogen level (P < 0.05). However, we showed that the higher urobilinogen level was caused by a false-positive result due to elevated urine PBG. Hence, we used serum total bilirubin, an upstream substance of urinary urobilinogen synthesis, for calibration. A remarkable increase in the urinary urobilinogen/serum total bilirubin ratio was observed in AHP patients. The area under the ROC curve of this ratio for AHP was 1.000 (95% confidence interval, 1.000–1.000, P < 0.01). A cutoff value of 3.22 for the urinary urobilinogen/serum total bilirubin ratio yielded a sensitivity of 100% and a specificity of 100% to distinguish AHP patients from the controls.Conclusion: A reported high urinary urobilinogen level that was adjusted by the serum total bilirubin level (urinary urobilinogen/serum total bilirubin ratio) could be used as a sensitive and specific indicator for AHP in patients with abdominal pain.

Risk factors analysis of hyperbilirubinemia after off-pump coronary artery bypass grafting: a retrospective observational study

Background Hyperbilirubinemia is a common complication after off-pump coronary artery bypass grafting (OPCAB), but the incidence and the risk factors are unclear. This study aimed to analyze the incidence and risk factors of postoperative hyperbilirubinemia in patients undergoing OPCAB. Methods From December 2016 to March 2019, a total of 416 consecutive patients undergoing OPCAB were enrolled in this single-center retrospective study. Patients were divided into the normal serum total bilirubin group and the hyperbilirubinemia group based on the serum total bilirubin levels. Perioperative variables between the two groups were compared by univariate logistic regression analysis. Then, multivariate binary logistic regression analysis was used to analyze the independent risk factors of developing hyperbilirubinemia in patients underwent OPCAB. P < 0.05 was considered as statistically significant. Results Thirty two of 416 (7.7%) patients developed postoperative hyperbilirubinemia. Univariate regression analysis showed significant differences in gender (73.96% vs. 93.75%, P = 0.012), preoperative total bilirubin levels (11.92 ± 4.52 vs. 18.28 ± 7.57, P < 0.001), perioperative IABP implantation (22.66% vs. 43.75%, P = 0.008), perioperative blood transfusion (37.50% vs. 56.25%, P = 0.037) between the two groups. Multivariate logistic regression analysis revealed that elevated preoperative serum total bilirubin levels (OR = 1.225, 95% CI 1.145–1.310, P < 0.001), perioperative blood transfusion (OR = 4.488, 95% CI 1.876–10.737, P = 0.001) and perioperative IABP implantation (OR = 4.016, 95% CI 1.709–9.439, P = 0.001) were independent risk factors for hyperbilirubinemia after OPCAB. Conclusions Hyperbilirubinemia is also a common complication after OPCAB. Elevated preoperative serum total bilirubin levels, perioperative blood transfusion, and perioperative IABP implantation were independent risk factors for patients developing hyperbilirubinemia after OPCAB. Further studies need to be conducted to confirm the risk factors of hyperbilirubinemia after OPCAB procedure.

Serum Total Bilirubin Level Is Associated With Hospital Mortality Rate in Adult Critically Ill Patients: A Retrospective Study

Background: Serum bilirubin level has been suggested to be associated with mortality for patients with severe sepsis. This study aimed to investigate the association of serum total bilirubin level with hospital mortality rate in adult critically ill patients.Method: Data were extracted from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Patients with measured serum total bilirubin levels that recorded within 24 h after admission were involved in this study. Association of serum total bilirubin level and hospital mortality rate was assessed using logistic regression analysis. Propensity score-matching (PSM) was used to minimize differences between different groups.Results: A total of 12,035 critically ill patients were herein involved. In patients with serum total bilirubin level ≥ 2 mg/dL, the hospital mortality rate was 31.9% compared with 17.0% for patients with serum total bilirubin level &lt; 2 mg/dL (546/1714 vs. 1750/10321, P &lt; 0.001). The results of multivariable logistic regression analysis showed that the odds ratio of mortality in patients with serum total bilirubin level ≥ 2 mg/dL was 1.654 [95% confidence interval (CI): 1.307, 2.093, P &lt; 0.001]. After propensity score matching, in patients with serum total bilirubin level ≥ 2 mg/dL, the weighted hospital mortality rate was 32.2% compared with 24.8% for patients with serum total bilirubin level &lt; 2 mg/dL, P = 0.001).Conclusions: Serum total bilirubin concentration was found to be independently associated with hospital mortality rate in adult critically ill patients.

Association of Serum Total Bilirubin Concentration with Telomere Length: The National Health and Nutrition Examination Survey

Introduction. Mildly increased bilirubin concentration has a protective effect on oxidative stress–related diseases. However, it remains unknown whether elevated circulating bilirubin is associated with longer telomere length. The aim of this cross-sectional study was to examine the association between total bilirubin concentration and telomere length. Methods. We used the data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The multivariable linear regression model was used to examine the association between total bilirubin concentration and telomere length. The nonlinear relationship was analyzed using a generalized additive model with the smoothing plot. Results. A total of 7818 participants with a mean age of 49.20 ± 18.82 years were included. Compared with the lowest concentration of total bilirubin (Q1), the highest quartile of total bilirubin concentration was associated with longer telomere length in male ( β = 0.04 , 95 CI%: 0.00, 0.07, P = 0.024 ) and female ( β = 0.04 , 95 CI%: 0.02, 0.04, P = 0.002 ). Furthermore, an inverted U-shaped relationship between total bilirubin and telomere length was found. On the left of turning points ( total bilirubin < 0.5 mg / dL ), total bilirubin concentration was positively associated with telomere length ( β = 0.23 , 95 CI%: 0.14, 0.32, P < 0.001 ). However, the association between total bilirubin concentration and telomere length was not significant ( β = 0.01 , 95% CI: -0.01, 0.04, P = 0.346 ) above the turning point. Conclusion. This is the first evidence based on a nationally representative survey demonstrating a positive and nonlinear association between total bilirubin concentration and telomere length. Future large-scale prospective studies are warranted to confirm our findings.

Deep-Learning-Based Smartphone Application for Self-Diagnosis of Scleral Jaundice in Patients with Hepatobiliary and Pancreatic Diseases

Outpatient detection of total bilirubin levels should be performed regularly to monitor the recurrence of jaundice in hepatobiliary and pancreatic disease patients. However, frequent hospital visits for blood testing are burdensome for patients with poor medical conditions. This study validates a novel deep-learning-based smartphone application for the self-diagnosis of scleral jaundice in such patients. The system predicts total serum bilirubin levels using the deep-learning-based regression analysis of scleral photos taken by the smartphone’s built-in camera. Enrolled patients were randomly assigned to either the training cohort (n = 90, 1034 photos) or the validation cohort (n = 40, 426 photos). The intraclass correlation coefficient value for predicted serum total bilirubin (PSB) derived from the images repeatedly taken at the same time for the same patient showed good reliability (0.86). A strong correlation between measured serum total bilirubin (MSB) and PSB was observed in the subgroup with MSB levels ≥1.5 mg/dL (Spearman rho = 0.70, p < 0.001). The receiver operating characteristic curve for PSB showed that the area under the curve was 0.93, demonstrating good test performance as a predictor of hyperbilirubinemia (p < 0.001). Using a cut-off PSB ≥1.5, the prediction sensitivity of hyperbilirubinemia was 80.0%, with a specificity of 92.6%. Hence, the tool is effective for patient monitoring.

The Impact of Comorbid Renal Dysfunction in Patients with Hepatocellular Carcinoma on Long-Term Outcomes after Curative Resection

Background:Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the number of patients with chronic kidney disease (CKD) is also on the rise because of the increase in lifestyle-related diseases. To establish a tailored management strategy for HCC patients, we evaluated the impact of comorbid renal dysfunction (RD), as stratified by using the estimated glomerular filtration rate (eGFR), and assessed the oncologic validity of hepatectomy for HCC patients with RD.Methods:We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 in our university hospital. We categorized patients into two (RD, eGFR < 60 mL/min/1.73m2; non-RD, 60 ≤ eGFR) and three groups (severe CKD, eGFR < 30; mild CKD, 30 ≤ eGFR < 60; control, 60 ≤ eGFR) according to renal function as defined by the eGFR. Overall survival (OS) and recurrence-free survival (RFS) were compared among these groups with the log-rank test, and we also analyzed survival by using a propensity score matching (PSM) model for excluding the influence of patient characteristics. The mean of postoperative observation period was 64.7 ± 53.0 months.Results:RD patients were significantly older and had lower serum total bilirubin, AST, and ALT levels than those in non-RD patients (P < 0.0001, P < 0.001, < 0.05, and < 0.01, respectively). No patient was introduced to maintenance hemodialysis after surgery. Although the overall postoperative complications rates were similar between RD and non-RD patients, the proportions of postoperative bleeding and surgical site infection were significantly higher in RD patients (5.5% vs. 1.8%; P < 0.05, 3.9% vs. 1.8%; P < 0.05, respectively), and postoperative bleeding was the highest in severe CKD group (P < 0.05). Regardless of the degree of comorbid RD, OS and RFS were comparative, even when using PSM between RD and non-RD groups to exclude the influence of patient characteristics, liver function, and other causes of death.Conclusions:Comorbid RD had a negligible impact on the prognosis of HCC patients who underwent curative hepatectomy with appropriate perioperative management, and close attention to severe CKD is necessary to prevent postoperative bleeding and surgical site infection. Hokkaido University Graduate School of Medicine under Clinical Research Number 016-0354