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.

Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia.

OBJECTIVE: To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20 mg/dL or underwent exchange transfusion). STUDY DESIGN: In this prospective cohort study, infants ≥34 weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. RESULTS: A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). CONCLUSIONS: Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34 weeks of gestational age.

Positive association between serum bilirubin within the physiological range and serum testosterone levels.

BACKGROUNDS: Research has demonstrated that elevated serum total bilirubin (STB) levels have a beneficial impact on various diseases, particularly metabolic syndrome. This study aims to investigate the association between STB levels and serum testosterone (STT) in order to determine if bilirubin plays a protective role in relation to testosterone deficiency (TD) risk. METHODS: In this study, a total of 6,526 eligible male participants aged 20 years or older were analyzed, all of whom took part in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2016. To investigate the relationship between STB and STT levels, we employed weighted multivariate regression models along with restricted cubic splines (RCS). Additionally, a subgroup analysis was conducted to explore the heterogeneity of this relationship across different subpopulations. RESULTS: Among the participants, 1,832 individuals (28.07%) were identified as having testosterone deficiency (TD), defined as an STT level below 300 ng/dL. A significant positive correlation between STB and STT levels was observed in both crude and adjusted models (all P < 0.0001). The association between STB and STT levels was found to be statistically significant up to a threshold of 17.1 µmol/L, after which it became statistically insignificant(P for non-linearity = 0.0035). Weighted logistic regression analysis indicated that a 1 µmol/L increase in STB was associated with a 4% decrease in the likelihood of TD (odds ratio = 0.96, P < 0.0001). Subgroup analysis showed that the inverse relationship was limited to individuals aged 60 and over, non-smokers/drinkers, and obese individuals. CONCLUSION: STB within the physiological range(17.1 µmol/L) was positively associated with STT in adult males. The potential protective role of bilirubin regarding testosterone levels merits further exploration.

Transcutaneous bilirubin reliability during and after phototherapy depending on skin color.

Measurement of transcutaneous bilirubin (TcB) is a non-invasive, widely used technique to estimate serum bilirubin (SB). However, its reliability in multiethnic populations during and after phototherapy is still controversial even in covered skin. The aim of this study was to determine the reliability of TcB in covered (cTcB) and exposed (eTcB) skin during and after phototherapy in a multiethnic population of term and preterm neonates according to Neomar's neonatal skin color scale. Prospective, observational study comparing SB and TcB. We determined SB when clinically indicated and, at the same time, measured cTcB under a photo-opaque patch and eTcB next to it with a jaundice meter (Dräger JM-105TM). All dyads TcB-SB were compared, both globally and according to skin color. We obtained data from 200 newborns (color1: 44, color2: 111, color3: 41, color4: 4) and compared 296 dyads TcB/SB. Correlation between cTcB and SB is strong during (0.74-0.83) and after (0.79-0.88) phototherapy, both globally and by color group. The SB-cTcB bias depends on gestational age during phototherapy and on skin color following phototherapy. The correlation between eTcB and SB during phototherapy is not strong (0.54), but becomes so 12 h after discontinuing phototherapy (0.78).  Conclusions: Our study supports the reliability of cTcB to assess SB during and after phototherapy, with differences among skin tones after the treatment. The use of cTcB and Neomar's scale during and mainly after phototherapy may help reduce the number of blood samples required. What is Known: • Controversies exist on the reliability of jaundice meters during and after phototherapy in covered skin. Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale. What is New: • We verified correlation between serum and transcutaneous bilirubin in covered skin in a multiethnic population depending on skin color based on our own validated neonatal skin color scale during and after phototherapy.

Validity of BiliDx as a point-of-care bilirubin measurement device to diagnose and monitor neonatal jaundice at Muhimbili National Hospital, an observational study.

BACKGROUND: Neonatal jaundice is a condition caused by elevated levels of bilirubin in the bloodstream. Laboratory determination of serum bilirubin concentration by total serum bilirubin (TSB) test is still considered as gold standard for clinical guidance and practice. In developed countries, diagnosis of neonatal jaundice is shifting towards point-of-care medical devices. BiliDx is a device developed to allow a fast, blood-based determination of bilirubin levels at the point of care. This study aimed to determine the accuracy of the BiliDx device relative to a standard laboratory total serum bilirubin to diagnose and monitor jaundice among neonates admitted at Muhimbili National Hospital (MNH). MATERIAL AND METHODOLOGY: This was a prospective hospital-based observational study conducted at the Neonatal Ward - MNH, Dar-es-Salaam, Tanzania from November 2022 to January 2023. A total of 180 neonates admitted at the neonatal ward with jaundice and whose parents consented were enrolled in the study. Blood samples were collected; 2 ml of venous blood into the vacutainer bottle for standard laboratory measurement of total serum bilirubin (TSB) and 25µL blood collected into a transfer pipette tube and applied to BiliDx. STATA version 15.1 was used for data analysis. RESULTS: Out of 180 neonates, 39.4% (71/180) had birth weight between 1500 - 2499.9 g, approximately 2/3rd (120/180) were preterm, 92/180 (51.1%) were males and 100/180 (55.6%) were undergoing phototherapy treatment the moment sample taken. The mean bilirubin concentration was 92 mmol/l for BiliDx and 118 mmol/l for standard laboratory TSB. The minimum and maximum values obtained with BiliDx were, 3.4 and 427.5 mmol/l respectively, compared with 10.7 and 382.1 mmol/l using standard laboratory TSB. A linear relationship and correlation coefficient of 0.8408 (p = 0.000) between BiliDx and standard laboratory TSB was found. The regression analysis showed the presence of constant error [coefficient of BiliDx/slope = 0.91, 95% CI (0.82-0.99), p = 0.000] and random error exclusively [coefficient of constant/y-intercept = 48.52, 95%CI (37.70-59.34), p = 0.000]. The Bland-Altman plot showed an acceptable mean difference of 39.1mmol/l, limits of agreement of -48.3mmol/l to 126.4mmol/l, and 179 points (179/180 = 99.4%) lying inside the limits of agreement. CONCLUSION: The results support the use of BiliDx for rapid and accurate testing of elevated levels of bilirubin in the bloodstream among neonates since 99.4% of the differences between BiliDx and standard laboratory TSB lie between the lines of agreement.

Bilirubin-Displacing Effect of Ceftriaxone in Infants With Unconjugated Hyperbilirubinemia Born at Term.

OBJECTIVE: To evaluate the effect of intravenous (IV) ceftriaxone on free bilirubin concentrations in infants with unconjugated hyperbilirubinemia born at term. STUDY DESIGN: A prospective study was performed with subjects serving as their own controls. Our inclusion criteria were infants born at term <7 days old with sepsis and receiving IV antibiotics for >3 days and resolving hyperbilirubinemia with total serum bilirubin levels between 6 and12 mg/dL by day 4 of life. Free bilirubin concentrations were measured by the peroxidase method using a UB analyzer and a Zone Fluidics device before (baseline) and 15 minutes after (follow-up) IV ceftriaxone administration on postnatal days 4 to 6. Paired measurements of free bilirubin were analyzed using a Student paired t-test or Wilcoxon signed-rank test. RESULTS: In total, 27 infants were studied. The mean free bilirubin (µg/dL) at follow-up was not different from that at baseline when measured by the UB analyzer (P = .78). The mean free bilirubin was significantly lower at follow-up compared with baseline when measured by the Zone Fluidics device (P = .02). The ratio of a free bilirubin with and without ceftriaxone, an index of displacing effect, was 1.02 (95% CI 0.89-1.14) using the UB analyzer and 0.58 (95% CI 0.30-0.86) using the Zone Fluidics device. CONCLUSIONS: Ceftriaxone is not associated with a bilirubin-displacing effect in infants with a mild unconjugated hyperbilirubinemia. Home therapy with once-daily intramuscular ceftriaxone may be an alternative option for management of sepsis in asymptomatic infants with a mild unconjugated hyperbilirubinemia born at term.

Predictive modeling of postoperative gastrointestinal dysfunction: the role of serum bilirubin, sodium levels, and surgical duration in gynecological cancer care.

OBJECTIVE: To elucidate the role of preoperative serum bilirubin and sodium levels, along with the duration of surgery, in predicting postoperative gastrointestinal dysfunction (POGD) following gynecological cancer surgery, informing tailored perioperative strategies. METHODS: We conducted a retrospective analysis of 281 patients undergoing gynecological cancer surgery between 2018 and 2023. This analysis focused on preoperative serum bilirubin and sodium levels and intraoperative factors (surgical duration) as potential predictors of POGD. Logistic regression models were utilized for analysis, controlling for relevant confounders. RESULTS: Elevated preoperative serum bilirubin was associated with a reduced risk of POGD (mean level in non-POGD cases: 14.172 ± 4.0701, vs. POGD cases: 9.6429 ± 3.5351; p <  0.001), suggesting a protective role. Lower preoperative sodium levels were identified in the POGD group (136.26 mEq/L [IQR: 135.2-137.63]) compared to the non-POGD group (139.32 mEq/L [IQR: 137.7-140.75]; p <  0.001), highlighting its predictive value. Additionally, longer surgical duration was associated with increased POGD incidence, with POGD cases experiencing surgeries lasting 6.1547 ± 1.9426 hours compared to 4.5959 ± 1.5475 hours in non-POGD cases (p <  0.001). CONCLUSION: Our findings underscore the importance of serum bilirubin, sodium levels, and surgical duration as significant predictors of POGD in patients undergoing gynecological cancer surgery. These indicators should be integrated into a predictive model, aiding clinicians in identifying high-risk patients, allowing for personalized perioperative care adjustments, potentially mitigating POGD risks.

Serum bilirubin levels in primary Sjögren's syndrome: an association with interstitial lung disease.

OBJECTIVE: We aimed to assess the association between serum bilirubin levels and interstitial lung disease (ILD) in patients with Primary Sjögren's syndrome (pSS). MATERIALS AND METHODS: The retrospectively analysis included 89 consecutive patients with pSS, we collected the clinical materials of pSS patients from the electronic medical records, and all pSS patients were divide into pSS with ILD group and pSS without ILD group. RESULTS: Serum bilirubin levels were significantly lower in pSS patients with ILD than those without ILD (p = 0.010). Serum bilirubin levels showed a significant negative correlation with erythrocyte sedimentation rate (ESR) (r = -0.321, p = 0.002) in patients with pSS. A multivariable logistic regression analysis confirmed that serum bilirubin presented an independent association with ILD in patients with pSS (OR = 0.841, 95%CI:0.728-0.972, p = 0.019). CONCLUSION: Serum bilirubin is independently associated with ILD and therefore may be a promising marker of ILD in patients with pSS.

The application value of mean red blood cell volume and red blood cell volume distribution width combined with total serum bilirubin in the early screening of neonatal hemolytic disease.

BACKGROUND: The hemolytic nature of hemolytic disease of the newborn (HDN) is described as the abnormal destruction and decomposition of red blood cells, causing heterogeneous manifestations such as abnormal red blood cell volume and morphology. Mean corpuscular volume (MCV) and red blood cell volume distribution width (RDW) are commonly used parameters related to red blood cell volume. Total serum bilirubin (TSB) is routinely monitored among newborns. This study aims to explore the value of MCV and RDW, combined with TSB, to improve the efficiency of HDN diagnosis. METHODS: Three hundred eighty-eight children with HDN and 371 children with non-HDN pathological jaundice who were diagnosed and treated in the neonatal department of our hospital from January 2019 to December 2020 were included in the study. Clinical data collected include examination results of laboratory indicators, such as MCV, coefficient of variation of red blood cell volume distribution width (RDW-CV), standard deviation of red blood cell volume distribution width (RDW-SD), and TSB. The differences in the indicators between the two groups of children were retrospectively analyzed. RESULTS: 1) The detection rate of HDN in children in the early group was higher than that in the late group (P < 0.001). 2) The early-stage group had lower TSB levels and higher values of MCV, RDW-CV and RDW-SD (P < 0.001). Compared with the children in the non-HDN group, the indices in the HDN group were higher in the early stage (P < 0.001). 3) In the early stage, the TSB, MCV, RDW-CV, and RDW-SD were positively correlated with the diagnosis of HDN (P < 0.001). Early monitoring of TSB, MCV, RDW-CV and RDW-SD was valuable for HDN detection, the area under the curve (AUC) was 0.729, 0.637, 0.715, and 0.685, respectively (P < 0.001). 4) After a binary logistic analysis at TSB > 163.3 µmol/L, MCV > 96.35fL, and RDW-CV > 16.05%, the diagnosis rate of HDN increased (P < 0.001). The AUC of the HDN detected using the combined indicators was 0.841. CONCLUSION: At MCV > 96.35fL or RDW-CV > 16.05%, children with jaundice in three days of birth (especially children with TSB > 163.3 µmol/L) should be screened for HDN. A combination of TSB, MCV, and RDW-CV can improve the early detection rate of HDN, contribute to reduce the readmission rate and risk of hyperbilirubinemia.

RELATIONSHIP BETWEEN SICKLE CELL NEPHROPATHY AND SOME BIOCHEMICAL MARKERS OF HAEMOLYSIS AMONGST PATIENTS WITH SICKLE CELL ANAEMIA IN KANO, NORTHWESTERN NIGERIA.

Introduction: Advancements in the care of patients with sickle cell anaemia have led to significant improvement in survival with many patients reaching adulthood. As they age, long-term complications of the disease manifest in them, notable amongst which is nephropathy which is one of the leading causes of morbidity and mortality in them. There is limited information about sickle cell nephropathy and some biochemical markers of haemolysis that can detect it early in our setting. This study aimed to determine the relationship between some indirect markers of haemolysis and sickle cell nephropathy. Methodology: The study was a descriptive cross-sectional one where 204 adolescent and adult patients with sickle cell anaemia attending the clinic of AKTH Kano were recruited. An interviewer-administered questionnaire was utilized. Blood samples were taken for determination of serum bilirubin, LDH, and reticulocyte count. Spot urine was used to quantitatively determine albumin to creatinine ratio. Data collated was analyzed using SPSS version 22.0. P-value <0.05 was considered significant. Result: Two hundred and four (204) participants were enrolled in to the study. Their mean age was 19.6±5years. Females were the majority 131/204 (64.2%). The median (IQR) serum lactate dehydrogenase, bilirubin, direct bilirubin, and reticulocyte count were 607.0(487.3-758.5) U/L, 54.5(37.0-119.0) umol/L, 16.0(11.3-29.0) umol/L and 4.0(3.0-8.4%) respectively. Sickle cell nephropathy was found in 29/204 (14.2%). There were positive significant associations between sickle cell nephropathy with raised serum bilirubin and serum lactate dehydrogenase (p-value = 0.02 and 0.032 respectively). Conclusion: Sickle cell nephropathy is common amongst patients with sickle cell anaemia and raised serum bilirubin and lactate dehydrogenase are predictors of sickle cell nephropathy.

Delayed cord clamping in small for gestational age preterm infants.

BACKGROUND: Infants with restricted growth for age are frequently exposed to insufficient placental circulation and are more likely to develop postnatal complications. Delayed cord clamping at birth for these infants requires further exploration. OBJECTIVE: This study aimed to compare the short-term neonatal outcomes of delayed cord clamping with that of early cord clamping in small for gestational age preterm infants and to explore whether the effects of delayed cord clamping in small for gestational age preterm infants are different from that in non-small for gestational age preterm infants. STUDY DESIGN: We conducted a national retrospective cohort study, including infants born at <33 weeks' gestation and admitted to the Canadian Neonatal Network units between January 2015 and December 2017. Small for gestational age infants (birthweight of <10th percentile for gestational age and sex) who received delayed cord clamping ≥30 seconds were compared with those who received early cord clamping. In addition, non-small for gestational age infants who received delayed cord clamping were compared with those who received early cord clamping. The main study outcomes included composite outcome of mortality or major morbidity, neonatal morbidity rate, mortality rate, peak serum bilirubin, and number of blood transfusions. Multivariable logistic and linear regression models with a generalized estimation equation approach were used to account for the clustering of infants within centers. RESULTS: Overall, 9722 infants met the inclusion criteria. Of those infants, 1027 (10.6%) were small for gestational age. The median (interquartile range) gestational age was 31 weeks (range, 28-32 weeks). After adjusting for potential confounders, delayed cord clamping in small for gestational age infants was associated with a reduction in the composite outcome of mortality or major morbidity (adjusted odds ratio, 0.60; 95% confidence interval, 0.42-0.86) compared with early cord clamping. There was no difference between the 2 groups in peak serum bilirubin. Many associated benefits of delayed cord clamping in small for gestational age infants were similar to those in non-small for gestational age infants. CONCLUSION: Delayed cord clamping in small for gestational age preterm infants was associated with decreased odds of mortality or major morbidity. Many of the benefits of delayed cord clamping in the small for gestational age preterm infants were similar to those identified in the non-small for gestational age preterm infants.

LOW SERUM BILIRUBIN LEVELS IN WOMEN WITH THE ANTIPHOSPHOLIPID SYNDROME.

OBJECTIVE: The aim: To investigate the relationship between serum bilirubin level and the presence of the APS in women with a history of spontaneous miscarriages. PATIENTS AND METHODS: Materials and methods: Fifty six women aged 22-38 (median 27) years with a history of spontaneous miscarriages were divided into two groups: 33 women with the APS and 23 without. Patients were tested for the presence of lupus anticoagulant, anticardiolipin, anti-ß2-glycoprotein 1, antiphospholipid antibodies and genetic thrombophilic defects. RESULTS: Results: Groups were comparable by age, blood pressure, BMI, co-morbidity (anemia, heart abnormality, thyroid disease, overweight). Median serum total bilirubin levels were 7,2 µmol/L (interquartile range [5,8-9,7]) in women with the APS and 10,5 µmol/L (interquartile range [7,5-15,1]) in control group, p=0.005. The chance of detecting a total bilirubin level of less than 8 µmol/L is 4.1 times higher in the APS patients than in the control group (OR 4,1; 95% CI 1,274-13,213). Logistic regression analysis found a statistically significant association between total bilirubin and the presence of the APS (odds ratio, 0.856; 95% CI, 0.734-0.997, p =0.046). Patients with the APS had elevated serum C-reactive protein (medians 2,3 vs 1,1 mg/L, p=0.01) and fibrinogen (medians 2,8 vs 2,5 g/L, p=0.006) levels compared with controls. Correlation analysis revealed a significant correlation between all types of bilirubin and inflammatory markers. CONCLUSION: Conclusions: All types of serum bilirubin (total, direct and indirect) are significantly reduced in women with APS, associated with higher inflammatory markers and lower levels of 25-hydroxyvitamin D, which may be the result of oxidative stress.

Comparison between the Transcutaneous and Total Serum Bilirubin Measurement in Malay Neonates with Neonatal Jaundice.

Background: This study aims to investigate the reliability of the Dräger Jaundice Meter JM-105 for the screening of neonatal jaundice in Malay neonates. Methods: A cross-sectional study was conducted in a university hospital involving 130 jaundiced neonates requiring serum bilirubin determination from day 2 to day 7 of life. Results: The mean total serum bilirubin (TSB) was 232 µmol/L, whereas the mean transcutaneous bilirubin (TcB) measured at the forehead and sternum were 222 µmol/L and 223 µmol/L, respectively. Further, TcB underestimates TSB with a mean difference of 10.10 µmol/L at the forehead and 9.27 µmol/L at the sternum. A positive linear relationship was observed between TSB with TcB forehead (r = 0.82) and TcB sternum (r = 0.80). A good discriminations ability was observed for both the TcB forehead (receiver operating characteristics [ROC] curve = 89.8%) and sternum (ROC curve = 89.7%) at a TSB level of 205 µmol/L. The sensitivity ranges from 84.4% to 85.3%, while the specificity ranges from 77.4% to 76.4%. Conclusion: Our study demonstrates a strong linear relationship and good diagnostic accuracy of TcB values compared to TSB values. To conclude, TcB measured at the forehead or sternum is a good alternative as a non-invasive screening tool for non-severe hyperbilirubinemia in Malay neonates.

Evaluation of role of hyperbilirubinemia as a new diagnostic marker of complicated appendicitis.

BACKGROUND: In appendicitis, elevated intra-luminal pressure and ischemic necrosis of mucosa causes tissue gangrene or perforation. This leads to cytotoxin facilitated progressive bacterial invasion or translocation into the hepatic parenchyma through portal system. This phenomenon interferes with the bilirubin excretion into the bile canaliculi. In the present study, establishment of a possible role of hyperbilirubinemia as a marker of gangrenous/perforated appendicitis has been studied. METHODS: After matching the inclusion and exclusion criteria, all cases of clinically diagnosed acute appendicitis were taken for this prospective, single center, observational study. Per-operative diagnosis was confirmed by histopathological examination. RESULTS: Out of 110 subjects of acute appendicitis 41 subjects (37.27%) had hyperbilirubinemia. Out of 35 subjects diagnosed as complicated appendicitis 32 subjects (91.42%) had raised total bilirubin levels, while the remaining 03 (8.58%) had normal levels. Among 75 subjects diagnosed as acute simple appendicitis 09 subjects (12%) had raised total bilirubin level, while the remaining 66 subjects (88%) had normal levels. It was Mixed Type of Hyperbilirubinemia in gangrenous/perforated appendicitis. The sensitivity of Total serum bilirubin in predicting complicated appendicitis was found 91.43% (76.942% to 98.196%), where as the specificity of this test was 88.00% (78.439% to 94.363%). positive predictive value and negative predictive value were 78.03% and 95.65% respectively. Positive likelihood ratio and negative likelihood ratio were found to be 7.619 and 0.097 respectively taking prevalence of complicated appendicitis be 31.80%. Receiver Operating Characteristic curve was obtained which shows optimal criterion at Total Bilirubin Level 1.06 mg/dl where sensitivity was 91.43% and specificity was 97.33% at 95% confidence interval with 31.8% disease prevalence. CONCLUSIONS: This is to conclude that Serum bilirubin level estimation, which is a simple, cheap and easily available laboratory test, can be added to the routine investigations in clinically suspected cases of acute appendicitis for early diagnosis of complications. Trial registration Registered with Clinical Trials Registry-India (ICMR-NIMS) with Registration number CTRI/2019/05/018879 Dated 01/05/2019. This was a prospective trial. Trial URL: http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=33113&EncHid=99780.32960&modid=1&compid=19%27,%2733113det%27 .

Error simulation modeling to assess the effects of bias and precision on bilirubin measurements used to screen for neonatal hyperbilirubinemia.

OBJECTIVES: Error simulation models have been used to understand the relationship between analytical performance and clinical outcomes. We developed an error simulation model to understand the effects of method bias and precision on misclassification rate for neonatal hyperbilirubinemia using an age-adjusted risk assessment tool. METHODS: For each of 176 measured total bilirubin (TSBM) values, 10,000 simulated total bilirubin (TBS) values were generated at each combination of bias and precision conditions for coefficient of variation (CV) between 1 and 15%, and for biases between -51.3 µmol/L and 51.3 µmol/L (-3 and 3 mg/dL) fixed bias. TBS values were analyzed to determine if they were in the same risk zone as the TSBM value. We then calculated sensitivity and specificity for prediction of ≥75th percentile for postnatal age values as a function of assay bias and precision, and determined the rate of critical errors (≥95th percentile for age TSBM with <75th percentile TBS). RESULTS: A sensitivity >95% for predicting ≥75th percentile bilirubin values was observed when there is a positive fixed bias of greater than 17.1 µmol/L (1.0 mg/dL) and CV is maintained ≤10%. A specificity >70% for predicting <75th percentile bilirubin values was observed when positive systematic bias was 17.1 µmol/L (1 mg/dL) or less at CV ≤ 10%. Critical errors did not occur with a frequency >0.2% until negative bias was -17.1 µmol/L (-1 mg/dL) or lower. CONCLUSIONS: A positive systematic bias of 17.1 µmol/L (1 mg/dL) may be optimal for balancing sensitivity and specificity for predicting ≥75th percentile TSB values. Negative systematic bias should be avoided to allow detection of high risk infants and avoid critical classification errors.

Home phototherapy for hyperbilirubinemia in term neonates-an unblinded multicentre randomized controlled trial.

The aim of this study was to assess whether home phototherapy was feasible and safe in a cohort of otherwise healthy term-born neonates who fulfilled the criteria for in-hospital phototherapy. This was a randomized controlled trial in which term newborns with a total serum bilirubin of 18-24 mg/dL (300-400 µmol) were randomized to either home phototherapy or conventional in-hospital phototherapy. The primary outcome measurements were safety and efficacy, length of stay and the number of failed treatments. The secondary outcomes were the number of blood samples and weight gain during treatment. One hundred forty-seven patients were recruited, 69 patients randomized to conventional phototherapy and 78 to home phototherapy. The results showed that no patients needed blood exchange and only 4% of the patients allocated to home phototherapy were admitted to the hospital. The duration of phototherapy, length of stay, amount of blood tests and weight change showed no statically significant differences.Conclusion: Home phototherapy could be a safe alternative to inpatient phototherapy for otherwise healthy newborns with hyperbilirubinemia if daily checkups and 24/7 telephone support can be provided. The parents should be informed to contact the hospital immediately if they fail to perform the treatment at home.Trial registration: Clinicaltrials.gov NCT03536078 What is Known: • Phototherapy in the hospital is a safe and effective treatment without major side effects. • Fibre optic equipment has made the choice of home phototherapy possible. What is New: • This is the first randomized controlled trial comparing home phototherapy with hospital phototherapy. • Results indicate that home phototherapy could be considered as a safe and feasible alternative when performed according to instructions given, to hospital treatment for otherwise healthy term newborns.

Reliability of transcutaneous bilirubin determination based on skin color determined by a neonatal skin color scale of our own.

Measurement of transcutaneous bilirubin (TcB) is widely used to estimate serum bilirubin (SB). However, its reliability depending on skin tone is still controversial. Ethnic classification does not correlate well with skin tone. We aimed to determine the reliability of transcutaneous bilirubin in a multiethnic population based on skin color according to our neonatal skin color scale. We conducted a prospective, observational study comparing SB and TcB among different skin colors. With the blood sample routinely obtained at 48-72 h for the screening of inborn errors of metabolism, we determined SB and TcB with a jaundice meter. We obtained data from 1359 newborns (color 1 337, color 2 750, color 3 249, color 4 23) and analyzed 1549 dyads SB/TcB. Correlation between TcB and serum bilirubin was very good (R2 = 0.908-0.956), globally and by color group, with slight differences between darker and lighter skin colors. Bland-Altman plots showed different mean bias depending on skin color. Conclusions: Our study not only supports the reliability of TcB to assess SB regardless of skin color, but also supports the fact that TcB tends to overestimate SB in a higher degree in dark-skinned neonates. This may help reduce the number of blood samples for newborns. What is Known: • Jaundice meters are extensively used to diagnose neonatal hyperbilirubinemia, although controversies exist on their reliability depending on skin color. • Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale. What is New: • We verified correlation between serum and transcutaneous bilirubin in a multiethnic population depending on skin color after classifying our neonates into color groups with our own validated neonatal skin color scale.

Lower serum bilirubin is associated with poor renal outcome in IgA nephropathy patients.

Aims: IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide. We conducted this study to explore the relationship between serum bilirubin and renal outcome of patients with IgAN. Methods: A total of 1492 biopsy proven IgAN patients were recruited and divided into two groups according to their median serum bilirubin concentration: the low bilirubin group (serum bilirubin≤9.7umol/L, n=753) and high bilirubin group (serum bilirubin>9.7umol/L, n=739). Basic clinical characteristics were assessed at the time of renal biopsy and the relationships between serum bilirubin and the combined endpoints were analyzed. The combined endpoints were defined as a 50% decline in estimate glomerular filtration rate (e-GFR), end-stage kidney disease (ESKD), renal transplantation and/or death. In addition, propensity score matching (PSM) was then performed to improve balance and simulate randomization between patients in different groups. Kaplan-Meier survival analysis was applied to explore the role of serum bilirubin in the progression of IgAN. Three clinicopathological models of multivariate Cox regression analysis were established to evaluate the association of serum bilirubin and renal prognosis of IgAN. Results: During median 5-year follow-up period, significant differences were shown in Kaplan-Meier analysis. In the unmatched group, 189 (12.7%) patients progressed to the renal combined endpoints. Among this, 122 in 753 patients (16.2%) were in low bilirubin group and 67 in 739 patients (9.1%) were in high bilirubin group (p<0.001). After PSM, there were 134 (11.8%) patients reached the combined endpoints, which included 77 in 566 patients (14.6%) in low bilirubin group and 57 in 566 patients (10.1%) in high bilirubin group (p=0.039). The results of three models (including demographics, pathological, clinical indicators and serum bilirubin) demonstrated that a lower basic serum bilirubin level was significantly associated with a higher risk of reaching combined endpoints in IgAN patients both in unmatched and matched cohort. Conclusion: Serum bilirubin level may be negatively associated with the progression of IgAN.

R-JaunLab: Automatic Multi-Class Recognition of Jaundice on Photos of Subjects with Region Annotation Networks.

Jaundice occurs as a symptom of various diseases, such as hepatitis, the liver cancer, gallbladder or pancreas. Therefore, clinical measurement with special equipment is a common method that is used to identify the total serum bilirubin level in patients. Fully automated multi-class recognition of jaundice combines two key issues: (1) the critical difficulties in multi-class recognition of jaundice approaches contrasting with the binary class and (2) the subtle difficulties in multi-class recognition of jaundice represent extensive individuals variability of high-resolution photos of subjects, huge coherency between healthy controls and occult jaundice, as well as broadly inhomogeneous color distribution. We introduce a novel approach for multi-class recognition of jaundice to detect occult jaundice, obvious jaundice and healthy controls. First, region annotation network is developed and trained to propose eye candidates. Subsequently, an efficient jaundice recognizer is proposed to learn similarities, context, localization features and globalization characteristics on photos of subjects. Finally, both networks are unified by using shared convolutional layer. Evaluation of the structured model in a comparative study resulted in a significant performance boost (categorical accuracy for mean 91.38%) over the independent human observer. Our work was exceeded against the state-of-the-art convolutional neural network (96.85% and 90.06% for training and validation subset, respectively) and showed a remarkable categorical result for mean 95.33% on testing subset. The proposed network makes a performance better than physicians. This work demonstrates the strength of our proposal to help bringing an efficient tool for multi-class recognition of jaundice into clinical practice.

A Comparison of Strategies for Managing the Umbilical Cord at Birth in Preterm Infants.

OBJECTIVE: To evaluate the rates of practice, and the associations between different cord management strategies at birth (delayed cord clamping [DCC], umbilical cord milking [UCM], and early cord clamping [ECC]) and mortality or major morbidity, rates of blood transfusion, and peak serum bilirubin in a large national cohort of very preterm infants. STUDY DESIGN: We retrospectively studied preterm infants <33 weeks of gestation admitted to the Canadian Neonatal Network between January 2015 and December 2017. Patients who received ECC (<30 seconds), UCM, or DCC (≥30 seconds) were compared. Multiple generalized linear/quantile logistic regression models were used. RESULTS: Of 12 749 admitted infants, 9729 were included; 4916 (50.5%) received ECC, 394 (4.1%) UCM, and 4419 (45.4%) DCC. After adjustment for potential confounders identified between groups in univariate analyses, the odds of mortality or major morbidity were higher in the ECC group when compared with UCM group (aOR, 1.18; 95% CI, 1.03-1.35). Mortality and intraventricular hemorrhage were associated with ECC as compared with DCC (aOR, 1.6 [95% CI, 1.22-2.1] and aOR, 1.29 [95% CI, 1.19-1.41], respectively). The odds of severe intraventricular hemorrhage were higher with UCM compared with DCC (aOR, 1.38; 95% CI, 1.05-1.81). Rates of blood transfusion were higher with ECC compared with UCM and DCC (aOR, 1.67 [95% CI, 1.31-2.14] and aOR, 1.68 [95% CI, 1.35-2.09], respectively), although peak serum bilirubin levels were not significantly different. CONCLUSIONS: Both DCC and UCM were associated with better short-term outcomes than ECC; however, the odds of severe intraventricular hemorrhage were higher with UCM compared with DCC.