Development of an equation to predict delta bilirubin levels using machine learning.

OBJECTIVE: Delta bilirubin (albumin-covalently bound bilirubin) may provide important clinical utility in identifying impaired hepatic excretion of conjugated bilirubin, but it cannot be measured in real-time for diagnostic purposes in clinical laboratories. METHODS: A total of 210 samples were collected, and their delta bilirubin levels were measured four times using high-performance liquid chromatography. Data collected included age, sex, diagnosis code, delta bilirubin, total bilirubin, direct bilirubin, total protein, albumin, globulin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, hemoglobin, serum hemolysis value, hemolysis index, icterus value (Iv), icterus index (Ii), lipemia value (Lv), and lipemia index. To conduct feature selection and identify the optimal combination of variables, linear regression machine learning was performed 1,000 times. RESULTS: The selected variables were total bilirubin, direct bilirubin, total protein, albumin, hemoglobin, Iv, Ii, and Lv. The best predictive performance for high delta bilirubin concentrations was achieved with the combination of albumin-direct bilirubin-hemoglobin-Iv-Lv. The final equation composed of these variables was as follows: delta bilirubin = 0.35 × Iv + 0.05 × Lv - 0.23 × direct bilirubin - 0.05 × hemoglobin - 0.04 × albumin + 0.10. CONCLUSION: The equation established in this study is practical and can be easily applied in real-time in clinical laboratories.

Newborn screening for biliary atresia using direct bilirubin: An implementation science study.

OBJECTIVE: Biliary atresia (BA) is a liver disease of infancy characterized by obstruction of the biliary tree. Infants with BA have the best outcomes when identified early and the Kasai portoenterostomy is performed before 45 days of life (DoL). In our hospital system, the average age at Kasai was 60 DoL. To address the problem of late presentation, we implemented a two-stage BA screening strategy utilizing direct bilirubin (DB). METHODS: New institutional policies were established that all newborns were tested at 24-48 h of life, and those with levels ≥0.5 mg/dL were followed further. The infant's primary care provider was contacted to recommend a repeat DB at 2 weeks of life. If the repeat DB was ≥1.0 mg/dL, the patient was evaluated by gastroenterology. RESULTS: Over the 16 months, 3880 infants were born and 3861 (99.5%) were screened; 53 infants (1.3%) had DB levels ≥0.5 mg/dL initially. Upon repeat testing at 2 weeks, there were three groups of infants: not retested (n = 1), retested <1.0 mg/dL (n = 40), and retested ≥1.0 mg/dL (n = 12). The average time to be seen by gastroenterology was 4.3 days or 18.3 DoL. DISCUSSION: The screening included a series of steps that needed to be implemented effectively. Screening had a net false positive rate of 0.3% (12 out of 3861) and identified causes of cholestasis other than BA. BA was excluded by 28 DoL on average. Our results can provide a template for other institutions interested in implementing a BA screening protocol in their practice.

Pregnancy cholestasis typically occurs in the third trimester of pregnancy and is a significant clinical condition.

AIM: The aim of this study is to determine the albumin/bilirubin ratio index and the aspartate aminotransferase (AST)/alanine aminotransferase ratio (ALT) index in patients diagnosed with cholestasis during pregnancy, and to demonstrate their correlation with liver damage. Additionally, potential strategies to prevent liver damage will be elucidated. MATERIALS AND METHOD: Our study is a retrospective study. A total of 4019 pregnant women aged between 18 and 40 years, presenting with itching complaints at 32-36 weeks of gestation, were screened at the Department of Obstetrics and Gynecology, Istanbul Training and Research Hospital of Health Sciences University between January 1, 2018, and December 31, 2023. Among them, 104 pregnant women without any other accompanying diseases were diagnosed with Gestational Cholestasis. Among the 104 diagnosed women, 78 met the inclusion criteria and were included in the study. Twenty-six women were excluded from the study due to missing albumin and total bilirubin values or due to blood samples being taken at different times. The serum albumin/bilirubin ratio index and the alanine aminotransferase/aspartate aminotransferase ratio index were calculated and statistically compared between pregnant women diagnosed with cholestasis and healthy pregnant women at the same gestational week. FINDINGS: We found that AST, ALT, albumin, and total bilirubin levels were significantly higher in pregnant women diagnosed with cholestasis compared to the control group (p < 0.05). The AST/ALT index in the case group was significantly lower compared to the control group. However, there were no significant differences found between the case and control groups regarding the albumin/total bilirubin index and ALBI grade. When comparing ALBI grades in cases, no significant differences were found in terms of patients' age, gestational week, AST, ALT, and AST/ALT index. When compared according to ALBI grades, the albumin level was higher in patients with ALBI grade I compared to grade II, and in patients with grade II compared to grade III. The total bilirubin level was significantly higher in patients with ALBI grade III compared to grades I and II, but there was no significant difference between grades I and II. No significant differences were found among the groups separated according to ALBI grades when FBA values were compared. CONCLUSION: In this study, the negative correlation between lower AST/ALT ratio and FBA values in patients with severe cholestasis suggests the need for careful consideration regarding future liver damage. The lack of difference in ALBI score between the case and control groups, as well as the absence of correlation with FBA values, indicates the necessity to evaluate ALBI score based on patients' long-term prognosis.

Concomitant determination of hematological indices supported the application of the albumin-bilirubin score in non-malignant liver diseases.

The albumin-bilirubin (ALBI) score is a useful prognostic marker that predicts mortality in patients suffering from terminal diseases. Recently, it has been reported that ALBI score is a predictor of non-malignant liver diseases. The cutoff point of the ALBI score that distinguishes hepatocellular carcinoma from non-malignant liver disease is still not identified. Therefore, the ALBI score is a sensitive rather than a specific predictor of the poor outcomes of liver diseases. There are many hematological indices and ratios that are utilized as prognostic biomarkers. Among these biomarkers are the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and platelet-hemoglobin ratio (PHR), which are useful discriminating prognostic biomarkers for liver diseases, e.g., hepatocellular carcinoma, hepatitis, liver fibrosis, etc. There is evidence that PLR and PHR are prognostic biomarkers that predict the poor outcomes of diseases. Therefore, concomitant measurements of ALBI score and PHR or ALBI score and PLR will improve the predictive value that can differentiate hepatocellular carcinoma from non-malignant diseases.

Modified Albumin-Bilirubin Grade After Curative Treatment: Predicting the Risk of Late Intrahepatic Recurrence of Hepatocellular Carcinoma.

BACKGROUND: We aimed to identify the prognostic factors for late intrahepatic recurrence (IHR), defined as recurrence more than two years after curative treatment of newly diagnosed hepatocellular carcinoma (HCC). METHODS: This retrospective cohort study included patients with newly diagnosed, previously untreated, very early, or early HCC treated with initial curative treatment and followed up without recurrence for more than two years, excluding early IHR defined as recurrence within two years in single center. Late IHR-free survival (IHRFS) was defined as the time interval from initial curative treatment to the first IHR or death without IHR, whichever occurred first. RESULTS: Among all the enrolled 2,304 patients, 1,427 (61.9%) underwent curative intent hepatectomy and the remaining 877 (38.1%) underwent local ablative therapy (LAT). During the follow-up after curative treatment (median, 82.6 months; range, 24.1 to 195.7), late IHR was detected in 816 (35.4%) patients. In the multivariable analysis, age, male sex, cirrhotic liver at diagnosis, type of initial treatment, and modified albumin-bilirubin (mALBI) grade were significant prognostic baseline factors. Furthermore, mALBI grade at three (2a vs. 1, P = 0.02, hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.04-1.70; 2b/3 vs. 1, P = 0.03; HR, 1.42; 95% CI, 1.03-1.94) and six months (2b/3 vs. 1; P = 0.006; HR, 1.61; 95% CI, 1.13-2.30) after initial curative treatment was also a significant prognostic factor for late IHR. CONCLUSION: After curative treatment for newly diagnosed early HCC, the mALBI grade at three and six months after initial curative treatment, as well as at baseline, was one of the most crucial prognostic factors for late IHR.

An Invisible Dermal Nanotattoo-Based Smart Wearable Sensor for eDiagnostics of Jaundice.

Despite substantial progress in the diagnosis of jaundice/hyperbilirubinemia as the most common disease and cause of hospitalization of newborns, on the eve of Industry/Healthcare 5.0, the development of accurate and reliable wearable diagnostic sensors for noninvasive smart monitoring of bilirubin (BIL) is still in high demand. Aiming to fabricate a smart wearable sensor for early diagnosis of neonatal jaundice and its therapeutic monitoring, we here report a fluorescent dermal nanotattoo that further coupled with an IoT-integrated wearable optoelectronic reader for minimally invasive, continuous, and real-time monitoring of BIL in interstitial fluid. Selective recovery of quenched fluorescence of the dermal tattoo sensor, composed of biocompatible dissolving/hydrogel microneedles loaded with fluorescent carbon quantum dots, upon blue light exposure used for jaundice phototherapy was utilized for highly selective BIL sensing. The fascinating features of our developed smart wearable tattoo sensor and its successful results with high correlation with blood BIL results make it a highly promising sensor for easy, minimally invasive, reliable, and smart eDiagnostics and continuous therapeutic eMonitoring of jaundice and other BIL-induced diseases at the point of care. We envision that the developed nanotattoo sensing bioplatform will inspire the development of future smart tattoo sensors in various diagnostic and monitoring scenarios.

Loss of biochemical response at any time worsens outcomes in UDCA-treated patients with primary biliary cholangitis.

Background & Aims: Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival. Methods: We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry). Results: A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results. Conclusion: Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy. Impact and implications: Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy.

Icteria interference for 34 clinical chemistry analytes on different analytical platforms: Method or analyzer dependent?

OBJECTIVES: In this study, we aimed to investigate the effect of increasing bilirubin concentration on 34 commonly measured clinical chemistry analytes on four different analytical platforms. We hypothesized that differences in icteria interference are not only method dependent, but also analyzer dependent. METHODS: Serum pool was prepared using leftover samples after routine laboratory blood testing. Serum pool was then spiked with dissolved bilirubin stock. Measurements were performed on all four locations at the same time. All measurements were done in duplicate. Mean value was calculated as: (value1 + value2)/2. Those values were multiplied by corresponding dilution factors obtained during the preparation of icteric samples. For each icteric sample (Ix), bias against native (I0) sample was calculated as ((value Ix- valueI0)/ valueI0) × 100 %. Bias was calculated with actual average values. Obtained bias values were compared against acceptance criteria according to External quality assurance (EQA) providers. Difference in bilirubin concentration across platforms was tested using Friedman ANOVA. P values < 0.05 were considered statistically significant. Data are collected and analyzed in MS Excel 2016 (Microsoft, Redmond, Washington) and MedCalc® Statistical Software version 20.015 (MedCalc Software Ltd, Ostend, Belgium). RESULTS: Many of the tested parameters demonstrated low sensitivity to icterus interference. The highest sensitivity to icterus was observed for triglycerides, cholesterol, and urate. CONCLUSIONS: Our results indicate that while some common icteric interferences were consistent across all tested platforms, others were specific to the analyzer used, even when employing the same analytical methods.

Biliary drainage in palliative and curative intent European patients with hilar cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis.

BACKGROUND AND AIMS: Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy - including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented. PATIENTS AND METHODS: We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients. RESULTS: 56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia. CONCLUSIONS: Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients.

The use of a simple and affordable skin patch for measurement of transcutaneous bilirubin levels in neonates during phototherapy.

Background: Transcutaneous bilirubin (TcB) measurements during and after phototherapy for hyperbilirubinemia must be performed on unexposed skin. There are commercially made skin patches for this purpose, but they are relatively unavailable in low-resource settings. We devised a simple cotton patch and tested its use for TcB during phototherapy. Methods: Measurements were taken in healthy neonates born at a gestational age of ≥35 weeks who were undergoing phototherapy for hyperbilirubinemia in western India before, 12 h after the start, and 12 h after the end of phototherapy. Total serum bilirubin (TSB) was measured using the diazo method in a clinical laboratory. TcB measurements were performed using a Dräger Jaundice Meter JM-105 placed over the sternum on two skin areas that were protected during and after treatment by a commercial (Philips BilEclipse) or self-made patch comprised of cotton gauze and wool. Results: In total, 47 neonates were included in our study. Before phototherapy, TSB and TcB values had a strong correlation (Pearson, r = 0.88), with a mean difference of -1.35 mg/dl. Correlations with TSB were good and equivalent for TcB values measured on skin covered by the commercial and self-made patches during (0.78 and 0.70, respectively) and after (0.57 and 0.58, respectively) phototherapy. TcB values measured on skin covered by the two patches correlated well both during and after phototherapy, with r = 0.82 and 0.90, respectively, and mean (95% confidence interval) differences of -1.21 and -0.32 mg/dl, respectively. Conclusions: Reliable TcB measurements taken during and after phototherapy can be achieved on skin covered with a simple and affordable cotton skin patch.

Use of fenofibrate as adjuvant to phototherapy in unconjugated neonatal hyperbilirubinemia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Most neonates have neonatal jaundice, with 5-15% requiring phototherapy. Although phototherapy is beneficial, it can potentially extend hospital stays and cause harm. This study's purpose was to analyze the effects of fenofibrate and phototherapy on total serum bilirubin (TSB) levels at 24 and 48 hours (primary outcome) after intervention. Furthermore, the phototherapy duration and adverse events were also of interest (secondary outcome). METHODS: The study protocol was registered in the PROSPERO database. Articles were searched on EMBASE, PubMed, Cochrane Library, and Google Scholar. Study selection was done following PRISMA and risk of bias studies were conducted. The Review Manager 5.4 was used for the meta-analysis. RESULTS: Nine studies, including 610 newborns, were identified and included in the meta-analysis. This meta-analysis discovered a significant change in TSB levels at 24 hours after intervention (mean difference (MD) -0.96 (95% CI -1.09, -0.83), p <  0.00001) with low heterogeneity and at 48 hours after intervention (MD -1.75 (95% CI -2.26, -1.24), p <  0.00001) with high heterogeneity. Significant shortening of phototherapy duration was observed in the interventional group (MD -15.28 (95% CI -20.65, -9.90), p <  0.00001) with high heterogeneities. One of the nine studies reported a non-significant occurrence of abdominal distension and diarrhea in the fenofibrate group. CONCLUSION: Fenofibrate might be applied as an adjuvant in unconjugated neonatal hyperbilirubinemia to reduce the average total serum bilirubin and shorten the length of phototherapy.

Unconjugated bilirubin promotes uric acid restoration by activating hepatic AMPK pathway.

Hyperuricemia and its development to gout have reached epidemic proportions. Systemic hyperuricemia is facilitated by elevated activity of xanthine oxidase (XO), the sole source of uric acid in mammals. Here, we aim to investigate the role of bilirubin in maintaining circulating uric acid homeostasis. We observed serum bilirubin concentrations were inversely correlated with uric acid levels in humans with new-onset hyperuricemia and advanced gout in a clinical cohort consisting of 891 participants. We confirmed that bilirubin biosynthesis impairment recapitulated traits of hyperuricemia symptoms, exemplified by raised circulating uric acid levels and accumulated hepatic XO, and exacerbated mouse hyperuricemia development. Bilirubin administration significantly decreased circulating uric acid levels in hyperuricemia-inducing (HUA) mice receiving potassium oxonate (a uricase inhibitor) or fed with a high fructose diet. Finally, we proved that bilirubin ameliorated mouse hyperuricemia by increasing hepatic autophagy, restoring antioxidant defense and normalizing mitochondrial function in a manner dependent on AMPK pathway. Hepatocyte-specific AMPKα knockdown via adeno-associated virus (AAV) 8-TBG-mediated gene delivery compromised the efficacy of bilirubin in HUA mice. Our study demonstrates the deficiency of bilirubin in hyperuricemia progression, and the protective effects exerted by bilirubin against mouse hyperuricemia development, which may potentiate clinical management of hyperuricemia.

Signal Quality in Continuous Transcutaneous Bilirubinometry.

Bilirubin is a product of the metabolism of hemoglobin from red blood cells. Higher levels of bilirubin are a sign that either there is an unusual breaking down rate of red blood cells or the liver is not able to eliminate bilirubin, through bile, into the gastrointestinal tract. For adults, bilirubin is occasionally monitored through urine or invasive blood sampling, whilst all newborns are routinely monitored visually, or non-invasively with transcutaneous measurements (TcBs), due to their biological immaturity to conjugate bilirubin. Neonatal jaundice is a common condition, with higher levels of unconjugated bilirubin concentration having neurotoxic effects. Actual devices used in TcBs are focused on newborn populations, are hand-held, and, in some cases, operate in only two wavelengths, which does not necessarily guarantee reliable results over all skin tones. The same occurs with visual inspections. Based on that, a continuous bilirubin monitoring device for newborns is being developed to overcome visual inspection errors and to reduce invasive procedures. This device, operating optically with a mini-spectrometer in the visible range, is susceptible to patient movements and, consequently, to situations with a lower signal quality for reliable bilirubin concentration estimates on different types of skin. Therefore, as an intermediate development step and, based on skin spectra measurements from adults, this work addresses the device's placement status prediction as a signal quality indication index. This was implemented by using machine learning (ML), with the best performances being achieved by support vector machine (SVM) models, based on the spectra acquired on the arm and forehead areas.

Prognostic Value of Easy Albumin-Bilirubin Score for Radical Surgery in Patients With Gallbladder Carcinoma.

BACKGROUND: To investigate the clinical significance of the easy albumin-bilirubin (EZ-ALBI) score as a prognostic indicator in postoperative patients with gallbladder carcinoma (GBC). METHODS: The comprehensive clinical and pathological records of 140 patients with GBC who underwent radical resection between January 2015 and December 2020 were retrospectively examined. Based on the EZ-ALBI score, the 140 GBC patients were categorized into two groups: a low EZ-ALBI score group (score ≤ -34.4) consisting of 108 patients and a high EZ-ALBI score group (score > -34.4) consisting of 32 patients. The association between the EZ-ALBI score and clinicopathological factors was assessed. Survival analysis was performed using the Kaplan-Meier method, and the Cox proportional hazard model was utilized to evaluate the impact of clinicopathological factors on prognosis. RESULTS: Significant differences were observed between the low EZ-ALBI score group and the high EZ-ALBI score group in terms of serum total bilirubin, serum albumin, CA19-9 levels, liver metastasis, and tumor TNM stage. The 5-year survival rate was significantly lower in the high EZ-ALBI score group compared to the low EZ-ALBI score group. Univariate analysis indicated that serum total bilirubin, lymph node metastasis, TNM stage, and EZ-ALBI score were closely related to overall survival (OS). Multivariate analysis identified TNM stage and EZ-ALBI score as independent prognostic factors for OS. CONCLUSIONS: The EZ-ALBI score is a significant independent prognostic factor for overall survival in GBC patient's post-radical resection, highlighting its potential utility in clinical prognosis and patient management.

Supramolecular nanoparticle loaded with bilirubin enhances cartilage protection and alleviates osteoarthritis via modulating oxidative stress and inflammatory responses.

Osteoarthritis (OA) is a chronic inflammation that gradually leads to cartilage degradation. Prolonged chondrocyte oxidative stress contributes to the development of diseases, including chondrocyte apoptosis, cartilage matrix degradation, and aggravation of articular cartilage damage. Bilirubin (BR) possesses strong antioxidant properties by scavenging reactive oxygen species (ROS) and potent protection effects against inflammation. However, its insolubility and short half-life limit its clinical use. Therefore, we developed a supramolecular system of ε-polylysine (EPL) conjugated by ß-cyclodextrin (ß-CD) on the side chain, and bilirubin was loaded via host-guest interactions, which resulted in the self-assemble of this system into bilirubin-loaded polylysine-ß-cyclodextrin nanoparticle (PB) with improving solubility while reducing toxicity and prolonging medication action time. To explore PB's potential pharmacological mechanisms on OA, we established in vitro and in vivo OA models. PB exerted ROS-scavenging proficiency and anti-apoptotic effects on rat chondrocytes by activating the Nrf2-HO-1/GPX4 signaling pathway. Additionally, PB reprogrammed the cartilage microenvironment by regulating the NF-κB signaling pathway to maintain chondrocyte function. Animal experiments further confirmed that PB had excellent scavenging ability for ROS and inflammatory factors related to charge adsorption with cartilage as well as long retention ability. Together, this work suggests that PB has superior protective abilities with beneficial effects on OA, indicating its great potential for intervention therapy targeting chondrocytes.

Validity of transcutaneous bilirubin measurements during and after phototherapy in term and late preterm infants.

The purpose of the study was to investigate correlation and concordance between total serum bilirubin (TSB) and transcutaneous bilirubin measured at covered (TcBC) and uncovered (TcBU) skin during and after discontinuation of phototherapy. A cross-sectional study included ≥ 34 weeks gestation infants requiring phototherapy for neonatal hyperbilirubinemia. In-house, photo-opaque patches were placed on infants' sternums before phototherapy initiation. Simultaneous blood sampling for TSB, TcBC, and TcBU measurements were performed. Among 103 infants included in the final analysis, 70% were full-term. Covering skin during phototherapy resulted in strong TcBC-TSB correlation (r = 0.91, 95% CI 0.87-0.94, P < 0.001) compared to TcBU (r = 0.53, 95% CI 0.37-0.65, P < 0.001), persisting post-phototherapy (r = 0.88, 95% CI 0.82-0.91, P < 0.001). Bland-Altman analysis showed a higher mean difference and wider 95% limits of agreement for TcBU-TSB during phototherapy (-6.3 mg/dL and -11.1 to -1.6) vs TcBC-TSB (0.9 mg/dL and -1.2 to 2.9). Passing-Bablok regression analysis confirmed good agreement between TcBC and TSB. CONCLUSIONS: The application of in-house, photo-opaque patches enhanced the correlation and agreement between TcBC and TSB during and after discontinuation of phototherapy. This may prove particularly useful in resource-limited settings where commercial devices are unavailable. WHAT IS KNOWN: • Transcutaneous bilirubin measurement has been widely used as a screening method for neonatal hyperbilirubinemia. • The accuracy of transcutaneous bilirubin measurements during and after phototherapy in infants with hyperbilirubinemia has been debated. WHAT IS NEW: • Our study demonstrated that utilizing carefully designed photo-opaque patches enhanced the accuracy of transcutaneous bilirubin measurement during and after phototherapy. • Effective in-house alternatives are crucial in resource-limited settings where commercial opaque patches are not always accessible or affordable.

Yellow Emissive Carbon Dots - A Robust Nanoprobe for Highly Sensitive Quantification of Jaundice Biomarker and Mitochondria Targeting in Cancer Cells.

The abnormally high level of bilirubin (BR) in biofluids (human serum and urine) indicates a high probability of jaundice and liver dysfunction. However, quantification of BR as the Jaundice biomarker is difficult due to the interference of various biomolecules in serum and urine. To address this issue, we developed a fluorescence-based detection strategy, for which yellow emissive carbon dots (YCDs) were produced from a one-step solvothermal process using phloroglucinol and thionin acetate as chemical precursors. The as-fabricated YCDs exhibited a strong fluorescence peak at the wavelength of 542 nm upon excitation at 390 nm. We used YCDs for detecting BR through the fluorescence turn-off mechanism, unveiling the excellent sensitivity in the linear range of 0.5-12.5 µM with a limit of detection (LOD) of 9.62 nM, which was far below the clinically relevant range. The analytical nanoprobe also offered excellent detection specificity for quantifying BR in real samples. Moreover, the biocompatible fluorescent nanoprobe was successfully employed to target mitochondria in live cancer cells. A colocalization study confirmed that YCDs possessed the ability to target mitochondria and overlapped completely with MitoTracker Red. The developed nanoprobe of YCDs turned out to be straightforward in their synthesis, noninvasive, and can be utilized for biomedical sensors to diagnose the onset of jaundice as well as for mitochondria targeting.

Association between serum total bilirubin with Parkinson's disease among American adults (NHANES 1999 to 2018).

Background: Currently, the existing evidence on the correlation between serum total bilirubin (STB) and Parkinson's disease (PD) is insufficient. The objective of this study was to clarify the relationship between STB levels and PD within the US (United States) population. Methods: A cross-sectional analysis was conducted using data from 25,637 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Weighted logistic regression, smooth curve fitting, subgroup analysis, and sensitivity analyses were employed to validate the research objectives. Results: Among all eligible subjects, the mean age was 57.11 ± 11.78 years. The prevalence of PD was 1.18 % overall, with 47.86 % in males. After adjusting for multiple variables, the odds ratio [OR] (95 % confidence interval [CI]) for PD associated with STB levels in T2 and T3 were 0.59 (95 % CI = 0.40-0.85, p = 0.006) and 0.67 (95 % CI = 0.45-0.99, p = 0.045), respectively, when compared to STB levels in T1. The analysis using restricted cubic splines (RCS) indicated an L-shaped relationship between STB levels and the prevalence of PD (p for nonlinearity = 0.004), with the lowest risk observed at 10.84 µmol/L. Comparable patterns of association were noted in subgroup analyses. Furthermore, consistent findings were derived from additional sensitivity analyses. Conclusions: Our study findings indicated that the level of STB is significantly negatively correlated with the prevalence of PD. Therefore, more prospective studies need to be designed to prove the causal relationship between them.