Ensemble learning for the early prediction of neonatal jaundice with genetic features

Background Neonatal jaundice may cause severe neurological damage if poorly evaluated and diagnosed when high bilirubin occurs. The study explored how to effectively integrate high-dimensional genetic features into predicting neonatal jaundice. Methods This study recruited 984 neonates from the Suzhou Municipal Central Hospital in China, and applied an ensemble learning approach to enhance the prediction of high-dimensional genetic features and clinical risk factors (CRF) for physiological neonatal jaundice of full-term newborns within 1-week after birth. Further, sigmoid recalibration was applied for validating the reliability of our methods. Results The maximum accuracy of prediction reached 79.5% Area Under Curve (AUC) by CRF and could be marginally improved by 3.5% by including genetic variant (GV). Feature importance illustrated that 36 GVs contributed 55.5% in predicting neonatal jaundice in terms of gain from splits. Further analysis revealed that the main contribution of GV was to reduce the false-positive rate, i.e., to increase the specificity in the prediction. Conclusions Our study shed light on the theoretical and practical value of GV in the prediction of neonatal jaundice.

Optimization of an ammonia assay based on transmembrane pH-gradient polymersomes

Reliable ammonia quantification assays are essential for monitoring ammonemia in patients with liver diseases. In this study, we describe the development process of a microplate-based assay for accurate, precise, and robust ammonia quantification in biological fluids, following regulatory guidelines on bioanalytical method validation. The assay is based on transmembrane pH-gradient polymersomes that encapsulate a pH-sensitive ratiometric fluorophore, the fluorescence signal of which correlates with the ammonia concentration in the sample. Using a four-parameter logistic regression, the assay had a large quantification range (30–800 μM ammonia). As for selectivity, the presence of amino acids or pyruvate (up to clinically relevant concentrations) showed no assay interference. In samples with low bilirubin levels, polymersomes containing the fluorophore pyranine provided accurate ammonia quantification. In samples with high bilirubin concentrations, billirubin’s optical interference was alleviated when replacing pyranine with a close to near-infrared hemicyanine fluorophore. Finally, the assay could correctly retrieve the ammonia concentration in ammonia-spiked human plasma samples, which was confirmed by comparing our measurements with the data obtained using a commercially available point-of-care device for ammonia.

Characteristics and Outcome of Adults with Severe Autoimmune Hemolytic Anemia Admitted in Intensive Care Unit: Results from a Large French Observational Study

Introduction : Adult' autoimmune hemolytic anemia (AIHA) can be life-threatening with an overall mortality rate of 8-10% which can rise up to 30% for patients admitted in intensive care unit (ICU). The factors associated with the need of management in ICU are partially unknown as only few data are available in the literature. To better describe the baseline characteristics and outcome of severe adult'AIHA admitted in ICU and to identify some prognostic factors, an observational multicentre study was set up by the French reference center of adult' immune cytopenias. Patients and Methods : This was an observational retrospective multicentre study. Patients had to fulfill the following inclusion criteria : 1) Age ≥ 18 years at time of AIHA onset ; 2) Definite diagnosis of primary or secondary warm (wAIHA), cold (cAIHA) or mixed AIHA ; 3) At least one admission in ICU specifically for the management of AIHA. Patients with AIHA admitted in ICU for another reason than the severity of AIHA were excluded. Patients' baseline characteristics at time of admission in ICU were recorded by means of a standardized form including the Charlson comorbidity score, the Knaus score, the Sequential Organ Failure Assessment (SOFA) and the Simplified Acute Physiology Score (SAPS II). Categorical variables were expressed as number (percentage) and quantitative variable as median [interquartile range]. To identify factors associated with death in ICU or after 1 year of follow-up, patients' characteristics were compared using usual tests. In order to identify some parameters associated with the risk of admission in ICU, the main characteristics of the patients were compared to those of controls (1 to 2 ratio) diagnosed with AIHA and followed over the same period who were never admitted in ICU. Univariate logistic regressions analyses were performed followed by a multivariate logistic regression using a backward stepwise selection procedure. A p-value <0.05 was considered as statistically significant. Results : In total, 62 patients (42% of females) from 11 centers fulfilling the inclusion criteria were included for a total of 69 admissions in ICU (see table for baseline characteristics). Of note, 57/62 patients (92%) had a low (< 121) bone marrow reticulocytes index (BMRI) reflecting an impaired erythropoiesis. The mortality rate in ICU was 13%; 3 patients died from massive pulmonary embolism. Compared to the 54 survivors the 8 patients who died in ICU had: a higher CRP level (p value = 0.011); a higher need for transfusion (median number of packed red cells was 12 versus 4, p value = 0.008); higher SOFA and IGS scores (p value = 0.006); a higher number of organ failures on admission (p value < 0.001), thrombotic events (p value = 0.024) and sepsis during the stay in ICU (p value = 0.019). Among the survivors, 9/49 (5 lost of follow-up) eventually died within a year after the admission in ICU leading to an overall mortality rate of 30% at 1 year. For the management of AIHA in ICU, 56 patients (90%) were transfused (median number of packed red cells = 4 [2-7]); recombinant Epo was administered to 14 patients (22.5%) and 5 patients (8%) had plasma exchange. In ICU, 58 patients (95%) were treated with corticosteroids, 29 (46%) received at least one other treatment line including mostly : rituximab (n = 22), intravenous immunoglobulin (n = 10), iv cyclophosphamide (n = 5), cyclosporin (n = 3). Other treatment lines including chemotherapy-based regimen (n=8) were given afterwards. The characteristics of the 62 patients were compared to those of 138 controls with AIHA who were never admitted in ICU. In univariate analyses, younger age, Evans' syndrome, Hb level < 6 g/dl; reticulocytes count < 100 x 10 9/L, BMRI <121 and high bilirubin level were significantly associated with an admission in ICU. In multivariate analysis, a low Hb level and a high bilirubin level were the only parameters that were significantly associated with the risk of admission in ICU Conclusion : Based on this retrospective study, the mortality rate of adult patients admitted in ICU for AIHA was lower than expected (13%) but the 1 year mortality rate in this population of patients rose up to 30%. Patients with AIHA and a Hb level < 6g/dl, a high bilirubin level and/or an inadequate reticulocytes count must be treated promptly and monitored closely beyond the initial phase of the disease in order to reduce the mortality rate. The treatment of severe refractory cases is not consensual and should be harmonized. Figure 1 Figure 1. Disclosures Comont: Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. Riviere: Octapharma: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees. Haioun: Janssen: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Miltenyi: Honoraria, Research Funding. Godeau: Amgen: Consultancy; Sobi: Consultancy; Novartis: Consultancy; Grifols: Consultancy. Michel: Amgen: Consultancy; Rigel: Honoraria; Alexion: Honoraria; UCB: Honoraria; Argenx: Honoraria; Novartis: Consultancy. OffLabel Disclosure: rituximab is commonly used off-label as a second line for adult' AIHA

EXPRESS: Novel cholesterol efflux assay using immobilized liposome-bound gel beads: Confirmation and improvement for application in clinical laboratory

Objectives Cholesterol efflux capacity (CEC), an atheroprotective function of high-density lipoprotein, is expected to be a potential biomarker for cardiovascular disease. However, CEC has not been widely introduced for application in clinical laboratories because of the complexity of the conventional CEC assay using cells and radioactive materials. Previously, we developed a novel CEC assay using immobilized liposome-bound gel beads (ILG), which solves these issues. We aimed to confirm the validation and further improve the ILG method for application in the clinical setting. Methods Cholesterol efflux capacity values by the ILG method assayed for shorter incubation time (4 h) were compared to those assayed for 16 h (our previous ILG method). To investigate a reference material that can correct the variation between ILG manufacturing lots, bovine serum albumin, human gamma-globulins, and globulin complexes were evaluated. CEC values were also estimated in plasmas obtained with different anticoagulants, serum treated with freeze-thaw cycles, and serum mixed with several interference substances. Results The CEC of 4- and 16-h incubation times were well correlated. Globulin complexes may be used as a reference material. Plasma can be used as the specimen. The serum and stored temperature of the specimen did not largely affect CEC. Hemoglobin and chyle did not have an effect on CEC, whereas high-bilirubin serum showed elevated CEC. The effect of bilirubin was nearly canceled by subtracting basal fluorescence intensity. Conclusions Present ILG method further fulfills some requirements for application in clinical laboratory. Using this reliable simple method, evaluation for clinical significance of CEC is expected.

THE SURGICAL BILIO-DIGESTIVE BYPASS BEFORE CEPHALIC PANCREATICODUODENECTOMY, REPORT OF EIGHT CASES

The cephalic pancreaticoduodenectomy (CPD) has a universally high morbidity and surgery in patients with obstructive jaundice is associated with a high risk of postoperative complications especially in patients with high bilirubin levels. For this reason, endoscopic preoperative biliary drainage (PBD) has been proposed to improve the postoperative courses.. Nevertheless, this solution is not always feasible and the use of a surgical bilio-digestive bypass may be necessary, which may complicate a later surgical procedure.In this work we report a case series of patients who underwent CPD preceded by a double surgical bypass and we analyze its impact on morbi-mortality.

Neonatal Physiological Jaundice and Repertoire of Movements on the Second or Third Days of Life

Physiological jaundice appears after the first day of life and has a mild form in most cases. High bilirubin levels can lead to jaundice of the basal ganglia and cause severe movement disorders in the form of extrapyramidal forms of cerebral palsy. The aim of the study was to assess the effect of bilirubin levels on the motor activity of infants and the relationship between bilirubin levels and selected sociometric and biometric characteristics. The study included a group of 77 newborns of both sexes. Medical records were analyzed to determine their socio- and biometric characteristics. Bilirubin levels were evaluated using transcutaneous bilirubin (TcB) measurement with a Minolta JM-103 jaundice meter according to Kramer’s method consisting in bilirubin measurements in different parts of the body. The head measurement was considered the most important for infants on the second or third day of life, and it was considered a reference for other variables. Analysis of neonatal activity was performed using video recording with a Sony camera with Full HD 1080p resolution (1920x1080, 60 fps). Each infant was assessed independently by three experts qualified in Prechtel's General Movements Assessment diagnosis. No statistically significant differences in quantitative movement characteristics were observed between infants with normal and elevated bilirubin levels. The relationships were found between sociometric and biometric characteristics and bilirubin levels measured on the head. The analyses indicated that in the course of physiological jaundice, the bilirubin levels had no effect on their qualitative and quantitative movement parameters in the group of infants studied.

Optimization of an Ammonia Assay based on Transmembrane pH-gradient Polymersomes

Reliable ammonia quantification assays are essential for monitoring ammonemia in patients with liver diseases. In this study, we describe the development process of a microplate-based assay for accurate, precise, and robust ammonia quantification in biological fluids, following regulatory guidelines on bioanalytical method validation. The assay is based on transmembrane pH-gradient polymersomes that encapsulate a pH-sensitive ratiometric fluorophore, the fluorescence signal of which correlates with the ammonia concentration in the sample. Using four-parameter logistic regression, the assay had a large quantification range (30–800 µM ammonia). As for selectivity, the presence of amino acids or pyruvate (up to clinically relevant concentrations) showed no assay interference. In samples with low bilirubin levels, polymersomes containing the fluorophore pyranine provided accurate ammonia quantification. In samples with high bilirubin concentrations, billirubin’s optical interference was alleviated when replacing pyranine with a close to near-infrared hemicyanine fluorophore. Finally, the assay could correctly retrieve the ammonia concentration in ammonia-spiked human plasma samples, which was confirmed by comparing our measurements with the data obtained using a commercially available point-of-care device for ammonia.

DESCRIPTION OF BILIRUBIN CONDITION CHECKING ON ALCOHOL CONSUMER IN EAST POHUWATO VILLAGE, POHUWATO DISTRICT

Based on 2014 WHO data, 61.7% of the world's population has consumed alcohol for more than 12 months which has caused around 3.3 million deaths or 5.9% of all deaths worldwide. For the 2018 RISKESDAS data in Indonesia, the first highest alcohol consumption area is North Sulawesi 16%, followed by East Nusa Tenggara 15.6, then Bali area 14%, and for Gorontalo area 11.3%. The purpose of this study was to determine the description of bilirubin levels in alcohol consumers in Pohuwato Timur Village, Pohuwato Regency including the length of time of consumption, age, types of drinks frequently consumed, frequency of alcohol consumption, and frequency of the amount of alcohol in one drink. This research uses descriptive research which is quantitative in nature. The population in the study was 55 samples with a sample size of 36 respondents who used the sampling technique, namely simple random sampling. The results showed that of the 36 respondents where the normal bilirubin levels were 14 respondents or if the percentage was 39%, while for the abnormal or high bilirubin levels there were 22 respondents or if the percentage was 61%. Based on the results obtained, it can be concluded that the results of the examination of bilirubin levels in alcohol consumers in Pohuwato Timur Village, Pohuwato Regency are more dominant with abnormal or high levels compared to normal bilirubin levels.