Decreasing Laboratory Testing for Neonatal Jaundice Through Revision of a Clinical Practice Pathway

OBJECTIVES: The purpose of this study was to minimize unnecessary laboratory services for hospitalized neonates with hyperbilirubinemia by revising a local clinical practice pathway (CPP). METHODS: A retrospective cohort study was performed to compare the number of laboratory tests and blood draws in patients hospitalized with neonatal hyperbilirubinemia before and after implementation of a revised CPP. The study included infants with neonatal hyperbilirubinemia <14 days old admitted after their birth hospitalization between April 2017 and October 2019. Primary outcome measures included the total number of blood draws and the number of laboratory tests obtained per patient and length of stay. Secondary outcome measures included 7-day readmission rate, charges, and discharge bilirubin level. RESULTS: The median number of blood draws per patient after implementation of the CPP decreased to 2 (interquartile range [IQR], 2–3) compared with 3 (IQR, 2–3) before implementation (Poisson model–based estimated mean difference, 1.1; 95% confidence interval, 1.0–1.3; P = .018). The median number of laboratory tests per patient after implementation decreased from 4 (IQR, 3–6) to 3 (IQR, 2–4; Poisson model–based estimated mean difference, 1.3; 95% confidence interval, 1.2–1.5; P < .0001). There was no significant change in length of stay, readmission rate, charges, or discharge bilirubin level. CONCLUSIONS: Implementation of a revised CPP was associated with a significant decrease in the number of blood draws and laboratory tests per patient for infants admitted to the hospital for neonatal hyperbilirubinemia.

The Nonlinear Relationship Between Total Bilirubin and Coronary Heart Disease: A Dose-Response Meta-Analysis

Background: Evidence suggests that the total bilirubin has a protective effect on coronary heart disease (CHD), but the dose-response relationship remains controversial, and there is no meta-analysis to assess the relationship.Methods: As of October 1, 2021, relevant literature was selected from four databases (PubMed, Web of Science, Cochrane Library, and Embase) by using a retrieval strategy. The dose-response curve between the total bilirubin and CHD was fitted by a restricted cubic spline. Stata 12.0 was used for statistical analysis.Results: A total of 170,209 (6,342 cases) participants from 7 prospective studies were analyzed in our meta-analysis. We calculated the pooled relative risks (RRs) and 95% CIs for the association between serum bilirubin level and risk of CHD using random-effects models. Compared with the first quantile, the bilirubin level in the third quantile had a protective effect on the risk of CHD (RR, 0.90; 95% CI, 0.82–0.99). The restricted cubic spline functions depicted a U-type curve relationship between bilirubin (3.42–49 μmol/L) and CHD (Plinear < 0.001). When the bilirubin level was in the range of 3.42–13μmol/L, the protective effect of bilirubin on CHD was enhanced with increasing bilirubin levels. When the bilirubin level exceeded 13μmol/L, the protective effect of bilirubin weakened, and a dangerous effect gradually appeared with further increases in bilirubin levels.Conclusions: Compared with a low bilirubin level, a high bilirubin level has a protective effect on the risk of CHD, and there was a U-shaped dose-response relationship between them.

Study of serum bilirubin as a diagnostic method to predict acute perforated appendicitis

Background: Acute appendicitis is the commonest cause of ‘acute surgical abdomen’. Appendicectomy is the most frequently performed urgent abdominal operation and is often the first major procedure performed by a surgeon in training. The aim of the study was to whether hyperbilirubinemia might be used as a diagnostic tool to predict perforated appendicitis.Methods: This study comprised patients who presented with the condition of appendicitis and abnormal liver function tests on admission and had a laparoscopic or open appendectomy. The age information, duration of symptoms, temperature, white blood cell counts, bilirubin levels, and histology data were gathered. Peritoneal fluid was cultured and examined for sensitivity.Results: The average bilirubin level of all participating patients was 0.92 mg/dl (range, 0.1-4.3 mg/dl). The mean bilirubin levels were higher for patients with simple appendicitis compared to those with a non-inflamed appendix (0.7 mg/dl and 0.4 mg/dl, p<0.001). Hyperbilirubinaemia was reported to have a specificity of 89% and a positive predictive value of 90.02% for acute appendicitis. Patients with appendiceal perforation, however, had a mean bilirubin level of 1.7 mg/dl and were more likely to have hyperbilirubinaemia (p<0.001). The specificity of hyperbilirubinaemia for perforation or gangrene was 73%.Conclusions: Patients with hyperbilirubinemia with appendicitis condition should be screened for a greater risk of appendiceal perforation than those with normal bilirubin levels.

Cord Bilirubin Value as a Predictor of Significant Hyperbilirubinemia in Abo Incompatiblity

Background: Hyperbilirubinemia is a condition in which the blood contains too much bilirubin and producing jaundice (yellow coloring of the eyes and skin). Low bilirubin levels in newborns are common and do not pose any problems; they will resolve on their own within the first week of life. Studying the cord bilirubin levels in new born babies is significant to predict the risk of abo incompatiblity. Methods: A total of 129 babies born to O blood group mother were included in the study. Out of which 111 babies were with risk of ABO incompatibility. Among them 17 babies developed pathological hyperbilirubinemia. None of the 0 positive babies developed pathological hyperbilirubinemia. Results: The peak bilirubin level was attained on 3rd and 4th day for all the babies and was taken as the outcome measure and cord serum bilirubin was taken as the predictive factor. The incidence of pathological hyperbilirubinemia is 13.2%. The mode of delivery had no positive association with the development of pathological hyperbilirubinemia. Male babies had positive ociation for pathological hyperbilirubinemia without any statistical significance. Incidence of pathological hyperbilirubinemia is higher in babies with a birth weight of <3 kg. Conclusion: A cord bilirubin value of 2.65 mg/dL can be used as a cut off for predicting pathological hyperbilirubinemia. Infants with bilirubin level more than the cutoff values were subjected to early intervention with complete recovery. None of the babies had developed encephalopathy and its sequelae.

The mildly decreased preoperative bilirubin level is a risk factor for periprosthetic joint infection after total hip and knee arthroplasty

Background Many serologic markers are routinely tested prior to joint arthroplasty, but only few are commonly used to guide surgeons in determining patients most at risk of periprosthetic joint infection (PJI). The objective of this study was to investigate the association between preoperative bilirubin level and PJI after primary hip and knee arthroplasty. Methods A retrospective analysis was performed on patients undergoing revision hip and knee arthroplasty at our hospital from January 2016 to December 2019. Laboratory biomarkers were collected before the primary arthroplasty, as well as general patient information. The association between the above serologic markers and postoperative PJI was analyzed. Results A total of 72 patients (30 hips/42 knees) were analyzed, including 39 patients with PJI and 33 patients without PJI. Except for total bilirubin (TB) and direct bilirubin (DB), there was no significant difference between the remaining laboratory biomarkers. The preoperative TB and DB in the PJI group were 10.84 ± 0.61 μmol/L and 3.07 ± 0.19 μmol/L, respectively, which were lower than those in the non-PJI group (14.68 ± 0.75 μmol/L and 4.70 ± 0.39 μmol/L, P < 0.001). The area under the curve (AUC) of preoperative TB to predict PJI was 0.755 (P < 0.001, cutoff = 11.55 μmol/L, sensitivity = 66.67%, specificity = 75.76%). Meanwhile, the AUC of preoperative DB was 0.760 (P < 0.001, cutoff = 4.00 μmol/L, sensitivity = 84.62%, specificity = 54.45%). Conclusions The serum levels of TB and DB before the primary arthroplasty were lower in PJI patients than in non-PJI patients, and the preoperative values lower than 11.55 μmol/L and 4.00 μmol/L could be considered as a risk factor for postoperative PJI.

Co-inheritance of G6PD deficiency and 211 G to a variation of UGT1A1 in neonates with hyperbilirubinemia in eastern Guangdong

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may manifest as neonatal hyperbilirubinemia, is the most prevalent erythrocytic enzyme-related disease in the world. Objective To investigate the association between neonatal hyperbilirubinemia and co-inheritance of G6PD deficiency and 211 G to A variation of UGT1A1 in Chaozhou city of eastern Guangdong province, the effects of G6PD deficiency and UGT1A1 gene variant on the bilirubin level were determined in neonates with hyperbilirubinemia. Method The activity of G6PD was assayed by an auto-bioanalyzer. PCR and flow-through hybridization were used to detect 14 common G6PD mutations in G6PD deficient neonates. 211 G to A variation of UGT1A1 was determined by PCR and sequencing. The data of neonatal bilirubin was collected and analyzed retrospectively. Results Seventy four cases of the 882 hyperbilirubinemia neonates were G6PD deficiency (8.39%) while 12 cases of the 585 non-hyperbilirubinemia neonates (control group) were G6PD deficiency (2.05%). The rate of G6PD deficiency in the hyperbilirubinemia group was higher than that of the control group. Moreover, the peak bilirubinin of the G6PD-deficient group of hyperbilirubinemia neonates was 334.43 ± 79.27 μmol/L, higher than that of the normal G6PD group of hyperbilirubinemia neonates (300.30 ± 68.62 μmol/L). The most common genotypes of G6PD deficiency were c.1376G > T and c.1388G > A, and the peak bilirubin of neonates with these two variants were 312.60 ± 71.81 μmol/L and 367.88 ± 75.79 μmol/L, respectively. The bilirubin level of c.1388G > A was significantly higher than that of c.1376G > T. Among the 74 hyperbilirubinemia neonates with G6PD deficiency, 6 cases were 211 G to A homozygous mutation (bilirubin levels 369.55 ± 84.51 μmol/L), 27 cases were 211 G to A heterozygous mutation (bilirubin levels 341.50 ± 63.21 μmol/L), and 41 cases were wild genotypes (bilirubin levels 324.63 ± 57.52 μmol/L). Conclusion The rate of G6PD deficiency in hyperbilirubinemia neonates was significantly higher than that of the non-hyperbilirubinemia neonates in Chaozhou. For the hyperbilirubinemia group, neonates with G6PD deficiency had a higher bilirubin level compared to those with normal G6PD. For hyperbilirubinemia neonates with G6PD deficiency, there was a declining trend of bilirubin levels among 211 G to A homozygous mutation, heterozygous mutation, and wild genotype, but there was no significance statistically among the three groups.

Role of Probiotics in Neonates with Hyperbilirubinemia Receiving Phototherapy

Study Objectives: To compare the mean duration of phototherapy in neonates with hyperbilirubinemia receiving phototherapy with vs. without probiotics. Study Design and Settings: It was a randomized controlled trial carried at Department of Pediatrics, DHQ Hospital Kasur from Jan 2021 to June 2021. Patients and Methods: The present research involved 94 neonates of both genders aged between 2 to 28 days of life diagnosed of neonatal hyperbilirubinemia (serum bilirubin level ≥15mg/dL and direct bilirubin level ≤1.5 mg/dL). These neonates were allocated into two groups randomly. Neonates in Group-I were given probiotics along with conventional treatment of phototherapy whereas neonates in Group-II received conventional phototherapy alone. Study outcome was described in terms of mean duration of phototherapy (phototherapy was stopped when serum bilirubin level was less than 10 mg/dl during the first week and less than 11 mg/dl after the first week) which was recorded and compared between the groups. An informed written consent was taken from parents of every neonate. Results of the Study: The mean age of the neonates was 6.54±4.96 days while the mean gestational age was 37.31±2.04 weeks. There were 55 (58.5%) baby boys and 39 (41.5%) baby girls with a boys to girls ratio of 1.4:1. The mean weight of the neonates was 2.89±0.49 Kg while the mean serum bilirubin level upon admission was 16.73±1.19 mg/dl. The mean duration of phototherapy was significantly shorter in neonates receiving probiotics along with phototherapy as compared to phototherapy alone (3.13±0.92 vs. 3.81±1.12 days; p=0.002). Similar significant difference was observed across various subgroups based on age, gender, gestational age, weight and serum bilirubin level upon admission. Conclusion: Addition of probiotics to conventional practice of phototherapy alone in jaundiced neonates was found to hasten the recovery evident from significant reduction in the mean duration of phototherapy advocating its routine use in future practice. Keywords: Neonatal Hyperbilirubinemia, Phototherapy, Probiotics

Positive direct antiglobulin test: is it a risk factor for significant hyperbilirubinemia in neonates with ABO incompatibility?

Objective: ABO incompatibility is a common cause of neonatal indirect hyperbilirubinemia. The direct antiglobulin test (DAT) can identify infants developing hemolytic disease. This study aims to evaluate the significance of DAT positivity among neonates with ABO incompatibility. Study Design: This retrospective study included 820 neonates with blood group A or B who were born to blood group O mothers. The study group consisted of neonates (n = 79) who had positive DAT, and the control group consisted of infants (n = 741) who had negative DAT. Demographic and clinical data of the neonates regarding jaundice were collected and compared statistically. Results: The bilirubin level at 24 hours of life (study group 8 ± 2.6 mg/dl, control group 6 ± 2.2 mg/dl, p < 0.001) and the highest bilirubin level (study group 12.7 ± 3.6 mg/dl, control group 10.4 ± 4.2 mg/dl, p < 0.001) were higher in infants with positive DAT. In the study group 37 (46.8%) infants and in the control group 83 (11.2%) infants received PT in the nursery (p < 0.001). In neonates with positive DAT; direct bilirubin level, duration of hospitalization, and PT in the nursery were higher (p = 0.002, p < 0.001, and p < 0.001), whereas hemoglobin level was lower (p < 0.001). Conclusion: In neonates with ABO incompatibility, a positive DAT is a risk factor for developing significant hyperbilirubinemia. Close follow-up of newborn infants with ABO incompatibility is crucial for early detection and treatment of neonatal jaundice to avoid early and late complications.

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 &lt;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 (&lt; 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 &lt; 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 &lt; 6 g/dl; reticulocytes count &lt; 100 x 10 9/L, BMRI &lt;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 &lt; 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

Common bile duct size in malignant distal obstruction and lumen-apposing metal stents: a multicenter prospective study

Background and study aims Feasibility of EUS-guided choledochoduodenostomy (EUS-CDS) using available lumen-apposing stents (LAMS) is limited by the size of the common bile duct (CBD) (≤ 12 mm, cut-off for experts; 15 mm, cut-off for non-experts). We aimed to assess the prevalence and predictive factors associated with CBD size ≥ 12 and 15 mm in naïve patients with malignant distal biliary obstruction (MDBO). Patients and methods This was a prospective cohort study involving 22 centers with assessment of CBD diameter and subjective feasibility of the EUS-CDS performance in naïve jaundiced patients undergoing EUS evaluation for MDBO. Results A total of 491 patients (mean age 69 ± 12 years) with mean serum bilirubin of 12.7 ± 6.6 mg/dL entered the final analysis. Dilation of the CBD ≥ 12 and 15 mm was detected in 78.8 % and 51.9 % of cases, respectively. Subjective feasibility of EUS-CDS was expressed by endosonographers in 91.2 % for a CBD ≥ 12 mm and in 96.5 % for a CBD ≥ 15 mm. On multivariate analysis, age (P < 0.01) and bilirubin level (P ≤ 0.001) were the only factors associated with both CBD dilation ≥ 12 and ≥ 15 mm. These variables were poorly associated with the extent of duct dilation; however, based on them a prediction model could be constructed that satisfactorily predicted CBD size ≥ 12 mm in patients at least 70 years and a bilirubin level ≥ 7 mg/dL. Conclusions Our study showed that at presentation in a large cohort of patients with MDBO, EUS-CDS can be potentially performed in three quarters to half of cases by expert and less experienced endosonographers, respectively. Dedicated stents or devices with different designs able to overcome the limitations of existing electrocautery-enhanced LAMS for EUS-CDS are needed.