Incidence and characterization of polyglucosan bodies in the cerebella of montserrat orioles (Icterus oberi).

Polyglucosan bodies are accumulations of insoluble glucose polymers and proteins that form intracytoplasmic inclusions in the brain, large numbers of which can be indicative of neurodegenerative diseases such as Lafora disease. Montserrat orioles (Icterus oberi) are an icterid passerine endemic to Montserrat with conservation populations maintained in captivity abroad. We demonstrate that polyglucosan bodies are unusually abundant in the cerebellar molecular and Purkinje cell layers and cerebellar peduncles of captive-bred and wild-caught Montserrat orioles. The bodies are periodic acid-Schiff positive and diastase resistant and label with concanavalin A and for ubiquitin, consistent with those seen in humans. We found no association of the polyglucosan bodies with concurrent neurological lesions or clinical signs, nor with EPM2A and EPM2B gene mutations associated with Lafora disease. We conclude that an abundance of cerebellar polyglucosan bodies may be a normal finding in aged Montserrat orioles and not a threat to the captive breeding population.

Evaluation of hemolysis, lipemia, and icterus interference with common clinical immunoassays.

OBJECTIVES: Hemolysis, icterus, and lipemia (HIL) are common sources of endogenous interference in clinical laboratory testing. Defining the threshold of interference for immunoassays enables appropriate reporting of their results when they are affected by HIL. METHODS: Pools of residual patient serum samples were spiked with a known amount of interferent to create samples with varying concentrations of hemolysate, bilirubin, and Intralipid that mimicked the effects of endogenous HIL. Samples were analysed on the Alinity i analyser (Abbott Diagnostics) for more than 25 immunoassays. The average recovery relative to the non-spiked sample was calculated for each interference level and was compared to a predefined allowable bias. RESULTS: C-peptide, estradiol, serum folate, free T4, homocysteine, insulin, and vitamin B12 were found to be affected by hemolysis, at hemoglobin concentrations between 0.3 to 20 g/L. Immunoassays for BNP, estradiol, free T3, and homocysteine were affected by icterus at conjugated bilirubin concentrations between 50 to 1,044 µmol/L. BNP, serum folate, and homocysteine were affected by Intralipid with measured triglyceride concentrations between 0.8 to 10 mmol/L. Lastly, serological immunoassays for HIV and hepatitis A, B and C were also affected by interferences. CONCLUSIONS: Immunoassays are impacted by varying degrees of HIL interference. Some measurands, in the presence of interference, are affected in a manner not previously indicated. The data presented herein provide an independent evaluation of HIL thresholds and will be of aid to resource-limited clinical laboratories that are unable to internally verify endogenous interferences when implementing the Alinity i analyser.

A simplified HPLC-based method for measuring unconjugated bilirubin, bilirubin-monoglucuronide, bilirubin-diglucuronide, and delta-bilirubin in plasma with increased conjugated bilirubin.

Prolonged icterus is an important and common problem in neonatology and accurate determination of the different bilirubin species, including differentiation between delta-bilirubin and mono- and di-conjugated bilirubin, is useful for diagnostic purposes. However, most bilirubin measurements routinely performed in the clinical laboratory are hampered by the lack of separation of the four bilirubin fractions (unconjugated bilirubin, mono-conjugated bilirubin, di-conjugated bilirubin, and delta-bilirubin). Herein, we propose a high-performance liquid chromatography-based method, independent of commercially available standards or reliable molar absorption coefficients, for the determination of bilirubin fractions in blood samples from icteric patients. The method is a robust and reliable candidate for a semi-automatized setup for measuring the various bilirubin fractions in a specialized laboratory handling samples from clinics with expertise in biliary disease.

Jaundice as a Diagnostic and Therapeutic Problem: A General Practitioner's Approach.

BACKGROUND: Jaundice is a common clinical finding in clinical practice of hepatologists and general practitioners. It occurs when serum bilirubin levels exceed 3 mg/dL. SUMMARY: In this review, we summarize the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and laboratory and imaging techniques. Clinical presentation of jaundice manifests through yellow skin and sclera coloration. Evaluation of every patient includes detailed medical history and examination. In the laboratory, evaluation of enzymes of hepatic inflammation as well as cholestatic enzymes with serum bilirubin must be included. Additional laboratory analysis and imaging modalities are needed in order to differentiate jaundice etiology. Moreover, imaging is available and needed in further evaluation, and treatment is dependent on the underlying cause. KEY MESSAGES: In this review, we will outline the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and diagnostic and treatment approach to these patients.

External quality assessment of serum indices: Spanish SEQC-ML program.

OBJECTIVES: Serum indices included in clinical chemistry instruments are widely used by laboratories to assess the quality of samples. Instruments that report quantitative results allow an evaluation of their diagnostic performance in a similar way to other biochemical tests. The Spanish Society of Laboratory Medicine (SEQC-ML) launched a monthly External Quality program of serum indices in 2018 using three lyophilized materials of simultaneous annual distribution. We present the results of the first three years of the program. METHODS: The use of four different quality control materials with different concentrations in three alternate months allows an annual evaluation of the participant's accuracy. Assigned values are established by consensus among homogeneous groups, considering necessary at least 10 participants for a comparison at instrument level. The average percentage difference results per instrument allow the assessment of bias among groups. RESULTS: The imprecision of the three indices ranges between 3 and 9%, with no major differences among instruments. Significant differences were observed in all indices among instruments with more than 10 participants (Roche Cobas, Abbott Architect, Abbott Alinity and Siemens Advia). The 90th percentile of the distribution of percentage differences was used as the analytical performance specification (APS). An improvement in performance was observed in the first three years of the program, probably due to the learning curve effect. In 2020, APS of 7.8, 12.2 and 9.7% were proposed for hemolytic, icteric and lipemic indices, respectively. CONCLUSIONS: Serum indices have a great impact on the quality and the reliability of laboratory test results. Participation in proficiency testing programs for serum indices is helpful to encourage harmonization among providers and laboratories.

Rare cause of obstructive icterus in a young patient.

In this case report is discussed the diagnosis of papillary carcinoma in the case of a patient in whose age the occurrence of the disease is very rare. The patient underwent a series of non-invasive and invasive examinations, the results of which eventually led to a surgical solution of the suspected lesion (Wipples procedure). Histological examination of the resection confirmed mixed type ampular adenocarcinoma. In the context of this finding, the results of the examination, their information value, interpretation and mutual interaction are discussed. In the postoperative period, the patient suffered from gastrointestinal bleeding, subileum and poor postoperative healing. After hospitalization, the patient was transferred to oncology care and indicated for genetic testing.

Neonatal jaundice, phototherapy and childhood allergic diseases: An updated systematic review and meta-analysis.

BACKGROUND: Neonatal jaundice and phototherapy have been associated with the development of allergic diseases. It has been suggested, however, that effect estimates of the associations might be smaller than expected. We sought to update the evidence of their associations including recently published large longitudinal studies. METHODS: We sought published and unpublished observational studies through the major databases. We used a random-effect meta-analysis model weighted by the inverse variance estimate, the Quality in Prognosis Studies tool to assess the methodological quality for each study, and the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the certainty of evidence (COE). RESULTS: Nineteen studies were enrolled in the qualitative syntheses, and fourteen studies were synthesized in the meta-analyses. Neonatal jaundice was associated with a higher risk of childhood-onset asthma (odds ratio [OR], 1.46; 95% confidence interval [95% CI], 1.39-1.53; COE, moderate), atopic dermatitis (AD; OR, 1.30; 95% CI, 1.07-1.57; COE, moderate), and allergic rhinitis (AR; OR, 3.01; 95% CI, 0.8810.30; COE, low). Neonatal phototherapy was also associated with a higher risk of childhood-onset asthma (OR, 1.24; 95% CI, 1.11-1.38; COE, moderate), AD (OR, 1.31; 95% CI, 1.24-1.39; COE, moderate), and AR (OR, 1.38; 95% CI, 0.93-2.04; COE, very low). There were no studies that reported effect estimates of the associations between childhood-onset food allergies and neonatal jaundice and phototherapy. CONCLUSION: Neonatal jaundice and phototherapy were probably a prognostic factor of childhood-onset allergic diseases; however, the associations were likely to be smaller than previously estimated.

Extrahepatic biliary obstruction can interfere with hepatic fibrosis prediction using two-dimensional shear wave elastography in dogs.

Two-dimensional shear wave elastography (2D-SWE) can be used to quantitatively evaluate the elastic modulus of the liver as shear wave velocity (SWV), which can noninvasively predict clinically relevant hepatic fibrosis in both dogs and humans. However, extrahepatic biliary obstruction (EHBO), regardless of the presence of clinically relevant hepatic fibrosis, can influence SWVs in humans and thus may interfere with hepatic fibrosis prediction using 2D-SWE in dogs. The aim of this prospective, observational, and one-group pretest-posttest study is to investigate whether SWV measured by 2D-SWE displays a difference between dogs with and without EHBO. A total of 20 dogs were included (7 with EHBO and 13 with gallbladder pathology but no EHBO) that underwent preoperative SWV measurement using 2D-SWE. In all dogs, stages of hepatic fibrosis were evaluated histopathologically using a scoring scheme. In addition, postoperative SWVs in dogs with EHBO relieved via laparotomy were also evaluated. The median (range) SWVs in the dogs with and without EHBO were 1.91 (1.81-2.54) m/s and 1.57 (1.37-1.64) m/s, respectively. Although there was no significant difference in the histopathological hepatic fibrosis stages between the dogs with and without EHBO, the preoperative SWVs in the dogs with EHBO were significantly higher than in dogs without EHBO (P = .0004), and SWVs were found to decrease significantly after surgery (P = .0097). This study demonstrates that EHBO can increase the SWV of dogs without clinically relevant hepatic fibrosis and can interfere with the prediction of noninvasive hepatic fibrosis using 2D-SWE.

Comparing global and local maps of the Caribbean pine forests of Andros, home of the critically endangered Bahama Oriole.

Forest loss is occurring at alarming rates across the globe. The pine rockland forests of Andros, The Bahamas, likely represent some of the largest stands of Bahamian subspecies of Caribbean pine in the world. Given the unique species that inhabit these pine forests, such as the endemic and critically endangered Bahama Oriole, monitoring habitats on Andros is crucial to inform conservation planning. We developed a 2019 land classification map to assess the status of nine terrestrial habitats on Andros. Our Random Forest classification model predicted habitat classes with high overall accuracy. Caribbean pine was the dominant land class making up roughly one-third of the total terrestrial area. Whereas much of the pine forest area was found as small patches, most were close to other patches of pine suggesting isolation of forest patches is low. We compared our known intact forest areas to recent forest loss identified by the Hansen et al. Global Forest Change product and assessed areas of habitat disturbance in high-resolution imagery. Our results suggest that this global map overpredicted forest loss on Andros. The small degree of true forest loss on Andros was driven mostly by anthropogenic activity. A cross-tabulation of the Hansen forest loss with fire data showed that understory fires were frequently associated with falsely classified deforestation. Given the threats of climate change to this open forest type-intensifying fire regimes, strengthening hurricanes, and sea level rise-monitoring changes in open forest extent is a critical task across the Caribbean region and the world.

Pitfalls of diagnosing autoimmune pancreatitis.

The diagnosis of the rare disease autoimmune pancreatitis (AIP) is demonstrated in the case of a patient who underwent a series of examinations that were unable to unequivocally prove the diagnosis of benignity. The disease as a form of chronic pancreatitis, and the most important and first objective of the examination is to exclude malignant disease of the pancreas and biliary tract. While imaging led to suspicion of malignancy, repeated histological examinations did not confirm it. After we were able to exclude suspected carcinoma according to the available diagnostic criteria, AIP was confirmed, and a diagnosis of type I was made, which belongs to the group of diseases characterized by high levels of immunoglobulin G4 (IgG4) in the blood serum. Successful treatment with glucocorticoids was initiated with induction of disease remission. However, AIP shows frequent relapses and this should also be borne in mind during treatment. Our case report also describes such a case.

Three non-classical mechanisms for anemic disease of the fetus and newborn, based on maternal anti-Kell, anti-Ge3, anti-M, and anti-Jra cases.

Maternal alloantibody-mediated hemolytic disease of the fetus and newborn (HDFN) ranges from no or mild symptoms to severe hydrops and intrauterine fetal demise. Hemolytic anti-D-mediated HDFN proceeds via a long-known mechanism, to which three other pathways to fetal/neonatal anemia may be added: (0) Fetal erythrocyte destruction can proceed by extravascular phagocytosis. (1) An apoptotic pathway has been described for anti-Kell, and anti-Ge3. (2) Erythropoietic suppression may arise from altered or deformed erythroblast architecture in anti-M-mediated disease. (3) Clonal escape from erythropoietic suppression is hypothesized to arise from maternal anti-Jra immune pressure, albeit this requires further elucidation. Alloantibody-mediated anemic disease of the fetus and newborn (ADFN) is a designation we favor for cases when hemolysis or hyperbilirubinemia are not the dominant features, such as those provoked by anti-Kell, anti-Ge3, anti-M, and anti-Jra.

[Leptospira-Zebra under the "corona herd"]. / Leptospira ­ Zebra unter der "Coronaherde".

This article reports an incidental finding of leptospirosis during a special consultation, which was initiated due to the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The focus on SARS-CoV­2 and the uncharacteristic symptoms of these two diseases make it much more difficult to find the correct diagnosis. Leptospirosis is predominantly a tropical zoonosis but also occurs in Germany.

Interference in the anti-Xa heparin activity assay due to hemolysis and icterus during pediatric extracorporeal life support.

Chromogenic anti-Xa assays for unfractionated heparin monitoring (heparin activity) are susceptible to interference from hemolysis and icterus. The purpose of this study was to better understand the effect of hemolysis and icterus on anti-Xa heparin activity and to predict the magnitude of the error. Increasing levels of hemoglobin and unconjugated bilirubin were added to pooled normal plasma or buffer containing known levels of heparin. Increased plasma hemoglobin or bilirubin produced falsely increased residual factor Xa activity as measured by the absorbance change (OD/min) in the Stago heparin activity assay. This increased absorbance change slope resulted in falsely lower estimates of heparin activity. The falsely lower heparin activity measurement occurred even when heparin was not present, indicating it was not due to heparin neutralization. In a sample containing 0.62 ± 0.06 U/mL heparin and 228 mg/dL hemoglobin, the measured heparin activity was 0.41 ± 0.03 U/mL, underestimating heparin activity by 0.21 ± 0.07 U/mL. Interference occurred if plasma hemoglobin was above 70 mg/dL or bilirubin was above 16 mg/dL, which happened in 16%-26% of samples from pediatric patients on extracorporeal life support (ECLS). In conclusion, hemolysis and icterus were common in ECLS patients, leading to underestimates of unfractionated heparin activity and potentially higher doses of heparin than intended. The magnitude of the heparin activity measurement error could be predicted based on plasma hemoglobin and bilirubin levels until these levels exceeded the technical limits of the assay, ~230 mg/dL hemoglobin and 55 mg/dL bilirubin.

Plants used for the treatment of icterus (jaundice) in Central India: A review.

Jaundice is one of the most common medical condition affecting infants, children, and adults. Jaundice is not a disease but it is a visible sign and symptom of liver disease which occurs when there is an increase in the amount of bilirubin circulating in the blood due to the abnormal metabolism and excretion in the urine. Medicinal plants are being used long ago by our ancestors for the treatment of jaundice. At the present era, consumption of these herbal medicines is increasing at a high speed, due to its less or no side effect and cost-effectiveness as compared to synthetic medicines. This review describes approximately 55 medicinal plants which are used by rural and tribal people of different area of Chhattisgarh for curing jaundice. The data was collected from different kinds of literature survey from the year 1993 to 2018. This review has been conferred in a systematic way which includes plant's vernacular name, botanical name along with its family, part used and ethnomedicinal uses in a tabulated form and also the description of scientific evidence behind the folklore uses of some medicinal plants along with their mechanism of action which have been reported in different kinds of literature. The current study may be useful for the development of new medicines for the treatment of jaundice.

Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: an open-label, uncontrolled clinical trial.

BACKGROUND: Although stem cell transplantation has been successfully performed for cerebral palsy (CP) related to oxygen deprivation, clinical trials involving the use of stem cell transplantation for CP related to neonatal icterus have not been reported. The aim of this study was to evaluate the effectiveness of transplantation of autologous bone marrow mononuclear cell (BMMC) for improving gross motor function and muscle tone in children with CP related to neonatal icterus. METHODS: This open-label, uncontrolled clinical trial, which included 25 patients with CP related to neonatal icterus who had a Gross Motor Function Classification System (GMFCS) score between level II and level V, was conducted between July 2014 and July 2017 at Vinmec International Hospital (Vietnam). BMMC were harvested from the patients' iliac crests. Two procedures involving BMMC transplantation via the intrathecal route were performed: the first transplantation was performed at baseline, and the second transplantation was performed 6 months after the first transplantation. Gross motor function and muscle tone were measured at three time points (baseline, 6 months, and 12 months) using the Gross Motor Function Measure (GMFM) and the Modified Ashworth Scale. RESULTS: In this trial, we observed significant improvement in gross motor function and a significant decrease in muscle tone values. Total score on the 88-item GMFM (GMFM-88), scores on each GMFM-88 domain, and the 66-item GMFM (GMFM-66) percentile were significantly enhanced at 6 months and 12 months after the first transplantation compared with the corresponding baseline measurements (p-values < 0.05). In addition, a significant reduction was observed in muscle tone score after the transplantations (p-value < 0.05). CONCLUSION: Autologous BMMC transplantation can improve gross motor function and muscle tone in children with CP related to neonatal icterus. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03123562 . Retrospectively registered on December 26, 2017.

Icteric human samples: Icterus index and method of estimating an interference-free value for 16 biochemical analyses.

BACKGROUND: Hemolysis, Icterus, and Lipemia constituting the HIL index, are the most common causes of interference with accurate measurement in biochemistry. This study focuses on bilirubin interference, aiming to identify the analyses impacted and proposing a way to predict nominal interference-free analyte concentrations, based on both analyte level and Icterus Index (Iict ). METHODS: Sixteen common analytes were studied: alanine aminotransferase (ALT), albumin (ALB), alkaline phosphatase (ALP), amylase (AMY), aspartate aminotransferase (AST), total cholesterol (CHOLT), creatinine (CREA, enzymatic method), fructosamine (FRUC), gamma-glutamyl transferase (GGT), HDL cholesterol (HDLc), total iron (Iron), lipase (LIP), inorganic phosphorus (Phos), total protein (PROT), triglycerides (TG), and uric acid (UA). Both the traditional 10% change in concentrations from baseline and the Total Change Level (TCL) were taken as acceptance limits. Nineteen pools of sera covering a wide range of values were tested on the Cobas® 6000 (Roche Diagnostics). Iict ranged from 0 to 60. RESULTS: Eight analytes increased (FRUC and Phos) or decreased (CHOLT, CREA, HDLc, PROT, TG, and UA) significantly when Iict increased. FRUC, HDLc, PROT, and UA showed a linear relationship when Iict increased. A non-linear relationship was found for TG, CREA, and for CHOLT; this also depended on analyte levels. Others were not impacted, even at high Iict . CONCLUSIONS: A method of estimating an interference-free value for FRUC, HDLc, PROT, Phos, UA, TG, and CREA, and for CHOLT in cases of cholestasis, is proposed. Iict levels are identified based on analytical performance goals, and equations to recalculate interference-free values are also proposed.

BILIRUBIN CONCENTRATIONS IN CLINICALLY HEALTHY AND DISEASED CAPTIVE WATERBUCK (KOBUS ELLIPSIPRYMNUS) AT THE SAN DIEGO ZOO SAFARI PARK.

Captive waterbuck ( Kobus ellipsiprymnus ) that appear clinically healthy have been noted to have high serum bilirubin concentrations compared with other ruminants; however, questions remain about the physiologic factors affecting bilirubin concentration and its potential association with underlying disease and icteric serum or mucous membranes. Serum bilirubin concentrations of healthy and diseased waterbuck housed at the San Diego Zoo Safari Park from 1989 to 2012 were retrospectively analyzed to determine any link between icteric serum, total bilirubin concentration (tBili), and disease entities in this species. Total bilirubin and direct (dBili) bilirubin concentrations and the prevalence of icteric serum were compared by subspecies, age group, and health status; associations with complete blood count and biochemical results and clinical diagnosis were assessed. No significant differences were found in tBili or dBili between Ellipsen (n = 32) and Defassa (n = 29) subspecies or in juveniles (n = 22) versus adults (n = 39). Clinically healthy waterbuck (n = 40) had significantly higher tBili (mean ± 2SD, 7.9 ± 1.2 mg/dl; P < 0.001) and dBili (3.7 ± 1.0 mg/dl; P < 0.001) than did diseased waterbuck (n = 21; tBili: 4.9 ± 2.56 mg/dl; dBili: 2.2 ± 0.8 mg/dl). No waterbuck had icteric tissues on physical examination. Twelve (19.7%) waterbuck (six healthy, six diseased) had icteric serum. Few minor correlations were seen between tBili or dBili and clinical, laboratory, or necropsy evidence of disease, though an inverse correlation between dBili and blood glucose was noted. Of the 40 healthy animals, reference intervals were calculated for tBili (5.5-10.3 mg/dl), dBili (1.7-5.7 mg/dl), and indirect bilirubin (2.2-6.2 mg/dl). These results suggest healthy waterbuck have relatively high tBili and dBili compared with related species. Icteric serum may be seen in up to 15% of healthy animals in the absence of icteric tissues.

Neonatal hyperbilirubinemia and childhood allergic diseases: a systematic review.

Studies have found a link between neonatal hyperbilirubinemia (NNH) and/or neonatal phototherapy (NPT) and childhood allergic diseases. The present systematic review was conducted to provide updated evidence and to provide direction regarding future research. A systematic search of the published literature was carried out. Observational studies including children up to 12 yr of age were included. Data extraction was carried out using a standardized data extraction form that was designed and pilot tested a priori. The analysis was carried out with the statistical software RevMan (version 5.2) [Protocol is registered at PROSPERO: CRD42014009943]. Of 79 citations retrieved, a total of 7 good quality studies (n = 101,499) were included in the final analysis. There was a significant increase in the odds of asthma and allergic rhinitis (AR) after NNH [asthma, OR 4.26 (95% CI 4.04-4.5); AR, OR 5.37 (95% CI 4.16-6.92)] and after NPT [asthma, OR 3.81 (95% CI 3.53-4.11); AR, OR 3.04(95% CI 2.13-4.32)]. A similar increase in the trend was noted for late onset of asthma after NNH [OR 4.1 (95% CI 2.82-5.94)], and hospitalization due to asthma after NPT [OR 3.56 (95% CI 2.93-4.33)]. The GRADE evidence generated was of 'low quality'. The current evidence finds a significant increase in the odds of childhood allergic diseases after NNH and/or NPT. As observational studies were included, the evidence generated was of 'low quality'. Future studies should try to elucidate the pathophysiologic link between NNH and/or NPT and childhood allergic diseases.