Elevated Bilirubin Research Articles

The applications of Ursodeoxycholic acid in infant with cholestasis: A retrospective cohort analysis

Biliary atresia is the predominant etiology of cholestasis in early infancy. Impairment of bile fluid excretion results in elevated bilirubin levels, causing a yellowing of the skin. Ursodeoxycholic acid is well-established to enhance liver function when taken promptly. The application of ursodeoxycholic acid for treating cholestasis in pediatric patients remains contentious. The objective of this study is to assess the impact of ursodeoxycholic acid treatment on liver biomarkers in infant with cholestasis. This was retrospective cohort study in infant with cholestasis who underwent ursodeoxycholic acid treatment for two weeks. Secondary data including aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin were extracted from the medical records of the outpatient clinic in the Department of Child Health at Dr. Soetomo General Hospital, Indonesia (January 2020 - December 2023). The data was devided into two groups based on biopsy and examined utilizing SPSS version 23. This study included 64 participants. Statistics show an equal gender ratio. Ursodeoxycholic acid treatment in paediatric cholestasis patients can lower liver biomarker level. Levels of total bilirubin and direct bilirubin diminished in individuals both groups. Notable levels were recorded in individuals with normal biopsy outcomes (p=0.007 and p=0.012). Administration of ursodeoxycholic acid markedly elevated ALT levels in both the normal and abnormal liver biopsy outcome groups (p=0.031 and p=0.006). Ursodeoxycholic acid has been shown to be effective in improving liver function in infant with cholestasis. In order to avoid negative effects, the medication must be carefully administered to people who already have liver fibrosis.

Cotoneaster Side Effects Following the Treatment of Neonatal Jaundice

Background: There has been significant interest in using Cotoneaster for treating jaundice or elevated bilirubin levels in newborns, and it has, in many cases, replaced phototherapy in herbal medicine. However, using these compounds to treat hyperbilirubinemia can lead to complications in neonates, potentially resulting in morbidity and even death. Objectives: This study examined the side effects of Cotoneaster consumption in jaundiced neonates admitted to the Children’s Medical Center between 2021 and 2022. Methods: We conducted a cross-sectional study involving healthy neonates who consumed Cotoneaster following treatment for neonatal jaundice and subsequently experienced complications. The data were recorded using pre-prepared questionnaire forms. Results: The most common complications following Cotoneaster derivatives were exaggerated hyperbilirubinemia, dehydration, and poor feeding. Conclusions: Given the sensitivity of neonates, the treatment of jaundice in babies should be approached with caution and supported by extensive studies. The use of herbal medicines in neonates remains questionable due to associated complications.

Artificial Intelligence Applied in Early Prediction of Lower Limb Fracture Complications

Background: Artificial intelligence has become a valuable tool for diagnosing and detecting postoperative complications early. Through imaging and biochemical markers, clinicians can anticipate the clinical progression of patients and the risk of long-term complications that could impact the quality of life or even be life-threatening. In this context, artificial intelligence is crucial for identifying early signs of complications and enabling clinicians to take preventive measures before problems worsen. Materials and methods: This observational study analyzed medical charts from the electronic archive of the Clinical Emergency Hospital in Galați, Romania, covering a four-year period from 2018 to 2022. A neural network model was developed to analyze various socio-demographic and paraclinical data. Key features included patient demographics, laboratory investigations, and clinical outcomes. Statistical analyses were performed to identify significant risk factors associated with deep venous thrombosis (DVT). Results: The analysis revealed a higher prevalence of female patients (60.78%) compared to male patients, indicating a potential gender-related risk factor for DVT. The incidence of DVT was highest among patients aged 71 to 90 years, affecting 56.86% of individuals in this age group, suggesting that advanced age significantly contributes to the risk of developing DVT. Additionally, among the DVT patients, 15.69% had a body mass index (BMI) greater than 30, categorizing them as obese, which is known to increase the risk of thrombotic events. Furthermore, this study highlighted that the highest frequency of DVT was associated with femur fractures, occurring in 52% of patients with this type of injury. The neural network analysis indicated that elevated levels of direct bilirubin (≥1.5 mg/dL) and prothrombin activity (≤60%) were strong predictors of fracture-related complications, with sensitivity and specificity rates of 78% and 82%, respectively. These findings underscore the importance of monitoring these laboratory markers in at-risk populations for early intervention. Conclusions: This study identified critical risk factors for developing DVT, including advanced age, high BMI, and femur fractures, which necessitate longer recovery periods. Additionally, the findings indicate that elevated direct bilirubin and prothrombin activity play a significant role in predicting DVT development. These results suggest that AI can effectively enhance the anticipation of clinical evolution in patients, aiding in early intervention and management strategies.

Assessment of Glecaprevir/Pibrentasvir Treatment’s Influence on Biochemical and Metabolic Markers in Patients with Chronic Hepatitis

Background/Objectives: Liver function tests (LFT) are essential for diagnosing and monitoring liver status in patients with chronic hepatitis. In addition, tracking the systemic implications reflected in the changes in metabolic parameters is essential for correctly managing the cases. This study addresses the critical gap in the literature by evaluating the effects of glecaprevir/pibrentasvir on key liver function markers (AST, ALT, GGT, TB) and metabolic parameters (TC, TG, HbA1c) in patients with chronic hepatitis C (CHC). Moreover, this study will evaluate the impact of glecaprevir/pibrentasvir on A2MG, which provides insights into its effects on liver fibrosis. Awareness of these effects is critical for the optimal management of patients during and following antiviral therapy to ensure that therapeutic success does not come at the expense of overall liver and metabolic health. These parameters should be monitored as they supply clinicians with essential data, informing treatment more accurately and ensuring a holistic approach in CH patients. Methods: This study consists of 104 patients with chronic hepatitis C treated with glecaprevir/pibrentasvir and monitored from January to June 2024. Assessments comprised standard liver markers, lipid profiles, glycated hemoglobin, and alpha-2-macroglobulin, as well as specific non-invasive tests of liver injury. Results: 95.2% of the patients experienced a sustained virologic response. Biochemical markers and total cholesterol values were significantly decreased with glecaprevir/pibrentasvir therapy. Non-significant elevations in total bilirubin and glycated hemoglobin support the drug’s favorable tolerability profile. Conclusions: In the treatment of chronic hepatitis C patients, glecaprevir/pibrentasvir therapy leads to normalization in biochemical markers (AST, ALT, and GGT), as well as in total cholesterol.

Elevated serum direct bilirubin is predictive of a poor prognosis for primary myelodysplastic syndrome.

The aim of this study was to assess the prognostic significance of serum direct bilirubin (DBIL) for patients newly diagnosed with myelodysplastic syndromes (MDS). The clinical, laboratory, and follow-up data of MDS patients were collected, and the associations of DBIL levels with overall survival (OS) and leukemia-free survival (LFS) were analyzed. In total, 262 MDS patients were assigned to the high DBIL level group or the normal DBIL level group in the retrospective study. High DBIL was associated with older age, reduced hemoglobin, higher levels of β2-microglobin, lactate dehydrogenase, and serum ferritin, along with the number of co-mutations (> 1) and a higher frequency of ASXL1, KIT, and KRAS mutations. Multivariate analyses found that high DBIL level was an independent adverse predictor for OS (p = 0.002, hazard ratio = 2.723, 95%CI = 1.442-5.143) but not for LFS (p = 0.057, hazard ratio = 1.678, 95%CI = 0.986-2.857). A novel nomogram based on DBIL, sex, age, β2-microglobulin, lactate dehydrogenase, the Revised International Prognostic Scoring System (IPSS-R) was constructed, which demonstrated superior accuracy compared with the IPSS-R (C-index, 0.790 vs. 0.731, respectively). An elevated DBIL level was identified as an independent adverse prognostic factor for MDS patients. An individualized prediction model was established and validated to improve prediction of OS and LFS.

New mutation in the β-spectrin gene in hereditary spherocytosis: A case report

In patients with recurrent anemia, jaundice, and splenomegaly, a thorough assessment of family history and peripheral blood smears is crucial for diagnosing hereditary spherocytosis (HS). Furthermore, gene sequencing can enhance diagnostic accuracy and facilitate the investigation of disease mechanisms at the molecular level. In this report, we present a case of HS caused by a heterozygous nonsense mutation in the SPTB gene, along with a family history of this specific mutation. A 35-year-old man was evaluated for jaundice and splenomegaly, which he had experienced since childhood. Blood tests revealed anemia, reticulocytosis, elevated indirect bilirubin levels, and an increased percentage of spherical red blood cells in the peripheral blood. His family history indicated that both his father and daughter exhibited similar clinical manifestations. Subsequently, genetic sequencing confirmed that the patient, along with his father and daughter, shared the heterozygous missense mutation c.155G > A (p.Arg52Gln) in the SPTB gene, which is absent in public population and animal sequence databases. Structural prediction analysis of the protein suggests that this mutation may lead to instability of SPTB mRNA, thereby affecting the synthesis of the spectrin protein and the integrity of the red blood cell membrane skeleton. Further research is needed to clarify the exact relationship between this mutation and the occurrence of HS.

Innovative fluorescent ratiometric probe from Oolong tea dreg for highly sensitive bilirubin detection

Bilirubin, a crucial component in heme degradation, is formed during the breakdown of red blood cells in the liver and spleen. Elevated bilirubin levels are closely associated with jaundice and serve as markers for various blood and liver-related disorders. Detection of BR has been approached through various methods with fluorescent methods gaining prominence due to their exceptional sensitivity, rapid response, and precision. Among the fluorescence methods, carbon dots have emerged as versatile optical probes, known for their unique optical properties, low toxicity, and ease of synthesis. However, carbon dots typically exhibit a single emission peak, limiting accuracy due to vulnerability to external interferences. To overcome this limitation, probes featuring multiple independent emission signals are preferred. Chlorophyll, abundant in nature and sourced from biomass, is recognized for its safe and fluorescent properties, making it a secure choice for fluorescence-based sensing. This study introduces an innovative approach utilizing Oolong tea dreg as a source of chlorophyll for creating a fluorescent probe to detect bilirubin. Chlorophyll was partially converted into carbon dots using a combination of extraction and hydrothermal techniques, producing a ratiometric probe with two emission signals. The fluorescence of the probe was quenched in the presence of the bilirubin through the inner filter effect. The proposed probe exhibited outstanding selectivity and a low limit of detection (0.8 µM) for bilirubin. Furthermore, the probe demonstrated satisfactory recovery rates when tested with artificial urine and human urine samples.

Safety and Tolerability of Nintedanib in Patients with Fibrosing Interstitial Lung Diseases: Post-marketing Data.

Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis-associated interstitial lung disease (ILD). We present global post-marketing safety data for nintedanib in these fibrosing ILDs. Data on adverse events in patients with fibrosing ILDs who were treated with nintedanib were collected via spontaneous reporting and solicited reporting in various studies (excluding clinical trials).Data were collected from 15 October 2014 (first regulatory approval) to 15 October 2023. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Cumulative exposure to nintedanib was estimated using sales data. Cumulative exposure to nintedanib was 380,557 patient-years. Diarrhoea was reported at a rate of 227.5 per 1000 patient-years. Only 2.6% of diarrhoea events were reported as serious. Of 39,788 (33.6%) diarrhoea events with a known time to onset, almost 60% occurred within the first 3months of treatment. The rate of serious liver enzyme and bilirubin elevations (including drug-induced liver injury) was 4.0 per 1000 patient-years. Bleeding was reported at a rate of 24.2 per 1000 patient-years. Most (81.3%) bleeding events were non-serious. The rates of myocardial infarction, ischaemic stroke, and venous thromboembolism were 3.3, 3.3, and 2.0 per 1000 patient-years, respectively. Gastrointestinal perforation was reported at a rate of 0.9 per 1000 patient-years. Post-marketing safety data on established and potential adverse events associated with nintedanib in patients with fibrosing ILDs, collected over 9years, demonstrated a safety profile that was similar to that established in clinical trials and provided in the product labels. Education of patients about the adverse events that may be associated with nintedanib, and the effective management of adverse events when they occur, is important to minimise the impact of adverse events and help patients remain on treatment.

Conditional over-expression of heme-oxygenase 1 in myelomonocytic cells reduces AngII-induced hypertension and vascular inflammation in mice

Abstract Background Systemic arterial Hypertension is one of the most important risk factor responsible for morbidity and mortality world-wide. Angiotensin II (Ang II), a potent vasoconstrictor and key player in the renin-angiotensin-aldosterone system (RAAS) is responsible for vascular dysfunction, inflammation, and tissue damage. Heme oxygenase-1 (HO-1) overexpression may confer antioxidant and anti-inflammatory properties in Ang II-induced hypertension through its action on heme catabolism, generating carbon monoxide (CO), ferritin and biliverdin/bilirubin by the action of biliverdin reductase A (BLVRA). Methods and results Male 9–12-weeks-old HO-1indxLySMCre/wt and LySMCre/wt mice were infused with AngII (1mgAngII/Day/Kg) for 7 days to induce hypertension and compared to sham treatment. Blood pressure monitoring by tail-cuff method, and endothelium-dependent vasodilator studies via organ chamber system using acetylcholine (ACh) in isolated aortic segments (~4 mm), revealed that overexpression of HO-1 in myeloid cells resulted in decreased systolic blood pressure and improved endothelial function in AngII-infused HO-1indxLySMCre/wt mice compared to controls. Concurrently, increased BLVRA expression in liver tissue and elevated plasma bilirubin levels were detected by transcriptome analysis and high-performance liquid chromatography, respectively. These results were supported by a reduction in the expression of inducible cytokines and cell adhesion molecules (CAMs) in the aorta, assessed using qPCR. Bone marrow transplant experiments demonstrated that bone marrow from LysMcre mice in HO-1indxLySMCre/wt mice abrogated the protective effect of HO-1, resulting in endothelial damage and increased blood pressure, potentially due to decreased liver BLVRA expression and the accumulation of bone marrow-derived cells in the vessel wall in response to AngII. Additionally, adeno-associated viral vector (AAV) transfection targeting specifically BLVRA activity in liver lead to an increase in blood pressure values and worse endothelium relaxation, in parallel with higher oxidative stress and the blood neutrophils concentration, as assessed in whole blood by using oxidative burst method and blood count system respectively. Conclusion The overexpression of HO-1 in myeloid cells confers anti-inflammatory protection in AngII-induced arterial hypertension in mice. Myeloid cells bone marrow-derived overexpressing HO-1 regulate the differentiation and infiltration of pro-inflammatory immune cells in the vasculature. BLVRA expression and bilirubin levels downstream of HO-1 play a critical role in protecting against vascular damage by reducing leukocyte infiltration.

Взаимосвязь уровня неконьюгированного билирубина и спирометрических показателей у подростков с бронхиальной астмой

Either a high-to-normal or slightly elevated total bilirubin level may have external respiration protective effect in patients with bronchial asthma (BA). However, Authors have searched but not found any studies related to the connection between the unconjugated bilirubin level and spirometric parameters in adolescents. The purpose of this research was to study the connection between unconjugated bilirubin level and spirometric parameters in adolescents with BA. Materials and methods used: a single-center observational cross-sectional pilot study of 74 adolescents aged 10 to 17 y/o with BA was conducted. All participants had undergone measurements of anthropometric and spirometric parameters, hematological parameters, both total and unconjugated bilirubin level. Results: elevated total bilirubin (17.1 mmol/l and higher) occurred in 40.5% (30) being the highest in homozygous carriers of UGT1A1 gene polymorphisms with an increased number of TA repeats, the differences were statistically insignificant. The unconjugated bilirubin level and such spirometric indicators as z-ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity of the lungs (FVC) and z-criterion of the mean forced expiratory flow during the 25-75% of FVC (MEF25-75) had statistically significant direct correlation (R=0,42, p<0,001, R=0,37, p=0,001, respectively). Patients with obstructive lung ventilation disorders at the time of examination (zFEV1/FVC less than -1.645) had lower levels of both total and unconjugated bilirubin, the differences were statistically significant (p=0.002 and p=0.004, respectively). Conclusion: statistically significant correlations between unconjugated bilirubin level and such spirometric parameters as zFEV1/FVC and zMEF25-75 as well as unconjugated bilirubin low level identification in patients with spirometric indicators of bronchial obstruction suggest a protective effect of unconjugated bilirubin on the development of bronchial obstruction in adolescents with BA.

A phase 1 study of the amino acid modulator pegcrisantaspase and venetoclax for relapsed or refractory acute myeloid leukemia

AbstractGlutamine dependency has been shown to be a metabolic vulnerability in acute myeloid leukemia (AML). Prior studies using several in vivo AML models showed that depletion of plasma glutamine, induced by long-acting crisantaspase (pegcrisantaspase [PegC]) was synergistic with the BCL-2 inhibitor venetoclax (Ven), resulting in significantly reduced leukemia burden and enhanced survival. Here, we report a phase 1 study of the combination of Ven and PegC (VenPegC) for treating adult patients with relapsed or refractory AML, including patients who had previously received Ven. The primary end points were the incidence of regimen-limiting toxicities (RLTs) and the maximum tolerated dose (MTD). Twenty-five patients received at least 1 PegC dose with Ven, and 18 efficacy-evaluable patients completed at least 1 VenPegC cycle; 12 (67%) had previously received Ven. Hyperbilirubinemia was the RLT and occurred in 60% of patients treated with VenPegC; 20% had grade ≥3 bilirubin elevations. MTD was determined to be Ven 400 mg daily with biweekly PegC 750 IU/m2. The most common treatment-related adverse events of any grade in 25 patients who received VenPegC included antithrombin III decrease (52%), elevated transaminases (36%-48%), fatigue (28%), and hypofibrinogenemia (24%). No thromboembolic or hemorrhagic adverse events or clinical pancreatitis were observed. The overall complete remission rate in efficacy-evaluable patients was 33%. Response correlated with alterations in proteins involved in messenger RNA translation. In patients with RUNX1 mutations, the composite complete rate was 100%. This study was registered at www.ClinicalTrials.gov as #NCT04666649.

Exploring the antioxidant and protective effects of Marsdenia thyrsiflora Hook.f. leaf extract against carbon tetrachloride-induced hepatic damage in rat models.

Medicinal plants are vital to healthcare, yet many remain unexplored. Marsdenia thyrsiflora Hook.f., from Bangladesh's Bhawal Forest, lacks research on its medicinal properties, especially its antioxidant capacities and protection against CCl4-induced liver toxicity. This study aims to evaluate the antioxidant properties of M. thyrsiflora leaf extract to determine its protective effects on rodents against CCl4-induced liver injury. After extraction, the total phenol, flavonoid content, and antioxidant capacity of the leaf extract were measured using established protocols. Free radical scavenging abilities were evaluated with 2,2'-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) assays. Additionally, reducing power was assessed through cupric-reducing and ferric-reducing assays. Based on the OECD 420 recommendation, acute toxicity was tested on Swiss albino mice to establish an effective and safe dosage. For the hepatoprotective study, Sprague-Dawley rats were pre-treated with M. thyrsiflora leaf methanolic extract (MTLM) at 250 and 500mg/kg body weight, and CCl4 was administered to induce liver damage. Serum hepatic enzyme levels (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)), lipid profile (total cholesterol, triglycerides), total bilirubin, and markers of lipid peroxidation (Malondialdehyde (MDA)) were measured. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were also evaluated to assess oxidative stress. The results demonstrated that MTLM, rich in phenolic and flavonoid content, exhibits significant antioxidant activities in DPPH and NO radical scavenging assays, as well as in reducing power assays. The acute toxicity study confirmed the safety of MTLM, with no adverse effects observed even at high doses. For the hepatoprotective study, rats were administered CCl4 to induce liver damage, followed by treatment with MTLM. Results showed that MTLM significantly reduces liver damage markers such as elevated serum hepatic enzyme levels, lipid profile, total bilirubin, and lipid peroxidation and improves the activities of GSH and key antioxidant enzymes such as SOD and CAT. Histopathological analysis corroborated these findings, displaying reduced necrosis, inflammation, and edema in liver tissues treated with MTLM. MTLM extract exhibits potent antioxidant and hepatoprotective properties. Its ability to attenuate oxidative stress, enhance antioxidant enzyme activities, and facilitate histopathological changes in the liver highlights its potential as a natural therapeutic agent for liver damage. However, further investigation is required to understand its molecular processes, safety profiles, and active component characterization.

Analysis of risk factors for bleeding as a complication of ultrasound-guided percutaneous liver biopsy examination

Objective: To explore the independent risk factors for bleeding in patients following percutaneous liver biopsy examination. Methods: The clinicopathological data of patients who underwent percutaneous liver biopsy examination at Nanjing Second Hospital from January 2012 to December 2021 were retrospectively collected. Univariate and multivariate logistic regression analysis were used to investigate the effect of age, gender, lesion type (diffuse liver parenchymal lesions, focal liver lesions), number of biopsies, tissue length, presence or absence of cirrhosis, presence or absence of portosystemic shunt, erythrocytes, white blood cells, hemoglobin, platelets, prothrombin time, fibrinogen, international normalized ratio, and liver biochemical indicators on bleeding following liver biopsy, as well as to screen independent risk factors. Results: A total of 3 331 patients were examined by percutaneous liver biopsy, and 3 060 cases were actually included by excluding 271 cases who took consultation from other hospitals. The overall postoperative hemorrhagic rate was 1.6% (49/3 060). Of which, forty-four cases (1.4%) had overt bleeding (hemodynamic changes or hemoglobin decreased by more than 20 g/L), five cases (0.2%) had minor bleeding, three cases had subcapsular hepatic hemaotma, and two cases had local bleeding from liver biopsy. Among the overt bleeding cases, two cases were in the off-label group (platelet<50×109/L or international normalized ratio>1.5), and the rest were in the non-off-label group. The results of univariate analysis showed that factors such as focal liver lesions, portosystemic shunt, prolonged prothrombin time, increased international normalized ratio, bilirubin, and alkaline phosphatase were associated with bleeding after liver biopsy in the non-off-label group. The multivariate collinearity diagnosis revealed statistically significant differences for the indicators. Multivariate logistic regression analysis finally included factors such as lesion type, portosystemic shunt, international normalized ratio, total bilirubin, and alkaline phosphatase. The results showed that patients with focal liver lesions were more prone to bleed after surgery than patients with diffuse liver parenchymal lesions (OR=3.396, P=0.002, 95%CI: 1.596-7.228). Patients with portosystemic shunt were more prone to bleed than those without portosystemic shunt (OR=3.301, P=0.018, 95%CI: 1.232-8.845). Patients were more likely to experience bleeding following liver biopsy when their total bilirubin levels were elevated (OR=1.006, P<0.001, 95%CI:1.003-1.008). Conclusion: Focal liver lesions, portosystemic shunts, and elevated total bilirubin are independent risk factors for bleeding after percutaneous liver biopsy.

A Method for Compensating Hemoglobin Interference in Total Serum Bilirubin Measurement Using a Simple Two-Wavelength Reflectance Photometer.

Neonatal hyperbilirubinemia (NH) is a common condition in newborns, with elevated bilirubin levels potentially causing neurological damage or death. Accurate and timely measurements of total serum bilirubin are essential to prevent these outcomes. Direct spectrophotometry, a reliable method for measuring bilirubin, is particularly useful in constrained settings due to its potential for portable low-cost instrumentation. However, this method is susceptible to interference from hemoglobin, often present due to hemolysis. Typically, this interference is reduced using complex optical filters, reagents, multiple wavelengths, or combinations thereof, which increase costs and complexity while reducing usability. This study presents a hemoglobin compensation algorithm applied to a simple, portable, two-wavelength (465 and 590 nm) reflectance photometer designed to receive 30 µL of plasma or whole blood samples and perform the measurement without any reagents. Testing across five bilirubin and hemoglobin levels (4.96 to 28 mg/dL and 0.06 to 0.99 g/dL, respectively) demonstrated that the algorithm effectively reduces hemoglobin interference and overestimation errors. The overall root mean square error was reduced from 4.86 to 1.45 mg/dL, while the measurement bias decreased from -4.46 to -0.10 mg/dL. This substantial reduction in overestimation errors supports future clinical trials with neonatal blood samples.

An Observational Study of Electrolytes and Other Metabolic Parameters in Patients with Delirium in Hospital Settings

Abstract Background: Despite extensive research, pathophysiology of delirium remains inadequately understood, with studies suggesting a role for inflammatory mediators, cholinergic deficiency, and metabolic disturbances. Aim: This study aims to explore the association of electrolytes and other metabolic parameters in hospitalized delirium patients as compared to age- and gender-matched nondelirious controls. Materials and Methods: The observational case–control study was conducted at a multispecialty hospital in eastern India where 100 inpatients diagnosed with delirium (cases) and an equal number of age- and gender-matched nondelirious inpatients (controls) were administered a semi-structured pro forma for sociodemographic variables and assessed for electrolytes and other metabolic parameters. Statistical analysis employed Pearson’s Chi-square test to assess the significance of differences between the two groups. Results: The study revealed statistically significant differences in metabolic disturbances in delirium cases as compared to controls with a greater association of hyperglycemia (P = 0.009), hyponatremia (P = 0.002), hypercalcemia (P = 0.001), hyperkalemia (P = 0.030), and hypokalemia (P = 0.005) among delirium patients. Hypoalbuminemia (P = 0.002) and elevated bilirubin levels (P = 0.014) as well as uremia (P &lt; 0.001) and elevated creatinine levels (P &lt; 0.001) also had a greater association with delirium cases than controls. Sociodemographic analysis revealed a higher incidence of delirium in older adults and males. Conclusion: There was a significant association between delirium and various biochemical disturbances, highlighting the importance of thorough metabolic workup to identify and correct these disturbances which would potentially enhance delirium outcomes. There is a need for further studies to explore the causal pathways of these associations and the impact of targeted metabolic interventions on delirium outcomes.

Analysis and validation of clinical subgroups of Kawasaki disease in children in China: a retrospective study

ObjectiveAlthough Kawasaki disease (KD) is commonly regarded as a single disease entity, clinical subgroups have recently been described. We aimed to validate previous research on clinical subgroups and establish a...

Spectrum of liver affection in children with sickle cell disease: case series

BackgroundSickle cell hepatopathy (SCH) is a relatively uncommon complication of sickle cell disease (SCD), yet it does not accommodate variations in presentation, outcome, or severity according to age.AimTo present SCH characteristics and assess the effect of implementation of a high-suspicion systematic diagnostic approach and early intervention plan of management.MethodsThis case series presented the characteristics of five children with SCD with variable hepatic manifestation and implemented a diagnostic approach that included testing the transaminases and bilirubin in any patient with any suspicion of liver affection.ResultsThe five patients had a complicated SCD history. They all presented with fever, abdominal pain, and deepening of jaundice. The final diagnosis was reached with a more individualized approach; two had significant coagulopathy and were diagnosed with sickle cell intrahepatic cholestasis, while one had normal synthetic functions of the liver with rising transaminases and bilirubin levels, as well as high titer of Epstein–Barr virus diagnosed as acute viral hepatitis complicated with sickle cell hepatic crisis. One other patient had markedly elevated bilirubin with mild elevation of transaminases, and magnetic resonance cholangiopancreatography showed acute extrahepatic biliary dilatation treated by endoscopic removal of the stone. The fifth patient proved to have portal vein thrombosis by portal duplex causing portal hypertension and decompensated liver. The management plan included early exchange transfusion to keep their hemoglobin S (HbS) below 15% which was performed in three of the patients, in addition to aggressive supportive measures for correction of coagulopathy with full recovery and normalization of their liver functions.ConclusionDespite the diagnostic challenges, the lack of standard diagnostic criteria, and the overlapping clinical presentation of SCH, the management and outcomes improved by following a systematic diagnostic approach.

6980 A Case Report Of Severe Hypercalcemia In Acute Decompensated Liver Cirrhosis

Abstract Disclosure: M.M. Eid: None. R.M. Sargis: None. Introduction: Hypercalcemia in advanced liver disease in the absence of malignancy is a rare condition. Case: A 26 year old female with history of liver cirrhosis secondary to alcohol use disorder, presented with hematemesis and ascites. She was diagnosed with acute decompensated liver cell failure and transferred to our facility for liver transplantation. On Day 10 of her hospital course, she had an acute rise in serum calcium (Ca) to 10.8 mg/dl (N 8.7-10.5),albumin (Alb) 2.6 g/dl, corrected calcium (CCa) 11.9mg/dl. On day 13 Ca peaked to 13.5 mg/dl, CCa 14 mg/dl, ionized Ca 6.5mg/dl (N 4.2-5.4 mg/dl). Serum Ca was normal on day 9, Ca 8.7mg/dl, Alb 2.5 g/dl and CCa 9.9 mg/dl. She was not taking lithium, vitamin A or antacid. No personal or family history of bone disorder, fracture or kidney stone. On exam, blood pressure 85/45, heart rate 110 bpm, jaundiced with abdominal distension and respiratory distress. Labs: hemoglobin 8.1 g/dl, WBC 32.5K/Ul, platelet 136 K/Ul, serum creatinine 1.82 mg/dl, Na 133 mmol/l, K 3.5 mmol/l, Total/Direct bilirubin 29.9/18.1 mg/dl, alkaline phosphatase 166 U/L, AST/ALT 60/42U/l, Mag 2.3 mg/dl, Phos 5 mg/dl, INR 3, PTT 50 sec, parathyroid hormone (PTH) 12 pg/ml (N12-88), TSH 1.02 mciu/ml (N 0.34-4), 25 hydroxy vitamin D 17 ng/ml (N 20-80), parathyroid related peptide (PTHrP) 3.9 pmol/l (N&amp;lt;3.4), 1,25 di-hydroxy vitamin D 9.8 pg/ml (N 19.9-79.3), alpha fetoprotein 9.1 ng/ml (N &amp;lt;9). Normal anti smooth muscle and anti mitochondrial antibodies. Negative viral hepatitis serology. CT abdomen did not reveal hepatobiliary mass or tumor nor kidney stone. She was intubated and mechanically ventilated. Vasopressor support was initiated. One dose of calcitonin 4 units/kg and zoledronic acid 4 mg were given. Serum Ca decreased to 12 mg/dl, CCa 12.6 mg/dL then to 10.2 mg/dl, CCa 11mg/dl within hrs. Calcium normalized to 8.4mg/dl, CCa 9.2 mg/dl, ionized Ca 4.3 mg/dl within 24 hrs. Her condition deteriorated and withdrawal of care was decided. Conclusion: Our case demonstrates non PTH and non vitamin D mediated severe hypercalcemia in setting of acute decompensated cirrhosis and absence of malignancy. Previous literature has noted poor prognosis of hypercalcemia with acute decompensated cirrhosis. While hypercalcemia in cirrhosis may arise from paraneoplastic processes, in absence of malignancy it is speculated that acute hypercalcemia may arise from the inflammatory mediators inducing osteoclastic bone resorption as osteoclast activating factor, prostaglandin and immobilization. Some reports found an association between hypercalcemia and elevations in bilirubin and creatinine(1). Further research is needed to understand the pathophysiology and the management of hypercalcemia in acute decompensated cirrhosis.

A-014 Fifth Generation Troponin T is Unaffected by Extreme Levels of Lipemia and Icterus

Abstract Background The tissue specific cardiac isoform of troponin (cTnT) originates exclusively from the myocardium; therefore, it is used as the primary diagnostic biomarker for myocardial infarction. Lipemia, caused by elevated lipoprotein particles, and icterus, caused by elevated bilirubin, are common endogenous interferences that can lead to erroneous results. According to the instructions for use (IFU), recovery is acceptable when bilirubin levels are ≤25 mg/dL (conjugation not specified) and intralipid levels are ≤1500 mg/dL. However, it is common in large hospital settings to observe higher levels for these potential interferents. The purpose of this study was to determine whether 5th generation cTnT results are negatively impacted by extreme levels of lipemia or conjugated or unconjugated bilirubin. Methods cTnT interference studies were performed on a cobas e602 (Roche Diagnostics). Low, mid, and high cTnT sample pools at approximate concentrations of 20 ng/L, 100 ng/L, and 1000 ng/L were split into target and control pools. To evaluate the effect of lipemia, target pools were spiked with intralipid solution to achieve a lipemia index (LI) ranging from 1500-2000 (correlates poorly with mg/dL triglycerides). Samples were analyzed in triplicate for cTnT and serum indices. To evaluate the effect of icterus, target pools were spiked with conjugated or unconjugated bilirubin to achieve an icterus index (II) ranging from 30-55 (approximately equal to mg/dL bilirubin). Samples were analyzed in triplicate for cTnT, conjugated and unconjugated bilirubin, and serum indices. Interference was determined by calculating the variance between the average target and corresponding control result. Results Conclusions cTnT has a high lipemia and icterus tolerance with recoveries &amp;lt;10% for all three cTnT concentrations.

A-133 Trusted Test Goes Awry: Investigating Dilution Aberrations for Total Bilirubin

Abstract Background A patient with acute decompensated cirrhosis was hospitalized due to lightheadedness and jaundice, undergoing evaluation for a liver transplant. The attending physician brought to the laboratory’s attention a perplexing pattern in the patient's total bilirubin results. Initially, the patient displayed a consistent trend of elevated total bilirubin levels above the upper limit of linearity, ULOL (&amp;gt; 30 mg/dL), which then plummeted to under the limit of quantification (&amp;lt; 0.1 mg/dL) before surging back to &amp;gt; 30 mg/dL. Methods The total bilirubin in heparinized plasma was measured on the AU5800 by Beckman Coulter. Samples &amp;gt; ULOL are diluted automatically 1:3 utilizing the instrument’s on-board dilution feature. The final test results are reported automatically to an electronic medical record. Following the reported incident, an investigation and troubleshooting plan was developed, encompassing the following steps: Repeat patient testing with total bilirubin concentration &amp;gt; 30 mg/dL and &amp;lt;0.1 mg/dL; Rule out the previously reported potential interferences, including Immunoglobin M and acetaminophen; Conduct a 90-day quality control (QC) review; Perform split test analysis on two instruments within the laboratory and at a reference laboratory; Conduct patient chart reviews to identify discrepancies based on previously reported values; Complete a root cause analysis and develop corrective/preventive action plan. Results Patient sample &amp;lt; 0.1 mg/dL was tested on an alternative instrument, resulting &amp;gt; 30 mg/dL. Patient with normal IgM of 161 mg/dL didn’t reveal any other potential drug interferences in chart review. The 3-month QC review found consistent with peer performance. Split comparison of 6 patients revealed discrepancies for samples &amp;gt; 30 mg/dL on one of the two instrument units. When total bilirubin &amp;gt; 30 mg/dL, the malfunctioning unit erroneously reported values &amp;lt; 0.1 mg/dL after dilution. Review of 34 patient charts showed the impact dates were spanned for 39 days. Since the on-board dilution feature is utilized by 10 other analytes, 892 diluted samples were analyzed for discrepancies. 36 discrepant results were identified among 4 affected assays including total bilirubin, direct bilirubin, creatine kinase, and alanine aminotransferase. These results were corrected, and providers were notified. Conclusions The root cause was traced to a malfunction in one instrument unit, despite no malfunction flags. The laboratory QC concentrations fell within the analytical measurement range, missing the dilution issue during the daily QCs. During an extensive repair period, the on-board dilution was disabled on the affected unit and samples were re-routed to alternative instrument for testing. Policy changes and operator training were initiated for a new result verification process, impacting the laboratory productivity. Autoverification of diluted sample results was disabled for all chemistry analyzers. The vendor identified the issue as sample transfer unit crane misalignment in the up/down direction. It is worth noting that proficiency testing or QCs often do not extend beyond the analytical measurement ranges, leading to undetected incidents. Additional quality measures like periodic patient chart reviews, patient sample comparisons, and other quality assurance tools can aid in on-going dilution performance verification. Open communication between the physicians and laboratories is crucial for prompt issue identification and resolution.