Elevated Total Bilirubin Levels Research Articles

Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors CAR, PPARα, and stress sensor, ATF4. When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep), and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.

Leptospirosis in a patient with cardiac manifestation: A case report study and literature review

Key Clinical MessageCommon cardiac arrhythmias seen in patients with leptospirosis are usually atrial fibrillation or first‐degree atrioventricular block, with bradyarrhythmia being rare in this group. It is essential to prioritize the examination of the patient's medical background, clinical symptoms, and comprehensive physical evaluation in order to promptly identify and address the patient's condition.AbstractLeptospirosis, a zoonotic disease that is widespread worldwide, has a significant impact on tropical areas and can affect various organs throughout the infection. During the initial stage, symptoms are typically non‐specific. Although cases of all three cardiac layers being affected have been reported, issues with the conduction system are especially significant in the early phase of the disease. The most frequent discoveries in these patients are atrial fibrillation or first‐degree atrioventricular block, with bradyarrhythmia being rare. We describe a 37‐year‐old male farmer who initially sought medical attention for general symptoms that had been deteriorating despite receiving outpatient treatment for 3 days for a presumed diagnosis of influenza. During his initial assessment, he exhibited sinus bradycardia, anemia, leukocytosis, elevated levels of direct and total bilirubin, and abnormal liver function test results. Through thorough history‐taking, physical examination, and laboratory analyses, a diagnosis of leptospirosis was conclusively established for him. Focusing on the patient's medical history, clinical manifestations, and thorough physical assessment is crucial for promptly diagnosing and treating patients. This becomes particularly significant for individuals who exhibit atypical symptoms, exemplified by our patient presenting with nonspecific indications and cardiac issues manifested as bradycardia.

Recovery from antibody-mediated biliary ductopenia and multiorgan inflammation after COVID-19 vaccination

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality. Spike messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 may contribute to immune-mediated injuries. Here we present a case of a previously healthy 47-year-old man, who developed progressive jaundice 2 weeks after receiving his 3rd COVID-19 vaccination (1st mRNA-based vaccine). Apart from elevated serum total bilirubin levels (peaked at >70 mg/dL), deteriorating renal (blood urea nitrogen: peak, 108.5 mg/dL; creatinine: peak, 6 mg/dL) and exocrine pancreas (amylase: peak, 1717 U/L; lipase: peak, 5784 U/L) profiles were also seen. Vanishing bile duct syndrome characterized by ductopenia and cholangiocyte vacuolation, positive C4d deposition, and high titer of anti-angiotensin II type 1 receptor antibody consistently explain the overall antibody-mediated pathogenesis resembling antibody-mediated “rejection” in the solid organ transplant setting. Corticosteroids and plasmapheresis were administered, leading to gradual resolution of the symptoms, and the jaundice completely resolved 2 months later. In conclusion, we reported a case of antibody-mediated multiorgan injury after an mRNA COVID-19 vaccine, characterized by severe cholangiopathy. The patient recovered with corticosteroids and plasmapheresis, and long-term follow-up is necessary.

Unconjugated bilirubin as a state marker in patients with schizophrenia in acute episode: an Egyptian study

BackgroundThere is a substantial body of evidence linking unconjugated bilirubin to schizophrenia. Most of the earlier research has found a statistically significant relationship between the two factors.Aim of the workTo study the level of unconjugated bilirubin in individuals with acute schizophrenia and to investigate its correlation with neuropsychological, psychopathological, and psychosocial aspects of the disorder.Patients and methodsEighty schizophrenia patients were included in the sample, they had multiple previous episodes and were in acute episodes at the time of recruitment. Forty healthy individuals were recruited for the control group. The DSM-IV was used to diagnose the subjects, and the Trail Making Test (TMT), Positive and Negative Syndrome Scale (PANSS), General Assessment of Function (GAF), and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) were used to evaluate the subjects’ social functioning, symptom severity, and cognitive functioning. A blood sample was drawn to measure serum bilirubin level. We analyzed the relationship and correlation of unconjugated bilirubin with the previous scale scores.ResultsCompared to healthy control individuals, who volunteered to participate, schizophrenia patients reported significantly higher levels of both total and indirect bilirubin. One subject (with schizophrenia) had an abnormally elevated total bilirubin level (> 1.2 mg/dL). Neither the direct nor the indirect bilirubin levels (> 0.3 mg/dl or > 1.2 mg/dL) were clinically abnormal in any of the patients. PANSS total score, PANSS N score, and PANSS G score were found to have a statistically significant positive connection with levels of total, direct, and indirect bilirubin. Age, gender, smoking, BMI, Total PANSS, PANSS P, PANSS N, PANSS G, GAF, TMT-A, TMT-B, antipsychotic medication, psychotic disorder duration, and duration of untreated psychosis were not predictive of total or indirect bilirubin levels, according to linear regression analysis. However, Total PANSS, PANSS N, and PANSS G were significantly predictive for direct bilirubin levels.ConclusionA statistically significant difference in total and unconjugated bilirubin mean serum levels between schizophrenia patients and healthy individuals was found. More studies are recommended to revise the contradictory results in literature on the unconjugated bilirubin and Schizophrenia.

Perioperative outcomes after open biliary bypass for malignant biliary obstruction (MBO) in resource-limited setups; a multicenter prospective cohort study, 2023

IntroductionObstructive jaundice is the most common symptom of malignant diseases of the extrahepatic biliary system and necessitates either non-operative or operative biliary bypass. Because of percutaneous and endoscopic approaches, the use of palliative surgical procedures has decreased in recent years. However, in resource-limited situations, open biliary bypasses remain a viable option. This study aimed to identify factors associated with adverse perioperative outcomes following open biliary bypass. MethodsFrom June 2022 to May 2023, 69 patients underwent open biliary bypass for malignant biliary obstruction. Postoperative morbidity and mortality within 30 days of surgery were assessed. A Kaplan-Meier was used for categorical variables, and a log-rank test was used to determine the statistically significant difference between variables. A Cox regression analysis was conducted to identify factors associated to time to develop complications. ResultsThe hazard of developing complications among those with preoperative cholangitis was 2.49 times higher than those without preoperative cholangitis (HR 2.49, 95% CI [1.06, 5.84]). For every hour increment in the length of surgery, the hazard of getting complications increased by 2.47 times (HR 2.47, 95% CI [1.28, 4.77]). As serum bilirubin increased by 1 mg/dl, the hazard of developing complications increased by 14% (HR 1.14, 95% CI [1.03, 1.17]). ConclusionPatients who had long operation times, preoperative cholangitis, and elevated total bilirubin levels are at increased risk for poor perioperative outcomes. Clinicians may use these results to optimize these patients to decrease their elevated risk of serious morbidity and mortality.

LABS score– a prognostic tool for FOLFOX4-treated advanced hepatocellular carcinoma and real-world efficacy: a single-center retrospective study

BackgroundNo widely used prognostic tool exists to demonstrate the benefit of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) in patients with advanced hepatocellular carcinoma (HCC). We aimed to establish a prognostic score and demonstrate the real-world efficacy of FOLFOX4 chemotherapy in Thai patients.MethodsBetween August 2017 and December 2021, we identified 58 FOLFOX4-treated patients with HCC. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were assessed. The prognostic score was constructed by stepwise Cox proportional hazards regression analysis to select variables for the best model with the lowest Akaike information criterion from all potential variables.ResultsForty-four patients (76%) received FOLFOX4 as first-line therapy. The ORR in the entire cohort was 8.6%, and the disease control rate was 29.3%. The PFS and OS were 3.7 and 4.8 months, respectively. Four clinically relevant variables were included in the new prognostic score to predict 6-month OS: L, the presence of lung metastasis; A, alcoholic cirrhosis; B, elevated total bilirubin level; and S, sorafenib-naïve status. Using the LABS score, patients were classified into low-, intermediate-, and high-risk groups, demonstrating OS values of 9.3, 4.2, and 2.1 months, respectively (p < 0.0001). The C-index and area under the receiver-operating characteristic curve of the score were 0.71 and 0.73, respectively.ConclusionsThe proposed LABS score could discriminate patients who would derive benefit from FOLFOX4 chemotherapy. FOLFOX4 chemotherapy is an option for patients who cannot receive immunotherapy and targeted therapy, particularly those with a low-risk score. However, further validation of this model via larger cohorts is warranted.

Smoke Signals: Unraveling the Link between Cigarette Smoking and Serum Liver Markers

Introduction: Cigarette smoking is a major cause of global mortality and morbidity. It exposes the body to many harmful substances, such as cytotoxic, carcinogenic and free radicals, that can damage various organs. This study aims to investigate the effects of different levels of tobacco exposure on liver tissue, by measuring some serum biochemical markers of liver function.&#x0D; Materials and Methods: The project conducted at T.N.M.C Mumbai from January to December 2021 involved 60 male participants (18–35 years old), divided into smokers (30) and non-smokers (30). Smokers had varying smoking durations (1-5 years). Excluded participants with diseases affecting liver enzymes. Groups were age-matched for analysis. Smokers defined as those smoking &gt;20 cigarettes daily for &gt;1 month. Collected 5.0 ml venous blood, processed in heparinized tubes, and centrifuged for plasma separation. Enzymes SGOT, SGPT, ALP, Total Bilirubin, Direct Bilirubin were measured, and statistical analysis revealed significant differences.&#x0D; Results: In the study, age comparison between smokers and non-smokers showed no significant difference (p = 0.71). However, smokers exhibited significantly higher mean serum concentrations of SGOT and SGPT compared to non-smokers (p = 0.002 and p &lt; 0.0001, respectively). Smokers also had elevated levels of ALP and total bilirubin with mean differences of 16.3 IU/L and 0.392 mg/dl, supported by 95% confidence intervals (6.72, 26.18) and (0.28, 0.504) and p values of 0.003 and 0.0004, respectively. No significant difference was observed in direct bilirubin levels (mean difference: 0.084 mg/dl, 95% CI: 0.065, 0.103, p = 0.191)&#x0D; Conclusion: In summary, the study suggests a correlation between smoking and elevated serum levels of liver enzymes and damage markers, indicating a potential adverse impact on liver function and increased susceptibility to liver diseases.

Prevalence and Associated Factors of Vertebral Fractures in Children with Chronic Liver Disease with and without Liver Transplantation.

To evaluate the prevalence of vertebral fracture (VF) in children with chronic liver disease (CLD) with and without liver transplantation (LT) and to determine the associated factors. A cross-sectional study was conducted. Patients aged 3-21 years with CLD both before and after LT were enrolled in the study. Lateral thoracolumbar spine radiographs were obtained and assessed for VF using Mäkitie's method. Clinical and biochemical data were collected. We enrolled 147 patients (80 females; median age 8.8 years [interquartile range 6.0-11.8]; 110 [74.8%] in the LT group and 37 [25.2%] in the non-LT group). VF was identified in 21 patients (14.3%): 17/110 (15.5%) in the LT group and 4/37 (10.8%) in the non-LT group (p=0.54). Back pain was noted in only three patients with VF. In the univariate analysis, a height z-score below -2.0 (p=0.010), pre-LT hepatopulmonary syndrome (p=0.014), elevated serum direct and total bilirubin levels (p=0.037 and p=0.049, respectively), and vitamin D deficiency at 1-year post-LT (p=0.048) were associated with VF in the LT group. In multivariate analysis, height z-score below -2.0 was the only significant associated factor (odds ratio, 5.94; 95% confidence interval, 1.49-23.76; p=0.012) for VF. All VFs in the non-LT group were reported in males. In children with CLD, VF is common before and after LT. Most patients with VF are asymptomatic. Screening for VF should be considered in patients with a height z-score below -2.0 after LT.

Peri-operative extracorporeal membrane oxygenation in adult and pediatric living donor liver transplantation: a single-center experience.

Extracorporeal membrane oxygenation (ECMO) is a potential rescue therapy for patients with acute cardiopulmonary dysfunction refractory to conventional treatment. In this study, we described the clinical profiles and outcomes of adult and pediatric living donor liver transplantation (LDLT) patients who received ECMO support during the peri-operative period. From June 1994 to December 2020, eleven out of the 1,812 LDLTs performed at Kaohsiung Chang Gung Memorial Hospital required ECMO support: six for respiratory failure, three for cardiogenic shock, and two for refractory septic shock. Comparison between the survivor and non-survivor groups was made. The survival rate for liver transplantation (LT) patients on ECMO support is 36.4%-40% in adults and 33.3% in pediatrics, while the survival rate per indication is as follows: acute respiratory distress syndrome (ARDS) (50%), cardiogenic shock (33.3%), and sepsis (0%). Shorter durations of LT-to-ECMO and pre-ECMO mechanical ventilation were observed in the survivor group. On the other hand, we observed persistently elevated total bilirubin levels in non-survivors, while none of the survivors had aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels >1,000 U/L. A higher proportion of non-survivors were on concurrent continuous renal replacement therapy (CRRT). Our experience has proven ECMO's utility during the peri-operative period for both adult and pediatric LDLT patients, more specifically for indications other than septic shock. Further studies are needed to better understand the factors leading to poor outcomes in order to identify patients who will more likely benefit from ECMO.

Vitamin B12 Deficiency and Hemolytic Anemia Presenting As Pseudo Thrombotic Microangiopathy: A Systematic Review

Introduction: Vitamin B12 deficiency is a common nutritional issue associated with mild anemia and neurological deficits. While rare, hemolytic anemia and low platelet count can be complications of this deficiency, often misdiagnosed as thrombotic microangiopathy (TMA), specifically thrombotic thrombocytopenic purpura (TTP). Pseudo TMA features can occur with B12 deficiency and can be effectively treated with vitamin B12 supplementation. In contrast, true TMA requires plasmapheresis. This systematic review aims to differentiate between pseudo TMA and TMA cases through an analysis of published case reports, providing valuable insights to avoid unnecessary treatments. Methods: We performed systematic review from Pubmed, Web of Science, and Scopus database. Twin independent reviewers (SY and BL) performed the screening using Covidence. Search keywords included “((hemolytic anemia) AND (vitamin B12 deficiency)) OR ((cobalamin deficiency) AND (hemolytic anemia)) Filters: English” for Pubmed, “(((ALL=(Cobalamin deficiency)) OR ALL=(vitamin B12 Deficiency))) AND ALL=(hemolytic anemia) Filter: English” for Web of Science and “( vitamin AND b12 AND deficiency OR cobalamin AND deficiency ) AND hemolytic AND anemia AND ( LIMIT-TO ( LANGUAGE , ”English“ ))” from Scopus. Only case reports in English with full-text availability and adult subjects were selected. Cases without final clinical outcome after treatment were excluded. After a comprehensive review, we identified 43 case reports and series with a total 53 patients that fulfilled our criteria. The details of selection process is illustrated in the prisma diagram (Figure 1). Results: The majority of cases involved males with low hemoglobin and platelet counts upon admission. Evidence of hemolysis was observed, indicated by increased lactate dehydrogenase (LDH), undetectable haptoglobin, and elevated or normal total and direct bilirubin levels. Peripheral blood films confirmed the presence of hemolytic anemia. Due to the co-occurrence of thrombocytopenia and hemolytic anemia, some cases were initially diagnosed as TTP, leading to the initiation of plasmapheresis. In 16 out of 53 reported case reports/series, patient received plasmapheresis. However, low reticulocyte index and normal ADAMTS 13 suggested an alternative diagnosis. Once ADAMTS 13 levels were normal, plasmapheresis was discontinued as TTP was ruled out. Diagnosis of B12 deficiency was confirmed by low B12 levels and elevated methylmalonic acid (MMA) levels. Leading cause for B12 deficiency were pernicious anemia in 28/53 cases, followed by dietary deficiency, and malabsorption due to surgery. Some patients also exhibiting concurrent iron deficiency anemia and folate deficiency. Treatment with subcutaneous B12 injections showed improvement in hemolysis as early as one week. Conclusion: Many cases of Vitamin B12 deficiency presenting with hemolytic anemia and thrombocytopenia are mistakenly diagnosed as TTP, leading to unnecessary and expensive plasmapheresis. Routine B12 level checks should be performed in all patients with hemolytic anemia, as B12 deficiency can be rapidly diagnosed and effectively treated, avoiding misdiagnoses and unnecessary interventions associated with TTP. The short turnover time for B12 levels (hours) compared to ADAMTS 13 activity (1-2 days) further supports the importance of routine B12 assessment in these patients.

Relationship between the Incidence of Neonatal Hyperbilirubinemia and Gestatinal Age as a Risk Factor

Neonatal hyperbilirubinemia (NH) or neonatal jaundice is characterized by elevated serum levels of total bilirubin in the blood and yellow color of the baby's skin, sclera, and mucous membranes. Neonatal hyperbilirubinemia can cause mild-moderate-severe neurological disorders, up to death, if left untreated. The incidence of neonatal hyperbilirubinemia (NH) in Indonesia in 2016 reached 51.47% of cases where 33.3% of the total NH cases were related to prematurity. The purpose of this study is to determine the incidence of NH in RSAB Harapan Kita This research is a type of quantitative analytical research with a cross sectional approach. The study population is babies born at RSAB Harapan Kita for the period January 2022 – December 2022. Using a random sampling technique with the slovin formula and a margin of error of 5%, a sample of 315 patients met the inclusion and exclusion criteria. Furthermore, statistical analysis was carried out using the chi-square test. As many as 158 (50.2%) babies born at RSAB Harapan Kita experienced NH with the most results of female babies (54.4%), aged 24-48 hours (48.1%), low birth weight (57%), and premature gestational age (67.7%). Bivariate analysis of the association of gestational age with NH incidence has a significance value of &lt;0.001 which proves a significant association. Conclusions: There is a significant association between preterm gestational age and NH incidence

Hyperbilirubinemia is a Predictor of Gangrenous or Perforated Appendicitis

Introduction: Acute appendicitis is the most common acute abdominal condition that requires surgical intervention in childhood. Patients with complicated appendicitis (CA) were reported to have elevated serum bilirubin or reduced serum sodium levels in several studies. Aim of the study: The purpose of this study was to establish the role of hyperbilirubinemia as a predictive parameter for the prediction of either acute, or gangrenous/perforated appendicitis. Methods: The present descriptive type observational study was accomplished in Department of Surgery, Faridpur Medical College Hospital, Bangladesh. Medical files of the patients, who underwent appendectomies between July 2015 and January 2016, were evaluated. Age, gender, preoperative white blood cell count (WBC), neutrophil count (NEU), neutrophil percentage (NEU %), C-reactive protein (CRP), total/ direct/indirect bilirubin levels, and preoperative presentation &amp; severity, complication of disease, outcome and postoperative hospital stay findings were recorded. The Fisher’s exact, Pearson’s χ2, ANOVA, and Kreskas–Wallis tests while logistic regression for multivariate analysis was performed. P value &lt; 0.05 was accepted as statistically significant\ for this study. Result: 50 patients of more than 15 years old participated in this study. Histopathological examinations revealed normal appendix in 11 (22%) patients, non-complicated acute appendicitis in 18 (36%), and appendiceal gangrene/perforation in 21 (42 %) patients. WBC, NEU, NEU%, and CRP levels were found significantly elevated in cases of acute and gangrenous/perforated appendicitis (p &lt; 0.01). Total and direct bilirubin levels were also significantly higher in patients with acute and gangrenous/perforated appendicitis (p &lt; 0.01). Multivariate analysis, higher levels of CRP were associated with 14 times, elevated total bilirubin levels were associated with five times, and elevated direct bilirubin levels were associated with 36 times greater risk ........

Therapeutics of L. Lanceolata and V. Doniana on Alcohol Induced Hepatic Pathology

Additive and stimulative properties of alcohol encourage large intake. Notwithstanding, chronic alcohol consumption causes severe hepatic damage, that alters normal biological function of the liver. The aim of this research was to assess the effects of Lophira lanceolata and Vitex doniana extracts on alcohol induced hepatotoxicity using rat model by examining liver serum enzymes (AST, ALT, ALP), lipid peroxidation level, antioxidant enzyme activity and haematological parameters. Thirty Wister rats weighing 70 to 120g were placed in six groups of fives per group. The negative control and treatment groups were familiarized with alcohol (42%) in drinking water before oral administration of 42% consumable alcohol (v/v, 1ml/100g body weight) for nine days. Afterward, the treatment groups were administered 600mg/kg body weight extracts of Lophira lanceolata, Vitex doniana and Vitamin C (as standard drug). Body weight and behavioural characters were monitored during the period. It was observed that, rats in the negative and treatment groups showed significant depletion in weight and negative changes in behaviour. Furthermore, biochemical assessment revealed significant elevated levels of liver serum enzymes (ALT, AST, ALP) activity, total and direct bilirubin, MDA, SOD and CAT while GSH and haematological parameters were significantly depleted at p&lt;0.05. However, the treated groups revealed significant reduction in the liver enzymes, MDA, SOD and CAT while GSH activity and haematological parameters were significantly increased. In conclusion, both extracts have ameliorative and antioxidant properties that could mitigates chronic alcohol hepatotoxicity.

The Clinical Presentations of Liver Abscess Development After Endoscopic Retrograde Cholangiopancreatography with Choledocholithiasis: A 17-Year Follow-Up.

Endoscopic Retrograde Cholangiopancreatography (ERCP), used for choledocholithiasis treatment, carries a risk of pyogenic liver abscess (PLA) due to communication between the biliary system and bowel contents. However, limited data exists on this issue. This study aims to identify the risk factors pertaining to liver abscesses following ERCP lithotomy. We conducted a retrospective case series across multiple centers to evaluate patients who developed PLA after ERCP for choledocholithiasis. Data was obtained from the Chung Gung Research Database (January 2001 to December 2018). Out of 220 enrolled patients, 195 were categorized in the endoscopic sphincterotomy (ES) group, while 25 were in the non-ES group for further analysis. The non-ES group had significantly higher total bilirubin levels compared to the ES group (4.3 ± 5.8 vs 1.9 ± 2.0, p<0.001). Abscess size, location, and distribution (single or multiple) were similar between the two groups. The most common pathogens were Klebsiella pneumoniae and Escherichia coli. Pseudomonas infection was significantly less prevalent in the ES group compared to the non-ES group (3.6% vs 16.7%, p=0.007). Patients with concurrent malignancies (HR: 9.529, 95% CI: 2.667-34.048, p=0.001), elevated total bilirubin levels (HR: 1.246, 95% CI: 1.062-1.461, p=0.007), multiple abscess lesions (HR: 5.146, 95% CI: 1.777-14.903, p=0.003), and growth of enterococcus pathogens (HR: 4.518, 95% CI: 1.290-15.823, p=0.001) faced a significantly higher risk of in-hospital mortality. PLA incidence was higher in the ES group compared to the non-ES group following ERCP for choledocholithiasis. Attention should be given to significant risk factors, including concurrent malignancies, elevated total bilirubin levels, multiple abscess lesions, and growth of enterococcus pathogens, to reduce in-hospital mortality.

Bilirubin Elevation Caused by Naproxen Overdose: A Case Report Highlighting Laboratory Interference.

BACKGROUND Overdoses on over-the-counter (OTC) drugs are increasing in the United States, which includes widely available non-steroidal anti-inflammatory drugs (NSAIDs) like naproxen. Symptoms of NSAID toxicity are well known and nonspecific, including nausea, vomiting, abdominal pain, and headaches. Extreme cases can present with confusion, seizures, and renal failure. CASE REPORT We present the case of 63-year-old man with a history of hyperthyroidism and polysubstance use who had an elevated total bilirubin level after attempting suicide via ingestion of 16 tablets of naproxen. The patient presented with vague abdominal pain and nausea in the setting of 2 weeks of worsening psychiatric symptoms, including suicidal ideation. Vital signs, physical examination, and review of systems revealed no significant findings. Medical workup was notable only for an elevated total bilirubin level; workup for hemolysis, biliary stasis, hepatic dysfunction was all within normal limits. Direct bilirubin was not elevated. The patient received intravenous fluids and antiemetic medications, and indirect hyperbilirubinemia resolved by the following day. After ruling out other causes of hyperbilirubinemia, it was determined that his elevated bilirubin was due a naproxen metabolite, O-desmethylnaproxen (ODMN), that has been shown to interfere with certain bilirubin assays when naproxen is ingested over the therapeutic dose. CONCLUSIONS Supratherapeutic naproxen ingestion can lead to laboratory findings of elevated total bilirubin in some assays due to ODMN interference. With the rise in suicide attempts in the United States with OTCs, clinicians should consider laboratory error in such clinical circumstances where the clinical data does not fit the history and physical examination.

Clinical characteristics and prognostic factors of 75 cases with acquired hemophagocytic syndrome

ABSTRACTObjectivesThe study's aim was to enhance awareness of acquired hemophagocytic syndrome (HPS) in adults by analyzing clinical features, and investigating the relationship between factors such as the Systemic Inflammation Index (SII) and the prognosis of HPS.MethodsClinical characteristics, survival data, and prognostic factors of 75 HPS patients admitted to our hospital between January 2012 and October 2022 were analyzed.ResultsIn the high SII group, red blood cells, white blood cells, platelets, neutrophils, fibrinogen, and CD4 + cell activity were higher, and survival time was longer compared to the low SII group. Conversely, total bilirubin and direct bilirubin were higher in the low SII group (P ≤ 0.05). After applying the log-Rank or Breslow tests, HPS patients in the high SII group and those following the HLH-2004 protocol experienced a notably longer survival time. (χ2 = 4.291, P < 0.05; χ2 = 5.210, P < 0.05). Patients with poor prognosis showed higher age of onset, elevated levels of total, direct, and indirect bilirubin, and a greater rate of EBV infection, but reduced levels of red blood cells, platelets, hemoglobin, albumin, globulin, and HLH-2004 protocol usage rate(P < 0.05). Multivariate analysis and ROC curve results indicate that special attention is needed for patients with platelets < 42.5 × 109/L, albumin < 27.7 g/L, fibrinogen < 1.085 g/L, those not following the HLH-2004 protocol, and those who are EBV (+).Discussion and ConclusionEarly diagnosis and following the HLH-2004 protocol are essential for patients with HPS clinical manifestations to improve prognosis. Additional research is necessary to examine the link between SII and HPS patients’ prognosis.

Long-term liver and renal dysfunction in patients with metastatic renal cell carcinoma treated with TKI monotherapy: COMPARZ study post-hoc analysis.

e16536 Background: Tyrosine kinase inhibitors (TKI) are currently the recommended treatment option for advanced renal cell carcinoma (aRCC) patient. Previous studies have shown some hepatorenal toxicity of TKI regimens, but differences in toxicity and long-term toxicity of TKIs have rarely been reported. This study aims to compare short- and long-term hepatorenal toxicity differences between pazopanib and sunitinib, and to explore the factors predisposing to hepatorenal toxicity. Methods: COMPARZ study was a randomized phase III non-inferiority study comparing pazopanib and sunitinib in aRCC patients. Patients without liver metastasis and with available alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin results were enrolled to evaluate the effect of TKI on liver function. Patients with available serum creatinine (Cr), blood urea nitrogen (BUN), urine protein/creatinine ratio (UPC), and creatinine clearance (CrCl) were enrolled to evaluate factors associated with abnormal renal function. Lab indicators were compared between baseline and at months 12, 24, and 36 by paired t-test respectively. Linear mixed models were used to compare the difference in changes between treatment arms. Multivariate logistic regression was performed to examine the factors associated with recorded adverse events of hepatorenal toxicities. Results: Patients with abnormal liver function tests at baseline had higher elevated ALT, AST and total bilirubin levels at 12 months after TKIs treatment compared with patients who had normal baseline results. ALT levels were not significantly different between pazopanib arm and sunitinib arm at 12, 24 and 36 months. However, patients in the sunitinib arm had significantly higher AST levels than the pazopanib arm at 12 months (p = 0.049). There was no significant difference in total bilirubin level between pazopanib and sunitinib arm. Asian race and pazopanib were two factors that was significantly associated with increased risk of developing abnormal liver function. At 12 months, Cr levels were higher in the sunitinib arm compared with the pazopanib arm . BUN levels were lower in the pazopanib arm at 12 months but conversely was higher in the sunitinib arm at 24 months. UPC levels were significantly elevated in both treatment arms at 12 months (p &lt; 0.001) and 24 months (p = 0.008). CrCl levels decreased in both treatment arms, and was more obvious in the sunitinib group at 12 months and 24 months. Notably, male patients, Asian race, high BMI, and sunitinib were risk factors that were significantly associated with abnormal renal function. Conclusions: Compared with sunitinib, pazopanib was associated with a higher risk of hepatoxicity but lower risk of nephrotoxicity. Overall, Asian patients have a higher risk of developing abnormal liver and renal functions after TKI treatment.

Correlation of ectopic distal location of papilla of Vater and clinical characteristics in pediatric choledochal cysts.

Ectopic distal location of papilla of Vater (EDLPV) is an obvious pathological feature of choledochal cyst (CDC). This study aimed to investigate the correlation between EDLPV and clinical characteristics of CDCs. Three groups were studied: Group 1 (G1), papilla in the middle third of second part of duodenum (n = 38); Group 2 (G2), papilla from the distal third of second part to the beginning of third part of duodenum (n = 168); Group 3 (G3), papilla from the middle of third part to fourth part of duodenum (n = 121). Relative variables among three groups were compared. Compared with G1 and G2, G3 patients had the largest cysts (relative diameter: 1.18 vs. 1.60 vs. 2.62, p < 0.001), the youngest age (20.52 vs. 19.47 vs. -3.40months, p < 0.001), the highest rate of prenatal diagnosis (26.32% vs. 36.31% vs. 62.81%, p < 0.001), the lowest occurrence of protein plugs in common channel (44.74% vs. 38.69% vs. 16.53%, p < 0.001), and the most elevated total bilirubin level (7.35 vs. 9.95 vs. 28.70μmol/L, p < 0.001). Prenatally diagnosed G3 patients had heavier liver fibrosis than G2 (13.16% vs. 1.67%, p = 0.015). The more distal papilla location, the more severe clinical characteristics of CDCs, suggesting a crucial role in its pathogenesis.

Characteristics and prognostic analysis of simultaneous bilateral sudden sensorineural hearing loss.

To evaluate the clinical characteristics of simultaneous bilateral sudden sensorineural hearing loss (Si-BSSNHL) as well as its prognostic factors. Patients with Si-BSSNHL who were admitted to the Department of Otology Medicine between December 2018 and December 2021 were enrolled in the case group. Propensity score matching (PSM) for sex and age was used to select the control group, which included people who had unilateral sudden sensorineural hearing loss (USSNHL) during the same time period. Hearing recovery, audiological examinations, vestibular function assessments, laboratory tests, and demographic and clinical manifestations were analyzed for intergroup comparisons. Binary logistic regressions were used for both univariate and multivariate analyses of Si-BSSNHL prognostic factors. Before PSM, the Si-BSSNHL and USSNHL groups differed significantly (p < 0.05) in terms of time from onset to treatment, initial pure-tone average (PTA), final PTA, hearing gain, audiogram curve type, proportion of tinnitus, high-density lipoprotein level, homocysteine level, and effective rate. After PSM, significant differences were also observed in time from onset to treatment, initial PTA, final PTA, hearing gain, total and indirect bilirubin levels, homocysteine level, and effective rate between the two groups (p < 0.05). There was a significant difference in the classification of therapeutic effects between the two groups (p < 0.001). For prognostic analysis, the audiogram curve type was significantly different between the effective group and the ineffective groups of Si-BSSNHL (p = 0.01), in which the sloping type was an independent risk factor for the prognosis of the right ear in Si-SSNHL (95% confidence interval, 0.006-0.549, p = 0.013). Patients with Si-BSSNHL had mild deafness, elevated total and indirect bilirubin and homocysteine levels, and poorer prognosis than those with USSNHL. Audiogram curve type was linked to the therapeutic effect of Si-BSSNHL, and the sloping type was an independent risk factor for a poor prognosis in the right ear of Si-SSNHL.

Association of Liver Function Serum Markers and Unfavorable Outcomes in Traumatic Liver Injury Patients

OBJECTIVE To evaluate serum markers in liver function tests (LFT) at various intervals after traumatic liver injury to identify serum markers associated with unfavorable outcomes. METHODS A retrospective cohort analysis was conducted of trauma center patients older than 18 years with traumatic liver injury. Liver function test (LFT) results of patients with favorable and unfavorable outcomes were compared at different post-injury time points. Statistical significance was established as p-value less than 0.05. RESULTS Of the 206 patients with severe liver injuries in the unfavorable outcome group, 119 (57.8%) needed intervention. Aspartate amino-transferase (AST) and alanine transaminase (ALT) were seen to increase in correlation with injury severity at initial admission. On days 1-5 and 6-10 after admission, the unfavorable outcome group had a slower decline in AST. In the unfavorable group, total bilirubin (TB) and direct bilirubin (DB) levels rose significantly 5 days after the injury and were higher than normal with a higher odds ratio (OR) of unfavorable outcome 11-15 days after injury in multivariable analysis [OR (95% confidence intervals): 2.7 (1.02-7.37) and 6.9 (1.08-44.14), respectively]. CONCLUSIONS Liver function tests can help identify individuals at risk for traumatic liver injury complications. Elevated levels of TB and DB are statistically significantly associated with adverse outcomes, particularly after day 5 following the injury. Early repeating LFT in first five days after injury may be less beneficial in determining patient risk. Blood test results may be affected by the amount of fluid resuscitation, particularly on the first day of admission in cases of high- grade injuries. KEYWORDS aspartate aminotransferase, liver injury, liver function test, unfavorable outcome, alanine transaminase, bilirubin