Elevated Bilirubin Levels Research Articles

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.

Safety Profile of Eltrombopag in Different Age Groups: An Analysis of Real-World Pharmacovigilance and Randomized Clinical Trials.

Eltrombopag is clinically approved for use in immune thrombocytopenia (ITP), chronic hepatitis C-related thrombocytopenia, and aplastic anemia and suitable for children; however, data on its overall safety profile are scarce. This study aimed to explore the clinical features of adverse drug events (ADEs) associated with eltrombopag in different age groups using individual case safety reports (ICSRs) from the World Health Organization database VigiBase and the US Food and Drug Administration Adverse Event Reporting System database from 2008 to 2022 in combination with a meta-analysis of data from randomized clinical trials in the literature from inception to July 28, 2022. We conducted disproportionality analyses by grouping patients into the following age groups: 0-17 (0-23 months, 2-11 years, and 12-17 years), 18-64, and ≥ 65 years. The ADEs about hepatobiliary disorders, thrombosis, skin and subcutaneous tissue disorders, infections, and so on were observed more differently in each age group. Meta-analysis results showed differences in the four system organ classes between adults and children with ITP: infections and infestations, general disorders and administration site conditions, skin and subcutaneous tissue disorders, and investigations. The adverse drug reactions in the latest version of instructions were searched in the databases to analyze their postmarketing safety signal strength. We observed signals of elevated alanine aminotransferase, aspartate aminotransferase, and blood bilirubin levels in all age groups. For children, urinary tract infection and back pain showed signals. Due to the inherent limitations of pharmacovigilance studies, more experiments are needed to assess the risks of eltrombopag in different ages.

Management of a pregnancy with Crigler-Najjar syndrome type 2: a case report

Objective: To report a case with Crigler-Najjar syndrome type 2 of elevated bilirubin levels who was treated with triple therapy. Case(s): Crigler-Najjar syndrome is a rare congenital disorder that causes non-obstructive non-hemolytic unconjugated jaundice. The syndrome is divided into two groups according to the severity and the clinical presentation of the disease. In these cases, there is an elevated risk of antenatal death or permanent neurological impairment of the fetus due to fetal kernicterus caused by excessively increased unconjugated bilirubin levels. Phototherapy, phenobarbital and plasmapheresis can be useful in reducing serum total bilirubin concentrations, thus adverse maternal and neonatal risks. Conclusion: At her 37 weeks of gestation, the patient delivered a healthy girl. No pathological neurological findings were found and the baby had normal growth with intact neurological development.

The Effects of Long-Term Self-Dosing of Cannabidiol on Drowsiness, Testosterone Levels, and Liver Function

Introduction: Previous research indicated that cannabidiol (CBD) may result in low levels of male total testosterone (TT), elevations in liver tests (LTs), and daytime drowsiness (DD). We investigated the prevalences of TT and LT in a large adult sample self-administering CBD and determined the effect self-dosing of CBD has on the severity of DD. Methods: Adult participants (18–75 years of age) who self-dose CBD orally for a minimum of 30 days were recruited for this decentralized observational study from companies that offer CBD products. Participants were sent their usual CBD regimen. A clinical study platform was used on a phone app to obtain consent and collect study data. Data included demographic information, reasons for self-dosing, dosage, current medications and dosage, medical history, adverse effects, effects on DD, and efficacy. After 30 days, LT and TT were obtained and follow-up LT was offered to participants who demonstrated elevated values of alanine transaminase (ALT). Results: A total of 28,121 individuals were contacted, 1,475 met the criteria and were enrolled, and 1,061 (female: 65.2%, male: 34.8%) completed the study. Most of the participants used full-spectrum CBD oil or CBD isolate with the mean ± SD daily dose of CBD for all users of 55.4 ± 37.8 mg. CBD use was associated with a significant decrease in DD and a decrease in the prevalence of low TT in males >40 years of age. The prevalences of elevations in ALT and aspartate aminotransferase were not significantly different from those of the general adult population, and the prevalences of elevated levels of alkaline phosphatase and bilirubin were less than those of a healthy adult population. There was no relationship between LT and CBD dose. Conclusions: In this large-sample study, self-dosing CBD was not associated with an increased prevalence of elevation of LT or low levels of TT in men. Furthermore, CBD administration decreased DD and was associated with a lower prevalence of low testosterone levels in older men as compared to age-adjusted population norms.

Effects of bilirubin on the development and electrical activity of neural circuits.

In the past several decades, bilirubin has attracted great attention for central nervous system (CNS) toxicity in some pathological conditions with severely elevated bilirubin levels. CNS function relies on the structural and functional integrity of neural circuits, which are large and complex electrochemical networks. Neural circuits develop from the proliferation and differentiation of neural stem cells, followed by dendritic and axonal arborization, myelination, and synapse formation. The circuits are immature, but robustly developing, during the neonatal period. It is at the same time that physiological or pathological jaundice occurs. The present review comprehensively discusses the effects of bilirubin on the development and electrical activity of neural circuits to provide a systematic understanding of the underlying mechanisms of bilirubin-induced acute neurotoxicity and chronic neurodevelopmental disorders.

Evaluation of lung function in a German single center cohort of young patients with sickle cell disease using EIT and standard techniques.

Sickle cell disease (SCD) is a very common autosomal recessive hemoglobinopathy leading to multiple pulmonary complications that are closely associated with mortality. The pathophysiology of chronic pulmonary involvement is not yet fully understood and no specific therapies are available. The aim of this cross-sectional study was to characterize the lung function of children and young adolescents with SCD in a German single-center cohort and to extend conventional lung function testing by the use of a new imaging method. We performed spirometry and body plethysmography in 35 children and young adults with hemoglobin SS, SC, S/β-thalassemia as well as 50 controls. These data were compared with clinical characteristics and typical laboratory parameters of hemolysis and disease activity in SCD. To identify lung inhomogeneities, for example due to atelectasis, hyperinflation, air trapping or vascular occlusions, we used the promising new method of electrical impedance tomography (EIT) and calculated global inhomogeneity indices. Lung function of patients with SCD was significantly reduced compared to that of healthy controls. When the result was found to be pathological, the most commonly observed type of breathing disorder was classified as restrictive. Laboratory parameters showed typical features of SCD including decreased levels of hemoglobin and hematocrit and elevated levels of leucocytes, platelets, lactate dehydrogenase and total bilirubin. However, there was no correlation between blood values and reduced lung function. Electrical impedance tomography (EIT) revealed no abnormalities in SCD patients compared to healthy controls. In particular, we were unable to demonstrate any regional inhomogeneities in lung ventilation. In our study, SCD patients showed impaired lung function, with a relevant percentage of patients suffering from restrictive breathing disorder. Signs of obstruction could not be detected. Electrical impedance tomography (EIT) measurements revealed no unevenness that would suggest air entrapment, blockage of blood vessels, excessive inflation, obstruction, or other forms of lung disease. Additionally, the reduction in lung function observed in SCD patients was not related to the disease severity or laboratory test results.

Noncirrhotic portal hypertension misdiagnosed as liver cirrhosis: A rare case

Noncirrhotic portal hypertension misdiagnosed as liver cirrhosis: A rare case

Abstract OT2-01-09: ABEMACARE: Abemaciclib in Combination with Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients with Symptomatic Visceral Metastases or High Tumor Burden – A prospective multicenter observational study

Abstract OT2-01-09: ABEMACARE: Abemaciclib in Combination with Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients with Symptomatic Visceral Metastases or High Tumor Burden – A prospective multicenter observational study

The liberal use of magnetic resonance cholangiopancreatography can be switched over to its selective use to detect choledocholithiasis

Background: Gallstone disease is known in 10-15% of adults in Western populations. Magnetic resonance cholangiopancreatography (MRCP) is the investigation of choice for choledocholithiasis; however, its use is varied, and guidelines are not well defined. The National Institute for Health and Care (NICE) guidelines recommends MRCP to be done when common bile duct (CBD) dilatation ≥8 mm or liver function tests (LFTs) are abnormal but do not quantify this further. The liberal use of MRCP is gaining popularity as a roadmap prior to cholecystectomy, aiming to assess primarily for the presence of migrated gallstones within the cystic duct or common bile duct, as well as providing information regarding the anatomical features of the extrahepatic biliary tree on an individualised basis. Due to these reasons MRCP at times is done unnecessarily which creates economic burden and restricts access to patients in real need of imaging slots. Methods: It is hospital based retrospective observational study. Time frame was July 2021 to July 2022 and sample size was 230 patients. Results: Our study showed that isolated elevated alanine aminotransferase (ALT) level should not be reason to evaluate patients for choledocholithiasis. It concluded that elevated serum bilirubin levels, alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Conclusions: To conclude elevated serum bilirubin levels, ALP and GGT are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Isolated elevated ALT should not be a reason to evaluate patients for CBD stones.

Relationship between elevated bilirubin levels and enhanced warfarin effects during biliary obstruction.

A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin. Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction. Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ = -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR. PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

Analysis of the impact of eliminating bolus 5-fluorouracil in metastatic colorectal cancer.

59 Background: 5-Fluorouracil (5-FU) is a component of first-line treatment regimens for metastatic colorectal cancer (mCRC). Historically, 5-FU is administered as a bolus followed by an infusion. However, the bolus dose adds substantial toxicity and is often withheld in patients with limited functional status or high-risk comorbidities, but its impact on treatment outcomes remains unclear. Small studies suggest that it may be omitted. The aim of this study was to determine whether omission of the 5-FU bolus is associated with a difference in overall survival (OS). Methods: An electronic health record-derived national multicenter oncology database from Flatiron Health was queried to select patients with mCRC who received a first-line 5-FU-containing regimen. Demographics, relevant labs, treatment details, and survival outcomes were collected. Propensity score (PrS) matching and OS analysis were performed incorporating age, race, sex, ECOG score, combination drug regimen, and baseline creatinine and bilirubin. Variables with p &lt; 0.10 in univariable Cox proportional hazards models were included in the multivariable analysis. Results: We included 9741 patients with mCRC who received 5-FU-based regimens. All individuals received a 5-FU infusion, and 7901 (81%) also received a 5-FU bolus. Among our entire cohort, 43% were female, 23% were &gt; 70 years, 66% were white, and 89% had ECOG ≤ 1. Over a median follow-up time of 19 months, 5847 patients (60%) died. In the unmatched univariable (HR 0.94, 95% CI 0.88-1.00, p = 0.06) and multivariable (aHR 0.85, 95% CI 0.93-1.06, p = 0.85) analyses, there was no association between the use of bolus 5-FU and OS. A number of factors were associated with an increased risk of death, including older age, high ECOG scores, and elevated bilirubin or creatinine levels. Similarly, in our PrS-matched dataset (n = 6126), the use of a 5-FU bolus was not associated with OS (HR 0.98; 95% CI 0.91-1.06; p = 0.64). Conclusions: The findings of our PrS-matched multicenter cohort study indicate that, after adjusting for host and treatment factors, 5-FU bolus dosing was not associated with an overall survival benefit among patients with mCRC. These results suggest that, in mCRC, the addition of a 5-FU bolus does not appear to add efficacy to regimens utilizing infusional 5-FU. Future work is necessary to determine the role of bolus dosing in the adjuvant setting and its impact on other clinically-relevant outcomes.

Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Acute suppurative terminal cholangitis: Clinical characteristics of a new subtype of acute cholangitis

BackgroundAcute suppurative terminal cholangitis (ASTC) is rarer than acute obstructive cholangitis and is not well studied. To explore this subtype of acute cholangitis, we described our clinical experience with ASTC. MethodsWe performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020. We analyzed their clinical characteristics, including etiology, clinical manifestations, imaging features, treatment and prognosis. ResultsA total of 32 ASTC patients were included in the analysis. The majority of the patients had a history of biliary operations, and clinical manifestations were occult and atypical. The positive rate of bacterial culture was 46.9%. All the patients had typical imaging features on computed tomography and magnetic resonance imaging. Treatment with effective antibiotics was provided as soon as diagnosis was established. After treatment, most patients had a good outcome. Elevated levels of total bilirubin, aspartate aminotransferase, procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis. ConclusionsOur results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis, and that earlier diagnosis and more personalized treatments are needed.

Modern view on pathogenesis, diagnosis and treatment of Gilbert's syndrome

Gilbert’s syndrome is an autosomal recessive inherited disorder of bilirubin glucuronidation characterized by unconjugated hyperbilirubinaemia in the absence of hepatocellular injury or hemolysis. Gilbert’s syndrome is characterized by mutations to the UGT1A1 gene which encodes the enzyme uridine disphosphate glucuronоsyltransferase which is required for the conjugation and subsequent excretion of bilirubin. Most Gilbert’s syndrome patients experience recurrent and short-term episodes of yellowing of the skin and sclera of eyes caused by bilirubin accumulation in the blood. Approximately 30 % of patients with Gilbert's syndrome do not experience any symptoms, but are detected by blood tests that show elevated levels of unconjugated bilirubin. In addition to traditional methods, genetic analysis of the UGT1A1 gene allows us to confirm the diagnosis of Gilbert's syndrome. The article presents modern concepts of the pathogenesis, diagnosis, differential diagnosis and treatment of Gilbert's syndrome. It is of interest to gastroenterologists, internists and general practitioners who treat such patients.

Favism: Clinical Features at Different Ages.

Favism is a hemolytic disease due to the ingestion of fava beans in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. There is wide inter- and intra-individual variability in the development of hemolytic crisis, and several factors influence it: quantity, quality, ripeness of fava beans, and age of onset. In this narrative review of case reports and case series, we reported the predisposing factors and clinical features for four different age groups classified as follows: pregnant women and infants (i.e., exclusively breastfed children); children, from weaned to 11 years; preadolescents and adolescents, from 11 to 18 years; and adults (18 years and older). Some symptoms developed only in specific age groups: death in infants; visual impairment in children; systolic murmur in infants, children, and adolescents; and renal failure in adults. In youngest children or pregnant women the severity is the highest. Some other symptoms were present in all: jaundice, increased bilirubin, splenomegaly, hepatomegaly, discolored urine, tachycardia, pallor, abdominal pain, malaise, vomit, nausea, and dizziness. Laboratory findings are characterized by anemia, reticulocytosis, elevated bilirubin level, and sometimes urinary urobilinogen and methemoglobinemia. In most cases the symptomatology is self-limited and does not release sequelae, but hospitalization and transfusion are often required.

Determination of risk factors for conversion from laparoscopic to open appendectomy in patients with acute appendicitis.

Acute appendicitis is the most common cause of surgical emergencies. It can be difficult to distinguish cases of acute appendicitis that should be managed by laparoscopic appendectomy (LA) from those that should be managed by open surgery. This study aimed to prevent the inappropriate choice of technique and associated complications by identifying potential risk factors for conversion from laparoscopic to open appendectomy (OA) at the time of initial surgical assessment. This is a retrospective analysis of patients who underwent laparoscopic exploration for acute appendicitis. The study included patients over 18 years of age between January 2016 and July 2021. Patients were divided into two groups according to the surgical approach: those who underwent a LA and those who initially underwent laparoscopic exploration first and then converted to OA. Demographics, perioperative factors, and outcomes were compared between groups. The study included 634 adults undergoing laparoscopic exploration for an appendectomy. About 80.8% had LA, and 19.2% (n=122) required COA. COA patients' average age was significantly higher than LA patients' (48.5 years vs. 37.8 years, P<0.001). The conversion rate for patients over 65 was 63.8%, compared to 15.6% for those under 65 (P<0.001). COA patients had higher bilirubin levels (36.1% vs. 13.5%, P<0.001), higher American Society of Anesthesiologists (ASA) scores (ASA >2, COA 52.5% vs. LA 7.8%, P<0.001), and a higher need for CT imaging (84.4% vs. 67.6%, P<0.001) than LA patients. An Alvarado score >6 significantly differenti-ated LA from COA (62.6% vs. 39.4%, P< p<0.001). COA patients experienced significantly increased periods until starting oral intake (31.6 vs. 9.9 h, P<0.001) and higher rates of complicated appendicitis (40.9% vs. 0.6%, P<0.001). After surgery, COA had higher rates of complications compared to LA: surgical site infections (8.2% vs. 2.7%, P=0.004), reoperation (13.1% vs. 0%, P<0.001), hospital re-admission (14.7% vs. 2.3%, P<0.001), and mortality (1.6% vs. 0%, P<0.004). Advanced age, especially over 65 years, elevated bilirubin levels, an ASA >2 score, and an increased need for pre-operative diagnostics using CT scans were found to be significant predictors of conversion to OA. In the conversion group, operative time, time to oral intake, and the incidence of complicated appendicitis were significantly higher. The conversion group had significantly higher rates of postoperative complications, surgical site infections, hospital readmissions, and mortality. To avoid the increased rate of complications associated with conversion to open surgery, the initial evaluation of a patient with prospective risk factors may be beneficial.

Hepatoprotective and antifibrotic effects of trans-chalcone against bile duct ligation-induced liver fibrosis in rats.

Several lines of research have shown that hepatic fibrosis is one of the leading causes of death worldwide. Trans-chalcone is a flavonoid precursor with anti-oxidant and anti-inflammatory effects. The present study was conducted to examine the antifibrotic properties of trans-chalcone on bile duct ligation (BDL)-induced liver cholestasis in rats. Following the BDL operation, trans-chalcone at doses of 12, 24, and 50 mg/kg was administered orally once a day for 45 consecutive days. Serum levels of liver indices, including alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, and lipid profile in addition to blood urea nitrogen (BUN) and creatinine, were measured. Additionally, catalase (CAT) and superoxide dismutase (SOD) activities were assessed in liver homogenates. Histopathological evaluations were performed using Masson trichrome (MT) and hematoxylin and eosin (H&E) staining. The elevated levels of liver enzymes, total and direct bilirubin, BUN, creatinine, cholesterol, triglyceride, and low-density lipoprotein (LDL) induced by BDL were significantly reduced following trans-chalcone administration; while serum level of high-density lipoprotein (HDL) increased. Besides, treatment with trans-chalcone elevated the activities of CAT and SOD in the liver tissues of the animals with BDL surgery. According to MT and H&E staining, BDL-induced histopathological changes, including infiltration of inflammatory cells, hepatocyte necrosis, ductal hyperplasia, and collagen deposition were ameliorated using trans-chalcone administration. It can be concluded from the present study that trans-chalcone, possibly by its anti-oxidant and anti-inflammatory properties, may exert hepatoprotective and antifibrotic effects in BDL-induced liver fibrosis.

Safety of Ultrasound-Guided Percutaneous Injection of Alcohol as a Scolicidal Agent for the Treatment of Liver Hydatid Cysts

Background: Hydatid disease is a health problem in the developing world. Percutaneous therapy with various scolicidal agents has been described; however, there is a paucity of literature on the use of absolute alcohol injection without reaspiration as a sole scolicidal agent. The study carried out in a tertiary hospital aimed to prospectively evaluate the safety and outcomes of ultrasound-guided percutaneous injection of alcohol for liver hydatid cyst. Methodology: Consecutive patients with liver hydatid cysts were evaluated with ultrasound, classified according to the WHO classification between June 2012 and January 2020. Eligible patients underwent ultrasound-guided percutaneous therapy after three courses of oral albendazole. Patients having elevated cyst fluid bilirubin levels were excluded. Patients who underwent percutaneous alcohol injection were followed up clinically and with imaging. Data were entered in Microsoft Excel spreadsheet and analyzed. Results: Fifty-two consecutive patients with hydatid cyst were evaluated during the study. Among these, 27 patients underwent percutaneous alcohol injection. Follow-up data were available for 25 patients. There was a favorable imaging outcome in 21/25 (84%). One patient developed anaphylaxis during cyst access, which was managed medically with an uneventful recovery. No instances of cholangitis or sepsis following injection were observed. Conclusion: Percutaneous alcohol injection therapy for liver hydatid cysts is a minimally invasive, safe, and an effective procedure in selected group of patients.

Association Between Serum Bilirubin and Atrial Fibrillation: A Mendelian Randomization Study.

The association between bilirubin and atrial fibrillation (AF) has been evaluated previously in observational studies but with contradictory results. This study evaluated the causal association between serum bilirubin level and AF using Mendelian randomization (MR) analysis. This cross-sectional study includes 8,977 participants from the Dong-gu Study. In the observational analysis, multivariate logistic regression was performed to evaluate the association between bilirubin and prevalent AF. To evaluate the causal association between bilirubin and AF, MR analysis was conducted by using the UGT1A1 rs11891311 and rs4148323 polymorphisms as instrumental variables. Elevated serum bilirubin levels were associated with an increased risk for AF in observational analysis (total bilirubin: odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.15-1.48 per 1 standard deviation [SD]; direct bilirubin: OR, 1.31; 95% CI, 1.18-1.46 per 1 SD), whereas the genetically predicted serum bilirubin levels in MR analysis did not show this association (total bilirubin: OR, 1.02; 95% CI, 0.67-1.53 per 1 SD; direct bilirubin: OR, 1.03; 95% CI, 0.61-1.73 per 1 SD). Genetically predicted bilirubin levels were not associated with prevalent AF. Thus, the observational association between serum bilirubin levels and AF may be non-causal and affected by reverse causality or unmeasured confounding.

Epidemiologic and Clinical Characteristics of Patients with Severe Fever with Thrombocytopenia Syndrome at Tertiary Hospital in Jeju for 10 years.

Severe fever with thrombocytopenia syndrome (SFTS), which was first discovered in China in 2009, is an infectious disease with a high mortality rate, particularly in East Asia. This study aimed to investigate the epidemiological and clinical characteristics and risk factors for mortality by analyzing SFTS cases accumulated for up to ten years in Jeju, Korea. Medical records of patients diagnosed with SFTS between March 2013 and August 2022 at a tertiary hospital in Jeju were analyzed retrospectively. We investigated data of patients with SFTS on the epidemiologic and clinical characteristics, laboratory findings, and administered treatments and compared the differences between fatal and non-fatal groups. We enrolled 91 SFTS-confirmed patients. The median age of patients was 62 years, and the fatality rate increased with age (P = 0.004). Fever was the most common symptom (84.6%), and diarrhea (37.4%) was also present in some cases. The overall fatality rate was 10.9%. Dyspnea (20.0% vs. 0.0%, P = 0.009) and changes in mental status (70.0% vs. 11.0%, P <0.001) were more frequent in fatal cases. Risk factor assessment revealed that a high aspartate aminotransferase /alanine aminotransferase ratio (odds ratio [OR]: 39.568, 95% confidence interval [CI]: 1.479 - 1,058.639, P = 0.028) and elevated total bilirubin levels (OR: 53.037, 95% CI: 1.064 - 2,643.142, P = 0.046) were also significantly associated with fatal cases. Plasma exchange (40.7%) was the most commonly administered treatment. SFTS has a high mortality rate; therefore, awareness of SFTS must be raised among physicians and citizens living in tick-inhabited areas, such as Jeju.