Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester.

Intrahepatic cholestasis of pregnancy (ICP) is a gestation-specific liver disorder, defined most often as the onset of pruritus, usually from the third trimester of pregnancy, associated with abnormal liver test results and/or increased total serum bile acids and spontaneous relief after delivery. The 21-year-old patient was admitted to our ward in the 11th week of pregnancy due to raised liver enzymes. The first onset of pruritus and jaundice appeared a month before hospitalization. Immunology tests and Toxoplasma gondii were negative. We excluded viral etiology, while alpha-1-antitrypsin, serum and urine copper levels, and thyroid hormones were within the reference values. The patient denied she had taken any medicines and herbal preparations before and during pregnancy. Total bile acids in the serum were significantly elevated (242 µmol/L). The abdominal ultrasound revealed a regular finding. Liver biopsy suggested a cholestatic liver disorder. After a presentation of all risks, the patient decided to stop the pregnancy. After a month, the hepatogram was within the reference values. Very rarely an ICP can occur in early pregnancy (first trimester), which calls for close monitoring. The risk of serious adverse fetal outcomes and spontaneous preterm delivery is proportional with increased levels of maternal serum bile acid.

The effect of self-explanation of pathophysiological mechanisms of diseases on medical students' diagnostic performance.

Self-explanation while diagnosing clinical cases fosters medical students' diagnostic performance. In previous studies on self-explanation, students were free to self-explain any aspect of the case, and mostly clinical knowledge was used. Elaboration on knowledge of pathophysiological mechanisms of diseases has been largely unexplored in studies of strategies for teaching clinical reasoning. The purpose of this two-phase experiment was to investigate the effect of self-explanation of pathophysiology during practice with clinical cases on students' diagnostic performance. In the training phase, 39 4th-year medical students were randomly assigned to solve 6 criterion cases (3 of jaundice; 3 of chest pain), either self-explaining the pathophysiological mechanisms of the findings (n = 20) or without self-explaining (n = 19). One-week later, in the assessment phase, all students solved 6 new cases of the same syndromes. A repeated-measures analysis of variance on the mean diagnostic accuracy scores showed no significant main effects of study phase (p = 0.34) and experimental condition (p = 0.10) and no interaction effect (p = 0.42). A post hoc analysis found a significant interaction (p = 0.022) between study phase and syndrome type. Despite equal familiarity with jaundice and chest pain, the performance of the self-explanation group (but not of the non-self-explanation group) on jaundice cases significantly improved between training and assessment phases (p = 0.035) whereas no differences between phases emerged on chest pain cases. Self-explanation of pathophysiology did not improve students' diagnostic performance for all diseases. Apparently, the positive effect of this form of self-explanation on performance depends on the studied diseases sharing similar pathophysiological mechanisms, such as in the jaundice cases.

Variable Clinical Presentations of ABO Incompatibility in Dizygotic Twins.

Newborns with ABO blood group incompatibility can have a spectrum of clinical presentations from remaining asymptomatic to severe hemolytic anemia with jaundice. This case presentation discusses dizygotic twins who demonstrated both ends of the clinical spectrum. Similar cases in which there is such extreme variation between twins were not attainable in the current literature, which prompted the authors to present it as a rare occurrence and one that was unexpected based on their past experience with ABO incompatibility both in singletons and in twins.

Glucose-6-phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol-induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy.

Autoimmune polyglandular syndrome presenting with jaundice and thrombocytopenia.

OBJECTIVE: To report an uncommon presentation of a rare case of autoimmune polyglandular syndrome type IIIb in an elderly woman. CLINICAL PRESENTATION AND INTERVENTION: A 62-year-old woman presented with anaemic symptoms and jaundice. Blood tests showed macrocytic anaemia due to vitamin B12 deficiency with Coombs negative haemolysis. A thyroid function test was consistent with hypothyroidism. Autoimmune antibody assays were positive for anti-parietal cell, anti-intrinsic factor and anti-thyroid peroxidase antibodies. A final diagnosis of autoimmune thyroiditis with pernicious anaemia, which constituted autoimmune polyglandular syndrome type IIIb, was made and the patient was treated with L-thyroxine, vitamin B12 injection and a blood transfusion. She was discharged uneventfully after a week of hospitalization. CONCLUSION: This case showed that the presence of one autoimmune endocrine disease should prompt clinicians to look for other coexisting autoimmune diseases which may be asymptomatic despite positive autoantibodies.

Jaundice increases the rate of complications and one-year mortality in patients with hypoxic hepatitis.

UNLABELLED: Hypoxic hepatitis (HH) is the most frequent cause of acute liver injury in critically ill patients. No clinical data exist about new onset of jaundice in patients with HH. This study aimed to evaluate the incidence and clinical effect of jaundice in critically ill patients with HH. Two hundred and six consecutive patients with HH were screened for the development of jaundice during the course of HH. Individuals with preexisting jaundice or liver cirrhosis at the time of admission (n = 31) were excluded from analysis. Jaundice was diagnosed in patients with plasma total bilirubin levels >3 mg/dL. One-year-survival, infections, and cardiopulmonary, gastrointestinal (GI), renal, and hepatic complications were prospectively documented. New onset of jaundice occurred in 63 of 175 patients with HH (36%). In patients who survived the acute event of HH, median duration of jaundice was 6 days (interquartile range, 3-8). Patients who developed jaundice (group 1) needed vasopressor treatment (P < 0.05), renal replacement therapy (P < 0.05), and mechanical ventilation (P < 0.05) more often and had a higher maximal administered dose of norepinephrine (P < 0.05), compared to patients without jaundice (group 2). One-year survival rate was significantly lower in group 1, compared to group 2 (8% versus 25%, respectively; P < 0.05). Occurrence of jaundice was associated with an increased frequency of complications during follow-up (54% in group 1 versus 35% in group 2; P < 0.05). In particular, infections as well as renal and GI complications occurred more frequently in group 1 during follow-up. CONCLUSION: Jaundice is a common finding during the course of HH. It leads to an increased rate of complications and worse outcome in patients with HH.

Paroxysmal cold hemoglobinuria: a case report.

A 15-month-old white male child was admitted to the pediatric intensive care unit with symptoms of upper respiratory tract infection, increased somnolence, pallor, jaundice, fever, and decreased activity level. The purpose of this case study is to report the clinical findings associated with the patient's clinical symptoms and differential laboratory diagnosis.

The incidence rate and influence factors of hemolysis, lipemia, icterus in fasting serum biochemistry specimens.

OBJECTIVE: Hemolysis, icterus, and lipemia (HIL) of blood samples have been a concern in hospitals because they reflect pre-analytical processes' quality control. However, very few studies investigate the influence of patients' gender, age, and department, as well as sample-related turnaround time, on the incidence rate of HIL in fasting serum biochemistry specimens. METHODS: A retrospective, descriptive study was conducted to investigate the incidence rate of HIL based on the HIL index in 501,612 fasting serum biochemistry specimens from January 2017 to May 2018 in a tertiary university hospital with 4,200 beds in Sichuan, southwest China. A subgroup analysis was conducted to evaluate the differences in the HIL incidence rate by gender, age and department of patients, and turnaround time of specimens. RESULTS: The incidence rate of hemolysis, lipemia and icterus was 384, 53, and 612 per 10,000 specimens. The male patients had a significantly elevated incidence of hemolysis (4.13% vs. 3.54%), lipemia (0.67% vs. 0.38%), and icterus (6.95% vs. 5.43%) than female patients. Hemolysis, lipemia, and icterus incidence rate were significantly associated with the male sex with an odds ratio (OR) of 1.174 [95% confidence interval (CI), 1.140-1.208], 1.757 (95%CI: 1.623-1.903), and 1.303 (95%CI: 1.273-1.333), respectively, (P<0.05). The hospitalized patients had a higher incidence of hemolysis (4.03% vs. 3.54%), lipemia (0.63% vs. 0.36%), and icterus (7.10% vs. 4.75%) than outpatients (P<0.001). Specimens with relatively longer transfer time and/or detection time had a higher HIL incidence (P<0.001). The Pediatrics had the highest incidence of hemolysis (16.2%) with an adjusted OR (AOR) of 4.93 (95%CI, 4.59-5.29, P<0.001). The Neonatology department had the highest icterus incidence (30.1%) with an AOR of 4.93 (95%CI: 4.59-5.29, P<0.001). The Neonatology department (2.32%) and Gastrointestinal Surgery (2.05%) had the highest lipemia incidence, with an AOR of 1.17 (95%CI: 0.91-1.51) and 4.76 (95%CI: 4.70-5.53), both P-value <0.001. There was an increasing tendency of hemolysis and icterus incidence for children under one year or adults aged more than 40. CONCLUSION: Evaluation of HIL incidence rate and HIL-related influence factors in fasting serum biochemistry specimens are impartment to interpret the results more accurately and provide better clinical services to patients.

[Primary research on daily administration times of rhubarb used to treat experimental jaundice in rats].

OBJECTIVE: To study the rational daily administration times of rhubarb when it is used to treat experimental jaundice in rats, at the same time, validate the accuracy and feasibility of the method which was previously established to research the rational daily administration times of rhubarb (PD-PK method), and consummate it. METHOD: After the rats were modeled by 4% ANIT (75 mg x kg(-1)) for two days, rhubarb extraction was drenched 3.6 g x kg(-1) once a day, 1.8 g x kg(-1) twice a day and 1.2 g x kg(-1) three times a day, respectively. Then the total bile and the flow rate of bile were observed. Blood was collected from the veins behind the eye sockets after different intervals and was used to investigate the biochemical indexes of the blood serum, such as TBIL, ALT, ALP, AST and GGT, and to determine the concentration of rheic acid in the blood plasma, then the time-effect curve and time-dose curve were obtained. The rational daily administration times of rhubarb was determined when it was used to treat experimental jaundice based on the comprehend analysis of time-effect and time-concentration relationships. RESULT: Compared with the groups which were administered once a day and three times a day, the total bile within 8 h of the rats which were administered twice a day was 1.56 and 1.7 times higher, respectively, while the TBIL was 23%, 22%, and ALT was 86%, 65% of the other two, ALP was 50%, 71% of the other two, respectively. With administrated twice a day, the blood concentration of rheic acid could maintain a high level for a longer time, which maybe the main reason for its effect. CONCLUSION: The method based on pharmacodynamics and pharmacokinetics is scientific and feasible to study the rational daily administration times of traditional Chinese medicine. Rhubarb is better to administrate two times a day to treat jaundice.

UGT1A1 gene polymorphisms in North Indian neonates presenting with unconjugated hyperbilirubinemia.

Genetic factors are implicated in pathogenesis of neonatal hyperbilirubinemia. In this nested case-control study, we determined 1) frequency of thymine-adenine (TA)n promoter polymorphism and Gly71Arg mutation in uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene in neonates > or =35-wk gestation presenting with bilirubin levels > or =18 mg/dL and controls, 2) interaction among (TA)n promoter polymorphism, glucose-6-phosphate dehydrogenase (G6PD) gene mutations, and peak bilirubin. The number of TA repeats was assessed by PCR-single-strand conformation polymorphism (SSCP) analysis and Gly71Arg mutation by PCR-RFLP. Fifty samples of both mutations were verified with DNA sequencing. One hundred twenty-seven neonates were enrolled (77 hyperbilirubinemics, 50 controls). The incidence of (TA)n polymorphism was higher in babies with hyperbilirubinemia [89.6% vs. 50%, OR 8.63 (95% CI, 3.2-24.1)]. Gly71Arg mutation was not found either in hyperbilirubinemics or controls. A novel polymorphism (Ala72Pro) at codon position 72 of exon 1 was detected in all 50 samples (21 hyperbilirubinemics, 29 controls), which were sequenced. Presence of variant (TA)n promoter (adjusted OR, 10.6; 95% CI, 3.3-34.2), G6PD deficiency (adjusted OR, 20.6; 95% CI, 3.6-117.3), and history of jaundice in sibling requiring phototherapy (adjusted OR, 12.6; 95% CI, 1.1-141.6) were independent risk factors for bilirubin levels > or =18 mg/dL.

Jaundice in a Service member Returning From Taiwan; Diagnostic Challenges in a Case of Acute Hepatitis E.

When the evaluation of newly elevated liver enzymes is unrevealing, a common diagnosis of exclusion is drug-induced liver injury. A 39-year-old active duty service member who presented with jaundice after returning from a mission in Thailand was found to have an acute hepatitis and developing acute liver failure. He was ultimately diagnosed with acute hepatitis E, but his diagnosis was initially confounded by multiple exposures to supplements known to cause drug-induced liver injury. This case illustrates the importance of broadened serologic testing in patients with acute liver injury returning from countries endemic with hepatitis E and also highlights the challenges in diagnosis of acute hepatitis E with currently available testing.

Neurotoxicity of Unconjugated Bilirubin in Mature and Immature Rat Organotypic Hippocampal Slice Cultures.

BACKGROUND: The physiopathology of bilirubin-induced neurological disorders is not completely understood. OBJECTIVES: The aim of our study was to assess the effect on bilirubin neurotoxicity of the maturity or immaturity of exposed cells, the influence of different unconjugated bilirubin (UCB) and human serum albumin (HSA) concentrations, and time of UCB exposure. METHODS: Organotypic hippocampal slices were exposed for 48 h to different UCB and HSA concentrations after 14 (mature) or 7 (immature) days of in vitro culture. Immature slices were also exposed to UCB and HSA for 72 h. The different effects of exposure time to UCB on neurons and astrocytes were evaluated. RESULTS: We found that 48 h of UCB exposure was neurotoxic for mature rat organotypic hippocampal slices while 72 h of exposure was neurotoxic for immature slices. Forty-eight-hour UCB exposure was toxic for astrocytes but not for neurons, while 72-h exposure was toxic for both astrocytes and neurons. HSA prevented UCB toxicity when the UCB:HSA molar ratio was ≤1 in both mature and immature slices. CONCLUSIONS: We confirmed UCB neurotoxicity in mature and immature rat hippocampal slices, although immature ones were more resistant. HSA was effective in preventing UCB neurotoxicity in both mature and immature rat hippocampal slices.

Clinical Indicators of Fatal Dengue in Two Endemic Areas of Colombia: A Hospital-Based Case-Control Study.

According to the World Health Organization, 98% of fatal dengue cases can be prevented; however, endemic countries such as Colombia have recorded higher case fatality rates during recent epidemics. We aimed to identify the predictors of mortality that allow risk stratification and timely intervention in patients with dengue. We conducted a hospital-based, case-control (1:2) study in two endemic areas of Colombia (2009-2015). Fatal cases were defined as having either 1) positive serological test (IgM or NS1), 2) positive virological test (RT-PCR or viral isolation), or 3) autopsy findings compatible with death from dengue. Controls (matched by state and year) were hospitalized nonfatal patients and had a positive serological or virological dengue test. Exposure data were extracted from medical records by trained staff. We used conditional logistic regression (adjusting for age, gender, disease's duration, and health-care provider) in the context of multiple imputation to estimate exposure to case-control associations. We evaluated 110 cases and 217 controls (mean age: 35.0 versus 18.9; disease's duration pre-admission: 4.9 versus 5.0 days). In multivariable analysis, retro-ocular pain (odds ratios [OR] = 0.23), nausea (OR = 0.29), and diarrhea (OR = 0.19) were less prevalent among fatal than nonfatal cases, whereas increased age (OR = 2.46 per 10 years), respiratory distress (OR = 16.3), impaired consciousness (OR = 15.9), jaundice (OR = 32.2), and increased heart rate (OR = 2.01 per 10 beats per minute) increased the likelihood of death (AUC: 0.97, 95% confidence interval: 0.96, 0.99). These results provide evidence that features of severe dengue are associated with higher mortality, which strengthens the recommendations related to triaging patients in dengue-endemic areas.

Preoperative resolution of jaundice following biliary stenting predicts more favourable early survival in resected pancreatic ductal adenocarcinoma.

INTRODUCTION: Despite the widespread use of endoscopic biliary stenting in patients presenting with potentially resectable pancreatic cancer, there is no general consensus regarding whether this represents a superior management approach over expeditious surgical intervention. The objective of this study was to investigate the influence of preoperative biliary stenting and resolution of jaundice on subsequent postoperative survival following resection for pancreatic cancer. METHODS: 155 patients undergoing partial pancreatoduodenectomy for pancreatic ductal adenocarcinoma between January 1997 and August 2007 were identified from a prospectively maintained database. RESULTS: There was no survival difference when comparing patients undergoing preoperative biliary drainage (n = 130) with those who did not (n = 25) (log rank, P = 0.981). When analysing individual prognostic factors as continuous variables in univariate Cox analysis, lower albumin levels (P = 0.016), elevated alkaline phosphatase levels (P = 0.011) and elevated CRP levels (P = 0.021) were associated with poorer overall survival. Multivariable Cox regression demonstrated that both albumin (P = 0.008) and CRP (P = 0.038) remained significant independent predictors of overall survival alongside lymph node ratio (P = 0.018). Although preoperative bilirubin levels were not associated with overall survival when analysed as a continuous variable (Cox, P = 0.786), the presence of jaundice (i.e., bilirubin >35 micromol/l) at the time of surgery was a significant adverse predictor of early survival in patients undergoing preoperative biliary drainage (Breslow-Gehan-Wilcoxon, P = 0.013) and remained a significant predictor of early survival when included in a further Cox analysis with censoring of cases who survived beyond 6 months (Cox, P = 0.017). CONCLUSION: These results suggest that the presence of jaundice at the time of resection has an adverse impact on early, but not overall, postoperative survival in pancreatic cancer patients undergoing preoperative biliary drainage.

Envenomation by the lowland viper (Proatheris superciliaris): severe case profile documentation.

This case report represents a documentation of severe envenomation by Proatheris superciliaris, a species for which no specific antivenom exists. A 27-year-old male bitten on the finger by an adult P. superciliaris developed immediate severe pain radiating up the limb and local ecchymotic features with tissue necrosis ensuing over the following 36h, requiring debridement of necrotic tissue. Approximately 72h post-envenomation jaundice and hemoglobinuria were observed, but no other clinical signs of coagulopathy or hemorrhage. Hemolysis was evidenced by fragmented red blood cells and hyperbilirubinemia. Declining renal function ensued. Hematology revealed a reduction in reticulocyte count, schistocytosis, and a marked thrombocytopenia. The coagulation profile showed partial thromboplastin time and fibrinogen values within normal range and slight prothrombin time elevation. Thrombotic microangiopathy similar to hemolytic uremic syndrome developed, and daily plasmapheresis was initiated on day 4. Erythropoietin therapy was started on the 9th day. Gradual resolution of acute systemic complications followed over a 3-month period. The debrided bite site healed and the fingernail-beds demonstrated the return of normal capillary refill. Neurotoxic effects of venom were not observed.

Increased sleep tendency in jaundiced infants: role of endogenous CO.

Carbon monoxide formed from the breakdown of heme to bilirubin is produced at a rate equal to the rate of bilirubin synthesis. During long-term clinical experiences we have observed that jaundiced newborns tend to sleep more than the unjaundiced ones. There is no clear evidence about the role of endogenous CO in sleep physiology, but increased CO production in jaundiced newborns probably plays role in increased sleep state due to the regulatory effects on sleep circadian rhythm and REM-sleep, via cholinergic system activation.

Jaundice in the emergency department: meeting the challenges of diagnosis and treatment [digest].

There are approximately 52,000 visits a year to emergency departments for patients presenting with jaundice. While many of these patients will not have immediately life-threatening pathology, it is essential that the emergency clinician understands the pathophysiology of jaundice, as this will guide the appropriate workup to detect critical diagnoses. Patients who present with jaundice could require intravenous antibiotics, emergent surgery, and, in severe cases, organ transplantation. This issue will focus on the challenge of evaluating and treating the jaundiced patient in the ED using the best available evidence from the literature. [Points & Pearls is a digest of Emergency Medicine Practice.].