Elevated Bilirubin Levels Research Articles

Impact of sympathetic hyperactivity induced by brain microglial activation on organ damage in sepsis with chronic kidney disease

BackgroundSympathetic nerve activity (SNA) plays a central role in the pathogenesis of several diseases such as sepsis and chronic kidney disease (CKD). Activation of microglia in the paraventricular nucleus of the hypothalamus (PVN) has been implicated in SNA. The mechanisms responsible for the adverse prognosis observed in sepsis associated with CKD remain to be determined. Therefore, we aimed to clarify the impact of increased SNA resulting from microglial activation on hemodynamics and organ damage in sepsis associated with CKD.Methods and resultsIn protocol 1, male Sprague–Dawley rats underwent either nephrectomy (Nx) or sham surgery followed by cecal ligation and puncture (CLP) or sham surgery. After CLP, Nx-CLP rats exhibited decreased blood pressure, increased heart rate, elevated serum creatinine and bilirubin levels, and decreased platelet count compared to Nx-Sham rats. Heart rate variability analysis revealed an increased low to high frequency (LF/HF) ratio in Nx-CLP rats, indicating increased SNA. Nx-CLP rats also had higher creatinine and bilirubin levels and lower platelet counts than sham-CLP rats after CLP. In protocol 2, Nx-CLP rats were divided into two subgroups: one received minocycline, an inhibitor of microglial activation, while the other received artificial cerebrospinal fluid (CSF) intracerebroventricularly via an osmotic minipump. The minocycline-treated group (Nx-mino-CLP) showed attenuated hypotensive and increased heart rate responses compared to the CSF-treated group (Nx-CSF-CLP), and the LF/HF ratio was also decreased. Echocardiography showed larger left ventricular dimensions and inferior vena cava in the Nx-mino-CLP group. In addition, creatinine and bilirubin levels were lower and platelet counts were higher in the Nx-mino-CLP group compared to the Nx-CSF-CLP group.ConclusionsIn septic rats with concomitant CKD, SNA was significantly enhanced and organ dysfunction was increased. It has been suggested that the mechanism of exacerbated organ dysfunction in these models may involve abnormal systemic hemodynamics, possibly triggered by activation of the central sympathetic nervous system through activation of microglia in the PVN.

Changes in nonfunctional adrenal incidentaloma after COVID-19 infection and a model for predicting benign and malignant adrenal incidentaloma.

To compare nonfunctional adrenal incidentalomas (NFAI) in individuals with and without a history of COVID-19 infection, while also establishing predictive models for distinguishing between benign and malignant adrenal incidentalomas (AI). A retrospective collection of data from patients with AI who underwent surgery and were verified in our hospital between April 2022 and June 2023 was conducted. A total of 121 patients were included in the study. Demographic information, tumor characteristics, functional indicators, and complications were compared among the patients. Statistical analyses utilized the t-test for continuous variables and Pearson chi-square test or Fisher's exact test for categorical variables. Patients with COVID-19 exhibited a higher prevalence of obesity (84.2% vs. 63.3%, P=0.048) and elevated direct bilirubin (DBIL) levels (44.1% vs. 19.2%, P=0.043) compared to those without COVID-19. Moreover, patients with Malignant AI, in contrast to Benign AI, showed higher normal total protein (TP) levels (28.8% vs. 57.1%, P=0.016) and larger tumor sizes (20 vs. 32.5mm, P=0.009). Univariate analysis identified low TP (OR=0.303, 95% CI=0.111-0.825, P=0.020) and tumor size (OR=1.045, 95% CI=1.011-1.080, P=0.009) as potential risk factors for multivariate analysis. A predictive model comprising clinical risk factors (tumor size and low TP) demonstrated an AUC of 0.754 (95% CI, 0.603-0.904) with a sensitivity of 0.75 and specificity of 0.775. The calibration curve revealed a bias-corrected AUC of 0.77. No discernible differences in the clinical manifestations of adrenal incidentalomas were observed between cases with and without a history of COVID-19 infection. However, AI with larger tumor diameters and lower than normal levels of total protein exhibited a more pronounced malignant potential.

Assessment of Knowledge and Attitudes of Parents Regarding Neonatal Jaundice in Abia State Children's Specialist Hospital, Umuahia, Nigeria: A Cross-Sectional Study.

Background Neonatal jaundice, characterized by the yellow discoloration of an infant's skin and eyes, is a common condition that affectsnewborns. It results from an elevated level of bilirubin in the blood and,when severe, if left untreated, can lead to complications such as acute bilirubin encephalopathy and kernicterus, which can cause permanent neurological damage or even death. In low-resource settings like Nigeria, delayed recognition and inadequate management of neonatal jaundice are significant contributors to neonatal morbidity and mortality. Parental knowledge and attitudes play a critical role in the early identification and timely intervention of neonatal jaundice. However, there is limited data on the awareness, understanding, and practices of parents regarding this condition in many regions, including Abia State, Nigeria. Aim This study sought to assess the knowledge and attitudes of parents at Abia State Children's Specialist Hospital, Umuahia, Nigeria, to inform strategies for improving early detection and management of neonatal jaundice. Research methodology This descriptive cross-sectional study was conducted at Abia State Children's Specialist Hospital. The study population included 385 parents (fathers and mothers) of neonates attending the pediatric and neonatal units. A systematic random sampling technique was used to select participants. Data were collected using a structured questionnaire and analyzed using IBM SPSS Statistics for Windows, Version 25, (Released 2017; IBM Corp., Armonk, New York, United States). Results The study revealed that 226 (58.70%) of parents had heard about neonatal jaundice, with the main perceived cause being an immature liver (148, 38.44%). While 216 (56.10%) of the parents recognized neonatal jaundice as a serious condition when severe, only 72 (18.70%) were very confident in identifying its signs. Most parents (369, 95.84%) would seek medical help if they suspected jaundice in their baby, yet 288 (74.81%) believed in the effectiveness of traditional remedies. Educational level and gender were significantly associated with knowledge about neonatal jaundice (p = 0.002 and p = 0.001, respectively). Conclusion The findings highlight a moderate level of awareness but varying confidence in identifying neonatal jaundice among parents. The reliance on traditional remedies suggests a need for enhanced health education to improve knowledge of and attitudes toward neonatal jaundice management.

Primary neuroendocrine tumor of the perihilar bile duct: A case report

Neuroendocrine tumors (NETs) arising from extrahepatic bile ducts are very rare. We present a patient with perihilar NET who was operated on with a preoperative diagnosis of Klatskin tumor. A 58-year-old female patient was admitted with abdominal pain and jaundice. Laboratory data showed elevated serum bilirubin levels and liver function tests. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) findings were consistent with perihilar bile duct tumor. The patient was operated on with a diagnosis of Klatskin tumor. She underwent right hepatectomy, resection of the extrahepatic bile duct, portal lymphadenectomy and Roux-en-Y hepaticojejunostomy. The final pathologic examination of the resected specimen demonstrated a well differentiated neuroendocrine tumor (Grade 1). NETs originating from perihilar bile ducts are extremely rare, and preoperative definite diagnosis is very difficult. It should be kept in mind that NET may be one of the rare causes of perihilar bile duct obstruction.

Surgical decision-making: key factors influencing the shift from laparoscopic to open cholecystectomy

Background: Recognizing the preoperatively and intraoperatively factors can aid surgeons in making timely decisions to shift from laparoscopic cholecystectomy (LC) to open cholecystectomy (OC). This study aims to identify the main factors leading to LC conversion to OC among Iraqi patients. Methods: One-year prospective research was performed using cross-sectional design between 1st April, 2023, and 3oth March, 2024, at Alkalis General Public Hospital and Al Hayat Private Hospital, Diyala, Iraq. Pre and intraoperative data were collected from the planned LC surgeries including demographics, medical history, laboratory and Ultrasound findings. Descriptive and bivariate analysis was carried out to compare variables between patients undergoing LC and those requiring conversion to OC. Results: Out of 172 LC patients (mean age 48.28±12.62), 52.9% were female, 55.8% obese, 50.6% aged 49+, 23.3% diabetic, and 19.8% had emergency cholecystectomy; 15 (8.7%) required conversion to open surgery. The conversion group was mainly men (66.7% vs. 46.5%, P = 0.001) and older (73.3% vs. 48.4% aged 49+, P = 0.003). Obesity (60.0% vs. 55.4%, P = 0.005) and diabetes (53.3% vs. 20.4%, P < 0.001) were more common. Public hospital referrals were higher (86.7% vs. 52.2%, P < 0.001). Elevated total bilirubin, direct bilirubin, and alkaline phosphatase levels were significant predictors of conversion to OC. Adhesions in Calot's triangle (20.0% vs. 13.4%, P = 0.021) were more common in the conversion group, along with unclear anatomy, thick gallbladder wall, bleeding, stone and bile spillage, and cystic duct injury. Conclusion: In conclusion, out of 172 LC patients, 15 (8.7%) required conversion to open surgery, predominantly older men with higher obesity, diabetes, and elevated bilirubin and alkaline phosphatase levels, and more adhesions in Calot's triangle.

The Predictive Value of Gamma-Glutamyl Transferase on Jaundice Clearance in Biliary Atresia: An Evidence-Based Case Report and Meta-Analysis

Background: Biliary atresia (BA) is a neonatal condition characterized by the obstruction of extrahepatic bile ducts. Case: A 2-year-old female with BA underwent a Kasai procedure at 3 months of age. Despite the surgery, she developed persistent jaundice and abdominal enlargement. Preoperative laboratory findings revealed elevated liver enzymes, GGT, and bilirubin levels. This case raises the clinical question of whether preoperative GGT levels can predict JC after the Kasai procedure, in addition to its role in diagnosis. Methods: A systematic literature search was performed on 4 databases (PubMed, Scopus, Cochrane, and Proquest) by using relevant keywords and identified seven high quality studies. Results: Five studies found higher GGT levels in patients who achieved JC following Kasai surgery, compared to those with unsuccessful jaundice clearance (JUC). However, two studies reported conflicting findings. A pooled analysis indicated a non-significant trend toward higher GGT levels in the JC group compared to the JUC group (WMD: 65.6, 95% CI: -58.6; 189.8). Conclusion: Elevated preoperative GGT levels may be associated with improved JC in BA patients. However, further investigation to validate these findings, determine the optimal role of GGT in assessing prognosis, and later, guiding treatment decisions in BA patients.

Peptidergic and adenosinergic drugs administration to comatose patients caused by alcohol consumption on early hospital period

Introduction. Medical care for patients diagnosed with the toxic effect of ethanol (according to ICD-10 code T51.0) it turns out to be in specialized toxicological centers or in emergency departments of multidisciplinary hospitals. The purpose of this study was to study the effectiveness of the drug моликсан® (molixаn) at different levels of medical care for patients diagnosed with the toxic effect of ethanol. Material and method. 128 patients were included in the study, of which 76 patients were taken to the emergency department of St. Petersburg State Medical Institution "Alexandrovskaya Hospital" and 52 patients were taken to the intensive care unit No. 11 of the St. Petersburg Scientific Research Institute of Emergency Medicine named after I.I. Dzhanelidze. All patients met the inclusion criteria: age 18–60 years; impaired consciousness of alcoholic genesis 21–30 points on the Glasgow–Pittsburgh coma scale (PBSS: Pittsburg Brain Stem Score, Kelsey S.F., et al. 1991); ethanol concentration in the blood is more than 2.5%. 72 patients were included in the моликсан® group, 56 patients in the Placebo group. Results. The use of the drug моликсан® has a positive effect on the dynamics of restoring the level of consciousness, which is reflected in higher values of the Glasgow–Pittsburgh scale after 1, 3 and 6 hours from the start of therapy (p<0.01), reducing the period of stay of the patient in a coma from 150 [75; 178] minutes to 60 [50; 161.5] minutes (p<0.05) and restoration of consciousness to a clear level after 3.5± 0.3 hours (p<0.05).It was also revealed, that in the group of patients using моликсан®, normalization of heart rate (p<0.05) and a decrease in the frequency and severity of tremor (p<0.05) were noted. The hepatoprotective efficacy of моликсан® was shown, which manifested itself in a decrease in ALT, AST, GGTP, alkaline phosphatase, total and direct bilirubin (p<0.001). Limitations. The clinical efficacy of моликсан® in the toxic effects of severe ethanol was carried out in patients with depression of consciousness and elevated levels of ALT, AST, GGTP, alkaline phosphatase, total and direct bilirubin, which indicated the presence of alcoholic hepatopathy. Conclusion. The conducted study showed the expediency of using моликсан® at a dosage of 3.0 mg/kg intravenously with the toxic effect of ethanol of moderate and severe severity of the disease.

EPIDEMIOLOGY OF BOVINE FASCIOLIASIS: PREVALENCE AND HAEMATO-BIOCHEMICAL ALTERATIONS IN KATSINA ABATTOIR NORTH WESTERN NIGERIA

Bovine fascioliasis, caused by liver flukes Fasciola hepatica and Fasciola gigantica, significantly affects cattle health and production globally. This study evaluated the prevalence and haemato-biochemical changes associated with bovine fascioliasis in 134 cattle at Katsina Central Abattoir. Using the sedimentation technique, faecal samples revealed a 3.73% infection rate, with females showing a higher prevalence (4.55%) than males (2.17%), though not statistically significant (P > 0.05). The age group 2-3 years had the highest prevalence (25.00%), with significant differences among age groups (P < 0.05). Among breeds, Wadara had the highest prevalence (20.00%) compared to White Fulani (4.93%), with a significant difference (P < 0.05). Medium-conditioned cattle showed the highest prevalence (6.67%) versus good-conditioned ones (1.37%) with significant difference (P < 0.05). Infected cattle exhibited significant reductions (P < 0.05) in packed cell volume (PCV), haemoglobin (Hb), and total erythrocyte count (RBC), as well as decreases in white blood cell count (WBC), mean cellular volume (MCV), and mean cellular haemoglobin concentration (MCHC). Biochemical analysis indicated elevated alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (TB) levels (P < 0.05), with reduced albumin (ALB), total protein (TP), and conjugated bilirubin (CB) levels (P < 0.05). These results highlight the significant impact of bovine fascioliasis on cattle health in Katsina State, emphasizing the need for effective control strategies.

Post cardiotomy extracorporeal membrane oxygenation in pediatric patients: Results and neurodevelopmental outcomes.

The increasing complexity of congenital cardiac surgery has led to greater utilization of extracorporeal membrane oxygenation (ECMO) support for children post-surgery. This study aims to identify risk factors for mortality and brain injury in pediatric patients requiring post-cardiotomy ECMO and to evaluate their neurological outcomes. This retrospective study includes pediatric patients with congenital heart diseases who required ECMO after surgery. Risk factors for in-hospital mortality and brain injury were assessed. Neurodevelopmental status was determined using the Pediatric Cerebral Performance Category (PCPC) Scale at discharge and during follow-up. Between October 2014 and May 2021, 2651 pediatric patients underwent cardiac surgery, with 90 (3.4%) requiring ECMO. The mean age was 0.6 years, ranging from 1 day to 13 years and 7 months. ECMO was implemented for 45 patients due to CPB weaning failure (NW-CPB), 24 due to postoperative low-cardiac output syndrome (LCOS), and 21 for extracorporeal cardiopulmonary resuscitation (E-CPR). ECMO weaning was achieved in 73 patients (81%), with an overall mortality rate of 36%. Pre-implant lactate levels (OR: 1.13, 95% CI: 1.03-1.25; p = 0.009) and peak bilirubin levels (OR: 1.04, 95% CI: 0.87-1.24; p = 0.69) were risk factors for in-hospital mortality. Survival rates were 79% for LCOS, 60% for NW-CPB, and 48% for E-CPR. Brain injury incidence was 33%, with E-CPR being a significant risk factor (p = 0.006) and NW-CPB being protective (p = 0.001). Follow-up in November 2023 showed significant improvement in neurodevelopmental status (p < 0.001). Elevated pre-implant lactate and elevated bilirubin levels during ECMO are major risk factors for mortality. E-CPR is the primary risk factor for brain injury. Follow-up revealed significant improvements in neurodevelopmental outcomes.

Comparison of Intermittent Versus Continuous Phototherapy in Neonatal Hyperbilirubinaemia

Background: Neonatal jaundice is a common condition characterized by elevated bilirubin levels, which, if untreated, can lead to severe complications such as kernicterus. Phototherapy is a widely used treatment modality, with two primary approaches: continuous and intermittent phototherapy. While both methods aim to reduce bilirubin levels, there is ongoing debate about their relative efficacy and safety. Objective: This study aimed to compare the efficacy and safety of intermittent versus continuous phototherapy in the management of neonatal hyperbilirubinaemia in terms of bilirubin reduction, treatment duration, and associated complications. Methods: A quasi-experimental study was conducted at the Department of Paediatrics, Combined Military Hospital, Rawalpindi, from January 2022 to December 2023. The study included 62 full-term neonates with indirect bilirubin levels &gt;15.0 mg/dL but ≤20 mg/dL. Neonates were randomly assigned to receive either intermittent phototherapy (two hours on, two hours off) or continuous phototherapy. Serum indirect bilirubin levels were measured at 24 and 48 hours post-initiation of phototherapy. The total duration of phototherapy, volume of milk consumed, and complications such as hyperthermia and hypocalcaemia were recorded. Data were analyzed using SPSS version 25, with a p-value ≤ 0.05 considered statistically significant. Results: At 24 hours post-treatment, the median indirect bilirubin level was 12.70 mg/dL (IQR: 1.20) in the intermittent group versus 12.50 mg/dL (IQR: 1.90) in the continuous group (p=0.893). At 48 hours, the levels were 6.40 mg/dL (IQR: 1.10) and 6.50 mg/dL (IQR: 1.10), respectively (p=0.821). The median total duration of phototherapy was significantly shorter in the intermittent group (22.0 hours, IQR: 2.0) compared to the continuous group (45.0 hours, IQR: 3.0; p&lt;0.001). Neonates in the intermittent group consumed more milk (420.0 mL, IQR: 93.0) than those in the continuous group (397.0 mL, IQR: 57.0; p=0.014). Hyperthermia was less frequent in the intermittent group (3.2% vs. 25.8%, p=0.026), as was hypocalcaemia (16.1% vs. 45.2%, p=0.013). Conclusion: Intermittent phototherapy is as effective as continuous phototherapy in reducing bilirubin levels and offers additional benefits, including a shorter treatment duration, improved feeding, and fewer complications. Intermittent phototherapy should be considered a preferred option for managing neonatal hyperbilirubinaemia in clinical practice.

Correlation and Diagnostic Agreement Between Ultrasonography and MRCP in Evaluating Obstructive Jaundice: A Prospective Study

Background: Obstructive jaundice is a clinical condition characterized by the yellow discoloration of the skin, sclera, and mucous membranes due to elevated bilirubin levels caused by bile flow obstruction. Accurate diagnosis of the obstruction's cause and site is essential for effective management. Ultrasonography (USG) is commonly used for initial screening, but it has limitations, especially in visualizing the distal common bile duct (CBD). Magnetic resonance cholangiopancreatography (MRCP) has emerged as a superior, non-invasive imaging modality with higher accuracy in evaluating biliary obstructions. Objective: To evaluate the correlation and agreement between USG and MRCP findings in patients with obstructive jaundice and to determine the diagnostic accuracy of each modality in detecting the level and cause of biliary obstruction. Methods: This prospective cohort study was conducted over six months at a tertiary care hospital in Rawalpindi. A total of 32 patients with clinical suspicion of obstructive jaundice were included. Each patient underwent both USG and MRCP. USG was performed using a GE Logiq-e machine, followed by MRCP on a Philips Achieva 1.5 Tesla MRI scanner. Data were analyzed using SPSS version 25. Pearson's correlation coefficient and kappa statistics were used to assess the correlation and agreement between the two modalities. The diagnostic accuracy of USG and MRCP was compared based on the detection of the level of obstruction and the identification of benign and malignant etiologies. Results: The mean age of the patients was 59.53 ± 13.41 years, with 65.6% being male. MRCP showed a diagnostic accuracy of 97.2% compared to 78.1% for USG. MRCP detected distal CBD calculi with 100% accuracy, while USG missed these in 11 cases. A positive correlation was found between USG and MRCP in detecting the site of obstruction (r = 0.48, p = 0.005), the porta hepatis as the site of obstruction (r = 0.47, p = 0.006), and the ampulla as the site of obstruction (r = 0.47, p = 0.006). However, the correlation for benign etiologies was weak (r = 0.094, p = 0.607), and for malignant etiologies, it was moderate (r = 0.31, p = 0.08). Conclusion: MRCP demonstrated superior diagnostic accuracy compared to USG in evaluating patients with obstructive jaundice, particularly in detecting distal CBD calculi and malignant lesions. While USG remains useful as an initial screening tool, MRCP should be considered the preferred imaging modality when detailed evaluation is required.

Automated Fibrosis-4 Index: Simplifying Non-Alcoholic Fatty Liver Disease for Diabetologists.

Background and Objectives: Patients with type 2 diabetes (T2D) have a high prevalence of non-alcoholic fatty liver disease (NAFLD) (55%) and are at increased risk for developing non-alcoholic steatohepatitis, a severe form of NAFLD. Early detection of advanced fibrosis in patients with T2D and NAFLD is crucial and can prevent progression to chronic liver disease, cirrhosis, and hepatocellular carcinoma. However, screening for liver disease and risk-stratification pathways are not established in patients with T2D. We evaluated the efficacy of using the automated fibrosis-4 (FIB-4) index in routine clinical settings to identify patients requiring further specialist evaluation. Materials and Methods: In this prospective cohort study, individuals diagnosed with T2D were recruited from diabetes clinics at a tertiary university hospital. Demographic, clinical, and laboratory data were comprehensively collected. The FIB-4 index was automatically calculated and integrated into the hospital's electronic medical records (EMRs), which were then stratified by age. Patients with advanced fibrosis (FIB-4 index ≥ 1.3) were referred to a specialist. Student's t-test or the Mann-Whitney U test was used to analyze variables associated with advanced fibrosis. Logistic regression was used to identify predictors of advanced fibrosis. Results: Among the 318 patients with T2D, 9.7% had advanced fibrosis. The majority were females (54.7%) and Saudi nationals (89.6%). Several factors, including age, platelet count, total bilirubin, serum albumin, total cholesterol, low-density lipoprotein, transaminases, and gamma-glutamyl transferase (GGT), showed significant associations with advanced fibrosis (all p < 0.05). Older age, elevated total bilirubin and GGT levels, and prolonged international normalized ratio emerged as independent predictors of advanced fibrosis. Conclusions: Integrating the FIB-4 index into the EMR during the routine care of patients with T2D proved to be a valuable tool in effectively identifying individuals at risk of advanced fibrosis. Our findings emphasize the need for further research to refine screening strategies in this high-risk population.

Two dose levels of once-weekly fosravuconazole versus daily itraconazole in combination with surgery in patients with eumycetoma in Sudan: a randomised, double-blind, phase 2, proof-of-concept superiority trial

Eumycetoma is an implantation mycosis characterised by a large subcutaneous mass in the extremities commonly caused by the fungus Madurella mycetomatis. Despite the long duration of treatment, commonly a minimum of 12 months, treatment failure is frequent and can lead to amputation. We aimed to compare the efficacy of two doses of fosravuconazole, a synthetic antifungal designed for use in onychomycosis and repurposed for mycetoma, with standard-of-care itraconazole, both in combination with surgery. This phase 2, randomised, double-blind, active-controlled, superiority trial was conducted in a single centre in Sudan. Patients with eumycetoma caused by M mycetomatis, who were aged 15 years or older, with a set lesion diameter (>2 cm and ≤16 cm) requiring surgery were included. There was a limit of 20 female patients in the initial enrolment, owing to preclinical toxicity concerns. Exclusion criteria included previous surgical or medical treatment for eumycetoma; presence of loco-regional lymphatic extension; osteomyelitis, or other bone involvement; pregnancy or lactation; severe concomitant diseases; a BMI under 16 kg/m2; contraindication to use of the study drugs; pre-existing liver disease; lymphatic extension; osteomyelitis; transaminase levels more than two times the laboratory's upper limit of normal, or elevated levels of alkaline phosphatase or bilirubin; or any history of hypersensitivity to any azole antifungal drug. Patients were randomly allocated in a 1:1:1 ratio to 300 mg fosravuconazole weekly for 12 months (group 1); 200 mg fosravuconazole weekly for 12 months (group 2); or 400 mg itraconazole daily for 12 months (group 3) using a random number list with non-disclosed fixed blocks of size 12, with equal allocation to each of the three arms within a block. To ensure masking between groups, placebo pills were used to disguise the difference in dosing schedules. All groups took pills twice daily with meals. In all groups, surgery was performed at 6 months. The primary outcome was complete cure at end of treatment at the month 12 visit, as evidenced by absence of mycetoma mass, sinuses, and discharge; normal ultrasonography or MRI examination of the eumycetoma site; and, if a mass was present, negative fungal culture from the former mycetoma site. The primary outcome was assessed in the modified intention-to-treat (mITT) population (all patients who received one or more treatment dose with one or more primary efficacy assessment). Safety was assessed in all patients who received one or more doses of the study drug. This study is registered with ClinicalTrials.gov (NCT03086226) and is complete. Between May 9, 2017, and June 10, 2021, 104 patients were randomly allocated (34 in group 1 and 2, respectively, and 36 in group 3). 86 (83%) of 104 patients were male and 18 (17%) patients were female. After an unplanned second interim analysis, the study was terminated early for futility. Complete cure at 12 months in the mITT population was 17 (50%) of 34 (95% CI 32-68) for group 1, 22 (65%) of 34 (47-80) for group 2, and 27 (75%) of 36 (58-88) in group 3. Neither dose of fosravuconazole was superior to itraconazole (p=0·35 for 200 mg fosravuconazole vs p=0·030 for 300 mg fosravuconazole). 83 patients had a total of 205 treatment-emergent adverse events, and two patients had serious adverse events that led to discontinuation, neither related to treatment. Treatment with either dose of fosravuconazole was not superior to itraconazole, and the two doses had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug-drug interactions compared with the relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery are warranted. Drugs for Neglected Diseases initiative.

Analysis of metagenome and metabolome disclosed the mechanisms of Dendrobium officinale polysaccharide on DSS-induced ulcerative colitis-affected mice

Currently, there is no known cause for ulcerative colitis (UC), an inflammatory bowel disease that is difficult to treat. This assay aimed to investigate the protective effects and mechanisms of Dendrobium officinale polysaccharide (DOP) in mice with acute UC induced by dextran sulphate sodium (DSS). We found that DOP could improve weight loss, decrease the disease activity index (DAI), and regulate the release of interleukin 2 (IL-2), IL-4, IL-6, and IL-10 in DSS-induced acute UC mice. Additionally, DOP preserved the integrity of the intestinal barrier in UC mice by increasing goblet cell density and maintaining tight junctions. DOP significantly enhanced total antioxidant capacity (T-AOC), and reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels in the bloodstream. In terms of serum biochemistry, DOP markedly elevated levels of bilirubin (BIL), alkaline phosphatase (ALP), total bile acid (TBA), creatinine (Crea), and creative kinase isoenzyme (CKMB). Furthermore, DOP increased the relative abundance of Lactobacillales. DOP also improved intestinal health and stimulated the synthesis of potent anti-inflammatory and antiviral substances by regulating the metabolism of purines, prostaglandins, and leukotrienes. Therefore, DOP can be considered a functional dietary supplement for the treatment of UC, as it improves the condition of DSS-induced UC mice.

Positive association between serum bilirubin within the physiological range and serum testosterone levels

BackgroundsResearch has demonstrated that elevated serum total bilirubin (STB) levels have a beneficial impact on various diseases, particularly metabolic syndrome. This study aims to investigate the association between STB levels and serum testosterone (STT) in order to determine if bilirubin plays a protective role in relation to testosterone deficiency (TD) risk.MethodsIn this study, a total of 6,526 eligible male participants aged 20 years or older were analyzed, all of whom took part in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2016. To investigate the relationship between STB and STT levels, we employed weighted multivariate regression models along with restricted cubic splines (RCS). Additionally, a subgroup analysis was conducted to explore the heterogeneity of this relationship across different subpopulations.ResultsAmong the participants, 1,832 individuals (28.07%) were identified as having testosterone deficiency (TD), defined as an STT level below 300 ng/dL. A significant positive correlation between STB and STT levels was observed in both crude and adjusted models (all P < 0.0001). The association between STB and STT levels was found to be statistically significant up to a threshold of 17.1 µmol/L, after which it became statistically insignificant(P for non-linearity = 0.0035). Weighted logistic regression analysis indicated that a 1 µmol/L increase in STB was associated with a 4% decrease in the likelihood of TD (odds ratio = 0.96, P < 0.0001). Subgroup analysis showed that the inverse relationship was limited to individuals aged 60 and over, non-smokers/drinkers, and obese individuals.ConclusionSTB within the physiological range(17.1 µmol/L) was positively associated with STT in adult males. The potential protective role of bilirubin regarding testosterone levels merits further exploration.

Case Series: Hyperbilirubinemia under elexacaftor/tezacaftor/ivacaftor in the presence of Gilbert’s syndrome

Liver-related side effects are a known complication of treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for cystic fibrosis (CF). Gilbert’s syndrome is caused by a genetic mutation that reduces activity of the enzyme UDP glucuronosyltransferase 1 polypeptide A1 (UGT1A1), causing elevated levels of unconjugated bilirubin in the blood and duodenal bile. The presence of Gilbert’s syndrome and CF might represent additive risk factors for liver-related adverse events during ETI treatment. This case series describes six people with CF (pwCF) in whom previously unknown Gilbert’s syndrome was unmasked after initiation of treatment with ETI. Although all patients had some level of hepatic dysfunction and/or elevated levels of bilirubin after initiation of ETI, the clinical course varied. Only one patient had to stop ETI therapy altogether, while the others were able to continue treatment (some at a reduced dosage and others at the full recommended daily dosage). All patients, even those using a lower dosage, experienced clinical benefit during ETI therapy. Gilbert’s syndrome is not a contraindication for ETI therapy but may be mistaken for a risk factor for liver-related adverse events in pwCF. This is something that physicians need to be aware of in pwCF who show liver adverse events during ETI therapy.

A novel experimental model of MetALD in male mice recapitulates key features of severe alcohol-associated hepatitis.

The recent increase in the incidence of alcohol-associated hepatitis (AH) coincides with the obesity epidemic in the United States. However, current mouse models do not fully replicate the combined insults of obesity, metabolic dysfunction-associated steatohepatitis, and alcohol. The aim of this study was to develop a new mouse model that recapitulates the robust inflammatory and fibrotic phenotype characteristic of human MetALD. Eight- to 10-week-old male C57BL/6 mice were fed chow or high fat-cholesterol-sugar diet (metabolic dysfunction-associated steatohepatitis diet) and in each group, some received alcohol in drinking water (ad libitum) and weekly alcohol binges (EtOH) for 3 months. The liver was assessed for features of AH. MetALD mice displayed increased liver damage indicated by highly elevated ALT and bilirubin levels compared to all other groups. Liver steatosis was significantly greater in the MetALD mice compared to all other experimental groups. The inflammatory phenotype of MetALD was also recapitulated, including increased IL-6 and IL-1β protein levels as well as increased CD68+ macrophages and Ly6G+ neutrophils in the liver. Sirius red staining and expression of collagen 1, alpha-smooth muscle actin indicated advanced fibrosis in the livers of MetALD mice. In addition, indicators of epithelial-to-mesenchymal transition markers were increased in MetALD mice compared to all other groups. Furthermore, we found increased ductular reaction, dysregulated hedgehog signaling, and decreased liver synthetic functions, consistent with severe AH. Alcohol administration in mice combined with metabolic dysfunction-associated steatohepatitis diet recapitulates key characteristics of human AH including liver damage, steatosis, robust systemic inflammation, and liver immune cell infiltration. This model results in advanced liver fibrosis, ductular reaction, decreased synthetic function, and hepatocyte dedifferentiation, suggesting a robust model of MetALD in mice.

Comparative Analysis of C-reactive Protein and Procalcitonin as Biomarkers for Prognostic Assessment in Pediatric Sepsis.

Background Sepsis poses a critical medical challenge due to its profound systemic inflammatory response, which frequently results in organ dysfunction and high mortality rates, especially in pediatric patients. The condition requires prompt recognition and aggressive management to mitigate its severe outcomes. Methods This prospective study enrolled 248 pediatric patients admitted with sepsis to the pediatric intensive care unit (PICU) at our tertiary care center. Patients were randomly assigned to either the C-reactive protein (CRP) or procalcitonin (PCT) groups, with biomarker levels measured upon admission (hour zero) and again at 72 hours post-admission. Clinical parameters such as the need for ionotropic support, use of steroids, incidence of acute kidney injury (AKI), requirement for invasive ventilation, patient outcomes, and changes in antibiotic management were assessed based on these biomarker levels. Results Procalcitonin-positive sepsis cases demonstrated notable clinical severity compared to their C-reactive protein counterparts, showing significantly lower systolic blood pressure (p = 0.012), heightened need for ionotropic support (p < 0.0001), and more pronounced liver and renal dysfunction as indicated by elevated serum bilirubin (p = 0.001) and creatinine levels (p = 0.0058). The incidence of AKIwas also higher in procalcitonin-positive cases. Despite these severe clinical parameters, there were no significant differences in the length of the PICU stay or in patient outcomes concerning discharge and mortality rates. Procalcitonin levels effectively guided antibiotic management, resulting in therapy adjustments in a substantial proportion of cases, with 67 (54%) experiencing downgrades and 33 (27%) requiring upgrades based on procalcitonin levels measured 72 hours post-admission. Conclusion Procalcitonin proves to be a valuable biomarker in assessing the severity and management of sepsis in pediatric patients. It correlates significantly with clinical parameters such as blood pressure, the need for ionotropic support, and markers of organ dysfunction.

Histopathological impact of SARS-CoV-2 on the liver: Cellular damage and long-term complications.

Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

ASGE Predictors for the Diagnosis of Choledocholithiasis: Validation in a Public Hospital of Merida, Yucatan, México

Background:: Choledocholithiasis is defined as the presence of calculus in the biliary tract, and is one of the main complications of cholelithiasis. Its prevalence among the Mexican pop-ulation is 14%. Objective:: To determine the validity of predictors of choledocholithiasis in patients attending the Hospital Agustin O’Horan from January 2019 to December 2020. Methods:: This was an observational, analytical, and retrospective study. It included patients with a diagnosis of choledocholithiasis, and it evaluated the sensitivity, specificity, as well as positive and negative predictive values for risk criteria of the American Society for Gastrointestinal Endoscopy (ASGE) Results:: Ninety-six medical histories were analyzed. Ninety were from women and six from males (94% and 6% respectively), and the average age was 40 years. The registry shows an increase of serum ALP, AST, and ALT in 98% of the reports, and elevated levels of bilirubin in 19% by 1.3-4 mg/dl, and 76% by &gt;4mg/dl of them. Moreover, the records showed pancreatitis and cholangitis (8% each one). The ultrasound reports indicates that 96% of the patients had a choledochal cyst higher than 5 mm, while 54% had a choledochal litho. Sensitivity and specificity of ASGE criteria for the diagnosis of choledocholithiasis was 96.6% and 45.5% respectively, and a Positive Predictive Value of 16% and a Negative Predictive Value of 99%. Conclusion:: It is considered that the diagnostic accuracy test of the ASGE criteria for the diagnosis of choledocholithiasis is high.