Evaluating the potential risk of ketamine-induced hepatotoxicity in the treatment of mood and anxiety disorders: A systematic review.

Off the Vent and on the Mend: Predicting Successful On-Table Extubation Following Liver Transplantation.

Breast cancer (BC) is the most commonly diagnosed malignancy in women worldwide, with over 2 million cases diagnosed each year. Almost 80% of invasive BC are estrogen receptor positive (ER+) with a large proportion of BC patients possessing elevated blood estrogen levels. Estrogen metabolism is regulated by glucuronidation, mediated by UDP-glucuronosyltransferases (UGTs), including UGT1A1. This pathway is shared between estrogen and other metabolites including unconjugated bilirubin (UCB), which has an overlapping binding site within UGT1A1. Ex vivo metabolic studies demonstrate reciprocal substrate-dependent competitive inhibition of glucuronidation between UCB and estrogens. Therefore, acutely or chronically elevated bilirubin levels could, hypothetically, reduce estrogen conjugation in vivo, increasing systemic estrogen concentrations. Similarly, elevated estrogen levels as observed in BC patients may affect UCB concentrations. Furthermore, reduced activity UGT1A1 polymorphisms (GS - Gilbert's syndrome) or mutation (CNS - Crigler-Najjar syndromes) in humans could also increase estrogen levels, increasing the risk of BC, as reported in clinical studies. This is the first review that integrates in vitro and clinical evidence demonstrating a potential interaction between estrogen and UCB metabolism. Recognition of this network could improve BC risk assessment and encourage earlier screening/surveillance strategies to prevent ER+BC.

Percutaneous Microwave Ablation for Viable Hepatic Cystic Echinococcosis: Real-World Outcomes from a Multicenter Study.

Gilbert syndrome is a human genetic disorder which affects bilirubin metabolism in the liver and results in unconjugated hyperbilirubinemia. While considered a benign condition with only occasional jaundice and possible alterations of metabolism of certain drugs, Gilbert syndrome can reduce cardiovascular disease (CVD) risk. The objective of this review was to summarize the evidence on the potential effect of Gilbert Syndrome on reducing CVD risk via lowering cholesterol and/or lipid levels in the body and is associated with other protective mechanisms which are related to higher blood levels of unconjugated bilirubin. A systematic review of articles returned from the online database PubMed was conducted using search terms: "Gilbert syndrome", "reduced cardiovascular disease risk", "cardiovascular disease", "cholesterol", and "lipid level". After filtering using the exclusion criteria and removing duplicates, eight articles were identified for the review. This review found that CVD risk was lower for people with Gilbert syndrome when compared to unaffected individuals. The reduced CVD risk was theorized to be due to elevated unconjugated bilirubin levels which lead to reduced concentrations of lipids, reduced inflammation biomarkers, decreased ABCA1 protein, increased serum antioxidant capacity expression, decreased BMI, and lower triglyceride levels. Individuals with Gilbert syndrome have a reduced CVD risk. Given that Gilbert syndrome reduces CVD risk in individuals and that Gilbert syndrome results in elevated serum levels of unconjugated bilirubin; elevation of unconjugated bilirubin could serve as a biomarker to monitor CVD risk reduction in the general population.

Futility of resection after neoadjuvant therapy in pancreatic ductal adenocarcinoma.

Maralixibat Improves Xanthomas and Hypercholesterolemia in Children with Alagille Syndrome: A Post Hoc Integrated Analysis From Two Clinical Trials.

Recent evidence suggests that moderately elevated bilirubin plasma concentrations possess protective effects against non-communicable diseases. One possible explanation for this might be that Gilbert's Syndrome (GS), a mildly hyperbilirubinaemic condition, leads to an enhanced lipid metabolism. Furthermore, there are first hints that individuals with GS may have a greater performance capacity. We hypothesize that GS participants have a greater maximal fat oxidation and performance capacity. To test this, we conducted an age- and gender-matched human case-control study. We included 40 people with GS and 40 controls, aged 18-65 years, who were all moderately physically active. 50% of the participants were over the age of 35. Participants performed a FatMax test on a bicycle ergometer. The study was performed from March 2023 to December 2023 at the University of Vienna. The group of GS participants over the age of 35 had a significantly higher FatMax (GS: median = 1.03 [maximum = 0.44; minimum = 2.42] W/kg body weight; C: median = 0.48 [minimum = 0.33; maximum = 1.61] W/kg body weight, p = 0.002) and a significantly greater oxygen consumption (GS: mean = 30.2 ± standard diviation (sd) = 8.09ml/min/ kg body weight; C: mean = 23.4 ± sd = 5.91ml/min/kg body weight, p = 0.005) at the respiratory compensation point. This is the first study to demonstrate that older GS individuals can generate more power whilst harnessing fatty acid metabolism and this may enhance their performance over prolonged periods of sub-maximal exercise.

The clinical differences between intra-aortic balloon pumping (IABP) and a microaxial flow pump (Impella) for left ventricular (LV) unloading in patients with fulminant myocarditis (FM) supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO) remain unclear. In this single-center, retrospective cohort study, we analyzed 27 consecutive patients with lymphocytic FM who received VA-ECMO support. Patients were stratified by the LV unloading device that was used: IABP (n=15); or Impella (n=12). The primary endpoint was a composite of all-cause mortality or implantation of an extracorporeal ventricular assist device (exVAD) within 30 days of VA-ECMO initiation. Temporal changes in laboratory and hemodynamic parameters during the first 7 days of support were also assessed. Baseline characteristics, including LV ejection fraction (IABP 16% vs. Impella 18%; P=0.814) and QRS duration (139 vs. 105 ms; P=0.805), were comparable between groups. Nine patients met the primary endpoint (mortality [n=7]; exVAD implantation [n=2]). Kaplan-Meier analysis revealed a significantly lower incidence of the primary endpoint in the Impella group (log-rank P=0.018). The Impella group also showed a significantly greater improvement in cardiac power output (group×time interaction, P=0.040). Hemolysis, elevated total bilirubin, and increased serum creatinine were more pronounced in the Impella group. In patients with FM requiring VA-ECMO, LV unloading with Impella was associated with improved short-term clinical outcomes compared with IABP.

Pentadesma butyracea (family Clusiaceae) bark is widely used in traditional medicine across sub‐Saharan Africa. However, the investigation of the safety profile of the gum exudate obtained from the stem bark of the plant is undocumented. This study evaluated the acute and subacute toxicity of the purified Pentadesma butyracea gum (PBG) in 36 male Sprague Dawley rats (8–10 weeks old; 100–182.08 g) to determine its safety profile for potential use as a pharmaceutical excipient. Acute toxicity was assessed using a single oral dose of 2000 mg/kg PBG, while subacute toxicity involved daily administration of 250, 500, and 1000 mg/kg PBG for 28 days. In the acute toxicity study, no mortality or significant adverse effects on behavior, body weight, relative organ weight, or histological features were observed, suggesting an LD50 greater than 2000 mg/kg PBG. Hematological and biochemical analyses revealed no harmful deviations, supporting the safety of PBG in acute exposure. In the subacute study, no mortality occurred across all doses, and body weight changes were minimal. Relative organ weights of the kidneys, heart, and lungs increased at higher doses, indicating potential dose‐dependent effects. Biochemical analyses revealed no significant alterations in liver enzymes (AST, ALT, and ALP) or markers of kidney function (urea and creatinine) at lower doses; however, slight elevations in bilirubin and creatinine were observed at 1000 mg/kg PBG, suggesting mild hepatic and renal stress. Histopathological analysis confirmed the absence of severe pathological changes, with only mild and reversible alterations at higher doses. Overall, PBG demonstrated a favorable safety profile at doses below 1000 mg/kg, supporting its potential use as a pharmaceutical excipient. The preliminary phytochemical screening also showed the presence of tannins, glycosides, coumarins, sterols, and triterpenoids. Further studies, including chronic toxicity and pharmacokinetic assessments, are recommended to establish the long‐term safety of PBG.

Clinical study of recombinant human thrombopoietin in platelet engraftment following autologous hematopoietic stem cell transplantation.

Acute cholangitis is a potentially life-threatening condition commonly caused by bacterial infections of the biliary tract. Here, we present an unusual case of acute cholangitis caused by Vibrio cholerae in a 76-year-old man with a history of hypertension, diabetes, asthma, and post-cholecystectomy who presented with upper abdominal pain, jaundice, and fatigue. Lab results showed elevated inflammatory markers and bilirubin. Imaging revealed gallstones and bile duct dilation. Blood cultures isolated non-toxigenic Vibrio cholerae, which was highly susceptible to all tested antibiotics. The patient was successfully treated with piperacillin/tazobactam and levofloxacin, along with supportive care. His symptoms resolved, and subsequent cultures were negative. This case highlights a rare instance of non-cholera Vibrio cholerae causing acute cholangitis and bacteremia in an elderly patient.

The current study was conducted to assess the effect of partial replacement of soyabean meal (SBM) (Glycine max) with defatted winged termite meal (WTM) (Macrotermes natalensis) inclusion levels on the performance, blood, and bone composition of Ross 308 broiler chickens in 42 days feeding trial. A total of 150 one-day-old, unsexed broiler chicks were allocated to 3 dietary treatments, replicated 5 times with 10 chickens per pen in a completely randomized design (CRD). Broilers were fed isonitrogenous, and iso-energetic experimental diets formulated to include WTM as follows: a control diet without WTM = WTM0; a basal broiler diet with 50g/kg of WTM = WTM5; a basal diet with 100g/kg of WTM = WTM10 to replace SBM. Average feed intake (FI), body weight gain (BWG) and feed conversion ratio (FCR) were measured at 1 to 14 days (starter), 15 to 28 days (grower) and 29 to 42 days (finisher). Hematology, serum biochemistry and right tibia bone traits of birds were determined on day 14, 28 and 42 in each growth phase. WTM inclusion had no effect (P > 0.05) on MR, BWG and FCR of broilers throughout the growth stages except FI that was higher (P< 0.05) in broilers fed WTM5 followed by WTM10 and WTM0 at starter phase. WTM inclusion had no (P> 0.05) influence on most hematology and serum parameters the growth period. However, elevated (P< 0.05) aspartate aminotransferase (AST) and bilirubin observed in chickens fed WTM5 than other groups at finisher phase. Dietary WTM inclusion had no influence (P> 0.05) on the majority of bone traits throughout the growth phase except bone density (TBD) that was higher (P< 0.05) in birds fed WTM5 than other treatment groups at starter phase whereas better (P< 0.05) bone breaking strength (BBS) was observed in birds on WTM5 compared to WTM0 and WTM10. It was concluded that WTM up to 10% could be partially included in diets without compromising growth performance, blood, and bone traits of Ross 308 broiler chickens during starter, grower and finisher phase.

Chemotherapy combined with immune checkpoint inhibitor have prolonged survival of patients with advanced biliary tract cancers (BTCs), and the previous studies showed the synergistic anti-tumor effect of chemotherapy, anti-angiogenesis therapy, and immunotherapy. Hepatic arterial infusion chemotherapy (HAIC) achieved a higher tumor response and survival benefit in previous phase II studies for advanced BTCs. Thus, we conducted this phase II trial to evaluate the efficacy and safety of HAIC combined with bevacizumab and toripalimab for advanced BTCs. Treatment-naïve participants with advanced BTCs were recruited for this phase II trial. Combination therapy, comprising HAIC with bevacizumab (300 mg, day 1), oxaliplatin (40 mg/m2, 2 h, days 1-3), and 5-fluorouracil (800 mg/m2, 22 h, days 1-3) plus intravenous toripalimab (240 mg, day 1 before HAIC), was repeated every 4 weeks for a maximum of six consecutive cycles. Intravenous toripalimab (240 mg) and bevacizumab (300 mg) were administered every 4 weeks as maintenance treatment. The primary endpoint was objective response rate (ORR) according to Immune-Modified Response Evaluation Criteria in Solid Tumors criteria, and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Olink proximity extension assay with a Target 96 Immuno-Oncology panel was exploratory investigated. Between July 2020 and January 2022, 32 participants were enrolled. The ORR was 84.38%, and the disease control rate was 96.88%. Median PFS and OS were 13.20 months [95% confidence interval (CI): 8.93-17.47] and 19.0 months (95% CI: 12.22-25.78), respectively. Grade 3 or higher adverse events (AEs) were observed in 10 participants (31.25%), and the most frequent grade 3 or higher AEs were elevated ALT/AST (4/32, 12.50%), elevated total bilirubin (3/32, 9.38%), and neutropenia (3/32, 9.38%). In exploratory analysis, Child-Pugh B [hazard ratio (HR): 22.65, 95% CI: 3.66-140.08, P=0.001] and high level of macrophage metalloproteinase-12 (HR: 5.99, 95% CI: 1.60-22.37, P=0.008) were indicated as the risk factors related to worse PFS. HAIC combined with bevacizumab and toripalimab may serve as an improved first-line treatment for advanced BTCs, which require a randomized control trial for verification. This trial is registered at ClinicalTrail.gov (NCT04217954).

Liver toxicity is a major health concern caused by pharmaceutical exposure, poisons like CCl4, or environmental contaminants. The CCl4-induced liver toxicity model is extensively used to study hepatic damage, such as oxidative stress and fibrosis. In current study, synergistic effect of natural compounds Lycopene (Lyc) and L-Carnitine (L-Car) possessing the antioxidant activity was assessed to mitigate the liver fibrosis induced by CCl4 in male rat model. CCl4 treated rats showed significant decrease in body weight (21.62% ± 0.83%) alongside elevated liver enzymes ALP (276 ± 6.62), AST (283 ± 4.53), ALT (138 ± 0.74), bilirubin (1.73 ± 0.74) and lactate dehydrogenase (LDH) an injury marker (0.778% ± 0.06%). After treatment of CCl4 induced fibrosis with Lyc + L-Car, significantly increased body weight of rats was observed (34.39% ± 0.77%). Liver enzymes also showed remarkable improvement after treatment with Lyc + L-Car (p ≤ 0.001). Combined Lyc + L-Car group showed reduced the LDH level (0.246% ± 0.02%), fibrosis gene markers TIMP-1 and Col1α1 (p ≤ 0.001) and increased antioxidant enzyme activity of SOD (0.56 ± 0.04 U/dL) and CAT (0.489 ± 0.004 U/dL). Histological analysis showed a marked improvement in liver architecture, with reduced fibrosis appearance. These findings suggest that combination of Lyc and L-Car supplementation effectively counteracts fibrosis, oxidative stress, and liver enzymes elevation, supporting its potential role as a dietary therapeutic agent for metabolic and hepatic disorders. Future recommendations include conducting long- term clinical trials in humans to validate these findings, exploring optimal dosages for dietary lycopene supplementation, and investigating its molecular mechanisms of action.

Curative resection of type IV hilar cholangiocarcinoma typically requires trisectionectomy, a procedure associated with high morbidity. The Taj Mahal hepatectomy, involving resection of segment IVb, V, and the caudate lobe, offers a parenchyma-preserving alternative.1 Since complete resection of segment IV facilitates caudate lobectomy, and inclusion of segment V provides no added benefit, a modified approach-removing only segment IV (IVa and IVb) with the caudate lobe-has been developed.2 The robotic performance of this modified procedure has not been reported previously in the English literature. This video demonstrates the standardized technique of robotic-modified Taj Mahal hepatectomy for type IV hilar cholangiocarcinoma. Patients with type IV hilar cholangiocarcinoma without vascular involvement are suitable candidates. A 59-year-old male with jaundice and 1-month weight loss underwent sequential percutaneous transhepatic biliary drainage (segment III and right posterior ducts) for elevated bilirubin (>30 mg/dL). Key steps included hepatoduodenal lymphadenectomy, distal bile duct division with frozen section, caudate mobilization via a left-sided approach, indocyanine green-guided segment IV resection with en bloc caudate lobectomy, and three separate cholangiojejunostomies. Operative time was 560 minutes with 300 mL blood loss. The postoperative course was uneventful, and the patient was discharged on day 8. Histopathology showed T2 moderately differentiated adenocarcinoma with negative margins and 14 tumor-free lymph nodes. At 11-month follow-up, the patient remained disease free. Four patients underwent this procedure over 12 months. Robotic-modified Taj Mahal hepatectomy is a safe, feasible, parenchyma-preserving option for selected patients with type IV hilar cholangiocarcinoma.

Acute renal replacement therapy in cardiogenic shock: Prognostic impact of timing, modality, and indications - Insights from the FRENSHOCK study.

Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D3 (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10-12. Hepatic injury was evaluated using 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic 99mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, 99mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses.

Background and AimsThe combination of transarterial chemoembolization (TACE) with molecular targeted therapy and/or immune checkpoint inhibitors (ICIs) has emerged as a cornerstone treatment for intermediate-to-advanced hepatocellular carcinoma (HCC). However, the risk of hepatotoxicity associated with these multimodal regimens remains inadequately characterized. This study aimed to evaluate the incidence, severity, and independent predictors of hepatotoxicity, and to develop a clinically practical prediction model.Materials and MethodsThis retrospective study analyzed data from 200 HCC patients treated at Shandong First Medical University Affiliated Cancer Hospital between October 2021 and July 2024. Patients received either TACE plus tyrosine kinase inhibitors (TKIs) (n=120) or TACE plus TKIs and ICIs (n=80). Hepatotoxicity was graded according to CTCAE v5.0 criteria. Multivariate logistic regression was employed to identify independent risk factors and construct a predictive nomogram.ResultsThe overall hepatotoxicity incidence was 38.00%, predominantly mild-to-moderate (Grade 1: 63.16%; Grade 2: 23.68%; Grade 3: 13.16%). No Grade 4 events occurred, and no significant difference was observed between treatment groups (P=0.637). Multivariate analysis identified four independent predictors: liver cirrhosis (OR=1.684), ALBI Grade 2/3 (OR=6.436), elevated total bilirubin (OR=1.040), and decreased prothrombin activity (OR=0.968). The resulting TCAP (Total bilirubin, Cirrhosis, ALBI grade, Prothrombin activity) nomogram demonstrated robust discriminatory performance (AUC=0.855) with a sensitivity of 82.00% and specificity of 79.10% at the optimal cut-off value of 0.419.ConclusionThe TCAP nomogram provides a reliable, evidence-based tool for individualized hepatotoxicity risk stratification in HCC patients undergoing TACE-based combination therapy.

Dengue-associated hemophagocytic lymphohistiocytosis (DA-HLH) is a rare but severe hyperinflammatory complication of dengue. Its clinical overlap with severe dengue often delays recognition. We describe the clinical, laboratory and therapeutic characteristics of pediatric patients with DA-HLH in a dengue-endemic region of Latin America. We conducted a retrospective cohort study of pediatric patients diagnosed with DA-HLH at a tertiary-care center in Cali, Colombia, between 2013 and 2024. HLH was diagnosed using HLH-2004 criteria and supported by the HScore. Clinical features, laboratory parameters, treatment regimens and outcomes were analyzed. Associations between extreme biomarker values (below Q1 or above Q3) and mortality were assessed using Fisher exact test. Nineteen patients were included, with a median age of 7 years. Fever and cytopenias were present in all cases, and hepatomegaly was frequently observed. Hyperferritinemia occurred in nearly all patients. Viral coinfections-most commonly Epstein-Barr virus and cytomegalovirus-were identified in over one-third of cases. Overall mortality was 21.1% and occurred exclusively among patients with significant underlying comorbidities. In this exploratory analysis, elevated total bilirubin was the only laboratory parameter associated with mortality. DA-HLH should be considered in pediatric patients with dengue who present with persistent fever, cytopenias, hepatic dysfunction and marked hyperferritinemia. In this exploratory analysis, elevated bilirubin appeared to reflect severe systemic and hepatic involvement rather than an independent prognostic factor, while viral coinfections may contribute to disease severity. Early recognition and individualized immunomodulatory management are essential, and larger multicenter studies are needed to validate these findings.