Posterior Circulation Ischemic Stroke Is Associated with More Severe Forward Head Posture in Patients with Cervicalgia.

INTRODUCTION: Chronic risk factors of posterior circulation ischemic strokes remain unknown. There is, however, evidence that anatomical variations within the vertebrobasilar system could potentially lead to the development of posterior circulation strokes. We investigated the association of forward head posturing (FHP), a chronic anatomic change seen in patients with cervicalgia, with posterior circulation strokes. METHODS: In this case control study, we identified adult patients diagnosed with cervicalgia and ischemic posterior circulation infarcts from 2007 to 2023. Patients were paired to cervicalgia controls without posterior circulation stroke and matched for known risk factors. Patients' C0-C2 angle, C2-C7 angle, and sagittal vertical axis (SVA) shift were measured as metrics for FHP severity on lateral cervical spine x-rays. Paired T-tests were applied to compare patient stroke risk factors and FHP between groups. RESULTS: 206 patients (103 cases and 103 controls) were included with an average age of 64.4 years with 51.5% female. There were no statistically significant differences between the patients' risk factors for stroke, including hypertension, hyperlipidemia, diabetes, smoking, hypercoagulable state, and atrial fibrillation. There were statistically significant differences in C0-C2 angle (30.7 degrees vs 23.2 degrees, P-value=0.002) and SVA shift (35.4 mm vs 25.3 mm, P-value<0.001). CONCLUSIONS: This case control matched pair study found that within adults with cervicalgia, posterior circulation ischemic stroke was associated with more severe FHP as noted in C0-C2 angle and SVA shift measurements. This study further speculates that this association may be because of chronic changes in circulation flow dynamics within the vertebrobasilar system with the postural change.

Liver transplantation for acute liver failure (ALF) and acute-on-chronic liver failure (ACLF).

Acute liver failure (ALF) and acute-on-chronic liver (ACLF) are distinct phenotypes of liver failure and thus need to be compared and contrasted for appropriate management. There has been a significant improvement in the outcomes of these patients undergoing liver transplantation (LT). Survival post-LT for ALF and ACLF ranges between 90-95% and 80-90% at 1 year, futility criteria have been described in both ALF and ACLF where organ failures define survival. Plasma exchange and continuous renal replacement therapy may serve as bridging therapies. Identifying the futility of LT is as necessary as the utility of LT in patients with ALF and ACLF. The role of regenerative therapies such as granulocyte colony-stimulating factors in ACLF and hepatocyte and Xenotransplantation in both conditions remains uncertain. Measures to increase the donor pool through increasing cadaveric transplants in Asian countries, living donations in Western countries, auxiliary liver transplants and ABO-incompatible liver transplants are necessary to improve the survival of these patients. In this review, we discuss the similarities and differences in clinical characteristics and the timing and outcomes of LT for ALF and ACLF, briefly highlighting the role of bridging therapies and providing an overview of recent advances in the management of ALF and ACLF.

Single Center Neurosurgical Outcomes and Trends in Endoscopic Endonasal Resection of 297 Sellar/Suprasellar Tumors Stratified by Duration of Neurosurgical Career.

BACKGROUND/OBJECTIVE: Endoscopic endonasal transsphenoidal surgery (EETS) is a common treatment for sellar and suprasellar tumors. While endoscopic training has improved over the years and formal fellowship training is now broadly available, the operative nuances of EETS conjectures the existence a learning curve as a neurosurgeon matures with experience. We aim to evaluate operative outcomes of 3 different experience levels of neurosurgeons over time at a single institution. METHODS: We reviewed all adult patients who underwent EETS at Loyola University Medical Center by 3 early career, 1 midcareer, and 2 late career neurosurgeons from 2007 to 2023. A comparative assessment of patient demographics, tumor features, and surgical outcomes was done using metrics such as length of surgery, rates of gross total resection (GTR) and symptomatic improvement, new postoperative steroid dependence, and development of diabetes insipidus (DI). T-tests and χ2 were used to statistically evaluate the study cohorts. RESULTS: A total of 297 patients underwent EETS. One hundred three (35%) were operated on by an early career, 122 (41%) by a mid-career, and 72 (24%) by a late career neurosurgeon. Late-career surgeons had shorter operation times (144 vs. 180 minutes with early and mid-career, P = 0.029) and increased GTR rates (P = 0.008). There were no significant differences between the symptomatic improvement rates amongst various surgeon experience levels. Although not statistically significant, early-career neurosurgeons had lower rates of new postoperative steroid dependence. Patients of early career surgeons experienced significantly less DI (15% vs. 40%, P = 0.004). CONCLUSIONS: Late-career neurosurgeons had shorter operation lengths, achieved higher rates of GTR, and their patients experienced significantly higher rates of DI. Overall outcomes remained stable throughout the course of 16 years between different surgeon experience levels.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in MAFLD-Related Acute-on-Chronic Liver Failure.

BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

Patients at Highest Risk of Missing Initial One-Year Follow up After Pituitary Adenoma Resection.

OBJECTIVE: Routine evaluation and surveillance imaging after pituitary adenoma (PA) endoscopic endonasal transsphenoidal resection (EETS) is a neurosurgical practice to identify tumor recurrence. This study aims to identify social and clinical factors that may contribute to patients missing their initial one-year follow-up appointment and provide guidance for targeted education to improve patient adherence with postoperative treatment plans, ultimately reducing unknown adenoma recurrence. METHODS: The authors performed a single-center retrospective review of patients who underwent EETS for PAs from 2007 to 2023. Patients who were analyzed for sociodemographic factors, presenting symptoms, time to surgery, surgical outcomes, and adherence to postoperative follow-up visits at one-year following surgery. RESULTS: 256 patients with PAs treated by EETS met inclusion criteria. 218 (85%) of these patients attended one-year follow-up; 38 (15%) missed this visit. Twenty-nine (76%) individuals who missed their one-year follow up were males (p-value=0.006). Divorced/widowed/separated patients were two times more likely to miss their follow-up compared to their married counterparts (p-value=0.008). Additional significant risk factors included older age, as the mean age for patients who missed their one-year appointment was 60.1 years compared to 54.7 years (p-value=0.028). Patients with visual field deficits at initial presentation were also less likely to follow-up at one-year (p-value=0.03). CONCLUSIONS: Risk factors of missed one-year follow-up appointments after PA resection include male sex, divorced/widowed/separated marital status, older age, and the presence of visual deficits at initial presentation. Increased education efforts can be selectively aimed at these at-risk patient cohorts to improve patient compliance and reduce consequences of undetected tumor recurrence.

Systemic Therapies for Hepatocellular Carcinoma in India.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in India. This review explores the epidemiological trends and the landscape of systemic therapy for HCC in the Indian context, acknowledging the recent shift in etiology from viral hepatitis to lifestyle-associated factors. A comprehensive review of the literature was conducted, including data from the Global Cancer Observatory and the Indian Council of Medical Research, along with a critical analysis of various clinical trials. The article investigates systemic therapies in-depth, discussing their mechanisms, efficacy, and adaptation to Indian healthcare framework. Progression-free survival with a hazard ratio of ≤0.6 compared to sorafenib, overall survival of ∼16-19 months, and objective response rate of 20-30% are the defining thresholds for systemic therapy clinical trials. Systemic therapy for advanced HCC in India primarily involves the use of tyrosine kinase inhibitors such as sorafenib, lenvatinib, regorafenib, and cabozantinib, with sorafenib being the most commonly used drug for a long time. Monoclonal antibodies such as ramucirumab and bevacizumab and immune-checkpoint inhibitors, such as atezolizumab, nivolumab, and pembrolizumab, are expanding treatment horizons. Lenvatinib has emerged as a cost-effective alternative, and the combination of atezolizumab and bevacizumab has demonstrated superior outcomes in terms of overall survival and progression-free survival. Despite these advances, late-stage diagnosis and limited healthcare accessibility pose significant challenges, often relegating patients to palliative care. Addressing HCC in India demands an integrative approach that not only encompasses advancements in systemic therapy but also targets early detection and comprehensive care models. Future strategies should focus on enhancing awareness, screening for high-risk populations, and overcoming infrastructural disparities. Ensuring the judicious use of systemic therapies within the constraints of the Indian healthcare economy is crucial. Ultimately, a nuanced understanding of systemic therapeutic options and their optimal utilization will be pivotal in elevating the standard of HCC care in India.

Role of point-of-care ultrasound (POCUS) in clinical hepatology.

Hospitalized patients with cirrhosis frequently require critical care management for sepsis, HE, respiratory failure, acute variceal bleeding, acute kidney injury (AKI), shock, and optimization for liver transplantation, while outpatients have unique care considerations. Point-of-care ultrasonography (POCUS) enhances bedside examination of the hepatobiliary system and relevant extrahepatic sites. POCUS includes cardiac US and is used to assess volume status and hemodynamic parameters like cardiac output, systemic vascular resistance, cardiac contractility, and pulmonary artery pressure, which aid in the early and accurate diagnosis of heart failure, cirrhotic cardiomyopathy, porto-pulmonary hypertension, hepatopulmonary syndrome, arrhythmia, and pulmonary embolism. This also helps in fluid management and vasopressor use in the resuscitation of patients with cirrhosis. Lung ultrasound (LUS) can help in differentiating pneumonia, effusion, and edema. Further, US guides interventions such as line placement, drainage of abdominal collections/abscesses, relief of tension pneumothorax, drainage of pleural and pericardial effusions, and biliary drainage in cholangitis. Additionally, its role is essential to assess liver masses foci of sepsis, for appropriate sites for paracentesis, and to assess for vascular disorders such as portal vein or hepatic vein thrombosis. Renal US can identify renal and postrenal causes of AKI and aid in diagnosis of prerenal AKI through volume assessment. In this review, we address the principles and methods of POCUS in hospitalized patients and in outpatients with cirrhosis and discuss the application of this diverse modality in clinical hepatology.

Early living donor liver transplantation for alcohol-associated hepatitis: Status in the era of increasing demand, unmet needs, and future considerations.

Hazardous alcohol consumption is the leading cause of liver disease worldwide. Alcohol-associated hepatitis (AH) is an acute and serious presentation of alcohol-associated liver disease (ALD) that is associated with high short-term mortality. Medical management remains limited to corticosteroid therapy and intensive nutrition but improves survival in less than 50% of individuals. Liver transplantation (LT) is increasingly recognized as a treatment option for many patients with AH and may lead to greater survival benefit than medical management alone. The rate of wait-listings and LTs for AH has doubled in recent years, especially in the US. Several studies from the West have reported early LT for AH to be successful, where deceased donor LT is the norm. The challenges of LT in living donor centers, particularly for those with AH, are unique and have previously not been discussed in depth. In this review, we aim to discuss the challenges unique to LDLT with respect to candidate and donor selection, ethical considerations, disparities in LDLT, post-LT alcohol relapse, and measures to prevent them while also addressing the definitions and outcomes of early-living donor liver LT (eLDLT) for AH.

Evaluating the Impact of the COVID-19 Pandemic on Late-Canceled and No-Show Appointments at the Department of Neurological Surgery.

The coronavirus disease 2019 (COVID-19) pandemic resulted in unprecedented restrictions on the general public and disturbances to the routines of hospitals worldwide. These restrictions are now being relaxed as the number of vaccinated individuals increases and as the rates of incidence and prevalence decrease; however, they left a lasting impact on healthcare systems that is still being felt today. This retrospective study evaluated the total number of canceled or missed outpatient clinic appointments in a Neurological Surgery department before and after peak COVID-19 restrictions and attempted to assess the impact of these disruptions on neurosurgical clinical attendance. We also attempted to compare our data with the data from another surgical subspecialty department. We evaluated 32,558 scheduled appointments at the Loyola University Medical Center Department of Neurological Surgery, as well as 139,435 scheduled appointments with the Department of Otolaryngology. Appointments before April 2020 were defined as pre-COVID, while appointments during or after April 2020 were defined as post-COVID. Here, we compare no-show and non-attendance rates (no-shows plus late-canceled appointments) within the respective time range. Overall, we observed that before COVID-19 restrictions were put into place, there was an 8.9% no-show rate and a 17.4% non-attendance rate for the Department of Neurological Surgery. After COVID restrictions were implemented, these increased to 10.9% and 18.3%, respectively. Greater no-show and cancellation rates (9.8% in the post-COVID era vs 8.0% in the pre-COVID era) were associated with varying socioeconomic and racial demographics. African-American patients (2.56 times higher), new-visit patients (1.67 times higher), and those with Medicaid/Medicare insurance policies (1.48 times higher) were at the highest risk of no-show in the post-COVID era compared to the pre-COVID era.

National Trends and Factors Associated with Voluntary Refusal of Glioblastoma Treatment: A Retrospective Review of the National Cancer Database.

OBJECTIVE: Adherence to combinatorial treatments are important predictors of improved long-term outcomes for patients with glioblastoma (GB); however, factors associated with refusal of surgery, chemotherapy, or radiotherapy (RT) by patients with GB have not been studied. METHODS: The National Cancer Database was queried from 2004 to 2018 to identify patients with a primary diagnosis of GB who underwent surgical resection alone or followed by either RT or chemotherapy. Adult patients who voluntarily rejected a physician's recommendations for 1 or more treatment were selected. Multivariable regression was used to identify factors associated with rejection of surgical resection, chemotherapy, and RT. Patients receiving treatment were 3:1 propensity score matched to those rejecting treatment and median overall survival (OS) was compared. RESULTS: 58,788 patients were included in the analysis. Factors associated with voluntary refusal of GB treatment included: old age, nonprivate insurance, female sex, Black race, comorbidities, treatment at a nonacademic facility, and living 55+ miles away from a treatment facility (P < 0.05). On propensity matched analysis, refusal of surgery conferred a 4 month decrease in OS (P < 0.001), RT an 8 month decrease in OS (P < 0.001), and chemotherapy a 7 month decrease in OS (P < 0.001). CONCLUSIONS: In patients with GB, age, sex, race, nonprivate insurance, medical comorbidities, distance from treatment facility, and geographic location were associated with refusal of surgery, postsurgical RT, and chemotherapy. In addition, treatment refusal had a significant impact on OS length.

A Predictive Model for Intraoperative Cerebrospinal Fluid Leak During Endonasal Pituitary Adenoma Resection Using a Convolutional Neural Network.

BACKGROUND: Cerebrospinal fluid (CSF) leak during endoscopic endonasal transsphenoidal surgery can lead to postoperative complications. The clinical and anatomic risk factors of intraoperative CSF leak are not well defined. We applied a two-dimensional (2D) convolutional neural network (CNN) machine learning model to identify risk factors from preoperative magnetic resonance imaging. METHODS: All adults who underwent endoscopic endonasal transsphenoidal surgery at our institution from January 2007 to March 2023 who had accessible preoperative stereotactic magnetic resonance imaging were included. A retrospective classic statistical analysis was performed to identify demographic, clinical, and anatomic risk factors of intraoperative CSF leak. Stereotactic T2-weighted brain magnetic resonance imaging scans were used to train and test a 2D CNN model. RESULTS: Of 220 included patients, 81 (36.8%) experienced intraoperative CSF leak. Among all preoperative variables, visual disturbance was the only statistically significant identified risk factor (P = 0.008). The trained 2D CNN model predicted CSF leak with 92% accuracy and area under receiver operating characteristic curve of 0.90 (sensitivity of 86% and specificity of 93%). Class activation mapping of this model revealed that anatomic regions of CSF flow were most important in predicting CSF leak. CONCLUSIONS: Further review of the class activation mapping gradients revealed regions of the diaphragma sellae, clinoid processes, temporal horns, and optic nerves to have anatomic correlation to intraoperative CSF leak risk. Additionally, visual disturbances from anatomic compression of the optic chiasm were the only identified clinical risk factor. Our 2D CNN model can help a treating team to better anticipate and prepare for intraoperative CSF leak.

Proteome allocation is linked to transcriptional regulation through a modularized transcriptome.

It has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigate whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions can be modularized in the same way to reveal novel relationships between their compositions. We find that; (1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, (2) the modules in the proteome often represent combinations of modules from the transcriptome, (3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and (4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.

A systematic review and meta-analysis of major blood protein biomarkers that predict unfavorable outcomes in severe traumatic brain injury.

INTRODUCTION: Severe traumatic brain injury (TBI) presentation and late clinical outcomes are usually evaluated by the Glasgow Outcome Scale-Extended (GOS-E), which lacks strong prognostic predictability. Several blood biomarkers have been linked to TBI, such as Tau, GFAP, UCH-L1, S-100B, and NSE. Clinical values of TBI biomarkers have yet to be evaluated in a focused multi-study meta-analysis. We reviewed relevant articles evaluating potential relationships between TBI biomarkers and both early and 6-month outcomes. METHODS: All PubMed article publications from January 2000 to November 2023 with the search criteria "Protein Biomarker" AND "Traumatic Brain Injury" were included. Amongst all comparative studies, the sensitivity means and range values of biomarkers in predicting CT Rotterdam scores, ICU admission in the early period, or predicting GOS-E < 4 at the 6-month period were calculated from confusion matrices. Sensitivity values were modeled for each biomarker across studies and compared statistically for heterogeneity and differences. RESULTS: From the 65 articles that met the criteria, 13 were included in this study. Six articles involved early-period TBI outcomes and seven involved 6-month outcomes. In the early period TBI outcomes, GFAP had a superior sensitivity to UCH-L1 and S-100B, and similar sensitivity to the CT Rotterdam score. In the 6-month period TBI outcomes, total Tau and NSE both had significant interstudy heterogeneity, making them inferior to GFAP, phosphorylated Tau, UCH-L1, and S-100B, all four of which had similar sensitivities at 75 %. This sensitivity range at 6-month outcomes was still relatively inferior to the CT Rotterdam score. Total Tau did not show any prognostic advantage at six months with GOS-E < 4, and phosphorylated Tau was similar in its sensitivity to other biomarkers such as GFAP and UCH-L1 and still inferior to the CT Rotterdam score. CONCLUSION: This data suggests that TBI protein biomarkers do not possess better prognostic value with regards to outcomes.

Downstaging with Atezolizumab-Bevacizumab: A Case Series.

Background/aims: Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC (uHCC) for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezobev remains unknown. Methods: In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Results: Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age: 58.5 years; women-17%; Barcelona Clinic Liver Cancer Stage System B/C:5/7) had received 3-12 cycles of atezo-bev, and 4 of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 (54-114) days following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 (4-30) months, none of the alive patients developed HCC recurrence or graft rejection. Conclusions: Surgical therapy, including LT, is possible after atezo-bev therapy in wellselected patients after downstaging.

Coke oven wastewater treatment using polymeric and ceramic membranes.

This research is aimed to investigate the efficacy of membrane separation technology in treating coke oven wastewater (COW). A comparative study was conducted using three types of membranes: commercial polymeric (CP) membrane, commercial ceramic (CC) membrane, and synthesized ceramic (SC) membrane. The potential of the SC membrane in COW treatment was assessed in comparison to the CC membrane, which had a molecular weight cut-off (MWCO) of 1 Kilo-Dalton. The experiments were conducted under various trans-membrane pressure (TMP) conditions ranging from 1 to 4 bar. Additionally, the effect of the CP membrane on COW treatment was examined at TMP levels ranging from 5 to 25 bar. The research findings revealed that the SC membrane exhibited promising results in terms of permeability and flux compared to the CC membrane. Also, a significant reduction was observed in various water parameters such as TSS decreased by 89.74%, chlorides by 8.24%, nitrogen by 10%, and hardness by 22%. Moreover, the study was carried out by implementing an anti-fouling mechanism to mitigate fouling effects on membrane performance.

An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .

Determinants, profile and outcomes of hepatitis A virus-associated severe acute liver injury in adults.

BACKGROUND AND OBJECTIVES: Hepatitis A virus (HAV)-related hepatitis is witnessing an epidemiological transition with increasing trends in adults. While uncomplicated hepatitis remains common, evidence suggests it to be a growing cause for acute liver failure (ALF). In between the two extremes exists severe acute liver injury (s-ALI) which has a propensity to transition to ALF. We aimed at describing the clinical profile of patients with HAV-related s-ALI and identifying potential predictors of progression to ALF. METHODS: This was a single-center retrospective analysis of adult patients admitted with HAV-related s-ALI between April 2022 and December 2023. Demographic and laboratory parameters were compared between patients with only s-ALI and those with ALF. Predictors of progression from s-ALI to ALF were identified using logistic regression. RESULTS: Forty-three patients satisfied criteria of s-ALI, of which 33 (76.7%) had only s-ALI, while 10 (23.3%) had ALF. Patients with s-ALI had lesser leukocytosis (6.3 ± 3 vs. 13.2 ± 4.8), less incidence of acute kidney injury (9.1% vs. 40%) and lower model for end-stage liver disease (MELD) (20 [18-24.5] vs. 31.5 [26-42]), arterial lactate (2.1 [1.3-3.1] vs. 6.3 [5.2-8.0]), arterial ammonia (94 [72-118] vs. 299 [188-573]), procalcitonin (0.5 [0.28-1.25] vs. 3.2 [1.2-6.1]) and ferritin (482 [213-1633] vs. 5186 [1341-11,053]) compared to HAV-ALF (p < 0.05 for all). Three patients (9.09%) with s-ALI progressed to ALF of whom one (3%) died. Baseline ammonia levels (unadjusted odds ratio [OR] 1.03 [1.01-1.06]) and leukocyte count (OR 1.00 [1.00-1.01]) tended to be associated with ALF progression, although none was significant after multi-variable adjustment. Ammonia levels had an area under receiver operating curve of 0.816 (0.64-0.93) (p = 0.009) (cut-off of 144 µmol/L). Additional comorbidities did not impact overall outcomes. CONCLUSION: HAV presents as s-ALI in young adults, with almost one in 10 progressing to ALF. Baseline ammonia may be an important predictor of progression even in s-ALI, but mandates larger well-designed studies.

APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

Hepatocellular Carcinoma Screening in a Contemporary Cohort of At-Risk Patients.

Importance: Cohort studies demonstrating an association of hepatocellular carcinoma (HCC) screening with reduced mortality are prone to lead-time and length-time biases. Objective: To characterize the clinical benefits of HCC screening, adjusting for lead-time and length-time biases, in a diverse, contemporary cohort of at-risk patients. Design, Setting, and Participants: This retrospective cohort study of patients with HCC was conducted between January 2008 and December 2022 at 2 large US health systems. Data analysis was performed from September to November 2023. Main Outcomes and Measures: The primary outcome was screen-detected HCC, defined by abnormal screening-intent abdominal imaging or α-fetoprotein level within 6 months before diagnosis. Cox regression analysis was used to characterize differences in overall survival between patients with screen-detected and non-screen-detected HCC; lead-time and length-time adjustments were calculated using the Duffy parametric formula. Results: Among 1313 patients with HCC (mean [SD] age, 61.7 [9.6] years; 993 male [75.6%]; 739 [56.3%] with Barcelona Clinic Liver Cancer stage 0/A disease), HCC was screen-detected in 556 (42.3%) and non-screen detected in 757 (57.7%). Patients with screen-detected HCC had higher proportions of early-stage HCC (393 patients [70.7%] vs 346 patients [45.7%]; risk ratio [RR], 1.54; 95% CI, 1.41-1.70) and curative treatment receipt (283 patients [51.1%] vs 252 patients [33.5%]; RR, 1.52; 95% CI, 1.34-1.74) compared with patients with non-screen-detected HCC. The screen-detected group had significantly lower mortality, which persisted after correcting for lead-time bias (hazard ratio, 0.75; 95% CI, 0.65-0.87) in fully adjusted models. Both groups had similar tumor doubling times (median [IQR], 3.8 [2.2-10.7] vs 5.6 [1.7-11.4] months) and proportions of indolent tumors (28 patients [35.4%] vs 24 patients [38.1%]; RR, 0.93; 95% CI, 0.60-1.43). Adjustment for length-time bias decreased survival estimates, although 3-year and 5-year survival for patients with screen-detected HCC remained longer than that for patients with non-screen-detected HCC. Conclusions and Relevance: The findings of this cohort study suggest that HCC screening is associated with reduced mortality even after accounting for lead-time and length-time biases. However, these biases should be considered in future studies.