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

BACKGROUND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence (AI) 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 AH patients per NIAAA criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day post-admission mortality, three AI algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined via Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce post-test probabilities. The ALCoholic Hepatitis Artificial INtelligence (ALCHAIN) Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30-day) and 27.9% (90-day) 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, MELD variations, ABIC, Glasgow, and modified Glasgow Scores (p<0.001). ALCHAIN Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCHAIN Ensemble score>0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing AI 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/.

Safety and Efficacy of Zavegepant in Treating Migraine: A Systematic Review.

Drugs that act on the calcitonin gene-related peptide (CGRP) pathway herald the dawn of a new era in the management of migraine headaches. The blockade of CGRP alleviates neural inflammation and has been associated with reduced pain sensitization. Zavegepant is a third-generation drug and is the first intranasal CGRP antagonist to be developed. This systematic review aims to assess the safety, efficacy, pharmacokinetics, and tolerability of Zavegepant as an abortive treatment for migraine. Studies that assessed the safety, tolerability, and efficacy of Zavegepant for migraine were identified through a systematic literature review of PubMed, Clinicaltrials.gov, and Cochrane databases in April 2023. Our systematic review yielded a total of six studies that fit our inclusion criteria. Of these, data from only two randomized control trials (RCTs) was homogenous; hence, forest plots of results pooled from the included studies were not reported. The included studies showed that Zavegepant is an efficacious and well-tolerated abortive treatment modality for episodic migraine in adult patients. Zavegepant showed safety and efficacy in migraine treatment according to various parameters throughout the six included studies. These parameters include adverse events, pharmacokinetic properties, CGRP inhibition, effect on blood pressure/electrocardiogram, pain freedom, and freedom from most bothersome symptoms.

Enhancing Radiation Safety Culture: Investigating the Mediating Role of Awareness Among Orthopedic Doctors and Operation Theatre Assistants.

INTRODUCTION: The increasing use of minimally invasive orthopedic procedures has led to a greater reliance on fluoroscopy, resulting in elevated radiation exposure for surgeons. This study aimed to evaluate the knowledge, awareness, and daily practices of orthopedic surgeons regarding radiation safety in an academic hospital. Understanding radiation safety is crucial to minimize patient exposure and prevent adverse effects on surgeons. METHODS: This cross-sectional study was conducted at the Department of Orthopedics of different tertiary care hospitals in Rawalpindi, Pakistan. Data were collected prospectively for two years, and a total of 505 participants, including residents, consultants, and operation theatre assistants, completed a questionnaire. The questionnaire was validated by experts and covered information on fluoroscopy usage, frequency of surgeries, awareness of radiation safety, and protective measures. Ethical approval was obtained, and data were analyzed using SPSS version 26.0. RESULTS: The majority of participants were male (74.1%), and the sample included various ranks of orthopedic surgeons. Only 56.2% of participants were aware of the usage of fluoroscopy, and 40.2% had read some research on the topic. While 44.6% used lead aprons for radiation protection, the usage of other protective measures and dosimeters was limited. The mediation analysis showed an insignificant indirect association between the rank of orthopedic surgeons, number of surgeries performed, and fluoroscopy usage as a mediator. Awareness and reading research on fluoroscopy were significantly associated with radiation protection. CONCLUSION: The knowledge, awareness, and daily practices of orthopedic surgeons regarding radiation safety in fluoroscopy use need improvement. The findings emphasize the importance of implementing training programs, providing radiation protection devices, and ensuring compliance with safety guidelines.

MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis.

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

The relationship between knowledge, attitude, and practice of plasma donation with age and gender as moderators: a cross-sectional survey.

Convalescent plasma therapy has gained worldwide notoriety since its inception as a form of soul treatment for terminally ill patients. This study investigates the link between knowledge, attitude, and practice of plasma donation while simultaneously probing the moderative role of age and gender in this context. Method: A cross-sectional study was undertaken in Rawalpindi, Pakistan, on COVID-19-recovered patients (coronavirus disease 2019). In all, 383 persons were chosen using simple random sampling. A prestructured questionnaire was first validated and then used as a tool for data collection. jMetrik version 4.1.1 and SPSS version 26 were used to enter and analyze the data. Reliability analysis, hierarchal regression, and logistic regression analysis were applied. Results: A total of 85.1% and 58.2% of 383 individuals had a favorable attitude and sufficient knowledge toward plasma donation, respectively. Plasma donation was observed in 109 (28.5%) of the individuals. Plasma donation practice was shown to be strongly related to plasma donation attitude [adjusted odds ratio (AOR)=4.48; P<0.05] and knowledge (AOR=3.78; P<0.001). Females who had more plasma donation knowledge and attitude tend to donate more compared to males. However, no interactional effect of gender×knowledge and attitude, and age×knowledge and attitude was found with plasma donation practice. Conclusion: Plasma donation was uncommon, even though the majority of individuals had a good mindset and were well-informed. Fear of getting a health problem was linked to the decreased practice.

Granulocyte colony-stimulating factor does not improve mortality in severe alcoholic hepatitis: a single-center experience from the United States.

Aim: To assess the role of granulocyte colony-stimulating factor (GCSF) in the patients with severe alcoholic hepatitis (SAH) using real world experience in the United States. Background: There are few effective treatments for severe alcoholic hepatitis, which has a significant fatality rate. GCSF has been associated with improved survival in a small number of Indian studies, while there is a dearth of information from other parts of the globe. Methods: We performed a single-center retrospective study of consecutive patients admitted to a tertiary care, liver transplant center with severe alcoholic hepatitis from May 2015 to February 2019. The patients receiving GCSF (5µg/kg subcutaneously every 12 hours for 5 consecutive days) (n=12) were compared to the patients receiving standard of care (n=42). Results: Thirty-day, 90-day and 1-year mortality rates was similar among groups (25% vs. 17%, P=0.58; 41% vs 29%, P=0.30; 41% vs 47%, P=0.44, respectively). There was no difference in liver transplant listing and orthotopic transplantation among groups. Conclusion: In this real-world, United States-based study, GCSF does not improved survival in the patient with several alcoholic hepatitis compared to standard of care.

Pattern of neurosurgical cases and procedures in Gilgit Baltistan: two-year experience at a newly established neurosurgical department.

BACKGROUND: In Pakistan, there are a total of 160 neurosurgeons that constitute a ratio of one neurosurgeon for a 5.5 million population. Gilgit Baltistan being a backward region does not have a single tertiary care facility. A new department of neurosurgery was established at Regional Headquarter City Hospital (RHQ) Gilgit with only one neurosurgeon. This study aimed to determine which neurosurgical diagnoses are common and which surgical interventions were performed at RHQ. METHODS: This is a retrospective cross-sectional study conducted at Regional Headquarter Hospital (RHQ) Gilgit in which data of patients operated for neurosurgical diseases between January 2020 and January 2022 was collected from patient record books. RESULTS: Of the total of 223 patients, 148 (66.3%) were males and 75 (33.6%) were females. A total of 92(41.2%) belonged to the pediatric age group. The top most diagnosis included Neurotrauma (46.6%), NTDs (13.9%) and CSDH (10.3%) while the most routinely performed procedures were craniotomy & hematoma evacuation (22.9%), debridement & elevation of DSF (20.6%), and burrhole evacuation (13.9%). In the pediatric age group, the top diagnosis was Neurotrauma (43.5%), NTDs (32.6%), and Hydrocephalus (19.6%) while in adults, neurotrauma (48.9%) was the leading diagnosis followed by CSDH (17.6%). In the pediatric age group, repair of NTDs (32.6%) was the most frequently performed procedure. CONCLUSION: This study shows different kinds of neurosurgical cases but because of a lack of diagnostic and therapeutic facilities, very limited operations were performed and many cases were referred to metropolitan cities. The hospitals in the region need further up-gradation to cater to the presenting burden.

Epidemiological Comparison of Anorectal Malformation With Other Gastrointestinal Abnormalities in Patients in the Pediatric Ward.

Background Anorectal malformations are congenital defects wherein there is defective development of the anus and rectum. For babies born with congenital anorectal malformations, prompt treatment is crucial which requires detection of the anomalies at the earliest. This study aimed to determine the epidemiology ofanorectal malformations in the Pediatric Unit of a tertiary care hospital in Pakistan over a period of 19 months. Methodology An analytical cross-sectional study was conducted retrospectively from January 2020 to September 2021 using a non-randomized consecutive sampling technique. Patients aged less than eight years were included, whereas burnt, torn, and incomplete records from the Hospital Management Information System (HMIS) were excluded. SPSS version 26 (IBM Corp., Armonk, NY, USA) was used for data entry and analysis. Binomial and multinomial logistic regression were applied for analyzing the association between explanatory and dependent variables. Results Of the 1,108 patients, 72 (6.5%) patients had anorectal malformations. Gastrointestinal diseases made up about 64.3% of all diseases. Among gastrointestinal causes, the prevalence of anorectal malformation was up to 10.1%. The mortality of anorectal malformation patients was low (2.85%) compared to mortalities due to other gastrointestinal abnormalities (8.25%). Anorectal malformation had significantly lower odds of mortality (adjusted odds ratio = 0.19, p < 0.05) compared to other gastrointestinal abnormalities. Conclusions This study has provided data about the prevalence of anorectal malformation and its mortality which were calculated as 6.5% and 2.58%, respectively. Female gender, neonates, and delayed presentation were seen to have higher mortality, highlighting the need to screen all neonates pre- and post-natally to avoid any misdiagnosis.

Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study.

BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).