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/.

A Case Reported With 46, XX Testicular Disorders Of Sexual Development And Its Possible Association With Dysembryoplastic Neuroepithelial Tumour.

The main factor determining differentiation of bipotential gonads into testes or ovaries is the presence or absence of SRY (sex-determining region on Y chromosome) gene. De la Chapelle syndrome is a chromosomal anomaly with chromosomal makeup of a female (46, XX) and phenotypic presentation of a male. Previously known as XX sex reversal, it is now called 46, XX testicular disorders of sexual development (DSD). Although rare, it presents as a major chromosomal anomaly, with SRY gene crossover proposed as an underlying aetiology in most patients. We report the case of a 25-year-old male who presented with infertility and was diagnosed with De 46, XX testicular DSD. He has a previous history of resected dysembryoplastic neuroepithelial tumour (DNT). The differential diagnosis of 46, XX DSD and possible association/coincidental finding of DNT have been discussed. Karyotyping should be a part of the workup for every patient who presents with infertility and has azoospermia and hypergonadotropic hypogonadism.

Unlocking Insights in IoT-Based Patient Monitoring: Methods for Encompassing Large-Data Challenges.

The remote monitoring of patients using the internet of things (IoT) is essential for ensuring continuous observation, improving healthcare, and decreasing the associated costs (i.e., reducing hospital admissions and emergency visits). There has been much emphasis on developing methods and approaches for remote patient monitoring using IoT. Most existing frameworks cover parts or sub-parts of the overall system but fail to provide a detailed and well-integrated model that covers different layers. The leverage of remote monitoring tools and their coupling with health services requires an architecture that handles data flow and enables significant interventions. This paper proposes a cloud-based patient monitoring model that enables IoT-generated data collection, storage, processing, and visualization. The system has three main parts: sensing (IoT-enabled data collection), network (processing functions and storage), and application (interface for health workers and caretakers). In order to handle the large IoT data, the sensing module employs filtering and variable sampling. This pre-processing helps reduce the data received from IoT devices and enables the observation of four times more patients compared to not using edge processing. We also discuss the flow of data and processing, thus enabling the deployment of data visualization services and intelligent applications.

Sample size reestimation and Bayesian predictive probability for single-arm clinical trials with a time-to-event endpoint using Weibull distribution with unknown shape parameter.

This manuscript consists of two topics. Firstly, we explore the utility of internal pilot study (IPS) approach for reestimating sample size at an interim stage when a reliable estimate of the nuisance shape parameter of the Weibull distribution for modeling survival data is unavailable during the planning phase of a study. Although IPS approach can help rescue the study power, it is noted that the adjusted sample size can be as much as twice the initially planned sample size, which may put substantial practical constraints to continue the study. Secondly, we discuss Bayesian predictive probability for conducting interim analyses to obtain preliminary evidence of efficacy or futility of an experimental treatment warranting early termination of a clinical trial. In the context of single-arm clinical trials with time-to-event endpoints following Weibull distribution, we present the calculation of the Bayesian predictive probability when the shape parameter of the Weibull distribution is unknown. Based on the data accumulated at the interim, we propose two approaches which rely on the posterior mode or the entire posterior distribution of the shape parameter. To account for uncertainty in the shape parameter, it is recommended to incorporate its entire posterior distribution in our calculation.

Non-Resolving Perihepatic Abscess Following Spilled Gallstones Requiring Surgical Management.

INTRODUCTION: Laparoscopic cholecystectomy (LC) is the treatment of choice for symptomatic cholelithiasis and is among the most frequently done procedures in United States. Spillage of gallstones occurs in up to 30 percent of these procedures and is associated with rare but important complications including abscess formation. CASE DESCRIPTION: We present a case of 44-year-old man with a peri-hepatic abscess developed three years after a laparoscopic cholecystectomy. Multiple percutaneous drainages and antibiotic courses had failed to provide a definitive resolution. CT scan showed signs of a developing abscess but no stones. A diagnostic laparoscopy was performed, and multiple retained stones were visualized. It was converted to open laparotomy and the abscess was drained along with resection of portions of liver and diaphragm. The patient remained vitally stable with no fever spikes following the procedure. DISCUSSION: Spillage of gallstones should be seriously considered in all patients presenting with peri-hepatic abscess with a history of previous LC, even if the imaging studies do not provide evidence of stones. Percutaneous drainage and antibiotics may provide temporary relief, but a surgical intervention is often the definitive management.

COPD Assessment Test: A Review of Extant Literature.

Chronic obstructive pulmonary disease (COPD) is a major health burden worldwide. Reasons for poor management include lack of awareness regarding COPD among healthcare providers and patients, insufficient use of diagnostic tests (such as spirometry), poor treatment decisions. Another major issue is poor doctor-patient communication which can lead to inaccurate assessment of a patient's clinical picture. The COPD Assessment Test (CAT) is a clinical tool which provides a quantitative measure of the severity of a patient's symptoms and their pulmonary health status. It is a brief patient-filled questionnaire that only takes a few minutes to fill out. This has the potential to help bridge deficiencies in the clinical history that may be left by any communication gap between the patient and the physician. Various studies have investigated the effectiveness of CAT in clinical settings. Herein we review these studies to examine the sensitivity, validity and reliability of the CAT as a clinical diagnostic and assessment tool in light of the existing literature.

High-risk liver transplant recipients with grade 3 acute on chronic liver failure should receive the good quality graft.

BACKGROUND & AIM: We aimed to develop a risk score for LT recipients and donor selection among patients with ACLF-3. METHODS AND RESULTS: A total of 7166 adult LT recipients (mean age 53 years, 63% males, 56% Caucasians, 42% obese, median MELD score 36.5) using deceased donor grafts in the UNOS database (01/2002-06/2018) who were in ACLF-3 at LT as per EASL-CLIF criteria were analysed. Cox regression model on the derivation dataset (N = 3583) showed recipient age, non-alcohol aetiology, pulmonary failure, brain failure and cardiovascular failure to be associated with 1-year patient survival. Observed and expected post-transplant 1-year survival showed excellent correlation (R = .920). Risk score from cox model on derivation dataset stratified 3583 recipients in validation cohort using cut-off scores 7.55 and 11.57 to low (N = 1211), medium (N = 1168) and high risk (N = 1199), with 1-year patient survival of 89%, 82% and 80% respectively. Based on poor versus good quality graft (donor risk index cut-off at 1.50), 1-year patient survival for low, medium and high-risk categories were 90 versus 89% (p = .490), 83 versus 82% (p = .390) and 83 versus 78% (p = .038) respectively. Among recipients with a high-risk score, donor factors of age ≥60 years, grafts obtained from national sharing and macro-steatosis >15% were associated with 1-year patient survival below 66%. CONCLUSION: Among ACLF-3 liver transplant recipients, those with high risk at the time of transplant receiving better quality graft will improve post-transplant outcomes. Prospective studies using additional characteristics are needed to derive an accurate risk score model in predicting post-transplant outcomes among recipients with ACLF-3.

Terminal Ileitis as the Presenting Feature of Henoch-Schönlein Purpura in a 22-Year-Old Male.

Henoch-Schönlein purpura (HSP) is a self-limited vasculitis that affects children and the preadolescent population. It is characterized by the deposition of immunoglobulin A immune complexes in tissues leading to palpable purpura, abdominal pain, arthritis, and nephropathy. When it occurs in adults, the clinical manifestations are the same; however, adults present with more significant renal involvement. While abdominal pain is the most common gastrointestinal (GI) manifestation, it can also present with GI bleeding, intussusception, bowel ischemia, and bowel perforation. Here, we report the case of a 22-year-old gentleman who presented with nonspecific GI complaints such as nausea, vomiting, and loose stools. He was later found to have terminal ileitis preceding the onset of rash, the biopsy of which confirmed HSP. Terminal ileitis is a rare GI manifestation of HSP and is not very commonly reported in the literature.

Energy Conservation for Internet of Things Tracking Applications Using Deep Reinforcement Learning.

The Internet of Things (IoT)-based target tracking system is required for applications such as smart farm, smart factory, and smart city where many sensor devices are jointly connected to collect the moving target positions. Each sensor device continuously runs on battery-operated power, consuming energy while perceiving target information in a particular environment. To reduce sensor device energy consumption in real-time IoT tracking applications, many traditional methods such as clustering, information-driven, and other approaches have previously been utilized to select the best sensor. However, applying machine learning methods, particularly deep reinforcement learning (Deep RL), to address the problem of sensor selection in tracking applications is quite demanding because of the limited sensor node battery lifetime. In this study, we proposed a long short-term memory deep Q-network (DQN)-based Deep RL target tracking model to overcome the problem of energy consumption in IoT target applications. The proposed method is utilized to select the energy-efficient best sensor while tracking the target. The best sensor is defined by the minimum distance function (i.e., derived as the state), which leads to lower energy consumption. The simulation results show favorable features in terms of the best sensor selection and energy consumption.

Quantum-enhanced nonlinear microscopy.

The performance of light microscopes is limited by the stochastic nature of light, which exists in discrete packets of energy known as photons. Randomness in the times that photons are detected introduces shot noise, which fundamentally constrains sensitivity, resolution and speed1. Although the long-established solution to this problem is to increase the intensity of the illumination light, this is not always possible when investigating living systems, because bright lasers can severely disturb biological processes2-4. Theory predicts that biological imaging may be improved without increasing light intensity by using quantum photon correlations1,5. Here we experimentally show that quantum correlations allow a signal-to-noise ratio beyond the photodamage limit of conventional microscopy. Our microscope is a coherent Raman microscope that offers subwavelength resolution and incorporates bright quantum correlated illumination. The correlations allow imaging of molecular bonds within a cell with a 35 per cent improved signal-to-noise ratio compared with conventional microscopy, corresponding to a 14 per cent improvement in concentration sensitivity. This enables the observation of biological structures that would not otherwise be resolved. Coherent Raman microscopes allow highly selective biomolecular fingerprinting in unlabelled specimens6,7, but photodamage is a major roadblock for many applications8,9. By showing that the photodamage limit can be overcome, our work will enable order-of-magnitude improvements in the signal-to-noise ratio and the imaging speed.

Some design considerations incorporating early futility for single-arm clinical trials with time-to-event primary endpoints using Weibull distribution.

Sample size calculation is an essential component of the planning phase of a clinical trial. In the context of single-arm clinical trials with time-to-event (TTE) endpoints, only a few options with limited design features are available. Motivated from ethical or practical considerations, two-stage designs are implemented for single-arm studies to obtain early evidence of futility. A major drawback of such designs is that early stopping may only occur at the conclusion of the first stage, even if lack of efficacy becomes apparent at any other time point over the course of the clinical trial. In this manuscript, we attempt to fill some existing gaps in the literature related to single-arm clinical trials with TTE endpoints. We propose a parametric maximum likelihood estimate-based test whose variance component accounts for the expected proportion of loss to follow-up and different accrual patterns (early, late, or uniform accrual). For the proposed method, we present three stochastic curtailment methods (conditional power, predictive power, Bayesian predictive probability) which can be employed for efficacy or futility testing purposes. Finally, we discuss the implementation of group sequential designs for obtaining an early evidence of efficacy or futility at pre-planned timings of interim analyses. Through extensive simulations, it is shown that our proposed method performs well for designing these studies with moderate to large sample sizes. Some examples are presented to demonstrate various aspects of the stochastic curtailment and repeated significance testing methods presented in this manuscript.

Higher Frequency of Hospital-Acquired Infections but Similar In-Hospital Mortality Among Admissions With Alcoholic Hepatitis at Academic vs. Non-academic Centers.

BACKGROUND: Alcoholic hepatitis (AH) is a unique syndrome characterized by high short-term mortality. The impact of the academic status of a hospital (urban and teaching) on outcomes in AH is unknown. METHODS: National Inpatient Sample dataset (2006-2014) on AH admissions stratified to academic center (AC) or non-academic center (NAC) and analyzed for in-hospital mortality (IHM), hospital resource use, length of stay in days (d), and total charges (TC) in United States dollars (USD). Admission year was stratified to 2006-2008 (TMI), 2009-2011 (TM2), and 2012-2014 (TM3). RESULTS: Of 62,136 AH admissions, the proportion at AC increased from 46% in TM1 to 57% in TM3, Armitage trend, p < 0.001. On logistic regression, TM3, younger age, black race, Medicaid and private insurance, and development of acute on chronic liver failure (ACLF) were associated with admission to an AC. Of 53,264 admissions propensity score matched for demographics, pay status, and disease severity, admissions to AC vs. NAC (26,622 each) were more likely to have liver disease complications (esophageal varices, ascites, and hepatic encephalopathy) and hospital-acquired infections (HAI), especially Clostridioides difficile and ventilator-associated pneumonia. Admissions to AC were more likely transfers from outside hospital (1.6% vs. 1.3%) and seen by palliative care (4.8% vs. 3.3%), p < 0.001. Use of endoscopy, dialysis, and mechanical ventilation were similar. With similar IHM comparing AC vs. NAC (7.7% vs. 7.8%, p = 0.93), average LOS and number of procedures were higher at AC (7.7 vs. 7.1 d and 2.3 vs. 1.9, respectively, p < 0.001) without difference on total charges ($52,821 vs. $52,067 USD, p = 0.28). On multivariable logistic regression model after controlling for demographics, ACLF grade, and calendar year, IHM was similar irrespective of academic status of the hospital, HR (95% CI): 1.01 (0.93-1.08, p = 0.70). IHM decreased over time, with ACLF as strongest predictor. A total of 63 and 22% were discharged to home and skilled nursing facility, respectively, without differences on academic status of the hospital. CONCLUSION: Admissions with AH to AC compared to NAC have higher frequency of liver disease complications and HAI, with longer duration of hospitalization. Prospective studies are needed to reduce HAI among hospitalized patients with AH.

Systematic review with meta-analysis: liver transplant provides survival benefit in patients with acute on chronic liver failure.

BACKGROUND: Data on liver transplantation (LT) in acute on chronic liver failure (ACLF) are scanty. AIM: To perform meta-analysis on outcomes after LT for ACLF compared with ACLF patients not receiving LT or with LT recipients for indications other than ACLF. METHODS: We pooled data from 12 studies on LT outcomes among ACLF patients. RESULTS: Among nine studies, 22 238 LT recipients for ACLF vs 30 791 for non-ACLF were younger by 1.1 years, less males (64% vs 66.4%), and higher model for end-stage disease score by 14.5 (14.4-14.6), P < 0.01 for all. Post-transplant patient survival at 30 day, 90 day, 6 months, 1 year and 5 years was lower in ACLF: 96.2% vs 98.1%, 92.6% vs 96.2%, 89.9% vs 94.4%, 86.0% vs 91.9%, 66.9% vs 80.7% respectively, P < 0.01 for all. ACLF patients stayed longer in hospital and ICU by 5.7 and 10.5 days respectively, P < 0.001, with similar post-transplant complications [74.4% vs 55.5%, P = 0.12]. Among three studies, 441 LT recipients for ACLF vs 301 ACLF patients not selected for LT had better 30 day and 1 year survival: 95.2% vs 60% and 85.3% vs 28.2% respectively, P < 0.001. Outcomes were worse in ACLF-3 and better for ACLF-1 and ACLF-2 patients at the time of LT. CONCLUSION: In this pooled analysis with a large sample size across the globe, LT for select patients with ACLF provided survival benefit. However, larger prospective studies are needed to further refine selection criteria, especially for ACLF-3 patients as basis for improving outcomes and optimal utilisation of scarce donor pool.

Identification of irrigation potential areas, using multi-criteria analysis in Khyber District, Pakistan.

This study explores the opportunities for irrigated agriculture in Khyber District of Former Federally Administered Tribal Area (FATA). Agriculture continues to be most important economic activity in Pakistan and former FATA is no exception. However, agriculture in the semi-arid Khyber District continues to suffer a decline due to excessive reliance on rainfall, which is drastically insufficient. Khyber District have large expanses of fertile land; however, farmers depend on unpredictable rain-fed agriculture, which has low productivity and food insecurity. There are a number of rivers in the region where great prospects exist for irrigated farming. Geographical information systems (GIS)-based multi-criteria analysis can be used to map areas with irrigation potential. The current study focused on different variables including soil texture, perennial rivers, land cover, topography, and dams. For this study, data was collected from diverse sources which include Google earth images, top sheets, land use land cover, soil texture map of FATA, and SRTM 30 Meter. The collected data was analyzed by using multi-criteria analysis in Arc GIS 10.2.2 by using MIF technique. The results of this research indicate that there is great potential for irrigated farming in the study area. Potential land for this purpose were divided into three categories, i.e., highly suitable which consisted of 678 km2, or 26% of the total area; 1044 km2 representing 40% were moderately suitable to irrigation; while the remaining 698 km2 representing 27% were considered least suitable for irrigation. Likewise, 204 km2 representing 7% were deemed unsuitable for irrigated agriculture mostly consisting of barren rocks. The results also illustrate how GIS as a tool can be used in the exploration of water resources in a scientific approach, thus making decision-making easier and more accurate.

Solitary Endobronchial Papilloma: A Rare Entity.

Solitary papillomas of the lower airways are uncommon clinical entities that present a diagnostic challenge because they are not usually considered among the differential diagnoses. Reliable clinical data about their presentation and treatment remain scarce. We describe a case of an elderly male who presented to us with cough and hemoptysis. He had been a smoker for 50 years. Chest radiograph revealed hyperinflated lungs and slight hilar enlargement on the right side. Bronchoscopy revealed a polypoid mass at the origin of the right upper lobe bronchus. Biopsy showed it to be a papillomatous growth composed of squamous epithelial cells. No malignant cells were detected microscopically. Patient declined surgical removal of this papilloma. He was fine on followup visits during the subsequent months. In patients with hemoptysis, solitary endobronchial papilloma should also be considered in the differential diagnosis.

Xanthogranulomatous Pyelonephritis: Synchronous Upper and Lower Gastrointestinal Bleed.

Xanthogranulomatous pyelonephritis (XGP) is a rare chronic granulomatous destructive process of the renal parenchyma. It is caused by a chronic inflammatory process due to recurrent urinary tract infections and/or obstructing renal calculi. Rarely, it presents with advanced complications including abscesses and fistula formations. In this article, we report a unique presentation of XGP with simultaneous upper and lower gastrointestinal bleeding in the setting of XGP with reno-gastric and reno-colic fistulas.

Serum Apo A-1 and Its Role as a Biomarker of Coronary Artery Disease.

OBJECTIVES: To evaluate the role of apolipoprotein(Apo A-1) as a biomarker of coronary artery disease (CAD) and its comparison with the traditional marker high-density lipoprotein (HDL). METHODOLOGY: One hundred patients proven to have coronary artery disease by angiography were recruited and their serum biomarkers were compared with 100 normal individuals adjusted for age and sex. RESULT: The mean +/-standard deviation (SD) value of plasma Apo A-1 levels in the normal individuals were observed to be 207.42 +/- 41.35 (mg/dL) against 90.69 +/- 20.77 (mg/dL) in the cardiac patients. On the other hand the serum HDL levels were 52.93 +/-33.58 (mg/dL) in the normal individuals and 37.86 +/- 23.19 (mg/dL) in the cardiac patients. Both of these differences were statistically significant (p < 0.001). For Apo A-1, a large proportion of patients (85%) were found to be in the abnormal range when compared to the control group in which only 7% had an abnormal value. For HDL, a majority (70%) of the cardiac patients had abnormal values while 40% of the normal individuals also had abnormal values. The sensitivity of Apo A-1 for detecting CAD was 85%, while for HDL, it was only 69%. Similarly, the specificity of Apo A-1 for detecting CAD was 93%, while for HDL, it was 60%. When plotted on a receiver operating characteristic (ROC) curve, Apo A-1 had a much larger area under the curve when compared to HDL. CONCLUSION: This study suggests that Apo A-1 may, in fact, be more sensitive than HDL as a predictor of CAD. However, to completely elucidate its role as a biomarker, to set target serum levels and to increase its clinical use, further studies are required.

Single-cell optoporation and transfection using femtosecond laser and optical tweezers.

In this paper, we demonstrate a new single-cell optoporation and transfection technique using a femtosecond Gaussian laser beam and optical tweezers. Tightly focused near-infrared (NIR) femtosecond laser pulse was employed to transiently perforate the cellular membrane at a single point in MCF-7 cancer cells. A distinct technique was developed by trapping the microparticle using optical tweezers to focus the femtosecond laser precisely on the cell membrane to puncture it. Subsequently, an external gene was introduced in the cell by trapping and inserting the same plasmid-coated microparticle into the optoporated cell using optical tweezers. Various experimental parameters such as femtosecond laser exposure power, exposure time, puncture hole size, exact focusing of the femtosecond laser on the cell membrane, and cell healing time were closely analyzed to create the optimal conditions for cell viability. Following the insertion of plasmid-coated microparticles in the cell, the targeted cells exhibited green fluorescent protein (GFP) under the fluorescent microscope, hence confirming successful transfection into the cell. This new optoporation and transfection technique maximizes the level of selectivity and control over the targeted cell, and this may be a breakthrough method through which to induce controllable genetic changes in the cell.