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Acute gastrointestinal (GI) bleed is a common reason for hospitalization with 2%-10% risk of mortality. In this study, we developed a machine learning (ML) model to calculate the risk of mortality in intensive care unit patients admitted for GI bleed and compared it with APACHE IVa risk score. We used explainable ML methods to provide insight into the model's prediction and outcome. We analyzed the patient data in the Electronic Intensive Care Unit Collaborative Research Database and extracted data for 5,691 patients (mean age = 67.4 years; 61% men) admitted with GI bleed. The data were used in training a ML model to identify patients who died in the intensive care unit. We compared the predictive performance of the ML model with the APACHE IVa risk score. Performance was measured by area under receiver operating characteristic curve (AUC) analysis. This study also used explainable ML methods to provide insights into the model's outcome or prediction using the SHAP (SHapley Additive exPlanations) method. The ML model performed better than the APACHE IVa risk score in correctly classifying the low-risk patients. The ML model had a specificity of 27% (95% confidence interval [CI]: 25-36) at a sensitivity of 100% compared with the APACHE IVa score, which had a specificity of 4% (95% CI: 3-31) at a sensitivity of 100%. The model identified patients who died with an AUC of 0.85 (95% CI: 0.80-0.90) in the internal validation set, whereas the APACHE IVa clinical scoring systems identified patients who died with AUC values of 0.80 (95% CI: 0.73-0.86) with P value <0.001. We developed a ML model that predicts the mortality in patients with GI bleed with a greater accuracy than the current scoring system. By making the ML model explainable, clinicians would be able to better understand the reasoning behind the outcome.

INTRODUCTION:Community-acquired Clostridium difficile infection (CA-CDI) is defined as Clostridium difficile infection (CDI) in patients who have not been in inpatient setting within 90 days of being tested positive for Clostridium difficile. The incidence of CA-CDI has been increasing in young individuals with no co-morbidities or recent antibiotic exposure. Recent research shows that up to 40% patients with CA-CDI need hospitalization, however, the risk factors associated with hospitalization of patients who test positive for CDI in outpatient setting has not been studied. The goal of this study is to look at patients diagnosed with CDI initially as outpatients and analyze the risk factors associated with hospitalization in these patients.METHODS:This study was approved by the Institutional Review Board. This is a retrospective chart review of 524 patients (189 males, 335 females, mean age 60 years) who were seen in the outpatient department from 2015 to 2018 and were tested for CDI. Inclusion criteria was patients over the age of 18 with positive C. difficile by nucleic acid amplification tests (NAATs). Exclusion criteria was prior diagnosis of C. difficile. For patients with positive C. difficile, the two outcomes selected were hospital admission within 2 weeks, and those remaining outpatients. The variables extracted from the electronic medical record included demographics, medications and co-morbidities. Utilizing a machine-learning algorithm, a Bayesian probabilistic predictive tool was constructed that evaluated a series of variables and their association with potential outcomes.RESULTS:Of the 524 patients that tested positive, 105 patients required admission within two weeks of diagnosis. The incidence of hospitalization among males and females was not significantly different. There was significant association between use of acid suppression medications (pantoprazole and famotidine) and risk of hospitalization for C. difficile (P-value <0.0001 and 0.002 for pantoprazole and famotidine, respectively). There was no association seen between co-morbidities such as coronary or carotid artery disease, peripheral vascular disease, diabetes mellitus and the risk of hospitalization.CONCLUSION:Although PPIs have been associated with increased risk of developing CDI, our study shows that acid suppression medications may also increase the risk of hospitalization for CDI. Providers should consider the risk versus benefit of continued use of acid suppression medications in patients with CDI.

INTRODUCTION:Gastroduodenal fistula (GDF) or double pylorus is a rare, often asymptomatic, condition with a prevalence of approximately 0.02-0.08%. The majority of previously reported cases have been in Asian countries and it has been found to be more prevalent in males than females. Although Helicobacter pylori and NSAID use has been associated with the formation of gastroduodenal fistulae, the actual mechanism of the condition is unknown.CASE DESCRIPTION/METHODS:We present the case of a 65-year old female with alcoholic cirrhosis and a long history of intractable vomiting due to unknown etiology. She was found to have a pre-pyloric gastric antral ulcer during an emergent endoscopy for an episode of hematemesis seven years ago. Follow up endoscopies over a course of three years found the antral ulcer to be healing. Seven years from the discovery of the initial lesion, a gastroduodenal fistula was found. The pre-pyloric antral ulcer in the process of healing fistulized into the duodenal bulb creating the appearance of a double pylorus.DISCUSSION:Gastroduodenal fistula or double pylorus can be acquired or congenital. Acquired GDF is a very rare complication of peptic ulcer disease. They can be a result of healing due to bridging fibrosis within the pylorus or, as in this case, fistulization from the gastric antral ulcer. Most GDF are found incidentally during endoscopy that was done for another reason. This case report follows the serial endoscopic examination of a cirrhotic patient with a pre-pyloric antral ulcer that developed into GDF. We propose that the GDF was caused by fistulization of a pre-pyloric antral ulcer with no other predisposing factors and gastrointestinal fistulization processes.

A line-field confocal optical coherence tomography (LC-OCT) combines confocal microscopy and optical coherence tomography into a single, rapid, easy-to-use device. This meta-analysis was performed to determine the reliability of LC-OCT for diagnosing malignant skin tumors. PubMed, EMBASE, Web of Science databases, and the Cochrane Library were searched for research studies in the English language from inception till December 2023. To assess quality and the risk of bias, the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. The sensitivity and specificity of each study were calculated. The bivariate summary sensitivity and specificity were calculated using the linear mixed model. Five studies with 904 reported per lesion analyses in our study; the specificity and sensitivity ranged from 67% to 97% and 72% to 92%, respectively. The pooled specificity and sensitivity were 91% (95% CI: 76–97%) and 86.9% (95% CI: 81.8–90.8%), respectively. The summary sensitivity and specificity from the bivariate approach are 86.9% (95% CI: 81.8–90.8%) and 91.1% (95% CI: 76.7–97.0%), respectively. The area under the curve is 0.914. LC-OCT shows great sensitivity and specificity in diagnosing malignant skin tumors. However, due to the limited number of studies included in our meta-analysis, it is premature to elucidate the true potential of LC-OCT.

Context Obesity‐related mortality in the United States has increased substantially over recent decades, yet long‐term national trends and demographic disparities remain incompletely characterized. Objective To evaluate nationwide trends in obesity‐related mortality among U.S. adults and identify disparities by age, sex, race, and geographic region from 1968 to 2025. Methods We performed a retrospective analysis using CDC WONDER mortality data from 1968 to 2025 (nearly six decades). Adults aged ≥ 25 years with obesity identified using International Classification of Diseases (ICD) codes listed as an underlying or contributing cause of death were included. Age‐adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population, and temporal trends were evaluated using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Results From 1968 to 2025, a total of 211,479 obesity‐related deaths were recorded among U.S. adults aged ≥ 25 years. AAMRs increased from 1.15 to 3.32 per 100,000, peaking in 2021 (4.54 per 100,000). Mortality rates were consistently higher among males, older adults, Black populations, and residents of the Southern United States, while younger adults (25–44 years) experienced the most rapid rise in mortality. Conclusion Obesity‐related mortality in the United States has more than tripled over nearly six decades, with substantial demographic and geographic disparities. These findings highlight the urgent need for targeted, culturally tailored, and age‐specific public health interventions to address the growing burden of obesity.

Adam Shlien, Peter Campbell, Uri Tabori and colleagues report genome and exome sequencing of biallelic mismatch repair deficiency cancer samples from 12 children, including 10 high-grade gliomas. The hypermutational signature of the malignant glioma samples was consistent with a driver role for observed mutations in DNA polymerases ɛ or δ. DNA replication−associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutation consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD). High-grade bMMRD brain tumors exhibited massive numbers of substitution mutations (>250/Mb), which was greater than all childhood and most cancers (>7,000 analyzed). All ultra-hypermutated bMMRD cancers acquired early somatic driver mutations in DNA polymerase ɛ or δ. The ensuing mutation signatures and numbers are unique and diagnostic of childhood germ-line bMMRD ( P < 10 −13 ). Sequential tumor biopsy analysis revealed that bMMRD/polymerase-mutant cancers rapidly amass an excess of simultaneous mutations (∼600 mutations/cell division), reaching but not exceeding ∼20,000 exonic mutations in <6 months. This implies a threshold compatible with cancer-cell survival. We suggest a new mechanism of cancer progression in which mutations develop in a rapid burst after ablation of replication repair.

Background Atrial fibrillation (AF) among patients with heart failure with reduced ejection fraction (HFrEF) is associated with adverse clinical outcomes. Our primary aim was to evaluate patient‐centered outcomes and surrogate outcomes following catheter ablation (CA) of AF among patients with HFrEF compared to standard medical therapy with or without device therapy (atrioventricular node ablation and cardiac resynchronization therapy). Methods A systematic literature review was performed limiting our searches to randomized control trials reporting outcomes of CA compared to standard medical therapy with or without device therapy were included. Patient‐centered outcomes were relative reduction in all‐cause mortality, heart failure readmissions, and recurrence of AF. Surrogate outcomes of interest were change in ejection fraction, change in peak oxygen consumption, reduction in brain natriuretic peptide levels, change in 6‐minute walk distance, and change in Minnesota living with heart failure score. Results Seven randomized control trials (Patient n = 721) met our inclusion criteria. All trials used radiofrequency energy for CA of AF. CA for AF was associated with significantly lower all‐cause mortality (Risk ratio [RR] = 0.52, 95% confidence interval [CI] = 0.35‐0.76, P = 0.001, I2 = 0%), lower rate of heart failure readmission (RR = 0.58, 95% CI = 0.46‐0.74, P < 0.001, I2 = 0%) and lower rate of AF recurrence (RR = 0.33, 95% CI = 0.22‐0.50, P < 0.001, I2 = 68%) as compared to standard medical therapy. Surrogate outcomes showed a similar benefit favoring CA. Conclusion and Relevance Catheter ablation for AF in HFrEF is associated with improvement in patient‐centered outcomes and surrogate outcomes when compared to standard medical therapy with or without device therapy.