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AbstractBackground and AimPatients with intestinal failure (IF) have abnormal intestinal anatomy, secretion, and dysmotility, which impairs intestinal homeostatic mechanisms and may lead to small intestinal bacterial overgrowth (SIBO). We conducted a systematic review and meta‐analysis to determine the prevalence of SIBO in patients with IF and to identify risk factors for SIBO.MethodsMEDLINE (PubMed) and Embase electronic databases were searched from inception to December 2023 for studies that reported the prevalence of SIBO in IF. The prevalence rates, odds ratio (OR), and 95% confidence intervals of SIBO in IF and the risk factors for SIBO in IF were calculated using random effects model.ResultsFinal dataset included nine studies reporting on 407 patients with IF. The prevalence of SIBO in IF was 57.5% (95% CI 44.6–69.4), with substantial heterogeneity in this analysis (I2 = 80.9, P = 0.0001). SIBO prevalence was sixfold higher in patients with IF who received parenteral nutrition (PN) compared with IF patients not on PN (OR = 6.0, 95% CI 3.0–11.9, P = 0.0001). Overall, the prevalence of SIBO in patients with IF using PPI/acid‐suppressing agents (72.0%, 95% CI 57.5–83.8) was numerically higher compared with IF patients not using these agents (47.6%, 95% CI 25.7–70.2).ConclusionsThis systematic review and meta‐analysis suggests that there is an increased risk of SIBO in patients with IF and that PN, and potentially, the use of PPI/acid‐suppressing agents is risk factors for SIBO development in patients with IF. However, the quality of evidence is low and can be attributed to lack of case–control studies and clinical heterogeneity seen in the studies.

While significant progress has been made in reducing disparities within the US health care system, notable gaps remain. This article explores existing disparities within pediatric congenital heart disease care. Congenital heart disease, the most common birth defect and a leading cause of infant death, has garnered substantial attention, revealing certain disparities within the US health care system. Factors such as race, ethnicity, insurance coverage, socioeconomic status, and geographic location are all commonalities that significantly affect health disparities in pediatric congenital heart disease. This comprehensive review sheds light on disparities from diverse perspectives in pediatric care, demonstrates the inequities and inequalities leading to these disparities, presents effective solutions, and issues a call to action for providers, institutions, and the health care system. Recognizing and addressing these disparities is imperative for ensuring equitable care and enhancing the long‐term well‐being of children affected by congenital heart disease. Implementing robust, evidence‐based frameworks that promote responsible and safe interventions is fundamental to enduring change.

Abstract Objectives The surge in patient portal messages (PPMs) with increasing needs and workloads for efficient PPM triage in healthcare settings has spurred the exploration of AI-driven solutions to streamline the healthcare workflow processes, ensuring timely responses to patients to satisfy their healthcare needs. However, there has been less focus on isolating and understanding patient primary concerns in PPMs—a practice which holds the potential to yield more nuanced insights and enhances the quality of healthcare delivery and patient-centered care. Materials and Methods We propose a fusion framework to leverage pretrained language models (LMs) with different language advantages via a Convolution Neural Network for precise identification of patient primary concerns via multi-class classification. We examined 3 traditional machine learning models, 9 BERT-based language models, 6 fusion models, and 2 ensemble models. Results The outcomes of our experimentation underscore the superior performance achieved by BERT-based models in comparison to traditional machine learning models. Remarkably, our fusion model emerges as the top-performing solution, delivering a notably improved accuracy score of 77.67 ± 2.74% and an F1 score of 74.37 ± 3.70% in macro-average. Discussion This study highlights the feasibility and effectiveness of multi-class classification for patient primary concern detection and the proposed fusion framework for enhancing primary concern detection. Conclusions The use of multi-class classification enhanced by a fusion of multiple pretrained LMs not only improves the accuracy and efficiency of patient primary concern identification in PPMs but also aids in managing the rising volume of PPMs in healthcare, ensuring critical patient communications are addressed promptly and accurately.

SummaryMetabolic and Bariatric Surgery (MBS) is effective in improving metabolic outcomes and reducing weight in patients with obesity and diabetes, with less explored benefits in type 1 diabetes (T1D). This study aimed to evaluate the impact of MBS on weight loss and insulin requirements in T1D patients compared to insulin‐treated type 2 diabetes (T2D) patients over a 5‐year period. This retrospective analysis included patients who underwent primary sleeve gastrectomy (SG) or Roux‐en‐Y gastric bypass (RYGB) with a confirmed preoperative diagnosis of either T1D or insulin‐treated T2D. Primary endpoints focusing on weight loss and secondary outcomes assessing changes in insulin dosage and glycemic control. After 5 years, weight loss was similar across groups, with total weight loss at 14.2% for T1D and 17.6% for insulin‐treated T2D in SG, and 22.6% for T1D vs. 26.8% for insulin‐treated T2D in RYGB. Additionally, there was a significant reduction in median daily insulin doses from 140.5 units at baseline to 77.5 units at 1 year postoperatively, sustained at 90 units at 5 years. The differential impact of MBS procedure was also highlighted, where RYGB patients showed a more pronounced and enduring decrease in insulin requirements compared to SG.

ObjectivesThere have been significant advances in the management of large (≥20 mm) laterally spreading tumors (LSTs) or nonpedunculated colorectal polyps; however, there is a lack of clear consensus on the management of these lesions with significant geographic variability especially between Eastern and Western paradigms. We aimed to provide an international consensus to better guide management and attempt to homogenize practices.MethodsTwo experts in interventional endoscopy spearheaded an evidence‐based Delphi study on behalf of the World Endoscopy Organization Colorectal Cancer Screening Committee. A steering committee comprising six members devised 51 statements, and 43 experts from 18 countries on six continents participated in a three‐round voting process. The Grading of Recommendations, Assessment, Development and Evaluations tool was used to assess evidence quality and recommendation strength. Consensus was defined as ≥80% agreement (strongly agree or agree) on a 5‐point Likert scale.ResultsForty‐two statements reached consensus after three rounds of voting. Recommendations included: three statements on training and competency; 10 statements on preresection evaluation, including optical diagnosis, classification, and staging of LSTs; 14 statements on endoscopic resection indications and technique, including statements on en bloc and piecemeal resection decision‐making; seven statements on postresection evaluation; and eight statements on postresection care.ConclusionsAn international expert consensus based on the current available evidence has been developed to guide the evaluation, resection, and follow‐up of LSTs. This may provide guiding principles for the global management of these lesions and standardize current practices.

ABSTRACT Background The unfolded protein response (UPR) is a proteostatic process that is activated in response to endoplasmic reticulum stress. It is currently unclear how aging influences the chronic and adaptive UPR in human skeletal muscle. Here we determined the effect of aging on UPR activation at rest, in response to exercise, and the associations with muscle function. Methods Thirty young (20–35 yr) and 50 older (65–85 yr) individuals were enrolled. Vastus lateralis biopsies were performed at rest and 3 and 48 h after a single bout of resistance exercise. The abundance of UPR-related transcripts and proteins was measured by RNA sequencing and Western blotting, respectively. Fractional synthetic rates of muscle protein were determined by mass spectrometry after intravenous infusion of 13 C 6 phenylalanine. Results Older adults demonstrated elevated transcriptional and proteomic markers of UPR activation in resting muscle. Resting UPR gene expression was negatively associated with muscle strength and power in older adults. The UPR is similarly activated by acute resistance exercise in young and older adults and positively associated with muscle function but not the anabolic response to exercise. Conclusions Skeletal muscle from older adults exhibits chronically activated UPR, which accompanies functional decline. The adaptive UPR is a proteostatic mechanism that is upregulated in response to exercise in young and older adults and positively associated with muscle function.

World record speeds at different distances for men and women in different age categories are used to develop a model to predict running performance as a function of race distance, age, and sex. This empirical model quantifies the decline in running speed with distance and age in a way that provides insight into the aerobic and anaerobic contributions to running speed and may help with developing training strategies for different age groups at various distances.

Objective The aim of this study was to formulate a retrospective study investigating the ocular findings and associated risk factors in long-term survivors after allogenic-hematopoietic stem cell transplantation (HSCT) in Saudi Arabia. Patients and methods This observational study was conducted on patients who underwent HSCT from 1996 to 2016 at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia. The study included 72 patients who were human leukocyte antigen-matched donors with identical matched sibling donors. Peripheral blood was the source of stem cells in 61 patients. The ophthalmological examination included visual acuity (VA) testing, refraction, tear break-up time, Schirmer’s test, slit-lamp biomicroscopy, and dilated ophthalmoscopy. Chronic ocular graft-versus-host disease (GVHD) inclusion was based on strict selection criteria. The patients identified with mild to moderate ocular GVHD had less than or equal to three corneal staining, 13–32 points ocular surface disease index (OSDI), and Schirmer’s test of 6–15 mm were classified as group 1, while those with severe ocular GVHD defined as having more than four corneal stainings, more than or equal to 33 points OSDI, and less than or equal to 5 mm Schirmer’s test were classified as group 2. Impairment of VA was classified as mild (20/22–20/50), moderate (20/70–>20/200), or severe (≤20/200) impairment. Results Chronic GVHD was diagnosed in 394 patients within the first 5 years after transplantation. Ocular GVHD was detected in 81 (20.56%) patients. They were classified into group 1 (65 patients, 80.25%) with mild to moderate ocular GVHD and group 2 (16 patients, 19.75%) with severe ocular GVHD. All patients had OSDI ranging from more than or equal to 13 to more than or equal to 33. Retinal changes were detected in five patients, optic disc changes in two patients, steroid-induced proliferative diabetic retinopathy in three patients, and old branch retinal vein occlusion in one patient. All patients with identical matched sibling donor showed normal or mild to moderate impaired VA except for two patients. All patients responded to topical eye drops except for nine who required surgical procedures. Normal or mild impaired VA was reported in 59 patients with statistical significance ( P =0.0053), while 42 male patients versus 29 females had normal or mild impaired VA with a statistically significant difference ( P =0.0179). Conclusion Ocular GVHD is a complex disease in our unique population. Every patient before allogenic HSCT be referred to a cornea specialist to evaluate the baseline parameters for the pre-HSCT diagnosis of dry eye disease.

Abstract The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step‐by‐step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. Highlights We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early‐changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later‐changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.

Abstract Extracellular vesicle (EV) secretion is mediated by purinergic receptor P2X 7 (P2RX7), an ATP‐gated cation channel highly expressed in microglia. We have previously shown that administration of GSK1482160, a P2RX7 selective inhibitor, suppresses EV secretion from murine microglia and prevents tauopathy development, leading to the recovery of the hippocampal function in PS19 mice, expressing P301S tau mutant. It is yet unknown, however, whether the effect of GSK1482160 on EV secretion from glial cells is specifically regulated through P2RX7. Here we tested GSK1482160 on primary microglia and astrocytes isolated from C57BL/6 (WT) and P2rx7 –/– mice and evaluated their EV secretion and phagocytotic activity of aggregated human tau (hTau) under ATP stimulation. GSK1482160 treatment and deletion of P2rx7 significantly reduced secretion of small and large EVs in microglia and astrocytes in both ATP stimulated or unstimulated condition as determined by nanoparticle tracking analysis, CD9 ELISA and immunoblotting of Tsg101 and Flotilin 1 using isolated EVs. GSK1482160 treatment had no effect on EV secretion from P2rx7 –/– microglia while we observed significant reduction in the secretion of small EVs from P2rx7 –/– astrocytes, suggesting its specific targeting of P2RX7 in EV secretion except small EV secretion from astrocytes. Finally, deletion of P2rx7 suppressed IL‐1β secretion and phagocytosed misfolded tau from both microglia and astrocytes. Together, these findings show that GSK1482160 suppresses EV secretion from microglia and astrocytes in P2RX7‐dependment manner, and P2RX7 critically regulates secretion of IL‐1β and misfolded hTau, demonstrating as the viable target of suppressing EV‐mediated neuroinflammation and tau propagation.