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Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .

Motility disorders, particularly gastroparesis, are prevalent complications following solid organ transplantation, significantly impacting quality of life, nutritional status, graft survival, and mortality. This comprehensive review synthesises evidence from PubMed, Scopus, and Embase databases on pathophysiology, clinical manifestations, diagnosis, management, and prognostic factors across transplant types. Mechanisms include vagal nerve injury (highest in lung transplants, prevalence 40–91%), immunosuppressive effects (e.g., tacrolimus accelerates motility; mycophenolate impairs it), surgical trauma, microbiome dysbiosis (reduced Firmicutes/Bacteroidetes ratio), and metabolic factors like post-transplant diabetes (OR 5.17 in kidney recipients). Pediatric and thoracic recipients face the highest risks, with lung transplant gastroparesis conferring a 2.7-fold increased mortality/retransplantation hazard (p < 0.05). Diagnosis relies on gastric emptying scintigraphy (gold standard, sensitivity 85–95%) and wireless motility capsules (100% sensitivity for delay), while management encompasses prokinetics (60–80% response), endoscopic G-POEM (85% success), gastric electrical stimulation (100% quality-of-life improvement in series), and nutritional support. Prognostic factors include younger age (better intervention response), aetiology (anatomical worse than metabolic), and early therapy success. Outcomes vary: lung recipients experience severe impacts on chronic allograft dysfunction (83% oesophageal motility abnormalities correlate with 66–67% rejection). Future directions emphasise microbiome therapies, AI predictive models (AUC 0.85), and wearables for continuous monitoring. Multidisciplinary approaches are essential to balance immunosuppression with GI management, addressing ethical dilemmas like drug interactions and access disparities. Ultimately, early screening and personalised interventions can mitigate complications, enhancing long-term transplant success.

Background/Objectives: Coronavirus disease 2019 (COVID-19) is associated with gastrointestinal (GI) symptoms. Small intestinal bacterial overgrowth (SIBO) is emerging as a significant GI sequela post-COVID-19 infection. This study aimed to evaluate the prevalence and incidence of SIBO post-COVID-19 infection across different age groups and to identify associated risk factors in a global cohort. Methods: A retrospective study utilized the TriNetX database and included adult patients (≥18 years) diagnosed with SIBO following COVID-19 infection (1 January 2022–30 May 2024). A propensity score matching (1:1) was used to adjust for demographics and SIBO risk factors. Kaplan–Meier survival analysis assessed the SIBO incidence within 12 months. Results: Among 1,660,092 COVID-19 patients and 42,322,017 controls, SIBO was diagnosed in 353 COVID-19 patients without hydrogen breath tests (BT) and 78 with BT, compared to 3368 controls without BT and 871 with BT. Age-specific analysis demonstrated a clear, progressive increase in the SIBO incidence, becoming distinctly significant by 6 months and highest at 12 months post-infection. The highest risks were noted in ages 60–69 (0.011% vs. 0.004%, OR 2.6, p = 0.0003) and 70–79 (0.011% vs. 0.005%, OR 2.0, p = 0.0004), with younger age groups (30–49 years) also showing significantly increased risks. The medication analysis revealed strong associations with chronic opioid, proton pump inhibitor, and antidiarrheal medication. Conclusions: COVID-19 significantly increased the risk of SIBO, particularly within the first 12 months post-infection, across various age groups and, notably, in association with certain chronic medications. Clinical vigilance and targeted management strategies are recommended to mitigate long-term GI consequences.

Recent guidelines on biliary cannulation are lacking. This guideline is an initiative of the World Endoscopy Organization (WEO) with the involvement of a panel of experts from Asia, Europe, and America. Relevant clinical questions on four areas (post‐endoscopic retrograde cholangiopancreatography [ERCP] pancreatitis [PEP] prophylaxis, biliary cannulation techniques, sphincterotomy/papillary balloon dilation, and biliary cannulation in special circumstances) were developed and answered after systematic reviews of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Successful biliary cannulation and sphincterotomy are cornerstones of ERCP and are indispensable for almost all therapeutic and advanced diagnostic procedures. However, adverse events, particularly PEP, may commonly occur and impair patients' outcomes. A high cannulation rate and a low rate of PEP are quality indicators for ERCP and should be the goal of all endoscopists. With this guideline we aimed to provide clinical practice advice applicable worldwide, regardless of resources and expertise availability. The main recommendations focus on specific aspects of ERCP, including pre‐, intra‐, and postprocedural measures to reduce the risk of PEP, the technique for an initial biliary cannulation attempt, options for cannulation in cases of difficult biliary access, alternatives to ERCP in case of failure (percutaneous‐ and endoscopic ultrasound‐guided), and biliary access in altered anatomy (periampullary diverticulum and postsurgical anatomy) and in the presence of duodenal stenosis.

Background: Although BP is associated with kidney outcomes, its clinical significance in living kidney donors (LKD) is unknown. We aim to examine the association between pre-donation BP and the risk of kidney function decline in LKD. Methods: A retrospective cohort study using OPTN/SRTR including adult LKD, who underwent donation between 6/1972 and 9/2022, was utilized to examine the association of quartile (Q) of pre-donation SBP and DBP with time-to-event of ≥35% decline in post-donation eGFR from pre-donation eGFR by multiple Cox regression. Results: Of 174,311 adult LKD, mean±SD age was 41±12 years and 60% were female. Mean pre-donation SBP and DBP were 122±13 and 74±9 mmHg, respectively. Mean pre-donation SBP in Q 1, 2, 3, and 4 were 106±6, 117±2, 126±3, and 140±9 mmHg, respectively and the corresponding DBP were 62±5, 71±2, 78±2, and 86±5 mmHg, respectively. The median (IQR) of pre-donation eGFR was 91 (75, 111) mL/min/1.73 m2. Median(IQR) eGFR at immediate post-donation, 6-, 12-, and 24-months post-donation were 50 (40, 62), 54 (44, 67), 55 (45, 68), and 57 (47, 70) mL/min/1.73 m2, respectively. Out of 38,780 LKD with post-donation eGFR data at 6, 12, or 24 months, 31,054 had the event of ≥35% decline in post-donation eGFR from pre-donation eGFR with a median time to follow-up of 6.77 months(IQR 5.93, 12.67). The incidence rate of the event was 0.08 person-months. Compared to patients with SBP in Q 1, those with SBP in Q 2, 3, and 4 had a significantly increased risk for the event(HRSBP Q2,3,4 1.05, 1.08, and 1.15; P <0.001 – 0.003) but only patients with DBP in Q 3 and 4 had a significantly increased risk for the event (HRSBP Q3,4 1.04 and 1.09). After adjusting for age, gender, race/ethnicity, U.S. citizenship, education level, history of pre-donation HTN, diabetes, pre-donation BMI, DBP, and urine protein:creatinine ratio, there was a J-shaped association between pre-donation SBP and post-donation eGFR decline and only patients in the Q 2 became significantly associated with lower the risk for the event (HR 0.87, 95%CI 0.76, 0.99; Fig1). The pre-donation DBP – post-donation eGFR association was similar to the SBP – eGFR association but there was no statistically significant in all Q (Fig2). There was no effect-measured modifier for all covariates. Conclusions: Pre-donation SBP in a normal range(113 - 120 mmHg) is associated with the lowest risk for a post-donation eGFR decline. BP control in the normal range should be achieved for potential LKD.

AbstractIntroductionDirect oral anticoagulants (DOACs) become the recommended treatment over vitamin K antagonists (VKA) in patients with non‐valvular atrial fibrillation (AF). However, their effectiveness in reducing cognitive impairment and dementia compared to VKA remains unclear.MethodsA systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Database. Randomized controlled trials, cohort, or case–control study that assessed incident dementia between AF patients who received DOAC compared to VKA were selected. Relevant study characteristics and the number of incident dementia diagnosis or hazard ratios (HRs) for incident dementia and each dementia subtypes were extracted. Random‐effects model was used to perform meta‐analysis. Standardized mean differences (SMDs) were used to estimate effect sizes for continuous data.ResultsTwelve cohort studies comprising 1 451 069 individuals were included. The incidence of dementia was lower in AF patients prescribed DOACs compared to VKA (HR 0.88, 95% CI 0.83–0.93, I 2 = 61.2%). A lower incident dementia in DOACs group relative to VKA was significantly observed in those less than 75 years of age (< 65 years, HR 0.83 (95% CI 0.72–0.97, I 2 = 0%); 65–74 years, HR 0.86 (95% CI 0.81–0.92, I 2 = 55.4%); and ≥ 75 years, HR 1.07 (95% CI 0.74–1.55, I 2 = 92.5%)) and for the subgroup of patients with vascular dementia (HR 0.91, 95% CI 0.824–0.997, I 2 = 0%).ConclusionsThis meta‐analysis reveals a reduction in incidence of dementia in AF patients prescribed DOACs compared to VKA, particularly in those less than 75 years old and in the vascular dementia subtype.

Abstract: The integration of artificial intelligence (AI) and big data in anterior segment (AS) imaging represents a transformative approach to glaucoma diagnosis and management. This article explores various AS imaging techniques, such as AS optical coherence tomography, ultrasound biomicroscopy, and goniophotography, highlighting their roles in identifying angle-closure diseases. The review focuses on advancements in AI, including machine learning and deep learning, which enhance image analysis and automate complex processes in glaucoma care, and provides current evidence on the performance and clinical applications of these technologies. In addition, the article discusses the integration of big data, detailing its potential to revolutionize medical imaging by enabling comprehensive data analysis, fostering enhanced clinical decision-making, and facilitating personalized treatment strategies. In this article, we address the challenges of standardizing and integrating diverse data sets and suggest that future collaborations and technological advancements could substantially improve the management and research of glaucoma. This synthesis of current evidence and new technologies emphasizes their clinical relevance, offering insights into their potential to change traditional approaches to glaucoma evaluation and care.

3053 Background: Recently, early studies have identified circulating stromal cells (CStCs), i.e. Cancer Associated Macrophage-Like cells (CAMLs), in patients (pts) with newly diagnosed invasive cancers, which are phagocytic myeloid immune cells emanating from primary tumors. However, no study has evaluated CAMLs as a pan solid tumor screening tool nor their clinical impact on pt outcomes. We analyzed the blood of untreated newly diagnosed cancer pts (n=441), or in non-malignant conditions (i.e. pancreatic cysts, n=77), or healthy controls (n=100). We found that CAMLs are prevalent (82%) in cancer pt blood, absent in healthy controls (0%) and less common in non-malignant conditions (36%), with correlations to worse clinical outcomes. Methods: Anonymized peripheral blood was taken from n=441 pts before or after confirmation of invasive malignancy [stage I (n=105), stage II (n=125), stage III (n=114), stage IV (n=97) with pathologically confirmed lung (n=84), pancreas (n=61), breast (n=73), prostate (n=65), esophageal (n=34), Renal Cell (n=29), Sarcoma (n=27), or Other (n=68). In addition, anonymized blood was taken from pts with untreated non-malignant conditions including benign breast masses (n=19), Lupus (n=11), liver Cirrhosis (n=6), rising PSA (n=24), or other benign mass (n=17); and from healthy control volunteers (n=100). CAMLs were isolated by CellSieve microfiltration, defined as enlarged polyploid cells with cytokeratin+ and/or CD45/CD14+. Pts were monitored for 0-8 years (median=2.6) for progression free survival (PFS) and overall survival (OS). Results: CAMLs were found in 82% of all cancer pts averaging 5.4 CAMLs, specifically, in 66% of Stage I, 85% Stage II, 84% Stage III, and 92% Stage IV. No CAMLs were found in any healthy controls, but were in 36% of non-malignant pts. CAML sensitivity in cancer vs healthy was 82% (CI95% 78-85%), specificity=100% (CI95% 96-100%), PPV=100% (CI95% 99-100%), NPV=55% (CI95% 50-60%). CAML sensitivity in cancer vs benign was 82% (CI95% 78-85%), specificity=64% (CI95% 32-44%), PPV=93% (CI95% 90-95%), NPV=38% (CI95% 32-44%). CAML presence was significantly associated with worse PFS (HR=2.0, 95%CI 1.4-2.9, p<0.0001) & OS (HR=2.2, 95%CI 1.4-3.3, p=0.0004), with engorged phagocytic CAMLs (>50um), highly significant for worse PFS (HR=3.3, 95%CI 2.5-4.5, p<0.0001) & OS (HR=3.0, 95%CI 2.1-4.3, p<0.0001). Further, in benign pts positive for CAMLs, 2 pts were in situ, 16 had histologies with increased cancer risk (i.e. IPMN, atypical hyperplasia), and 5 pts died within 3 years. Conclusions: CAMLs appear to be a highly sensitive blood based biomarker that can identify invasive carcinoma in all stages of cancer regardless of subtype, but are not found in healthy controls & rare in non-malignant conditions. Further, enlarged phagocytic CAMLs appeared to correlate with shorter PFS and OS prior to treatment induction.