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INTRODUCTION: Chronic neurogastroduodenal disorders are heterogeneous and thought to lie on a spectrum of disease encompassing both sensory and neuromuscular pathologies. Abnormalities of interstitial cells of Cajal (ICC), a subset of which generate pacemaker signals and subsequently motility, have been implicated in their pathophysiology. We systematically reviewed the literature to pool ICC deficits observed in chronic neurogastroduodenal disorders. METHODS: Studies quantifying gastric ICC from the corpus or antrum, in adult patients with gastroparesis, functional dyspepsia (FD), or chronic nausea and vomiting syndromes (CNVS) were analyzed (PROSPERO: CRD42024613226). MEDLINE, Embase and CENTRAL databases were searched systematically. Random effects meta-analyses were used to compare ICC counts by disorder group with subgroup analysis by quantification methodology. RESULTS: Overall, 2,158 studies were screened and 22 included. Comparative studies (n = 12) showed patients with chronic neurogastroduodenal disorders (n = 167 with gastroparesis, n = 19 with FD ± CNVS) had lower ICC counts than nondiabetic controls (n = 130); standardized mean difference −1.58, 95% confidence interval −2.09 to −1.07, P < 0.0001, with more severe deficits in gastroparesis compared to FD ± CNVS (standardized mean difference [SMD] −0.44, P = 0.048). A spectrum of ICC deficits was evident in a subgroup of studies using gold-standard methods with c-KIT antibody and 4',6-diamidino-2-phenylindole-stained nuclei confirmation (7 studies, 246 patients: mean ICC counts 2.29 in gastroparesis vs 3.49 in FD ± CNVS, and 5.27 in controls; P < 0.001 all comparisons). Most studies were at high risk of bias (n = 21). DISCUSSION: Marked depletion of ICC is a consistent finding in neurogastroduodenal disorders. A spectrum of disease is revealed, with greater depletion associated with delayed emptying. Techniques for clinically defining ICC-driven gastric neuromuscular dysfunction should be prioritized.

Abstract Background Indigenous populations worldwide experience unjust inequities in surgical outcomes. In Aotearoa New Zealand, Indigenous Māori experience poorer health outcomes, including higher rates of postoperative mortality. The aim of this study was to quantify ethnic disparities in ‘failure to rescue’ (FTR), complications, and mortality following gastrointestinal cancer surgery and to analyse trends over time. Methods A retrospective national population-based cohort study of patients undergoing resection for gastrointestinal and hepatopancreatobiliary cancers from 2005 to 2020 was conducted. Self-reported ethnicity data were collected at the time of surgery. The primary outcome was FTR, defined as mortality following a complication within 90 days of surgery. Results In total, 31 185 patients were included; 2479 (7.9%) were Māori, 46.5% were female, and the median age was 71 (interquartile range 62–78) years. Māori patients were younger and had higher levels of socio-economic deprivation and co-morbidity. Māori had higher age-standardized rates of mortality (5.9% versus 3.2%), complications (52.9% versus 42.4%), and FTR (10.8% versus 7.2%), compared with European/Other. Multivariable regression demonstrated higher odds of mortality (adjusted OR (aOR) 1.45 (95% c.i. 1.15–1.82)), complications (aOR 1.30 (95% c.i. 1.17–1.45)), and FTR (aOR 1.29 (95% c.i. 1.01–1.62)) for Māori. Analysis over time showed a significant improvement in risk-adjusted rates of mortality (6.2% in 2005–2008 versus 3.4% in 2017–2020) and FTR (7.3% in 2005–2008 versus 4.0% in 2017–2020) for European/Other, but no change for Māori (rates of mortality were 6.6% in 2005–2008 versus 5.4% in 2017–2020 and rates of FTR were 7.8% in 2005–2008 versus 6.3% in 2017–2020). Conclusion Widening inequities in FTR have worsened disparities in postoperative mortality for Māori patients. ‘Complication rescue’ is a target to reduce inequities and improve perioperative care for Māori patients.

Space exploration exposes astronauts to unique conditions such as microgravity and space radiation, potentially influencing gene expression and triggering carcinogenesis. Paradoxically, these extreme environments could uncover other pro-treatment aspects of cancer biology. Despite numerous reviews addressing these aspects in isolation, a comprehensive synthesis of the effects of space stressors on cancer development is incomplete. This scoping review aims to provide a holistic perspective on the influence of spaceflight and associated stressors—including gravitation (hyper- and microgravity), radiation, and vibration—on the potential for cancer development and altered cellular mechanisms. We adhered to the PRISMA-ScR checklist for our review. A multitiered search strategy was employed in English, starting with a preliminary keyword identification in Google Scholar and PubMed. Subsequently, the main search was conducted across five databases—Cochrane, Embase, PubMed, Scopus, and Web of Science—until 22 February 2024. All included studies were thoroughly assessed by two independent reviewers. Of the 15,553 identified articles, 158 were deemed eligible. The majority (92%) were experimental studies, predominantly cell-based (74.17%). Breast (15.19%), thyroid (13.92%), and hematopoietic (11.40%) cancers were the most frequently examined. Spaceflight stressors could affect different biological systems variably, with microgravity impacting spatial growth and metastasis, and cosmic radiation exerting both tumor-suppressive and mutagenic effects. Our findings highlight the need for large-scale, prolonged analog studies mimicking space conditions to enhance mission safety and shed light on the nuanced effects of space stressors on cancer. Additionally, further extensive studies need to be performed in the true weightlessness of spaceflight, both animal-based and on human tissue (cell cultures and potentially whole perfusion organ models), in addition to crew pre/intra/post-flight long-duration evaluations. Furthermore, this unique research avenue may reveal cancer cell sensitivities to these stressors, opening new pathways for innovative therapeutic strategies in cancer treatment.

5041 Background: Prior studies suggest that chemotherapy-naïve pts with mCRPC treated with AA have a higher CV event-related hospitalization risk than those treated with ENZA. To further explore this association, this real-world, comparative causal inference study used a large US dataset to assess CV event risk in chemotherapy-naïve pts with mCRPC who initiated treatment (Tx) with ENZA or AA and provide outcome data based on history of (h/o) CV disease (CVD). Methods: Using US Medicare fee-for-service claims (Jan 2010–Dec 2022), we identified chemotherapy-naïve pts aged ≥65 years with mCRPC who initiated ENZA or AA between Sep 2014 and May 2017. The primary endpoint was a 4-point major adverse CV event (MACE-4; composite of acute myocardial infarction [AMI], stroke, unstable angina/revascularization [UA/R], and heart failure). Atrial fibrillation (AFib), venous thromboembolism (VTE), and all-cause death were also analyzed. Groups were propensity score matched (PSM) to adjust for differences in pt characteristics, assessed using standardized mean difference (SMD). Cause-specific Cox proportional hazards models were used to comparethe risk of CV outcomes between intention-to-treat cohorts, with death as a competing event. Subgroup analyses were conducted based on h/o CVD. Sensitivity analysis was performed with a MACE-5 endpoint, defined as MACE-4 or CV-related death. Results: Of 6319 pts in the total study population (ENZA: 2934; AA: 3385), 2913 PSM pts were included from each group. The ENZA and AA cohorts had similar baseline characteristics even before PSM (SMD<0.1), with a mean (standard deviation) age of 78.8 (7.3) years; 76% of pts had prior CVD. Compared with pts on ENZA, pts on AA had a significantly higher risk of experiencing MACE-4—particularly UA/R—as well as a higher risk of AFib and VTE (Table). Similar results were found in the subgroup of pts with a h/o CVD and the sensitivity analyses. Additionally, pts on AA had a higher risk of all-cause death than pts on ENZA, regardless of CVD history (h/o CVD hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.07–1.21, P =0.0001; no h/o CVD HR: 1.12, 95% CI: 1.01–1.26, P =0.036). Conclusions: This matched analysis of US Medicare beneficiaries showed an increased risk for MACE-4, AFib, and VTE in pts with mCRPC treated with AA compared to ENZA, in the overall pt population and pts with a h/o CVD. The risk of all-cause death was higher with AA in all pts. These findings provide insights into Tx decision-making for pts with mCRPC, especially those at high risk of CV events. Outcomes HR* (95% CI) P -value MACE-4 1.12 (1.02–1.24) 0.028 AMI 1.01 (0.76–1.32) 0.987 Stroke 0.92 (0.70–1.20) 0.505 UA/R 1.13 (1.01–1.26) 0.041 Heart failure 1.19 (0.90–1.58) 0.237 AFib 1.73 (1.31–2.29) 0.0001 VTE 1.37 (1.02–1.85) 0.037 All-cause death 1.13 (1.07–1.19) 0.0001 *ENZA = reference group.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Abstract Introduction: Over 90% of adolescents (18-24 years) have a social media account. In 2021, an estimated 18.3% of 18-24-year-olds used electronic cigarettes. This age group is more likely to use social media as a health information resource than other sources. The social media platform TikTok is the fastest growing platform among adolescents. There is growing interest in vaping cessation among adolescents, and vaping cessation posts have grown accordingly. Our hypothesis is there are diverse vaping cessation methods described by TikTok users important for clinicians to understand. The use of qualitative methods informed by netnography represents an ideal way to evaluate TikTok videos. Methods: TikTok videos describing at least one vaping cessation method posted in English uploaded after January 1, 2022 were eligible for inclusion. Any post associated with advertising, sponsorship, corporations, or retail entities were excluded. Reposts of any kind were excluded. A total of 200 videos were reviewed in duplicate for eligibility. NVivo Version 14 transcription cloud and coding software was used. Coding was conducted independently by the study team until thematic saturation was reached. This study was deemed exempt by the Mayo Clinic Institutional Review Board as social media data is public domain and no identifiers were collected. Results: A total of 52 videos were included. Included videos had an average of 2.4 million views, 285,000 likes, and 11,000 shares. There were a wide variety of vaping cessation methods described. Some methods, such as hand motions mimicking vaping, limiting exposures, and use of nicotine replacement are supported by cigarette smoking cessation literature. There were also numerous videos outlining methods known to be ineffective or harmful, including instructions to vape continuously until illness occurs, and utilizing negative self-affirmations to “scold” yourself when using electronic cigarettes. Themes of inner strength, motivations, and shame were also discussed, and multiple users described their “wake up call” to quit vaping. Conclusions: Social media platforms are growing in popularity with adolescents and individuals under age 18. The inability for users to discriminate between evidence-based health advice and anecdotal experiences represents a key issue for clinicians to be aware of when counseling patients. Given the age demographics of social media users, this issue will grow as the population ages. Clinicians should engage in conversations with their patients about sources of reputable health information, and future directions may include novel methods such as partnering with influencers or social media companies.

Objectives/Goals: Aspiration causes or aggravates lung diseases. While bedside swallow evaluations are not sensitive/specific, gold standard tests for aspiration are invasive, uncomfortable, expose patients to radiation, and are resource intensive. We propose the development and validation of an AI model that analyzes voice to noninvasively predict aspiration. Methods/Study Population: Retrospectively recorded [i] phonations from 163 unique ENT patients were analyzed for acoustic features including jitter, shimmer, harmonic to noise ratio (HNR), etc. Patients were classified into three groups: aspirators (Penetration-Aspiration Scale, PAS 6–8), probable (PAS 3–5), and non-aspirators (PAS 1–2) based on video fluoroscopic swallow (VFSS) findings. Multivariate analysis evaluated patient demographics, history of head and neck surgery, radiation, neurological illness, obstructive sleep apnea, esophageal disease, body mass index, and vocal cord dysfunction. Supervised machine learning using five folds cross-validated neural additive network modelling (NAM) was performed on the phonations of aspirator versus non-aspirators. The model was then validated using an independent, external database. Results/Anticipated Results: Aspirators were found to have quantifiably worse quality of sound with higher jitter and shimmer but lower harmonics noise ratio. NAM modeling classified aspirators and non-aspirators as distinct groups (aspirator NAM risk score 0.528+0.2478 (mean + std) vs. non-aspirator (control) risk score of 0.252+0.241 (mean + std); p Discussion/Significance of Impact: We report the use of voice as a novel, noninvasive biomarker to detect aspiration risk using machine learning techniques. This tool has the potential to be used for the safe and early detection of aspiration in a variety of clinical settings including intensive care units, wards, outpatient clinics, and remote monitoring.

INTRODUCTION: Gastroparesis is a debilitating gastroduodenal disorder for which gastric peroral endoscopic myotomy (GPOEM) has emerged as an efficacious treatment option. However, response to GPOEM varies between 50% and 80%, such that preoperative predictors of treatment success are needed to guide patient selection. METHODS: We performed a systematic review to identify predictors of clinical and functional response to GPOEM among adult patients with gastroparesis (PROSPERO: CRD42023457359). MEDLINE, Embase, and CENTRAL databases were searched systematically for studies reporting outcomes after GPOEM in September 2023. A narrative synthesis of predictive factors on univariable and multivariable analysis was performed with consideration of response rates through meta-analysis and evaluation of discrimination if prognostic models were developed. Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) was used for risk of bias assessment. RESULTS: Of 1899 articles reviewed, 30 were included. The GPOEM response rate was 63.1% (95% confidence interval 56.3%–69.5%) with most studies defining clinical success on the basis of improvement in gastroparesis cardinal symptom index (87%, 26/30). Older age, shorter duration of gastroparesis, nondiabetic etiology, lower body mass index, and response to intrapyloric botulinum toxin were associated with positive response to GPOEM on multivariable analyses. Predictors on physiological tests such as EndoFLIP or gastric emptying scintigraphy were inconsistent. No prognostic models underwent external validation. DISCUSSION: Currently, there are limited reproducible predictors of response to GPOEM among patients with refractory gastroparesis. Robust prospective studies investigating scalable, reproducible, and actionable biomarkers of treatment response are required.

Introduction: Living in an area with high Area Deprivation Index (ADI) is linked to worse cardiovascular disease (CVD) outcomes. However, the association of ADI with type 2 diabetes (T2D), a major CVD risk factor, is incompletely described. This knowledge may guide primary CVD prevention. Method: Rochester Epidemiology Project is a medical record linkage system of persons in southeast Minnesota and southwest Wisconsin. We identified 253,890 persons (aged 4–98 yrs on July 1, 2015) in 9 counties with >90% population coverage. ADI scores, from 2015 home addresses, were grouped into quartiles of low (Q1) to high (Q4) deprivation. We excluded persons with type 1 diabetes (T1D) or history of T2D and identified new T2D cases (2015-2020) using ICD codes, HbA1c and medications. We examined the association between ADI quartile and risk of incident T2D using Cox regression with persons right censored at death, T2D, T1D or last visit. Models were adjusted for age and gender, and reported adjusted hazard ratios (aHR [95% confidence interval]). Results: Age, gender, and race statistically differed across ADI quartiles (Table). Age × ADI interaction was significant ( P <.001). T2D incidence ranged from 6.3 (Q1) to 9.0 (Q4) per 1000 person-years ( P <.001). Women vs. men/non-binary persons (combined due to limited non-binary persons) had 30% lower risk of incident T2D (aHR 0.70 [0.67–0.72]). Risk of incident T2D was higher in persons from higher ADI areas. At median age of 48.6 yrs, the risk was 30% higher in Q2 (aHR 1.3 [1.22–1.38]), 38% higher in Q3 (aHR 1.38 [1.30–1.47]) and 53% higher in Q4 (aHR 1.53 [1.43–1.62]) vs. Q1. Higher ADI was associated with higher incident T2D in younger persons, with risk attenuation with increasing age (Figure). Conclusion: In this population cohort, persons, particularly of younger age, living in more deprived areas had a higher risk of incident T2D. ADI may help identify areas for targeted T2D screening, with implications for CVD screening and prevention.