RESUMEN
BACKGROUND & AIMS: Interleukin (IL)33/IL1F11 is an important mediator for the development of type 2 T-helper cell (Th2)-driven inflammatory disorders and has also been implicated in the pathogenesis of gastrointestinal (GI)-related cancers, including gastric carcinoma. We therefore sought to mechanistically determine IL33's potential role as a critical factor linking chronic inflammation and gastric carcinogenesis using gastritis-prone SAMP1/YitFc (SAMP) mice. METHODS: SAMP and (parental control) AKR mice were assessed for baseline gastritis and progression to metaplasia. Expression/localization of IL33 and its receptor, ST2/IL1R4, were characterized in corpus tissues, and activation and neutralization studies were both performed targeting the IL33/ST2 axis. Dissection of immune pathways leading to metaplasia was evaluated, including eosinophil depletion studies using anti-IL5/anti-CCR3 treatment. RESULTS: Progressive gastritis and, ultimately, intestinalized spasmolytic polypeptide-expressing metaplasia (SPEM) was detected in SAMP stomachs, which was absent in AKR but could be moderately induced with exogenous, recombinant IL33. Robust peripheral (bone marrow) expansion of eosinophils and local recruitment of both eosinophils and IL33-expressing M2 macrophages into corpus tissues were evident in SAMP. Interestingly, IL33 blockade did not affect bone marrow-derived expansion and local infiltration of eosinophils, but markedly decreased M2 macrophages and SPEM features, while eosinophil depletion caused a significant reduction in both local IL33-producing M2 macrophages and SPEM in SAMP. CONCLUSIONS: IL33 promotes metaplasia and the sequelae of eosinophil-dependent downstream infiltration of IL33-producing M2 macrophages leading to intestinalized SPEM in SAMP, suggesting that IL33 represents a critical link between chronic gastritis and intestinalizing metaplasia that may serve as a potential therapeutic target for preneoplastic conditions of the GI tract.
Asunto(s)
Gastritis/etiología , Gastritis/patología , Interleucina-33/fisiología , Neoplasias Gástricas/etiología , Neoplasias Gástricas/patología , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Eosinófilos , Mucosa Gástrica/patología , Metaplasia , RatonesRESUMEN
OBJECTIVE: To determine whether rural Medicare FFS beneficiaries are more likely to be admitted to an urban hospital in 2018 than in 2010. DATA SOURCES: We combined data from the 2010 to 2018 Hospital Service Area File (HSAF) and the 2010-2017 American Hospital Association (AHA) survey. STUDY DESIGN: We conducted a fixed-effects negative-binomial regression to determine whether urban hospital admissions from rural ZIP codes were increasing over time. We also conducted an exploratory geographically weighted regression. DATA COLLECTION: We transformed the HSAF data into a ZIP code-level file with all rural ZIP codes. We defined rural as having a Rural-Urban Commuting Area (RUCA) code ≥4. A hospital's system affiliation status was incorporated from the AHA survey. PRINCIPAL FINDINGS: Controlling for distance to the nearest hospitals, an increase of 1 year was associated with a 2.0% increase (p < 0.001) in the number of admissions to urban hospitals from each rural ZIP code. New system affiliation of the nearest rural hospital was associated with an increase of 1.7% (p < 0.001). CONCLUSIONS: Even when controlling for distance to the nearest rural hospital (which reflects hospital closures), rural patients were increasingly likely to be admitted to an urban hospital.
Asunto(s)
Accesibilidad a los Servicios de Salud , Medicare , Anciano , Hospitales Rurales , Hospitales Urbanos , Humanos , Población Rural , Estados UnidosRESUMEN
Introduction: The COVID-19 pandemic has created unique challenges for primary care practices while also highlighting their importance in the pandemic response. To understand primary care practice needs, a survey was conducted of practices in Western North Carolina. Methods: Phase 2 of a primary care needs assessment was administered to 63 practices in Western North Carolina over the course of six weeks, from July 23 to August 31, 2021. Results: Most practices were operating with normal hours, though some still operated with reduced hours. Many practices reported insufficient personal protective equipment (PPE) supplies. While most practices provided at least some care via telehealth, practices cited different barriers to providing telehealth, with patient technology challenges being the most frequently cited. Discussion: Practices have adapted to the restrictions of the pandemic, but many are still vulnerable, and the patients they serve may face reduced access to care due to practice limitations or barriers to telehealth. Practices play a critical role in providing care to patients throughout the pandemic and continue to assist in pandemic response by providing COVID-19 testing and other services. Conclusion: Primary care practices in Western North Carolina continue to provide care to patients and support the overall pandemic response. The pandemic has highlighted the need to include primary care in emergency response efforts. Ongoing work will allow North Carolina to reach practices more effectively in future crises via the newly created NC Responds system, which allows primary care practices to be contacted in the event of a public health emergency.