An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission.

Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15+ macrophages, PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand-receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.

Endogenous Levels of Circulating Androgens Are Not Associated with Risk of Microscopic Colitis.

BACKGROUND: Microscopic colitis is a chronic inflammatory disease that most commonly affects post-menopausal women. Exogenous hormone use has recently been linked with increased risk of microscopic colitis. Yet, it is unclear whether levels of endogenous sex hormones are also associated with risk of microscopic colitis. AIM: To evaluate the association between prediagnostic plasma androgens and subsequent risk of microscopic colitis. METHODS: We conducted a case-control study nested within prospective cohort studies of the Nurses' Health Study (NHS) and NHSII. Cases of microscopic colitis were each matched to two controls according to age, cohort, menopause status, fasting status, and season of plasma collection. Prediagnosis plasma levels of androgens including dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of microscopic colitis using conditional logistic regression models. RESULTS: Our study included 96 cases of microscopic colitis matched to 190 controls. Plasma levels of testosterone were not associated with risk of microscopic colitis (Ptrend = 0.70). Compared to participants in the lowest quartile of plasma testosterone levels, the aOR of microscopic colitis for women in the highest quartile was 0.88, 95% CI 0.45-1.71. Similarly, we did not observe an association between dehydroepiandrosterone sulfate and sex hormone-binding globulin and risk of microscopic colitis (all Ptrend > 0.52). CONCLUSION: Among women, prediagnostic circulating levels of testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin are not associated with risk of microscopic colitis.

Performance of a Triage Protocol for Monoclonal Antibodies in a Mixed Vaccinated and Unvaccinated Cohort of COVID-19 Patients Treated With Intravenous Infusion or Subcutaneous Injection.

Background: Several monoclonal antibodies (mAbs) have been shown to reduce rates of hospitalization in patients with coronavirus disease 2019 (COVID-19) who have risk factors for severe disease. Due to capacity constraints, many health systems have been unable to provide mAbs to all eligible patients. There is little evidence regarding the performance of triage protocols for allocation or the relative effectiveness of subcutaneous administration vs intravenous infusion. Methods: This was a retrospective cohort study of 1063 patients with COVID-19 consecutively referred for monoclonal antibody therapy in a single large academic health care system, who were prioritized for mAb therapy using an allocation protocol grouping patients by risk. Results: A triage protocol prioritizing patients who were not fully vaccinated and were at high risk of severe COVID-19 and patients who were heavily immunosuppressed performed well in terms of differentiating between groups of patients by risk of severe disease. The number needed to treat (NNT) to prevent 1 hospitalization was 4.4 for the highest priority group, 8.5 for the next highest priority group, and 21.7 for the third highest priority group. There was no significant correlation between route of administration and hospitalization for symptoms related to COVID-19 (odds ratio, 1.26 in the intravenous group compared with the subcutaneous group; 95% CI, 0.56-2.8; P = .58). Conclusions: This study demonstrates that triaging mAbs for patients with COVID-19 by risk can optimize benefit in terms of reducing rates of hospitalization and that rates of hospitalization may be no different between patients treated with subcutaneous injection and patients treated with intravenous infusion.

Bamlanivimab Efficacy in Older and High-BMI Outpatients With COVID-19 Selected for Treatment in a Lottery-Based Allocation Process.

BACKGROUND: Given the challenges associated with timely delivery of monoclonal antibody (mAb) therapy to outpatients with coronavirus disease 2019 (COVID-19) who are most likely to benefit, it is critical to understand the effectiveness of such therapy outside the context of clinical trials. METHODS: This was a case-control study of 1257 adult outpatients with COVID-19, ≥65 years of age or with body mass index (BMI) ≥35, who were entered into a lottery for mAb therapy. RESULTS: Patients who were called to be offered mAb therapy had a statistically significant 44% reduction in the odds of hospitalization within 30 days of a positive severe acute respiratory syndrome coronavirus 2 test compared with those who were not called (odds ratio [OR], 0.56; 95% CI, 0.36-0.89; P=.01). Patients who actually received bamlanivimab had a statistically significant 68% reduction in the odds of hospitalization compared with those who did not receive bamlanivimab (OR, 0.32; 95% CI, 0.11-0.93; P=.04). CONCLUSIONS: This study supports the effectiveness of bamlanivimab in reducing COVID-19-related hospitalizations in patients ≥65 or with BMI ≥35.

Thoracic aortic remodeling with endografting after a decade of thoracic endovascular aortic repair experience.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) results have been studied in short-term time frames. This study aimed to evaluate midterm and long-term outcomes of TEVAR, emphasizing postoperative aortic remodeling and need for reintervention. METHODS: This is an institutional retrospective review of TEVAR for isolated descending thoracic aortic aneurysms. Data were collected from 2004 to 2018. Primary outcomes studied included aneurysm sac remodeling, freedom from reintervention, and all-cause mortality. Other outcomes studied include endoleak rates, neurologic complication rates, and any overall postoperative complication rates. RESULTS: During the study period, 219 patients underwent TEVAR for descending thoracic aortic aneurysms. The median effect of TEVAR on sac diameter was a 0.7-cm decrease in size (interquartile range, -1.4 to 0.0 cm). During the study period, 80% (n = 147) of patients experienced aneurysm sac regression or stability. Perioperative neurologic complications occurred in 16% (n = 34) of patients. Significant predictors of sac growth were endoleak (odds ratio [OR], 65; P < .001), preoperative carotid-subclavian bypass (OR, 8; P = .003), and graft oversizing <20% (OR, 15; P = .046). Every 1-mm increase in aortic diameter at the proximal TEVAR landing zone led to an increased odds of endoleak (OR, 2; P = .049). Access complications (OR, 8) and subclavian artery coverage (OR, 6) significantly increased the odds of reintervention, whereas every percentage of graft oversizing protected against reintervention (OR, 0.005). Life-table analysis revealed an overall survival of 78% (71%-83%) at median follow-up. At 3 years, survival was 88% (80%-93%) for those with aneurysm sac stability or regression, whereas it was 70% (49%-84%) for those with aneurysm sac growth (P = .0402). Cox proportional hazards model showed that the only protective factor for mortality was percentage oversizing, with every 1% of oversizing having a hazard ratio (HR) of <.001 (P = .032). This was counterbalanced by the fact that patients with graft oversizing >30% had an increased odds of mortality with HR >10 (P = .049). Other significant factors that increased the odds of mortality included endoleak (HR, 3.6; P = .033), diabetes (HR, 4.1; P = .048), age (every 1-year increase in age; HR, 1.2; P = .002), year of surgery (every year subsequent to 2004; HR, 1.3; P = .012), and peripheral artery disease (HR, 5.2; P = .041). CONCLUSIONS: The majority of patients (80%) experience sac stability or regression after TEVAR, which offers a clear survival advantage. Endoleaks are predictive of sac growth, conferring increased mortality. Rigorous surveillance is necessary to prevent future aortic events through reintervention.