Citations

OBJECTIVES: To investigate whether severe hyperoxia predisposes to end-organ complications and whether these complications contribute to in-hospital mortality among cardiogenic shock (CS) patients supported in venoarterial extracorporeal membrane oxygenation (VA-ECMO). DESIGN: Adult patients with CS from the Extracorporeal Life Support Organization Registry between 2010 and 2023 were categorized into normoxia (Pao 2 60–150 mm Hg), mild hyperoxia (Pao 2 151–300 mm Hg), and severe hyperoxia (Pao 2 > 300 mm Hg) based on their Pao 2 at 24 hours. The primary outcome was in-hospital mortality. End-organ complications were analyzed using multivariate logistic regression models, and causal mediation analysis was performed to estimate the direct and indirect effects of hyperoxia on mortality. SETTING: Multicenter, multinational prospective cohort study. PATIENTS: Adults with CS supported on VA-ECMO. INTERVENTIONS: Partial pressure of oxygen at 24 hours after VA-ECMO cannulation. MEASUREMENTS/MAIN RESULTS: A total of 10,541 patients were included (normoxia: 48.4%, mild hyperoxia: 30.0%, severe hyperoxia: 21.5%). There was higher in-hospital mortality in patients with severe hyperoxia (71.7%, adjusted OR [aOR]: 2.17; 95% CI, 1.19–2.50) and mild hyperoxia (63.8%, aOR: 1.34; 95% CI, 1.19–1.50) compared normoxia (52.7%; referent group). Severe hyperoxia was associated with more end-organ complications, which incrementally predicted higher mortality (aOR: 1.42; 95% CI, 1.25–1.61). Mediation analysis demonstrated that hyperoxia primary exerted a direct effect on mortality (86%), with contributions from neurologic (3.1%), hepatic (3.9%), renal (3.5%), and bleeding (2.3%) complications. CONCLUSIONS: Severe hyperoxia in patients with CS receiving VA-ECMO is associated with increased mortality and more end-organ complications. However, most of the effect of severe hyperoxia on mortality occurs via direct effects, independent of end-organ complications. These findings highlight the potential direct toxicity of hyperoxia and underscore the need for strategies to optimize oxygen delivery in this critically ill population.

Health problems associated with post-acute COVID-19, also known as “Long COVID,” range from mild to severe. The best defense against this potentially serious condition is to prevent COVID-19 infection and reinfection. The same preventive measures for COVID-19 may be used to help prevent the spread of Long COVID. This study used the Health Belief Model (HBM) to examine whether and how public understanding and awareness of Long COVID and its prevention shape the adoption of COVID-19 preventive behaviors. N = 605 English-speaking U.S.-based adults were recruited via Qualtrics. Predictors of intention to carry out COVID-19 preventive behaviors were investigated. Outcomes included behaviors relevant to preventing both acute and Long COVID. Across all models, except the one examining intent to get a vaccine booster, Black respondents were more likely than White respondents to express intent to carry out COVID-19 preventive behaviors. In addition, HBM constructs added significantly to the regression models. Susceptibility to Long COVID was significant for all behavioral outcomes (all p s < .05), self-efficacy for wearing a mask ( p < .001), and self-efficacy for testing for COVID-19 after exposure and before a social event ( p s < .001). In addition, perceived benefits for Long COVID prevention predicted intent of mask-wearing ( p < .001), testing before a social event ( p = .002), and getting a vaccine booster ( p = .001). Perceived severity of Long COVID did not significantly predict adherence to preventive behaviors. U.S. adults are more likely to express intent to carry out COVID-19 preventive behaviors, such as masking and receiving booster vaccines, when they report feeling greater susceptibility to Long COVID as well as greater self-efficacy for engaging in these preventive behaviors. Public health messaging about Long COVID with incorporation of HBM constructs may be an effective means of increasing continued recommended COVID-19 preventive behaviors, which also hold co-benefits for prevention of infections, such as influenza and measles, as well as emerging viruses such as avian flu.

ABSTRACT Transformed follicular lymphoma (tFL) is typically associated with chemotherapy resistance and a poor prognosis. There are limited data regarding outcomes after CD19‐directed chimeric antigen receptor T‐cell (CAR T) therapy in relapsed/refractory (R/R) tFL. A total of 923 adult patients with R/R tFL who received commercial CD19 CAR T therapy between 2017 and 2023 were identified in the Center for International Blood and Marrow Transplant Research registry. Median age was 64 years (range: 30–86) and median prior lines of therapy was 4 (range: 1–18). Most patients (78%) received axicabtagene ciloleucel, with 67% of patients having resistant disease at the time of CAR T infusion. At a median follow‐up of 25 months (range: 1–72) from CAR T infusion, the 2‐year overall survival (OS) was 57% (95% CI: 53–60) and progression‐free survival (PFS) was 43% (95% CI: 40–47). The 2‐year cumulative incidences of relapse or progression (rel/prog) and non‐relapse mortality (NRM) were 47% (95% CI: 44–51) and 9% (95% CI: 7–11), respectively. The overall response rate to CAR T was 76%, with a complete response rate of 63%. Grade ≥ 3 cytokine release syndrome (CRS) was observed in 7.1% and grade ≥ 3 immune effector cell–associated neurologic syndrome (ICANS) in 21.6% of patients. Multivariable analysis suggested that resistant disease status at the time of CAR T, use of bridging therapy, and high comorbidity index ≥ 3 were associated with inferior PFS and OS. Older age ≥ 60 significantly increased the risk of NRM. Our study suggests that CD19 CAR T is effective and safe for tFL.

Type 1 diabetes is characterized by the autoimmune destruction of pancreatic β cells, resulting in permanent loss of glucose homeostasis. Islet transplantation is a promising potential cure that remains hindered by immune rejection. We previously showed that ST8Sia6 expression on tumors reduced immune surveillance and hypothesized that this sialyltransferase could protect β cells from autoimmune destruction. Here, we demonstrate that ectopic expression of ST8Sia6 in β cells of female nonobese diabetic mice (NOD βST) decreased the spontaneous incidence of diabetes by 90% and preserved β cell mass. NOD βST mice had comparable insulitis at 8 weeks of age that did not progress over time compared with littermate controls. β Cell–autoreactive B and T cells were present in NOD βST mice, indicating a peripheral rather than central mechanism of immune tolerance. The islets of NOD βST mice displayed a dampened type 1 immune response and reduced IL-12p35 expression in dendritic cells compared with those of littermate controls. The peripheral protection persisted even after removal of ST8Sia6 expression at 20 weeks of age, indicating that transient expression was sufficient for establishment of tolerance. These results demonstrate that ST8Sia6 protects β cells from immune-mediated attack and rejection, highlighting its therapeutic potential for autoimmune disorders.

The Dublin ISUP Consensus Conference covered the proceedings on the best practice recommendations on nonurachal glandular lesions of the urinary bladder, bladder diverticular cancers, and molecular features of bladder and urachal glandular lesions. The conference proceedings on urachal neoplasms (except for their molecular features) are published elsewhere. The rationale for convening this conference was the lack of structured and consented pathologic recommendations in these rare lesions. Consensus by participants was reached on the following statements: (1) intestinal metaplasia with dysplasia is considered to be a precursor to primary bladder adenocarcinoma; (2) dysplasia arising from cystitis glandularis should be reported in terms of focality (focal or nonfocal) and grade (low or high); (3) the term “adenocarcinoma” should only be used for carcinomas showing pure (nonurothelial) morphology and should not be used interchangeably in urothelial carcinoma with “glandular differentiation” because of the pathobiological differences and management implications; (4) the different histologic subtypes of bladder adenocarcinoma should be specified in the report; (5) immunohistochemistry has an ancillary role in the work up of bladder adenocarcinoma versus gastrointestinal or Müllerian-type adenocarcinomas; (6) lymphovascular invasion should be included as a parameter when reporting bladder adenocarcinoma; (7) representative or targeted sampling will be sufficient for bladder diverticulum resection specimens; and (8) molecular analysis in genomic profiling should be performed only in advanced or metastatic bladder and urachal adenocarcinomas for targetable therapy. This report on glandular (nonurachal) lesions of the bladder from the Dublin ISUP consensus conference will serve as a best practice recommendation and as a guide for future research on these relatively rare lesions.

Abstract There is an urgent need to improve dementia ascertainment robustness in real-world studies assessing drug effects on dementia risk. We developed algorithms to dementia identification algorithms using Medicare claims (inpatient/outpatient/prescription) from 3318 Visit 5 (2011-2013) and 1828 Visit 6 (2016-2017) participants of the Atherosclerosis Risk in Communities (ARIC) Study, validated against ARIC's rigorous syndromic dementia classification. Algorithm performance was compared to existing algorithms (Jain, Bynum, Lee). We further evaluated algorithms effectiveness in a 20% random Medicare sample aged ≥70 years who initiating liraglutide or dipeptidyl peptidase 4 inhibitors (DPP4i) to assess 3-year adjusted risk difference (aRD) for dementia. Our incident dementia algorithm required two dementia diagnostic codes within 1-year, or one dementia code plus a new dementia prescription within 90 days. It achieved a positive predictive value (PPV) of 69.2%, specificity of 99.0%, and sensitivity of 34.6% (population prevalence: 8.8%), comparable to extant algorithms (PPV, 58.7–68.6%; sensitivity 25.5–40.4%). Prevalent dementia algorithm (without requiring incident diagnoses/prescriptions) demonstrated similar performance. In the Medicare sample, dementia risk ranged from 3.0% to 12.5%, aRD comparing liraglutide to DPP4i varied −1.2% to −3.6%, with our algorithm closely matching the Bynum algorithm. Algorithm selection significantly impacts treatment effect estimates, highlighting its importance in in pharmacoepidemiologic research.

AbstractThe American Academy of Otolaryngology–Head and Neck Surgery Foundation has published a supplement to this issue of Otolaryngology–Head and Neck Surgery featuring the updated “Clinical Practice Guideline: Adult Sinusitis”. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 developed recommendations address diagnostic accuracy for adult rhinosinusitis, the appropriate use of ancillary tests to confirm diagnosis and guide management (including radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function), and the judicious use of systemic and topical therapy. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, an immunocompromised state, and ciliary dyskinesia. An updated guideline is needed as a result of new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.

AbstractThe American Academy of Otolaryngology–Head and Neck Surgery Foundation has published the updated “Clinical Practice Guideline: Adult Sinusitis” as a supplement to this issue of Otolaryngology–Head and Neck Surgery. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 developed recommendations address diagnostic accuracy for adult rhinosinusitis, the appropriate use of ancillary tests to confirm diagnosis and guide management (including radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function), and the judicious use of systemic and topical therapy. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia. An updated guideline is needed as a result of new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.MethodsThis executive summary describes the guideline developed using the 55‐page protocol published as the American Academy of Otolaryngology–Head and Neck Surgery Foundation's Clinical Practice Guideline Development Manual (3rd edition), which summarizes the methodology for assessments of current data, topic prioritization, development of key action statements, application of value judgements, and related procedures. The guideline update group represented the disciplines of otolaryngology–head and neck surgery, infectious disease, family medicine, allergy and immunology, advanced practice nursing, and a consumer advocate.Differences from Prior GuidelineThis clinical practice guideline is as an update, and replacement, for an earlier guideline published in 2015 by the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO‐HNSF).1 An update was planned for 5 years after the initial publication date and was further necessitated by new primary studies and systematic reviews that might suggest a need for modifying clinically important recommendations.2 Changes in content and methodology from the prior guideline include the following: New evidence from 14 guidelines, 194 systematic reviews, and 133 RCTs. Emphasis on patient education and counseling with new explanatory tables. Expanded action statement profiles to explicitly state quality improvement opportunities, confidence in the evidence, intentional vagueness, and differences of opinion. Enhanced external review process to include public comment and journal peer review. New algorithm to clarify decision making, watchful waiting, action statement relationships. Extension of watchful waiting (without antibiotic therapy) as an initial management strategy to all patients with uncomplicated acute bacterial rhinosinusitis (ABRS) regardless of severity, not just patients with “mild” illness (prior guideline). Clarified the recommended timeline for the diagnosis, conservative management and antibiotic treatment of ABRS. Change in recommendation to first‐line antibiotic therapy for ABRS amoxicillin, with or without clavulanate, from amoxicillin alone (prior guideline). Addition of aspirin exacerbated respiratory disease (AERD) as a chronic condition that modifies management of chronic rhinosinusitis (CRS). Three new key action statements on managing CRS that focus on the use of biologics (recommend against when patients do not have polyps and educate patients about them when they do) and a recommendation against the empiric use of antibiotics for CRS solely as a third‐party requirement for surgery or imaging.

Pelvicalyceal invasion (PCI) is a relatively novel pT3a staging parameter for renal cell carcinoma (RCC) nephrectomies. While interobserver reproducibility staging studies of sinus/vascular invasion in RCC exist, a similar evaluation for PCI has not been performed. Moreover, in our experience, there is also diagnostic variability in how pathologists interpret PCI. Herein, we explore interobserver reproducibility among genitourinary (GU) pathologists. Twenty hematoxylin and eosin-stained digitized slides from RCCs (all grossly approaching the renal pelvis) were distributed to 31 GU pathologists to classify each as PCI or not PCI based on their respective clinical practices; slides with concomitant sinus/fat/vascular invasion were excluded. Slides were then evaluated for the following 4 morphologic features: tumor abutting renal pelvis, tumor pushing/indenting into the renal pelvis, polypoid configuration of tumor into the renal pelvis, and tumor eroding through renal pelvic urothelium. Interobserver reproducibility was assessed, and the morphologic features were correlated with PCI. Relationships between pathologists’ interpretations, morphologic features, and PCI were evaluated using hierarchical clustering. Although the diagnosis of PCI was relatively uniform with a majority agreement (>67%) reached in 16/20 slides, overall interobserver reproducibility was only moderate (kappa=0.601). While all 4 morphologic features were sensitive for PCI, polypoid configuration of the tumor into the renal pelvis and the tumor eroding through the renal pelvic urothelium were most specific (90%, 100%, respectively). Although we show general consensus among genitourinary pathologists on PCI assessment, clarifying the diagnostic guidelines with specific criteria should be included in pathologic staging systems.