Mullan, Aidan F.

Purpose: The anatomic position of the appendix may influence both the clinical presentation and diagnostic imaging accuracy in pediatric appendicitis, but its impact remains uncertain. This study aimed to determine the prevalence of retrocecal appendicitis in children and to evaluate whether appendix positioning affects ultrasound diagnostic performance or clinical outcomes. Methods: This was a retrospective cohort study including all children 0 to 18 years of age who presented to the Mayo Clinic Rochester Emergency Department between 2018 and 2023 and were diagnosed with appendicitis during their evaluation or subsequent hospitalization. Appendix location was determined by imaging or surgical documentation. Demographics, symptoms, signs, and complication rates were collected for patients with retrocecal appendicitis (RCA) and non-retrocecal appendicitis (NRCA). Results: Four hundred seven patients were included with 12.5% having RCA. Ultrasound was obtained in 92% of patients with RCA versus 82% of NRCA (rate difference: 10%, 95% CI: 2%-19%, P =0.018). In patients who received ultrasound imaging, findings were equivocal or falsely negative in 53% of RCA patients versus 30% of NRCA patients (RD = 24%, 9%-39%; P =0.003). Computed tomography (CT) was obtained in 51% of RCA patients versus 29% of NRCA (RD = 22%, 8%-37%; P =0.003) and was equivocal or falsely negative at similar rates in RCA (12%) and NRCA (13%; P =0.88). Clinically, there were no differences in diarrhea, emesis, location of abdominal pain, or white blood cell counts between RCA and NRCA. Rates of perforation, abscess formation, hospitalization longer than 7 days, and repeat hospitalizations were also similar. Conclusions: Retrocecal appendicitis is a common anatomic variant in children that presents with similar clinical features and outcomes compared with non-retrocecal appendicitis. However, its retrocecal position reduces the diagnostic sensitivity of limited abdominal ultrasound, often necessitating additional imaging with computed tomography. Despite these diagnostic challenges, retrocecal positioning is not associated with a worsened clinical course.

Objectives: To determine the frequency with which emergency medical services (EMS) clinicians recognize patients enrolled in hospice and describe their prehospital management. Methods: Observational cohort study of patients enrolled in hospice who were transported by EMS within a health system between May 5, 2018, and June 4, 2023. Two physicians reviewed each encounter to determine whether interventions were comfort-focused (hospice philosophy) or life-sustaining care. Interrater reliability was 100% (k = 1.0). Descriptive statistics are provided. Results: EMS clinicians identified hospice enrollment in 51% ( n = 46) of 88 encounters. Most patients (90%, n = 79) received comfort-focused care. Life-sustaining care was provided to four patients identified as hospice-enrolled and included cardiopulmonary resuscitation, an advanced airway, and vasopressors ( n = 1, 25%); spinal immobilization ( n = 2, 50%), and naloxone ( n = 1, 25%). Conclusion: Most patients received care consistent with the philosophy of hospice. However, EMS clinicians may have only identified half of patients enrolled in hospice. This demonstrates an opportunity to improve recognition of patients’ care preferences, starting in the out-of-hospital setting.

Abstract Delirium is a state of acute confusion characterized by deficits in attention that occurs commonly in hospitalized older adults and is associated with adverse outcomes. Delirium may have significant implications for cognitive health, however the relationship of delirium to mild cognitive impairment (MCI) and dementia is not fully understood. To evaluate the impact of delirium on cognitive health trajectories, we leveraged the Mayo Clinic Study of Aging (MCSA), a population-based cohort study of cognitive health and aging in residents of Olmsted County, Minnesota, who are between the ages of 30 and 89 and without a previous diagnosis of dementia at enrollment. Emergency Department and hospital encounters were identified for all patients enrolled in the MCSA, and clinical notes following each encounter up to 30 days were analyzed using a previously validated natural language processing (NLP) algorithm for delirium detection. The association between delirium within 30 days of hospitalization and the development of MCI or dementia was assessed using Cox proportional hazards regression, adjusted for patient age, sex, and level of education. Initial MCSA assessment indicated normal cognition for all individuals in this cohort. We found that delirium was significantly associated with development of MCI and dementia, with 42 individuals experiencing delirium within 30 days of hospitalization; hazard ratio of 10.07 (95% CI 4.14, 24.49) for developing MCI and 19.10 (95% CI 8.40, 43.47) for dementia compared to those without delirium. Our results suggest that hospitalization with an episode of delirium can significantly impact cognitive trajectories in older adults.

Objective Dysautonomia affects many patients with Parkinson's disease and correlates with increased cardiovascular mortality. We describe the frequency and onset time of autonomic dysfunction relative to disease onset in early‐onset Parkinson's disease (EOPD) and explore its association with mortality. Methods We identified all incident Parkinson cases with motor‐symptom onset before age 50 years evaluated at the Mayo Clinic Health System (1990–2022) including sex‐ and age‐matched controls for each patient. Medical record review confirmed clinical diagnosis and assessed the presence and onset of autonomic symptoms, relative to Parkinson onset. Results We included 829 patients with EOPD and 829 healthy controls. The median age at disease onset was 42 years (interquartile range [IQR] = 37–46 years). Autonomic symptoms were present in 63.4% of patients, compared with 27.0% of unaffected controls, and proceeded motor symptoms in 91.4%. Forty‐seven percent of patients with early‐onset Parkinson's disease had constipation, 27.4% had bladder urgency, 19.3% had orthostatic intolerance, and 15.4% had sweat dysfunction. Among male patients, 36.8% had erectile dysfunction. In our EOPD population only, the presence of any autonomic‐impairment symptoms correlated with a 2.71‐fold increased mortality risk; each additional reported symptom increased the relative mortality risk by 50% ( p < 0.001). Patients with constipation or orthostatic intolerance had a 3.22‐ and 2.78‐fold higher mortality than patients without these symptoms. Interpretation Autonomic impairment affects 63.4% of patients with EOPD and carries a 3‐fold higher mortality risk, which increases with every additional autonomic symptom reported. In our cohort, autonomic symptoms appeared most commonly after motor onset, contrasting with prodromal autonomic impairment seen in late‐onset Parkinson's disease (LOPD). ANN NEUROL 2026;99:964–975

Importance The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial. Objective To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults. Design, Setting, and Participants This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded. Exposure Administration of etomidate or ketamine as the induction agent for RSI. Main Outcomes and Measures The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups. Results Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes. Conclusions and Relevance In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.

Importance Validation of prognostic tools is an essential component of their integration into clinical practice. Objective To validate 4 delirium risk stratification tools in an independent emergency department (ED) cohort. Design, Setting, and Participants This prognostic study included a retrospective cohort of patients 65 years or older who presented to an academic ED between January 1, 2021, and December 31, 2024. Data were analyzed from February 10 to August 21, 2025. Exposure Delirium screening included the Delirium Triage Screen followed by the brief Confusional Assessment Method as part of the standard of care. Four delirium risk scores were obtained, including the Kennedy rule, the Zucchelli rule, the Mayo Delirium Prediction (MDP) tools, and the Recognizing Delirium in Emergency Medicine (REDEEM) score. Main Outcomes and Measures Main outcomes included risk score performances and diagnostic test accuracy measured using the area under the receiver operating characteristics curve (AUROC), sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and positive and negative likelihood ratios (LRs) with 95% CIs. Secondary outcomes were discriminative and calibration measures. Results A total of 44 578 patients were included, of whom 1701 (3.8%) were diagnosed with delirium. The median age was 80.0 (IQR, 75.0-85.0) years, and 22 786 patients (51.1%) were female. The Kennedy rule had an AUROC of 0.777 (95% CI, 0.766-0.789). At a cutoff of 5, sensitivity was 0.55 (95% CI, 0.52-0.57); specificity, 0.85 (95% CI, 0.84-0.85); positive LR, 3.54 (95% CI, 3.37-3.72); negative LR, 0.54 (95% CI, 0.51-0.57); PPV, 0.12 (95% CI, 0.12-0.13); and NPV, 0.98 (95% CI, 0.98-0.98). The Zucchelli tool had an AUROC of 0.701 (95% CI, 0.686-0.713). At a cutoff of 5, sensitivity was 0.68 (95% CI, 0.66-0.70); specificity, 0.66 (95% CI, 0.65-0.66); positive LR, 1.99 (95% CI, 1.92-2.06); negative LR, 0.49 (95% CI, 0.45-0.52); PPV, 0.07 (95% CI, 0.07-0.08); and NPV, 0.98 (95% CI, 0.98-0.98). The MDP tool had an AUROC of 0.898 (95% CI, 0.891-0.905). At a 30% cutoff, sensitivity was 0.51 (95% CI, 0.48-0.53); specificity, 0.95 (95% CI, 0.95-0.95); positive LR, 9.69 (95% CI, 9.11-10.31); negative LR, 0.52 (95% CI, 0.50-0.55); PPV, 0.28 (95% CI, 0.26-0.29); and NPV, 0.98 (95% CI, 0.98-0.98). The REDEEM score demonstrated the highest AUROC at 0.921 (95% CI, 0.914-0.929). Using a cutoff of 11 or greater, sensitivity was 0.83 (95% CI, 0.81-0.85); specificity, 0.92 (95% CI, 0.91-0.92), negative LR, 0.18 (95% CI, 0.17-0.20); positive LR, 9.91 (95% CI, 9.54-10.29); PPV, 0.28 (95% CI, 0.27-0.29); and NPV, 0.99 (95% CI, 0.99-0.99). Conclusions and Relevance In this prognostic study comparing 4 delirium tools to improve delirium detection and identify high-risk patients, the REDEEM score and the MDP tool had better performance for delirium detection in the ED. These findings lay the groundwork for integrating validated risk stratification into ED workflows to improve early delirium detection and inform prevention strategies for high-risk older adults.

ABSTRACT Background The Geriatric Emergency Department (ED) guidelines recommend screening older adults for delirium using evidence‐based screening tools, but these tools are often underutilized. We aimed to identify barriers and facilitators to implementing an electronic health record (EHR)‐based delirium screening tool as intended. Methods This mixed methods and focused ethnographic study combined a review of structured delirium screening data with observations of real‐time delirium screenings and semi‐structured in‐person interviews at an academic ED that previously implemented the Delirium Triage Screen (DTS) and Brief Confusion Assessment Method (bCAM) tool. Content analysis of field notes from observations and interview transcripts was guided by the Exploration, Preparation, Implementation, and Sustainment implementation framework. Results From a total of 40,818 ED visits, 6196 (15.2%) had incomplete screens (i.e., without fidelity). We observed 62 encounters, of which 25 (40.3%) screenings were implemented without fidelity due to (1) not asking the required screening questions, (2) assuming patient responses, or (3) not completing the screen due to uncertainty regarding a patient's baseline mentation. We conducted 32 interviews. Identified barriers included staff prioritization of other tasks (e.g., stroke code, cleaning patients), limited knowledge of the screen's importance and utility, and language discordance. Facilitators included care partners providing baseline mental status information and nurses prefacing the screening to increase patient engagement. Conclusion The fidelity of ED delirium screening is influenced by an interplay of environmental, patient, provider, and caregiver factors. Fidelity may be improved by focusing education on the importance of screening, training screeners on how to determine whether a patient's mentation is acutely changed, providing clear action steps when a patient screens positive, and addressing how to administer the delirium screen to patients who do not speak English fluently.

Key Points Increased protein expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase was observed in old adults compared with young adults. In old adults, overexpressed proteins were enriched in mitochondrial processes while under expressed proteins enriched in RNA metabolism. Validated differentially expressed proteins were not significantly correlated with kidney pathology after adjusting for age. Background Kidney aging is characterized by a loss of glomeruli, predominantly in the superficial cortex, with a resultant decline in GFR and an increased risk of various kidney-related diseases. The early molecular alterations in glomeruli associated with the aging process are not well studied. Methods We combined laser capture microdissection and mass spectrometry–based unbiased proteomic analysis of nonsclerosed, nonischemic glomeruli in the superficial cortex from young and old adults who underwent a radical nephrectomy for a tumor to understand the age-related molecular changes in glomeruli. Twenty-four young and 30 old adults were used for the discovery dataset, and the significant differentially expressed proteins were further validated using an independent set comprising six young and eight old adults. Results Kidneys from old adults had lower eGFR, less kidney parenchyma on computed tomography imaging, and more glomerulosclerosis and arteriosclerosis on histology. Quantitative proteomic analysis of nonsclerosed, nonischemic glomeruli identified increased expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase in old adults that were further validated in an independent set. Pathway analysis indicated that proteins with increased expression in old adults were enriched in mitochondrial translational processes, aerobic respiration, and TCA cycle, whereas proteins with decreased expression in old adults were enriched in mRNA splicing, mRNA processing, and nonsense mediated decay. Furthermore, validated differentially expressed proteins did not show any significant correlation with the kidney pathology independent of age group. Conclusions Overall, this study identified proteins that are specifically associated with the aging process in otherwise normal-appearing glomeruli.

Background and importance Emergency airway management in the emergency department (ED) is a high-risk procedure associated with patient outcomes. First-attempt success is a widely recognized quality metric, as multiple attempts are associated with an increased risk of peri-intubation complications. In Brazil, where emergency medicine is a recently established specialty, many ED are staffed by physicians without formal emergency medicine training. The association between emergency medicine training and intubation outcomes in this setting has not been well characterized. Objective To assess the association of physician specialty with first-attempt success and immediate peri-intubation complications in Brazilian EDs. Design Secondary analysis of a multicenter, prospective cohort study from the Brazilian Airway Registry Cooperation. Setting and participants This study included adult patients who underwent tracheal intubation in EDs between March 2022 and April 2024. Patients were excluded if the intubation occurred outside the ED, during cardiopulmonary resuscitation, or for elective procedures. Intubations performed by medical students were also excluded. Physicians were categorized by specialty as emergency medicine or nonemergency medicine. Outcome measures and analysis The primary outcome was first-attempt success; secondary outcomes included peri-intubation complications (severe hypoxemia, hemodynamic instability, and cardiac arrest). Multivariable logistic regression was used to assess the association between physician specialty and outcomes. Main results Among 2582 patients, 1087 (42.1%) were intubated by emergency physicians and 1495 (57.9%) by other physicians (mainly internal medicine and surgery). Intubations by emergency physicians were associated with a higher rate of first-attempt success [80.4 vs. 70.9%, adjusted odds ratio [aOR]: 1.63, 95% confidence interval (CI): 1.34–1.97]. There was also a higher odds of intubations without major complications (aOR: 1.20, 95% CI: 1.01–1.42). Conclusion In this study, there was a higher rate of first-attempt success in intubations performed by board-certified emergency physicians compared with other physicians working in Brazilian EDs.