Etiology and characteristics of non-aneurysmal thunderclap headache presenting to an acute setting.

OBJECTIVES: To describe the characteristics and causes of non-aneurysmal thunderclap headache (TCH) and compare serious from benign underlying causes. METHODS: Retrospective cohort study of consecutive adult patients with TCH presenting to a tertiary care academic medical center between 2010 and 2020. Aneurysmal subarachnoid hemorrhage cases were excluded. Cases were categorized into serious or benign; serious TCH was defined as any condition in which delayed diagnosis and treatment could result in neurological disability or death. Risk factors for serious TCH were analyzed. We adhere to standardized guidelines for reporting observational studies. RESULTS: A total of 932 patients presented with TCH. After exclusion of 393 patients with aneurysmal-type subarachnoid hemorrhage, 539 were included in the analysis. One-half (n = 275, 51.0 %) had a serious cause. Median age was 51 years, 69.0 % were female. Most frequent diagnoses were intracranial hemorrhage (n = 102, 18.9 %), reversible cerebral vasoconstriction syndrome (n = 97, 18.0 %), and idiopathic TCH (n = 102, 38.6 %). A multivariable logistic regression model for prediction of serious TCH included age, hypertension, migraines, recurrent TCH, level of consciousness and other clinical exam findings, and achieved an AUROC of 0.732. This score had a sensitivity of 79.9 % (95 % CI 73.5-83.5 %) for the identification of serious TCH. A 0.5-point increase in the risk score was associated with a 73 % increase in the odds of serious TCH (odds ratio 1.73, 95 % CI 1.53-1.95, p < 0.001). CONCLUSION: Our study describes the relative frequency of presentation and etiologies among patients with TCH This score can aide clinicians in recognising patients with potentially serious cause of TCH, for whom additional imaging and neurological consultation is necessary.

Incidence of Acute Mountain Sickness in Adolescents Backpacking at Philmont Scout Ranch.

INTRODUCTION: Individuals ascending to elevations above 2500 m are at risk of developing altitude illness. We sought to establish the incidence and to determine what risk factors, if any, increased the likelihood of developing acute mountain sickness (AMS) in adolescents at Philmont Scout Ranch (PSR) in Cimarron, New Mexico. PSR, with elevations ranging from 2011 to 3792 m, attracts thousands of adolescent participants each year, many of whom arrive from lower elevations with little or no experience ascending to high altitude. METHODS: We conducted a prospective observational study of adolescent participants aged 14 to 19 years who ascended to a minimum of 3000 m while trekking from June to July 2021. Prior to the start of each participant's trek, pretrek survey data were obtained at PSR's basecamp (2011 m). During the trek at 3048 m, the Lake Louise AMS score was used to diagnose AMS. RESULTS: The incidence of AMS in our study was 13.7%. Participants reporting a history of daily headaches had more than four times the risk of developing AMS. A history of gastrointestinal problems carried three times the risk of developing AMS, and a prior history of AMS increased the risk of developing AMS by 44%. CONCLUSIONS: Our findings enhance our understanding of AMS risk in adolescents and may provide guidance to youth for developing AMS. For individuals with a history of headaches or gastrointestinal problems or a prior history of AMS, there may be an opportunity to reduce the risk of developing AMS.

Air Pollution and Parkinson Disease in a Population-Based Study.

Importance: The role of air pollution in risk and progression of Parkinson disease (PD) is unclear. Objective: To assess whether air pollution is associated with increased risk of PD and clinical characteristics of PD. Design, Setting, and Participants: This population-based case-control study included patients with PD and matched controls from the Rochester Epidemiology Project from 1998 to 2015. Data were analyzed from January to June 2024. Exposures: Mean annual exposure to particulate matter with a diameter of 2.5 µm or less (PM2.5) from 1998 to 2015 and mean annual exposure to nitrogen dioxide (NO2) from 2000 to 2014. Main Outcomes and Measures: Outcomes of interest were PD risk, all-cause mortality, presence of tremor-predominant vs akinetic rigid PD, and development of dyskinesia. Models were adjusted for age, sex, race and ethnicity, year of index, and urban vs rural residence. Results: A total of 346 patients with PD (median [IQR] age 72 [65-80] years; 216 [62.4%] male) were identified and matched on age and sex with 4813 controls (median [IQR] age, 72 [65-79] years, 2946 [61.2%] male). Greater PM2.5 exposure was associated with increased PD risk, and this risk was greatest after restricting to populations within metropolitan cores (odds ratio [OR], 1.23; 95% CI, 1.11-1.35) for the top quintile of PM2.5 exposure compared with the bottom quintile. Greater NO2 exposure was also associated with increased PD risk when comparing the top quintile with the bottom quintile (OR, 1.13; 95% CI, 1.07-1.19). Air pollution was associated with a 36% increased risk of akinetic rigid presentation (OR per each 1-µg/m3 increase in PM2.5, 1.36; 95% CI, 1.02-1.80). In analyses among patients with PD only, higher PM2.5 exposure was associated with greater risk for developing dyskinesia (HR per 1-µg/m3 increase in PM2.5, 1.42; 95% CI, 1.17-1.73), as was increased NO2 exposure (HR per 1 µg/m3 increase in NO2, 1.13; 95% CI, 1.06-1.19). There was no association between PM2.5 and all-cause mortality among patients with PD. Conclusions and Relevance: In this case-control study of air pollution and PD, higher levels of PM2.5 and NO2 exposure were associated with increased risk of PD; also, higher levels of PM2.5 exposure were associated with increased risk of developing akinetic rigid PD and dyskinesia compared with patients with PD exposed to lower levels. These findings suggest that reducing air pollution may reduce risk of PD, modify the PD phenotype, and reduce risk of dyskinesia.

Outcomes associated with prehospital epinephrine in adult and pediatric patients with anaphylaxis.

BACKGROUND: Prompt epinephrine administration is important to improve outcomes in anaphylaxis. OBJECTIVE: To assess the impact of prehospital epinephrine on clinical outcomes of hospital admission, biphasic reactions, and emergency department (ED) length of stay (LOS) in a cohort of ED patients who had anaphylaxis including both children and adults. METHODS: We conducted a single-center prospective and retrospective cohort study of patients who had anaphylaxis from April 2008 to December 2022. Associations between prehospital epinephrine administration with biphasic reactions and ED LOS were assessed with univariable models and the association with ED disposition was assessed with both univariable and multivariable logistic regression. RESULTS: A total of 1107 patient visits were included for analysis. The median patient age was 29 (IQR: 14-50), 593 (53.6%) patients were of female sex, and 366 (33.1%) were younger than 18 years of age. Patients in the prehospital epinephrine group were also less likely to experience a biphasic reaction (5.4% vs 9.3%; odds ratio [OR] 0.56, 95% CI: 0.34-0.92) and had a decreased ED LOS (median 4.0 hours vs 4.7 hours). There was no difference in hospital admission between patients with and without prehospital epinephrine in both the univariable (19.5% vs 15.7%; OR 1.30, 95% CI: 0.94-1.79) and multivariable (adjusted OR 1.08, 95% CI: 0.71-1.64) models. CONCLUSION: Prehospital epinephrine administration reduced the odds of a biphasic reaction and decreased ED LOS but did not reduce hospitalization in this cohort of ED patients who had anaphylaxis. Our findings suggest that timely administration of prehospital epinephrine is associated with improved patient outcomes.

Incidence of Primary Progressive Apraxia of Speech and Primary Progressive Aphasia in Olmsted County, MN, 2011-2022.

BACKGROUND AND OBJECTIVE: No epidemiologic studies have formally assessed the incidence of primary progressive aphasia (PPA) and primary progressive apraxia of speech (PPAOS). Thus, we decided to assess the incidence of these disorders in Olmsted County, MN, between 2011 and 2022, and to characterize clinical, radiographic, and pathologic characteristics of these patients. METHODS: This was a retrospective examination of data from a population-based cohort of patients with PPA and PPAOS prospectively identified in Olmsted County, MN, from 2011 to 2022. The incidence of PPA among adults (older than 18 years) was calculated for Olmsted County as the number of patients per 100,000 person-years during the study period. The adult population of Olmsted County was determined by the annual catchment population reported by the Rochester Epidemiological Project for each year 2011-2022. A behavioral neurologist verified the clinical diagnoses and determined subtypes. RESULTS: We identified 10 patients (60% female) within the study period (median age of symptoms onset: 70 years; range: 66-73), 8 with PPA and 2 with PPAOS. Of the 8 patients with PPA (6 female patients, 2 male patients), 2 met criteria for non-fluent variant PPA (nfvPPA), 3 for logopenic variant PPA (lvPPA), and 3 for semantic variant (svPPA). Speech evaluation confirmed the clinical diagnoses in all patients and all showed typical imaging findings consistent with their respective subtype. Six patients (2 PPAOS, 2 nfvPPA, 2 lvPPA) died and 3 underwent autopsy (2 PPAOS, 1 nfvPPA), confirming the pathologic diagnosis of progressive supranuclear palsy. The incidence of PPA + PPAOS was 0.70 persons per 100,000 person-years (95% CI 0.34-1.29 persons per 100,000) during the study period. The incidence of PPAOS was 0.14 persons per 100,000 person-years (95% CI 0.02-0.55 persons per 100,000), whereas for the 8 patients with PPA, the incidence was 0.56 persons per 100,000 person-years (95% CI 0.24-1.10 cases per 100,000). The incidence of nfvPPA was 0.14 persons per 100,000 person-years (95% CI 0.02-0.55), 0.21 persons per 100,000 person-years (95% CI 0.04-0.61) for lvPPA, and 0.21 persons per 100,000 person-years (95% CI 0.04-0.61) for svPPA. DISCUSSION: As a group, PPA and PPAOS are a relatively rare group of diseases. PPAOS has a slightly lower incidence than PPA as a group but similar incidence to the individual PPA variants.

Reproductive life factors and estro-progestin exposure in women with early-onset Parkinson's disease compared to late-onset disease and controls: A retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is more common in men than women. Although hormonal factors may partially explain this difference, there are no studies evaluating reproductive life factors and exogenous estroprogestin exposure in women with Early Onset Parkinson Disease (EOPD). OBJECTIVE: To compare reproductive life factors and exogenous estroprogestin exposure among female patients with EOPD, late-onset Parkinson's disease (LOPD), and EOPD-matched unaffected controls. METHODS: We identified female patients with EOPD from 1989 to 2021, defining EOPD as PD with motor-symptoms onset before age 50 and LOPD as PD with motor onset after 50. We paired EOPD patients to age-matched, unaffected controls. We reviewed medical records to determine demographic characteristics, clinical history, and reported reproductive menopausal history (reviewing medical records). RESULTS: We included 87 EOPD patients, 84 LOPD patients, and 91 unaffected controls with information about reproductive life factors and exogenous estroprogestin exposure in their medical records. There were no significant differences in race, ethnicity, or BMI between the three groups. EOPD patients were more likely to have used hormonal contraception than LOPD patients (23/49 (47 %) vs 0/84 (0 %), p < 0.001). LOPD patients had higher numbers of pelvic surgeries (48/84 [57 %] in LOPD, 23/87 [26 %] in EOPD, p < 0.001) and higher usage of perimenopausal hormonal therapy (52/84 [62 %] in LOPD, 10/87 [11 %] in EOPD, p < 0.001) in LOPD than EOPD. CONCLUSIONS: Our study reports no significant difference in reproductive life factors and exogenous estroprogestin exposure between controls and EOPD patients, except for higher exposure to hormonal contraception in EOPD. There was no apparent difference in reproductive life factors and exogenous estroprogestin exposure between EOPD and LOPD patients. Our findings therefore do not observe that hormonal exposure is different between earlier onset of female EOPD compared to female LOPD patients, or between female EOPD patients and unaffected female controls.

Providing Performance Feedback and Patient Outcome Follow-Up to Emergency Medical Services (EMS) is Associated with Subsequent Improved Clinical Performance.

OBJECTIVE: Emergency Medical Services (EMS) clinicians desire performance feedback (PF) and patient outcome follow-up (POF). Within our agency, both a peer-review and feedback/outcome (PF/POF) process exist. Our objective was to determine whether receiving feedback and outcome data improved future clinical care amongst EMS, based upon peer-review scores. METHODS: This retrospective cohort study took place between 1/1/2020 and 6/7/2023 within an EMS agency site with 22,000 average annual 9-1-1 calls. Requests for PF/POF were submitted on an individual basis beginning June 2020 and completed by a dedicated EMS nurse, EMS physician, or emergency medicine (EM) resident. Peer-review of select high-acuity cases were scored by two Quality Assurance (QA) specialists within the categories of assessment, treatment, disposition/outcome and process/administrative guidelines. Association between overall peer-review score and number of PF/POF requests at time of assessment was evaluated by linear regression. RESULTS: A total of 378 PF/POF requests were received, with the most common patient complaints being cardiac (n = 105; 27.8%, including 49 (13.0%) out of hospital cardiac arrests), altered mental status/neurologic (n = 103; 27.2%), trauma (n = 61; 16.1%, including 2 (0.5%) traumatic arrests); and respiratory distress (n = 47; 12.4%). A total of 378 runs meeting QA criteria were peer-reviewed post-PF/POF process implementation, including 337 (89.2%) cardiac/respiratory arrests, 27 (7.1%) with difficult airway management, and 14 (3.7%) major trauma/traumatic arrests. The number of prior PF/POF requests made by the team leader was associated with higher overall peer-review scores. Team leaders with >5 prior PF/POF requests had a peer-review score 0.39 points greater (95% CI: 0.16 - 0.62, p = 0.001) than those with <5 prior requests. The number of prior PF/POF requests amongst the entire crew was also associated with higher peer-review scores. Crews that collectively had >5 prior PF/POF requests had an increase in peer-review score 0.32 points greater (95% CI: 0.14 - 0.50, p < 0.001) than those with <5 prior requests. CONCLUSION: Providing performance feedback and patient outcome follow-up to EMS is associated with improved peer-review scores of clinical performance. Future studies should assess if those that are submitting cases for feedback/outcome are higher performers at baseline or if the process of receiving feedback/outcome improves their performance.

Improving emergency medicine resident pediatric lumbar puncture procedural performance through a brief just-in-time video intervention.

BACKGROUND: Emergency medicine (EM) trainee comfort level with lumbar puncture (LP) has decreased over time due to changing practice guidelines, particularly amongst pediatric patients. We implemented a "just in time" (JIT) brief educational video based on a previously published LP Performance Scoring Checklist to improve trainee efficiency and competence in LP performance. METHODS: Our pilot quasi-experimental study took place January-June 2022 within a large, academic Midwestern emergency department (ED) with an established 3-year EM residency program. All 9 interns performed a timed diagnostic LP on an infant LP model in January, scored according to the LP Performance Scoring Checklist. In June, interns repeated the timed LP procedure directly after watching a brief educational video based on major checklist steps. The study was deemed exempt by the Institutional Review Board. RESULTS: All interns completed both assessments. At baseline, interns had logged performance of median 2 (IQR 0-5) LPs and spent 12.9 (10.3-14.4) minutes performing the procedure. Post-intervention, interns had logged an additional median 2 (0-5) LPs and completed the procedure faster with an average time of 10.3 (9.7-11.3) minutes (p = 0.004). A median of 5 (4-7) major steps were missed at baseline, compared to 1 (1-2) at time of post-intervention assessment (p = 0.015). CONCLUSION: Development of a brief educational video improved efficiency and competency amongst our intern class in performing an infant LP when viewed Just-In-Time. Similar efforts may improve education and performance of other rare (or decreasing in frequency) procedures within EM training.

Impulse control disorders and use of dopamine agonists in early onset Parkinson's disease.

Introduction: Impulse control disorders (ICDs) are defined as excessive and repetitive behaviors that may affect Parkinson's disease (PD) patients exposed to dopamine agonists. Current data on ICDs in patients with early-onset Parkinson's disease (EOPD) is lacking. In this study we aim to assess the frequency of use of dopamine agonists, the prevalence of ICDs, and to explore potential factors associated with their development in patients with EOPD. Methods: We used the Mayo Clinic Data Explorer system to investigate a population-based cohort of EOPD patients between 1990 and 2022 at Mayo Clinic, Rochester, MN. We used ICD coding for parkinsonism; then, we reviewed all the clinical records and included only those patients with a clinical diagnosis of PD with symptoms onset at or before the age of 50, and who developed ICDs after using therapeutic doses of dopamine agonists. Results: A total of 831 (513 males and 318 females) patients with EOPD were included with a median age at symptom onset of 42 years of age (CI: 37-46). Dopamine agonists were used in 49.7% of all patients; of these, only 14.5% developed symptoms of one or more ICDs. Hypersexuality was the most commonly observed ICD (38.3%), and the only one having a statistically significant male predominance (p = 0.011). Conclusion: ICDs are common in EOPD, particularly when associated with the use of dopamine agonists.

A Population-Based Approach to the Argument on Brain-First and Body-First Pathogenesis of Lewy Body Disease.

OBJECTIVE: To explore the clinical progression of the brain-/body-first categories within Lewy body disease (LBD): Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD dementia. METHODS: We used of the Rochester Epidemiology Project to establish a population-based cohort of clinically diagnosed LBD. We used two definitions for differentiating between brain- and body-first LBD: a previously hypothesized body-first presentation in patients with rapid eye movement sleep behavior onset before motor symptoms onset; and an expanded definition of body-first LBD when a patient had at least 2 premotor symptoms between constipation, erectile dysfunction, rapid eye movement sleep behavior, anosmia, or neurogenic bladder. RESULTS: Brain-first patients were more likely to be diagnosed with PD (RR = 1.43, p = 0.003), whereas body-first patients were more likely to be diagnosed with DLB (RR = 3.15, p < 0.001). Under the expanded definition, there was no difference in LBD diagnosis between brain-first and body-first patients (PD: RR = 1.03, p = 0.10; DLB: RR = 0.88, p = 0.58) There were no patterns between brain- or body-first presentation, PD dementia under either definition (original: p = 0.09, expanded: p = 0.97), and no significant difference in motor symptoms between brain-first and body-first. INTERPRETATION: Our findings do not support the dichotomous classification of body-first and brain-first LBD with the currently proposed definition. Biological exposures resulting in PD and DLB are unlikely to converge on a binary classification of top-down or bottom-up synuclein pathology. ANN NEUROL 2024;96:551-559.

Flexible endoscopic intubation in emergency medicine: A mixed-methods needs assessment.

Objectives: This needs assessment aimed to improve understanding of flexible endoscopic intubation training and practice in emergency medicine (EM), providing insights to educators and practice leaders seeking to improve education and practices. Methods: We conducted a multicenter, mixed-methods needs assessment of emergency physicians (EPs) incorporating focus groups and a survey. Focus groups comprised community EPs, academic EPs, and resident EPs. We analyzed focus group transcripts using grounded theory, qualitatively describing EM endoscopic intubation. The qualitative analysis shaped our survey instrument, which we deployed in cross-sectional fashion. We report survey data with descriptive statistics. Results: Focus groups with 13 EPs identified three themes: indications for use of endoscopic intubation, factors impacting a physician's decision to endoscopically intubate, and attaining and maintaining endoscopic intubation competency. Of 257 surveyed EPs (33% response rate), 79% had received endoscopic intubation training during residency, though 82% had performed this procedure 10 or fewer times in their career. Despite 97% acknowledging the necessity of competency, only 23% felt highly confident in their ability to perform endoscopic intubation. Participants (93%) reported scarce opportunities to perform the procedure and identified factors believed to facilitate competency acquisition and maintenance, including opportunities to perform endoscopic intubation in practice (98%), local champions (93%), and performing nasopharyngoscopy (87%). Conclusions: While most EPs acknowledged the importance of competency in endoscopic intubation, they reported scarce procedural opportunities and commonly expressed low confidence. Further research is needed on this topic, and we propose avenues to enhance education and practices related to endoscopic intubation. These include development of robust procedural curricula, support of local champions, and incorporating nasopharyngoscopy into EM practice.

Association between school learning models and psychological and social health visits to the emergency room.

Objectives: We aimed to assess the impact of in-person and distance school learning models on children's visits to the emergency department (ED) for psychological or social ("psychosocial") complaints. Methods: We analyzed presentations to one emergency department in a mid-sized Midwestern city. We used the public school system schedule to determine in-person and distance learning periods by the grade level. We calculated the incidence of visits to the emergency department during academic years 2018-2019, 2019-2020, and 2020-2021, with particular attention to the time after March 13, 2020, which was the pandemic period. We compared the incidence of visits during in-person versus distance learning school models. Results: A total of 7181 visits occurred during the academic years studied, 17.1% due to psychosocial complaints. The incidence of psychosocial visits to the ED was lower during distance learning than during the pandemic in-person learning period (given per 1000 student years: 20.5 vs. 24.1, p = 0.14). This difference was statistically significant among middle schoolers (23.3 vs. 46.6, p < 0.001). While not statistically significant, the difference among high schoolers was pragmatically relevant (38.2 vs. 49.3, p = 0.086). Conclusions: Distance learning was associated with a decrease in the incidence of psychosocial visits to the emergency department relative to in-person learning. Future investigation is required to verify results and better understand any causative relationships.

Payer Type and Emergency Department Visit Prices.

This cross-sectional study assesses list prices, cash prices, and negotiated rates for emergency department services.

Risk of falls is associated with 30-day mortality among older adults in the emergency department.

OBJECTIVE: Falls in older adults correlate with heightened morbidity and mortality. Assessing fall risk in the emergency department (ED) not only aids in identifying candidates for prevention interventions but may also offer insights into overall mortality risk. We sought to examine the link between fall risk and 30-day mortality in older ED adults. METHODS: Observational cohort study of adults aged ≥ 75years who presented to an academic ED and who were assessed for fall risk using the Memorial Emergency Department Fall Risk Assessment Tool (MEDFRAT), a validated, ED-specific screening tool. The fall risk was classified as low (0-2 points), moderate (3-4 points), or high (≥5) risk. The primary outcome was 30-day mortality. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 941 patients whose fall risk was assessed in the ED were included in the study. Median age was 83.7 years; 45.6% were male, 75.6% lived in private residences, and 62.7% were admitted. Mortality at 30 days among the high fall risk group was four times that of the low fall risk group (11.8% vs 3.1%; HR 4.00, 95% CI 2.18 to 7.34, p < 0.001). Moderate fall risk individuals had nearly double the mortality rate of the low-risk group (6.0% vs 3.1%), but the difference was not statistically significant (HR 1.98, 95% CI 0.91 to 4.32, p = 0.087). CONCLUSION: ED fall risk assessments are linked to 30-day mortality. Screening may facilitate the stratification of older adults at risk for health deterioration.

Relationship between individual and country-level socio-economic background, USMLE step scores, and demographics of international medical graduates and residency match results.

PURPOSE: Twenty five percent of practicing physicians in the US are International Medical Graduates (IMGs) - physicians who completed their medical school training outside of the United States and Canada. There are multiple studies demonstrating higher socio-economic background is associated with medical school matriculation in the US. However, despite a substantial prevalence of IMGs in the American healthcare system, studies of the association between demographics, socio-economic background, and securing a residency position in the match are lacking. METHODS: We created a survey with questions on residency match-related data and information on personal socio-economic background. An invitation to participate in the study was sent to all IMGs that applied to the included residency programs after the conclusion of the 2022 residency match. We used multivariable logistic regression to compare survey responses to the odds of securing a residency match. RESULTS: The total number of survey respondents was 744 (response rate 15.1%). We found that younger age, higher United States Medical License Examination (USMLE) scores, higher-income country of origin (including the United States), fewer match attempts, applying to fewer specialties, having parents with college degree or higher, and coming from higher-than-average or lower-than-average family income were independently associated with increased odds of matching. Gender, personal income, and visa status did not demonstrate significant associations with residency match. CONCLUSIONS: Residency match is a significant expense for IMGs, especially for those from lower-income countries. International applicants from higher socio-economic backgrounds might have advantages in securing medical residency positions in the United States when controlling for other variables.

Association of Kidney Cysts With Progressive CKD After Radical Nephrectomy.

RATIONALE & OBJECTIVE: Simple kidney cysts, which are common and usually considered of limited clinical relevance, are associated with older age and lower glomerular filtration rate (GFR), but little has been known of their association with progressive chronic kidney disease (CKD). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Patients with presurgical computed tomography or magnetic resonance imaging who underwent a radical nephrectomy for a tumor; we reviewed the retained kidney images to characterize parenchymal cysts at least 5mm in diameter according to size and location. EXPOSURE: Parenchymal cysts at least 5mm in diameter in the retained kidney. Cyst characteristics were correlated with microstructural findings on kidney histology. OUTCOME: Progressive CKD defined by dialysis, kidney transplantation, a sustained≥40% decline in eGFR for at least 3 months, or an eGFR<10mL/min/1.73m2 that was at least 5mL/min/1.73m2 below the postnephrectomy baseline for at least 3 months. ANALYTICAL APPROACH: Cox models assessed the risk of progressive CKD. Models adjusted for baseline age, sex, body mass index, hypertension, diabetes, eGFR, proteinuria, and tumor volume. Nonparametric Spearman's correlations were used to examine the association of the number and size of the cysts with clinical characteristics, kidney function, and kidney volumes. RESULTS: There were 1,195 patients with 50 progressive CKD events over a median 4.4 years of follow-up evaluation. On baseline imaging, 38% had at least 1 cyst, 34% had at least 1 cortical cyst, and 8.7% had at least 1 medullary cyst. A higher number of cysts was associated with progressive CKD and was modestly correlated with larger nephrons and more nephrosclerosis on kidney histology. The number of medullary cysts was more strongly associated with progressive CKD than the number of cortical cysts. LIMITATIONS: Patients who undergo a radical nephrectomy may differ from the general population. A radical nephrectomy may accelerate the risk of progressive CKD. Genetic testing was not performed. CONCLUSIONS: Cysts in the kidney, particularly the medulla, should be further examined as a potentially useful imaging biomarker of progressive CKD beyond the current clinical evaluation of kidney function and common CKD risk factors. PLAIN-LANGUAGE SUMMARY: Kidney cysts are common and often are considered of limited clinical relevance despite being associated with lower glomerular filtration rate. We studied a large cohort of patients who had a kidney removed due to a tumor to determine whether cysts in the retained kidney were associated with kidney health in the future. We found that more cysts in the kidney and, in particular, cysts in the deepest tissue of the kidney (the medulla) were associated with progressive kidney disease, including kidney failure where dialysis or a kidney transplantation is needed. Patients with cysts in the kidney medulla may benefit from closer monitoring.

Exploring the single-cell immune landscape of kidney allograft inflammation using imaging mass cytometry.

Kidney allograft inflammation, mostly attributed to rejection and infection, is an important cause of graft injury and loss. Standard histopathological assessment of allograft inflammation provides limited insights into biological processes and the immune landscape. Here, using imaging mass cytometry with a panel of 28 validated biomarkers, we explored the single-cell landscape of kidney allograft inflammation in 32 kidney transplant biopsies and 247 high-dimensional histopathology images of various phenotypes of allograft inflammation (antibody-mediated rejection, T cell-mediated rejection, BK nephropathy, and chronic pyelonephritis). Using novel analytical tools, for cell segmentation, we segmented over 900 000 cells and developed a tissue-based classifier using over 3000 manually annotated kidney microstructures (glomeruli, tubules, interstitium, and arteries). Using PhenoGraph, we identified 11 immune and 9 nonimmune clusters and found a high prevalence of memory T cell and macrophage-enriched immune populations across phenotypes. Additionally, we trained a machine learning classifier to identify spatial biomarkers that could discriminate between the different allograft inflammatory phenotypes. Further validation of imaging mass cytometry in larger cohorts and with more biomarkers will likely help interrogate kidney allograft inflammation in more depth than has been possible to date.

Development of a machine learning algorithm based on administrative claims data for identification of ED anaphylaxis patient visits.

Background: Epidemiologic studies of anaphylaxis commonly rely on International Classification of Diseases (ICD) codes to identify anaphylaxis cases, which may lead to suboptimal epidemiologic classification. Objective: We sought to develop and assess the accuracy of a machine learning algorithm using ICD codes and other administrative data compared with ICD code-only algorithms to identify emergency department (ED) anaphylaxis visits. Methods: We conducted a retrospective review of ED visits from January 2013 to September 2017. Potential ED anaphylaxis visits were identified using 3 methods: anaphylaxis ICD diagnostic codes (method 1), ICD symptom-based codes with or without a code indicating an allergic trigger (method 2), and ICD codes indicating a potential allergic reaction only (method 3). A machine learning algorithm was developed from administrative data, and test characteristics were compared with ICD code-only algorithms. Results: A total of 699 of 2191 (31.9%) potential ED anaphylaxis visits were classified as anaphylaxis. The sensitivity and specificity of method 1 were 49.1% and 87.5%, respectively. Method 1 used in combination with method 2 resulted in a sensitivity of 53.9% and a specificity of 68.7%. Method 1 used in combination with method 3 resulted in a sensitivity of 98.4% and a specificity of 15.1%. The sensitivity and specificity of the machine learning algorithm were 87.3% and 79.1%, respectively. Conclusions: ICD coding alone demonstrated poor sensitivity in identifying cases of anaphylaxis, with venom-related anaphylaxis missing 96% of cases. The machine learning algorithm resulted in a better balance of sensitivity and specificity and improves upon previous strategies to identify ED anaphylaxis visits.

Risk of hospitalization in synucleinopathies and impact of psychosis.

Background: Few studies have investigated the risk of hospitalization among patients with synucleinopathies (Parkinson disease, Dementia with Lewy Bodies, Parkinson disease dementia, Multiple System Atrophy) with associated psychosis and the impact of antipsychotic treatments on hospital admissions and duration of the stay. Objective: To determine the risk of hospitalization among patients with synucleinopathies and in patients with associated psychosis. To evaluate the impact of antipsychotic treatments on hospital admission of patients with synucleinopathies and psychosis in an incident cohort study in Olmsted County, Minnesota (MN). Methods: We used the Rochester Epidemiology Project (REP) to define an incident cohort of patients with clinically diagnosed synucleinopathies (1991-2010) in Olmsted County, MN. A movement disorder specialist reviewed all medical records to confirm the clinical diagnosis of synucleinopathies using the NINDS/NIMH unified diagnostic criteria. Results: We included 416 incident cases of clinically diagnosed synucleinopathies from 2,669 hospitalizations. 409 patients (98.3%) were admitted to the hospital at least once for any cause after the onset of parkinsonism. The median number of hospitalizations for a single patient was 5. In total, 195 (46.9%) patients met the criteria for psychosis: patients with psychosis had a 49% (HR = 1.49, p < 0.01) increased risk of hospitalization compared to patients without psychosis. Among patients with psychosis, 76 (39%) received antipsychotic medication. Treatment with antipsychotic medications did not affect the risk of hospitalization (HR = 0.93, p = 0.65). The median length of hospitalization among the entire cohort was 1 (IQR 0-4) day. There was no difference between hospitalization length for patients with no psychosis and patients with active psychosis (RR = 1.08, p = 0.43) or patients with resolved psychosis (RR = 0.79, p = 0.24). Conclusion: Psychosis increases the risk of hospitalization in patients with clinically defined synucleinopathies; however, it does not affect the length of hospital stays in our cohort. Antipsychotic treatment does not affect the risk of hospitalization in our study.

Sleep Disorders in Early-Onset Parkinsonism: A Population-Based Study.

BACKGROUND: Sleep disturbances are common in parkinsonian disorders; however, whether sleep disorders affect individuals with early-onset parkinsonism and whether they differ from individuals with typical-onset parkinsonism is unknown. OBJECTIVE: To compare the prevalence and incidence of sleep disorders before and after parkinsonian motor symptom onset between individuals with early onset parkinsonism (age ≤50 at motor symptom onset) and typical-onset parkinsonism (age >50 at motor symptom onset). METHODS: We used a population-based, 1991 to 2015 incident-cohort study of parkinsonism including 38 patients with early-onset and 1,001 patients with typical-onset parkinsonism. Presence or absence and type of sleep disorder as well as the relationship between motor and sleep symptoms were abstracted from the medical records. Rates of sleep disorders before and after onset of parkinsonism were compared with logistic regression and Cox proportional hazards models. RESULTS: The prevalence of sleep disorders prior to the onset of parkinsonism in early vs. typical parkinsonism (24% vs. 16% p = 0.19) and incidence of sleep disorders after parkinsonism onset (5.85 cases per 100 person-years vs. 4.11 cases per 100 person-years; HR 1.15 95% CI: 0.74-1.77) were similar between the two groups. Early-onset parkinsonism had a higher risk for developing post-motor insomnia compared with typical-onset parkinsonism (HR 1.73, 95% CI: 1.02-2.93); the risk for developing all other sleep disorders considered was similar between groups. CONCLUSION: Sleep disorders are common in individuals with early-onset parkinsonism and occur with similar frequency to those with typical-onset parkinsonism, except for insomnia, which was more frequent in the early-onset group.