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.

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.

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.

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.

The Number and Size of Individual Kidney Medullary Pyramids is Associated with Clinical Characteristics, Kidney Biopsy Findings, and CKD Outcomes among Kidney Donors.

SIGNIFICANCE STATEMENT: Segmentation of multiple structures in cross-sectional imaging is time-consuming and impractical to perform manually, especially if the end goal is clinical implementation. In this study, we developed, validated, and demonstrated the capability of a deep learning algorithm to segment individual medullary pyramids in a rapid, accurate, and reproducible manner. The results demonstrate that cortex volume, medullary volume, number of pyramids, and mean pyramid volume is associated with patient clinical characteristics and microstructural findings and provide insights into the mechanisms that may lead to CKD. BACKGROUND: The kidney is a lobulated organ, but little is known regarding the clinical importance of the number and size of individual kidney lobes. METHODS: After applying a previously validated algorithm to segment the cortex and medulla, a deep-learning algorithm was developed and validated to segment and count individual medullary pyramids on contrast-enhanced computed tomography images of living kidney donors before donation. The association of cortex volume, medullary volume, number of pyramids, and mean pyramid volume with concurrent clinical characteristics (kidney function and CKD risk factors), kidney biopsy morphology (nephron number, glomerular volume, and nephrosclerosis), and short- and long-term GFR <60 or <45 ml/min per 1.73 m 2 was assessed. RESULTS: Among 2876 living kidney donors, 1132 had short-term follow-up at a median of 3.8 months and 638 had long-term follow-up at a median of 10.0 years. Larger cortex volume was associated with younger age, male sex, larger body size, higher GFR, albuminuria, more nephrons, larger glomeruli, less nephrosclerosis, and lower risk of low GFR at follow-up. Larger pyramids were associated with older age, female sex, larger body size, higher GFR, more nephrons, larger glomerular volume, more nephrosclerosis, and higher risk of low GFR at follow-up. More pyramids were associated with younger age, male sex, greater height, no hypertension, higher GFR, lower uric acid, more nephrons, less nephrosclerosis, and a lower risk of low GFR at follow-up. CONCLUSIONS: Cortex volume and medullary pyramid volume and count reflect underlying variation in nephron number and nephron size as well as merging of pyramids because of age-related nephrosclerosis, with loss of detectable cortical columns separating pyramids.

Age-Based Versus Young-Adult Thresholds for Nephrosclerosis on Kidney Biopsy and Prognostic Implications for CKD.

SIGNIFICANCE STATEMENT: Nephrosclerosis (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) is the defining pathology of both kidney aging and CKD. Optimal thresholds for nephrosclerosis that identify persons with a progressive disease are unknown. This study determined a young-age threshold (18-29 years) and age-based 95th percentile thresholds for nephrosclerosis on the basis of morphometry of kidney biopsy sections from normotensive living kidney donors. These thresholds were 7.1-fold to 36-fold higher in older (70 years or older) versus younger (aged 18-29 years) normotensive donors. Age-based thresholds, but not young-age threshold, were prognostic for determining risk of progressive CKD among patients who underwent a radical nephrectomy or a for-cause native kidney biopsy, suggesting that age-based thresholds are more useful than a single young-age threshold for identifying CKD on biopsy. BACKGROUND: Nephrosclerosis, defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA), is a pathology of both kidney aging and CKD. A comparison of risk of progressive CKD using aged-based thresholds for nephrosclerosis versus a single young-adult threshold is needed. METHODS: We conducted morphometric analyses of kidney biopsy images for %GSG, %IFTA, and IFTA foci density among 3020 living kidney donors, 1363 patients with kidney tumor, and 314 patients with native kidney disease. Using normotensive donors, we defined young-age thresholds (18-29 years) and age-based (roughly by decade) 95th percentile thresholds. We compared age-adjusted risk of progressive CKD (kidney failure or 40% decline in eGFR) between nephrosclerosis that was "normal compared with young," "normal for age but abnormal compared with young," and "abnormal for age" in patients with tumor and patients with kidney disease. RESULTS: The 95th percentiles in the youngest group (18-29 years) to the oldest group (70 years or older) ranged from 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm 2 for IFTA foci density. Risk of progressive CKD did not differ between persons with nephrosclerosis "normal compared with young" versus "normal for age but abnormal compared with young." Risk of progressive CKD was significantly higher with %GSG, %IFTA, or IFTA foci density that was abnormal versus normal for age in both cohorts. CONCLUSIONS: Given that increased risk of progressive CKD occurs only when nephrosclerosis is abnormal for age, age-based thresholds for nephrosclerosis seem to be better than a single young-age threshold for identifying clinically relevant CKD.

An Improved Method for Estimating Nephron Number and the Association of Resulting Nephron Number Estimates with Chronic Kidney Disease Outcomes.

SIGNIFICANCE STATEMENT: Nephron number currently can be estimated only from glomerular density on a kidney biopsy combined with cortical volume from kidney imaging. Because of measurement biases, refinement of this approach and validation across different patient populations have been needed. The prognostic importance of nephron number also has been unclear. The authors present an improved method of estimating nephron number that corrects for several biases, resulting in a 27% higher nephron number estimate for donor kidneys compared with a prior method. After accounting for comorbidities, the new nephron number estimate does not differ between kidney donors and kidney patients with tumor and shows consistent associations with clinical characteristics across these two populations. The findings also indicate that low nephron number predicts CKD independent of biopsy and clinical characteristics in both populations. BACKGROUND: Nephron number can be estimated from glomerular density and cortical volume. However, because of measurement biases, this approach needs refinement, comparison between disparate populations, and evaluation as a predictor of CKD outcomes. METHODS: We studied 3020 living kidney donors and 1354 patients who underwent radical nephrectomy for tumor. We determined cortex volume of the retained kidney from presurgical imaging and glomerular density by morphometric analysis of needle core biopsy of the donated kidney and wedge sections of the removed kidney. Glomerular density was corrected for missing glomerular tufts, absence of the kidney capsule, and then tissue shrinkage on the basis of analysis of 30 autopsy kidneys. We used logistic regression (in donors) and Cox proportional hazard models (in patients with tumor) to assess the risk of CKD outcomes associated with nephron number. RESULTS: Donors had 1.17 million nephrons per kidney; patients with tumor had 0.99 million nephrons per kidney. A lower nephron number was associated with older age, female sex, shorter height, hypertension, family history of ESKD, lower GFR, and proteinuria. After adjusting for these characteristics, nephron number did not differ between donors and patients with tumor. Low nephron number (defined by <5th or <10th percentile by age and sex in a healthy subset) in both populations predicted future risk of CKD outcomes independent of biopsy and clinical characteristics. CONCLUSIONS: Compared with an older method for estimating nephron number, a new method that addresses several sources of bias results in nephron number estimates that are 27% higher in donors and 1% higher in patients with tumor and shows consistency between two populations. Low nephron number independently predicts CKD in both populations.

Tubular and Glomerular Size by Cortex Depth as Predictor of Progressive CKD after Radical Nephrectomy for Tumor.

SIGNIFICANCE STATEMENT: Glomerular size differs by cortex depth. Larger nephrons are prognostic of progressive kidney disease, but it is unknown whether this risk differs by cortex depth or by glomeruli versus proximal or distal tubule size. We studied the average minor axis diameter in oval proximal and distal tubules separately and by cortex depth in patients who had radical nephrectomy to remove a tumor from 2019 to 2020. In adjusted analyses, larger glomerular volume in the middle and deep cortex predicted progressive kidney disease. Wider proximal tubular diameter did not predict progressive kidney disease independent of glomerular volume. Wider distal tubular diameter showed a gradient of strength of prediction of progressive kidney disease in the more superficial cortex than in the deep cortex. BACKGROUND: Larger nephrons are prognostic of progressive kidney disease, but whether this risk differs by nephron segments or by depth in the cortex is unclear. METHODS: We studied patients who underwent radical nephrectomy for a tumor between 2000 and 2019. Large wedge kidney sections were scanned into digital images. We estimated the diameters of proximal and distal tubules by the minor axis of oval tubular profiles and estimated glomerular volume with the Weibel-Gomez stereological model. Analyses were performed separately in the superficial, middle, and deep cortex. Cox proportional hazard models assessed the risk of progressive CKD (dialysis, kidney transplantation, sustained eGFR <10 ml/min per 1.73 m 2 , or a sustained 40% decline from the postnephrectomy baseline eGFR) with glomerular volume or tubule diameters. At each cortical depth, models were unadjusted, adjusted for glomerular volume or tubular diameter, and further adjusted for clinical characteristics (age, sex, body mass index, hypertension, diabetes, postnephrectomy baseline eGFR, and proteinuria). RESULTS: Among 1367 patients were 62 progressive CKD events during a median follow-up of 4.5 years. Glomerular volume predicted CKD outcomes at all depths, but only in the middle and deep cortex after adjusted analyses. Proximal tubular diameter also predicted progressive CKD at any depth but not after adjusted analyses. Distal tubular diameter showed a gradient of more strongly predicting progressive CKD in the superficial than deep cortex, even in adjusted analysis. CONCLUSIONS: Larger glomeruli are independent predictors of progressive CKD in the deeper cortex, whereas in the superficial cortex, wider distal tubular diameters are an independent predictor of progressive CKD.

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.

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.

Prediction of measured GFR after living kidney donation from pre-donation parameters.

BACKGROUND: One of the challenges in living kidney donor screening is to estimate remaining kidney function after donation. Here we developed a new model to predict post-donation measured glomerular filtration rate (mGFR) from pre-donation serum creatinine, age and sex. METHODS: In the prospective development cohort (TransplantLines, n = 511), several prediction models were constructed and tested for accuracy, precision and predictive capacity for short- and long-term post-donation 125I-iothalamate mGFR. The model with optimal performance was further tested in specific high-risk subgroups (pre-donation eGFR <90 mL/min/1.73 m2, a declining 5-year post-donation mGFR slope or age >65 years) and validated in internal (n = 509) and external (Mayo Clinic, n = 1087) cohorts. RESULTS: In the development cohort, pre-donation estimated GFR (eGFR) was 86 ± 14 mL/min/1.73 m2 and post-donation mGFR was 64 ± 11 mL/min/1.73 m2. Donors with a pre-donation eGFR ≥90 mL/min/1.73 m2 (present in 43%) had a mean post-donation mGFR of 69 ± 10 mL/min/1.73 m2 and 5% of these donors reached an mGFR <55 mL/min/1.73 m2. A model using pre-donation serum creatinine, age and sex performed optimally, predicting mGFR with good accuracy (mean bias 2.56 mL/min/1.73 m2, R2 = 0.29, root mean square error = 11.61) and precision [bias interquartile range (IQR) 14 mL/min/1.73 m2] in the external validation cohort. This model also performed well in donors with pre-donation eGFR <90 mL/min/1.73 m2 [bias 0.35 mL/min/1.73 m2 (IQR 10)], in donors with a negative post-donation mGFR slope [bias 4.75 mL/min/1.73 m2 (IQR 13)] and in donors >65 years of age [bias 0.003 mL/min/1.73 m2 (IQR 9)]. CONCLUSIONS: We developed a novel post-donation mGFR prediction model based on pre-donation serum creatinine, age and sex.

Frequency of headache in emergency department patients with anaphylaxis: A cross-sectional study.

BACKGROUND: Multiple anaphylaxis mediators have been demonstrated to provoke migraine-like attacks following intravascular infusion, suggesting that anaphylaxis could cause headache; however, headache is rarely noted in anaphylaxis and is not included among diagnostic criteria. OBJECTIVE: Our study objectives were to estimate the frequency of headache among prospectively enrolled emergency department (ED) patients with anaphylaxis and assess the association of headache with patient and anaphylaxis characteristics. METHODS: A cross-sectional study of ED patients aged ≥5 years who met anaphylaxis diagnostic criteria from January 8, 2020 to September 9, 2022 was conducted. The primary outcome of interest was headache frequency among patients who met at least one anaphylaxis criterion. We explored the association of headache with patient characteristics and anaphylaxis characteristics. RESULTS: We included 63 patients with anaphylaxis. In all, 17 (27%, 95% confidence interval [CI] 17%-40%) patients reported the presence of a headache. Female patients had more than a nine times increased odds of having headache (odds ratio [OR] 9.3, 95% CI 1.14-77.1, p = 0.016). Presentation with headache was associated with the presence of dyspnea (OR 5.5, 95% CI 1.56-19.7, p = 0.006). CONCLUSION: Headache in anaphylaxis may be more common than previously recognized, especially in females. Larger prospective studies are needed to characterize headache as a marker of neurological involvement in anaphylaxis.

Stercoral Colitis in the Emergency Department: A Retrospective Review of Presentation, Management, and Outcomes.

STUDY OBJECTIVE: Stercoral colitis is inflammation of the bowel wall caused by fecal impaction. Despite reported high morbidity and risk of perforation, little research assessing outcomes is available. This study characterizes the presentation, management, and outcomes of emergency department patients with stercoral colitis. METHODS: We performed a retrospective chart review of ED patients with stercoral colitis identified on computed tomography (CT) scan. Of 814, 522 visits to multiple EDs across the US, 269 met the inclusion criteria. Variables regarding patient presentation, management, and outcomes were extracted from electronic medical records. Results were analyzed with percentages and 95% confidence intervals (CIs). RESULTS: Of 269 patients, the median age was 76 years. The most common chief concern was abdominal pain/distension (33.8%). However, abdominal pain was documented as absent in 62.1% of cases. The most common CT findings included fecal impaction (96.7%), bowel wall inflammation (72.9%), and fat stranding (48.3%). Eighty-four (31.2%) patients were discharged home from the ED, and over half of these (45/84, 53.6%) received no enema, laxatives, or disimpaction. Overall, 9 patients (3.3%, 95% CI 1.6% to 6.5%) required surgical management of a related complication within 3 months, 27 (10.0%, 95% CI 6.8% to 14.4%) returned to the ED within 72 hours, and 9 (3.3%, 95% CI 1.6% to 6.5%) died from a cause related to stercoral colitis within 3 months. CONCLUSION: Patients with stercoral colitis often present in a nonspecific manner, and short-term mortality is substantial. In this study, most discharged patients did not receive recommended treatment. This represents the largest ED study of stercoral colitis and provides further evidence linking this diagnosis with adverse outcomes.

Association of delirium with increased short-term mortality among older emergency department patients: A cohort study.

STUDY OBJECTIVE: To evaluate the association between delirium and subsequent short-term mortality in geriatric patients presenting to the emergency department (ED). METHODS: This was an observational cohort study of adults age ≥75 years who presented to an academic ED and were screened for delirium during their ED visit. The Delirium Triage Screen followed by the Brief Confusion Assessment Method were used to ascertain the presence of delirium. In-hospital, 7-day, and 30-day mortality were compared between patients with and without ED delirium. Odds ratios with 95% confidence intervals (CIs) were calculated through logistic regression after adjusting for confounders including age, sex, history of dementia, ED disposition, and acuity. RESULTS: A total of 967 ED visits were included for analysis among which delirium was detected in 107 (11.1%). The median age of the cohort was 83 years (IQR 79, 88), 526 (54.4%) were female, 285 (29.5%) had documented dementia, and 171 (17.7%) had a high acuity Emergency Severity Index triage level 1 or 2. During the hospitalization, 5/107 (4.7%) of those with delirium and 4/860 (0.5%) of those without delirium died. Within 7 days of ED departure, 6/107 (5.6%) of those with delirium and 6/860 (0.7%) of those without delirium died (unadjusted OR 8.46, 95% CI 2.68-26.71). Within 30 days, 18/107 (16.8%) of those with delirium and 37/860 (4.3%) of those without delirium died (unadjusted OR 4.50, 95% CI 2.46-8.23). ED delirium remained associated with higher 7-day (adjusted OR 5.23, 95% CI 1.44-19.05, p = 0.008) and 30-day mortality (adjusted OR 2.82, 95% CI 1.45-5.46, p = 0.002). CONCLUSION: Delirium is an important prognostic factor that ED clinicians and nurses must be aware of to optimize delirium prevention, management, disposition, and communication with patients and families.

Comparison of clinical note quality between an automated digital intake tool and the standard note in the emergency department.

BACKGROUND: Medical encounters require an efficient and focused history of present illness (HPI) to create differential diagnoses and guide diagnostic testing and treatment. Our aim was to compare the HPI of notes created by an automated digital intake tool versus standard medical notes created by clinicians. METHODS: Prospective trial in a quaternary academic Emergency Department (ED). Notes were compared using the 5-point Physician Documentation Quality Instrument (PDQI-9) scale and the Centers for Medicare & Medicaid Services (CMS) level of complexity index. Reviewers were board certified emergency medicine physicians blinded to note origin. Reviewers received training and calibration prior to note assessments. A difference of 1 point was considered clinically significant. Analysis included McNemar's (binary), Wilcoxon-rank (Likert), and agreement with Cohen's Kappa. RESULTS: A total of 148 ED medical encounters were charted by both digital note and standard clinical note. The ability to capture patient information was assessed through comparison of note content across paired charts (digital-standard note on the same patient), as well as scores given by the reviewers. Reviewer agreement was kappa 0.56 (CI 0.49-0.64), indicating moderate level of agreement between reviewers scoring the same patient chart. Considering all 18 questions across PDQI-9 and CMS scales, the average agreement between standard clinical note and digital note was 54.3% (IQR 44.4-66.7%). There was a moderate level of agreement between content of standard and digital notes (kappa 0.54, 95%CI 0.49-0.60). The quality of the digital note was within the 1 point clinically significant difference for all of the attributes, except for conciseness. Digital notes had a higher frequency of CMS severity elements identified. CONCLUSION: Digitally generated clinical notes had moderate agreement compared to standard clinical notes and within the one point clinically significant difference except for the conciseness attribute. Digital notes more reliably documented billing components of severity. The use of automated notes should be further explored to evaluate its utility in facilitating documentation of patient encounters.

The Minnesota attributable risk of kidney donation (MARKD) study: a retrospective cohort study of long-term (> 50 year) outcomes after kidney donation compared to well-matched healthy controls.

BACKGROUND: There is uncertainty about the long-term risks of living kidney donation. Well-designed studies with controls well-matched on risk factors for kidney disease are needed to understand the attributable risks of kidney donation. METHODS: The goal of the Minnesota Attributable Risk of Kidney Donation (MARKD) study is to compare the long-term (> 50 years) outcomes of living donors (LDs) to contemporary and geographically similar controls that are well-matched on health status. University of Minnesota (n = 4022; 1st transplant: 1963) and Mayo Clinic LDs (n = 3035; 1st transplant: 1963) will be matched to Rochester Epidemiology Project (REP) controls (approximately 4 controls to 1 donor) on the basis of age, sex, and race/ethnicity. The REP controls are a well-defined population, with detailed medical record data linked between all providers in Olmsted and surrounding counties, that come from the same geographic region and era (early 1960s to present) as the donors. Controls will be carefully selected to have health status acceptable for donation on the index date (date their matched donor donated). Further refinement of the control group will include confirmed kidney health (e.g., normal serum creatinine and/or no proteinuria) and matching (on index date) of body mass index, smoking history, family history of chronic kidney disease, and blood pressure. Outcomes will be ascertained from national registries (National Death Index and United States Renal Data System) and a new survey administered to both donors and controls; the data will be supplemented by prior surveys and medical record review of donors and REP controls. The outcomes to be compared are all-cause mortality, end-stage kidney disease, cardiovascular disease and mortality, estimated glomerular filtration rate (eGFR) trajectory and chronic kidney disease, pregnancy risks, and development of diseases that frequently lead to chronic kidney disease (e.g. hypertension, diabetes, and obesity). We will additionally evaluate whether the risk of donation differs based on baseline characteristics. DISCUSSION: Our study will provide a comprehensive assessment of long-term living donor risk to inform candidate living donors, and to inform the follow-up and care of current living donors.

Psychosocial and behavioral outcomes in the adult workforce during the COVID-19 pandemic: a 1-Year longitudinal survey.

BACKGROUND: Efforts to limit the spread of COVID-19 have included public space closures, mask usage, and quarantining. Studies regarding the impact of these measures on the psychosocial and behavioral health outcomes of the workforce have focused frequently on healthcare employees. To expand the literature base, we deployed a one-year longitudinal survey among mostly non-healthcare employees assessing changes in select psychosocial outcomes, health behaviors, and COVID-19-related transmission prevention behaviors and perceptions. METHODS: We deployed the CAPTURE baseline survey across eight companies from November 20, 2020-February 8, 2021. The baseline survey included questions on psychosocial outcomes, health behaviors, and COVID-19 transmission prevention behaviors, with several questions containing a retrospective component to cover the time period prior to the pandemic. Additional questions on vaccination status and social support were subsequently added, and the updated survey deployed to the same baseline participants at three, six, and 12 months after baseline survey deployment. We analyzed data descriptively and performed Friedman's and subsequent Wilcoxon-signed rank tests, as appropriate, to compare data within and between time points. RESULTS: A total of 3607, 1788, 1545, and 1687 employees completed the baseline, 3-month, 6-month, and 12-month CAPTURE surveys, respectively, with 816 employees completing all four time points. Employees reported higher stress, anxiety, fatigue, and feelings of being unsafe across all time points compared to pre-pandemic. Time spent sleeping increased initially but returned to pre-pandemic levels at follow-up. Lower rates of physical activity and higher rates of non-work screen time and alcohol consumption relative to pre-pandemic were also reported. Over 90% of employees perceived wearing a mask, physical distancing, and receiving the COVID-19 vaccine as 'moderately' or 'very important' in preventing the spread of COVID-19 across all time points. CONCLUSIONS: Relative to pre-pandemic, poorer psychosocial outcomes and worsened health behaviors were observed across all time points, with values worse at the baseline and 12-month time points when COVID-19 surges were highest. While COVID-19 prevention behaviors were consistently deemed to be important by employees, the psychosocial outcome and health behavior data suggest the potential for harmful long-term effects of the pandemic on the well-being of non-healthcare employees.

Automated Segmentation of Kidney Cortex and Medulla in CT Images: A Multisite Evaluation Study.

BACKGROUND: In kidney transplantation, a contrast CT scan is obtained in the donor candidate to detect subclinical pathology in the kidney. Recent work from the Aging Kidney Anatomy study has characterized kidney, cortex, and medulla volumes using a manual image-processing tool. However, this technique is time consuming and impractical for clinical care, and thus, these measurements are not obtained during donor evaluations. This study proposes a fully automated segmentation approach for measuring kidney, cortex, and medulla volumes. METHODS: A total of 1930 contrast-enhanced CT exams with reference standard manual segmentations from one institution were used to develop the algorithm. A convolutional neural network model was trained (n=1238) and validated (n=306), and then evaluated in a hold-out test set of reference standard segmentations (n=386). After the initial evaluation, the algorithm was further tested on datasets originating from two external sites (n=1226). RESULTS: The automated model was found to perform on par with manual segmentation, with errors similar to interobserver variability with manual segmentation. Compared with the reference standard, the automated approach achieved a Dice similarity metric of 0.94 (right cortex), 0.90 (right medulla), 0.94 (left cortex), and 0.90 (left medulla) in the test set. Similar performance was observed when the algorithm was applied on the two external datasets. CONCLUSIONS: A fully automated approach for measuring cortex and medullary volumes in CT images of the kidneys has been established. This method may prove useful for a wide range of clinical applications.

Prognostic Implications of a Morphometric Evaluation for Chronic Changes on All Diagnostic Native Kidney Biopsies.

BACKGROUND: Semiquantitative visual inspection for glomerulosclerosis, interstitial fibrosis, and arteriosclerosis is often used to assess chronic changes in native kidney biopsies. Morphometric evaluation of these and other chronic changes may improve the prognostic assessment. METHODS: We studied a historical cohort of patients who underwent a native kidney biopsy between 1993 and 2015 and were followed through 2021 for ESKD and for progressive CKD (defined as experiencing 50% eGFR decline, temporary dialysis, or ESKD). Pathologist scores for the percentages of globally sclerosed glomeruli (GSG), interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis (luminal stenosis) were available. We scanned biopsy sections into high-resolution images to trace microstructures. Morphometry measures were percentage of GSG; percentage of glomerulosclerosis (percentage of GSG, ischemic-appearing glomeruli, or segmentally sclerosed glomeruli); percentage of IFTA; IFTA foci density; percentage of artery luminal stenosis; arteriolar hyalinosis counts; and measures of nephron size. Models assessed risk of ESKD or progressive CKD with biopsy measures adjusted for age, hypertension, diabetes, body mass index, eGFR, and proteinuria. RESULTS: Of 353 patients (followed for a median 7.5 years), 75 developed ESKD and 139 experienced progressive CKD events. Visually estimated scores by pathologists versus morphometry measures for percentages of GSG, IFTA, and luminal stenosis did not substantively differ in predicting outcomes. However, adding percentage of glomerulosclerosis, IFTA foci density, and arteriolar hyalinosis improved outcome prediction. A 10-point score using percentage of glomerulosclerosis, percentage of IFTA, IFTA foci density, and any arteriolar hyalinosis outperformed a 10-point score based on percentages of GSG, IFTA, and luminal stenosis >50% in discriminating risk of ESKD or progressive CKD. CONCLUSION: Morphometric characterization of glomerulosclerosis, IFTA, and arteriolar hyalinosis on kidney biopsy improves prediction of long-term kidney outcomes.

Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis.

INTRODUCTION: Cirrhosis is associated with cardiac dysfunction and distinct electrocardiogram (ECG) abnormalities. This study aimed to develop a proof-of-concept deep learning-based artificial intelligence (AI) model that could detect cirrhosis-related signals on ECG and generate an AI-Cirrhosis-ECG (ACE) score that would correlate with disease severity. METHODS: A review of Mayo Clinic's electronic health records identified 5,212 patients with advanced cirrhosis ≥18 years who underwent liver transplantation at the 3 Mayo Clinic transplant centers between 1988 and 2019. The patients were matched by age and sex in a 1:4 ratio to controls without liver disease and then divided into training, validation, and test sets using a 70%-10%-20% split. The primary outcome was the performance of the model in distinguishing patients with cirrhosis from controls using their ECGs. In addition, the association between the ACE score and the severity of patients' liver disease was assessed. RESULTS: The model's area under the curve in the test set was 0.908 with 84.9% sensitivity and 83.2% specificity, and this performance remained consistent after additional matching for medical comorbidities. Significant elevations in the ACE scores were seen with increasing model for end-stage liver disease-sodium score. Longitudinal trends in the ACE scores before and after liver transplantation mirrored the progression and resolution of liver disease. DISCUSSION: The ACE score, a deep learning model, can accurately discriminate ECGs from patients with and without cirrhosis. This novel relationship between AI-enabled ECG analysis and cirrhosis holds promise as the basis for future low-cost tools and applications in the care of patients with liver disease.