Citations

Introduction: Hypertension (HTN) is highly prevalent among patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), uncontrolled HTN as well as high blood pressure variability (BPV) can significantly impact cardiovascular health. This study aims to understand the impact of BPV in patients with ESKD following arteriovenous fistula (AVF) creation for hemodialysis, to better understand its association with age, sex, BMI, and cardiovascular risk. Methods: A retrospective analysis was conducted on 83 patients who underwent AVF creation between February 2019 and October 2020 at University of Miami Hospital. During 20 months, blood pressure measurements were collected from medical records at four different times during AVF access creation process, and BPV was quantified using machine learning clustering techniques. Results: The study identified three distinct clusters among the 83 patients with ESKD who underwent AVF creation. Cluster 1 ( n = 28) was characterized by high blood pressure variability, with a mean systolic blood pressure standard deviation of 16.2 mmHg. This cluster exhibited a significantly higher cardiovascular risk rate of 42.9% compared to Cluster 2 ( n = 30) and Cluster 3 ( n = 25), which had lower variability with mean systolic blood pressure standard deviations of 10.3 and 8.7 mmHg, respectively, and cardiovascular risk rates of 16.7% and 12.0%. Age, sex, and BMI did not differ significantly across the clusters. Conclusion: This study underscores the association between blood pressure variability and the increased risk of cardiovascular events, including myocardial infraction, stroke or heart failure in patients with ESKD undergoing AVF creation. Our findings highlight the critical need for vigilant monitoring of blood pressure fluctuations in this population and demonstrate how these variations are influenced by individual demographic factors. Further research is needed to develop targeted interventions to mitigate this risk.

Objectives: To determine associations between physician sex and use of postoperative healthcare resources among patients undergoing common surgeries in Ontario, Canada. Background: Prior studies have shown that patients of female physicians experience better outcomes and have lower healthcare costs compared with patients of male physicians. Understanding differences in resource utilization may offer insights into the care pathways and practice patterns contributing to these differences. Methods: We conducted a population-based, retrospective cohort study of adults (≥18 years of age) undergoing 1 of 25 common surgeries, between January 1, 2007, and December 31, 2019, in Ontario, Canada. The primary outcome was the utilization of one of the following: intensive care unit admission, other medical interventions (eg, tracheostomy, new dialysis starts, and home oxygen), and discharge care needs (eg inpatient rehab, long-term care, and home care use) within 30 days. The data were summarized using descriptive statistics and adjusted using multivariable generalized estimating equations. Results: This population-based study included 1,100,193 patients (61.8% female). Patients treated by male surgeons had higher use of postoperative resources versus those with female surgeons within 30 days (adjusted rate 33.1; 95% confidence interval [CI]: 28.0–39.2 versus 31.2; 95% CI: 25.8–37.7), 90 days, and 1 year. Consistent with these findings, following adjustment for patient, surgeon, procedural, and hospital characteristics, patients treated by male surgeons were significantly more likely to utilize postoperative resources within 30 days (adjusted odds ratio: 1.14; 95% CI: 1.03–1.27; P = 0.010) and at other time points. This difference was primarily driven by the higher use of home care among patients with a male versus female surgeon at all time points (30 days: adjusted odds ratio, 1.13; 95% CI: 1.05–1.21; P = 0.002). Conclusions: Patients with male surgeons had higher postoperative resource utilization when compared with those treated by female surgeons, which was almost entirely driven by the higher use of home care. Further mixed-methods investigation is needed to better understand other potentially relevant factors including surgical outcomes, individual patient preferences, and surgical team decision-making.

Abstract Parkinson’s disease (PD) is the fastest growing neurodegenerative disease in the world 1 . Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD 2,3,4 . We investigated peripheral relationships that may underlie mechanisms along the gut-blood axis that contribute to PD pathogenesis. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be the catalyst that primes circulating immune cells to body-first PD pathogenesis.

ABSTRACT Background Dementia often goes undetected in hospital settings, where cognitive assessments are challenging due to illness severity and delirium. This study aimed to (1) evaluate the accuracy of the Clinical Dementia Rating (CDR), based solely on knowledgeable informant reports, for detecting preexisting dementia and cognitive impairment in hospitalized patients compared to a gold‐standard diagnosis, (2) and compare its performance to the 16‐item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE‐16). Methods This cross‐sectional study assessed consecutive patients aged ≥ 65 admitted to inpatient units from five hospitals in Brazil. The informant‐based CDR was administered to knowledgeable informants within 48 h of admission, capturing patients' cognitive status 3 months before hospitalization to avoid the influence of acute cognitive impairments. Blinded experts provided a gold standard clinical diagnosis of dementia or cognitive impairment no dementia (CIND) based on a 90‐min comprehensive assessment, including a standardized neuropsychology battery. Areas under the curve (AUC) examined diagnostic accuracy. Results Of 65 participants (mean age = 79.4 years; women = 54%), 34% had dementia and 32% had CIND . Compared to the gold standard, the informant‐based CDR showed excellent diagnostic accuracy for detecting dementia ( AUC = 0.92; 95% confidence interval [ CI ] = 0.86–0.98) and cognitive impairment ( AUC = 0.93; 95% CI = 0.88–0.98), with a cutoff of ≥ 1 showing 98% specificity for dementia and a cutoff of ≥ 0.5 showing 98% sensitivity for cognitive impairment. Compared to the IQCODE ‐16, the informant‐based CDR had similar performance in detecting dementia and a nonsignificant slight advantage in identifying cognitive impairment ( AUC = 0.93 vs. 0.84, p = 0.069), reducing unrecognized cognitive impairment based on medical record documentation from 70% to 2%. Conclusions Informant‐based CDR is a valid and efficient tool for detecting dementia and cognitive impairment in hospitalized older adults, supporting early diagnosis and guiding multidisciplinary interventions in acute care. Its use in routine hospitals may help clinicians reduce undetected cognitive impairment, enhance decision making, and improve patient care.

Background The Woven EndoBridge (WEB) device is a prevalent treatment for intracranial aneurysms. While many studies have assessed the obliteration rate post-WEB embolization, few have focused on long-term outcomes in partially thrombosed aneurysms. Objective To assess whether partially thrombosed aneurysms are at higher risk of recurrence or retreatment following WEB embolization compared with non-thrombosed aneurysms. Methods We evaluated data from 22 academic institutions, focusing on previously untreated cerebral aneurysms treated with the WEB device. Logistic regression was utilized to analyze factors predicting long-term aneurysm obliteration and retreatment necessity. Results Among 1303 patients, 26 presented with a partially thrombosed aneurysm. In the partially thrombosed group, the mean aneurysm maximal diameter was 10.7±4 mm with a neck ratio of 1.99±1.19 mm, larger than in the control group where the mean aneurysm maximal diameter was 6.81±2.37 mm with a neck ratio of 1.64±0.51 mm (P<0.001 for both maximal diameter and neck ratio). At the final follow-up, partially thrombosed aneurysms treated by the WEB device had a 38.5% retreatment rate, compared with 7.0% for non-thrombosed aneurysms (P<0.001). Among partially thrombosed aneurysms, the Raymond-Roy type IIIa/b occlusion rate was higher (38.5% vs 9.9%, P<0.001). On multivariate analysis, partially thrombosed aneurysms compared with non-thrombosed aneurysms had an increased rate of retreatment (OR 3.64, 95% CI 1.28 to 10.1). Conclusion Partially thrombosed aneurysms are associated with a poorer occlusion rate and a higher rate of retreatment following WEB embolization. For partially thrombosed aneurysms, the WEB device appears suboptimal as a first-line treatment, and therefore alternative techniques should be prioritized.

Context: There is need for an up-to-date comprehensive review of baseball interval throwing programs in the literature. Objective: To (1) understand the origin and basis of interval throwing programs; (2) evaluate the content of programs in the peer-reviewed literature including target audience, initiation criteria, throwing specifics, arm care, and performance evaluation metrics; (3) classify these variables as well defined, ambiguous, or missing; and (4) analyze variability in key aspects including starting criteria, length, progression, and completion criteria. Data Sources: Medline, Embase, Cochrane Reviews, Web of Science, and Scopus Study Selection: The full text of studies, in English, had to be available. Included studies had to contain a complete interval throwing program designed for baseball players. Study Design: Systematic review. Level of Evidence: Level 4. Data Extraction: Initial screening was conducted based on article title and abstract. Full text of the remaining articles was evaluated for fulfillment of inclusion criteria. Results: Nine studies initially met inclusion criteria. The programs’ comprehensiveness was poor, with a mean Interval Throwing Program Checklist score of 20 (range 14-23) on a scale of 0 to 30. There were a variety of components, including progressive long toss, weighted ball, and throwing mechanics exercises. The programs identified had significant heterogeneity in duration, intensity, progression, and focus. Overall, there was a significant lack of attempts at validation or formal study of efficacy for published throwing programs. Conclusion: Current published interval throwing programs are mostly variations of an original program published many years ago and were based on principles of progressive loading with pain as sign of injury that should be monitored carefully. However, these programs have minimal clinical validation and objective measures to quantify their effectiveness. This work identifies several limitations in the current literature and can serve as a foundation for future development of evidence-based interval throwing programs.

ABSTRACT Knowledge of Treponema pallidum subspecies pallidum ( TPA ) outer membrane protein (OMP) sequence variability is essential for understanding spirochete proliferation within endemic populations as well as design of a globally effective syphilis vaccine. Our group has identified extracellular loops (ECLs) of TPA BamA (TP0326) and members of the FadL family (TP0548, TP0856, TP0858, TP0859, and TP0865) as potential components of a multivalent vaccine cocktail. As part of a consortium to explore TPA strain diversity, we mapped the variability of BamA and FadL orthologs in 186 TPA strains from Malawi, China and Colombia onto predicted 3D structures. The 186 genomes fell into eight subclades (five Nichols-, three SS14-lineage) with substantial geographic restriction. Single nucleotide variants accounted for the large majority of proteoforms, with variability notably higher within the Nichols-lineage strains. Most mutations were in regions of the proteins predicted to be extracellular and harboring B cell epitopes. We observed a striking difference in the degree of variability between the six OMPs, suggesting that these proteins are following divergent evolutionary paths. Concatenation of OMP sequences recapitulated the phylogenetic structure of the TPA strains, effectively segregating within clades and largely clustering by subclades. Lastly, we noted that BamA and FadL candidate ECL vaccinogens previously shown to elicit antibodies that kill treponemes during in vitro cultivation are well conserved. Taken as a whole, our study establishes a structural-phylogenetic approach for analyzing the forces shaping the host-pathogen interface in syphilis within endemic populations while informing selection of vaccine targets. IMPORTANCE Syphilis remains a major global health concern, reinforcing the need for a safe and effective vaccine. Understanding the variability of TPA OMPs is essential for tracking pathogen evolution and informing vaccine design. Here, we analyzed the variability of six TPA OMPs in 186 strains from Malawi, China, and Colombia, identifying protein-specific evolutionary patterns. Most mutations were localized in extracellular regions and, notably, appeared to correlate with the phylogenetic structure of TPA . Despite OMP heterogeneity, several candidate vaccinogens remained highly conserved, reinforcing their potential as globally effective vaccine targets. Our study establishes a structural-phylogenetic framework for dissecting the forces shaping the host-spirochete interface within endemic populations and provides a foundation for designing a globally effective syphilis vaccine.