Faculty Bibliography

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths of the sulci. Currently, CTE can be diagnosed only postmortem, but can present with an array of cognitive, behavioral, mood, and motor symptoms. However, traumatic brain injury is also associated with increased risk of Alzheimer's disease (AD) and may lead to comorbid neuropathology. Characterization of the in vivo biomarkers of CTE is a necessary next step to facilitate accurate diagnoses. We examined the profile of cerebrospinal fluid (CSF) biomarkers of amyloid-β, total tau (tTau), and phospho-tau (pTau) in a cohort of former professional (PRO, n = 100) and college (COL, n = 40) football players at high risk of CTE compared to asymptomatic unexposed controls (UE, n = 43). CSF was collected under controlled conditions using collection, processing, and cryostorage kits provided by the DIAGNOSE CTE Research Project Biomarker Core, and concentrations of Aβ₄₀, Aβ₄₂, tTau, and pTau (pTau₁₈₁, pTau₂₁₇, pTau₂₃₁) were measured at the University of Gothenburg, Sweden, using immunoassays. Associations between CSF biomarker levels with football history, and diagnosis of traumatic encephalopathy syndrome (TES) were examined using linear regression, and corrected for age, education, APOE-ε4 allele status, race, and body mass index. Our analysis revealed that football exposure affected both CSF Aβ₄₀ (p = 0.039) and Aβ₄₂ (p = 0.038), particularly among those under 60 years of age in the PRO compared to the UE exposure group. Among former football players, estimates of RHI exposure were not generally associated with CSF Aβ, tTau, and pTau biomarker levels. CSF Aβ₄₀ (p = 0.0041) and Aβ₄₂ (p = 0.011) were lower in former football players with TES diagnosis compared to unexposed participants, although CSF Aβ, tTau, and pTau biomarker levels did not differ between former players with and without a TES diagnosis. Among former football players, reduced CSF Aβ₄₀ (p = 0.011) and Aβ₄₂ (p = 6e-04) were observed in those with cognitive impairment compared to those with neurobehavioral dysregulation. The findings of significant associations of reduced CSF Aβ levels with RHI in elite football players are in line with recent postmortem studies; however, the lack of relationship with CSF tTau and pTau species observed to be altered in the setting of AD suggests that the pathological features of CTE reflected in fluid biomarkers are complex and require further study. The overlapping comorbid age-dependent features of neurodegeneration that occur in those at risk for CTE suggest that tau pathology in CTE is not reliably reflected by currently available fluid biomarkers and that the use of multiple biomarkers related to the compound characteristics of CTE may be required for early detection.

PURPOSE/OBJECTIVE:Hemorrhagic radiation cystitis (HRC), a complication of pelvic radiation therapy, results from hypoxic and ischemic injury and causes urinary symptoms like hematuria, dysuria, frequency, urgency, and retention. Hyperbaric Oxygen Therapy (HBOT), where patients breathe 100% oxygen at increased atmospheric pressure, enhances tissue oxygenation, promoting neovascularization and reducing inflammation. The optimal pressure remains unclear, though pressures above 1.41 ATA are efficacious, with higher pressures increasing side effect risks. This study compares the efficacy and side effects of 2.0 versus 2.5 ATA therapy at two sites. MATERIALS AND METHODS/METHODS:A retrospective chart review of 93 patients treated for HRC at two sites was conducted. Data on demographics, efficacy (symptom reduction), and side effects were analyzed using GraphPad Prism. Chi-squared and Mann-Whitney tests were used for statistical analysis. Mixed effects logistic regression models were used. RESULTS AND CONCLUSIONS/CONCLUSIONS:Fewer patients treated at 2.5 ATA experienced gross hematuria within 1-year post-therapy compared to those treated at 2.0 ATA (p < 0.05). However, time to hematuria recurrence showed no difference between the groups (10.2 vs. 9.6 months). No difference was observed in other urinary symptoms. Adverse events were increased at 2.5 ATA when analyzed with a mixed effects logistic regression model. Other treatment parameters, including treatment number and duration, were similar across groups. These findings suggest an association between 2.5 ATA treatment and lower rates of hematuria recurrence, but further randomized studies are necessary to determine causality. Future studies should also assess quality of life and explore variations in treatment protocol for efficacy and safety. CLINICAL TRIAL REGISTRATION/BACKGROUND:As this is a retrospective study, no clinical trial registration is necessary.

BACKGROUND:Varicocele severity has traditionally been associated with larger testicular vein size, but the true relationship to decreased fertility remains debatable. In clinical practice, the largest testicular vein diameter is an often-used parameter to screen for potential surgical intervention, even though current research provides weak support for this. More recent studies have found venous reflux patterns and total testicular volume (TTV) to be significantly associated with total motile sperm count (TMSC). This study compares largest testicular vein size and arterial flow rates, assessing the predictive value of each for identifying patients at risk for reduced semen analysis (SA) parameters. METHODS:We conducted a retrospective, single-institution chart review over 14 years of 487 Tanner V adolescents. Patients were included if they had a palpable, primary left-sided varicocele and underwent at least one SA and scrotal Doppler ultrasound (SDUS) to assess vein diameter and arterial blood flow including peak systolic and end-diastolic velocities. Abnormal TMSC was defined by WHO 2010 criteria. Descriptive statistics, ROC analysis and univariate as well as multivariate logistic regression analyses were performed using SPSS. RESULTS:148 Tanner V adolescent males were included. Mean age ± SD was 18.24 ± 1.38 years. Median diameter of largest vein on US was 3.5 mm (IQR 3.1-4.6), median peak systolic velocity (PSV) of the left testicular artery was 10.4 cm/s (IQR 9.1-12.5), median end-diastolic velocity (EDV) of the left testicular artery was 5.1 cm/s (IQR 4.3-5.9), and median value of PSV/EDV was 2.1 (IQR 1.8-2.3), with a median TMSC of 37.4 million sperm (IQR 15.8-84.2). On ROC analysis regarding prediction of abnormal TMSC (<9 million sperm/ejaculate), left testicular PSV was found to have the greatest AUC at 0.73 (95 % CI 0.62-0.85) with Youden index analysis determining an ideal cutoff of 10.22 cm/s. Based on this cutoff, the positive predictive value for identifying a patient with abnormal TMSC was 23.6 %, corresponding to a number needed to screen of approximately 4 patients to identify one with abnormal sperm parameters. Left testicle largest vein diameter was found to have an AUC of 0.48. On univariate logistic regression, PSV <10.22 cm/s was predictive of abnormal TMSC (OR: 5.51 [1.84-16.46], p = 0.002, which persisted on multivariate logistic regression with adjustment for age (OR: 5.49 [1.83-16.43], p = 0.002). CONCLUSION/CONCLUSIONS:Left testicular PSV was the parameter most significantly correlated with TMSC in this cohort. A PSV <10.22 cm/s was found to be predictive of an abnormally low TMSC. There was no significant predictive value of larger veins for abnormal TMSC. When assessing varicocele severity by US, left testicular artery PSV should be measured to help stratify future fertility risk and provide important context regarding shared decision making about potential surgical intervention.

AIMS/OBJECTIVE:To describe management of life with a left ventricular assist device (LVAD) by patients and caregivers and to determine the fit of self- and family management as a guiding concept in LVAD research. METHODS AND RESULTS/RESULTS:We applied dimensional analysis techniques to this concept analysis, beginning with a literature search (2010-25) of PubMed, CINAHL, Embase, PsycINFO, and Web of Science. Two reviewers screened and analysed 28 articles capturing perspectives on daily LVAD management among patients, caregivers, and healthcare professionals. Fourteen studies were qualitative, 12 were quantitative, and 2 were mixed methods. We identified five dimensions of patient and family management of LVAD therapy: patient facilitators and barriers; caregiver facilitators and barriers; processes of self- and family management; clinician facilitators and barriers/processes; and outcomes. These dimensions align with the concept of self- and family management and with core components of the Middle Range Theory of Self- and Family Management of Chronic Illness. CONCLUSION/CONCLUSIONS:This dimensional concept analysis advances understanding of managing life with an LVAD by clarifying the collaborative roles of patients, caregivers, LVAD coordinators, and other healthcare professionals. Our analysis supports the use of self- and family management as a guiding concept and the application of the Middle Range Theory of Self- and Family Management of Chronic Illness in LVAD research. A new conceptual definition of LVAD self- and family management reflects this theoretical grounding. Our work offers direction for future research, clinical practice, and education aimed at improving outcomes for patients and caregivers managing life with an LVAD.

The prevalence and incidence of prediabetes in children and youth continue to increase in parallel with the obesity epidemic. While prediabetes is defined by elevated HbA1c and/or impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), the risk of clinical disease is a continuum. Individuals with prediabetes are at a higher risk of developing youth-onset type 2 diabetes, which is considered a more aggressive form of the disease. This condition is associated with increased cardiovascular and metabolic risks and leads to an earlier onset of complications compared to adults with type 2 diabetes. Additionally, significant damage to beta cells may occur even before dysglycemia develops. Recent data indicate that mortality rates are higher in youths with type 2 diabetes compared to those with type 1 diabetes. Childhood prediabetes and cardiovascular complications associated with it are a significant health concern. This review provides the latest insights into this complex issue. We will present an overview of pathophysiology, screening methods, and therapeutic options to prevent the progression from prediabetes to type 2 diabetes in children. In summary, it is crucial to identify prediabetes in children, as this underscores the importance of appropriate screening and timely intervention.

IMPORTANCE/UNASSIGNED:Mental disorders have been associated with traditional cardiovascular risk factors that may mediate the risk of acute coronary syndrome (ACS). OBJECTIVE/UNASSIGNED:To estimate the association of ACS among patients with mental disorders, as compared with patients without mental disorders. DATA SOURCES/UNASSIGNED:MEDLINE, Embase, and PubMed were searched for studies between July 1, 2025, and date of database inception. STUDY SELECTION/UNASSIGNED:Study screening was performed in duplicates with conflicts resolved upon consensus. Inclusion criteria were as follows: (1) observational or randomized study, (2) measured association with ACS (incident events, risk ratio, odds ratio, hazard ratio [HR]), and (3) investigated any clinical mental disorder (based on DSM and International Classification of Diseases) before ACS events. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data extraction was performed in duplicate and resolved on consensus. Data were quantitatively synthesized through random-effects meta-analysis. The National Institutes of Health Study Quality Assessment Tools were used to assess the quality of included studies. Studies were analyzed from January 1966 to October 2021. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Association and/or risk of ACS. RESULTS/UNASSIGNED:Among 3616 initially identified studies, 25 full-text articles met inclusion criteria with 22 048 504 participants of median (IQR) age 48.0 (34.5-56.1) years, with 13 019 897 males (59.1%). Depressive disorder (HR, 1.40; 95% CI, 1.11-1.78; P = .01; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty = very low), anxiety disorder (HR, 1.63; 95% CI, 1.40-1.89; P < .001; GRADE certainty = low), sleep disorder (HR, 1.60; 95% CI, 1.22-2.10; P < .001; GRADE certainty = low), and posttraumatic stress disorder (PTSD; HR, 2.73; 95% CI, 1.94-3.84; P < .001; GRADE certainty = moderate) were associated with increased risk of ACS. Bipolar (HR, 1.48; 95% CI, 0.47-4.61; P = .28; GRADE certainty = very low) and psychotic (HR, 0.97; 95% CI, 0.01-178.30; P = .06; GRADE certainty = very low) disorders were not significantly associated with increased risk of acute myocardial infarction, although they had similar point estimates to some other mental disorders. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Results of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.