Faculty Bibliography

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.

Drug-induced liver injury describes the result of toxicity to the liver from offending drugs and/or their metabolites. Most cases are acute and resolve quickly after the medication is discontinued. It is a diagnosis of exclusion after ruling out other causes of liver injury, such as infectious and autoimmune etiologies. When drug-induced liver injury is suspected, the culprit can be determined by establishing a temporal relationship between drug exposure and the development of signs and symptoms of liver injury. In this case presentation, we discuss a patient who developed liver injury from pyridostigmine in the management of acute colonic pseudo-obstruction (Ogilvie syndrome).

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.

BACKGROUND:Physical activity and sedentary behavior are associated with adolescent mental health. However, prior studies have not assessed whether these associations differ across varying levels of mental health severity. This study uses objectively measured physical activity and sedentary behavior to examine their associations with adolescent mental health and to determine how these associations vary across the distribution of mental health symptoms. METHODS:This longitudinal prospective study examined data from the Adolescent Brain Cognitive Development (ABCD) Study, a large cohort of children and adolescents recruited from 21 study sites in the United States. This analysis included 5640 participants whose physical activity and sedentary behavior data were recorded using Fitbit wearable devices when aged 11-12 years. Outcomes were internalizing and externalizing symptoms assessed a year later by the caregiver using the Child Behavior Checklist. RESULTS:More daily steps (b = -0.43, 95% CI [-0.58, -0.29]), longer moderate-to-vigorous physical activity (MVPA) (b = -0.34, 95% CI [-0.47, -0.22]) and less sedentary time (b = 0.32, 95% CI [0.15, 0.48]) were each associated with fewer internalizing symptoms a year later. The associations were stronger for youth at higher internalizing symptom quantiles. Limited or no effects were found for externalizing symptoms. Sex differences were also observed. CONCLUSION/CONCLUSIONS:Objectively measured daily steps, MVPA, and sedentary behavior are prospectively associated with adolescent internalizing symptoms. The associations differ substantially among adolescents with varying levels of symptom severity and between sexes. Findings may inform targeted physical activity interventions to enhance adolescent mental health.

CONTEXT:The hallmark condition of Prader-Willi syndrome, a rare, genetic neurobehavioral/metabolic disorder is life-threatening hyperphagia. OBJECTIVE:We assessed the efficacy and safety of recently FDA-approved diazoxide choline extended-release (DCCR) tablets for the treatment of hyperphagia in adults and children four years of age and older with Prader-Willi syndrome. METHODS:We conducted a 16-week, randomized withdrawal study in children and adults with Prader-Willi syndrome and hyperphagia. Participants who previously completed randomized (13-week DCCR or placebo) and open-label (2.5-4.5 years DCCR) studies were randomized one:one to receive once-daily DCCR or placebo. The primary endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score change from baseline to 16 weeks. Secondary endpoints included Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I); exploratory endpoints included weight and body mass index (BMI) z-score. RESULTS:Seventy-seven participants were randomized (DCCR:38; placebo:39). Statistically significant increases in HQ-CT from baseline to week 16 were observed with placebo versus DCCR (least square [LS] mean [standard error] change 7.6 [1.09] with placebo and 2.6 [1.12] with DCCR; P=0.0022). CGI scores favored DCCR but were not significantly changed. Consistent with the hyperphagia response, the placebo cohort gained more weight and increased their BMI z-score more than the DCCR cohort (LS mean weight difference (95% confidence interval) -1.6 kg (-3.1, -0.1); LS mean z-score difference -0.09 (-0.17, -0.01). Adverse events were similar with both treatments, with no serious adverse events in the DCCR arm. CONCLUSIONS:Continued DCCR treatment was superior to placebo for hyperphagia. DCCR appears to offer meaningful therapeutic benefits for people with Prader-Willi syndrome.

ObjectiveWe designed a survey to determine the prevalence of sexual dysfunction among cancer patients and to understand the gaps in provider-patient communication.MethodsAn IRB-approved 36-item survey was distributed through the Jefferson Recruitment Enhancement Service team and social media. Questions assessed the impact of cancer treatment on sexual health, provider communication, how sexual health was assessed, and possible interventions. Chi-square test or Fisher's exact test were used to compare the group differences with a P-value threshold (α) of 0.05 for statistical significance.Results916 patients responded to the survey, with most being diagnosed with breast (n = 271, 29.6%) and prostate cancer (n = 358, 39.1%). 71.8% of patients experienced an impact on sexual function by cancer treatment. Most experienced issues with their sexual desire, body image, arousal, comfort during intercourse, and ability to achieve orgasm (α < 0.001). Only 35.5% reported being asked about their sexual health by an oncologist and only 22.2% were given a questionnaire to assess their sexual health (α < 0.001). 49.8% of breast patients and 15.4% of prostate patients were never told their sexual health could be affected by their cancer treatment (α < 0.001). 60.3% of prostate patients were formally asked about their sexual health by an oncologist compared to 21.4% of breast patients (α < 0.001). 74% of respondents stated it is essential for oncologists to speak to patients about sexual health.ConclusionCancer survivors believe it is important for providers to discuss sexual health. However, providers are more inclined to address sexual health concerns with male patients than with female counterparts.