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ABSTRACTBackgroundHidradenitis suppurativa (HS) is a chronic inflammatory condition. While obesity is linked to increased HS severity in adults, data on its impact in pediatric HS remain limited. This study investigates the relationships between obesity, HS severity, HS‐related comorbidities, and therapeutic management in pediatric patients.MethodsThis is a retrospective cohort analysis on patients diagnosed with HS before 18 years of age. Data were collected on disease severity, comorbidity development, and treatments. Trends were compared between HS patients with and without obesity and with healthy controls for comorbidity development.ResultsThere was no difference in disease severity using Hurley staging between patients with and without obesity (p = 0.679). Patients with obesity were more likely to be prescribed biologics (p = 0.012), but not other treatments. The risk of developing dyslipidemia, anxiety, depression, and thyroid disease was elevated in pediatric HS patients, even after controlling for BMI (p < 0.001).ConclusionsIn this study, obesity was not associated with HS disease severity in children. However, children with obesity were more likely to be prescribed biologics. HS may independently increase the risk of dyslipidemia, anxiety, depression, and thyroid disease.

Abstract INTRODUCTION There is a need to understand the clinical meaningfulness of symptom score changes in treatment trials of dementia‐related agitation. We estimated minimal clinically important differences (MCIDs) for commonly employed agitation scales and contextualized their clinical application. METHODS We employed anchor‐ and distribution‐based approaches to determine changes in scores corresponding to minimal symptom improvement. An opinion‐based approach assessed expert clinicians’ agreement on the meaningfulness of score changes through three clinical vignettes. RESULTS Minimal symptom improvement for Cohen‐Mansfield Agitation Inventory total score ranged from −4 (over <1 month) to −11 (over 1 to 3 months) points. Greater symptom severity correlated with higher MCID estimates. The clinical importance of score changes was influenced by treatment duration, pharmacological side effects, and impacts on caregiver distress/time resources. DISCUSSION The clinical meaningfulness of agitation scale MCIDs is influenced by trial‐specific and clinical factors. Shorter trial durations and measuring caregiver distress/time resources enhance the clinical interpretation of agitation treatment outcomes. Highlights For the CMAI total score, the MCID was −4 points over shorter time scales and −11 points for longer time scales. Worse agitation severity was associated with higher MCID estimates. There was high expert consensus that a noticeable treatment benefit was not worthwhile if it occurred after 12 weeks or had no impact on caregiver/staff distress/time resources.

BACKGROUND: Thresholds to define prognosis with hs-cTnI (high-sensitivity cardiac troponin I) have not been systematically addressed in wild-type transthyretin amyloid cardiomyopathy, in part because of the multiplicity of hs-cTnI assays. The aims of this study were: first, to assess the prognostic performance of hs-cTnI measured with different assays in patients with wild-type transthyretin amyloid cardiomyopathy and, second, to identify assay-specific hs-cTnI thresholds for prognosis that could be integrated into staging systems for risk stratification. METHODS: Observational multicenter study of stable wild-type transthyretin amyloid cardiomyopathy patients from different cohorts using the Abbott Architect Stat hs-cTnI assay and the Beckman Coulter Access hs-cTnI assay (testing cohorts) and the Siemens Centaur XPT hs-cTnI assay (validation cohort). Outcome was all-cause mortality. RESULTS: In the Abbott cohort (n=136; median follow-up 22 [13–41] months; 31 [23%] deaths) and Beckman cohort (n=98; median follow-up 19 [12–28] months; 16 [16%] deaths), natural log-transformed hs-cTnI was an independent predictor of mortality (age- and sex-adjusted hazard ratio, 1.62 [95% CI, 1.11–2.35]; P =0.012 and 2.47 [95% CI, 1.48–4.14]; P <0.001, respectively). The best hs-cTnI threshold for 18-month mortality of the combined Abbott/Beckman cohorts (n=234) was 81 ng/L, rounded to 80 ng/L for simplicity of clinical use. A 2-variable staging system (based on the Mayo Clinic system) using hs-cTnI (>80 ng/L) and NPs (natriuretic peptides; NT-proBNP [N-terminal pro-B-type natriuretic peptide] >3000 ng/L or BNP [B-type natriuretic peptide] >250 ng/L) identified 3 groups with progressively worse prognosis. The staging system (using hs-cTnI >80 ng/L and NT-proBNP>3000 ng/L) was then applied to an independent cohort evaluated with the hs-cTnI Siemens assay (n=345, median follow-up 32 [24-42] months, 119 [34%] deaths). The significant differences between the groups were maintained. CONCLUSIONS: In patients with wild-type transthyretin amyloid cardiomyopathy, hs-cTnI is a strong and independent predictor of mortality. A threshold of hs-cTnI of 80 ng/L for these 3 assays provides effective risk stratification alone and in a staging system with NP.

Abstract The use of radiofrequency ablation (RFA) of benign, symptomatic thyroid nodules is growing in clinical practice. Objective outcomes of symptom relief are needed to support the use of this treatment. Thus, a previously established thyroid nodule symptom scoring system was prospectively administered to patients prior to RFA of symptomatic thyroid nodules and then at 1, 3, 6, and 12 months following ablation. A total of 38 patients of mean age 57 years were treated with RFA between August 2022 and January 2024 and completed at least 1 follow-up survey. Five of these patients underwent simultaneous ablation of 2 thyroid nodules; the remainder had a single nodule treated. Mean modified symptom score prior to RFA was 3.5 (SD 1.6) with higher scores correlating with increasing baseline nodule volume (R = 0.46, P = 0.0038). Patient symptom scores decreased at the first 1-month survey (mean 1.2; SD 1.3) and 3-month survey (mean 0.9; SD 1.3) with durable response in those patients with more extended follow-up. In those patients with imaging follow-up, decreasing nodule size was shown to correlate with decreasing symptoms. The early results of this study show that RFA of benign, symptomatic thyroid nodules results in quantifiable symptom relief within 3 months of treatment. Such objective measures of symptom relief may be used to measure long-term durability of treatment.

Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines.

Abstract Molecular mechanisms underlying disruptions in brain glucose uptake and metabolism, linked with cognitive decline in Alzheimer’s disease (AD) patients, are only partially understood. This study investigated how soluble amyloid beta (sAβ) peptides affect glucose transport at the blood-brain barrier (BBB), the primary portal for glucose entry into the brain. We demonstrated that [ 18 F]-fluorodeoxyglucose ( 18 FDG) uptake is reduced in sAβ overproducing APP,PS1 transgenic mice compared to wild-type mice. Moreover, the influx rate of 18 FDG decreased in sAβ40 or sAβ42 pre-infused mice, highlighting the inhibitory effect of sAβ peptides on glucose transport at the BBB. Consistently, the expression of GLUT1, the primary glucose transporter at the BBB, is reduced in polarized human cerebral microvascular endothelial cell (hCMEC/D3) monolayers upon exposure to sAβ peptides and in Aβ-laden cerebral vasculature in vivo. The study further examined the influence of sAβ on the insulin-AKT pathway, known to regulate glucose uptake through modulation of thioredoxin-interacting protein (TXNIP) expression. Results showed that sAβ peptides suppress AKT phosphorylation and reduce GLUT1 expression by upregulating TXNIP levels in hCMEC/D3 monolayers. Co-incubation of resveratrol with sAβ peptides reduced TXNIP expression and rectified reductions in GLUT1 expression. In summary, toxic sAβ impairs BBB glucose transport by disrupting the insulin/AKT/TXNIP axis.

Purpose: To develop and validate an explainable machine learning (ML) tool to help clinicians predict the risk of propofol-associated hypertriglyceridemia in critically ill patients receiving propofol sedation. Methods: Patients from 11 intensive care units (ICUs) across five Mayo Clinic hospitals were included if they met the following criteria: a) ≥ 18 years of age, b) received propofol infusion while on invasive mechanical ventilation for ≥24 h, and c) had a triglyceride level measured. The primary outcome was hypertriglyceridemia (triglyceride >400 mg/dL) onset within 10 days of propofol initiation. Both COVID-inclusive and COVID-independent modeling pipelines were developed to ensure applicability post-pandemic. Decision thresholds were chosen to maintain model sensitivity >80%. Nested leave-one-site-out cross-validation (LOSO-CV) was used to externally evaluate pipeline performance. Model explainability was assessed using permutation importance and SHapley Additive exPlanations (SHAP). Results: Among 3922 included patients, 769 (19.6%) developed propofol-associated hypertriglyceridemia, and 879 (22.4%) had COVID-19 at ICU admission. During nested LOSO-CV, the COVID-inclusive pipeline achieved an average AUC-ROC of 0.71 (95% confidence interval [CI] 0.70–0.72), while the COVID-independent pipeline achieved an average AUC-ROC of 0.69 (95% CI 0.68–0.70). Age, initial propofol dose, and BMI were the top three most important features in both models. Conclusion: We developed an explainable ML-based tool with acceptable predictive performance for assessing the risk of propofol-associated hypertriglyceridemia in ICU patients. This tool can aid clinicians in identifying at-risk patients to guide triglyceride monitoring and optimize sedative selection.

Background: Malignant mesenchymal tumors involving the parotid gland are uncommon, characteristically aggressive, and little is known with few reports documented. Study Design: Retrospective case series. Setting: Single institution tertiary care center, 2010 to 2022. Method: Patients were identified from an institutional parotid tumor database. Patient history, demographics, pathologic diagnosis, treatment, and follow up were documented. Results: Eight patients were identified, 3 were males. The average age was 61 years old, and the most common tumors identified were pleomorphic sarcomas (3 patients). Presenting symptoms included: preauricular/cheek mass in 7 patients, facial pain (4), otalgia (4), aural fullness (3), and numbness (1). All patients received a parotidectomy, and 4 patients received adjuvant therapy of either radiation or chemoradiation. Post-operatively, there were 3 cases of distant recurrence, 2 cases of regional recurrence, and 1 case of local recurrence. There were 2 reports of death. Conclusion: Malignant mesenchymal tumors of the parotid are rare, represent varied histologies. Due to their aggressive nature, surgical resection with radiation and close follow-up may be an appropriate treatment regimen in controlling the disease.