Analysis of publicly available adverse events reported for pediatric patients treated with Janus kinase inhibitors.

Janus kinase inhibitors (JAKi) are drugs that block tyrosine kinases responsible for transducing cytokine signals. The first JAKi was approved by the US Food and Drug Administration (FDA) in 2011 to treat rheumatoid arthritis in adults. A pediatric indication was not approved until 8 years later, for acute graft-versus-host disease. Since then, topical and oral formulations have gained FDA approval for pediatric patients with dermatologic diseases. While increasing evidence supports the safety of these medications in adults, data are limited in children. We sought to determine whether JAKi adverse events (AEs) as reported in clinical trials and via postapproval pharmacovigilance services are comparable in adult and pediatric patients. Pharmacovigilance data were extracted from the FDA's Adverse Event Reporting System and the Canada Vigilance Adverse Reaction Online Database for baricitinib, upadacitinib, abrocitinib, ruxolitinib, and tofacitinib. The pooled data were analyzed to detect the most common AEs for specific JAKi and for the drug class. We assessed 399,649 AEs from 133,216 adults and 2883 AEs from 955 patients under 18 years old and identified slightly different AE profiles for the two age groups. Both populations had increased risk for infections and gastrointestinal AEs. However, pediatric patients reported a higher proportion of blood and lymphatic disorders, while reports of nervous system and musculoskeletal/connective tissue disorders were more common in adults. The spectrum of AEs extracted from pharmacovigilance reports was similar to clinical trials. The JAKi AE profiles we observed may prove helpful in counseling patients and their parents before starting therapy and for monitoring once patients are on therapy.

Comprehensive considerations for dermatologists: the application of FDG-PET in evaluating cutaneous lesions in pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a complex disorder characterized by the clonal proliferation of Langerhans cells, primarily affecting children and adolescents. This condition exhibits a wide spectrum of clinical presentations, necessitating a multidisciplinary approach for diagnosis, treatment, and follow-up. Cutaneous manifestations of LCH are significant, mimicking common dermatoses and posing diagnostic challenges. [18F]Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) has emerged as an important tool in the evaluation of pediatric LCH, offering insights into disease activity, extent, and therapeutic response. Moreover, FDG-PET provides a non-invasive means to distinguish between active LCH skin lesions and other dermatological conditions with similar clinical appearances, enhancing diagnostic accuracy and aiding in disease monitoring. This educational review summarizes the utility of nuclear imaging techniques, with a focus on PET scans, in the diagnosis and management of cutaneous pediatric LCH. A comprehensive literature search identified seven relevant articles, including retrospective studies and case reports. These studies highlight the efficacy of FDG-PET in localizing active LCH skin lesions, monitoring disease activity, and guiding treatment decisions. FDG-PET represents a valuable imaging modality for dermatologists, oncologists, and pediatricians managing pediatric LCH patients with cutaneous involvement. This non-invasive technique contributes to improved diagnostic accuracy and facilitates early intervention, ultimately enhancing patient care and outcomes.

FDG-PET in the diagnosis of primary progressive aphasia: a systematic review.

Primary progressive aphasia (PPA) is a disease known to affect the frontal and temporal regions of the left hemisphere. PPA is often an indication of future development of dementia, specifically semantic dementia (SD) for frontotemporal dementia (FTD) and logopenic progressive aphasia (LPA) as an atypical presentation of Alzheimer's disease (AD). The purpose of this review is to clarify the value of 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-positron emission tomography (PET) in the detection and diagnosis of PPA. A comprehensive review of literature was conducted using Web of Science, PubMed, and Google Scholar. The three PPA subtypes show distinct regions of hypometabolism in FDG-PET imaging with SD in the anterior temporal lobes, LPA in the left temporo-parietal junction, and nonfluent/agrammatic Variant PPA (nfvPPA) in the left inferior frontal gyrus and insula. Despite the distinct patterns, overlapping hypometabolic areas can complicate differential diagnosis, especially in patients with SD who are frequently diagnosed with AD. Integration with other diagnostic tools could refine the diagnostic process and lead to improved patient outcomes. Future research should focus on validating these findings in larger populations and exploring the therapeutic implications of early, accurate PPA diagnosis with more targeted therapeutic interventions.

Predictors of Extended Length of Stay After Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND: Despite their asymptomatic occurrence, unruptured intracranial aneurysms (UIAs) account for a significant proportion of hospital charges and healthcare resource utilization in the United States. Hospital length of stay (LOS) is a reimbursement metric utilized to incentivize value-based care. Our study identifies predictors of extended LOS (eLOS) after elective treatment of UIAs. METHODS: This was a retrospective study of 525 patients who underwent elective treatment of an UIA at a single institution. Data were collected with regard to demographics, clinical presentation, treatment characteristics, and postoperative outcomes. The primary outcome, eLOS, was defined as hospital stay in the upper quartile of the median (≥75th percentile). Univariate and multivariate analyses were performed to identify factors predictive of eLOS in this cohort. RESULTS: The average age of the cohort was 61.40, standard deviation=11.41. 77.3% of the cohort was female. The median duration of LOS was 2 days (interquartile range: 1-5). 11.6% experienced eLOS (≥5 days). Multivariate logistic regression identified age (OR: 1.04, 95% confidence interval [CI]: 1.01-1.07), coexistent vascular pathology (OR: 21.33, 95% CI: 8.06-56.39), open surgery (OR: 3.93, 95% CI: 1.85-8.34), and postoperative stroke (OR: 11.72, 95% CI: 3.18-43.18) as independent predictors of eLOS. CONCLUSIONS: Our study identified predictors of eLOS that could help promote risk stratification prior to treatment of UIAs. Future research that identifies predictors of long-term outcomes based on treatment modality could help identify ways to improve healthcare resource utilization in this cohort.

Positron Emission Tomography (PET) in presurgical planning of anterior temporal lobectomy: A systematic review of efficacy and limitations.

INTRODUCTION: Temporal lobe epilepsy (TLE), a debilitating neurological disorder, necessitates refined diagnostic and treatment strategies. This comprehensive review appraises the potential of positron emission tomography (PET) in enhancing the presurgical planning of Anterior Temporal Lobectomy (ATL) for patients afflicted with TLE. METHODS: A comprehensive literature search was conducted using the PubMed, SCOPUS, and ScienceDirect databases from 1985 to 2022, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies investigating PET and ATL. This review studied a range of radiotracers, including FDG, H2O, FMZ, MPPF, and FCWAY, analyzing their efficacy in detecting epileptogenic foci, establishing resection boundaries, and predicting postoperative outcomes. The study paid special attention to cases where MRI findings were inconclusive. RESULTS: A total of 52 studies were included in the final analysis. Our analysis revealed that FDG-PET imaging was instrumental in identifying seizure foci and predicting postoperative results. It exhibited significant value in situations where structural abnormalities were absent on MRI scans. Furthermore, newer radiotracers such as 5-HT1A antagonists, FCWAY and MPPF, presented promising potential for localizing seizure foci, particularly in MRI-negative TLE, despite their comparatively limited current usage. CONCLUSION: PET imaging, although challenged by issues such as radiation exposure, limited accessibility, and high costs, offers considerable promise. Integration with other imaging modalities, such as EEG and MRI, has contributed to improved localization of epileptogenic foci and subsequently, enhanced surgical outcomes. Further research must focus on establishing the relative efficacy and optimal combinations of these radiotracers in the orchestration of ATL surgical planning and prognostication of postoperative outcomes for TLE patients. Encouragingly, these advancements hold the potential to revolutionize the management of TLE, delivering a better quality of life for patients.

The Era of Radial-Specific Catheters: A Multicenter Comparison of the Armadillo and RIST Catheters in Transradial Procedures.

BACKGROUND AND OBJECTIVES: As the radial approach is gaining popularity in neurointervention, new radial-specific catheters are being manufactured while taking into consideration the smaller size of the radial artery, different trajectories of angles into the great vessels from the arm, and subsequent force vectors. We compared outcomes of transradial procedures performed using the Armadillo catheter (Q'Apel Medical Inc.) and the RIST radial guide catheter (Medtronic). METHODS: This is a retrospective multicenter study comparing outcomes of transradial neuroendovascular procedures using the Armadillo and RIST catheters at 2 institutions between 2021 and 2024. RESULTS: The study comprised 206 patients, 96 of whom underwent procedures using the Armadillo and 110 using the RIST. Age and sex were comparable across cohorts. In most procedures, 1 target vessel was catheterized (Armadillo: 94.8% vs 89.1%, P = .29) with no significant difference between cohorts. The use of an intermediate catheter was minimal in both cohorts (Armadillo 5.2% vs RIST: 2.7%, P = .36), and the median number of major vessel catheterization did not significantly differ between cohorts (Armadillo: 1 [1-4] vs RIST: 1 [0-6], P = .21). Failure to catheterize the target vessel was encountered in 1 case in each cohort (Armadillo: 1.0% vs RIST: 0.9%, P = .18), and the rate did not significantly differ between cohorts. Similarly, the rate of conversion to femoral access was comparable between cohorts (Armadillo: 2.1% vs RIST: 1.8%, P = .55). There was no significant difference in access site complications (Armadillo: 1% vs RIST: 2.8%, P = .55) or neurological complications (Armadillo: 3.1% vs RIST: 5.5%, P = .42) between cohorts. CONCLUSION: No significant difference in successful catheterization of target vessels, procedure duration, triaxial system use, complication rates, or the need for transfemoral cross-over was observed between both catheters. Both devices offer high and comparable rates of technical success and low morbidity rates.

Telescoping Flow Diverters for the Treatment of Brain Aneurysms: Indications and Outcome.

OBJECTIVE: Few studies have reported the impact of telescoping flow diverters (FDs) in intracranial aneurysm treatment. Our study compared aneurysms treated using telescoping FDs to those treated with a single FD and identified predictors of telescoping. METHODS: This was a single-center retrospective review of a prospectively maintained database of aneurysms treated with FDs between 2011 and 2023. All patients who were treated with FDs for intracranial aneurysms were included in the study. RESULTS: The study comprised 750 patients with 750 aneurysms treated using 871 FDs. The study cohort was divided into 85 patients requiring telescoping FDs and 655 who did not. Rates of hemorrhage (7.1% vs. 1.8%, P < 0.001), symptomatic stroke (5.9% vs. 2.6, P < 0.001), and asymptomatic stroke (1.2% vs. 0.8%, P < 0.001) were significantly higher in the telescoping cohorts. At final follow-up, the rate of nonocclusion (9.8% vs. 5.1%, P = 0.029) and the rate of complete occlusion (88.5% vs. 81.1%, P = 0.029) were significantly higher in the telescoping cohort. On multivariate analysis, fusiform morphology (odds ratio [OR]: 2.4, 95% confidence interval [CI] 1.0-5.0, P = 0.03), increasing aneurysm height (OR: 1.0, 95% CI 1.0-1.1, P= 0.034), and the use of the Pipeline Embolization Device FD (OR: 2.4, 95% CI 1.3-4.4, P = 0.005) were independent predictors of telescoping. CONCLUSIONS: Aneurysms with fusiform morphology, increasing aneurysm height and those that underwent flow diversion using Pipeline Embolization Device had higher odds for telescoping. Significantly higher rates of angiographic occlusion with the use of telescoping FD add to the literature on its efficacy in treating aneurysms of varying morphology.

The Role of FDG-PET in the Evaluation of Hidradenitis Suppurativa: A Systematic Review.

Hidradenitis suppurativa (HS) is a chronic skin disorder characterized by nodules, comedones, and sinus tracts that often leave prominent scarring. In recent years, non-invasive imaging techniques have been used to assess the inflammatory activity, vascularization, and treatment response of lesions. Specifically, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans may aid in identifying systemic inflammation in patients with HS, improving diagnosis. Inflamed hypermetabolic tissues exhibit a greater uptake of FDG due to increased glucose uptake and vascularity. A systematic review was conducted to summarize the utility of nuclear imaging techniques in the diagnosis and treatment follow-up of HS. PubMed, Scopus, and ScienceDirect databases were utilized for relevant articles discussing the utility of PET scans in managing HS. A total of 51 citations were identified in the initial search. Following the review of titles, abstracts, and duplicates, 43 articles were excluded, leaving a total of eight articles for analysis. Data were extracted from each article, encompassing the number of patients, imaging techniques employed, and final results. An analysis of the data demonstrated that FDG-PET showed evidence of identifying subclinical lesions of the disease, improving the visualization of HS, and providing an objective method of assessing severity.

Bilateral Carotid Artery Molecular Calcification Assessed by [18F] Fluoride PET/CT: Correlation with Cardiovascular and Thromboembolic Risk Factors.

Atherosclerosis, a leading cause of mortality and morbidity worldwide, involves inflammatory processes that result in plaque formation and calcification. The early detection of the molecular changes underlying these processes is crucial for effective disease management. This study utilized positron emission tomography/computed tomography (PET/CT) with [18F] sodium fluoride (NaF) as a tracer to visualize active calcification and inflammation at the molecular level. Our aim was to investigate the association between cardiovascular risk factors and [18F] NaF uptake in the left and right common carotid arteries (LCC and RCC). A cohort of 102 subjects, comprising both at-risk individuals and healthy controls, underwent [18F] NaF PET/CT imaging. The results revealed significant correlations between [18F] NaF uptake and cardiovascular risk factors such as age (ß = 0.005, 95% CI 0.003-0.008, p < 0.01 in LCC and ß = 0.006, 95% CI 0.004-0.009, p < 0.01 in RCC), male gender (ß = -0.08, 95% CI -0.173--0.002, p = 0.04 in LCC and ß = -0.13, 95% CI -0.21--0.06, p < 0.01 in RCC), BMI (ß = 0.02, 95% CI 0.01-0.03, p < 0.01 in LCC and ß = 0.02, 95% CI 0.01-0.03, p < 0.01 in RCC), fibrinogen (ß = 0.006, 95% CI 0.0009-0.01, p = 0.02 in LCC and ß = 0.005, 95% CI 0.001-0.01, p = 0.01), HDL cholesterol (ß = 0.13, 95% CI 0.04-0.21, p < 0.01 in RCC only), and CRP (ß = -0.01, 95% CI -0.02-0.001, p = 0.03 in RCC only). Subjects at risk showed a higher [18F] NaF uptake compared to healthy controls (one-way ANOVA; p = 0.02 in LCC and p = 0.04 in RCC), and uptake increased with estimated cardiovascular risk (one-way ANOVA, p < 0.01 in LCC only). These findings underscore the potential of [18F] NaF PET/CT as a sensitive tool for the early detection of atherosclerotic plaque, assessment of cardiovascular risk, and monitoring of disease progression. Further research is needed to validate the technique's predictive value and its potential impact on clinical outcomes.

Stroke and molecular imaging: a focus on FDG-PET.

Stroke is the leading cause of disability worldwide, the second most common cause of dementia and the third leading cause of death. Though the etiology of stroke has been explored extensively, there remains open questions in the scientific and clinical study of stroke. Traditional imaging techniques, such as magnetic resonance imaging and computed tomography, have been applied extensively and remain mainstays in clinical practice. Nevertheless, positron emission tomography has proven to be a powerful molecular imaging tool in exploring the scientific aspects of neurological disease, and stroke remains an area of great interest. This review article examines the role of positron emission tomography in the study of stroke including its contributions to elaborating related pathophysiology and delving into possible clinical applications.

Aging and Cerebral Glucose Metabolism: 18F-FDG-PET/CT Reveals Distinct Global and Regional Metabolic Changes in Healthy Patients.

Alterations in cerebral glucose metabolism can be indicative of both normal and pathological aging processes. In this retrospective study, we evaluated global and regional neurological glucose metabolism in 73 healthy individuals (mean age: 35.8 ± 13.1 years; 82.5% female) using 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). This population exhibited a low prevalence of comorbidities associated with cerebrovascular risk factors. We utilized 18F-FDG-PET/CT imaging and quantitative regional analysis to assess cerebral glucose metabolism. A statistically significant negative correlation was found between age and the global standardized uptake value mean (SUVmean) of FDG uptake (p = 0.000795), indicating a decrease in whole-brain glucose metabolism with aging. Furthermore, region-specific analysis identified significant correlations in four cerebral regions, with positive correlations in the basis pontis, cerebellar hemisphere, and cerebellum and a negative correlation in the lateral orbital gyrus. These results were further confirmed via linear regression analysis. Our findings reveal a nuanced understanding of how aging affects glucose metabolism in the brain, providing insight into normal neurology. The study underscores the utility of 18F-FDG-PET/CT as a sensitive tool in monitoring these metabolic changes, highlighting its potential for the early detection of neurological diseases and disorders related to aging.

Advancements in dendritic cell vaccination: enhancing efficacy and optimizing combinatorial strategies for the treatment of glioblastoma.

Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of DCV, assesses previous clinical trials, and discusses future strategies for the integration of DCV into glioblastoma treatment protocols. To conclude, the review discusses challenges associated with the use of DCVs and highlights the potential of integrating DCV with standard therapies.

The Enterprise stent still useful after all these years.

BACKGROUND: The Enterprise stent (Codman Neuro, Massachusetts, USA) received Food and Drug Administration (FDA) approval in 2007 for stent-assisted coiling (SAC). Since its introduction, newer stents and devices for aneurysm treatment have been developed resulting in a shift in the utilization of this stent from SAC to other off-label indications. OBJECTIVE: To describe our experience with the Enterprise stent being used for SAC and other off-label indications. METHODS: This is a multi-center retrospective review of the use of the Enterprise stent between 2018 and 2023. All patients in which the Enterprise stent was successfully deployed were included in the study. RESULTS: Our study cohort comprised of 194 patients, mostly females (n = 112, 57.7%), with a mean age of 63.2 years ± 14.3. The Enterprise stent was used for SAC in only 24 (12.4%) patients and was used for rescue stenting in stroke in 101 patients (52.1%), treatment of intracranial stenosis in 53 patients (27.3%), treatment of in-stent stenosis in 1 patient (0.5%), and for treatment of dissections in 15 patients (7.7%). From 2018 to 2023, the use of Enterprise stents for SAC significantly decreased (p < 0.0001) while the use of Enterprise stents for non-SAC purposes was insignificantly variable (p = 0.05). CONCLUSION: Our study shows that the Enterprise stent remains a reliable tool in neuroendovascular procedures, even if its original intended use has been supplanted by other devices.

Alterations in cerebral glucose metabolism as measured by 18F-fluorodeoxyglucose-PET in patients with persistent postconcussion syndrome.

BACKGROUND: Many patients who have traumatic brain injury experience a wide range of psychiatric and neurological symptoms (including impairment in functional status, cognition, and mood), and if persistent are referred to as persistent postconcussion syndrome (PCS). To our knowledge, this is the first study to broadly evaluate metabolic dysregulation in a heterogenous patient population meeting the criteria for PCS. METHODS: A total of 64 PCS patients and 37 healthy controls underwent 18F-fluorodeoxyglucose-PET (18F-FDG-PET) scanning, and 70 brain structures (including left and right structures where appropriate) were analyzed in each subject. RESULTS: Compared to the brains of healthy controls, those of PCS patients demonstrated 15 hypermetabolic and 23 hypometabolic regions. Metabolic changes in the brains of PCS patients were subsequently correlated with various indices of symptom severity, mood, and physical/cognitive function. Among PCS patients, increased metabolism in the right cingulate gyrus correlated with the severity of postconcussion symptoms. Conversely, increased metabolism in the left temporal lobe was associated with both improved mood and measures of adaptability/rehabilitation. Furthermore, increased metabolism in the bilateral orbitofrontal regions correlated with improved working memory. CONCLUSIONS: Overall, these findings suggest a complex pattern of cerebral metabolism in PCS patients, with a mixture of hypometabolic and hypermetabolic regions that correlate with various symptoms, highlighting both potential pathological and compensatory mechanisms in PCS. The findings also suggest that FDG PET is useful for providing neurophysiological information in the evaluation of patients with PCS and may help guide future targeted therapies.