Citations

Abstract Background Identification of the microorganisms causing infection in children with central nervous system infection is important. Conventional cerebrospinal fluid (CSF) tests may provide limited pathogen detection. CSF metagenomic next-generation sequencing (mNGS) may provide broader pathogen detection in a single assay. Methods Results of CSF mNGS testing performed at Mayo Clinic on patients and nonpatients between January 2024 and June 2025 were retrospectively analyzed. The subcohort of children treated at Mayo Clinic was analyzed to assess test performance as compared with conventional CSF diagnostics and potential clinical impact. Results In total 134 patients (138 CSF mNGS tests) from 22 US states and 2 international sites were included. Overall positivity was 16% with viruses representing most (59%) detections. In the Mayo Clinic subcohort (n = 15), test positivity was 27%: organisms included single detections of Streptococcus mitis group and HIV type 1, as well as 2 detections of Epstein-Barr virus, all confirmed by conventional tests. Positive results were associated with CSF pleocytosis (P = .026). Higher yield was observed in participants whose care was overseen by pediatric infectious diseases (PID) specialists (P = .026) and when a specimen hold strategy was applied (P = .033). Most results (87%) did not alter antimicrobial therapy, with 2 negative results contributing to antimicrobial de-escalation. Conclusions CSF mNGS demonstrated higher diagnostic yield in patients whose specimens showed CSF pleocytosis and in those who had PID consultation. Diagnostic stewardship strategies were applied, including specimen hold approaches and PID consultation.

Abstract Background Nearly 40,000 people in the U.S. experience recurrent pericarditis with up to 90% of cases having no identifiable cause, often making the journey to diagnosis arduous. Understanding the challenges that patients and health care professionals (HCP) face will help address gaps and barriers in patient diagnosis and care. In addition, the lack of U.S. based guidelines for recurrent pericarditis clinical care, coupled with the time lapse from the last published European guideline, has created an opportunity to discover workflow solutions for U.S. based healthcare professionals. Purpose The American Heart Association’s (AHA) Addressing Recurrent Pericarditis Initiative is a three-year effort utilizing a quality improvement approach to address gaps/barriers in patient care, educate HCPs, and develop patient education resources to improve diagnosis, treatment, and quality of life. To accomplish this, the lived experiences and challenges patients face on their journey to diagnosis was integrated into the qualitative research process. Methods To assess quality improvement opportunities, the AHA engaged HCPs with recurrent pericarditis experience from 15 diverse health systems to participate in a learning collaborative strategy for quality improvement and implementation to share successful strategies, provide input on professional education topics, and participate in process mapping. Data collection strategies include 1:1 consultations, quarterly learning collaborative calls, surveys and questionnaire completion. To assess patient education needs, the AHA Market Research Team held 1-hour video interviews with ten diverse patients. Results AHA-led HCP interviews produced process maps of clinical workflows and identified opportunities for standardization to improve clinical workflow and patient outcomes (Figure 1). From these data collection methods, preliminary results include care coordination across clinical settings, exploring treatment options, standardization of follow-up cadence, and provider awareness of misdiagnoses/underdiagnosis rates. The patient interviews revealed that there is a lack of symptom recognition, persistent rate of misdiagnosis, delay in accurate diagnosis and treatment, and discrepancies in diagnosis and treatment for various demographics including female and younger adult patients (Figure 2). Conclusion(s) In Year 2 of this three-year initiative, we will continue to refine identified areas of opportunities to improve patient outcomes by creating and disseminating educational materials and launch awareness campaigns, while also producing a national education series for HCPs that provide guidance for system-level quality improvement to emphasize consistency in care and reductions in health inequities. Key findings from this study highlight the care coordination involved in the treatment of patients with recurrent pericarditis and the need to provide multidiscipline educational approaches to achieve this goal.Figure. 1 Summary of care pathway Figure. 2 Summary of patient interviews

Ruxolitinib (RUX) cream 1.5%, a selective Janus kinase (JAK) 1 and 2 inhibitor initially developed for myelofibrosis, has emerged as a novel therapeutic agent in dermatology. It is the first topical JAK inhibitor approved by the Food and Drug Administration for atopic dermatitis (AD) and non-segmental vitiligo. This article reviews the pharmacological profile, mechanism of action, and clinical efficacy of topical RUX in immune-mediated skin conditions. RUX inhibits cytokine-induced JAK-signal transducer and activator of transcription signaling, reducing inflammation and pruritus with minimal systemic absorption and a favorable safety profile. In phase III TRuE-AD1/AD2 trials, RUX demonstrated significant improvements in the investigator’s global assessment, eczema area and severity index scores, and pruritus in patients with mild-to-moderate AD. Similarly, in the TRuE-V1/V2 studies for vitiligo, RUX achieved superior rates of facial vitiligo area scoring index (F-VASI75) and other repigmentation measures compared to vehicle, with sustained benefits at week 52. Common adverse effects included application site reactions such as burning, acne, and pruritus. Beyond its approved indications, emerging evidence supports off-label use in conditions such as lichen planus, alopecia areata, and cutaneous lupus, among others. While preliminary data suggest a positive impact on the skin microbiome, further studies are warranted. RUX cream represents a promising advancement in targeted dermatological therapy, offering localized efficacy with minimal systemic risk.

Post-COVID syndrome comprises persistent neuropsychiatric manifestations for more than 12 weeks after recovery from acute SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. Ferroptosis, an iron-dependent form of cell death with three hallmarks, iron dysregulation, antioxidant failure, and lipid peroxidation, seems to be involved in COVID-19/post-COVID-19 pathophysiology. Here, we administered the SARS-CoV-2 spike protein S1 subunit intranasally to K18-hACE2 transgenic mice and quantified ferroptotic marker protein expression in four brain regions (hippocampus, prefrontal cortex, cerebellum, and olfactory bulb) at 2, 6, and 12 weeks post-administration, alongside ultrastructural assessment by transmission electron microscopy (TEM) that was limited to the hippocampus and prefrontal cortex. Two-way ANOVA revealed region- and time-dependent modulation of iron-handling, antioxidant, and lipid peroxidation markers. In the hippocampus, FPN1 was significantly increased at 2 weeks, while TFR1 showed a time-dependent pattern without significant week-specific differences. In the prefrontal cortex, DMT1 significantly increased at 2 weeks, and GPx4 showed an overall treatment effect with a trend of increase at 6 weeks. The cerebellum exhibited early increases in FPN1 and GPx4 and a delayed increase in MDA-conjugated proteins. In the olfactory bulb, FPN1 increased at 12 weeks, with GPx4 showing an overall treatment effect and an early trend of decrease. TEM identified ferroptosis-consistent features in the hippocampus and prefrontal cortex at all time points. These findings suggest that spike protein exposure may be associated with time-dependent and brain-region-specific alterations of ferroptosis-related markers. These preliminary findings are based on a limited sample size, which needs further research to elucidate the clinical implication and to study the mechanism in more depth as well as future validation with pharmacological inhibitors.

Background Mepolizumab blocks IL-5, targeting eosinophilic type-2 inflammation. Due to existing phenotype driven patient selection, evidence of its effectiveness in primary diffuse CRS and CRS without nasal polyps (CRSsNP) and in real-world populations is limited. Our objective was to evaluate the real-world effectiveness of mepolizumab in patients with primary diffuse CRS, regardless of nasal polyp status, and to assess outcomes across CRS phenotypes and prior surgical history. Methods Adults with primary diffuse CRS treated with mepolizumab for ≥6 months were identified. Pre- and post-therapy outcomes included serum eosinophil counts, Lund-Mackay CT scores, Lund-Kennedy endoscopic scores, and SNOT-22 symptom scores. Subgroup analyses were performed by CRS phenotype (CRSwNP vs . CRSsNP) and prior endoscopic sinus surgery (ESS). Biologic switching and discontinuation were recorded. Results Among 277 patients (mean age 60.8 ± 14.7 years; 54.9% female), 93.5% had type-2 comorbidities, 29.6% had CRSsNP, and 27.8% were ESS-naïve. The median duration of mepolizumab therapy was 31 months. Mepolizumab therapy significantly reduced serum eosinophils (median 0.57 to 0.07 ×10 9 /L, p<0.001) and Lund-Mackay scores (median 14 to 10, p<0.001), which was consistent across all subgroups. Improvements in SNOT-22 and endoscopic scores were modest and not consistently significant. CRSwNP patients were more likely to undergo ESS during therapy, but time to first post-therapy ESS was longer than in CRSsNP. There were no differences in likelihood of undergoing ESS during therapy, time to subsequent ESS, or oral corticosteroid use between prior ESS and ESS-naïve patients. Biologic switching occurred in 24.9%, and discontinuation in 16.6%, primarily due to disease recalcitrance. Conclusion Mepolizumab effectively reduced systemic eosinophilia and radiographic disease burden in primary diffuse CRS, independent of phenotype or prior ESS. Symptom improvement was variable, highlighting the heterogeneity of clinical response. These findings support an endotype-driven approach to biologic therapy and suggest that IL-5 blockade may benefit selected CRSsNP patients.

Pediatric heart failure is a heterogeneous, high-risk clinical syndrome that differs fundamentally from adult heart failure in its etiologies, pathophysiology, and therapeutic responses. Although its absolute prevalence is lower, children experience disproportionate morbidity and mortality, with up to 40% of patients with symptomatic cardiomyopathy progressing to death or transplantation within 2 years of diagnosis. Congenital heart disease, cardiomyopathies, and genetic or metabolic disorders dominate the etiologic spectrum, while developmental differences in myocardial signaling, neurohormonal activation, and ventricular remodeling limit direct extrapolation of adult guideline-directed medical therapy. Evidence supporting pharmacologic treatment remains limited, and most therapies are symptom-modifying rather than outcome-modifying, particularly in single-ventricle physiology. Advances in mechanical circulatory support and heart transplantation have substantially improved survival, yet pose unique anatomic, physiological, and ethical challenges in children. This review synthesizes contemporary evidence across medical, device-based, and transplant therapies, highlights lesion- and age-specific considerations, and identifies critical research gaps needed to advance outcomes in pediatric heart failure.

Background: Plasma cell dyscrasia (PCD) is a rare but important cause of end stage kidney disease (ESKD). Kidney transplant is the treatment of choice in patients with ESKD. However, the complexity of PCD care and risk of disease recurrence poses challenges to kidney transplant candidacy and outcomes. We examined the current clinical practice patterns of clinicians who care for patients with PCD and identified barriers to kidney transplantation for patients with PCD. Methods: A web-based survey was developed and distributed from January to July 2024 to kidney transplant clinicians (American Society of Transplant (AST) members), hematologists (PCD experts), and onco-nephrologists. Results: Seventy clinicians (50 transplant nephrologists, 18 hematologists, and two surgeons) from 42 transplant centers in the US participated in the survey. Clinical practice patterns pre and post kidney transplant for patients with PCD are highly variable among institutions, and only 36% reported having a protocol for pre- and post-transplant management for patients with PCD. Particularly, the requirement for pre-transplant hematologic remission criteria, induction and maintenance immunosuppression regimens and protocols for prophylaxis and screening for opportunistic infection are areas of future study. Clinicians listed lack of data and practice guidance as well as communication challenges among multiple specialties especially hematology and kidney transplant clinicians as notable barriers. Conclusions: Our study identified the highly variable current practice patterns when evaluating and managing patients with PCD for kidney transplant. Our findings emphasize the need for collecting and sharing clinical data to support standardized practices and serve as a basis for the upcoming multi-societal management recommendation for kidney transplant for patients with PCD.

Abstract Background: Exercise capacity (VO 2peak ) predicts mortality in adult patients with CHD. There is a lack of paediatric exercise capacity data based on specific CHD lesions, limiting the ability to contextualise interpretation based on expected performance during testing. The primary aim of this study was to establish VO 2peak percentiles for paediatric patients with repaired CHD undergoing treadmill-based cardiopulmonary exercise testing (CPET). Methods: Retrospective analysis of CPET data from 2004 to 2022. CPETs were analysed for patients with CHD aged 6–18 years. Patients with repaired CHD were categorised based on their most haemodynamically significant CHD lesion. Percentiles and age-based trends were plotted for each group. Results: A total of 887 patients were included. CHD patients were divided into ten diagnostic subgroups. The mean percent expected VO 2peak for each of the subgroups were as follows: Atrial and ventricular septal defect (94.5 ± 25.1%), pulmonary valve repair (88.1 ± 18.4%), aortic valve repair (92.7 ± 16.4%), tricuspid and mitral valve repair (81.3 ± 20.4%), coarctation of the aorta (93.6 ± 18.8%), transposition of the great arteries (90.5 ± 19.4%), double outlet right ventricle and truncus arteriosus (80.5 ± 16.2%), tetralogy of Fallot (85.6 ± 20.9%), left ventricle dominant Fontan (74.7 ± 18.3%), and right ventricle dominant Fontan (75.7 ± 16.7%). Conclusion: There is a varying degree of reduced exercise capacity in paediatric patients with repaired CHD. Univentricular hearts and tricuspid and mitral valve repair have the lowest VO 2peak . These CHD-specific percentiles may help providers risk-stratify and counsel patients with CHD.

Alcohol use disorder (AUD) is a significant public health challenge, affecting multiple organs and organ systems, and fetal health. Additionally, AUD also significantly contributes to self-harm and road accidents. Beyond its health effects, AUD creates economic and political challenges, including escalating treatment costs and the complex alcohol regulation policies. Despite global impact, AUD remains under-addressed in countries like India due to cultural norms and limited resources. Early recognition of AUD is vital for better outcomes, relying on thorough clinical evaluation and patient history. However, denial, inebriation, or lack of awareness often delays diagnosis. Imaging techniques like ultrasound, CT, and MRI effectively depict AUD-related organ damage and aid in detecting chronic alcohol use. Radiologists play a crucial role in identifying these manifestations, contributing to its early detection and treatment. This review article highlights the imaging of alcohol use related disorders and diseases affecting different organs and organ systems at various stages. The review is presented in two parts: the first focuses on alcohol burden, alcohol metabolism and toxicity, and imaging findings of AUD-related abdominal diseases and disorders.