C.S. Mott Children's Hospital is a pediatric acute care hospital located in Ann Arbor, Michigan. The hospital has 244 pediatric beds and is affiliated with the University of Michigan Medical School. The hospital provides comprehensive pediatric specialties and subspecialties to infants, children, teens, and young adults 0-21 throughout Michigan and the surrounding states. The hospital sometimes also treats older adults that require pediatric care. C.S. Mott Children's Hospital also features a Level 1 Pediatric Trauma Center, 1 of 3 in the state. Attached to the children's hospital is the Von Voigtlander Women's Hospital that provides maternal and gynecological care for women. The hospital moved to a newly constructed building in 2011. Although commonly understood to be a physical health complex, C.S. Mott Children's Hospital also includes a youth and adolescent psychiatric ward separate from the rest of the children's hospital. The C. S. Mott Children's and Von Voigtlander Women's Hospital employs about 4,000 people and is gradually hiring 500 more now that the hospital expansion is complete.
There are few prospective studies of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) for pediatric lupus nephritis (pLN) and none evaluating rituximab (RTX). The Prospective Pediatric Lupus Nephritis Registry (ProPeL-R) enrolled patients < 21 years within 4 weeks of an initial kidney biopsy diagnostic of pLN. Demographic, clinical, and laboratory data were collected prospectively at enrollment, 3 months, 6 months, and then every 6 months thereafter for up to 5 years of follow-up. For this study, we compared patients receiving initial therapy with corticosteroids (CS) and either MMF (n = 33) vs. CYC (n = 18), and those treated with CS, either MMF or CYC, with RTX (n = 20) vs. without RTX (n = 51). Histology consisted of 18
PURPOSE:This study addresses critical gaps in automated lymphoma segmentation from PET/CT imaging, often overlooked in prior work. While deep learning has been applied to this task, few studies evaluate generalizability on external or out-of-distribution data. Similarly, intra- and inter-observer variability analyses remain rare, limiting understanding of task difficulty. Moreover, most methods emphasize global segmentation metrics, neglecting lesion-level characteristics that are crucial for clinical decision-making. METHODS:We propose a clinically-relevant evaluation framework to assess four commonly used deep segmentation networks (ResUNet, SegResNet, DynUNet, SwinUNETR) on 611 PET/CT cases from multi-institutional datasets spanning varied lymphoma subtypes and lesion characteristics. In addition to the Dice similarity coefficient (DSC), we compute prediction errors on clinical lesion measures and analyze DSC performance as a function of these measures. Additionally, we use traditional lesion-specific detection criteria (1 and 2), providing insights into network's performance in identifying and localizing lesions respectively, and propose an additional Criterion 3 for segmenting lesions based on metabolic characteristics. Finally, we contextualize network performance by comparing it to expert human observers through intra- and inter-observer variability analyses. RESULTS:Networks perform best on large, metabolically active lesions. Their error patterns closely resemble those of expert annotators, while small and faint lesions remain challenging for both networks and physicians. CONCLUSION:Our clinically-relevant benchmarking framework enables more consistent and meaningful evaluation of lymphoma segmentation models, supporting robust decision-making in patient care. The approach is extensible to other architectures and disease types. Code is available at: https://github.com/microsoft/lymphoma-segmentation-dnn.
OBJECTIVES:Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in diet, and it is a precursor to inflammatory lipid mediators called oxylipins. The role of LA and its oxylipins in pediatric sepsis and organ injury is uncertain. Recently, pediatric sepsis phenotypes were described, with phenotype D characterized by the highest proportion of acute kidney injury (AKI), multiple organ failure, and risk of death. We aimed to test the hypothesis LA may play a role in sepsis-associated organ dysfunction. We therefore investigated whether increasing plasma LA and LA-derived lipoxygenase oxylipins are associated with sepsis phenotype D and with AKI in a cohort of critically ill children with sepsis. DESIGN:We studied a subset of 108 patients from the Phenotyping Sepsis-Induced Multiple Organ Failure Study (PHENOMS) cohort by means of untargeted metabolomics of heparinized plasma samples. Primary outcome was phenotype group. Key secondary outcomes included AKI (defined as both creatinine > 1 mg/dL and oliguria < 0.5 mL/kg/hr), other organ dysfunctions, and hospital mortality. Patients were followed up until discharge or 28 days. SETTING:ICU. PATIENTS:One hundred eight patients with sepsis. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Higher LA levels were associated with sepsis phenotype D as compared with phenotypes A-C (odds ratio [OR], 1.67; 95% CI, 1.05-2.65; p = 0.03). LA-derived oxylipins 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid (9-HODE/13-HODE) were also associated with sepsis phenotype D (jointly reported in one variable; OR, 1.26; 95% CI, 1.01-1.57; p = 0.04). Higher LA showed a trend and 9-HODE/13-HODE was associated with AKI (OR, 1.52; 95% CI, 0.97-2.38; p = 0.07 and OR, 1.27; 95% CI, 1.03-1.56; p = 0.02, respectively). Neither LA nor oxylipins were associated with hospital mortality. CONCLUSIONS:LA levels and LA-derived lipoxygenase oxylipins are associated with pediatric sepsis phenotype D and AKI. These results support future mechanistic studies to investigate lipid metabolism in the pathophysiology of sepsis.
Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to impact overall survival (OS). The influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium (PIDTC) from 1990-2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced intensity regimens were associated with lower T cell and myeloid donor chimerism, particularly when non-busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hotspot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS following HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This study was registered at www.clinicaltrials.gov as #NCT02064933.
OBJECTIVE:To assess associations between the presence of genetic diagnoses and survival and morbidity of patients with symptomatic tetralogy of Fallot (sTOF) requiring neonatal intervention. STUDY DESIGN:We performed an analysis of a multicenter, retrospective study of sTOF patients from 2005 to 2017 from the Congenital Cardiac Research Collaborative. The primary outcome was transplant-free survival, evaluated by Cox proportional hazards regression modeling, adjusted for center, repair strategy, anatomical diagnosis, prematurity, and invasive ventilation before intervention. Genetic diagnoses were retrospectively collected from hospital records. RESULTS:The study group included 572 neonates with sTOF, of whom 151 (26.4%) had an identifiable genetic diagnosis, including 22q11 deletion (n = 63, 41.7%), trisomy 21 (n = 28, 18.5%), and other genetic diagnoses (n = 60, 39.7%). At a median follow-up of 4.12 (1.53, 7.47) years, there was no significantly increased hazard ratio of death in patients with a genetic diagnosis (adjusted hazard ratio 1.71 [95% CI 0.96-3.07], P = .07). However, patients with a genetic diagnosis had longer median intensive care unit and total hospital stays ([13 vs 9 days, P < .001] and [32.5 vs 24 days, P < .001], respectively) and were more likely to be discharged with feeding tubes (OR 2.1 [95% CI 1.31-3.37], P = .002). CONCLUSIONS:Neonates with sTOF with a genetic diagnosis had no significant survival difference to those without but did have a higher risk for other hospital morbidities, including longer admissions and the need for feeding tubes. Genetic testing in this population can inform clinicians and families regarding these important considerations within this congenital heart disease population.
