Pediatric Evans Syndrome Diagnostic Evaluation Patterns: Survey Results From the Pediatric ITP Consortium of North America

ABSTRACT Background Evans syndrome (ES) is a rare immune‐mediated disorder involving two or more cytopenias, including immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and/or immune neutropenia. ES may occur secondary to another condition or be idiopathic. While consensus recommendations exist for adults, there is no standardized diagnostic approach for pediatric Evans syndrome (pES). This study aimed to describe typical diagnostic evaluations conducted by clinicians caring for pES patients. Methods A cross‐sectional survey of the Pediatric ITP Consortium of North America (ICON) assessed typical diagnostic workup for pES, the influence of clinical features on testing, evaluation for underlying disorders, including immune defects and autoimmune disease, subspecialty involvement, and genetic testing practices. Results Sixty percent (28/47) of respondents reported performing the same evaluation for all pES patients. There was no consensus on specific diagnostic tests. Providers consistently evaluated for autoimmune conditions, but varied in testing for inborn errors of immunity (IEI). Rheumatology and immunology were most often consulted. Most respondents (85%, n = 40) obtained genetic testing through commercial laboratories, frequently encountering insurance‐related barriers. Conclusions Even among experts, diagnostic approaches to pES vary widely. Standardized frameworks are needed to guide comprehensive evaluation for this complex disorder.

Glycosylated LGALS3BP is highly secreted by bladder cancer cells and represents a novel urinary disease biomarker

Bladder cancer incidence has recently risen, making it the ninth most diagnosed cancer, highlighting an urgent need for novel and effective diagnostic and therapeutic strategies to improve patient outcomes. Here, we report on a secreted glycoprotein, Galectin‐3‐binding protein (LGALS3BP), as a potential biomarker and therapeutic target for bladder cancer. We found a significantly elevated LGALS3BP expression in bladder cancer tissues, correlating with disease progression. Moreover, urinary and serum levels of LGALS3BP were significantly higher in patients compared to healthy individuals, with a strong correlation observed between elevated urinary protein levels and tumor grade. Of note, LGALS3BP produced by tumor cells treated with a mannosidase I inhibitor, Kifunensine, exhibited increased reactivity to a therapeutic antibody (denoted as “1959”), suggesting that glycosylation of LGALS3BP may influence antibody recognition and protein function. Furthermore, administration of 1959‐sss/DM4 antibody–drug conjugate in two xenograft mouse models of human bladder cancer resulted in complete inhibition of tumor growth. In summary, findings presented here highlight LGALS3BP as a promising candidate for further investigation into its potential as a urinary biomarker and a therapeutic target for bladder cancer.

Interleukin‐6 as a Key Biomarker in Facioscapulohumeral Dystrophy: Evidence From Longitudinal Analyses

ABSTRACT Objective Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is a progressive neuromuscular disorder with no approved treatments. Identifying reliable biomarkers is critical to monitor disease severity, activity, and progression. Interleukin‐6 (IL‐6) has been proposed as a candidate biomarker, but longitudinal validation is limited. Methods We analyzed pooled data from two prospective longitudinal cohorts: CTRN‐FSHD France (NCT04038138) and Cytokine FSHD (NCT04694456), each comprising 30 genetically confirmed ambulant FSHD1 patients. Serum IL‐6 levels and clinical assessments were collected at baseline (M0), 12 months (M12), and 18 months (M18); whole‐body muscle MRI (T1‐weighted and STIR sequences) was obtained at M0 and M12. Associations between IL‐6 levels and clinical severity scores, functional measures, and MRI‐derived muscle composition were evaluated. Results Serum IL‐6 levels correlated significantly with clinical severity metrics, including Clinical Severity Score, 6‐Minute Walk Test, Manual Muscle Testing, and Motor Function Measure Domain 1 at all time points. Higher IL‐6 levels were associated with increased muscle fat infiltration and free water content compatible with muscle edema on MRI. Longitudinal analyses showed that increases in IL‐6 over 12 months were significantly correlated with changes in T1 (fat infiltration) and STIR (muscle edema) composite scores, reflecting structural and inflammatory disease progression. Interpretation These findings validate IL‐6 as a biomarker of FSHD1 severity and underscore its potential as an activity and progression biomarker. The correlation between IL‐6, clinical scores, and MRI‐based muscle composition changes highlights its potential utility for monitoring disease evolution and evaluating therapeutic responses in FSHD1 patients.

Comparison of the Performance of Fluorescent, Phosphorescent, and TADF Luminophores for Explosives Sensing

ABSTRACT This study investigates how the emission mechanism (fluorescence, phosphorescence, or thermally activated delayed fluorescence, TADF) of a luminescence‐quenching chemical sensor influences the sensitivity of explosives detection. Steady‐state and time‐resolved photoluminescence measurements were used to evaluate the quenching kinetics of representative emitters in the presence of 2,4‐dinitrotoluene ( DNT ), a model nitroaromatic explosive. Linear Stern‐Volmer behavior was observed for the fluorescent and phosphorescent emitters, whereas the TADF compound exhibited a pronounced downward deviation in steady‐state measurements, arising from the simultaneous but distinct quenching of singlet and triplet exciton populations. To describe this behavior, we derived a modified Stern–Volmer formalism comprising separate relationships for the prompt and delayed fluorescence. The quenching dynamics of the TADF system were found to be strongly dependent on the intrinsic parametersϕ I S C 0 ϕ R I S C 0 phi}}_{{{ISC 0{{\phi}}_{{{RISC 0$ , k Stot and k Ttot , with the singlet and triplet populations being quenched with different efficiencies. These insights highlight the potential of TADF luminophores to act as sensitive photoinduced electron transfer‐based explosives sensors.

A Robotic Urinary Bladder Enabling Volume Monitoring and Assisted Micturition

The urinary bladder is considered a highly complex organ, capable not only of storing urine but also of sensing intra‐vesical volume and dynamically expanding and contracting. Consequently, fully replicating its functions following radical cystectomy remains a significant technological challenge. Hereinafter, an implantable robotic bladder is presented that can change shape and expand its internal volume up to 400 mL, based on the amount of urine collected from kidneys, and monitor the volume in real‐time. It can apply on‐demand mechanical compression to assist urination, by means of an origami‐designed enclosure, coupled to miniaturized mechatronic components. In vitro characterization in a human phantom is demonstrated, and volume monitoring is validated following a realistic filling routine. The tests demonstrate successful expansions for collecting urine, with an average volume reconstruction error of 8.4 ± 6.1 mL, and then 99% of the volume is voided in less than 2 min. The work paves the way for developing active robotic solutions and reproducing bladder functions in patients with cancer and organ removal or impairment.

Trends in GVHD Epidemiology, Prophylaxis and Management: The Gruppo Italiano per il Trapianto di Midollo Osseo, Cellule Staminali Emopoietiche e Terapia Cellulare ( GITMO ) GVHD24 Study

Compared to historical reports, both aGVHD and cGVHD appeared to have decreased in the recent transplant era, possibly due to the extension of T‐cell depletion, the availability of effective second‐line approaches in SR/D GVHD and improved anti‐infectious prophylaxis and treatments.

Impact of CSF3R Mutations on Leukemic Transformation in Severe Congenital Neutropenia: A Retrospective Analysis From the Italian Neutropenia Registry

Effect of Using the Food Quotient as a Proxy of the Respiratory Quotient in the Calculation of Energy Expenditure by the Doubly Labeled Water Method in Older Adults

ABSTRACT Background and Aims Accurate measurement of total energy expenditure (TEE) is critical for maintaining energy balance and body weight. This study aimed to analyze differences in TEE assessed by the doubly labeled water method (DLW‐TEE), using food quotient (FQ) derived from self‐reported 24‐h dietary recalls, respiratory quotient measured by indirect calorimetry (RQ‐IC), and usual respiratory quotient of 0.85 (RQ‐0.85) based on Western‐type diet intakes. Methods Secondary analysis from a cross‐sectional study conducted in a sample of 41 independent (21 women) older people (≥ 60 years). FQ was obtained from three self‐reported 24‐h dietary recalls, RQ‐IC was measured after an overnight fast under resting conditions. Repeated measures analysis of variance was used to compare differences in DLW‐TEE calculated with FQ, RQ‐IC, and RQ‐0.85. Results DLW‐TEE was significantly different between the three approaches ( p  = 0.025). The RQ approaches on DLW‐TEE did not differ significantly between sexes ( p  = 0.325). The overall mean DLW‐TEE RQ‐0.85 was 2253 (SD = 529, 95% CI: 2086, 2420) kcal/day, DLW‐TEE RQ‐IC was 2251 (SD = 541, 95% CI 2090, 2431) kcal/day, and DLW‐TEE FQ was 2208 (SD = 534, 95% CI 2039, 2376). DLW‐TEE calculated with FQ significantly reduced TEE compared to the mean DLW‐TEE with RQ‐0.85 values (ΔTEE −45 kcal/day, p  < 0.001). Conclusion Self‐reported dietary intake data may provide a more context‐specific estimate of the FQ than relying solely on RQ from indirect calorimetry or the fixed RQ of 0.85 in DLW‐based TEE calculations. Although the resulting differences in TEE are modest, they can lead to overestimation of energy requirements over time.

Congenital Alopecia, Hypoplastic Kidneys, Growth Restriction, Growth Hormone Resistance, and Liver Fibrosis: Confirmation of a New Syndrome Caused by Biallelic Variants in ZPR1

ABSTRACT We report two female siblings, a 13‐month‐old and a newborn, with multiple anomalies including hypoplastic kidneys, severe growth restriction, facial dysmorphism, and alopecia, both found to be homozygous for the c.587 T>C variant in ZPR1 . Their clinical features are strikingly similar to those previously reported in a patient who was homozygous for the same variant. Our report confirms that homozygosity for c.587 T>C in ZPR1 underlies a novel genetic syndrome with autosomal recessive inheritance and that c.587 T>C is a founder variant for ZPR1 disorder in the Middle Rio Grande Valley. We expand our understanding of the phenotype by describing abnormal glucose homeostasis, growth hormone resistance, and progressive liver disease with decompensated portal hypertension and esophageal varices despite the absence of cirrhosis.

Program of the Forty‐Sixth Meeting of The American Society of Primatologists