Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients

No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients

Background: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. Patients and methods: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. Results: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). Conclusions: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocol

Conspicuity and muscle-invasiveness assessment for bladder cancer using VI-RADS: a multi-reader, contrast-free MRI study to determine optimal b-values for diffusion-weighted imaging

To (1) compare bladder cancer (BC) muscle invasiveness among three b-values using a contrast-free approach based on Vesical Imaging-Reporting and Data System (VI-RADS), to (2) determine if muscle-invasiveness assessment is affected by the reader experience, and to (3) compare BC conspicuity among three b-values, qualitatively and quantitatively

Follow-up of multi-messenger alerts with the KM3NeT ARCA and ORCA detectors

The strength of multi-messenger astronomy comes from its capability to increase the significance of a detection through the combined observation of events coincident in space and time. This is particularly valuable for transient events, since the use of a narrow time window can allow a reduction of background of the search. In KM3NeT, we are actively monitoring and analysing a variety of external triggers in real-time, including alerts like IceCube neutrinos, HAWC gamma-ray transients, LIGO-Virgo- KAGRA gravitational waves, SNEWS neutrino alerts, and others. In this contribution, we present the follow-up of various external alerts using the comple- mentary capabilities of the two KM3NeT detectors, ORCA (covering the few GeV to few TeV energy range) and ARCA (ranging from sub-TeV energies up to tens of PeV). Both detectors were collecting high-quality data with partial configurations during the period of the studied alerts, which goes from December 2021 until June 2023

Optimization of window settings for coronary arteries assessment using spectral CT-derived virtual monoenergetic imaging

Purpose: To determine the optimal window setting for virtual monoenergetic images (VMI) reconstructed from dual-layer spectral coronary computed tomography angiography (DE-CCTA) datasets. Material and methods: 50 patients (30 males; mean age 61.1 ± 12.4 years who underwent DE-CCTA from May 2021 to June 2022 for suspected coronary artery disease, were retrospectively included. Image quality assessment was performed on conventional images and VMI reconstructions at 70 and 40 keV. Objective image quality was assessed using contrast-to-noise ratio (CNR). Two independent observers manually identified the best window settings (B-W/L) for VMI 70 and VMI 40 visualization. B-W/L were then normalized with aortic attenuation using linear regression analysis to obtain the optimized W/L (O-W/L) settings. Additionally, subjective image quality was evaluated using a 5-point Likert scale, and vessel diameters were measured to examine any potential impact of different W/L settings. Results: VMI 40 demonstrated higher CNR values compared to conventional and VMI 70. B-W/L settings identified were 1180/280 HU for VMI 70 and 3290/900 HU for VMI 40. Subsequent linear regression analysis yielded O-W/L settings of 1155/270 HU for VMI 70 and 3230/880 HU for VMI 40. VMI 40 O-W/L received the highest scores for each parameter compared to conventional (all p &lt; 0.0027). Using O-W/L settings for VMI 70 and VMI 40 did not result in significant differences in vessel measurements compared to conventional images. Conclusion: Optimization of VMI requires adjustments in W/L settings. Our results recommend W/L settings of 1155/270 HU for VMI 70 and 3230/880 HU for VMI 40.</p

Feasibility of virtual non-iodine coronary calcium scoring on dual source photon-counting coronary CT angiography:a dynamic phantom study

Background: The aim of our current systematic dynamic phantom study was first, to optimize reconstruction parameters of coronary CTA (CCTA) acquired on photon counting CT (PCCT) for coronary artery calcium (CAC) scoring, and second, to assess the feasibility of calculating CAC scores from CCTA, in comparison to reference calcium scoring CT (CSCT) scans. Methods: In this phantom study, an artificial coronary artery was translated at velocities corresponding to 0, &lt; 60, and 60–75 beats per minute (bpm) within an anthropomorphic phantom. The density of calcifications was 100 (very low), 200 (low), 400 (medium), and 800 (high) mgHA/cm3, respectively. CCTA was reconstructed with the following parameters: virtual non-iodine (VNI), with and without iterative reconstruction (QIR level 2, QIR off, respectively); kernels Qr36 and Qr44f; slice thickness/increment 3.0/1.5 mm and 0.4/0.2 mm. The agreement in risk group classification between CACCCTA and CACCSCT scoring was measured using Cohen weighted linear κ with 95% CI. Results: For CCTA reconstructed with 0.4 mm slice thickness, calcium detectability was perfect (100%). At &lt; 60 bpm, CACCCTA of low, and medium density calcification was underestimated by 53%, and 15%, respectively. However, CACCCTA was not significantly different from CACCSCT of very low, and high-density calcifications. The best risk agreement was achieved when CCTA was reconstructed with QIR off, Qr44f, and 0.4 mm slice thickness (κ = 0.762, 95% CI 0.671–0.853). Conclusion: In this dynamic phantom study, the detection of calcifications with different densities was excellent with CCTA on PCCT using thin-slice VNI reconstruction. Agatston scores were underestimated compared to CSCT but agreement in risk classification was substantial. Clinical relevance statement: Photon counting CT may enable the implementation of coronary artery calcium scoring from coronary CTA in daily clinical practice. Key Points: Photon-counting CTA allows for excellent detectability of low-density calcifications at all heart rates. Coronary artery calcium scoring from coronary CTA acquired on photon counting CT is feasible, although improvement is needed. Adoption of the standard acquisition and reconstruction protocol for calcium scoring is needed for improved quantification of coronary artery calcium to fully employ the potential of photon counting CT.</p

Long-Term Outcome of Fanconi Anemia Patients From the Italian Registry on Behalf of the Marrow Failure Study Group of the AIEOP (Italian Association for Pediatric Haematology-Oncology)

We analyzed 193 Fanconi anemia patients from the Italian Registry, focusing on hematological outcome, cancer risk, and mortality, both in transplanted (n = 130, 67.4% of the cohort) and non-transplanted (n = 63, 36.6% of the cohort) patients. After a median follow-up of 7 years, almost all patients developed cytopenia that was more frequent in patients receiving hematopoietic stem cell transplantation (HSCT). The cumulative overall survival from birth was 91.0% at age 10 years, 71.6% at age 20, and 47.4% at age 30 years; the median survival age was 29.1 years. When stratifying patients by indication for transplantation (moderate vs. severe cytopenia vs. persistent poor prognosis cytogenetic alterations/acute myeloid leukemia), we found a 5-year cumulative mortality higher, though not significantly (p = 0.281) in the last group. Cancers were the second most common cause of death in the whole cohort after infections. Head and neck squamous cell carcinoma was the most frequent cancer, followed by hematologic neoplasms. The cumulative incidence of solid/hematological malignancy remarkably increased after 20 years of age and was 51.7% at age 40 years. The risk of malignancies was greater in subjects who received HSCT (sub-distribution azard ratio 2.9, 95% CI: 1.1–7.5, p = 0.024). We also identified a small group of patients with stable or even improved cytopenia over time without transplant, thus confirming that bone marrow failure is not automatic in all patients and heightening the importance of tight monitoring to surveil on the worsening of hematopoietic function and cancer occurrence. Overall, this study provides important findings that may help to make robust clinical decisions

Inter-observer Variability of Expert-derived Morphologic Risk Predictors in Aortic Dissection

OBJECTIVES: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning. METHODS: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a composite of three expert-observers (observers 2-4) using a standardized workflow. A second inter-observer variability assessment on 30 out of the 47 CTA scans compared observers 3 and 4 with a constrained, standardized workflow. A third inter-observer variability assessment was done after specialized training and tested between observers 3 and 4 in an external population of 25 CTA scans. Inter-observer agreement was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: Pre-training ICCs of the four morphologic features ranged from 0.04 (-0.05 to 0.13) to 0.68 (0.49-0.81) between observer 1 and observers 2-4 and from 0.50 (0.32-0.69) to 0.89 (0.78-0.95) between observers 3 and 4. ICCs improved after training ranging from 0.69 (0.52-0.87) to 0.97 (0.94-0.99), and Bland-Altman analysis showed decreased bias and limits of agreement. CONCLUSIONS: Manual morphologic feature measurements on CTA images can be optimized resulting in improved inter-observer reliability. This is essential for robust ground-truth determination for machine learning models. KEY POINTS: • Clinical fashion manual measurements of aortic CTA imaging features showed poor inter-observer reproducibility. • A standardized workflow with standardized training resulted in substantial improvements with excellent inter-observer reproducibility. • Robust ground truth labels obtained manually with excellent inter-observer reproducibility are key to develop reliable machine learning models