Citations

ABSTRACT Background Patients at high risk for cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplant (HCT) should receive CMV prophylaxis. Historically, ganciclovir has been the preferred agent. However, its side effect profile, particularly myelosuppression, is undesirable. Letermovir is a newer agent that is not myelosuppressive and has replaced ganciclovir as the preferred agent for CMV prophylaxis in high‐risk adult patients. Methods The primary objective was to compare the incidence of dose modifications or discontinuation of CMV prophylaxis between pediatric patients who received ganciclovir versus letermovir. Secondary objectives included comparing the use of granulocyte colony‐stimulating factor (G‐CSF) support and the incidence of CMV DNAemia. We reviewed records of all pediatric patients who received an HCT at our institution between 2000 and 2024 and received either ganciclovir/valganciclovir or letermovir for CMV prophylaxis. Results Between 2000 and 2024, 65 pediatric patients receiving prophylactic ganciclovir, valganciclovir, or letermovir were evaluated. The median age at transplant was 12.2 years. No patients receiving letermovir required dose modification or discontinuation as opposed to 14 (29.2%) patients receiving ganciclovir ( p = 0.014). After engraftment, 12 (25%) patients receiving ganciclovir required G‐CSF support compared to seven (41.2%) patients receiving letermovir ( p = 0.23). In the ganciclovir group, 10 (20.8%) patients experienced CMV infection versus one (5.9%) patient receiving letermovir ( p = 0.26). Conclusion Compared with those receiving letermovir, a significantly higher proportion of patients in the ganciclovir/valganciclovir group experienced dose modifications or discontinuation of CMV prophylaxis due to adverse effects. Letermovir shows great promise as a CMV prophylactic agent in pediatric HCT patients due to its favorable side effect profile.

ABSTRACT HLA‐DQA1*05:01:21 differs from HLA‐DQA1*05:01:01:02 by one nucleotide substitution in codon 198 (TGC > TGT) in exon 4.

OBJECTIVE This study aimed to develop an artificial intelligence (AI) model for automatically detecting Hounsfield unit (HU) values at the L1 vertebra in preoperative thoracolumbar CT scans. This model serves as a screening tool for osteoporosis in patients undergoing spine surgery, offering an alternative to traditional bone mineral density measurement methods like dual-energy x-ray absorptiometry. METHODS The authors utilized two CT scan datasets, comprising 501 images, which were split into training, validation, and test subsets. The nnU-Net framework was used for segmentation, followed by an algorithm to calculate HU values from the L1 vertebra. The model’s performance was validated against manual HU calculations by expert raters on 56 CT scans. Statistical measures included the Dice coefficient, Pearson correlation coefficient, intraclass correlation coefficient (ICC), and Bland-Altman plots to assess the agreement between AI and human-derived HU measurements. RESULTS The AI model achieved a high Dice coefficient of 0.91 for vertebral segmentation. The Pearson correlation coefficient between AI-derived HU and human-derived HU values was 0.96, indicating strong agreement. ICC values for interrater reliability were 0.95 and 0.94 for raters 1 and 2, respectively. The mean difference between AI and human HU values was 7.0 HU, with limits of agreement ranging from −21.1 to 35.2 HU. A paired t-test showed no significant difference between AI and human measurements (p = 0.21). CONCLUSIONS The AI model demonstrated strong agreement with human experts in measuring HU values, validating its potential as a reliable tool for automated osteoporosis screening in spine surgery patients. This approach can enhance preoperative risk assessment and perioperative bone health optimization. Future research should focus on external validation and inclusion of diverse patient demographics to ensure broader applicability.

OBJECTIVE The objective of this study was to develop a deep learning model for automated pituitary adenoma segmentation in MRI scans for stereotactic radiosurgery planning and to assess its accuracy and efficiency in clinical settings. METHODS An nnU-Net–based model was trained on MRI scans with expert segmentations of 582 patients treated with Leksell Gamma Knife over the course of 12 years. The accuracy of the model was evaluated by a human expert on a separate dataset of 146 previously unseen patients. The primary outcome was the comparison of expert ratings between the predicted segmentations and a control group consisting of original manual segmentations. Secondary outcomes were the influence of tumor volume, previous surgery, previous stereotactic radiosurgery (SRS), and endocrinological status on expert ratings, performance in a subgroup of nonfunctioning macroadenomas (measuring 1000–4000 mm 3 ) without previous surgery and/or radiosurgery, and influence of using additional MRI modalities as model input and time cost reduction. RESULTS The model achieved Dice similarity coefficients of 82.3%, 63.9%, and 79.6% for tumor, normal gland, and optic nerve, respectively. A human expert rated 20.6% of the segmentations as applicable in treatment planning without any modifications, 52.7% as applicable with minor manual modifications, and 26.7% as inapplicable. The ratings for predicted segmentations were lower than for the control group of original segmentations (p < 0.001). Larger tumor volume, history of a previous radiosurgery, and nonfunctioning pituitary adenoma were associated with better expert ratings (p = 0.005, p = 0.007, and p < 0.001, respectively). In the subgroup without previous surgery, although expert ratings were more favorable, the association did not reach statistical significance (p = 0.074). In the subgroup of noncomplex cases (n = 9), 55.6% of the segmentations were rated as applicable without any manual modifications and no segmentations were rated as inapplicable. Manually improving inaccurate segmentations instead of creating them from scratch led to 53.6% reduction of the time cost (p < 0.001). CONCLUSIONS The results were applicable for treatment planning with either no or minor manual modifications, demonstrating a significant increase in the efficiency of the planning process. The predicted segmentations can be loaded into the planning software used in clinical practice for treatment planning. The authors discuss some considerations of the clinical utility of the automated segmentation models, as well as their integration within established clinical workflows, and outline directions for future research.

The importance of having region-specific data when planning health interventions has become evident in recent years. Nonetheless, several world regions, including Latin America and the Caribbean (LAC), still face significant challenges. These regions need to develop strategies specifically designed to consider the inherent characteristics of their population composite and sociodemographic characteristics. More than 20% of the global cancer incidence arises in LAC. Yet, treatment, prevention, and follow-up guidelines in the area are frequently based on studies that mainly include patients from North America, Europe, and Asia. As personalized approaches become ubiquitous in medical practice, the amount of information emerging from LAC has risen considerably. In this review, we seek to present a comprehensive summary of the frequency of germline genetic variants in hereditary cancer syndromes in patients from LAC. The data highlight relevant differences in variants associated with LAC patients, including founder and recurrent variants, while showcasing potential features that might be relevant in oncology practices.

T cell aging contributes to the lower vaccine efficacy in older adults, yet the molecular mechanism remains elusive. Here, we show the density of initially responding naïve CD4 + T cells is instructive in T follicular helper (TFH) cell fate decisions and declines with age. A lower number of initially responding cells did not affect TFH differentiation at peak responses after immunization but accounted for an increased contraction phase manifesting as a larger loss of CXCR5 expression. Mechanistically, cells activated at a lower initial density had more sustained mammalian target of rapamycin complex 1 (mTORC1) activities that impair CXCR5 maintenance. YAP-dependent regulation of SLC7A5 involved in the cell density–dependent regulation of mTORC1 activities and TFH loss. Old mice fed with a leucine-restricted diet after peak responses showed smaller TFH loss and improved humoral immune responses. Attenuating mTORC1 signaling after peak response is a strategy to boost vaccine responses in older individuals.

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T- and B-cell recovery have improved survival and decreased treatment-related mortality (TRM). A total of 2089 patients were included who underwent first allo-HCT for acute myeloid leukemia/acute lymphoblastic leukemia/myelodysplastic syndrome from 2008 to 2019 reported to the Center for International Blood and Marrow Transplant Research with available CD4 counts at days 100 and 180. Patients (median age, 51 years [range, 2-75]) were categorized into 4 groups based on graft-versus-host disease (GVHD) prophylaxis: ex vivo T-cell depletion (TCD/CD34), posttransplant cyclophosphamide, calcineurin inhibitor alone (CNI), or CNI with antithymocyte globulin. Based upon survival, we could identify optimal cutoff points for CD4+ T cells in pediatric (age of &lt;20 years) patients: 248 × 106/L and 420 × 106/L at days 100 and 180, respectively; and in adult (age of &gt;20 years) patients: 104 × 106/L and 115 × 106/L at days 100 and 180, respectively. In adults, day-100 CD4 count was associated with overall survival (OS), progression-free survival (PFS), and TRM but not relapse, incidence of infections, or chronic GVHD. Similarly, CD4 counts above the cutoff point at day 180 in adults were associated with improved OS, PFS, and TRM but no other outcomes. No clinical associations for CD4 counts were identifiable in pediatric patients. These findings underscore the importance of tailoring transplant strategies for adults to optimize immune recovery and improve patient outcomes.