Citations

PURPOSE Chemotherapy-induced peripheral neuropathy is a potentially debilitating adverse effect of cancer therapy that can lead to delay, reduction, or discontinuation of cancer treatment. Population-based data on peripheral neuropathy incidence among young cancer survivors are lacking. METHODS Using a linkage between Medicaid, the California Cancer Registry, and hospitalization and emergency department data, we identified 6,028 adolescents and young adults (15-39 years) with Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), breast cancer, colorectal cancer, or testicular cancer and 418 children (<15 years) with HL or NHL during 2005-2017. We determined the cumulative incidence of peripheral neuropathy and its association with neurotoxic chemotherapy identified from Medicaid claims, using multivariable Cox proportional hazards regression models. RESULTS Of 6,446 patients, 1,007 were diagnosed with peripheral neuropathy. Across each cancer type, incidence was higher among patients receiving neurotoxic drugs. For example, compared with non-neurotoxic agents, 5-year cumulative incidence was higher with oxaliplatin for colorectal cancer (24.0% v 6.2%) and paclitaxel for breast cancer (22.6% v 5.1%). In multivariable analysis, the agents most strongly associated with peripheral neuropathy were brentuximab (±other neurotoxic drugs) for HL (hazard ratio [HR], 9.53 [95% CI, 5.95 to 15.26]); brentuximab (±vinca alkaloids; HR, 7.00 [95% CI, 4.13 to 11.87]) for NHL, paclitaxel for breast cancer (HR, 4.03 [95% CI, 3.05 to 5.31]); oxaliplatin for colorectal cancer (HR, 3.46 [95% CI, 2.23 to 5.36]); and cisplatin and etoposide for testicular cancer (HR, 2.06 [95% CI, 1.37 to 3.11]). CONCLUSION The high incidence of peripheral neuropathy highlights the need for frequent monitoring, new supportive care approaches, and development of novel therapeutic agents to minimize toxicity while maintaining treatment efficacy.

Withdrawal Statement The authors have withdrawn the manuscript because the data it contained has been updated. Consequently, they request that this work should not be cited as a reference for any projects to ensure the use of the most current information. For any questions or further clarifications, readers are encouraged to contact the corresponding author directly

INTRODUCTION: The recent US Food and Drug Administration approval of resmetirom for treating metabolic dysfunction-associated steatohepatitis in patients necessitates patient selection for significant fibrosis or higher (≥F2). No existing vibration-controlled transient elastography (VCTE) algorithm targets ≥F2. METHODS: The mAchine Learning ADvanceD fibrosis and rIsk metabolic dysfunction-associated steatohepatitis Novel predictor (ALADDIN) study addressed this gap by introducing a machine-learning-based web calculator that estimates the likelihood of significant fibrosis using routine laboratory parameters with and without VCTE. Our study included a training set of 827 patients, a testing set of 504 patients with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease from 6 centers, and an external validation set of 1,299 patients from 9 centers. Five algorithms were compared using area under the curve (AUC) in the test set: ElasticNet, random forest, gradient boosting machines, XGBoost, and neural networks. The top 3 (random forest, gradient boosting machines, and XGBoost) formed an ensemble model. RESULTS: In the external validation set, the ALADDIN-F2-VCTE model, using routine laboratory parameters with VCTE (AUC 0.791, 95% confidence interval [CI]: 0.764–0.819), outperformed VCTE alone (0.745, 95% CI 0.717–0.772, P < 0.0001), FibroScan-aspartate aminotransferase (0.710, 0.679–0.748, P < 0.0001), and Agile-3 model (0.740, 0.710–0.770, P < 0.0001) regarding the AUC, decision curve analysis, and calibration. The ALADDIN-F2-Lab model, using routine laboratory parameters without VCTE, achieved an AUC of 0.706 (95% CI: 0.668–0.749) and outperformed Fibrosis-4, steatosis-associated fibrosis estimator, and LiverRisk scores. DISCUSSION: Along with the steatosis-associated fibrosis estimator model developed to target significant fibrosis or higher, ALADDIN-F2-VCTE (https://aihepatology.shinyapps.io/ALADDIN1) uniquely supports a refined noninvasive approach to patient selection for resmetirom without the need for liver biopsy. In addition, ALADDIN-F2-Lab (https://aihepatology.shinyapps.io/ALADDIN2) offers an effective alternative when VCTE is unavailable.

ABSTRACTObjectivesCeliac disease (CeD), an autoimmune disorder triggered by gluten ingestion, induces intestinal inflammation and varied symptoms. Treatment entails a strict gluten‐free diet (GFD), posing challenges for students, especially in schools with limited food choices. Nonadherence worsens symptoms, yet research on CeD's impact on students is scarce.MethodsThe CeliacKIDS study, conducted across 11 United States academic medical centers, evaluated gluten exposure risk in pediatric CeD patients via a cross‐sectional survey from August 2020 to August 2021. Participants recruited from treating institutions were approved by respective Institutional Review Boards.ResultsOne hundred and sixty children aged 5–18 (65% female, 34% male, 1% other) participated. Only 12% had GF food options at school, 31% brought their own for celebrations, and 41% lacked gluten free (GF) snacks after school. Thirty‐six percent lacked a 504 plan, with 5% misinformed. Hand hygiene concerns included 24% using sanitizer and 10% rarely washing hands before eating. Sixty‐two percent disclosed CeD, 35% when prompted, and 3% refused, mainly 13‐year‐old males. Two percent hesitated to request GF options, and 2% consumed potentially gluten‐containing food from friends.ConclusionMany US schools provide GF accommodations under the Americans with Disabilities Act (ADA) but lack national standards. Diverse GF options and education on GF‐safe practices are crucial for GFD adherence. Discrepancies in parent–child perceptions emphasize the need for better communication. Adolescents, particularly females aged 12–13 with 2+ years on a GF diet, face higher risks. Transparent family–school communication is vital for optimizing the school experience and ensuring GFD adherence. Comprehensive nationwide school training is essential for celiac patients' well‐being.

Abstract Approximately 50% of prostate cancer (PCa) patients harbor fusions involving the TMPRSS2 and ERG genes. Despite this, tailored therapies targeting the fused gene, tERG , remain undeveloped. Our study analyzed biopsy samples from two clinical trials assessing the efficacies of androgen receptor (AR) signaling inhibitors (ARSIs). The results revealed that tERG promotes resistance to ARSIs and is associated with elevated levels of the glucocorticoid receptor (GR). Subsequent assays showed that GR directly interacts with tERG, alleviates allosteric autoinhibition and prevents chemotherapy-induced tERG degradation. In PCa models, either inhibiting GR or lowering cortisol levels suppressed tumor growth in tERG-positive models, but not in fusion-negative models. In addition, patient-derived fusion-positive xenografts displayed enhanced sensitivity to combined GR and AR inhibitors. Collectively, these findings highlight TMPRSS2-ERG as a new biomarker and propose that simultaneous inhibition of GR and AR may specifically benefit tERG -positine patients. However, GR stimulatory corticosteroid therapies may not be advisable for this patient subgroup.

Background: The Latarjet and other bony augmentation procedures are commonly used to treat anterior shoulder instability in the setting of significant glenoid bone loss. Although several fixation strategies have been reported, the biomechanical strength of these techniques remains poorly understood. Purpose: To perform a systematic review of the biomechanical strength of glenoid bony augmentation procedures for anterior shoulder instability. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic search of the Medline, Embase, Web of Science, and Cochrane Library databases was performed to identify biomechanical studies evaluating various fixation strategies for coracoid and other bone transfer procedures for anterior shoulder instability. Biomechanical results included load to failure with both compression and traction forces, stiffness, and cyclic displacement. The quality of included articles was assessed based on the Quality Appraisal for Cadaveric Studies (QUACS) scale. Results: A total of 21 biomechanical studies comprising 486 specimens were included. The number of screws used and the addition of washers were found to significantly increase rigidity and load to failure. The comparison of fixation techniques demonstrated mixed results in load to failure between screw and alternative constructs including suture buttons and suture anchors. However, studies that tested graft displacement consistently found more graft displacement in buttons compared with screws. The median and mean of the QUACS scale were both 12, with a range of 10-13. Conclusion: Biomechanical studies consistently demonstrated that when glenoid bone grafts were fixed with screws, the number of screws and use of washers significantly increased construct rigidity and load to failure. Different metal screw materials and sizes did not consistently demonstrate a significant difference in biomechanical strength. There are mixed results when comparing suture buttons to screw fixation. The evaluated studies revealed that all double metal screw constructs and the majority of suture button and anchor constructs were able to withstand the glenohumeral load reflective of activities of daily living using a 150-N threshold.

Abstract Myelodysplastic syndromes/neoplasms (MDSs) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the US Food and Drug Administration, (eg, luspatercept, ivosidenib, decitabine/cedazuridine, and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories, including criteria for risk stratification and eligibility, response definitions, time-to-event end points, transfusion end points, functional assessments, and biomarker development. Strategies to address these challenges and optimize future clinical trial design for patients with MDS are presented here.

SummaryThe age‐associated mutational state of clonal haematopoiesis (CH) is linked to multiple adverse health outcomes. As higher risk CH can lead to progressive neoplastic or vascular disease, there is interest in developing clinical trials to mitigate risk associated with CH. Given the high prevalence of CH, data from clinical trials could have broad public health implications for screening and therapy. Thoughtful consideration is needed to design trials that are both clinically relevant and avoid overmedicalization. Here, we summarize clinical studies of CH to date and provide suggestions and guidance on how to approach designing CH‐focused therapeutic clinical trials. These recommendations are derived from discussions among clinical researchers and scientists emanating from the Inaugural Meeting on Somatic Mutations and Predisease in October 2021.