Citations

Background/Objectives: Scaphoid fractures are notorious for a high rate of nonunion, resulting in chronic pain and impaired wrist function. The decision for surgical intervention often involves extensive imaging and prolonged conservative management, leading to delays in definitive treatment. The effectiveness of such treatment remains a subject of ongoing clinical debate, with no universally accepted predictive tool for surgical success. The objective of this study was to train a deep learning algorithm to reliably identify cases of nonunion with a high probability of subsequent union following operative revision. Methods: This study utilized a comprehensive database of 346 patients diagnosed with scaphoid nonunions, with preoperative and postoperative X-rays available for analysis. A classical logistic regression for clinical parameters was used, as well as a TensorFlow deep learning algorithm on X-rays. The latter was developed and applied to these imaging datasets to predict the likelihood of surgical success based solely on the preoperative anteroposterior (AP) X-ray view. The model was trained and validated over six epochs to optimize its predictive accuracy. Results: The logistic regression yielded an accuracy of 66.3% in predicting the surgical outcome based on patient parameters. The deep learning model demonstrated remarkable predictive accuracy, achieving a success rate of 93.6%, suggesting its potential as a reliable tool for guiding clinical decision-making in scaphoid nonunion management. Conclusions: The findings of this study indicate that the preoperative AP X-ray of a scaphoid nonunion provides sufficient information to predict the likelihood of surgical success when analyzed using our deep learning model. This approach has the potential to streamline decision-making and reduce reliance on extensive imaging and prolonged conservative treatment.

Kidney transplantation remains the gold standard for managing end-stage kidney disease, providing superior survival and quality-of-life outcomes compared to dialysis. Despite the ongoing gap between organ availability and demand, it is inevitable that kidney transplantation will continue to grow. This is owed to broader organ sharing, increased comfort of transplant programs with marginal kidney utilization, and the expansion of paired exchange among living donor kidneys. The evolution of kidney transplantation could not have been possible without the availability of effective immunosuppressive regimens that prevent rejection and maintain graft function. Mycophenolic acid and calcineurin inhibitors continue to serve as the foundation of modern maintenance immunosuppression. While these agents have markedly reduced acute rejection rates, their long-term efficacy in graft survival remains suboptimal. Alternative immunosuppressive therapies, including belatacept and mammalian target of rapamycin inhibitors, have demonstrated potential benefits. However, concerns regarding an increased risk of rejection have limited their widespread adoption as primary treatment options. In addition to ongoing efforts to refine steroid- and calcineurin inhibitor-sparing strategies, the identification of practical and quantifiable biomarkers for predicting long-term graft survival remains a critical objective. This review evaluates contemporary immunosuppressive protocols, highlights existing challenges, and explores future directions for optimizing long-term transplant outcomes.

BACKGROUND Tumor-to-tumor metastasis (TTM) is an exceptionally rare phenomenon. To date, only 12 cases of the metastasis of clear cell renal cell carcinoma (ccRCC) to a meningioma have been reported in the literature. The authors present a unique case of TTM involving ccRCC metastasizing to a meningioma in a patient with a history of both primary cancers. OBSERVATIONS A 58-year-old male with a history of 2 primary cancers developed a biphasic tumor diagnosed as TTM of ccRCC to meningioma. The patient initially presented with left lower-extremity (LLE) weakness and underwent subtotal resection of his meningioma. Postsurgical imaging revealed rapid tumor progression, for which the patient completed adjuvant radiotherapy. Concurrently, the patient developed hematuria and was diagnosed with ccRCC. Subsequent recurrent LLE weakness and intracranial tumor progression prompted re-resection, revealing a TTM. LESSONS In patients with a history of multiple cancers who present with recurrent intracranial disease progression radiographically and/or clinically, it is worth considering TTM in the differential diagnosis to facilitate multidisciplinary workup, management, and treatment. https://thejns.org/doi/10.3171/CASE24670

Limited scalability and restricted affordability impede the equitable deployment of curative models of care despite advances achieved with regenerative medicine therapeutics. Mitigating the risk of widening health disparities mandates actions that would improve the availability and accessibility of new classes of biotherapeutics. Namely, the use of Smart Manufacturing empowered by artificial intelligence to increase therapeutic production capacity while reducing cost is an emerging strategy central to the future of the regenerative care economy. Establishing an efficient and effective biomanufacturing ecosystem is essential to building regenerative pipelines into broadly available regenerative therapeutics options. This ecosystem must provide not only necessary cell environment controls and computer process power, but also the sensing technologies to feed critical process parameters to the algorithms in real-time. Here we outline key elements that are in development to support Smart Biomanufacturing, such as machine learning, advanced analytics, digital twins, and modular cytocentric production. The aim of integrating these technologies is to drive down costs, improve access to new regenerative medicine therapeutics, address regulatory science expectations, and in doing so, improve health equity.

Abstract Gallium-68-DOTA-Tyr3-Octreotate (Ga-68-DOTATATE) positron emission tomography/computed tomography (PET/CT) has recently been shown to have utility for the localization of phosphaturic mesenchymal tumors (PMT) that cause tumor-induced osteomalacia (TIO), a rare renal phosphate-wasting disorder. The aim of this study was to evaluate the accuracy of Ga-68-DOTATATE PET/CT in localizing PMTs causing TIO and to compare its performance with other functional imaging modalities. Prospective recruitment and retrospective chart review of 30 patients with suspected TIO and evaluation with Ga-68-DOTATATE PET/CT between 2017 and 2023 were conducted at a tertiary medical center. True positive (TP) lesions were defined by histological confirmation of PMT. There were 22 TP lesions identified among 18 patients, with a mean SUVmax of 16.8 (±10.9). Sensitivity, specificity, and accuracy of Ga-68-DOTATATE PET/CT were 85.7%, 77.8%, and 83.3% on patient-based analysis, and 84.6%, 56.3%, and 73.8% on lesion-based analysis. Lesions such as subacute fractures, parathyroid adenomas, thymus uptake, vertebral hemangiomas, bone enchondromas, liver hemangiomas, and avascular necrosis were some of the pitfalls in interpretation. Ga-68-DOTATATE PET/CT led to a significant impact on clinical management in 24 (80%) of patients. The presence of DOTATATE-avid fractures was significantly associated with a localizing scan on univariable (OR 15.0, 95% CI 2.80-110, p = .001) and multivariable analysis (OR 9.45, 95% CI 1.33-98.4, p = .003). Ga-68-DOTATATE PET/CT has good accuracy for the localization of TIO, with superior sensitivity compared to F-18-FDG PET/CT. This significantly impacted clinical treatment decisions. Although DOTATATE-avid fractures may be a source of false positives, they may also indicate a higher probability of a localizing study.

ABSTRACT The PIM family of serine/threonine kinases (PIM1, PIM2, and PIM3) are involved in the development of cancer and represent promising therapeutic targets. We investigated the therapeutic potential of targeting PIM kinases in diffuse large B‐cell lymphoma (DLBCL), particularly the activated B‐cell‐like (ABC) subtype, using the pan‐PIM inhibitor AZD1208. We demonstrated that PIM1 and PIM2 are more highly expressed in ABC‐ cells than in germinal center B‐cell‐like (GCB) ‐DLBCL cells, and that ABC‐DLBCL cell lines are more sensitive to PIM inhibition with AZD1208. Transcriptome analysis of ABC‐DLBCL cell lines treated with AZD1208 revealed a downregulation of genes involved in NF‐κB signaling, a crucial pathway for ABC‐DLBCL. We also explored synergistic drug combinations using a high‐throughput screen, which identified BCL2 and glutaminase inhibitors as effective partners for AZD1208, particularly in aggressive ABC‐DLBCL and double‐hit cell lines. The combination of AZD1208 with the clinically available BCL2 inhibitor venetoclax was synergistic in most DLBCL cell lines, and this combination induced apoptosis and reduced levels of AKT and MCL1 proteins. In conclusion, our findings suggested that AZD1208, especially when combined with BCL2 inhibitors like venetoclax, holds promise as a treatment strategy for aggressive lymphomas. These combinations may enable lower doses of PIM inhibitors, leading to increased tolerability and improved anti‐tumor activity in clinical settings. The study also highlighted the potential for targeting PIM kinases in combination with other therapies to overcome drug resistance in DLBCL.

Abstract Objective To assess the performance and cost implications of contrast-enhanced mammography-guided biopsy (CEM Bx). Methods This is a prospective study from May 5, 2021, to April 18, 2022, across 2 U.S. academic centers, evaluating technical success, patient/radiologist feedback, and operational factors of CEM Bx. Inclusion criteria included that patients be 40 years or older and recommended for biopsy with suspicious findings on contrast-enhanced mammography (CEM). Descriptive statistics are reported for clinical outcomes, length of procedure, and user and participant feedback. An estimate of cost was made by comparing general Medicare costs that are being billed for CEM Bx and post-clip mammogram ($475.48) to the Medicare costs of MRI-guided biopsy (MRI Bx) and post-clip placement mammogram ($845.94). Results Eighty-two participants enrolled. Twenty-two were excluded at the time of CEM Bx (22/82, 27%). Sixty participants were included (mean age 57 years, range 33 to 81 years) with 63 suspicious CEM lesions. The malignancy rate was 22% (14/63). A technical success rate of 100% was achieved. Average CEM Bx time was 29% to 33% the average reported MRI-guided breast biopsy times (CEM Bx = 11 minutes; MRI Bx = 33 to 38 minutes), indicating operational efficiencies. A positive opinion of CEM Bx was reported by 78% of radiologists, 93% of technologists, and 98% of patients. The estimated cost for each CEM Bx was ~ 45% lower than MRI Bx. Conclusion CEM Bx demonstrates high success rates and satisfaction scores. CEM Bx resulted in shorter procedure times, enhanced operational efficiency, and ~45% reduction in costs compared with MRI Bx. As advancements continue, we anticipate CEM Bx will offer a cost-efficient and timely option for breast biopsy.

Abstract Objective To estimate the real‐world risk of cardiovascular events among patients with migraine treated with erenumab and other migraine preventive medications. Background Migraine preventive treatment with calcitonin gene‐related peptide (CGRP) pathway inhibitors, such as erenumab and others, may theoretically result in cardiovascular effects due to a lack of compensatory vasodilation with CGRP pathway inhibition. Methods In this retrospective observational cohort study, we estimated the unadjusted cumulative risk (CR) of new‐onset hypertension, acute myocardial infarction (MI), or stroke among patients with migraine newly treated with erenumab, other anti‐CGRP pathway monoclonal antibodies (mAbs), standard oral preventive medications, and onabotulinumtoxinA using data from the MarketScan® Commercial and Medicare Supplemental medical claims database. Comparative analyses to assess the relative risk (RR) of vascular events were gated on the comparability of treatment groups with respect to baseline demographics and clinical characteristics. Potential bias due to unmeasured confounding was evaluated via negative control outcome (NCO) analyses. Confounding based on measured covariates and differential informative censoring were addressed with inverse probability weights. Results A total of 108,019 new users of migraine preventive medications were included. Unadjusted CR (95% confidence interval [CI]) of hypertension at 12 months of treatment was: erenumab, 9.34% (8.79–9.89%); other anti‐CGRP pathway mAbs, 9.42% (8.92–9.92%); standard oral preventive medications, 9.09% (8.77–9.41%); and onabotulinumtoxinA, 9.10% (8.39–9.81%). NCO analyses identified minimal concerns related to unmeasured confounding in erenumab versus other mAbs and erenumab versus onabotulinumtoxinA comparisons. Adjusted RRs (95% CIs) of acute MI and stroke, respectively, at 36 months of treatment were 1.02 (0.45–1.59) and 0.90 (0.56–1.25) for erenumab versus other mAbs and 0.87 (0.19–1.55) and 0.97 (0.42–1.52) for erenumab versus onabotulinumtoxinA. Conclusions In this analysis of the MarketScan medical claims database, we found no difference in the risk of vascular events in patients treated with erenumab versus other anti‐CGRP pathway mAbs or onabotulinumtoxinA.