Citations

Introduction: Manual measurement of leg length (LL) and offset can be tedious. This study developed an automated algorithm for measuring LL and offset from pre- and postoperative AP pelvis radiographs in a large cohort of THA patients. Methods: Using a deep learning model trained on 1100 total AP pelvis radiographs, an algorithm was developed to calculate LL and offset. Algorithm measurements were compared with manual measurements by 4 raters on a sample of 100 pre- and postoperative image pairs. Inter- and intra-rater consistency was calculated using the intraclass correlation coefficient (ICC). The algorithm was applied to calculate the pre- and postoperative LL and offset discrepancies and the change in LL and offset bilaterally in a cohort of 15,951 image pairs. Results: ICC values between the algorithm and human raters ranged from 0.83 to 0.88 for offset measurements and 0.92 to 0.97 for LL measurements. Human raters demonstrated good-to-excellent inter-rater ICC and uniformly excellent intra-rater ICC. Entire database measurements demonstrated shorter LLs for arthritic joints versus the contralateral leg preoperatively and reduced LL discrepancy post-arthroplasty. Conclusions: We present a deep learning algorithm for calculating LL and offset using AP pelvis radiographs. This tool can support population-level studies and may assist operative management.

Abstract Recent therapeutic advances, including bispecific antibodies (bsAbs), have improved outcomes for patients with relapsed/refractory multiple myeloma (RRMM). However, early mortality (EM) remains a significant challenge, even in the era of novel immunotherapies. We conducted a multicenter, retrospective analysis of real-world patients with RRMM treated with commercial bsAbs to evaluate the incidence and causes of EM. Between May 2022 and June 2025, a total of 441 patients were treated across 7 countries. EM, defined as death within 12 months of therapy initiation, occurred in 148 patients (34%), with a median time from bsAb initiation to death of 2.87 months (interquartile range, 1.38-6.85). The leading cause of EM was progressive disease (72%), followed by infection (13%); regardless of the cause of death, 82% had active disease at the time of death. Our findings highlight that despite encouraging efficacy, EM remains high among real-world bsAb recipients, emphasizing the need for improved disease control strategies and supportive care interventions.

Objective: Esophageal cancer is a leading cause of cancer-related mortality, with a 5-year survival rate of 20%. Surgical resection remains the primary treatment for early and locally advanced disease. Anastomotic leak is a major concern, which significantly increases morbidity and mortality. Impaired conduit perfusion and tissue ischemia are key risk factors. This series describes the use of ELUXEO Oxygen Saturation Endoscopic Imaging (OXEI) technology (Fujifilm Healthcare Americas Corp, Lexington, MA, USA) to assess tissue oxygen saturation during esophagectomy. Methods: OXEI was used in 6 cases to evaluate conduit perfusion during esophagectomy procedures. Real-time hemoglobin oxygen saturation imaging identified ischemic areas, with StO 2 levels ranging from 17% in poorly perfused regions to 92% in well-perfused areas. OXEI findings were congruent with indocyanine green fluorescence imaging but avoided dye-related limitations. Results: OXEI technology offered a dye-free alternative that allowed real-time assessment of tissue oxygenation, facilitating accurate perfusion quantification. Its reproducibility without dye administration and limitations of tissue saturation or washout concerns added reliability, especially during long multistage procedures. In addition, OXEI has been shown to be consistent irrespective of distances from the targeted area, providing precise tissue saturation quantification throughout critical steps of esophagectomy. These findings highlight the potential of this technology as a valuable adjunct in esophageal surgery. Conclusions: The experience with ELUXEO technology in esophagectomy is promising. It provides a reliable, dye-free method for real-time perfusion assessment, potentially reducing the incidence of anastomotic leaks, preventing dye-associated complications, and improving surgical outcomes. Further studies are warranted to validate these findings in esophagectomies.

Abstract Recent updates to monocyte count thresholds recognize oligomonocytic chronic myelomonocytic leukemia (OM-CMML) as an early form of CMML. However, the clinical validity of these changes remains uncertain without incorporating biological and genomic factors. In this study, we analyzed a cohort of 911 patients (249 with OM-CMML, 359 with overt CMML, and 303 with myelodysplastic syndromes) using unsupervised clustering to evaluate the role of genomic determinants in refining CMML diagnosis. Our findings show that CMML molecular signatures (biallelic TET2 mutations or SRSF2-TET2 comutations) are linked to a distinct transcriptome, monocytic bias, classical monocytosis, and a higher risk of progression to overt CMML in OM-CMML cases. We developed a weighted genomic model and diagnostic workflow showing that combining genomic signatures with bone marrow monocyte frequencies in OM-CMML more accurately predicts progression to overt CMML. These findings support integrating genomic determinants and our clinic-ready diagnostic workflow into the CMML diagnostic framework to improve accuracy. Significance: Through comprehensive clinical and genomic profiling of a large patient cohort, alongside immunophenotypic and transcriptional cellular analyses, this study provides evidence that incorporating genomic determinants into the diagnostic criteria for OM-CMML improves diagnostic accuracy and refines the identification of early-stage CMML, thereby preventing misclassification.

Background: For women in the United States desiring implant-based breast reconstruction, the maximum volume of commercially available silicone breast implants has, to date, been 800 cc. The authors evaluated the safety of Mentor larger-size MemoryGel Ultra-High Profile breast implants (≥930 cc) in women undergoing postmastectomy breast reconstruction. Methods: This 10-year, multicenter, open-label, prospective, investigational study assessed the safety and effectiveness of larger-volume implants in women undergoing postmastectomy 2-stage primary or revision reconstruction. Three-year Kaplan-Meier curves and multivariable Cox regression analyzed the association between patient and treatment characteristics and surgical outcomes. The BREAST-Q was used to assess effectiveness at 3 years. Results: A total of 400 women were enrolled (225 primary and 175 revision reconstruction). Mean body mass index was 35.8 kg/m 2 ; 81% had a body mass index greater than or equal to 30 kg/m 2 . At 3 years, the cumulative incidence of postoperative complications (excluding rupture) was 63.0% (95% confidence interval, 58.1% to 67.9%). The reoperation rate was 24.5% (95% CI, 20.4% to 29.1%), and the explantation rate was 15.8% (95% CI, 23.5% to 19.9%). Independent predictors of complications included radiation therapy and a history of smoking. There were no significant associations between postoperative complications and implant volume greater than or equal to 1135 cc or less than 1135 cc. BREAST-Q scores at year 3 showed significant improvements from baseline in Satisfaction with Breasts, Psychosocial Well-Being, Sexual Well-Being, and Physical Well-Being (all P < 0.0001). The mean score for Satisfaction with Outcome was 79.9. Conclusions: These 3-year results demonstrate that larger-volume silicone breast implants represent a safe and effective option for patients with larger breasts who are requesting postmastectomy implant-based reconstruction.

Background/Objectives: Traumatic spinal cord (SC) injury (SCI) is a debilitating neurological condition. Minimally invasive approaches to monitor in real time the functional state of the neuromotor apparatus in animal models of SCI (at rest and movement) to assess effectiveness of therapy are needed in preclinical studies. We aimed to develop such a bioethically acceptable platform for SCI studies on non-human primates (Rhesus macaques). Methods: Epidural and myographic electrode implantation (EI) (wireless and wired, connected via a head plug) was performed. After EI, motor responses caused by electrical stimulation of the SC at the level of the cervical and lumbar thickening were recorded; electromyography of the limb muscles was recorded during quadrupedal movement of the animal on a treadmill with simultaneous assessment of movements’ kinematic parameters. Five weeks after EI, three animals underwent lateral hemisection of the SC in the C4–C5 segment under the control of a surgical microscope and intraoperative recording of motor- and sensory-evoked potentials. Results: Within 30 days after SCI, during treadmill testing, a decrease in electromyographic activity of the limb muscles and the volume of angular movement in the joints on the side of the injury was detected. Electrical stimulation at the L2–S1 segments of the SC at a frequency of 30 Hz led to the appearance of a locomotor pattern in the muscles of the hind limbs and an increase in the range of motion. Conclusions: Our platform can be used for pathophysiological studies of various neuromodulation modes and as a basis for the development of control neurointerfaces.

Abstract Multiple myeloma (MM) with t(11;14)(CCND1;IGH) remains the only subset sensitive to the BCL2 inhibitor venetoclax. However, not all patients with t(11;14)(CCND1;IGH) respond to treatment, and some progress early after initial response. To investigate this, we examined 44 whole-genome and whole-exome sequencing data samples from 34 patients with t(11;14) MM treated with venetoclax. The presence of mutations in the RAS pathway was strongly associated with shortened progression-free survival (PFS) and was validated in an independent cohort of 21 patients with MM. The presence of 1q gain was also associated with shorter PFS in patients without RAS mutations. In 10 patients with paired prevenetoclax and postvenetoclax treatment samples, postvenetoclax progression was recurrently driven by the selection of genomic events in the BCL2/MCL1 and RAS pathways and of high-risk features (eg, loss of TP53 and CDKN2C). Overall, our study shows that comprehensive genomic profiling can identify most mechanisms underlying resistance to BCL2 inhibition in t(11;14)(CCND1;IGH) MM.

Abstract Objective Memory impairments are common in neurological disorders, especially drug‐resistant epilepsy, where cognitive deficits such as accelerated long‐term forgetting may occur before surgery due to interictal/ictal discharges, antiseizure medications, and disease progression. Postsurgical memory decline affects 40%–60% of patients. Understanding the neural mechanisms of memory encoding is essential for identifying critical network hubs and guiding surgical interventions that preserve cognitive function. Methods We analyzed intracranial electroencephalographic recordings from epilepsy patients ( n = 15) performing a verbal memory encoding task to identify key structures involved in successful memory formation. Functional connectivity was computed using multiple features across several frequency bands. Temporal dynamics of connectivity were examined to characterize pre‐encoding and encoding phases. Results The middle temporal gyrus (MTG) consistently emerged as a verbal memory hub across features and frequency bands. The inferior frontal gyrus (IFG) was identified as a beta‐band‐specific hub via phase synchrony. Temporal analyses revealed that MTG exhibited stable and widespread connectivity differences across all encoding phases, suggesting a role in pre‐encoding network priming. In contrast, IFG displayed a transient decrease in connectivity and spatial extent during early encoding, indicating a more focal and dynamic contribution. Significance These findings suggest that successful memory encoding relies on widespread, frequency‐specific connectivity patterns centered on MTG, complemented by transient, localized IFG activity. Identifying such hubs may inform surgical planning by highlighting regions critical for cognitive outcomes, ultimately supporting strategies to preserve memory in epilepsy surgery.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs) can cause radiation-induced changes (RIC), but its interactions with AVM embolization are not well established. The aim of this study was to assess the effect of previous embolization on RIC in SRS-treated AVM patients. METHODS: Data of AVM patients treated with single-session SRS from 1987 to 2018 were retrieved from the International Radiosurgery Research Foundation. Univariable and stepwise backward logistic regression models were used to identify RIC predictors. Patients were stratified into those who received pre-SRS embolization (E + SRS) vs those who did not (SRS-only). Radiologic RIC (rRIC) was the primary end point. Secondary outcomes included symptomatic RIC (sRIC) and permanent symptomatic RIC (pRIC). RESULTS: Among 1187 AVM patients, the mean age was 36.4 years (SD 16.8), with 50.4% female patients. AVMs had a mean untreated AVM volume of 5.2 cm 3 . A total of 130 patients (11%) underwent neoadjuvant embolization (E + SRS). The overall rRIC and sRIC rates were 32.8% and 12.1%, respectively, with time to rRIC and sRIC being significantly longer in the E + SRS vs SRS-only cohorts (103.6 ± 339.4 vs 11.3 ± 12.5 and 60.4 ± 262.9 vs 9.5 ± 9.0 months, respectively). Seizures at presentation and ≥3-cm untreated AVM volume significantly correlated with a higher likelihood of rRIC (adjusted odds ratio [aOR] 2.32 [1.25-4.30] and aOR 2.77 [1.24-6.16], respectively). Age and pre-SRS embolization were associated with a significantly lower risk of rRIC (aOR 0.97 [0.96-0.99] and aOR 0.32 [0.13-0.74], respectively). The E + SRS cohort had significantly reduced odds of rRIC (aOR = 0.37 [0.15-0.89]) and pRIC (aOR = 0.04 [0.00-0.30]) after adjusting for significant covariates. CONCLUSION: Seizures at presentation and larger untreated AVM volume were independently associated with an increased risk of rRIC, whereas older age and pre-SRS embolization were protective. Notably, patients who underwent embolization before SRS had lower odds of rRIC and pRIC, with delayed onset of complications compared with SRS-only.

Abstract Chimeric antigen receptor T (CART) cell therapy has shown unprecedented success in the treatment of hematological malignancies. However, the immunosuppressive tumor microenvironment of both solid and liquid tumors is a major barrier for CART efficacy. Immunosuppressive myeloid cells inhibit CART efficacy. Colony-stimulating factor 1 receptor (CSF1R) promotes macrophage proliferation, survival, and anti-inflammatory response and is upregulated on myeloid cells in many cancers, making CSF1R an appealing therapeutic target. We aimed to test the interactions between CSF1R, myeloid cells, and CART response, and to study CSF1R targeting in the context of CART cell therapy. We utilized CD19-targeted CART cell therapy (CART19) in lymphoma preclinical models and thyroid-stimulating hormone receptor (TSHR)-targeting CART cell therapy (TSHR-CART) in thyroid cancer models. We first measured CSF1R expression on myeloid cells in vitro. Suppressive myeloid cells, polarized from healthy donor monocytes using an anaplastic thyroid cancer (ATC) cell line, 8505c, or mantle cell lymphoma cell line, JeKo-1, significantly upregulate CSF1R (p=0.0002) compared to media control. After polarization, myeloid cells significantly inhibit TSHR-CART and CART19 antigen-specific proliferation compared to freshly isolated monocytes (p=0.012, p&lt;0.01, respectively) indicating that suppressive myeloid cells contribute to CART failure in multiple tumor types. We then performed single cell RNA sequencing on peripheral blood taken at baseline from patients with mantle cell lymphoma treated with CART19. We found a significant increase of CSF1R on monocyte subsets in CART19 non-responders vs responders (padj=0.0037). Next, we determined the impact of CSF1R blockade on CART cell therapy in vivo. Using lymphoma models, B6 mice were engrafted with the luciferase+ CD19+ murine lymphoma cell line TBL-12 (1x106 cells i.v. 1 day after 250 mg/kg cyclophosphamide). Tumor burden was significantly reduced after 7 days of treatment with low dose CART19 (0.5x106 i.v.) + anti-mouse CSF1R antibody (16mg/kg i.p. twice weekly) vs CART19 + IgG control (p=0.0146). We then tested the impact of CSF1R blockade in mice experiencing tumor relapse. After TBL-12 engraftment, mice were treated with anti-mouse CSF1R or IgG control antibody followed two days later with high dose CART19 (1x106 i.v.) to induce remission. Mice were re-challenged with TBL-12 14 days later. Mice treated with anti-mouse CSF1R antibody showed increased tumor control and significantly higher survival (p=0.0416). Using thyroid cancer models, first we identified high macrophage infiltration in biopsy specimens of patients with ATC compared to normal thyroid tissue and benign thyroid tumors through immunohistochemistry (IHC) of patient samples (p&lt;0.01, p&lt;0.0001, respectively). To test if macrophages are associated with CART failure in ATC, NSG mice were subcutaneously engrafted with 1x106 TSHR+ THJ529 tumors, an ATC cell line derived from patient biopsy samples from the Mayo Clinic thyroid cancer biobank, followed by i.v. treatment with 1x107 TSHR-CART or untransduced T cell control (UTD). IHC staining of tumor tissue collected at experimental endpoints revealed a dose-dependent, significant infiltration of human CD3+ T cells into the tumors which inversely correlated with murine F4/80+ myeloid cell and murine YM-1+ M2 macrophage infiltration. This led us to hypothesize that myeloid cell targeting with CSF1R blockade can improve TSHR-CART efficacy. We utilized the same ATC model described above to test CSF1R targeting. When TSHR+ THJ529 tumors reached approximately 100 mm3, mice were randomized by tumor volume and treated with CSF1R inhibitor PLX5622 (600mg/kg) or vehicle control, followed by either UTD or TSHR-CART cells 5x106 i.v. Mice treated with TSHR-CART + PLX5622 showed significantly improved tumor control vs TSHR-CART + vehicle control (p&lt;0.0001) or UTD + PLX5622 (p&lt;0.0001). Together, our results highlight immunosuppressive myeloid cells which express CSF1R as a major cell type limiting CART efficacy in both solid and liquid tumors. We also identified a strategy to overcome myeloid-mediated suppression of CART cells by targeting CSF1R with antibody or small molecule inhibitors.