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Background: Total knee arthroplasty (TKA) and hindfoot reconstruction (HFR) are often used to treat osteoarthritis and deformities of the knee and hindfoot. Despite the proven clinical effectiveness of these treatments, postoperative patient dissatisfaction is high. The knee and ankle are adjacent joints in the lower extremity, and angular deformity of either joint is known to affect positioning of the anatomical and mechanical axes of the entire limb. Although it is understood this relationship exists, there are limited studies evaluating outcomes of ipsilateral procedures on patients with pathologies of both knee and hindfoot. This article aims to evaluate whether TKA or TAA/HFR sequencing influences postoperative outcome. The study hypothesis is that TKA prior to TAA/HFR results in lower reoperation. Methods: A retrospective chart review using Current Procedural Terminology ( CPT ) codes was performed encompassing all patients who underwent TKA in conjunction with a variety of hindfoot procedures. All procedures were performed at a single academic medical site between 2000 and 2022. Exclusion criteria included those patients not having both ipsilateral TKA and hindfoot procedures or those lacking conclusive postoperative data. The primary outcome of this study was to identify significant reoperations such as adjacent joint arthrodeses, hardware removal, or unrelated ipsilateral limb surgery. Secondary outcomes included identification of revision procedures including revision TKA or revision HFR and other postoperative complication data. Results: This study included 158 patients, with 79 patients in each group. In the TKA-first group, the mean follow-up time was 10.24 years (range, 1.10-22.42 years) and the mean time to HFR was 5.94 years. In the HFR-first group, the mean follow-up time was 9.01 years (range, 1.01-23.55 years) and the mean time to TKA was 5.51 years. In patients who underwent TKA first, the mean reoperation rate was not significantly different from those who underwent HFR/TAA first, 30.4% vs 19.0% ( P = .12). In patients who underwent TKA first, the rate of HFR reoperations (22.78%) was greater than TKA reoperations (7.59%) ( P < .01). The revision rate was higher in the TKA-first group (17.7%) when compared to the HFR-first group (6.3%) ( P = .03). Additionally, there were more revision HFR procedures in the TKA-first group (9/79) compared with the HFR-first group (1/79) ( P = .009). Conclusion: In contrast to the study hypothesis that TKA first would result in less reoperation, our study found that TAA or HFR performed before TKA had an overall lower complication rate. However, these findings should be interpreted cautiously as the sample size was limited. Level of Evidence: Level III, retrospective cohort study.

BACKGROUND AND OBJECTIVES: Schwannomas are benign, slow-growing peripheral nerve sheath tumors. Approximately 8% of intracranial schwannomas originate from the trigeminal nerve. No consensus exists regarding superiority of outcomes after resection vs stereotactic radiosurgery (SRS) in the treatment of trigeminal schwannomas (TS). The aim of this study was to compare the efficacy and outcomes of resection vs SRS for TS management. METHODS: Embase, PubMed, and SCOPUS databases were queried from the date of inception to July 2023 for primary data reporting TS treatment outcomes after SRS or resection. Risk of bias was reported under Newcastle-Ottawa Scale. RESULTS: Overall, 29 retrospective observational studies comprising 949 patients were included in the analysis. A total of 13 studies (n = 589) reported outcomes after SRS, and 16 studies (n = 360) reported outcomes after surgical resection, and 182 patients in the SRS group had previous resection. To ensure statistical validity of comparing the cohorts, 3 checkpoints were assessed: the median age (SRS: 48 vs surgery: 40 years old, P < .01), tumor volume (5.2 vs 8.9 cm 3 , P = .06), and median follow-up (53.9 vs 48.5 months, P = .59), which reflected the choice of treatment. Compared with surgical resection, the SRS group demonstrated significantly higher rates of facial hypesthesia improvement (44% vs 12%, P < .01) and lower rates of new onset (4% vs 15%, P = .051) at last follow-up. Facial pain was less likely to improve (58% vs 81%, P = .024) after SRS compared with surgery. However, worsened (5% vs 1%, P = .71) and new facial pain (2% vs 1%, P = .55) were comparable between cohorts. CONCLUSION: SRS seems to offer improvement in rates of hypesthesia and trigeminal motor deficits compared with surgical resection for TS. However, facial pain improvement was more favorable after surgery. These findings highlight the importance of individualized treatment decisions based on patient characteristics, tumor profile, and pretreatment symptoms.

Study Design: Single-center retrospective analysis. Objective: To establish an empirically derived threshold to define both coronal and sagittal malalignment (CM & SM) based on preoperative patient-reported outcomes (PROs). Summary of Background Data: Currently, no radiographic alignment threshold defines preoperative CM in adult spinal deformity (ASD) patients based on disability. In a cohort of ASD patients undergoing corrective surgery, we sought to establish a threshold to define both CM and SM based on PRO and assess the clinical impact of CM and combined with SM. Methods: ASD patients with ≥6 level fusions were included. CVA and SVA were measured. PROs included preoperative ODI and SRS-22r scores. CVA and SVA thresholds were derived to accurately differentiate patients with ODI >40 and SRS-pain+function <5. Patients were then separated into 4 groups: (1) neutral alignment (NA); (2) CM; (3) SM; and (4) combined coronal and sagittal malalignment (CCSM). Results: Totally, 368 patients were included. Thresholds to distinguish patients with ODI ≥40 and SRS-pain/function <5 were: (1) CVA=3.96 cm (ODI) and 3.17 cm (SRS); (2) SVA=4.97 cm (ODI) and 7.52 cm (SRS). The lower numbers were chosen to define each threshold: CVA=3 cm and SVA=5 cm. Alignment breakdown was: NA=179 (48.6%), CM=66 (17.9%), SM=65 (17.7%), and CCSM=58 (15.8%). Both SM=( P =0.006) and CCSM ( P <0.001) patients had significantly worse ODI scores than NA patients, and CCSM patients were significantly worse than SM alone ( P =0.010). On the basis of preoperative total SRS-22r scores, only CCSM ( P =0.003) patients were significantly worse than the NA group. CVA significantly correlated with 4/7 (57.1%) preoperative PROs (ODI/SRS-total/function/image), while SVA correlated with 5/7 (71.4%) preoperative PROs (ODI/SRS-total/function/image/pain). A linear relationship was seen between increasing CVA and worsening ODI (β=0.92, 95% CI: 0.37–1.48, P =0.001). A significant and slightly stronger relationship was seen between increasing SVA and worsening ODI (β=1.28, 95% CI: 1.00–1.56, P <0.001). Conclusions: CM and SM thresholds that accurately distinguished ASD patients with severe pain and disability preoperatively were 3 cm for CVA and 5 cm for SVA, respectively. Preoperative CM was significantly associated with worse ODI, SRS-22r total/function/image scores. CCSM led to more disability than SM alone.

AbstractThe intricate role of the autonomic nervous system (ANS) in regulating cardiac physiology has long been recognized. Aberrant function of the ANS is central to the pathophysiology of cardiovascular diseases. It stands to reason, therefore, that neuroscience‐based cardiovascular therapeutics hold great promise in the treatment of cardiovascular diseases in humans. A decade after the inaugural edition, this White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology and pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases. image

AbstractBackgroundThe 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).ObjectiveTo investigate the association between CNVs and structural forms on 17q.21.31 with the risk of PSP.MethodsUtilizing whole genome sequencing data from 1684 PSP cases and 2392 controls, the three large CNVs (α, β, and γ) and structural forms within 17q21.31 were identified and analyzed for their association with PSP.ResultsWe found that the copy number of γ was associated with increased PSP risk (odds ratio [OR] = 1.10, P = 0.0018). From H1β1γ1 (OR = 1.21) and H1β2γ1 (OR = 1.24) to H1β1γ4 (OR = 1.57), structural forms of H1 with additional copies of γ displayed a higher risk for PSP. The frequency of the risk sub‐haplotype H1c rises from 1% in individuals with two γ copies to 88% in those with eight copies. Additionally, γ duplication up‐regulates expression of ARL17B, LRRC37A/LRRC37A2, and NSFP1, while down‐regulating KANSL1. Single‐nucleus RNA‐seq of the dorsolateral prefrontal cortex analysis reveals γ duplication primarily up‐regulates LRRC37A/LRRC37A2 in neuronal cells.ConclusionsThe copy number of γ is associated with the risk of PSP after adjusting for H1/H2, indicating that the complex structure at 17q21.31 is an important consideration when evaluating the genetic risk of PSP. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objective To assess Advanced Bionics (AB) HiRes Ultra and Ultra 3D initial version (V1) cochlear implant electrode failures over time at four large cochlear implant programs. Study Design Retrospective cohort. Setting Four tertiary referral centers. Patients Patients receiving AB HiRes Ultra and Ultra 3D initial version (V1) devices as of December 31, 2022. Main Outcome Measures Failure rate, revision surgery, speech recognition scores. Results Over a span of 7 years, 205 (42.6%) of 483 implanted V1 devices have failed. Device failure rate varied across institutions from 32 to 67%. Of the 205 detected failures, 163 (79%) have undergone revision surgery, with 94% of revisions being performed with Advanced Bionics devices. Average time from implantation to diagnosis of device failure was 2.7 ± 1.2 years. Most patients (89.8%) with available testing were matched or exceeded their best prefailure speech performance after implant revision. After revision, patients had an average CNC score improvement of 24.7 percentage points over their most recent pre-revision scores and demonstrated average datalogging of 12.7 ± 4.1 h/d at most recent evaluation. Conclusions Comparison of patients across multiple high-volume implant centers confirms the presence of ongoing device failures. There is variability across institutions in the rate of revision surgery once a patient is diagnosed with a V1 device failure, as well as in the rate of device failure detection. Inter-institutional variability in failure rates may be explained by the variation in the routine use of electrical field imaging. Reimplantation with a new device typically results in a return to prefailure peak performance. Professional Practice Gap & Educational Need To our knowledge, a comparison of AB HiRes (V1) device failures across multiple institutions has not been conducted. Learning Objective To identify device failure rate across multiple institutions with different testing protocols. Desired Result Providers will have an improved understanding of the trajectory of device failures for HiRes (V1) devices over time. Level of Evidence Level IV—Historical cohort or case-controlled studies. Indicate IRB or IACUC IRB #230017; IRB #22-000183; IRB #STU-032018-085; IRB #H-49479.

Abstract Clonal hematopoiesis (CH) is characterized by expanding blood cell clones carrying somatic mutations in healthy aged individuals and is associated with various age-related diseases and all-cause mortality. While CH mutations affect diverse genes associated with myeloid malignancies, their mechanisms of expansion and disease associations remain poorly understood. We investigate the relationship between clonal fitness and clinical outcomes by integrating data from three longitudinal aging cohorts (n=713, observations=2,341). We demonstrate pathway-specific fitness advantage and clonal composition influence clonal dynamics. Further, the timing of mutation acquisition is necessary to determine the extent of clonal expansion reached during the host individual’s lifetime. We introduce MACS120, a metric combining mutation context, timing, and variant fitness to predict future clonal growth, outperforming traditional variant allele frequency measurements in predicting clinical outcomes. Our unified analytical framework enables standardized clonal dynamics inference across cohorts, advancing our ability to predict and potentially intervene in CH-related pathologies.

AbstractPortosystemic collateral pathways are a significant concern in interventional radiology, frequently manifesting in patients with cirrhosis or portal vein thrombosis. These pathways can lead to severe clinical complications, including gastrointestinal bleeding, hepatic encephalopathy, and liver failure. A thorough understanding of the anatomy, hemodynamic alterations, and clinical implications of these shunts is crucial for interventional radiologists to provide effective treatment while minimizing risks. This article reviews the clinical presentations associated with portosystemic shunts, explores the anatomical variants and altered flow dynamics, and discusses the latest endovascular treatment strategies to optimize patient outcomes.

PURPOSE Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), two B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). We compare safety, efficacy, and survival among patients with RRMM treated with standard-of-care (SOC) ide-cel or cilta-cel. METHODS Data were from a retrospective chart review of patients with RRMM leukapheresed by December 31, 2022, with the intent to receive SOC ide-cel or cilta-cel at 19 institutions. An inverse probability of treatment weighting (IPTW) approach was used to compare outcomes by therapy type. RESULTS A total of 641 patients were leukapheresed by December 31, 2022, with ide-cel (n = 386) and cilta-cel (n = 255). Five hundred eighty-six patients were infused (n = 350 for ide-cel; n = 236 for cilta-cel) with a median follow-up of 12.6 and 13.0 months for ide-cel and cilta-cel, respectively. After IPTW, patient characteristics were well balanced. Cilta-cel was associated with higher likelihood of grade ≥3 cytokine release syndrome (CRS; odds ratio [OR], 6.80 [95% CI, 2.28 to 20.33]), infections (OR, 2.03 [95% CI, 1.41 to 2.92]), second primary malignancies (OR, 1.77 [95% CI, 0.89 to 3.56]), and delayed neurotoxicity (OR, 20.07 [95% CI, 4.46 to 90.20]). Cilta-cel was also associated with better treatment responses (≥complete response: OR, 2.42 [95% CI, 1.63 to 3.60]), longer progression-free survival (hazard ratio [HR], 0.48 [95% CI, 0.36 to 0.63]), and longer overall survival (HR, 0.67 [95% CI, 0.46 to 0.97]). No associations were observed between therapy type and immune effector cell–associated neurotoxicity syndrome, any CRS, severe cytopenia at days 30 and 90, or nonrelapse mortality. We observed consistent findings when repeating the analyses restricting the ide-cel cohort to patients infused during the same time period as Food and Drug Administration approval for cilta-cel (≥March 2022). CONCLUSION Cilta-cel demonstrated superior efficacy and survival, with higher incidence of certain toxicities, compared with ide-cel.

520 Background: The annual incidence of renal cancer is 0.02% among the general United States population. End stage renal disease (ESRD) and exposure to dialysis are thought to be the primary drivers of increased risk of renal cancer in renal transplant patients rather than immunosuppression. This has been evidenced by how the incidence of RCC in heart transplant recipients is no different than the normal population. In this study, we aim to characterize RCC incidence among kidney transplant patients (usually exposed to ESRD/dialysis) versus other solid organ transplant patients (usually unexposed to ESRD/dialysis). Methods: We used CPT codes to search for patients who had received a solid organ transplant (kidney, liver, heart, lung, pancreas) at all Mayo Clinic sites from 1/1/2018 to 1/1/2024. Within this cohort, we identified those who had been diagnosed with kidney cancer after initiating dialysis or receiving a transplant, and retrospectively extracted data related to demographics, cancer diagnosis, and transplant details. Results: We identified 10873 patients who had received a solid organ transplant (Table 1). Of these, 178 (1.76%) were diagnosed with kidney cancer after either starting dialysis or receiving a transplant. These 178 patients were of median age 56 years at time of cancer diagnosis (STD 12), 71% male, 70% white, 20% black, 4.5% Asian, 2.8% American Native. Of 5792 patients who had received a kidney transplant (with or without another solid organ transplant), 172 (2.97%) were diagnosed with kidney cancer after having started dialysis or receiving a kidney transplant. Of these 172, 156 (91%) were exposed to dialysis (107 primarily hemodialysis and 48 peritoneal). Of 4392 patients who had received a solid organ transplant other than kidney (liver, heart, lung, and/or pancreas), 6 (0.14%) were diagnosed with kidney cancer after having received a kidney transplant. Of these 6, none underwent dialysis. Conclusions: Patients with kidney transplants are at increased risk of kidney cancer compared to patients with non-kidney solid organ transplants (2.97% vs 0.14%). This supports prior evidence showing ESRD plays a significant role in the pathogenesis of kidney cancer. Patients who received solid organ transplants at Mayo Clinic from 2018-2024 and were subsequently diagnosed with kidney cancer. n % With RCC after TXP 178 1.7587% Cancer Diagnosis after Kidney HD/TXP 172 2.9696% Cancer Diagnosis after Other TXP 6 0.1386% Patients who received solid organ transplants at Mayo Clinic from 2018-2024 n % Unique Patients 10121 100% Kidney Transplant 5792 57.23% Alone 5088 50.27% &Liver 332 3.28% &Heart 119 1.18% &Lung 8 0.08% &Pancreas 245 2.42% Non-kidney Transplant (Liver, Heart, Lung, or Pancreas) 4329 42.77% TXP: Transplant, HD: Hemodialysis.