Citations

Objectives: There are few studies that have closely evaluated the outcomes of ulnar collateral ligament repair and reconstruction (UCLR) in position players (PP). The objective of this study was to determine the outcome of UCLR in professional baseball players who play in non-pitcher positions, i.e. PP. Methods: The approval of the Major League Baseball (MLB) Research Committee was obtained. All PP who underwent surgery for their UCL while active on an MLB or Minor League Baseball (MiLB) team were identified using The MLB Health and Injury Tracking System. PP who underwent UCLR from 2010 to 2023 were analyzes, however for data that concerned PP time to return to professional play, only players who underwent UCL surgery from 2010 to 2021 were evaluated in order to ensure the presence of a minimum of 2-year follow-up data. Return to play (RTP) was defined as a player who played in at least 1 game at any professional level (A, AA, AAA, or MLB). Players were deemed to return to the same level of play (RTSLP) if they played in at least 1 game at the same competition level or higher that they played in prior to their UCL surgery. PP who had a time to RTP or a time to RTSLP that exceeded 800 days were excluded from any analysis that concerned the time to return to play. PPs were also compared to a cohort of professional baseball pitchers who had also undergone UCL surgery. Results: From 2010 to 2023, 241 PP underwent surgery for their UCL at a mean age of 23.4 ± 4.3 years old (Table 1). Overall, PP had their UCL surgery at approximately a mean of 3.7 ± 3.3 years after the start of their professional career (Table 1). Further, apart from the year 2020, the annual number of UCL surgeries performed in MLB and MiLB PP demonstrated an upward trend from 2010 to 2023, although no trends in the distribution of UCL surgeries across position type or between major and minor players exist. No statistically significant differences in RTP nor RTSLP rates following UCL surgery in PP existed when comparing across position type (catcher vs. infielder vs. outfielder) and across surgery type (repair vs. reconstruction vs. reconstruction with augmentation) (Table 2). PP who underwent repairs were able to RTP at a median of 221 days (IQR: 81), which was sooner than PP who underwent reconstruction surgery (median: 383 days, IQR: 316) or reconstructions with augmentation (median: 456 days, IQR: 219) (P = 0.002) (Table 3). PP with UCL repairs were also able to RTSLP sooner (median: 234 days, IQR: 64) than PP who underwent reconstructions (median: 394 days, IQR: 305) or reconstructions with augmentation (median: 462 days, IQR: 242) ( P = 0.003) (Table 3). Further, infielders RTP sooner (median: 335 days, IQR: 157) than catchers (median: 396 days, IQR: 283) and outfielders (median: 412 days, IQR: 366) ( P = 0.036) (Table 3). Similarly, infielders RTSLP sooner (median: 334 days, IQR: 162) than catchers (median: 470 days, IQR: 281) and outfielders (median: 426 days, IQR: 354) ( P = 0.016) (Table 3). Following UCL surgery, PP were able to RTSLP, on average, more than 2 months sooner than pitchers (429 ± 177 days for PP vs 499 ± 153 days for pitchers, P < 0.001). PP who underwent repair of their UCL were able to RTSLP over 4.5 months, on average, sooner than pitchers who underwent UCL repair (269 ± 125 days for PPs vs 405 ± 153 days for pitchers, P < 0.001) and PP who underwent reconstruction of their UCL were able to RTSLP just under 50 days sooner than pitchers who had their UCLs reconstructed (450 ± 175 days for PPs vs 498 ± 151 days for pitchers, P < 0.001) (Figure 1). Conclusions: Few studies have examined PP outcome data following UCLR surgery. As such, there is little understanding as to the differences in return to game rates between various baseball non-pitcher positions as well as the differences in the time it takes to RTP and RTSLP. This study highlights that the annual number of UCLR surgeries demonstrates an upward trend. This retrospective analysis also highlights that PP with UCL repairs were able to RTP and RTSLP sooner than PP who underwent UCL reconstructions and UCL reconstructions with augmentation. Furthermore, infielders were able to RTP and RTSLP sooner than catchers as well as outfielders. The results of this study demonstrate that the type of UCL surgery as well as the player’s position does not seem to significantly impact whether or not a player actually returns to playing professional baseball, however it does impact the speed at whichthey are able to return (provided they do return to playing baseball). As such, the results of this study may be used to counsel PP regarding speed at which a return to playing baseball can be expected.

Objectives: The medial ulnar collateral ligament (MUCL) is the primary stabilizer of valgus forces across the elbow. Injury to the MUCL has a large impact on the throwing athlete, particularly in baseball. The incidence of MUCL injury in baseball pitchers is on the rise. Surgical treatment and rehabilitation is evolving to improve outcomes and improve return to sport time frames. The purpose of this study was to highlight the trends in MUCL repair and reconstruction in professional baseball pitchers, describe relevant outcomes such as return to any level of play (RTP) for surgical repair and reconstruction, and distinguish what factors might impact these outcomes. The authors hypothesize that primary and revision MUCL surgery is increasing with revision surgery requiring the greatest time to RTP. Methods: The Major League Baseball (MLB) Health and Injury Tracking System (MLB HITS) database was used to procure data during the targeted study period (2010 – 2023). All professional pitchers who underwent MUCL surgery within the study period were included. Variables analyzed included age, career length, and level of play. Surgical variables included date and type of procedure, RTP status, time required to RTP, return to same level of play (RTSL), career length before and after surgery, number of revision surgeries, and time between surgeries. Successful RTP was designated if a pitcher had returned in at least one professional game after index surgery. Analyses of trends over time were performed. The year 2020 was considered an outlier and omitted from the analysis of trends due to the coronavirus pandemic which limited games played. Results: A total of 2,287 pitchers underwent MUCL surgery during the study period (Table 1). The annual number of MUCL surgeries on all pitchers increased year over year (R 2 = 0.821, p < 0.001), as did the annual number of reconstructions with internal brace (IB) augmentation (R 2 = 0.896, p < 0.001) (Figure 1). The RTP rate (93%) for MLB pitchers was significantly higher compared to the RTSL rate (71%, P < 0.001). This difference was not observed in Minor League Baseball (MiLB) (RTP 76% vs. RTSL 74%, P = 0.142) (Figure 2). The percentage of players who RTP after revision surgery was significantly lower compared to primary surgery (71%vs. 80% respectively, P = 0.020). Mean time to RTP is significantly shorter (470 ± 135 days) compared to the mean time to RTSL (499 ± 153 days, P < 0.001) (Figure 3). The annual number of revision MUCL surgeries on all pitchers increased year over year as well (R 2 = 0.322, p = 0.043). Conclusions: MUCL surgery continues to increase, also leading to increasing numbers of revisions in professional pitchers. Overall, 80% of pitchers were able to RTP at a mean of 470 days (15.5 months), while only 71% were able to RTSL at a mean of 499 days (16.5 months), but this varied based on level of play. Surgical techniques continue to evolve as MUCL repairs and reconstructions with IB augmentation have increased significantly in recent years. This study will help guide athlete expectations and surgeon decision-making.

Background: Spasticity is common in spinal cord injury (SCI) and multiple sclerosis (MS), and it can manifest as repeated, rhythmic muscle contractions called clonus. The spontaneous nature of clonus can disrupt independent performance of activities of daily living and negatively impact overall health and quality of life. Objectives: To quantify biomarkers of clonus and explore management of clonus in individuals with SCI or progressive MS using epidural spinal cord stimulation (ES) or dorsal root stimulation (DRS). Methods: Four male participants were included in this case series study: 3 with SCI and 1 with MS. All participants underwent temporary percutaneous ES lead placement over the dorsolateral thoracolumbar region of the spinal cord. Participants with SCI were also implanted with DRS leads at the L4 dorsal root. Clonus was elicited mechanically at the ankle while recording electromyography of the soleus muscle synchronized to direct spinal cord field potential recordings from ES and DRS percutaneous leads. Results: Clonus was evident as a prominent band (5-8 Hz) in recordings from ES leads, DRS leads, soleus muscle, and accelerometry. In 4 participants, percutaneous spinal stimulation reduced median clonus duration and cycle count. Clonus was immediately suppressed upon activation of spinal cord stimulation, and the suppression persisted even when clonus was reinitiated after turning off the stimulation. Conclusion: The use of objective biomarkers, including spinal cord potentials, to quantify clonus in real time combined with the immediate and reversible effects of stimulation highlight the potential of neuromodulation as a therapeutic tool for managing clonus. These data demonstrate preliminary efficacy of ES and DRS for clonus monitoring and treatment in 4 participants.

ABSTRACT Objectives To characterize practice patterns and outcomes in the management of low‐ and intermediate‐grade salivary gland carcinoma prior to the existence of treatment guidelines. Methods Analysis of a registry of patients who underwent parotid and submandibular gland resections for low‐and intermediate‐grade carcinomas between 2010 and 2019. Results Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial ( n = 384, 53%) or total ( n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was associated with a significant increase in transient facial weakness (72/177 (41%) vs. 82/311 (26%), RR 0.65, 95% CI 0.50–0.84, p < 0.05) and permanent facial nerve weakness (23/176 (13%) vs. 16/301 (5%), RR 0.41, 95% CI 0.22–0.75, p < 0.05) compared to superficial parotidectomy. Adjuvant radiation therapy ( RT ) was delivered to 285 (36%) patients. The proportion of patients receiving adjuvant RT declined significantly over the time period from 2015 to 2019 compared to 2010 to 2014 at 162/504 (32%) and 123/282 (44%), respectively ( RR 0.74, 95% CI 0.61–0.89, p < 0.05). When comparing the time periods from 2015 to 2019 and 2010 to 2014, there was no significant difference in local control rates ( RR 0.52, 95% CI 0.26–1.04, p = 0.06) or regional control rates ( RR 0.75, 95% CI 0.26–2.13, p = 0.58). Conclusions Management of low‐ and intermediate‐grade salivary cancer from 2010 to 2019 was variable, which is expected given the rarity and heterogeneity of the disease and the lack of treatment guidelines prior to 2021. Most patients with parotid malignancies underwent superficial or total parotidectomy. The extent of parotidectomy had an impact on facial nerve function outcomes. Delivery of adjuvant radiation trended down with time. The data presented here will support dissemination of the guidelines and provide data that could inform future trials. Level of Evidence 2b.

Abstract BACKGROUND Tau‐derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid‐beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long‐term anti‐Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them. METHODS A post‐hoc analysis of the DIAN‐TU‐001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab ( n = 50), gantenerumab ( n = 52), or placebo ( n = 40). High‐resolution mass spectrometry quantified CSF tau species over four years. RESULTS Phosphorylated tau (p‐tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab‐mediated Aβ plaque reduction. Nearly a decade later, MTBR‐tau243 and p‐tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression. DISCUSSION Initially changing soluble p‐tau species track Aβ plaque reduction, while ptau205 and MTBR‐243 reflect tau tangle pathology, informing different pathways of therapeutic strategies. Highlights p‐tau217 and p‐tau231 correlate with Aβ‐PET and respond to Aβ‐plaque lowering therapies. Aβ immunotherapy trials support a direct link between p‐tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT‐related biomarkers. Blood‐based p‐tau217 assays may provide a non‐invasive tool to monitor Aβ therapies. MTBR‐tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT‐targeting therapies.

Summary We investigated the outcomes of patients with advanced systemic mastocytosis (AdvSM) undergoing allogeneic haematopoietic cell therapy (alloHCT) in the US. Twenty‐seven adult (median age, 58 years) patients with AdvSM received alloHCT from 2014 to 2021. Most patients were white (93%), male (63%) and had systemic mastocytosis (SM) with associated haematological neoplasm (SM‐AHN, 70%), received peripheral blood grafts (89%) and non‐myeloablative regimens. KIT mutation was detected in 14 of the reported 16 patients (87.5%). Post‐transplantation cyclophosphamide (PTCy) was used in approximately 50% of the cohort. Approximately 1 year after alloHCT, median bone marrow mast cell burden decreased from 15% pre‐alloHCT to 1.5% (range 0–8) at 1 year post‐alloHCT. The median serum tryptase decreased from 55 ng/mL (range 3–400 ng/mL) pre‐alloHCT to 18 ng/mL (range 0–481 ng/mL) at 1 year post‐alloHCT. At 1 year, progression‐free survival (PFS) and overall survival (OS) were 59% (95% confidence interval [CI], 41%–77%) and 74% (95% CI, 56%–89%) respectively. In the subset of patients with SM‐AHN, 1‐year PFS and OS were 74% (52%–91%) and 79% (95% CI, 58%–94%) respectively. The cumulative incidence of relapse/progression for the entire population of patients with SM ( n = 27) was 4% (95% CI, 0–14) at 100 days and 15% (95% CI, 4–31) at 1 year. For the subset of patients with AHN, the cumulative incidence was 11% (95% CI, 1–28) at 100 days and 21% (95% CI, 6–42) at 1 year. Relapse/progression was the cause of death in six of 12 patients (5 died of AHN and 1 died of SM progression). Eighteen and nine patients received a KIT inhibitor before alloHCT and after alloHCT respectively. In addition, six patients received a KIT inhibitor for the treatment of relapse/progression of SM after alloHCT. Although it is difficult to delineate the exact effect of alloHCT and KIT inhibitors because of the size of the study in this era, the use of alloHCT and KIT inhibitors pre‐ and post‐ alloHCT is increasing. In the near future, larger studies are required to provide further insights into this subject.

Objectives Directly compare the brain glucose patterns seen with [F‐18] fluorodeoxyglucose (FDG) positron emission tomography (PET) between 2 genetically determined forms of Alzheimer's disease: Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD). Methods Cross‐sectional analyses of FDG were performed in individuals with DS (n = 76) from the Alzheimer Biomarker Consortium‐Down Syndrome (ABC‐DS), ADAD (n = 297), and neurotypical familial controls (n = 188) from the Dominantly Inherited Alzheimer Network (DIAN). Within‐group linear regression models and generalized additive models were performed for select regional FDG uptake measures (isthmus cingulate and inferior parietal, precuneus, middle temporal gyrus, and precentral gyrus). Age, sex, apolipoprotein (APOE) ε4 carrier status, and cortical amyloid burden were included within these analyses. Results Even 20 years before expected onset of clinical symptoms, FDG uptake was lower for DS compared to neurotypical familial controls ( p < 0.01). ADAD baseline FDG was similar to neurotypical familial controls until 7 years before expected symptom onset. Both symptomatic individuals with DS and ADAD had lower FDG compared to neurotypical familial controls ( p < 0.01). A higher amyloid burden was associated with lower FDG for both genetic forms, with similar rates of decline in FDG uptake for DS and ADAD who were amyloid positive. Interpretation Brain glucose metabolism is substantially lower for people with DS, even in individuals who are cognitively stable. The patterns of FDG decline are distinct in these 2 genetically determined forms of AD. The diagnostic utility of FDG‐PET is specific to the genetic form of AD. ANN NEUROL 2025;98:1237–1248

Background Endovascular thrombectomy (EVT) has transformed acute ischemic stroke (AIS) care, with onset-to-puncture (OTP) time widely recognized as a critical determinant of outcome. However, emerging evidence suggests that in-hospital procedure time (PT)—from arterial puncture to final recanalization—may have an equally or more significant impact. This study examines the relative contribution of PT versus OTP to functional outcomes in patients with AIS undergoing EVT. Methods A retrospective analysis was conducted of 6644 patients with AIS treated at 44 international stroke centers from the Stroke Thrombectomy and Aneurysm Registry (STAR; 2016–2023). Multivariable regression, time-equivalence analysis, and marginal effects modeling were used to assess associations between PT, OTP, and 90-day modified Rankin Scale (mRS) outcomes. Centers were stratified by procedural efficiency and compared using propensity score matching (PSM). Mediation analysis evaluated whether PT accounted for inter-center differences. Results PT and OTP were independently associated with functional outcomes; however, PT had a significantly stronger effect (adjusted OR for mRS 0–2: PT=0.56 vs OTP=0.96 per hour). Each 5 min increase in PT was equivalent to 78–100 min of additional OTP in outcome impact. Centers with faster average PT had higher rates of functional independence (number needed to treat (NNT)=10), fewer complications, and lower symptomatic intracranial hemorrhage rates. PT significantly mediated the relationship between center tier and outcomes (Sobel’s P<0.001). Conclusion While minimizing OTP remains important, PT exerts a greater influence on outcomes after EVT. Procedural efficiency should be emphasized in stroke systems of care and included in center performance metrics to improve patient outcomes.

Abstract Despite homologous recombination (HR) deficiency being an important predictor of survival in high-grade serous ovarian carcinoma (HGSC), its status is rarely considered in large-scale studies of prognostic signatures and biomarkers. We sought to develop a gene expression-based classifier of HR deficient (HRD) HGSCs, suitable for archival FFPE tumor samples, to determine whether established prognostic markers were dependent on HR status. Using 361 HGSCs from The Cancer Genome Atlas (TCGA) where HR status was defined by the genomic gold standard, a HRD score, we trained and tested a ridge penalized logistic regression model. This 218-gene mRNA expression signature was then applied in 6002 HGSCs from the Ovarian Tumor Tissue Analysis (OTTA) consortium to predict the probability of a sample being HRD. In this large cohort of FFPE samples, we sought to understand the relationship between HR and overall survival. Applying Kaplan-Meier analyses and multivariate Cox proportional hazard regression modelling, adjusting for age and stratified by stage and study, we examined the relationship between HR status and the PrOTYPE subtype, SPOT prognostic score and other known prognostic markers in HGSC. Our machine learning model was 84% accurate in a held-out subset of the TCGA (n=73). Of the 6002 OTTA HGSCs, 40.4% were predicted to be HRD. These cases were significantly younger, were enriched for early stage (FIGO I/II) and had improved outcomes when compared to HR proficient (HRP) cases (hazard ratio [HZR]=0.71, 95% confidence interval [CI]=0.66-0.76, p&lt;2x10-16). A linear increase in survival time was observed as the probability of a sample being HRD increased. HGSCs with &gt;75% likelihood of being HRD had a median 5-year survival of 49.3% (95%CI=46.2-52.6%) which was a 17.7% increase from those with &lt;25% likelihood. Both PrOTYPE and SPOT were significantly associated with survival, independent of HR status (p&lt;2x10-16 and p&lt;2x10-16 respectively). Notably the probability of being HRD was negatively correlated with an unfavorable SPOT score (R=-0.32, p&lt;2x10-16), suggesting that SPOT partially captures the survival advantage of HR deficiency. Several individual biomarkers, assessed in 1248 to 2858 cases, showed HR dependent survival associations. HRD HGSCs with high GMNN expression had significantly improved, long-term outcomes (4-10years, HZR=0.39, 95%CI=0.20-0.78, p=0.01), and may be a marker of exceptional survival, while AR negative HRD cases had poorer outcomes, earlier in disease progression (0-4years, HZR=1.43, 95%CI=1.03-1.98, p=0.03). Significantly poorer prognoses were observed in HRP cases expressing PTEN (HZR=1.39, 95%CI=1.04-1.87, p=0.03), and in HRD cases with high expression of MyD88 (HZR=1.21, 95%CI=1.01-1.45, p=0.04). RB1 and FOXJ1 protein expression, and CD8+ T cell abundance were prognostic irrespective of HR status. Our study contributes to understanding the association between HR and HGSC survival in a statistically powered cohort and demonstrates heterogeneity in outcomes through clinically relevant prognostic signatures and biomarkers. Citation Format: Ashley L. Weir, Derek Chiu, Aline Talhouk, Mike S. Anglesio, Dale W. Garsed, Anna DeFazio, Holly H. Harris, Joellen M. Schildkraut, Andrew Berchuck, Ellen L. Goode, Paul D.P. Pharoah, David Huntsman, David Bowtell, Jen A. Doherty, Nadia M. Davidson, Martin Köbel, Susan J. Ramus. Homologous recombination DNA repair dependent survival associations in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis consortium study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B046.