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OBJECTIVE This study examined the extent to which preoperative depression predicts dysphagia after cervical spine surgery. METHODS A prospectively collected multi-institutional quality registry was retrospectively reviewed. Patients undergoing cervical surgery were categorized based on preoperative depression, and correlations with pre- and postoperative Eating Assessment Tool-10 (EAT-10) dysphagia questionnaire scores were assessed. Mixed-effects logistic regressions were performed to assess the impact of preoperative depression on the incidence of dysphagia. RESULTS Of 2002 patients meeting inclusion criteria, 524 (26%) reported having preoperative depression. Depression was associated with a higher incidence of dysphagia at baseline (25% vs 12%, p < 0.001) and at 1 (62% vs 54%, p = 0.038), 3 (36% vs 26%, p < 0.001), and 12 months (36% vs 22%, p < 0.001) postoperatively. Including baseline dysphagia as a fixed effect, multivariable analysis revealed that depression is not a significant independent predictor of postoperative dysphagia at 1 (OR 1.14, p = 0.5), 3 (OR 1.09, p = 0.6), or 12 months (OR 1.27, p = 0.2). Patients with depression and no baseline dysphagia (395 of 524) were significantly more likely to report new dysphagia at 12 months (26% vs 18%, p = 0.006), but not at 1 (53% vs 52%, p = 0.7) or 3 months (28% vs 22%, p = 0.06). The average change in EAT-10 scores between baseline and 12 months was significantly worse in patients with preoperative depression and no baseline dysphagia (2.552 [SD 5.041] vs 1.634 [SD 4.095], p < 0.001). Post hoc multivariable analyses excluding those with baseline dysphagia did not significantly affect the results. CONCLUSIONS Although patients with preoperative depression report dysphagia more often at baseline and at 1, 3, and 12 months after cervical surgery, preoperative depression is not an independent predictor of postoperative dysphagia. Preoperative depression may be valuable to consider as a risk factor for developing dysphagia after cervical surgery, but the heightened dysphagia risk in patients with depression may be attributed to secondary factors associated with depression such as comorbid conditions.

Cardiovascular morbidity and mortality rise precipitously during the 6th–9th decades of life, identifying aging as a critical risk factor. Simultaneously, older individuals are susceptible to severe viral infection, raising the question whether shared mechanisms exist that predispose to both cardiovascular disease (CVD) and failing anti-viral immunity. The aging process causes steady decline in immune fitness (immune aging), which undermines the ability to generate protective anti-viral immune responses. Paradoxically, the aging immune system supports unopposed inflammatory pathways (inflammaging), which exacerbates tissue inflammation in CVD, specifically atherosclerosis. Here, we review the current evidence of how innate and adaptive immune aging promotes tissue-destructive inflammation in atherosclerosis while failing to fight viral infections. Further, we consider how these two disease processes mutually influence each other. We propose that mounting an effective anti-viral response induces off-target bystander activation and exhausts immune cells, ultimately exacerbating CVD. Additionally, we explore how atherosclerotic CVD impacts innate immunity through epigenetic modification of hematopoietic precursors and metabolically conditioning immune cells, leading to a dysfunctional immune system that accelerates plaque inflammation while simultaneously impairing host defense.

Background: Injury to the medial ulnar collateral ligament (MUCL) is a common setback for throwing athletes, often requiring reconstruction with 12 to 18 months of rehabilitation. The authors previously described a more anatomic technique with improved mechanical strength as compared with the docking technique, which may allow for an accelerated return to sport. Purpose: To evaluate return-to-sport rates, time to return to sport, and the effect on the functional performance of amateur and professional throwing athletes who underwent anatomic MUCL reconstruction with suture tape augmentation. Study Design: Case series; Level of evidence, 4. Methods: A retrospective case series was performed including baseball players who underwent anatomic MUCL reconstruction with suture tape augmentation by a single surgeon from 2018 to 2022. Inclusion criteria consisted of a minimum 2-year follow-up, participation in baseball, and utilization of autograft (palmaris longus or gracilis). Patients who underwent previous MUCL reconstruction were excluded from the study. All patients initially followed an accelerated rehabilitation protocol. Outcome measures were collected, including Kerlan-Jobe Orthopaedic Clinic (KJOC), Single Assessment Numeric Evaluation (SANE), and Conway-Jobe scores, as well as throwing metrics such as ball velocity and spin rate. Results: Thirty-four baseball players (mean ± SD age, 21 ± 3 years) underwent primary MUCL reconstruction. Time of final follow-up was 36.1 ± 10.3 months. Of these, 16 were professional athletes and 18 were amateur. All throwers returned to live gameplay at a mean 10.1 ± 2.0 months after reconstruction (professional, 10.6 ± 2.3; amateur, 9.7 ± 1.8). Furthermore, 97% (94% professional, 100% amateur) advanced through the accelerated postoperative protocol without issues, and 91% (88% professional, 94% amateur) returned to the same role and 85% (75% professional, 94% amateur) to the same level of play. Professional postinjury KJOC scores improved from 42.6 ± 16 to 87.5 ± 8.3 and SANE scores from 25.0 ± 11.2 to 95.6 ± 4.2. Amateur postinjury KJOC scores improved from 35.6 ± 10.7 to 90.9 ± 8.6 and SANE scores from 57.5 ± 16.9 to 95.2 ± 7.2. No significant difference was identified in preinjury versus postreconstruction throwing velocity, ball spin rate, or horizontal/vertical ball movement. The overall failure rate was 2.9%, with 1 professional pitcher requiring revision for graft rupture at 3 years postoperatively. Conclusion: Anatomic reconstruction of the MUCL with suture tape is a viable option for MUCL injuries, allowing an expedited return to sport at 10.1 ± 2.0 months (professional, 10.6 ± 2.3; amateur, 9.7 ± 1.8) in baseball players, with a low failure rate.

Background: Anterior vertebral body tethering (AVBT) is a promising fusionless alternative for treating idiopathic scoliosis; however, limited data exist on the learning curve for this procedure. Previous studies are limited by single-center and short-term complication data. This multicenter study assesses the learning curve by evaluating improvements in operative characteristics over time and radiographic measurements up to 2 years postoperatively. Methods: As recorded from a multicenter registry, surgeons with ≥10 index AVBT procedures for patients with idiopathic scoliosis aged 16 years and below were included. Relationships between case number and multiple surgical variables were determined using Pearson correlation and linear regression testing. For identification of an inflection point, consecutive cases were plotted against operative time per level and fitted with a locally weighted scatterplot smoothing curve. Independent samples t test and χ 2 test were used to compare outcomes between cases before and after the inflection point. Outcomes of interest included demographic, surgical, and radiographic information at the baseline, immediate postoperative, and 2-year timepointswhere available. Results: Eight surgeons and 325 index AVBT patients met the inclusion criteria. Inverse relationships were identified between case number and estimated blood loss, operative time, anesthesia time, and fluoroscopic time per level ( P < 0.005). The inflection point was identified at 15 cases. Operative time, anesthesia time, and fluoroscopy time per level were greater in the first 15 cases compared with those after ( P < 0.05). There were no significant differences in demographic variables, intraoperative complications, or length of stay between the early and late cases. Greater correction in the major coronal curve, minor coronal curve, and coronal balance occurred in the cases performed after the inflection point ( P < 0.05). Conclusions: AVBT is a safe alternative to posterior spinal fusion and demonstrates a predictable improvement in surgical performance over time. Large improvements can be expected during the first 15 AVBT cases performed with minimal differences in complications. Level of Evidence: Level III.

ABSTRACT Background Given the Centers for Medicare and Medicaid Services' coverage of screening CT colonography (CTC) beginning in January 2025, we evaluated the cost‐effectiveness of CTC for colorectal cancer (CRC) screening by race (Black and White) and gender, considering real‐world screening adherence. Methods A microsimulation model compared CRC screening strategies in average‐risk adults by race and gender, incorporating 2010–2019 U.S. data on disease progression and real‐world screening adherence for colonoscopy and fecal immunochemical test (FIT). Five strategies were compared: (1) status quo (choice between colonoscopy and FIT); (2) CTC every 5 years; (3) colonoscopy every 10 years; (4) annual FIT; and (5) multitarget stool DNA test every 3 years, plus no screening. Lifetime costs, quality‐adjusted life years gained (QALYG), and incremental cost‐effectiveness ratios were projected. A willingness‐to‐pay threshold of $100,000/QALYG was used. Results Under the status quo, Black adults showed higher CRC cases and greater utilization for FIT over colonoscopy than White adults. Compared to the status quo, the CTC strategy yielded more QALYG and fewer CRC cases among Black adults, but fewer QALYG and more CRC cases among White adults. Both status quo and CTC strategies outperformed other strategies across races. The CTC strategy was the dominant strategy for Black adults. For White adults, the status quo was cost‐effective with incremental cost‐effectiveness ratios of $34,998–$73,428/QALYG, while the CTC strategy was cost saving compared to no screening. Conclusions CTC could be cost‐effective for CRC screening in Black adults under real‐world screening adherence, supporting Medicare coverage to address specific population needs and structural barriers to screening.

Abstract Introduction/Objective Mutations in KIT and PDGFRA drive the majority of gastrointestinal stromal tumors (GIST) and inform targeted therapy selection. While single-driver mutations are typical, a subset of cases harbors multiple KIT mutations, complicating clinical interpretation. This study investigated the frequency, distribution, and inferred hierarchy of primary and secondary KIT mutations using DNA-based sequencing in a large GIST cohort. Methods/Case Report We retrospectively reviewed 579 GIST cases that underwent DNA-based next-generation sequencing using a custom panel targeting all coding exons of KIT and PDGFRA. Tumor-rich formalin-fixed paraffin-embedded (FFPE) tissue was required. In double-mutant cases, the mutation with higher variant allele frequency (VAF) was presumed to be primary. Results Mutations in KIT or PDGFRA were detected in 482/579 cases (83.2%). Among KIT-mutant cases, 28 had two mutations and one had three. Secondary mutations frequently occurred in exons 13, 14, and 17 and were significantly more common in non-gastric tumors (p &lt; 0.0001). Primary mutations most often involved exon 11. Conclusion VAF analysis enabled classification of mutation hierarchy in cases with multiple KIT mutations. The distinct anatomical and exon-specific distribution of primary vs. secondary mutations highlights their potential therapeutic implications and warrants further study.

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented. Purpose: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair. Study Design: Prospective cohort study; Level of evidence, 2. Methods: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 were selected. Six-year follow-up was obtained to determine whether any subsequent surgery had occurred since their initial revision ACLR. If so, operative reports were obtained, whenever possible, to verify pathological condition and treatment. Results: In total, 221 patients from 1234 revision ACLRs underwent concurrent primary meniscal repairs (18% of the cohort). There were 238 repairs performed: 173 medial and 65 lateral. The majority of these repairs (n = 181; 76%) were performed with an all-inside technique. Six-year surgical follow-up was obtained in 77% (171/221) of the cohort, or 189 of 238 (79%) of the repairs (136 medial, 53 lateral). The meniscal repair failure rate, defined as reoperation, was 16% (31/189) at 6 years. Of the 31 failures, 28 were medial (24 all-inside, 4 inside-out; 28/136 = 20.6% failure rate) and 3 were lateral (2 all-inside, 1 inside-out; 3/53 = 5.7% failure rate). Three medial failures were treated in conjunction with a subsequent repeat revision ACLR. Medial tears underwent reoperation for failure at a significantly higher rate than lateral tears (20.6% vs 5.7%; P = .01) and had a significantly shorter survival time compared with lateral tears ( P = .02). No difference was found between the failure and nonfailure groups when it came to tear type, tear length, repair technique utilized, suture/implant type, or number of sutures used between the 2 groups. Conclusion: Meniscal repair in the revision ACLR setting has a 16% failure rate at 6 years. Failure rates for medial tears (20.6%) were found to be higher than that for lateral tears (5.7%), which aligns with previous studies in both the revision and primary ACLR setting.

Abstract Glioblastoma is an aggressive brain cancer with poor prognosis. Recent evidence implicates metabolic reprogramming, including the hexosamine biosynthetic pathway (HBP) and pentose phosphate pathway (PPP), as critical for tumor survival, therapy resistance, and progression. HBP inhibition with a proprietary small molecule (G2Bz) reduced stemness and migration and increased apoptosis of GBM in vitro. HBP inhibition was concomitant with an accumulation of metabolites in the Pentose Phosphate Pathway (PPP). Therefore, we further inhibited HBP with G2Bz and/or PPP with 6-aminonicotinamide (6-AN) in primary patient-derived GBM lines and evaluated additive or synergistic effects. Ultrastructural and functional changes were examined by electron microscopy (EM), high content imaging of endoplasmic reticulum (ER) and lipid droplets (LD), extracellular-flux analysis, and lipid profiling. Synergism was validated in an orthotopic model receiving lipoparticle-encapsulated G2Bz via intranasal delivery and/or intraperitoneal 6-AN; tumor burden was monitored via bioluminescence. Dual inhibition of HBP/PPP revealed additive or synergistic anti-proliferative effect. EM displayed severe ultrastructural cell damage with mitochondrial disorganization, ER dilation, and cytoskeletal remodeling. These changes coincided with increased ROS generation and reduced spare respiratory capacity suggesting higher sensitivity and lower ability to fight stress. Reduced ER–mitochondria contacts accompanied by increased expression of BiP and ER expansion suggest an unfolded protein response. Loss of LDs were associated with downregulation of lipid biosynthesis regulator SREBF1 and an increase in free fatty acids with a rise in lipid peroxidation. Reduced mitochondria–LD contacts correlate with lower endogenous fatty acid oxidation and a shift to exogenous fatty acid utilization. Dual inhibition in-vivo, suppressed tumor growth compared to control. These findings support that dual inhibition of HBP/PPP synergistically disrupts tumor metabolism, promoting organelle disorganization and lipid remodeling and highlight metabolic co-targeting as a strategy to impair GBM metabolism.

Abstract BACKGROUND Understanding long-term sequelae of cancer care is critical. Cognitive impairment is a common and disabling survivorship issue. Because sex influences tumor biology, therapy exposure, and dementia risk, we examined whether cancer care for a prior malignancy alters late-life cognitive outcomes differently in males and females. METHODS We assessed adults ≥50 years, cognitively normal at study entry, from a longitudinal, population-based cohort (Mayo Clinic Study of Aging). Participants were linked to our institutional cancer registry (excluding non-melanoma skin cancers). Mild cognitive impairment (MCI) and dementia were adjudicated by consensus. We fitted multivariable Cox proportional-hazards models to estimate how prevalent cancer diagnosis influenced the risk of developing MCI/dementia. Sex-specific effects were determined by incorporating a cancer×sex interaction term and by generating separate hazard ratios. Analyses were controlled for age, APOE4 status, education, and presence of vascular/metabolic conditions. RESULTS 5793 MCSA participants (female: 49.4%, APOE4 positive: 27.5%) were included in the study, with a mean age of 73 years at study entry. Incident MCI was recorded in 866 participants, and 737 were diagnosed with incident dementia. About 20% (n=1176) of the cohort had a cancer diagnosis, most commonly prostate (n=423) and breast (n=277). There was no independent relationship between history of cancer and risk for MCI or dementia. We found that males with cancer had an increased risk for MCI (HR 1.28, 95% CI 1.04-1.57, p=0.003) and dementia (HR 1.29, 95% CI 1.04-1.6, p=0.053). Conversely, females with cancer had a lower risk for MCI (HR 0.79, 95% CI 0.61-1.01, p=0.063), although this was not statistically significant. CONCLUSIONS Our data suggests male cancer survivors may be more susceptible to cognitive impairment, independent of age, APOE4 status, education, and vascular/metabolic burden. Elucidating the hormonal, treatment-related, and systemic pathways driving this should be a priority for future mechanistic studies.