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OBJECTIVE Cervical spondylotic myelopathy (CSM) is often accompanied by neck pain, which, along with more recognized neurological deficits like motor and sensory changes, significantly impacts patients’ quality of life. The authors examined whether age influences improvements in neck disability and related quality-of-life measures after surgery for CSM. Using the Neck Disability Index (NDI) as the primary outcome, they compared long-term outcomes at 24 months among patients aged ≥ 65, ≥75, and < 65 years, exploring the effects of surgical intervention on both pain-related disability and functional recovery in older adults. METHODS Using the Quality Outcomes Database, the authors conducted a detailed propensity score–matched analysis on cohorts aged ≥ 65 and ≥ 75 years compared with a < 65-year-old cohort while controlling for baseline NDI scores, other demographic variables, health status, underlying pathology, number of levels, indication for surgery, surgical approach, and type of surgery. Differences in NDI total and subdomain scores at 24 months postoperatively were the primary measures of improvement. Age-related variability in NDI differential was assessed. EQ-5D and calculated SF-6D were secondary measures. RESULTS Of the 1141 patients in the cohort (January 2016 to December 2018), 687 patients were < 65 years, 325 were 65 to < 75 years, and 129 were ≥ 75 years of age. After propensity score matching, 197 patients each were well matched in the ≥ 65-year (mean 71.4 years) and < 65-year (mean 55.3 years) cohorts; similarly, 57 patients each were matched in the ≥ 75-year (mean 78.3 years) and < 65-year (mean 55.8 years) cohorts. Improvements in NDI scores and subdomain scores, EQ-5D, and calculated SF-6D were consistent at 3, 12, and 24 months postoperatively across all cohorts. At 24 months, patients ≥ 65 years showed NDI score improvements (−14.7 ± 22.3) similar to those < 65 years (−13.0 ± 21.3, p = 0.454), and patients ≥ 75 years demonstrated NDI improvements (−15.0 ± 19.7) comparable to those < 65 years (−17.6 ± 20.4, p = 0.499). A sensitivity analysis for linear relationship found that NDI improvement was statistically greater in older patients (7.5 points every 30 years, p < 0.0001), but this difference was below the minimal clinically important difference. Other clinical outcomes were similar between cohorts. CONCLUSIONS Surgical intervention for CSM yields substantial and similar improvements in NDI scores and other metrics among various age groups, including those aged at least 65 and 75 years. These results highlight the effectiveness of surgery across a broad patient demographic, underscoring its value in treating CSM irrespective of age.

ImportanceThe De-escalated Adjuvant Radiation Therapy (DART) phase 3 randomized clinical trial (RCT) showed that in patients with human papillomavirus (HPV)−associated oropharyngeal squamous cell carcinoma, postoperative minimal residual disease (MRD), detected through circulating tumor HPV DNA (ctHPVDNA), was associated with a higher risk of disease progression. When considered along with pathologic factors, postoperative ctHPVDNA assessment may improve patient selection for adjuvant treatment de-escalation; however, more data are needed to demonstrate how it may be used in personalizing treatment intensity.ObjectiveTo determine the association of postoperative MRD status with progression-free survival (PFS) after surgery for HPV-associated oropharyngeal squamous cell carcinoma.Design, Setting, and ParticipantsThis was a secondary analysis of the DART RCT, which was conducted from October 2016 to August 2020 in multiple sites in the US. Participants from the de-escalated adjuvant radiation therapy group and the standard of care group with available blood specimen data were included. Reports from 3-month posttreatment surveillance visits were used to assess associations and outcomes. Data analyses were performed from March 2023 to March of 2025.InterventionsThe DART group received 30 to 36 Gy of radiation therapy in 1.5 to 1.8 Gy twice daily, plus docetaxel, 15 mg/m2, on days 1 and 8. The standard of care group received 60 Gy with or without weekly cisplatin, 40 mg/m2.Main Outcome and MeasurePFS.ResultsThe analysis included 140 patients (mean [SD] age, 59.1 [8.4] years; 12 [8.6%] females and 128 [91.4%] males; 97 [69.3%] with no smoking history); characteristics were similar to the overall DART RCT population. Of these, 17 patients (12.1%) had postoperative MRD (13 of 96 [13.5%] receiving DART and 4 of 44 [9.1%] receiving standard of care). For all patients, postoperative MRD positivity was strongly associated with worsened PFS at 24 months (MRD positivity, 69.5%; MRD negativity, 95.9%; hazard ratio [HR], 0.19; 95% CI, 0.06-0.59). MRD positivity was associated with PFS when evaluating only those patients in the DART group, where 24-month PFS was 68.4% compared to 92.6% for MRD-negative patients (HR, 0.28; 95% CI, 0.08-0.93). Three months after completion of all treatment, 8 of 117 patients (6.8%) had detectable ctHPVDNA, whereas 109 of 117 (93.2%) did not, and detection was highly associated with PFS (HR, 20.48; 95% CI, 6.91-60.67).Conclusions and RelevanceThis secondary analysis of the DART RCT found that patients with detectable ctHPVDNA after surgery had a higher risk of disease progression. When added to the pathologic factors considered, ctHPVDNA assessment may improve selection of patients for treatment de-escalation. In addition, the 3-month posttreatment time point, early in surveillance, may identify a sizable portion of patients with progression and may guide intervention and surveillance after surgery for HPV-associated oropharyngeal squamous cell carcinoma.Trial RegistrationClinicalTrials.gov Identifier: NCT02908477

Background Right ventricular (RV) maladaptation to elevated pulmonary afterload is the primary determinant of outcomes in pulmonary artery (PA) hypertension; however, the pathobiological mechanisms underlying RV decompensation remain poorly understood. Methods We performed global untargeted metabolomics on plasma from 55 patients who underwent gold‐standard RV‐PA coupling measurements using multibeat pressure volume loop assessment in a single‐center cohort and from 1027 patients with coupling surrogate measurements in a larger multicenter cohort, the PVDOMICS (Pulmonary Vascular Disease Phenomics) study. Age and sex‐adjusted linear regression was performed to identify associations between metabolites and coupling metrics. Additionally, we performed a metabolic flux analysis using gene expression data from RV tissue in an independent cohort of 32 patients. Partial least squares–discriminant analysis was used to identify metabolites and reactions characteristic of the decompensated RV. Results RV‐PA coupling was negatively associated with tricarboxylic acid (TCA) cycle intermediate levels. Specifically, plasma α‐ketoglutarate and fumarate were significantly associated with all coupling metrics in both cohorts. Metabolic flux analysis indicated that decompensated RVs exhibited aberrant TCA cycle activity, including reduced acetyl coenzyme A entry and increased lactate elimination, suggesting a shift from the TCA cycle toward glycolysis at the RV tissue level. Conclusions We identify an association between circulating TCA cycle intermediate levels and RV‐PA uncoupling in 2 independent cohorts, and dysregulated TCA cycle metabolism in decompensated PA hypertension RVs, suggesting that aberrant TCA cycle metabolism could represent a hallmark of RV maladaptation in PA hypertension. Further study of this pathway is warranted to develop novel biomarkers of RV function or RV‐targeted therapies.

ABSTRACTObjectiveThere is currently not a marker of disease severity in idiopathic subglottic stenosis (iSGS). Our objective was to characterize iSGS patients' disease severity using endoscopic surgery rates.MethodsThis was a two‐center retrospective analysis of iSGS patients with a minimum of 4 years of follow up following an initial endoscopic procedure (laser wedge excision (LWE) or endoscopic dilation (ED)). Disease severity was classified into Groups A–C, based on whether patients had fewer (Group A), the same number (Group B), or more surgeries (Group C) in years 3–5 compared to years 1 and 2. Disease severity proportions were compared across institutions using chi‐square analysis. Nonparametric testing compared clinical characteristics such as age, BMI, and GERD across severity groups.ResultsThere were 104 patients from institution 1 and 53 patients from institution 2 that were all female and predominantly Caucasian. Both institutions had clinically and statistically similar proportions of patients in Group A (64% vs. 62%), Group B (20% vs. 19%), and Group C (16% vs. 19%) disease (p > 0.05). No clinical characteristic (e.g., age, sex, race, BMI, GERD) was associated with disease severity.ConclusionAcross tertiary care institutions there is a consistent proportion of iSGS patients who either demonstrate nonrecurrent/decelerating (Group A), stable but persistent (Group B), or rapidly recurring disease (Group C). Two‐year surgery rates appear to be an important timepoint for providing expectations to patients on the likelihood of possessing severe disease.Level of Evidence4

AbstractObjectiveLow‐grade parotid malignancies have high overall survival rates; however, controversy remains about the appropriate extent of surgery. We aim to explore the trends in the extent of parotidectomy performed over time in low‐grade parotid malignancies in the United States, with a hypothesis that there has been a trend towards less aggressive surgery.Study DesignRetrospective cohort study of all low‐grade (grade I) acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC) in the Surveillance, Epidemiology, and End Results (SEER) from 2004 to 2020.SettingGeographic areas served by SEER.MethodsTrends were assessed using Cochran‐Armitage tests and logistic regression; Kaplan‐Meier survival curves were used to analyze overall and cancer‐specific survival, and chi‐square tests were used to analyze patient characteristics.ResultsIn total, 1288 patients were identified (916 MEC; 372 ACC). Most patients (n = 772, 60%) were non‐Hispanic white, with an average age of 50.6 years and had a slight female predominance (1.58:1). Most of the cohort presented with tumor stage T1 or T2 (84%), N0 (90.1%), and M0 (96.9%). Treatment with total parotidectomy decreased significantly (34.6 vs 17.7%, P = .02) whereas sacrificing the facial nerve (FN) slightly decreased (20 vs 15.7%, P = .1). A significant increase in N0 patients (71%‐94%, P < .0001) was observed, whereas T staging remained stable (61%‐64%, P = .3). Overall, both ACC and MEC had excellent cancer‐specific survival.ConclusionOver the last 17 years, there has been a significant de‐escalation in the extent of parotidectomy for low‐grade parotid malignancy in the United States.

BACKGROUND AND OBJECTIVES: There has been limited assessment between anterior cervical diskectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) on patient-reported outcome measures (PROMs) in the treatment of cervical spondylotic myelopathy. We sought to compare PROMs from two-level ACDF with single-level ACCF procedures. We evaluate these results in the context of minimum clinically important difference (MCID) thresholds, which have not been performed previously. METHODS: This retrospective analysis of prospectively collected data from the Quality Outcomes Database Spine Collaborative Research Study Group compared two-level ACDF and single-level ACCF at 3-, 12-, and 24 months postoperatively. PROMs included arm pain Numeric Rating Scale, neck pain Numeric Rating Scale, Neck Disability Index, and North American Spine Society Patient Satisfaction Index. Multivariate logistic regression was used to determine differences in perioperative outcomes, as well as the impact of two-level ACDF vs one-level ACCF on PROMs. MCID thresholds were based off previously established limits. RESULTS: Three hundred and thirty patients were included (236 ACDF, 94 ACCF), and the follow-up rate was 82% at 2 years. There was a significantly higher baseline age, American Society of Anesthesiologists grade, proportion of diabetes, osteoarthritis, ambulation dependence, and myelopathy severity in the ACCF cohort. On multivariable analysis, the ACCF group had greater average length of stay and estimated blood loss. There were no significant differences between reoperation rates or nonroutine discharge. There were similar rates of MCID achievement for PROMs at all time points. CONCLUSION: This study suggests that both ACDF and ACCF procedures for cervical spondylotic myelopathy are able to achieve similar, clinically meaningful improvements in PROMs by 2 years. Patients undergoing single-level ACCF have more estimated blood loss and longer length of stay, as well as worse baseline myelopathy. Both procedures have efficacious, durable outcomes. It is reasonable that other factors, such as radiographic characteristics and patient symptoms, may influence patient selection for ACDF vs ACCF.

Aims To determine the associations between measures of oestrogen exposure and Fuchs endothelial corneal dystrophy (FECD) severity. Methods Clinic-based cross-sectional study of 32 postmenopausal women and 11 men with mild or severe FECD, age>55 years. Participants completed questionnaires for data on demographics, anthropometric factors, medical history and potential risk factors for FECD. Women completed an additional reproductive history questionnaire used to calculate the months of lifetime oestrogen exposure. Slit-lamp biomicroscopy, specular microscopy, corneal Scheimpflug tomography and laboratory testing ( TCF4 repeat expansion quantification, total estradiol, free estradiol, sex hormone binding globulin (SHBG), calcaneal bone density) were performed. Logistic regression models were developed to predict FECD severity based on three-way interactions of each oestrogen exposure measure, sex and TCF4 genotype. Results 43 patients were enrolled in the study (mild FECD: 17 women, 3 men; severe FECD: 15 women, 8 men). Serum-free estradiol was higher in the severe compared with mild FECD group (0.21±0.2 vs 0.09±0.1 pg/mL; p=0.046). When stratified by sex, men showed no significant associations between oestrogen measures and FECD severity. However, in women, the odds of severe FECD were increased with more months of lifetime oestrogen exposure (all women; log OR (95% credible interval): 1.3 (0.14 to 4.3)), higher concentrations of free estradiol (all women; 2.1 (0.0049 to 10)), greater % free estradiol (only women without TCF4 repeat expansion; 1.3 (0.16 to 3.8)) and higher concentrations of SHBG (only women with TCF4 repeat expansion; 2.2 (0.45 to 9.1)). Conclusions While the application of these data is constrained by the limited number of participants, a clinic-based sample, small number of men compared with women and single-point measures of serum hormone measures, these data suggest that FECD severity is associated with higher oestrogen exposures in women but not men and may be dependent on TCF4 repeat expansion status.

ABSTRACT Objective There is limited consensus on endoscopic skull base surgery (ESBS) reconstruction principles. This study aims to generate comprehensive themes regarding ESBS reconstruction by pooling the experiences of ESBS experts, with comparison to a literature review of current published evidence. Methods Structured qualitative interviews of ESBS experts regarding postoperative management and reconstruction of various defect locations were conducted. Results A total of 68 experts comprising 40 academic teams across 13 countries with an average of 18 years of ESBS experience were included. We propose 10 stepwise algorithms for common skull base reconstruction scenarios based on these expert interviews. When available, the nasoseptal flap is used for all high_flow cerebrospinal leak defects. Multilayered reconstruction is favored at all anatomical subsites with increasing number of layers for increasing defect size and complexity. Heterogeneity exists in terms of inlay technique and materials, free grafting versus various pedicled flap options for low‐flow defects or in the absence of a nasal septum, nasal packing, tissue sealant, lumbar drain use, and postoperative management. Commonalities and discrepancies between experts were summarized. Conclusion Skull base reconstruction and post‐ESBS management is highly complex with a wide variety of practice patterns and expert strategies. Further research of higher quality evidence is warranted to identify optimal management patterns, though the current work aims to inform surgeons on these controversial areas by drawing from numerous experiences.

Purpose: To develop and validate an explainable machine learning (ML) tool to help clinicians predict the risk of propofol-associated hypertriglyceridemia in critically ill patients receiving propofol sedation. Methods: Patients from 11 intensive care units (ICUs) across five Mayo Clinic hospitals were included if they met the following criteria: a) ≥ 18 years of age, b) received propofol infusion while on invasive mechanical ventilation for ≥24 h, and c) had a triglyceride level measured. The primary outcome was hypertriglyceridemia (triglyceride >400 mg/dL) onset within 10 days of propofol initiation. Both COVID-inclusive and COVID-independent modeling pipelines were developed to ensure applicability post-pandemic. Decision thresholds were chosen to maintain model sensitivity >80%. Nested leave-one-site-out cross-validation (LOSO-CV) was used to externally evaluate pipeline performance. Model explainability was assessed using permutation importance and SHapley Additive exPlanations (SHAP). Results: Among 3922 included patients, 769 (19.6%) developed propofol-associated hypertriglyceridemia, and 879 (22.4%) had COVID-19 at ICU admission. During nested LOSO-CV, the COVID-inclusive pipeline achieved an average AUC-ROC of 0.71 (95% confidence interval [CI] 0.70–0.72), while the COVID-independent pipeline achieved an average AUC-ROC of 0.69 (95% CI 0.68–0.70). Age, initial propofol dose, and BMI were the top three most important features in both models. Conclusion: We developed an explainable ML-based tool with acceptable predictive performance for assessing the risk of propofol-associated hypertriglyceridemia in ICU patients. This tool can aid clinicians in identifying at-risk patients to guide triglyceride monitoring and optimize sedative selection.

Background: Malignant mesenchymal tumors involving the parotid gland are uncommon, characteristically aggressive, and little is known with few reports documented. Study Design: Retrospective case series. Setting: Single institution tertiary care center, 2010 to 2022. Method: Patients were identified from an institutional parotid tumor database. Patient history, demographics, pathologic diagnosis, treatment, and follow up were documented. Results: Eight patients were identified, 3 were males. The average age was 61 years old, and the most common tumors identified were pleomorphic sarcomas (3 patients). Presenting symptoms included: preauricular/cheek mass in 7 patients, facial pain (4), otalgia (4), aural fullness (3), and numbness (1). All patients received a parotidectomy, and 4 patients received adjuvant therapy of either radiation or chemoradiation. Post-operatively, there were 3 cases of distant recurrence, 2 cases of regional recurrence, and 1 case of local recurrence. There were 2 reports of death. Conclusion: Malignant mesenchymal tumors of the parotid are rare, represent varied histologies. Due to their aggressive nature, surgical resection with radiation and close follow-up may be an appropriate treatment regimen in controlling the disease.