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OBJECTIVE Chronic spinal degenerative diseases have been associated with reduced quality of life and dependency on others for personal needs and care. The change between preoperative and postoperative care dependency has yet to be explored in patients with cervical spondylotic myelopathy (CSM). In this retrospective study of a prospectively collected database, the authors evaluated the return to independence in performing self-care following surgical intervention for CSM. METHODS The CSM dataset of the Quality Outcomes Database (QOD) Spine CORe study group was queried. Care dependency was assessed using the personal care component of the Neck Disability Index (NDI) questionnaire, having an ordinal scale from 0 to 5, with 5 representing the inability to independently perform activities of daily living. Numeric rating scale (NRS) scores for arm pain and neck pain were recorded at a 24-months postoperative follow-up. Multivariable logistic regression analyses were performed to identify baseline risk factors for an inability to care for oneself and the symptoms leading to care dependency at 24 months postoperatively. Satisfaction with surgery was measured using the 4-point North American Spine Society (NASS) index. RESULTS Of the 1137 patients with CSM and baseline personal care scores, 167 (14.7%) were care dependent at baseline (NDI personal care score ≥ 3). Patients with care dependency at baseline were predominantly Medicare beneficiaries and had a high school or lower level of education. Long-term follow-up rates for this study were 82.5% for NDI, 84.8% for patient satisfaction with surgery, 82.4% for NRS arm pain, and 81.8% for NRS neck pain. Of the care-dependent patients, more than 80% became independently able to care for themselves by the 24-month follow-up. Patients with resolved care dependency at 24 months had demonstrated lower baseline NDI and NRS neck pain scores (p < 0.01 for both). Neck pain was significantly associated with care dependency at 24 months’ follow-up (p < 0.01). Patients who reported improvement in their ability to care for themselves noted higher postoperative satisfaction (NASS score 1–2) at the 3-month (89.4% vs 80.2%, p < 0.01) and 24-month (88.2% vs 67.4%, p < 0.01) follow-ups. CONCLUSIONS Fifteen percent of patients with CSM depended on others for care preoperatively. After surgery to treat CSM, 81.8% of those who had depended on others for care became independent. Patients with improvements in care dependency noted higher postoperative satisfaction at the 3-month and 24-month follow-ups. Patients with resolved care dependency on long-term follow-up had lower NDI and NRS neck pain scores at baseline. Surgery had a significant impact on patients’ attainment of independence.

2030 Background: Brain metastases (BM) are common and arise in 30% of lung adenocarcinoma (LUAD) patients. Patients with LUAD that develop BM have significantly poorer outcomes, with a 10-16 month median overall survival. Unfortunately, current clinical practice for BM prediction is limited and so BM are typically detected after they develop and grow to cause neurological symptoms. Once BM are detected, currently neurosurgical tumor biopsies are performed to enable BM diagnosis via neuropathological evaluation. The aims of this study were to develop DNA methylation-based models that predict LUAD BM and non-invasively detect BM in blood to enable early diagnosis and treatment. Methods: DNA methylomes were acquired from 402 tumor tissue and plasma samples in a cohort of 346 LUAD and BM patients. Machine learning models were built using DNA methylation signatures that stratify BM risk in tissue and detect BM in plasma. Models were evaluated in independent validation datasets. A predictive nomogram was developed using the BM prediction model together with clinical factors to provide composite patient-specific scores reflecting BM risk. Results: The methylation-based BM predictor accurately stratified BM risk in a univariable Cox model using validation set data (HR = 5.65, 95%CI 1.85–17.2, p = 0.0023). Model utility was independent of the predictive value of clinical factors in a multivariable Cox model using validation set data (Table 1: HR = 8.92, 95%CI 1.97–40.5, p = 0.0046). The 5-year model accuracy was 0.81 and significantly higher than a similarly built cancer stage-based model (0.65), demonstrating utility over current practice. The combinatorial clinical-methylomic predictive nomogram had enhanced utility with an accuracy of 0.82 univariable Cox HR of 17.2 (95%CI 4.13–71.3, p < 0.0001), demonstrating comprehensive patient-specificity. The plasma-based model accurately classified BM from gliomas and lymphomas (AUROC=0.80), as typical clinical differential diagnoses, in validation set data. The models were validated further in additional external data. Conclusions: DNA methylation-based modeling of BM can accurately predict LUAD patients at risk for BM development and can non-invasively detect BM that develop. Future treatment approaches may tailor initial LUAD treatment and ongoing cancer surveillance to a patient’s BM risk, allowing for the potential to prevent and treat BM early. DNA methylation-based BM prediction is independent of clinical factors in a multivariable Cox proportional hazards model. Variable HR 95% CI p Methylome risk score 8.92 1.97–40.5 0.005 Age Years 0.96 0.92–1.02 0.177 Smoking Pack-years 0.99 0.95–1.03 0.496 EGFR Mutant vs wildtype 0.92 0.25–3.34 0.895 T T2 vs T1 1.58 0.41–6.04 0.505 T3−4 vs T1 1.49 0.28–7.98 0.642 N N1 vs N0 1.05 0.31–3.58 0.943 N2−3 vs N0 1.00 0.27–3.69 0.995 M M1 vs M0 145 12.2–1730 <0.001

Opioid use disorders (OUDs) pose a substantial global health burden, with methadone maintenance treatment (MMT) widely adopted as an intervention; however, MMT is associated with immunosuppression, metabolic disturbances, and dysbiosis of the gut microbiota. Despite the potential of acupuncture in reducing methadone dosages and opioid addiction, the underlying biological mechanisms remain unclear. Therefore, we aimed to integrate clinical trial data with multi-omics analysis, including single-cell sequencing, transcriptomics, metabolomics, and metagenomics, to evaluate the effects of acupuncture in patients undergoing MMT. We collected peripheral blood mononuclear cells, plasma, and fecal samples from 48 MMT participants in a randomized, placebo-controlled trial. Participants were divided into acupuncture ( n = 25) and sham-acupuncture ( n = 23) groups. After 8 weeks of intervention, 84% of patients in the acupuncture group achieved ≥20% reduction in methadone dosage, compared to 39% in the sham-acupuncture group ( P < 0.01). Our findings revealed that acupuncture may activate the defense response to viruses, with altered immune cell functions in classical monocytes correlating with clinical responses to reduced methadone doses. Acupuncture might ameliorate intestinal microbial disruptions caused by OUD by up-regulating Bilophila and modulating bile acid metabolism. Furthermore, acupuncture up-regulated galectin-9 (LGALS9)-mediated intercellular communication between classical monocytes and other immune subsets. To further validate the mechanistic link between bile acid metabolism and immune regulation, we conducted in vitro experiments using THP-1 monocytes treated with cholic acid. The results showed that bile acid exposure suppressed galectin-9 and IFN-γ expression, while low-dose bile acid (simulating acupuncture effects) partially reversed this effect. These findings support a bile acid–galectin–interferon axis that may be modulated by acupuncture in OUD. Collectively, our results provide clinical and mechanistic evidence supporting acupuncture as a potential adjunct therapy to mitigate the adverse effects of long-term opioid use.

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.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

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.

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.

AbstractINTRODUCTIONIdentifying individuals with dementia is crucial for prevalence estimation and service planning, but reliable, scalable methods are lacking. We developed novel set algorithms using both structured and unstructured electronic health record (EHR) data, applying Diagnostic and Statistical Manual of Mental Disorders criteria for dementia case identification.METHODSOur cohort (n = 1082) included individuals aged ≥ 60 with dementia identified through specialist clinics and a comparison group without dementia. Clinicians from Australia and the United States informed predictor selection. We developed algorithms through a biostatistics stream for structured data and a natural language processing (NLP) stream for text, synthesizing results via logistic regression.RESULTSThe final structured model retained 16 variables (area under the receiver operating characteristic curve [AUC] 0.853, specificity 72.2%, sensitivity 80.6%). NLP classifiers (logistic regression, support vector machine, and random forest models) performed comparably. The final, combined model outperformed all others (AUC = 0.951, P < 0.001 for comparison to structured model).DISCUSSIONEmbedding text‐derived insights within algorithms trained on structured medical data significantly enhances dementia identification capacity.Highlights Algorithmic tools for detection of individuals with dementia are available; however, previous work has used heterogeneous case definitions which are not clinically meaningful, and has relied on proxies such as diagnostic codes or medications for case ascertainment. We used a novel, dual‐stream algorithmic development approach, simultaneously and separately modeling a clinically meaningful outcome (diagnosis of dementia according to specialized clinical impression) using structured and unstructured electronic health record datasets. Our clinically grounded case definition supported the inclusion of key structured variables (such as dementia International Classification of Disease codes and medications) as modeling predictors rather than outcomes. Our algorithms, published in detail to support validation and replication, represent a major step forward in the use of routinely collected data for detection of diagnosed dementia.

Abstract Tumor cells develop various strategies to evade immune surveillance, one of which involves altering the metabolic state of the tumor microenvironment. In response to metabolic stress in the tumor microenvironment, several tumor-infiltrating immune subsets upregulate CD36 to take up lipids. This leads to impaired antitumor immunity, as intratumoral regulatory T cells exhibit increased survival and suppressive activity, whereas CD8+ T cells become more susceptible to ferroptosis and exhaustion. In this study, we develop a humanized anti-CD36 IgG4 antibody, PLT012, against the lipid-binding domain of CD36 with excellent safety and favorable pharmacokinetic features in mice and cynomolgus monkeys. PLT012 alone or in combination with PD-L1 blockade or standard-of-care immunotherapy results in robust antitumor immunity in both immunotherapy-sensitive and -resistant hepatocellular carcinomas (HCC). Notably, PLT012 also reprograms the immune landscape of human HCC ex vivo. Our findings provide proof-of-concept evidence that PLT012 reprograms antitumor immunity in HCC, positioning it as a first-in-class immunotherapy targeting CD36. Significance: Despite the success of cancer immunotherapies, like immune checkpoint inhibitors, many patients still fail to demonstrate significant responses because of metabolic constraints in tumors. PLT012 rejuvenates antitumor immunity by targeting metabolic pathways to reprogram the immune landscape of liver cancer and liver metastasis, with potential to influence future HCC immunotherapy.