Citations

BACKGROUND AND OBJECTIVES: Transforaminal lumbar interbody fusion (TLIF) allows for direct and indirect decompression and segmental lordosis in sagittal plane correction. This study compares the effectiveness of “Bullet” type and “Banana” type devices for sagittal plane correction. METHODS: Patients who underwent 1-level or 2-level TLIF for degenerative pathology at a single tertiary care center were identified. Details were extracted on demographics, interbody dimensions, and preoperative and postoperative lumbopelvic parameters from upright radiographs. Cages were categorized as “Bullet” or “Banana” type based on morphology and manufacturer description of optimal position. Univariable comparisons between levels treated with “Bullet” and “Banana” type interbodies were performed. Multivariable linear regression was performed to identify independent predictors of postoperative segmental lordosis and change in segmental lordosis. RESULTS: One hundred and ninety eight unique patients (median 66.6 years; [IQR 59.5, 73.7]; 56.6% female) were included with 241 levels treated, of which 114 (52.7%) were treated with “Banana” type interbodies and 127 (47.3%) with “Bullet” type. “Banana” type interbodies afforded both greater postoperative segmental lordosis (8.1 [6.2, 10.7] vs 7.5 [5.2, 9.6]; P = .048) and greater increase in segmental lordosis (3.3 [0.7, 7.0] vs 2.3 [0.1, 4.2]; P = .015). On multivariable linear regression, only preoperative segmental lordosis (β = 0.322 per degree; [0.244, 0.399]; P < .001), implant listed lordosis (β = 0.146 per degree; 95% CI [0.048, 0.244]; P = .004), preoperative pelvic incidence (0.072 per degree; [0.034, 0.111]; P < .001), and use of bilateral TLIF windows (β = 3.133; [1.213, 5.053]; P = .001) were predictive of postoperative segmental lordosis. CONCLUSION: The present analysis suggests that baseline lumbopelvic anatomy, interbody lordosis, and the use of bilateral TLIF windows are the most important predictors of postoperative segmental lordosis. Use of “Banana” vs “Bullet” type interbodies was not predictive of segmental lordosis achieved on immediate postoperative upright radiographs. Further work is merited to determine whether the 2 interbody types demonstrate differences regarding subsidence risk or maintenance of correction.

BACKGROUND AND OBJECTIVES: Aggressive resection for primary tumors of the spine are associated with a high rate of adverse events (AEs), but the impact of AEs on patient-reported outcomes (PROs) remains unknown and is critical to the shared decision-making. Our primary objective was to assess the impact of surgical AEs on PROs using an international registry. Assessing the impact on clinical outcomes and identifying risk factors for AEs were our secondary objectives. METHODS: Patients who underwent surgery for a primary spinal tumor were selected through the Primary Tumor Research and Outcomes Network. Our primary outcome was the impact of AEs on PROs at 3 and 12 months after surgery (measured with Spinal Oncology Study Group Outcomes Questionnaire, Short-Form 36, and EuroQol 5 Dimension). We also assessed the impact on clinical outcomes (local control, surgical margins, readmission, reoperation, and mortality). We stratified our results according to severity of AEs, histology, and type of resection. RESULTS: 374 patients met inclusion criteria (219 males/155 females). The mean age of the cohort was 48.7 years. The most frequent histology was chordoma (37.3%) followed by chondrosarcoma (8.8%). Sixty-seven patients (17.9%) experienced at least 1 intraoperative AE and 117 patients (31.3%) had at least 1 postoperative AE within 3 months. Overall, 159 patients (42.5%) experienced AEs. The readmission rate was significantly higher in patients who experienced AEs (Any AE: 10.1% vs no AE: 1.9% within 3 months; P = <0.001). PROs were not significantly affected by AEs in most questionnaires. Local control, risk of reoperation, mortality, and achieving preplanned margins were similar between AE groups. CONCLUSION: The rate of surgical AEs is considerable in this population. Surgical AEs seem to be associated with a higher number of readmissions, but do not seem to result in significant differences in PROs or in a higher risk of reoperation, mortality, and failure to achieve preplanned margins.

Background Our study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC. Methods This is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers. Results 30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%–91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%–94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively. Conclusions Perioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS.

ObjectiveThe objective was to determine the mortality rate as well as the causes and predictors of death in antiphospholipid antibody (aPL)–positive patients with and without antiphospholipid syndrome (APS) classification.MethodsThe inclusion criterion for the multicenter international Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) registry is positive aPLs according to the Revised Sapporo Classification Criteria tested within one year before enrollment. Patients are observed every 12 ± 3 months with clinical data and blood collection. For this prospective analysis, we first analyzed the causes of death for patients reported as “deceased.” Secondly, we analyzed risk factors for death using the adjusted Cox proportional hazards model and calculated survival probability using the Kaplan‐Meier model based on different age groups.ResultsOf 967 patients, 43 (5%) were deceased after a median follow‐up of 5.3 years. Based on the univariate analysis, deceased patients, compared to living patients, were more likely to be older and have a history of arterial thrombosis, catastrophic APS, concomitant systemic autoimmune diseases (SAIDs), and baseline cardiovascular disease (CVD) risk factors. Based on the Cox proportional hazards model adjusted for age and for each of the strongest predictors of death, arterial thrombosis (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.50–5.76), concomitant SAIDs (HR 2.97, 95% 1.56–5.63), and baseline any CVD risk factor (HR 2.43, 95% CI 1.05–5.71) were significantly associated with mortality.ConclusionIn our cohort of persistently aPL‐positive patients, the mortality rate was 5% after a median follow‐up of five years and was highest for patients ≥60 years old at registry entry. History of arterial thrombosis, concomitant SAIDs, and baseline any CVD risk factor independently predicted future death.

AbstractBackgroundLate‐Onset Alzheimer’s Disease (LOAD) is characterized by genetic heterogeneity and there is no single model explaining the genetic mode of inheritance. To date, more than 70 genetic loci associated with AD have been identified but they explain only a small proportion of AD heritability. Structural variants (SVs) may explain some of the missing AD heritability, and specifically, their segregation in AD families has yet to be investigated.MethodWe analyzed WGS data from 197 NHW families (926 subjects, 58.5% affected) and 214 CH families (1,340 subjects, 59.17% affected). Manta, Absinthe, and MELT were used for large insertions/deletions calling from short‐read WGS, combined with Sniffles2 calls from 4 ONT‐sequenced genomes and an external SV call set from HGSVC on 32 PacBio‐sequenced genomes from the 1000 Genomes Project. Genotyping produced a unified project‐level VCF. We identified 45,251 insertions and 76,566 deletions genome‐wide. Variants were tested for segregation and pathogenicity using Annot‐SV, cadd‐SV, and Variant Effect Predictor. Segregation required SV presence in all affected family members and only in unaffected members five years younger than average disease onset.ResultWe identified 453 insertions and 598 deletions segregating in 78.68% and 87.31% of NHW families, respectively. In CH families, 432 insertions and 460 deletions were segregating in 75.23% and 72.90% of the families, respectively. Genes overlapping with the SVs exhibited high expression levels in brain tissues. Notably, around 93% of insertions and 76% of deletions segregating in NHW and CH families were less than 1 kilobase pair (1kbp) in length. A total of 79 insertions and 96 deletions were found to be segregating in both NHW and CH families. Interestingly, a segregating insertion was observed in CH families overlapping within the CACNA2D3 gene, which was previously reported in a CH GWAS for clinical AD. A deletion segregating in NHW overlapped with the PSEN1, and another in a CH family overlapped with the PTK2B gene.ConclusionOur findings suggested that there are several SVs associated with familial AD across CH and NHW families. Prioritizing the SVs based on their effects on gene function and expression will be helpful in understanding their contributions in AD.

Abstract Context Tumor-induced osteomalacia (TIO), a paraneoplastic disorder characterized by renal phosphate wasting, is cured by surgical removal of the culprit tumor. Despite correct localization, some remain refractory to intervention, resulting in substantial long-term medical complications. Objective We aim to identify risk factors associated with a refractory outcome. Methods This is a retrospective cohort of 44 patients with TIO diagnosed from 1998 to 2023 who underwent targeted intervention following successfully localization. Cure was defined as maintenance of normophosphatemia without supplementation for ≥1 month, maintained at last follow-up. Results Twenty-nine patients achieved cure and 15 had a refractory outcome. On univariate Cox regression, the HR for predicting cure was 3.43 (95% CI 1.45-8.11, P = .005) for patients diagnosed after 2013 (compared to before), and that for a negative surgical tumor margin was 2.56 (95% CI 1.20-5.45, P = .015) compared to positive/unspecified margins. After adjustment for year of diagnosis, tumors originating from soft tissue (HR 2.72 vs bone, 95% CI 1.22-6.09, P = .015) or located outside the spine (HR 0.22 for spine vs nonspine, 95% CI 0.05-0.96, P = .043) had higher chances of cure. Size of tumor, age, gender, or baseline biochemistry including levels of fibroblast growth factor (FGF)23, phosphorus, 1,25-dihydroxyvitamin D, or alkaline phosphatase were not predictive of cure. Postprocedural FGF23 was the best biochemical marker of cure (area under curve 0.899, 95% CI 0.764-1.00, P &lt; .001). Conclusion Tumors diagnosed within the past decade with clear resection margins had more favorable prognoses. With regards to tumoral factors, baseline biochemistry was uninformative in predicting cure, while bone and/or spine localizations were associated with a refractory outcome.

Background Value-based care payment and delivery models such as the recently implemented Merit-based Incentive Payment System (MIPS) aim to both provide better care for patients and reduce costs of care. Gender disparities across orthopaedic surgery, encompassing reimbursement, industry payments, referrals, and patient perception, have been thoroughly studied over the years, with numerous disparities identified. However, differences in MIPS performance based on orthopaedic surgeon gender have not been comprehensively evaluated. Questions/purposes After controlling for potentially confounding variables such as experience, geography, group size, and Medicare beneficiary characteristics, does MIPS performance differ between men and women orthopaedic surgeons? Methods The Medicare Physician and Other Practitioners and the Physician Compare databases were queried for years 2017, the first year MIPS was incorporated, and 2021, the most recent year with MIPS data published, to identify all physicians with a self-reported specialty of orthopaedic surgery. Together, these databases include all physicians who submitted at least 11 Medicare claims each year. Physician gender, US census region, years in practice, group practice size, billing practices, and patient demographic characteristics were collected for each surgeon. The MIPS Performance database was used to extract an overall MIPS performance score for each surgeon for each year. Payment adjustments, which are determined based on overall MIPS performance score, were derived for each surgeon based on the thresholds published by the Centers for Medicare & Medicaid Services. Payment adjustments include a negative adjustment, neutral adjustment, positive adjustment, or exceptional performance bonus and are associated with different thresholds each year. Statistical differences based on surgeon gender were assessed utilizing chi-square tests for categorical data, Student t-test for parametric continuous data, and Wilcoxon signed-rank test for nonparametric continuous data. Univariable and multivariable analyses were performed to analyze the relationship between surgeon gender and MIPS performance. Results After controlling for other patient and surgeon variables, woman gender was associated with a slightly increased MIPS performance score in 2021 (β 1.5 [95% confidence interval (CI) 0.02 to 3.00]; p = 0.047). However, this finding was statistically fragile, with the lower bound 95% CI being very close to the line of no difference. No association between surgeon gender and MIPS performance score was found in 2017 (β 2.2 [95% CI -0.5 to 4.9]; p = 0.11). Additionally, no relationship was found between gender and receiving either an exceptional performance MIPS bonus or a MIPS penalty in either year. Conclusion Women orthopaedic surgeons scored slightly higher on the MIPS in 2021, after controlling for surgeon and patient variables, despite providing care for a higher percentage of dual Medicare-Medicaid eligible patients and more medically complex patients. However, this finding was statistically fragile, with a small effect size, a 95% CI close to 0, and no consistent association in MIPS performance in 2017. Additionally, with no differences in MIPS performance bonuses or penalties, the clinical monetary impact of this difference may be minimal. Clinical Relevance The observed association between surgeon gender and MIPS performance scores in 2021, with women orthopaedic surgeons achieving slightly higher scores, raises interesting questions about potential differences in practice behaviors, communication styles, care quality, or other unmeasured variables. These findings may reflect true differences in how care is delivered or documented as scored by the MIPS. However, given the small effect size, statistical fragility, and inconsistency across years, there is a chance that this finding may be spurious. That being so, future research should aim to validate or refute these findings by examining a broader range of variables including documentation practices, practice behaviors, institutional differences, potential systemic biases in scoring methodologies, and patient outcomes. Understanding whether these differences are true is important to ensure that performance metrics like MIPS accurately and equitably reflect care quality.

Abstract Background Temozolomide (TMZ) treatment has demonstrated a variable impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes. Methods We evaluated TMZ-related survival associations of pathogenic germline SNPs and genetically predicted transcript levels within 34 DNA repair genes among 1504 glioma patients from the University of California San Francisco Adult Glioma Study (UCSF AGS) and Mayo Clinic, whose diagnoses spanned pre- and post-TMZ eras within the major known glioma prognostic molecular subtypes. Results Among those who received TMZ, 5 SNPs were associated with overall survival, but not in those who did not receive TMZ. Only rs2308321-G, in MGMT, was associated with decreased survival (hazard ratio = 1.21, P = .019) for all glioma subtypes. Rs73191162-T (near UNG), rs13076508-C (near PARP3), rs7840433-A (near NEIL2), and rs3130618-A (near MSH5) were only associated with survival and TMZ treatment for certain subtypes, suggesting subtype-specific germline chemosensitization. Genetically predicted elevated expression of PNKP, compared to normal brain expression, was associated with markedly poor survival in TMZ-treated patients with isocitrate dehydrogenase (IDH)-mutant and 1p/19q non-codeleted gliomas (P = .015), with a median difference of over 70 months in overall survival times. Similarly, NEIL2 and TDG expressions were associated with altered TMZ-related survival only among certain subtypes. Conclusions Functional germline alterations within DNA repair genes were associated with TMZ sensitivity, measured by overall survival among adults with glioma. These variants should be evaluated in prospective analyses and functional studies.

Abstract Context A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis. Objective The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis. Methods This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022. The primary outcome was the proportion of patient-quarter observations with ODT use stratified by age, sex, fragility fracture, and documented osteoporosis. Cuzick tests were performed to assess trends ODT use. Results Analysis of 166 673 420 patient-quarter observations revealed that over 70% of patients with fragility fractures did not have documented osteoporosis. Among women aged ≥65 years with documented osteoporosis, ODT fill rates increased between 2011 and 2022 from 36.3% to 50.1% for women without fragility fractures (P &lt; .001) and from 30.8% to 43.7% for women with fragility fractures (P &lt; .001). However, ODT fill rates declined (9.2% to 7.4% between 2011 and 2022) for women with fragility fractures and no documented osteoporosis (P = .015). Similar trends were observed among women aged 50-64 years and men. Conclusion ODT use for patients with documented osteoporosis has increased but remains low. Low rates of ODT use for patients with fragility fractures in the absence of documented osteoporosis suggests that underdiagnosis of osteoporosis contributes to underuse of ODTs.