Citations

OBJECTIVE Surgery is typically indicated for mechanical pain in metastatic spine disease or severe neurological compromise, but how radicular pain responds to oncological treatment is not well described. The primary aim of this study was to describe how radicular pain responds to oncological treatment, while secondary aims included pain outcomes between patients with mechanical and tumoral pain and motor improvement in patients with weakness due to nerve root compression. METHODS Patients treated with surgery and/or radiotherapy for spinal metastases were identified from an international multicenter prospective cohort. The primary outcome was the numeric rating scale (NRS) score for pain at 3 months posttreatment. Motor recovery from radicular compression in patients with myotomic weakness and low-grade epidural compression was also analyzed. RESULTS Of 284 patients, 129 (45%) had radicular pain ± axial pain and 155 (55%) had axial pain alone. The two groups did not significantly differ in age, comorbidities, tumor characteristics, or treatment. Two hundred two patients (71%) underwent surgery ± radiotherapy, whereas 82 (29%) had radiotherapy alone. The NRS score of patients with radicular pain improved from 6.7 to 3.4 at 3 months, a statistically significantly higher magnitude than in patients with isolated axial pain (p = 0.021). The NRS score at 3 months was similar for both groups (p = 0.876). Patients with radicular pain experienced a larger improvement with surgery compared with radiotherapy alone (p = 0.007) but had higher pretreatment pain (mean NRS score 7.0 vs 5.6, p = 0.013). Twenty-three patients identified with radicular/myotomic weakness (mean American Spinal Injury Association score 96.3 ± 3.2) at baseline improved 2.1 ± 3.8 points at 3 months. CONCLUSIONS The magnitude of pain improvement for patients with radicular pain following surgery and radiotherapy for metastatic spine disease is higher than for patients with axial pain alone. Surgery is associated with a larger improvement in radicular pain than radiotherapy alone. These results will allow clinicians to tailor treatment options for patients with metastatic spine disease.

OBJECTIVE The aim of this study was to determine independent risk factors for vertebral compression fracture (VCF) following stereotactic body radiation therapy (SBRT) in metastatic spine disease. METHODS Patients treated with SBRT for spinal metastasis at a single tertiary care center between 2008 and 2019 were retrospectively identified. Patients with CT scans obtained within 1 year of SBRT completion were included. Variables collected included demographics, Spine Instability Neoplastic Score (SINS), primary tumor pathology, Weinstein-Boriani-Biagini (WBB) classification, chemoradiation treatment details, and bone quality as assessed by Hounsfield units (HUs) on CT. HUs were measured for the medullary bone of the metastatic level, the tumor, and the vertebral bodies cephalad and caudal to the metastasis. Multivariable logistic regression was used to identify predictors of post-SBRT pathological fracture. RESULTS A total of 292 patients (mean age 66 years) with 392 unique lesions were included. The most common pathologies were prostate (n = 193), kidney/renal cell (n = 46), and lung (n = 33). The most common tumor levels were thoracic (n = 206 lesions) and lumbar (n = 128 lesions). SBRT was generally delivered in 1–3 fractions with doses ranging from 16 to 24 Gy in 1 fraction and 24–36 Gy in 3 fractions. Of the 392 lesions, 73 suffered VCF: 21 (29%) with < 25% height loss, 15 (21%) with 25%–40% height loss, and 37 (51%) with > 40% height loss. On univariate analysis, patients with VCF had lower average HUs (156 ± 52 vs 202 ± 89, p < 0.001), more WBB sectors involved (3 ± 2 vs 3 ± 1, p < 0.001), higher SINSs (8 ± 3 vs 6 ± 2, p < 0.001), were more commonly female (33% vs 22%, p = 0.05), and more commonly had nonprostate pathology (67% vs 47%, p = 0.003). VCF rates were similar between moderate (< 20 Gy in 1 fraction, < 30 Gy in 3 or 5 fractions) and high-dose (> 20 Gy in 1 fraction, > 30 Gy in 3 or 5 fractions) radiation schema (15% VCF vs 16% no VCF, respectively; p = 0.99). On multivariable logistic regression, independently significant predictors of VCF were HUs ≤ 229 (OR 6, p < 0.001), affected levels ≥ 3 WBB segments (OR 3, p < 0.001), and an SINS ≥ 8 (OR 2, p = 0.02). CONCLUSIONS Low pre-radiation HUs, involvement of more WBB sectors, and a higher SINS were independent predictors of VCF following SBRT for metastatic spine disease.

Abstract Context Data on cardiovascular outcomes in patients with chronic hypoparathyroidism (hypoPT) are limited. Objective To investigate the risk of cardiovascular outcomes, acute myocardial infarction, atrial fibrillation/flutter, heart failure, valvular heart disease, peripheral artery disease, and stroke/transient ischemic attack (TIA) in patients with chronic hypoPT. Design The Swedish National Patient Registry, the Swedish Prescribed Drug Registry, and the Total Population Registry, 1997-2018. Settings Population-based cohort study in Sweden. Patients National registries were used to identify patients with chronic hypoPT and matched controls. Results A total of 1982 with chronic hypoPT and 19 499 controls were included. After adjustment for cardiovascular risk factors, patients with chronic hypoPT had higher risk of valvular heart disease [hazard ratio (HR) 2.08; 95% confidence interval (CI) 1.67-2.60], peripheral artery disease (HR 1.78; 95% CI 1.41-2.26), heart failure (HR 1.66; 95% CI 1.44-1.90), atrial fibrillation/flutter (HR 1.58; 95% CI 1.38-1.81), acute myocardial infarction (HR 1.31; 95% CI 1.05-1.64), and fatal cardiovascular disease (HR 1.59; 95% CI 1.40-1.80) compared to matched controls. No significant difference in risk of stroke/TIA was observed. Cardiovascular outcomes did not differ between patients with surgical and nonsurgical chronic hypoPT. Females with hypoPT had a significantly increased risk of valvular heart disease, peripheral artery disease, heart failure, atrial fibrillation, myocardial infarction, and fatal cardiovascular disease compared to female controls. There were no differences in any cardiovascular outcomes between males with hypoPT and male controls. Conclusion The risk of cardiovascular diseases was increased in patients with chronic hypoPT, particularly among women. These findings highlight the need for close monitoring and preventive management of cardiovascular risk factors, especially in women.

Background: Although it is well established that the type of organism can be a risk factor for failure in patients with periprosthetic joint infection (PJI), no study to date has examined the impact of the number of positive cultures on treatment outcomes in patients undergoing 2-stage exchange. The purpose of this multicenter study was to determine the prognostic utility of multiple positive cultures at resection as a predictor of failure following reimplantation. Methods: This retrospective multicenter study identified 437 patients with chronic knee PJI who had undergone 2-stage exchange arthroplasty with a minimum of 1 year of follow-up following reimplantation. PJI was defined with use of the 2013 Musculoskeletal Infection Society (MSIS) criteria. Patients with culture-negative PJI were excluded (n = 138). Treatment failure was defined as either any reoperation for infection or PJI-related mortality. Multivariable regression controlling for risk factors for failure after a 2-stage arthroplasty was performed to determine whether ≥2 positive intraoperative cultures at resection can predict outcomes following reimplantation when compared with a single positive culture. Results: Two hundred and ninety-nine patients were included. At a mean follow-up of 6.2 ± 2.6 years, 48 patients (16.1%) experienced failure. Patients who had a failure were more likely to have had a longer interstage interval (p = 0.038) and were also more likely to have had ≥2 positive cultures at the time of resection arthroplasty (95.8% versus 75.3%; p = 0.001). On regression analysis, ≥2 positive cultures at resection was the only variable that was identified as a risk factor for failure following reimplantation in both the univariate (odds ratio [OR], 7.55 [95% CI, 2.24 to 47.0]; p = 0.006) and multivariable models (OR, 8.12 [95% CI, 2.31 to 51.9]; p = 0.005). Conclusions: This is the first study to examine the impact of the number of positive cultures on outcomes in patients with PJI. We found that the presence of ≥2 positive cultures at resection was an indicator of a poor prognosis and resulted in a greater than eightfold increase in the risk of treatment failure in patients undergoing a 2-stage exchange. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Background/Purpose APS ACTION Registry was created to study the natural course of antiphospholipid syndrome (APS) over 10 years in persistently antiphospholipid antibody (aPL) positive patients with or without systemic autoimmune rheumatic diseases (SARDs). Our primary objective was to compare the characteristics of aPL-positive patients with or without thrombocytopenia (TP) and/or autoimmune hemolytic anemia (AIHA). Methods The registry inclusion criteria are positive aPL based on the Revised Sapporo APS Classification Criteria, tested at least twice within 1 year prior to enrollment. For the primary comparison of demographic, clinical, and serologic characteristics in this retrospective study, we divided patients into two groups: TP/AIHA ever and never. Thrombocytopenia was defined as a platelet count of <100,000 x 10 9 /L tested twice at least 12 weeks apart, and AIHA was defined as anemia with hemolysis and a positive direct antiglobulin test (DAT). For the secondary analysis, we compared patients with TP versus AIHA, and the immunosuppressive use stratified by systemic lupus erythematosus (SLE) classification. Results As of April 2022, of 1,039 patients (primary aPL/APS: 618 [59%]; SLE classification: 334 [31%]) included in the registry, 228 (22%) had baseline (historical or current) TP and/or AIHA (TP only: 176 [17%]; AIHA only: 35 [3%], and both: 17 [2%]). Thrombocytopenia and/or AIHA was significantly associated with Asian race, SLE classification, cardiac valve disease, catastrophic/microvascular APS, triple aPL (lupus anticoagulant, anticardiolipin antibody, and anti-β 2 -glycoprotein-I antibody) positivity, and SLE-related serologic and inflammatory markers. When 101/618 (16%) primary aPL/APS patients and 101/334 (34%) SLE patients with TP and/or AIHA were compared, azathioprine and mycophenolate mofetil were more commonly reported in lupus patients, however corticosteroid, intravenous immunoglobulin, and rituximab use were similar between groups. Conclusion In our large multi-center international cohort of persistently aPL-positive patients, approximately one-fifth had active or historical TP and/or AIHA at registry entry; half of these patients had additional SLE. Cardiac valve disease, catastrophic/microvascular APS, and triple aPL-positivity were aPL-related clinical and laboratory manifestations associated with TP and/or AIHA, suggesting a more severe APS clinical phenotype in aPL-patients with TP and/or AIHA.

Study Design Narrative Review. Objectives To summarize the work of the AO Spine Knowledge Forum Tumor, specifically studies from the Epidemiology, Process and Outcomes in Spine Oncology (EPOSO) study. Methods A narrative review of all published manuscripts from the EPOSO study was undertaken. EPOSO represents a multicenter, prospective registry effort across 10 North American and European sites to enroll patients with metastatic disease of the spine. Results The current review summarized all studies from the EPOSO network, divided into the following five sections: (1) quality of life and satisfaction, (2) overall survival, (3) spinal instability, (4) neurologic outcome in patients with metastatic epidural spinal cord compression or radicular pain, and (5) patient and tumor-specific factors. Several important findings were elucidated. Patient evaluation should include SINS, nutritional status, severity and duration of neurologic deficit, extent of metastatic tumor burden, and differentiation of axial from radicular pain. Moreover, SOSGOQ2.0 serves as a useful and validated instrument for patient-reported outcome instrument. Despite the palliative nature of metastatic spine surgery, clear improvement in quality-of-life is seen. Even in patients with short-survival, the remaining weeks and months of life result in improved quality-of-life. Metastatic spine surgery often improves neurologic function, potentially enhancing survival through increased performance status. Conclusions Several noteworthy results have come from the EPOSO network, highlighting important trends in metastatic spine care. The AO Spine Knowledge Forum Tumor has helped advancing metastatic spine tumor research as well as ensure these new findings reach and benefit clinicians and their patients.

Understanding the key drivers of brain aging is essential for effective prevention and treatment of neurodegenerative diseases. Here, we integrate human brain and physiological data to investigate underlying mechanisms. Functional MRI analyses across four large datasets (totaling 19,300 participants) show that brain networks not only destabilize throughout the lifetime but do so along a nonlinear trajectory, with consistent temporal “landmarks” of brain aging starting in midlife (40s). Comparison of metabolic, vascular, and inflammatory biomarkers implicate dysregulated glucose homeostasis as the driver mechanism for these transitions. Correlation between the brain’s regionally heterogeneous patterns of aging and gene expression further supports these findings, selectively implicating GLUT4 (insulin-dependent glucose transporter) and APOE (lipid transport protein). Notably, MCT2 (a neuronal, but not glial, ketone transporter) emerges as a potential counteracting factor by facilitating neurons’ energy uptake independently of insulin. Consistent with these results, an interventional study of 101 participants shows that ketones exhibit robust effects in restabilizing brain networks, maximized from ages 40 to 60, suggesting a midlife “critical window” for early metabolic intervention.

Objective: This post hoc analysis evaluated the efficacy of abaloparatide treatment in a subgroup of postmenopausal women from the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE; NCT01343004) study who met high fracture risk criteria (defined in several professional society guidelines). Methods: Women from ACTIVE meeting ≥1 of the following fracture risk criteria were included: fracture within the past 12 months or prevalent vertebral fracture, baseline T score of <−3.0 at any site, very high fracture risk probability by FRAX (ie, 10-yr major osteoporotic fracture >30% or hip fracture >4.5%), or multiple prior fractures at baseline since age ≥45 years. Results: A total of 2,026 participants met ≥1 fracture risk criteria defined in clinical guidelines (abaloparatide, n = 664; placebo, n = 677; teriparatide, n = 685). New vertebral fracture risk was reduced in participants receiving abaloparatide (4 [0.72%]) and teriparatide (6 [0.99%]) versus placebo (28 [4.77%]; both P < 0.0001). Estimated Kaplan-Meier cumulative incidence of nonvertebral fracture was 3.0%, 5.3%, and 3.0% in the abaloparatide, placebo, and teriparatide groups, respectively; 4.0%, 9.0%, 4.3% for clinical fracture; 1.6%, 6.8%, 3.0% for major osteoporotic fractures; and 1.1%, 2.1%, 2.1% for wrist fracture. Abaloparatide was associated with bone mineral density gains from baseline at the lumbar spine, total hip, and femoral neck at all time points (6, 12, and 18 mo; P < 0.0001 for all). Common adverse events reported in participants treated with abaloparatide were hypercalciuria (11.5%), dizziness (11.0%), and arthralgia (8.9%). Conclusions: Abaloparatide reduced fracture incidence and increased bone mineral density in participants at highest fracture risk, consistent with the overall ACTIVE study.