Citations

With continued improvements in systemic cancer therapies, there has been an increase in the survivorship of patients with spinal metastases. However, many patients with spinal metastases are frail and may not be able to tolerate the morbidity of open surgery. For these patients, percutaneous ablation techniques offer a minimally invasive approach that can facilitate local tumor control and pain relief. Here we describe the currently employed modalities—radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and laser interstitial thermal therapy (LITT)—summarize the clinical support for their use, and overview the relative risks and benefits for each. All these technologies offer to help improve local tumor control and improve oncologic pain associated with vertebral metastases, and they have become a staple of multidisciplinary spine metastasis care at many centers. As clinical experience with these technologies continues to grow, their use will likely become more widely adopted, and so understanding of their indications, risks, and benefits will become increasingly important to the practicing spine oncologist.

Abstract Repetitive head impacts are associated with structural brain changes and an increased risk for chronic traumatic encephalopathy, a progressive neurodegenerative disease that can only be diagnosed after death. Chronic traumatic encephalopathy is defined by the abnormal accumulation of phosphorylated tau protein, particularly at the depths of the superior frontal sulci, suggesting that sulcal morphology may serve as a relevant structural biomarker. Contact sport athletes, such as former football players, are at elevated risk due to their prolonged exposure to repetitive head impacts. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease. This study investigated sulcal morphological differences in former football players and examined associations with age, football-related exposure, clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for chronic traumatic encephalopathy pathology, neuropsychological performance, and positron emission tomography imaging using flortaucipir. We analysed structural magnetic resonance imaging data from 169 male former football players (mean age 57.2 (8.2) years, range 45–74) and 54 age-matched, unexposed asymptomatic male controls (mean age 59.4 (8.5) years, range 45–74). Sulcal depth and width were quantified using the CalcSulc, focusing on two regions in each hemisphere commonly affected by chronic traumatic encephalopathy pathology: the superior frontal and occipitotemporal sulci. Generalized least squares models were used to assess group differences and interactions with age and football exposure variables, including age of first exposure, total years played, and cumulative head impact exposure. An analysis of covariance evaluated relationships between sulcal morphology, clinical measures, and flortaucipir uptake, adjusting for age, race, body mass index, education, imaging site, apolipoprotein E4 status, and total intracranial volume. Former football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed controls. Earlier age of first exposure and longer football careers were associated with greater widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure was linked to reduced sulcal depth in the left superior frontal region. However, sulcal morphology was not associated with clinical diagnosis, levels of certainty, neuropsychological test performance, or flortaucipir imaging. These findings suggest that sulcal morphology may reflect cumulative exposure to repetitive head impacts, particularly in brain regions vulnerable to chronic traumatic encephalopathy pathology. Future ante- and post-mortem validation studies are needed to determine whether sulcal morphology can serve as a reliable in vivo biomarker of risk.

Abstract Rationale Inflammation is central to chronic obstructive pulmonary disease (COPD) pathogenesis but incompletely represented in COPD prognostic models. The neutrophil-to-lymphocyte ratio (NLR) is a readily available inflammatory biomarker. Objectives To explore the associations of NLR with smoking status, clinical features of COPD, and future adverse outcomes. Methods We analyzed NLR calculated from the complete blood count of participants who currently or formerly smoked (n = 2,624) and tobacco-naive control subjects (n = 187) in the SPIROMICS multicenter observational cohort study. We assessed the stability of NLR at 6 weeks and 1 year, the association with select blood biomarkers, and the impact of smoking on NLR and cell counts. We stratified participants by NLR quartiles to compare cross-sectional clinical features at enrollment, prospectively observed exacerbations at 1 year, and mortality during longitudinal follow up. Results Higher NLR quartiles were broadly associated with more severe clinical features of COPD. NLR values were repeatable at 6 weeks (intraclass correlation coefficient, 0.74) and 1 year (intraclass correlation coefficient, 0.62). The impact of smoking on NLR varied with the severity of airflow limitation, mediated by an interaction between smoking, forced expiratory volume in 1 second percent predicted, and neutrophil counts but not lymphocyte counts. The highest NLR quartile (>3.11) was associated with an increased risk of exacerbation over 1 year (adjusted odds ratio, 1.51; 95% confidence interval, 1.18, 1.92) and increased risk of mortality (adjusted hazard ratio, 1.41; 95% confidence interval, 1.20, 1.66) compared with quartiles 1–3. Conclusions Elevated NLR in stable COPD is a widely available biomarker associated with increased risk for exacerbation and death. The impact of cigarette smoking on NLR varies with disease severity.

Abstract Background Patients with end-stage heart failure and chronic kidney disease requiring dual-organ transplantation (DOT) face significant challenges in utilizing durable mechanical circulatory support due to the risks associated with renal replacement therapies (RRTs) and multi-organ failure. Given the limited options available for long-term support in this patient population, there remains a critical need for alternative strategies to optimize end-organ function and bridge patients safely to transplant. With prolonged waitlist times for DOT, we present our experience with the Impella 5.5 as temporary mechanical circulatory support, demonstrating its potential to provide hemodynamic stability and support as a bridge to transplantation (BTT) in this complex cohort. Methods A single-centre retrospective review was completed of all patients listed for single-organ transplantation or DOT between December 2019 and November 2022 at Mayo Clinic in Florida, supported by the Impella 5.5 intended as BTT. The focus of this analysis was patients requiring RRT or listed for heart/kidney transplantation. Data were extracted from the electronic health record at baseline and during their transplant episode of care after institutional review board approval as exempt status for retrospective data collection. Results A total of 41 patients were supported with Impella 5.5, intended as BTT. All patients underwent successful transplantation. We focus on the 10 patients with Impella support who underwent DOT. In the DOT group, the median age at transplantation was 63 years (59–66), with nine males and one female. The baseline median ejection fraction was 19% (15–22), with 50% Caucasian and 50% African American and an even split between ischaemic and non-ischaemic aetiology. Median body mass index was 30 kg/m2 (26–31), and 60% were in blood group O. The median time on the waitlist for DOT patients was 53 days (29–75). Perioperative management of DOT Impella patients demonstrated baseline haemodynamics of RA 11 mmHg (7–16), mean PA 36 mmHg (32–47), PCWP 29 mmHg (21–35), mixed venous saturation (SVO2%) 51 (46–61) and Fick CI 2.03 L/min/m2 (1.66–2.5). Post-Impella placement haemodynamics demonstrated significant improvements in RA pressure to 5 mmHg (4–8), P = 0.02, SVO2 to 70% (65–72), P = 0.002, and Fick CI to 5.5 (5.2–8), P = 0.03. The average duration of support was 44 days (range 10–94). The median glomerular filtration rate at baseline was 27 mmol/L (16–29). Twenty-four hour urine protein averaged 168 mg/24 h (range 87–328), with the 24 h creatinine clearance of 29 mg/24 h (range 24–35). Eight of the 10 patients required continuous or intermittent RRT before DOT. The median total duration of RRT (including Impella support) was 36 days (9–72). DOT recipients had a 1 year survival of 90%, with an average follow-up of 432 days. Conclusions Our findings demonstrate that prolonged use of the Impella 5.5 provides safe and effective haemodynamic support for patients with end-stage heart and kidney failure awaiting dual-organ transplantation. With a 1 year survival rate of 90%, our data suggest that Impella 5.5 can be a viable alternative to traditional support strategies, particularly in patients who are otherwise limited by RRTs. As dual-organ transplantation becomes more prevalent, the Impella 5.5 offers a promising bridge to transplant, improving both short-term and long-term outcomes in this complex patient population.

Background: Tumefactive demyelination (TD) is a rare variant of multiple sclerosis (MS) characterized by tumor-like lesions that often require aggressive management. Genome-wide association studies (GWAS) identified variants associated with MS; similar analyses in TD are lacking. Objective: A GWAS was performed to identify variants associated with TD. Methods: The case–control study included 142 TD cases and 293 controls. TD patients were required to have a demyelinating event and magnetic resonance imaging (MRI) showing one or more lesions. Controls were patients without a neurologic or systemic inflammatory disease or cancer. Logistic regression was used to compare cases versus controls for each variant; age, sex, and principal components were included as covariates. A p -value threshold of 5 × 10 −8 was GWAS significant and 5 × 10 −6 nominally significant. A polygenic risk score (PRS) was compared across TD and controls. Results: Variants on chromosome 14 (rs117797734, p = 2.06 × 10 −11 , odds ratio (OR) = 13.14) and chromosome 6 (most significant rs6936540, p = 5.5 × 10 −7 , OR = 2.61) near DCBLD1 were significant. Seven non-MHC and two MHC variants associated with MS were associated with TD. The PRS was significantly higher in TD versus controls. Conclusion: We identified novel regions associated with TD, demonstrating the importance of performing GWAS in homogeneous subtypes of MS. Further validation and functional experiments are necessary.

Background: Although patients often aim to lose weight after total hip arthroplasty (THA) or total knee arthroplasty (TKA), long-term changes in body mass index (BMI) are unknown. We analyzed BMI at 2, 5, and 10 years after primary THA and TKA and determined predictors of BMI change. Methods: We identified patients who underwent primary THA or TKA for osteoarthritis between 2001 and 2011 and had a BMI at surgery and at 2, 5, and 10 years postoperatively. This resulted in 763 patients (310 who underwent THA and 453 who underwent TKA). The mean patient age was 66 years, and 60% of patients were female. BMI changes were analyzed with repeated-measures analysis of variance. Multinomial logistic regression determined predictors of BMI change. Results: Following THA, the mean BMI increased from 30.3 kg/m 2 at surgery to 30.9 kg/m 2 at both 2 years (p = 0.003) and 5 years (p = 0.002). Following TKA, the mean BMI increased from 32.7 kg/m 2 at surgery to 33.1 kg/m 2 at both 2 years (p = 0.053) and 5 years (p = 0.040). By 10 years, the mean BMI was 30.6 kg/m 2 (p = 0.453) for patients undergoing THA and 32.6 kg/m 2 (p = 0.947) for patients undergoing TKA, similar to the BMIs at surgery. At 10 years, 27% of patients who underwent THA and 30% of patients who underwent TKA had a BMI decrease of >5%, whereas 30% of patients who underwent THA and 32% of patients who underwent TKA had a BMI increase of >5%. Female sex among patients who underwent THA increased the odds of a >5% BMI increase at 10 years (odds ratio [OR], 2.1; p = 0.006). Older age among patients who underwent TKA decreased the odds of a >5% BMI increase at 10 years (OR per year, 0.95; p < 0.001). Conclusions: Although most patients experienced a BMI change of >5% at 10 years, the mean BMI did not meaningfully change 2, 5, or 10 years after THA or TKA. Arthroplasty should not be viewed as a gateway to BMI improvement for patients overall, but female sex and older age may predict clinically important weight changes 10 years after arthroplasty. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.