Citations

Abstract Aims The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems‐level analysis. Methods Imaging‐based cortical structural maps from a large‐scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell‐type deconvolution, differential expression analysis and cell‐type enrichment analyses were used to identify differences in cell‐type distribution. These differences were followed up in post‐mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell‐type‐specific depletion was used in a murine model of acquired epilepsy. Results We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post‐mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non‐spatial memory test seen in epileptic mice not depleted of microglia. Conclusions These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Abstract Articular cartilage defects are common and can result in substantial pain and disability, prompting operative intervention, which commonly includes chondral debridement. Controlled defect preparation up to but not beyond the calcified cartilage layer is key to clinical success, but this remains technically challenging. We present a technique highlighting the substantial decrease in curette stroke volume and associated shift to a lower pitch when achieving satisfactory open cartilage defect debridement. These audiologic cues correlate well with histologic accuracy of debridement. Therefore, quantifiable pitch and volume changes serve as valuable technical cues for precise defect preparation at the time of joint preservation surgery. Classifications I: knee, II: cartilage. Technique Video video See video under supplementary data.

Abstract Aim The aim of this study was to compare long-term all-cause mortality between patients receiving percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) using multiple (MAG) or single arterial grafting (SAG). Methods and results The current study is a post hoc analysis of the SYNTAX Extended Survival Study, which compared PCI with CABG in patients with three-vessel (3VD) and/or left main coronary artery disease (LMCAD) and evaluated survival with ≥10 years of follow-up. The primary endpoint was all-cause mortality at maximum follow-up (median 11.9 years) assessed in the as-treated population. Of the 1743 patients, 901 (51.7%) underwent PCI, 532 (30.5%) received SAG, and 310 (17.8%) had MAG. At maximum follow-up, all-cause death occurred in 305 (33.9%), 175 (32.9%), and 70 (22.6%) patients in the PCI, SAG, and MAG groups, respectively (P < 0.001). Multiple arterial grafting [adjusted hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.49–0.89], but not SAG (adjusted HR 0.83, 95% CI 0.67–1.03), was associated with significantly lower all-cause mortality compared with PCI. In patients with 3VD, both MAG (adjusted HR 0.55, 95% CI 0.37–0.81) and SAG (adjusted HR 0.68, 95% CI 0.50–0.91) were associated with significantly lower mortality than PCI, whereas in LMCAD patients, no significant differences between PCI and MAG (adjusted HR 0.90, 95% CI 0.56–1.46) or SAG (adjusted HR 1.11, 95% CI 0.81–1.53) were observed. In patients with revascularization of all three major myocardial territories, a positive correlation was observed between the number of myocardial territories receiving arterial grafts and survival (P trend = 0.003). Conclusion Our findings suggest that MAG might be the more desirable configuration for CABG to achieve lower long-term all-cause mortality than PCI in patients with 3VD and/or LMCAD. Trial registration Registered on clinicaltrial.gov. SYNTAXES: NCT03417050 (https://clinicaltrials.gov/ct2/show/NCT03417050); SYNTAX: NCT00114972 (https://www.clinicaltrials.gov/ct2/show/NCT00114972).

Objectives: Meniscus root tears are increasingly being recognized. Meniscus extrusion has previously been associated with medial root tears; however, the relationship between secondary meniscus restraints, such as the meniscotibial (MT) ligament, extrusion, and root tears has yet to be formally evaluated. The purpose of this study was to better understand the association between MT ligament competence, medial meniscus extrusion, and medial meniscus posterior root tears (MMPRT), as well as to determine the progression of meniscus extrusion over time. Methods: Serial MRI’s from our institution were reviewed for patients who showed evidence of medial meniscus extrusion and MMPRT on at least one of 2+ available MRI’s. All patients were symptomatic at the time of diagnosis. All MRI’s were analyzed independently by two board-certified musculoskeletal radiologists. MT ligament disruption, medial meniscus extrusion, and MMPRT presence was recorded for each MRI. The time between MRI’s, presence of insufficiency fractures, and Outerbridge classification for the medial femur and tibia were also evaluated. Results: 27 knees in 26 patients were included in this study, with a total of 63 MRI’s analyzed (21 knees with 2 MRI’s, 3 with 3 MRI’s, and 3 with 4 MRI’s). All patients demonstrated clear medial meniscus extrusion and meniscotibial ligament disruption prior to the subsequent development of MMPRTs (p < 0.001). Mean extrusion at the time of initial MRI was 3.3 ± 1.1 mm, and increased significantly to 5.5 ± 1.8 mm at the time of first imaging with an identified MMPRT (p < 0.001). The average time between initial MRI and the first identification of MMPRT on a later MRI was 1.7 ± 1.6 years. Conclusions: In a sample of 27 symptomatic knees with serial MRI’s both before and after MMPRT diagnosis, all patients demonstrated MT ligament disruption and associated meniscus extrusion prior to the development of subsequent medial meniscus root tears. These findings suggest that MT ligament disruption and medial meniscus extrusion represent early and predisposing events contributing to MMPRT. Therefore, this provides a possible explanation of why meniscus extrusion is not corrected with medial meniscus root repair.

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher ( P <0.001), and there were fewer women ( P =0.046) in the AF than in the non‐AF group. Left ventricular ejection fraction was significantly lower ( P =0.001), and cardiogenic shock was more often observed ( P <0.001) in the AF group. Both in‐hospital ( P <0.001) and long‐term mortality ( P <0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long‐term mortality (hazard ratio, 2.31; 95% CI, 1.50–3.55; P <0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in‐hospital and long‐term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in‐hospital and long‐term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01947621.

Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.

Introduction: Compared to other racial and ethnic groups, African Americans experience greater negative psychosocial factors (depression, stress), which are related to increased risk of cardiovascular disease (CVD). Little research has examined the association of positive psychosocial factors (optimism) with cardiovascular health in this population. Using the Jackson Heart Study (JHS) data, we examined the association of optimism with the American Heart Association Life’s Simple 7 TM (LS7), a measure of seven metrics that assesses a person’s cardiovascular health. Hypothesis: Higher levels of optimism are positively associated with individual LS7 metrics, and positively associated with the total LS7 score. Methods: We evaluated cross-sectional associations of optimism with each LS7 metric [cigarette smoking, physical activity, diet, body mass index (BMI), blood pressure, cholesterol, glucose] and with a composite LS7 score among 4,761 participants, 21-95 years old (women=3,070; men=1,691) enrolled in the JHS, a single-site, community-based cohort of African Americans residing in Jackson, MS. Optimism was measured in tertiles (low, moderate, high) to examine threshold effects. Each LS7 metric was classified as poor, intermediate, and ideal. LS7 metrics were also summed to create a total continuous score (0-13) categorized in tertiles (low, moderate, high). Multinomial logistic regression estimated the odds ratios (OR, 95% confidence interval-CI) of intermediate (vs. poor) and ideal (vs. poor) LS7 metric by levels of optimism. Multinomial regression also estimated the odds of moderate (vs. low) or high (vs. low) total LS7 score by optimism. Models adjusted for demographics, SES, and depressive symptoms. Results: Descriptive findings showed that participants who reported high optimism had ideal physical activity, nutrition, smoking, blood pressure, glucose and high total LS7 score (all p<0.01). After adjustment for age, sex, education, income, marital status, and insurance status, participants who reported high (vs. low) optimism had a 39% increased odds of having ideal (vs. poor) physical activity (OR 1.39; 95% CI 1.10-1.76) and a 33% increased odds of having ideal (vs. poor) smoking (OR 1.33; 95% CI 1.02-1.73). Participants who reported high (vs. low) optimism had a 34% greater odds of having a high (vs. low) total LS7 score (OR 1.34 95% CI 1.03-1.74) after full adjustment. Conclusion: Optimism is associated with ideal physical activity and ideal smoking, which is important for promoting cardiovascular health and reducing the risk of CVD among African Americans in this sample.

AbstractIntroductionProximal femur replacement (PFR) in the setting of tumor resection is associated with a high rate of postoperative complication. The online American College of Surgeons‐National Surgical Quality Improvement Program (ACS‐NSQIP) surgical risk calculator is approved by the Center of Medicare and Medicaid services to estimate 30‐day postoperative complications. This study was to determine if the ACS‐NSQIP can predict postoperative complications following PFR.MethodsWe reviewed 103 (61 male and 42 female) patients undergoing PFR using the Current Procedural Terminology (CPT) codes available in the calculator: 27125 (hemiarthroplasty), 27130 (total hip), 27132 (conversion to total hip), 27134 (revision total hip), 27137 (revision acetabulum), 27138 (revision femur), and 27365 (excision tumor hip). The predicted rates of complications were compared with the observed rates.ResultsComplications occurred in 54 (52%) of patients, with the predicted risk based on CPT codes: 27125 (21.5%); 27130 (7.8%); 27132 (16.6%), 27134 (17.8%), 27137 (14.4%), 274138 (22.7%), and 27365 (16.2%). The calculator was a poor predictor of complications (27125, area under the curve [AUC] 0.576); (27130, AUC 0.489); (27132, AUC 0.490); (27134, AUC 00.489); (27137, AUC 0.489); (27138, AUC 0.471); and (27365, AUC 0.538).ConclusionOncologic PFR is known for complications. The ACS‐NSQIP does not adequately predict the incidence of complications, and therefore cannot reliably be used in their shared decision‐making process preoperative.

Background: Cardiovascular disease (CVD) remains the leading cause of death for African-American (AA) adults. There is a low prevalence of ideal cardiovascular health (CVH) (as defined by the American Heart Association’s Life’s Simple 7 TM (LS7)), especially diet, physical activity and obesity among AAs placing them at a disproportionately high risk for CVD. The identification of psychosocial stress that may influence ideal CVH could assist in the development of more effective behavior change interventions among AAs. Objectives: The aim of this study is to examine the associations of multidimensional stressors (chronic stress, minor stressors, and major life events - MLEs) with the LS7 components (classified as poor, intermediate and ideal) in AAs. We hypothesize that stress is negatively associated with the likelihood of achievement of intermediate/ideal levels of the LS7 components and LS7 composite score after adjusting for traditional socio-demographic factors. Methods: Using the Jackson Heart Study (JHS), a cohort of AAs based in Jackson, Mississippi (n=4383), we conducted a cross-sectional analysis of the association of stress measures with LS7 components (smoking, diet, physical activity, body mass index, blood pressure, total cholesterol and glucose). This association was measured using logistic regression which assessed the odds ratios (OR, 95% confidence interval (CI)) of the achievement of intermediate/ideal levels of CVH with progressive adjustment for demographic, socioeconomic, behavioral and biomedical factors. A composite LS7 score was calculated [range 0-14; categorized as 0 to 6 (poor), 7 to 8 (intermediate) and 9 to 14 (ideal)]. We also constructed a cumulative stress score as a summation of tertiles of each stress measure (range 3-9). Results: Fewer participants achieved intermediate or ideal CVH for the LS7 components including diet (39%), physical activity (51%) and BMI (47%). Higher chronic stress and minor stressors scores were associated a decreased likelihood of achievement of ideal/intermediate levels for smoking [OR 0.80; 95% CI 0.73-0.88 and OR 0.84; 95% CI 0.75-0.94, respectively). Higher MLE scores were associated decreased likelihood of achievement of ideal/intermediate levels for smoking (OR 0.84; 95% CI 0.76-0.92) and glucose (OR 0.90; 95% CI 0.82-0.98). Those with higher minor stressors and MLE scores were less likely to achieve intermediate or ideal LS7 composite score categories (OR 0.89; 95% CI 0.81-0.97 and OR 0.91; 95% CI 0.84-0.98, respectively). There was no statistically significant association between LS7 composite scores and cumulative stress scores. Conclusions: Our results suggest that key stress measures may contribute adversely to CVH among AAs. These findings provide support for future lifestyle interventions which integrate a focus on alleviating stressors in this high risk population to improve CVH.