Citations

Abstract This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich‐club) brain regions on functional outcome post‐stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3‐months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI‐GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas‐defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non‐rich club regions. In spatial specificity analyses, we randomized the split into “rich club” and “non‐rich club” regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex‐specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female‐specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club‐combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long‐term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

Abstract The advent of single-cell biology opens a new chapter for understanding human biological processes and for diagnosing, monitoring, and treating disease. This revolution now reaches the field of cardiovascular disease (CVD). New technologies to interrogate CVD samples at single-cell resolution are allowing the identification of novel cell communities that are important in shaping disease development and direct towards new therapeutic strategies. These approaches have begun to revolutionize atherosclerosis pathology and redraw our understanding of disease development. This review discusses the state-of-the-art of single-cell analysis of atherosclerotic plaques, with a particular focus on human lesions, and presents the current resolution of cellular subpopulations and their heterogeneity and plasticity in relation to clinically relevant features. Opportunities and pitfalls of current technologies as well as the clinical impact of single-cell technologies in CVD patient care are highlighted, advocating for multidisciplinary and international collaborative efforts to join the cellular dots of CVD.

Abstract Objective To investigate the relation between biomarkers of inflammation and subsequent development of GCA. Method Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30 447), established 1991–96, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth and year of screening were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on eigenvalues, proteins with a factor loading of >0.50 were investigated. Results Ninety-four cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-γ was positively associated with GCA [odds ratio (OR) per s.d. 1.52; 95% CI 1.00, 2.30]. Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-γ (OR 2.37; 95% CI 1.14, 4.92) and monocyte chemotactic protein 3 (MCP3) (OR 4.27; 95% CI 1.26, 14.53) were particularly associated with increased risk of GCA in the subset sampled <8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25. Conclusion Elevated IFN-γ levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.

Objective: The aim of this multicentric registry was to assess the outcomes of “anteRior versus posteRior divisional bRanches Of the hYpogastric artery as distAl landing zone for iLiac branch devices (R3OYAL).” Methods: The main exposure of interest for the purpose of this study was the internal iliac artery (IIA) divisional branch (anterior vs posterior) that was used as distal landing zone. Early endpoints included technical success and adverse events. Late endpoints included survival, primary/secondary IIA patency, and IIA branch instability. Results: A total of 171 patients were included in the study, of which 50 received bilateral implantation of iliac branch devices (IBDs). This resulted in a total of 221 incorporated IIAs included in the final analysis, of which 40 were anterior divisional branches and 181 were posterior divisional branches. Technical success was high in both groups (anterior division: 98% vs posterior division: 100%, P = .18). Occurrence of any adverse event was noted in 14% of patients in both groups ( P = 1.0). The overall rate of freedom from the composite IBD branch instability did not show significant differences between patients receiving distal landing in the anterior or posterior division of the IIA at 3 years (79% vs 87%, log-rank test = .215). The 3-year estimates of IBD patency were significantly lower in patients who received distal landing in the anterior divisional branch than those who received distal landing in the posterior divisional branch (primary patency: 81% vs 96%, log-rank test = .009; secondary patency: 81% vs 97%, log-rank test < .001). Conclusions: The use of the anterior or posterior divisional branches of the IIA as distal landing zone for IBD implantation shows comparable profiles in terms of immediate technical success, perioperative safety, and side-branch instability up to 3 years. However, IBD patency at 3 years was higher when the distal landing zone was achieved within the posterior divisional branch of the IIA. Clinical Impact The results from this large multicentric registry confirm that use of the anterior or posterior divisional branches of the internal iliac artery (IIA) as distal landing zone for implantation of iliac branch devices (IBD) shows comparable profiles of safety and feasibility, thereby allowing to extend the indications for endovascular repair of aorto-iliac aneurysms to cases with unsuitable anatomy within the IIA main trunk. Although mid-term rates of device durability and branch instability seem to be similar, the rates of primary and secondary IBD patency at three years was favored when the distal landing zone was achieved in the posterior divisional branch of the IIA.

Objectives To assess whether recommendations of individually oriented lifestyle interventions (IOLIs) in guidelines from the National Institute for Health and Care Excellence (NICE) were underpinned by evidence of benefit, and whether harms and opportunity costs were considered. Design Cross sectional survey. Setting UK. Data sources NICE guidelines and supporting evidence. Eligibility criteria All NICE pathways for IOLI recommendations (ie, non-drug interventions that healthcare professionals administer to adults to achieve a healthier lifestyle and improve health) were searched systematically on 26 August 2020. One author screened all retrieved pathways for candidate guidelines, while a second author verified these judgments. Two authors independently and in duplicate screened all retrieved guidelines and recommendations for eligibility, extracted data, and evaluated the evidence cited and the outcomes considered. Disagreements were noted and resolved by consensus. Results Within 57 guidelines, 379 NICE recommendations were found for IOLIs; almost all (n=374; 99%) recommended the lifestyle intervention and five (1%) recommended against the intervention. Of the 379 recommendations, 13 (3%) were supported by moderate or high certainty evidence of a beneficial effect on patient relevant outcomes (n=7; 2%) or surrogate outcomes (n=13; 3%). 19 (5%) interventions considered psychosocial harms, 32 (8%) considered physical harms, and one (<1%) considered the opportunity costs of implementation. No intervention considered the burden placed on individuals by these recommendations. Conclusion Few NICE recommendations of lifestyle interventions are supported by reliable evidence. While this finding does not contest the beneficial effects of healthy habits, guidelines recommending clinicians to try to change people’s lifestyle need to be reconsidered given the substantial uncertainty about the effectiveness, harms, and opportunity costs of such interventions.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

AbstractPurposeAccurate prediction of outcome following hip arthroscopy is challenging and machine learning has the potential to improve our predictive capability. The purpose of this study was to determine if machine learning analysis of the Danish Hip Arthroscopy Registry (DHAR) can develop a clinically meaningful calculator for predicting the probability of a patient undergoing subsequent revision surgery following primary hip arthroscopy.MethodsMachine learning analysis was performed on the DHAR. The primary outcome for the models was probability of revision hip arthroscopy within 1, 2, and/or 5 years after primary hip arthroscopy. Data were split randomly into training (75%) and test (25%) sets. Four models intended for these types of data were tested: Cox elastic net, random survival forest, gradient boosted regression (GBM), and super learner. These four models represent a range of approaches to statistical details like variable selection and model complexity. Model performance was assessed by calculating calibration and area under the curve (AUC). Analysis was performed using only variables available in the pre‐operative clinical setting and then repeated to compare model performance using all variables available in the registry.ResultsIn total, 5581 patients were included for analysis. Average follow‐up time or time‐to‐revision was 4.25 years (± 2.51) years and overall revision rate was 11%. All four models were generally well calibrated and demonstrated concordance in the moderate range when restricted to only pre‐operative variables (0.62–0.67), and when considering all variables available in the registry (0.63–0.66). The 95% confidence intervals for model concordance were wide for both analyses, ranging from a low of 0.53 to a high of 0.75, indicating uncertainty about the true accuracy of the models.ConclusionThe association between pre‐surgical factors and outcome following hip arthroscopy is complex. Machine learning analysis of the DHAR produced a model capable of predicting revision surgery risk following primary hip arthroscopy that demonstrated moderate accuracy but likely limited clinical usefulness. Prediction accuracy would benefit from enhanced data quality within the registry and this preliminary study holds promise for future model generation as the DHAR matures. Ongoing collection of high‐quality data by the DHAR should enable improved patient‐specific outcome prediction that is generalisable across the population.Level of evidenceLevel III.

OBJECTIVE The goal of microsurgical resection of vestibular schwannoma (VS) is gross-total resection (GTR) to provide oncological cure. However, a popular strategy is to halt the resection if the surgical team feels the risk of cranial nerve injury is imminent, achieving a maximally safe subtotal resection (STR) instead. The tumor remnant can then be treated with stereotactic radiosurgery (SRS) once the patient has recovered from the immediate postoperative period, or it can be followed with serial imaging and treated with SRS in a delayed fashion if residual tumor growth is seen. In this study, the authors evaluated the efficacy of this multimodality approach, particularly the influence of timing and dose of SRS on radiological tumor control, need for salvage treatment, and cranial nerve function. METHODS VS patients treated with initial microsurgery and subsequent radiosurgery were retrospectively included from two tertiary treatment centers and dichotomized depending on whether SRS was given upfront (defined as before 12 months) or later. Radiological tumor control was defined as less than 20% tumor volume expansion and oncological tumor control as an absence of salvage treatment. Facial and cochlear nerve functions were assessed after surgery, at the time of SRS, and at last follow-up. Finally, a systematic literature review was conducted according to PRISMA guidelines. RESULTS A total of 110 VS patients underwent SRS following microsurgical resection, with a mean preradiosurgical tumor volume of 2.2 cm3 (SD 2.5 cm3) and mean post-SRS follow-up time of 5.8 years (SD 4.1 years). The overall radiological tumor control and oncological tumor control were 77.3% and 90.9%, respectively. Thirty-five patients (31.8%) received upfront SRS, while 75 patients (68.2%) were observed for a minimum of 12 months prior to SRS. The timing of SRS did not influence the radiological tumor control (p = 0.869), the oncological tumor control (p = 0.560), or facial nerve (p = 0.413) or cochlear nerve (p = 0.954) function. An escalated marginal dose (> 12 Gy) was associated with greater tumor shrinkage (p = 0.020) and superior radiological tumor control (p = 0.020), but it did not influence the risk of salvage treatment (p = 0.904) or facial (p = 0.351) or cochlear (p = 0.601) nerve deterioration. CONCLUSIONS Delayed SRS after close observation of residuals following STR is a safe alternative to upfront SRS regarding tumor control and cranial nerve preservation in selected patients.