Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Traces of trauma – a multivariate pattern analysis of childhood trauma, brain structure and clinical phenotypes

Background: Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context. Methods: We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels. Results: We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample. Conclusions: Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research

A fully radiopaque hybrid stent retriever versus a precursor device: Outcome, efficacy, and safety in large vessel stroke

Background and Purpose The aim of this multicenter study was to compare the clinical outcome, safety, and efficacy of the full-length radiopaque Aperio Hybrid stent retriever (APH) with the precursor Aperio thrombectomy device (AP). Methods Multicentric retrospective analysis of patients with stroke, treated with the APH and AP due to an acute ischemic stroke by large vessel occlusions in the anterior or posterior circulation, was performed. We focused on the comparison of favorable clinical outcome (modified Rankin Scale, 0-2) after 3 months, favorable reperfusion rates (thrombolysis in cerebral infarction scale >= 2b), and the complication rate. Results A total of 51 patients (female: n = 33, 64.7%, mean age 73 +/- 16 years) with a median baseline National Institutes of Health Stroke Scale: 15 were treated with the APH or AP. Favorable outcome in patients treated with APH was excellent (44.0%) and comparable to the AP (36.8%). The rate of final favorable reperfusion for both devices was outstanding (APH 31/31 and AP 20/20). The overall complication rate for the APH was slightly higher compared to the AP (32.3%/15.0%). Symptomatic intracranial hemorrhage was recorded in 0 of 51 cases. The all-cause mortality rate at 90 days was 20.0% for the APH and comparable for the AP (21.1%). Conclusions Comparable clinical outcome, efficacy, and safety of the AP and the recently introduced APH were demonstrated. Both devices appeared feasible, efficient, and safe with regard to endovascular treatment in large vessel occlusion

3D-Printed Simulation Device for Orbital Surgery

OBJECTIVES: Orbital surgery is a challenging procedure because of its complex anatomy. Training could especially benefit from dedicated study models. The currently available devices lack sufficient anatomical representation and realistic soft tissue properties. Hence, we developed a 3D-printed simulation device for orbital surgery with tactual (haptic) correct simulation of all relevant anatomical structures. DESIGN, SETTING, AND PARTICIPANTS: Based on computed tomography scans collected from patients treated in a third referral center, the hard and soft tissue were segmented and virtually processed to generate a 3D-model of the orbit. Hard tissue was then physically realized by 3D printing. The soft tissue was manufactured by a composite silicone model of the nucleus and the surrounding tissue over a negative mold model also generated by 3D-printing. The final model was evaluated by a group of 5 trainees in oral and maxillofacial surgery (1) and a group of 5 consultants (2). All participants were asked to reconstruct an isolated orbital floor defect with a titanium implant. A stereotactic navigation system was available to all participants. Their experience was evaluated for haptic realism, correct representation of surgical approach, general handling of model, insertion of implant into the orbit, placement and fixation of implant, and usability of navigated control. The items were evaluated via nonparametric statistics (1 [poor]-5 [good]). RESULTS: Group 1 gave an average mark of 4.0 (+/- 0.9) versus 4.6 (+/- 0.6) by group 2. The haptics were rated as 3.6 (+/- 1.1) [1] and 4.2 (+/- 0.8) [2]. The surgical approach was graded 3.7 (+/- 1.2) [1] and 4.0 (+/- 1.0) [2]. Handling of the models was rated 3.5 (+/- 1.1) [1] and 4 (+/- 0.7) [2]. The insertion of the implants was marked as 3.7 (+/- 0.8) [1] and 4.2 (+/- 0.8) [2]. Fixation of the implants was also perceived to be,realistic with 3.6 (+/- 0.9) [1] and 4.2 (+/- 0.45) [2]. Lastly, surgical navigation was rated 3.8 (+/- 0.8) [1] and 4.6 (+/- 0.56) [2]. CONCLUSION: In this project, all relevant hard and soft tissue characteristics of orbital anatomy could be realized. Moreover, it was possible to demonstrate that the entire workflow of an orbital procedure may be simulated. Hence, using this model training expenses may be reduced and patient security could be enhanced. ((C) 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Accelerated Clustered Sparse Acquisition to Improve Functional MRI for Mapping Language Functions

Background Functional magnetic resonance imaging (fMRI) is a useful method for noninvasive presurgical functional mapping. However, the scanner environment is inherently unsuitable for the examination of auditory and language functions, due to the loud acoustic noise produced by the scanner. Interleaved acquisition methods alleviate this problem by providing a silent period for stimulus presentation and/or response control (sparse sampling) but at the expense of a diminished amount of data collected. There are possible improvements to these sparse acquisition methods that increase the amount of data by acquiring several images per event (clustered sampling). We tested accelerated clustered fMRI acquisition in comparison with conventional sparse sampling in a pilot study. Methods The clustered and sparse acquisition techniques (7.4 minutes scanning time per protocol) were directly compared in 15 healthy subjects (8 men; mean age: 24 +/- 3 years) using both a motor (tongue movement) and a language (overt picture-naming) task. Functional imaging data were analyzed using Statistical Parametric Mapping software (SPM12 Wellcome Department of Imaging Neuroscience, London, UK). For both tasks, activation levels were compared and Euclidean distances (EDs) between cluster centers (i.e., local activation maxima and centers of gravity) were calculated. Overlaps and laterality indices were computed for the picture-naming task. In addition, the feasibility of the clustered acquisition protocol in a clinical setting was assessed in one pilot patient. Results For both tasks, activation levels were higher using the clustered acquisition protocol, reflected by bigger cluster sizes ( p < 0.05). Mean ED between cluster centers ranged between 9.9 +/- 5.4 mm (left superior temporal gyrus; centers of gravity) and 16.6 +/- 13.2 mm (left inferior frontal gyrus; local activation maxima) for the picture-naming task. Overlaps between sparse and clustered acquisition reached 88% (Simpson overlap coefficient). A similar activation pattern for both acquisition methods was also confirmed in the clinical case. Conclusion Despite some drawbacks inherent to the acquisition technique, the clustered sparse sampling protocol showed increased sensitivity for activation in language-related cortical regions with short scanning times. Such scanning techniques may be particularly advantageous for investigating patients with contraindications for long scans (e.g., reduced attention span)

Extending the Indication of Woven EndoBridge (WEB) Embolization to Internal Carotid Artery Aneurysms: A Multicenter Safety and Feasibility Study

OBJECTIVE: Woven Endobridge (WEB) embolization is an approved technique for endovascular treatment of wide-necked and bifurcation aneurysms. However, the WEB has not yet been routinely used for internal carotid artery (ICA) sidewall aneurysms. In this multicenter study, we evaluate the safety and efficacy of WEB for treatment of these aneurysms. METHODS: We reviewed all patients with ICA sidewall aneurysms who were treated with WEB at 3 German neurovascular centers between 2011 and 2018. Technical success, complication rates, and angiographic outcome were retrospectively assessed. RESULTS: Twenty patients (mean age, 56.3 +/- 13.0 years) with 20 ICA aneurysms (6 ruptured) were identified. The aneurysms were located at the paraophthalmic segment (n = 10), the posterior communicating artery segment (n = 9), and the anterior choroidal artery segment (n = 1). The mean aneurysm size was 8.1 +/- 5.2 mm and 60% were wide-necked. The aneurysms were treated with a single WEB (n = 11) or in combination with coiling and/or stent implantation (n = 7). WEB implantation failed in 2 aneurysms because of a sharp aneurysm angle. There were 1 periprocedural thromboembolic event and 1 in-stent stenosis at follow-up, which remained asymptomatic in both cases. There was no procedure-related morbidity and mortality. At follow-up, complete occlusion was achieved in 76.5%, neck remnants in 17.6%, and aneurysms remnants in 5.9%. CONCLUSIONS: The WEB device can be used for treatment of ICA sidewall aneurysms with a high level of procedural safety and a high degree of technical success

Long-Term Follow-Up and Clinical Relevance of Incidental Findings of Fibrin Sheath and Thrombosis on Computed Tomography Scans of Cancer Patients with Port Catheters

Purpose: This retrospective study examined the incidence, progression, and clinical relevance of catheter-related thrombosis (CRT) and/or fibrin sheaths presenting as incidental findings on routine staging computed tomography (CT) scans performed in cancer patients. Patients and Methods: Patients who underwent central venous port catheter (CVC) placement in a tertiary care hospital between September 2010 and August 2013 were followed up for up to five years. Two radiologists assessed the presence of fibrin sheath and thrombosis in consensus in staging CT scan. Patient demographics, type of cancer, preoperative comorbidities, date of CVC placement and CTs, preexisting anticoagulation, as well as the type and treatment of catheter-related complications were determined from the electronic medical record. Results: A total of 194 patients with 530 CT scans and a mean follow-up time of 394 days were included. Fibrin sheaths and thromboses were seen on 46 scans (8.7%) in 30 patients and 80 scans (15.1%) in 35 patients. The incidence of fibrin sheaths and thromboses was found to be 15.5% and 18%, respectively. The comparison to initial CT reports results indicated that fibrin sheaths or thromboses were missed in 106 examinations (20%). Catheter-associated complications were reported in 14 patients (21.5%) without specific therapy. Conclusion: Fibrin sheaths and CRTs are often overlooked on routine CT scans when patients are asymptomatic. The subsequent high complication rate demonstrates the clinical relevance of the initial incidental finding on CT scan. Further studies should elucidate the effect of thrombolytic agents and interventional radiologic treatment in asymptomatic patients