Citations

Background and Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans. Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts. Results: In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the HNF1A gene that reached genome-wide significance ( P =4.62×10 −8 ) and an additional 29 variants with suggestive evidence of association ( P <1×10 −6 ), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction P value of 2.08×10 −3 (0.05/24 unique loci), we were able to validate associations at the HNF1A locus in both SiGN ( P =8.18×10 −4 ) and METASTROKE ( P =1.72×10 −3 ) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the HNF1A gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the SFXN4 and TMEM108 genes represent potential novel ischemic stroke loci. Conclusions: These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.

Abstract Evidence-based medicine asks us to integrate the best available evidence with clinical experience and patient values. In the modern intensive care unit, the primary focus is on complex technology and electronic health records, often away from the bedside. Excess interventionism is the norm. The term “intensivist” itself implies an intensive management strategy, which can lead us away from a patient-centered practice and toward iatrogenic harm. Under the hashtag #zentensivist, an international, multiprofessional group of clinicians has begun to discuss via Twitter how to apply key principles of history taking, physical examination, physiology, pharmacology, and clinical research in a competent, compassionate, and minimalist fashion. The term “zentensivist” intentionally combines concepts seemingly at odds—Zen philosophy and intensive care—to describe a holistic approach to the art of caring for the critically ill. We describe the key tenets of zentensivist practice and how we may inspire these actions in those we lead and educate.

Sports-related concussion has been examined extensively in collision sports such as football and hockey. However, historically, lower-risk contact sports such as soccer have only more recently garnered increased attention. Here, we review articles examining the epidemiology, injury mechanisms, sex differences, as well as the neurochemical, neurostructural and neurocognitive changes associated with soccer-related concussion. From 436 titles and abstracts, 121 full texts were reviewed with a total of 64 articles identified for inclusion. Concussion rates are higher during competitions and in female athletes with purposeful heading rarely resulting in concussion. Given a lack of high-level studies examining sports-related concussion in soccer, clinicians and scientists must focus research efforts on large-scale data gathering and development of improved technologies to better detect and understand concussion.

Objective: To compare the clinical outcomes of static versus dynamic external fixation for elbow fracture-dislocations with persistent instability after surgical management. Design: Comparative, retrospective review. Setting: Two tertiary referral upper-extremity centers. Patients: Twenty-four elbows requiring external fixation for persistent elbow instability within 90 days of surgical management of an elbow fracture-dislocation. Intervention: Static and dynamic external fixation was used in 16 and 8 patients, respectively, for a median of 39 days (interquartile range, 33–48 days). Main Outcome Measurements: Elbow range of motion, complications, and revision surgeries. Results: Immediately after static and dynamic external fixation removal, there was no difference in elbow extension [33 degrees ± 16 degrees vs. 41 degrees ± 13 degrees, mean difference (MD) 7 degrees, 95% confidence interval (CI) −6 degrees–22 degrees] or flexion (114 degrees ± 35 degrees vs. 118 degrees ± 11 degrees, MD 4 degrees, 95% CI -23 degrees–132 degrees), respectively. At last follow-up, static and dynamic external fixation groups had no difference in elbow extension (27 degrees ± 13 degrees vs. 24 degrees ± 10 degrees, MD -3 degrees, 95% CI –15 degrees–7 degrees) or flexion (129 degrees ± 12 degrees vs. 128 degrees ± 14 degrees, MD -1 degree, 95% CI -13 degrees–10 degrees), respectively. Static and dynamic external fixation groups had no difference in complications [7 (44%) vs. 5 (63%), difference 19%, 95% CI -23%–54%] or revision surgeries [6 (38%) vs. 4 (50%), difference 13%, 95% CI -27%–49%]. Conclusions: No difference in range of motion, complications, and revision surgeries was detected after static versus dynamic external fixation of persistently unstable elbow fracture-dislocations. Due to ease of application, static external fixation is our preferred treatment for these injuries. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Abstract Background: Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism.Method: Metabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods.Results: Univariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules. Multivariate analysis with leave one-out cross validation allowed classification of samples as belonging to one of the two groups with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8-15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules.Conclusions: Mothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2-5 years after birth.

Background: Although diastolic dysfunction is common among patients treated with cancer therapy, no clear evidence has been shown that it predicts systolic dysfunction. This study evaluated the correlation of longitudinal diastolic strain time (Dst) with the routine echocardiography diastolic parameters and to estimated its role in the early detection of cardiotoxicity among patients with active breast cancer. Methods: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients referred to the cardio-oncology clinic. All patients with breast cancer, planned for Doxorubicin therapy were included. Echocardiography, including Global longitudinal systolic strain (GLS) and Dst, was assessed at baseline before chemotherapy (T1), during Doxorubicin therapy (T2) and after the completion of Doxorubicin therapy (T3). Cardiotoxicity were determined by GLS relative reduction of ≥15%. Dst was assessed as the time measured (ms) of the myocardium lengthening during diastole. =diastolic time (ms) measured. Results: Among 69 patients, 67 (97.1%) were females with a mean age 52±13years. Diastolic strain timeDst measurement was significantly associated with the standard routine diastolic parameters. Significant GLS reduction was observed in 10 (20%) patients at T3 . Both in a univariate and a multivariate analyses the change in Ds basal time from T1 to T2 emerged to be significantly associated with GLS reduction at T3 (p<0.04). Conclusions: Among breast cancer patients, Dst time showed high correlation to standard the routine diastolic echocardiography parameters. Relative reductionChange in Ds basal time emerged associated with clinically significant systolic dysfunction as measured by GLS reduction.