Citations

Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration United States National Institutes of Health Clinicaltrials.gov NCT02089217

Background: The effects of targeted neuromuscular training (TNMT) on movement biomechanics associated with the risk of anterior cruciate ligament (ACL) injuries are currently unknown. Purpose/Hypotheses: To determine the effectiveness of TNMT specifically designed to increase trunk control and hip strength. The hypotheses were that (1) TNMT would decrease biomechanical and neuromuscular factors related to an increased ACL injury risk and (2) TNMT would decrease these biomechanical and neuromuscular factors to a greater extent in athletes identified as being at a high risk for future ACL injuries. Study Design: Controlled laboratory study. Methods: Female athletes who participated in jumping, cutting, and pivoting sports underwent 3-dimensional biomechanical testing before the season and after completing TNMT. During testing, athletes performed 3 different types of tasks: (1) drop vertical jump, (2) single-leg drop, and (3) single-leg cross drop. Analysis of covariance was used to examine the treatment effects of TNMT designed to enhance core and hip strength on biomechanical and neuromuscular characteristics. Differences were also evaluated by risk profile. Differences were considered statistically significant at P < .05. Results: TNMT significantly increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. Athletes with a high risk before the intervention (risk profile III) had a more significant treatment effect of TNMT than low-risk groups (risk profiles I and II). Conclusion: TNMT significantly improved proximal biomechanics, including increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. TNMT that focuses exclusively on proximal leg and trunk risk factors is not, however, adequate to induce significant changes in frontal-plane knee loading. Biomechanical changes varied across the risk profile groups, with higher risk groups exhibiting greater improvements in their biomechanics.

Study Design: Retrospective multicenter case series study. Objective: Because cervical dural tears are rare, most surgeons have limited experience with this complication. A multicenter study was performed to better understand the presentation, treatment, and outcomes following cervical dural tears. Methods: Multiple surgeons from 23 institutions retrospectively identified 21 rare complications that occurred between 2005 and 2011, including unintentional cervical dural tears. Demographic data and surgical history were obtained. Clinical outcomes following surgery were assessed, and any reoperations were recorded. Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), Nurick classification (NuC), and Short-Form 36 (SF36) scores were recorded at baseline and final follow-up at certain centers. All data were collected, collated, and analyzed by a private research organization. Results: There were 109 cases of cervical dural tears among 18 463 surgeries performed. In 101 cases (93%) there was no clinical sequelae following successful dural tear repair. There were statistical improvements ( P < .05) in mJOA and NuC scores, but not NDI or SF36 scores. No specific baseline or operative factors were found to be associated with the occurrence of dural tears. In most cases, no further postoperative treatments of the dural tear were required, while there were 13 patients (12%) that required subsequent treatment of cerebrospinal fluid drainage. Analysis of those requiring further treatments did not identify an optimum treatment strategy for cervical dural tears. Conclusions: In this multicenter study, we report our findings on the largest reported series (n = 109) of cervical dural tears. In a vast majority of cases, no subsequent interventions were required and no clinical sequelae were observed.

Purpose The stiffness of a myocardial infarct affects the left ventricular pump function and remodeling. Magnetic resonance elastography (MRE) is a noninvasive imaging technique for measuring soft‐tissue stiffness in vivo. The purpose of this study was to investigate the feasibility of assessing in vivo regional myocardial stiffness with high‐frequency 3D cardiac MRE in a porcine model of myocardial infarction, and compare the results with ex vivo uniaxial tensile testing. Methods Myocardial infarct was induced in a porcine model by embolizing the left circumflex artery. Fourteen days postinfarction, MRE imaging was performed in diastole using an echocardiogram‐gated spin‐echo echo‐planar‐imaging sequence with 140‐Hz vibrations and 3D MRE processing. The MRE stiffness and tensile modulus from uniaxial testing were compared between the remote and infarcted myocardium. Results Myocardial infarcts showed increased in vivo MRE stiffness compared with remote myocardium (4.6 ± 0.7 kPa versus 3.0 ± 0.6 kPa, P = 0.02) within the same pig. Ex vivo uniaxial mechanical testing confirmed the in vivo MRE results, showing that myocardial infarcts were stiffer than remote myocardium (650 ± 80 kPa versus 110 ± 20 kPa, P = 0.01). Conclusions These results demonstrate the feasibility of assessing in vivo regional myocardial stiffness with high‐frequency 3D cardiac MRE. Magn Reson Med 79:361–369, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

9 Background: Early salvage radiation therapy (SRT) following radical prostatectomy (RP) has been shown to reduce biochemical recurrence and distant metastases. We aim to identify factors predictive of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) from a consortium database from 10 academic institutions. Methods: 2,454 node-negative patients (pts) with detectable post-prostatectomy PSA ( ≥ 0.01 ng/mL) treated with SRT ± neoadjuvant/concurrent androgen deprivation therapy (N/C ADT) were included. Cumulative incidence and Kaplan-Meier methods were used to estimate rates of PCSM and ACM, respectively. Univariate and multivariable analyses (MVA) were performed by competing risks regression and Cox proportional hazards methods for PCSM and ACM. Results: Median follow-up was 5 years from SRT completion and 8 years from date of RP; 24% had pathologic Gleason score (GS) of ≤ 6, 56% GS 7, and 19% GS ≥ 8; 56% extraprostatic extension (EPE), 18% seminal vesicle invasion (SVI), 58% positive surgical margins, and 16% received N/C ADT. Median age at RP and SRT were 62 years (IQR 56-66) and 64 years (59-69), respectively. Median SRT dose was 66 Gy (IQR 65-68) and median pre-SRT PSA was 0.5 ng/mL (IQR 0.3-1.1). MVA performed from SRT completion date demonstrated higher pre-SRT PSA (HR = 2.1), higher GS (GS 7 vs. ≤ 6: HR 2.0; GS ≥ 8 vs. 6: HR 3.3) , SVI (HR 2.5), year of SRT (2000-2004, 1995-1999, 1985-1994 vs. 2005-2012; HR 2.9, HR 2.5, HR 3.6, respectively) were significantly associated with higher PCSM. These same variables were all significantly associated with higher PCSM and ACM rates calculated from both SRT completion date and date of RP. Conclusions: Initiation of early SRT at lower post-operative PSA levels following RP is associated with reduced risk of PCSM and ACM, even when calculated from RP date to account for lead time bias. Other factors significantly associated with PCSM include higher GS, SVI, and earlier year of SRT. [Table: see text]

Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics for treating C9ORF72 -associated amyotrophic lateral sclerosis.

Background: Obesity as a cause of lower extremity deformity in children has been well established. This deformity is most often seen as tibia vara, however, at our institution we have observed more obese children and adolescents over age 7 years with excessive or progressive idiopathic genu valgum. Our hypothesis is that children with idiopathic genu valgum have high rates of obesity which impact the severity of their disease. Methods: Retrospective review of existing data was performed on 66 consecutive children/112 limbs over age 7 years with idiopathic genu valgum, seen from 2010 to 2013. Children with known metabolic or skeletal disease were excluded. Genu valgum was defined as mechanical axis in zone II or III and mechanical tibiofemoral angle ≥4 degrees on standing anteroposterior radiograph of the lower extremities. Body mass index (BMI) was calculated and classified by Center for Disease Control percentiles. Skeletal maturation was rated by closure of pelvic and peri-genu physes. Severity of genu valgum was also assessed by femoral and tibial mechanical axes and the mechanical axis deviation. Results: Mean patient age was 12.2±2.2 years. 47% of patients had BMI≥30 and 71% were categorized as obese (>95th percentile). No sex differences were identified. Skeletal maturation explained 25% of the variance in the mechanical axis deviation and 22% of the mechanical tibiofemoral angle. BMI predicted 9.8% of the tibial valgus. Because of its skewed distribution, BMI percentile was a less useful parameter for assessment. Conclusions: The 71% obesity rate found in our children with idiopathic genu valgum is significantly higher than the normal population. Higher BMI is associated with more tibial valgum but skeletal maturation was the main predictor of overall valgus severity. This suggests that obesity may play a role in the etiology of idiopathic genu valgum which progresses with skeletal maturation, thereby increasing the risk of osteoarthritis in adulthood. Level of Evidence: Level III.