Citations

The expansion of technologies available for the study of migraine pathophysiology has evolved greatly over the last 15 years. Two areas of rapid progress are investigations focusing on the genetics of migraine and others utilizing novel functional neuroimaging techniques. Genetic studies are increasingly focusing on sporadic migraine and the utilization of unbiased searches of the human genome to identify novel variants associated with disease susceptibility. At the same time, neuroimaging studies have provided novel insights into the altered neuronal and network dynamics of the migrainous brain. These 2 parallel approaches provide complementary insights into the complexity and heterogeneity of migraine.

Background— Outpatient cardiac rehabilitation (CR) decreases mortality rates but is underutilized. Current median time from hospital discharge to enrollment is 35 days. We hypothesized that an appointment within 10 days would improve attendance at CR orientation. Methods and Results— At hospital discharge, 148 patients with a nonsurgical qualifying diagnosis for CR were randomized to receive a CR orientation appointment either within 10 days (early) or at 35 days (standard). The primary end point was attendance at CR orientation. Secondary outcome measures were attendance at ≥1 exercise session, the total number of exercise sessions attended, completion of CR, and change in exercise training workload while in CR. Average age was 60±12 years; 56% of participants were male and 49% were black, with balanced baseline characteristics between groups. Median time (95% confidence interval) to orientation was 8.5 (7–13) versus 42 (35 to NA [not applicable]) days for the early and standard appointment groups, respectively ( P <0.001). Attendance rates at the orientation session were 77% (57/74) versus 59% (44/74) in the early and standard appointment groups, respectively, which demonstrates a significant 18% absolute and 56% relative improvement (relative risk, 1.56; 95% confidence interval, 1.03–2.37; P =0.022). The number needed to treat was 5.7. There was no difference ( P >0.05) in any of the secondary outcome measures, but statistical power for these end points was low. Safety analysis demonstrated no difference between groups in CR-related adverse events. Conclusions— Early appointments for CR significantly improve attendance at orientation. This simple technique could potentially increase initial CR participation nationwide. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01596036.

BackgroundIn recent years, percutaneous device closure has become commonplace for treatment of atrial septal defect (ASD) and patent foramen ovale (PFO). However, the effect of device closure on aortic valve regurgitation (AR) has been questioned.ObjectiveThe purpose of this study was to define changes in AR using echocardiography, before and after device closure of ASD or PFO.MethodsWe retrospectively reviewed all patients who had percutaneous device closure of ASD or PFO at our institution between 2005 and 2009. We compared the preprocedure echocardiogram to the most recent follow‐up study. All investigators were blinded to referral diagnosis, patient demographics, and size and type of the device placed. Aortic regurgitation was graded as none/trivial, mild, moderate, or severe.ResultsOverall, 322 patients qualified for inclusion; 204 with PFO and 118 with ASD. Mean age at time of closure was 48 ± 20 years (range 3–85 years). Mean duration of follow‐up was 1.2 years (range 2 months to 5 years). Only two patients (0.6%) demonstrated any appreciable increase in AR severity. However, both of these patients manifested a clinically insignificant change from a trivial to mild grade of aortic regurgitation.ConclusionsPercutaneous device closure of PFO or ASD does not increase the incidence or severity of AR over medium‐term follow‐up. © 2012 Wiley Periodicals, Inc.

R231H Causes a High Penetrance for Familial AFBackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is expected to grow. A genetic predisposition for AF has long been recognized, but its manifestation in these patients likely involves a combination of rare and common genetic variants. Identifying genetic variants that associate with a high penetrance for AF would represent a significant breakthrough for understanding the mechanisms that associate with disease.Method and ResultsCandidate gene sequencing in 5 unrelated families with familial AF identified the KCNQ1 missense mutation p.Arg231His (R231H). In addition to AF, several of the family members have abnormal QTc intervals, syncope or experienced sudden cardiac arrest or death. KCNQ1 encodes the voltage‐gated K+ channel that conducts the slowly activating delayed rectifier K+ current in the heart. Functional and computational analyses suggested that R231H increases KCNQ1 current (IKCNQ1) to shorten the atrial action potential (AP) duration. R231H is predicted to minimally affect ventricular excitability, but it prevented the increase in IKCNQ1 following PKA activation. The unique properties of R231H appeared to be caused by a loss in voltage‐dependent gating.ConclusionsThe R231H variant causes a high penetrance for interfamilial early‐onset AF. Our study indicates R231H likely shortens atrial refractoriness to promote a substrate for reentry. Additionally, R231H might cause abnormal ventricular repolarization by disrupting PKA activation of IKCNQ1. We conclude genetic variants, which increase IKs during the atrial AP, decrease the atrial AP duration, and/or shorten atrial refractoriness, present a high risk for interfamilial AF.

ABSTRACTObjectives:Despite a paucity of published supporting data, 5‐aminosalicylate (5‐ASA) use in pediatric ulcerative colitis (UC) is common. The present study describes the use and outcome of a large multicenter inception cohort of children with UC treated with 5‐ASA.Methods:Data were obtained from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, a prospective North American observational study of children newly diagnosed as having inflammatory bowel disease ages 16 years or younger. Patient data are recorded at diagnosis, 30 days, and then quarterly. Patients are managed by physician dictate, not protocol. Disease activity is classified by physician global assessment. The primary outcome examined was corticosteroid (CS) free, inactive UC at 1 year following initiation of 5‐ASA within 30 days of diagnosis (with or without concomitant CS use) without the need for rescue therapy (immunomodulators, biologics, or colectomy).Results:Study subjects included 213 patients newly diagnosed as having UC who received oral 5‐ASA compounds (115 of whom also received CS) during the first 30 days after diagnosis, and no other oral therapies for the treatment of UC. Of these 213 patients, 86 (40%) were CS free and physician global assessment inactive at 1 year without rescue. Outcome was not associated with disease severity at diagnosis, demographic or laboratory factors examined, or initial dose of 5‐ASA used.Conclusions:Forty percent of children taking 5‐ASA as primary maintenance therapy at diagnosis are in CS‐free remission after 1 year of treatment. Further pediatric studies will be needed to address whether increased adherence and/or higher dosing schedules will improve outcomes.

Abstract The inv(16)(p13q22)/t(16;16)(p13;q22) in acute myeloid leukemia results in multiple CBFB-MYH11 fusion transcripts, with type A being most frequent. The biologic and prognostic implications of different fusions are unclear. We analyzed CBFB-MYH11 fusion types in 208 inv(16)/t(16;16) patients with de novo disease, and compared clinical and cytogenetic features and the KIT mutation status between type A (n = 182; 87%) and non–type A (n = 26; 13%) patients. At diagnosis, non–type A patients had lower white blood counts (P = .007), and more often trisomies of chromosomes 8 (P = .01) and 21 (P < .001) and less often trisomy 22 (P = .02). No patient with non–type A fusion carried a KIT mutation, whereas 27% of type A patients did (P = .002). Among the latter, KIT mutations conferred adverse prognosis; clinical outcomes of non–type A and type A patients with wild-type KIT were similar. We also derived a fusion-type–associated global gene-expression profile. Gene Ontology analysis of the differentially expressed genes revealed—among others—an enrichment of up-regulated genes involved in activation of caspase activity, cell differentiation and cell cycle control in non–type A patients. We conclude that non–type A fusions associate with distinctclinical and genetic features, including lack of KIT mutations, and a unique gene-expression profile.

Object The object of this study was to determine the potential of magnetic resonance elastography (MRE) to preoperatively assess the stiffness of meningiomas. Methods Thirteen patients with meningiomas underwent 3D brain MRE examination to measure stiffness in the tumor as well as in surrounding brain tissue. Blinded to the MRE results, neurosurgeons made a qualitative assessment of tumor stiffness at the time of resection. The ability of MRE to predict the surgical assessment of stiffness was tested using a Spearman rank correlation. Results One case was excluded due to a small tumor size. In the remaining 12 cases, both tumor stiffness alone (p = 0.023) and the ratio of tumor stiffness to surrounding brain tissue stiffness (p = 0.0032) significantly correlated with the surgeons' qualitative assessment of tumor stiffness. Results of the MRE examination provided a stronger correlation with the surgical assessment of stiffness compared with traditional T1- and T2-weighted imaging (p = 0.089), particularly when considering meningiomas of intermediate stiffness. Conclusions In this cohort, preoperative MRE predicted tumor consistency at the time of surgery. Tumor stiffness as measured using MRE outperformed conventional MRI because tumor appearance on T1- and T2-weighted images could only accurately predict the softest and hardest meningiomas.