Citations

OBJECT Action motorsports, including motocross, have been gaining popularity among children and adolescents, raising concerns for increased risk of concussions in participating youth. The authors undertook this study to test the following hypotheses: 1) that there is a high rate of concussion symptoms associated with a number of preventable or adjustable risk factors, and 2) that a high percentage of these symptoms are not be reported to adults and medical personnel. METHODS The authors identified all motocross riders under the age of 18 at a regional racetrack during the riding season between May and October 2010. The participants completed questionnaires pertaining to demographic characteristics and variables associated with motocross. The questionnaire results were compared with the incidence of self-reported concussion symptoms. RESULTS Two hundred two riders were identified who met the criteria for participation in the study, and 139 of them completed the study questionnaire. Of these 139 riders, 67 (48%) reported at least 1 concussion symptom during the season. The majority of riders (98%) reported “always” wearing a helmet, and 72% received professional help with fitting of their helmets. Proper helmet fitting was associated with a 41% decreased risk of concussion symptoms (RR 0.59, 95% CI 0.44–0.81, p < 0.01). Sixty-six riders (47%) reported having received sponsor support for motocross participation. Sponsor support conferred a relative risk for concussion symptoms of 1.48 (95% CI 1.05–2.08, p = 0.02). CONCLUSIONS Nearly half of all motocross competitors under the age of 18 reported concussion symptoms. Preventive measures are necessary to limit the negative impact from concussions. The risk of concussive injury can be decreased for pediatric motocross riders if they receive professional help with proper helmet fitting and through implementation of stricter guidelines regarding sponsorship.

Key Points Weekly oral proteasome inhibitor ixazomib appears generally well tolerated with manageable toxicity, limited grade 1/2 neuropathy. Data show that more than 25% of 30 evaluable relapsed/refractory myeloma patients who received the MTD had clinically meaningful responses.

Background Aneurysmal bone cysts (ABCs) are a benign aggressive tumor that occurs rarely in the pelvis in the pediatric population. Pelvic ABCs may involve the triradiate cartilage and/or the acetabulum, which increases the technical difficulty of surgical treatment and has potential implications on the growth and development of the hip joint. This study examines the clinical presentation, rate of surgical complications, and recurrence rate, as well as, long-term clinical and functional outcomes of children with pelvic ABCs treated at a single institution by a single treatment modality. Methods Between 1988 and 2008, 142 children with histologically confirmed ABCs were treated at our institution. Seventeen (12 %) tumors were located in the pelvis. A total of 13 pelvic ABCs (5 ilium-periacetabular, 4 pubic, 3 ilium-iliac wing, and 1 ischium) were included in this study. There were eight male and five female patients with a mean age of 12.9 years (range 4.1–17.5 years) at the time of surgery. The Toronto Extremity Salvage Score (TESS), the Musculoskeletal Tumor Society 1993 (MSTS’93) score, and the Short Form Health Survey Sf-36 were obtained at a minimum 5-year follow-up in all patients (mean follow-up 11.5 years, range 5.5–19.8 years). The mean age at follow-up was 24.3 years (range 14.6–32.6 years). Results All patients were treated surgically with intralesional curettage extended with a high-speed burr and bone grafting. Eight patients received adjunctive therapy with phenol. Five patients had preoperative selective arterial embolization. Of the 13 patients, 1 had a local recurrence diagnosed at 6 months after surgery. The only complication in the cohort was a superficial wound infection. At the latest follow-up, all patients were free of disease. The mean TESS score was 95 and the mean MSTS’93 score was 93 %. The mean self-rated general health score, according to the SF-36 was 87 % of total points possible. Conclusions Extended curettage and bone grafting of pelvic ABCs in the pediatric population can yield high clinical and functional scores at an average of 11 years follow-up with a low rate of complications and recurrence. Level of evidence IV, case series.

Summary Objective To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. Methods Randomized multicenter double‐blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period ( OLP ) to complete 2 years of postimplant follow‐up. Results All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was −37.9% in the active and −17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. Significance Responsive stimulation to the seizure focus reduced the frequency of partial‐onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial‐onset seizures.

Background— Cardiac dysfunction in failing hearts of human patients and animal models is associated with both microtubule densification and transverse-tubule (T-tubule) remodeling. Our objective was to investigate whether microtubule densification contributes to T-tubule remodeling and excitation–contraction coupling dysfunction in heart disease. Methods and Results— In a mouse model of pressure overload–induced cardiomyopathy by transaortic banding, colchicine, a microtubule depolymerizer, significantly ameliorated T-tubule remodeling and cardiac dysfunction. In cultured cardiomyocytes, microtubule depolymerization with nocodazole or colchicine profoundly attenuated T-tubule impairment, whereas microtubule polymerization/stabilization with taxol accelerated T-tubule remodeling. In situ immunofluorescence of heart tissue sections demonstrated significant disorganization of junctophilin-2 (JP2), a protein that bridges the T-tubule and sarcoplasmic reticulum membranes, in transaortic banded hearts as well as in human failing hearts, whereas colchicine injection significantly preserved the distribution of JP2 in transaortic banded hearts. In isolated mouse cardiomyocytes, prolonged culture or treatment with taxol resulted in pronounced redistribution of JP2 from T-tubules to the peripheral plasma membrane, without changing total JP2 expression. Nocodazole treatment antagonized JP2 redistribution. Moreover, overexpression of a dominant-negative mutant of kinesin 1, a microtubule motor protein responsible for anterograde trafficking of proteins, protected against JP2 redistribution and T-tubule remodeling in culture. Finally, nocodazole treatment improved Ca 2+ handling in cultured myocytes by increasing the amplitude of Ca 2+ transients and reducing the frequency of Ca 2+ sparks. Conclusion— Our data identify a mechanistic link between microtubule densification and T-tubule remodeling and reveal microtubule-mediated JP2 redistribution as a novel mechanism for T-tubule disruption, loss of excitation–contraction coupling, and heart failure.

We present an overview of strategies our institution has taken to understand the state of its inpatient diabetes management. We first describe how we utilized information systems to assess inpatient glycemic control and insulin management in noncritically ill patients and discuss our findings regarding mean bedside glucose levels, the prevalence and frequency hypoglycemic and hyperglycemic events, the patterns of insulin therapy, and evidence of inpatient clinical inertia. We also review the development of a survey to determine practitioner attitudes and beliefs about inpatient diabetes. Results of this survey study found that, in general, practitioners believed in the importance of controlling hyperglycemia but were not comfortable with many aspects of inpatient diabetes care, particularly with the use of insulin. Finally, we suggest steps to follow in developing a quality-improvement program for hospitals.

To determine the role insulin resistance may play in the catabolic effect of high-dose prednisone therapy, healthy volunteers were studied on four occasions with the hormone-clamp technique at two insulin infusion rates. Subjects were studied after 5 days of prednisone (60 mg/day) or no steroid treatment and were infused with somatostatin, glucagon, growth hormone, [3H]glucose, [14C]leucine, and insulin (0.1 or 0.2 mil · kg1 · min1). At each rate of insulin infusion, the rate of leucine oxidation was increased (P &lt; .001) after steroid treatment. Leucine flux, an indicator of whole-body proteolysis, was similar in the presence or absence of steroid treatment (2.26 ± 0.08 vs. 2.13 ± 0.04 μmol · kg1 · min1 respectively) at the lower rate of insulin infusion but was higher during steroid treatment (2.18 ± 0.06 vs. 1.84 ± 0.13 μmol · kg1 · min1) at the 0.2-mU · kg1 · min1 insulin infusion. Steroid pretreatment had no significant effect on the nonoxidative rates of leucine disappearance. These data provide strong evidence that the protein wasting associated with glucocorticosteroid therapy is in part the result of steroid-induced resistance to the antiproteolytic effect of insulin and an increase in the oxidation (and thus wasting) of one essential amino acid, leucine.