Citations

Background: Patellofemoral instability is common in the pediatric and adolescent population, yet prognosis after the first dislocation has been difficult to determine. Purpose: To describe the demographics of pediatric and adolescent patients with a first-time patellofemoral dislocation and to determine predictors of recurrent instability. Study Design: Case-control study; Level of evidence, 3. Methods: A search of the Mayo Medical Index database between 1998 to 2010 was performed, and 2039 patients were identified. Inclusion criteria were (1) age 18 years or younger, (2) no history of patellofemoral subluxation/dislocation of the affected knee, (3) radiographs within 4 weeks of the initial instability episode, and (4) a dislocated patella requiring reduction or convincing history/findings suggestive of acute patellar dislocation (effusion/hemarthrosis, tenderness along medial parapatellar structures, and apprehension with lateral patellar translation). Radiographs were evaluated for trochlear dysplasia (Dejour classification) and patella alta (Caton-Deschamps and Insall-Salvati indices). Skeletal maturity was graded based on the distal femoral and proximal tibial physes (open, closing, or closed). Results: A total of 222 knees (120 male [54.1%] and 102 female [45.9%]) in 210 patients with an average age of 14.9 years (range, 9-18 years), met the inclusion criteria. Twenty-four patients (10.8%) underwent early surgery. All others were initially treated nonoperatively. Of the 198 patients in this group, 76 (38.4%) had recurrent instability, and 39 (51.3%) of these required surgical treatment. Recurrent instability was associated with trochlear dysplasia ( P < .01). Patients with both immature physes and trochlear dysplasia had a recurrence rate of 69% (33/48), with a hazard ratio of 3.3. Age, sex, body mass index, and patella alta were not statistically associated with recurrent instability. Conclusion: Nonoperative treatment for first-time patellofemoral dislocation resulted in a 62% success rate. However, skeletally immature patients with trochlear dysplasia had only a 31% success rate with nonoperative management. Nearly half of patients with recurrent instability required surgical intervention to gain stability.

Background and purposeTo evaluate the association between systolic, diastolic and pulse pressure, and increase in ventricular size (VS). Observations in laboratory animals suggest intraventricular pulse pressure (systolic–diastolic) may play a role in ventricular enlargement.MethodsInitial magnetic resonance (MR) scans and vascular risk factors evaluation were performed in 1812 Atherosclerosis Risk in Communities participants in 1994–1995. In 2004–2006, 1130 participants underwent repeat MR. VS was rated using a validated nine‐point scale. Multiple logistic regression analysis assessed association between blood pressure measures and pulse pressure, and the change between the MR scans of VS controlling for age, sex and race.ResultsAt baseline 1112 participants (385 black women, 200 black men, 304 white women and 223 white men) had a mean age of 61.7 ± 4.3 years. In adjusted models pulse pressure at baseline was associated with an increase in VS [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01–1.40], as was systolic pressure (OR 1.28, 95% CI 1.03–1.58).ConclusionsSystolic pressure and pulse pressure are associated with future development of increased VS. The findings are consistent with the animal literature that increased pulse pressure predisposes to risk of future increased VS. High pulse pressure might play a role in the pathogenesis of normal pressure hydrocephalus.

Pazopanib and paclitaxel produce cytotoxic synergy in thyroid cancer models through inhibition of aurora kinase A.

ObjectivesThe clinical severity of aortic stenosis (AS) is based largely on symptoms. However, AS severity is primarily determined by estimating the aortic valve area (AVA) and pressure gradients (ΔP). Conditions may arise in which there is a mismatch in severity between AVA and ΔP determinations secondary to errors in measurement and/or assumption, alterations of flow, or variations in the magnitude of pressure recovery. The cause of discrepancy between area and gradient determinations must be deciphered so as to best counsel patients on the most ideal treatment strategy. (J Interven Cardiol 2013;26:183–194)

Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoA-specific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous. VEGF caused translocation of Syx from cell junctions, promoting junction disassembly, whereas Ang1 maintained Syx at the junctions, inducing junction stabilization. The VEGF-induced translocation of Syx from EC junctions was caused by PKD1 (protein kinase D1)-mediated phosphorylation of Syx at Ser806, which reduced Syx association to its junctional anchors. In support of the pivotal role of Syx in regulating EC junctions, syx−/− mice had defective junctions, resulting in vascular leakiness, edema, and impaired heart function.

Background and Purpose— Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. Methods— We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family’s proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. Results— There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04–2.27]; P =0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22–3.22]; P =0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05–8.24], P =0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34–2.46]; P <0.001). Conclusions— In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.

Background and objective Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10 −5 ) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10 −7 ), rs981621 (p=1.65×10 −7 ) and rs16861827 (p=3.75×10 −7 ), respectively. 131 SNPs with p≤10 −5 were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10 −7 ) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.