Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Comparison of digital systems and conventional dental film for the detection of approximal enamel caries

Objectives

The aims of this study were (1) to compare the accuracy of the detection of approximal enamel caries lesions using three intraoral storage phosphor plate digital systems and one conventional film-based radiographic system; and (2) to determine whether there is a correlation between the histological and radiographic measurements of enamel caries.

Methods

160 approximal surfaces were radiographed under standardized conditions using three storage phosphor stimulable systems (DenOptix and Digora FMX with white and blue plates), and one film system (Insight film). 17 observers scored the images for the presence and depth of caries using a 4-point scale. The presence of caries was validated histologically (gold standard). Two-way analysis of variance was used to test the differences in sensitivity, specificity and overall accuracy (TP + TN). The data from the radiographic and histological measurements were statistically analysed by Spearman’s rank correlation coefficient.

Results

Two-way analysis of variance and the post hoc t-test demonstrated that Digora (white plate) had higher specificity and overall accuracy values than DenOptix (P = 0.021); there was no statistically significant difference among the other imaging modalities (P > 0.05). There was no significant correlation between the histological depth measurements and the radiographic measurements from Digora (blue plate) (P = 0.43), Digora (white plate) (P = 0.15), DenOptix (P = 0.17) and Insight film (P = 0.06).

Conclusions

The results suggest that (1) the performance of the three storage phosphor image plate systems was similar to that of the Insight film for detection of approximal enamel caries, and (2) the increase in histological depth of enamel caries was not significantly correlated with radiographic measurements.     

Use of CO2 to move structures as an aid to percutaneous procedures

By injecting small amounts of CO2 through a needle, one can move bowel or bladder from the intended path of instruments during interventional procedures. The technique worked well in six of seven cases in the pelvis and retroperitoneum; it was not effective in the mediastinum or midabdomen (n = 6).     

Denosumab Reduces Cortical Porosity of the Proximal Femoral Shaft in Postmenopausal Women With Osteoporosis

Hip fractures account for over one‐half the morbidity, mortality, and cost associated with osteoporosis. Fragility of the proximal femur is the result of rapid and unbalanced bone remodeling events that excavate more bone than they deposit, producing a porous, thinned, and fragile cortex. We hypothesized that the slowing of remodeling during treatment with denosumab allows refilling of the many cavities excavated before treatment now opposed by excavation of fewer new resorption cavities. The resulting net effect is a reduction in cortical porosity and an increase in proximal femur strength. Images were acquired at baseline and 36 months using multidetector CT in 28 women receiving denosumab and 22 women receiving placebo in a substudy of FREEDOM, a randomized, double‐blind, placebo‐controlled trial involving women with postmenopausal osteoporosis. Porosity was quantified using StrAx1.0 software. Strength was estimated using finite element analysis. At baseline, the higher the serum resorption marker, CTx, the greater the porosity of the total cortex (r = 0.34, p = 0.02), and the higher the porosity, the lower the hip strength (r = –0.31, p = 0.03). By 36 months, denosumab treatment reduced porosity of the total cortex by 3.6% relative to baseline. Reductions in porosity relative to placebo at 36 months were 5.3% in total cortex, 7.9% in compact‐appearing cortex, 5.6% in outer transitional zone, and 1.8% in inner transitional zone (all p < 0.01). The improvement in estimated hip integral strength of 7.9% from baseline (p < 0.0001) was associated with the reduction in total porosity (r = –0.41, p = 0.03). In summary, denosumab reduced cortical porosity of the proximal femoral shaft, resulting in increased mineralized matrix volume and improved strength, changes that may contribute to the reduction in hip and nonvertebral fractures reported with denosumab therapy. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Diagnosis and treatment of sudden-onset sensorineural hearing loss: a study of 51 patients.

OBJECTIVE: The study purpose was to determine the efficacy of steroid and antiviral therapy in the management of idiopathic sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: We conducted a retrospective study of patients presenting to an academic tertiary care center. Fifty-one patients were evaluated. All patients were placed on the same treatment protocol. RESULTS: Thirty-seven patients (73%) had recovery of hearing. Ninety-one percent of patients with vertigo and all patients with mid-frequency hearing loss and up-sloping hearing loss recovered with treatment (P < 0.05). Recovery was significantly related to age, onset of hearing loss, and audiogram type; however outcome was not significantly related to gender, vertigo, tinnitus, or laterality (P < 0.05). CONCLUSION: Our treatment protocol produced a recovery rate, which exceeds the spontaneous recovery rate. Unlike prior studies, all patients with up-sloping and mid-frequency SSNHL had recovery. In addition, vertigo did not indicate a poor prognosis. SIGNIFICANCE: Antiviral therapy and increased length of steroid treatment may play a role in the improved recovery rates.