PDGFRA Amplification is Common in Pediatric and Adult High‐Grade Astrocytomas and Identifies a Poor Prognostic Group in IDH1 Mutant Glioblastoma

High‐grade astrocytomas (HGAs), corresponding to World Health Organization grades III (anaplastic astrocytoma) and IV (glioblastoma; GBM), are biologically aggressive, and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non‐amplified (normal and polysomy) or amplified (low‐level and high‐level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and isocitrate dehydrogenase 1 (IDH1)^R132H mutation was a significant independent prognostic factor (P = 0.01). In HGAs, PDGFRA amplification is common and can manifest as high‐level and focal or low‐level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs.     

The effect of periodontal treatment on glycemic control in patients with type 2 diabetes mellitus

BACKGROUND, AIMS: This study was designed to explore the effect of periodontal therapy on glycemic control in persons with type 2 diabetes mellitus (DM). METHODS: 36 patients with type 2 DM (treatment group) received therapy for adult periodontitis during an 18-month period. A 36-person control group was randomly selected from the same population of persons with type 2 DM who did not receive periodontal treatment. RESULTS: These groups were well matched for most of the parameters investigated. During the nine-month observation period, there was a 6.7% improvement in glycemic control in the control group when compared to a 17.1% improvement in the treatment group, a statistically significant difference. Several parameters that could confound or moderate this glycemic control were explored. These included the treatment of non-dental infections, weight and medication changes. No moderating effect was associated with any of these variables. However, there were too few subjects in the study to have the statistical power necessary to assess these possible moderators of glycemic control. CONCLUSIONS: We interpret the data in the study to suggest that periodontal therapy was associated with improved glycemic control in persons with type 2 DM.     

Association of incident restless legs syndrome with outcomes in a large cohort of US veterans

Restless legs syndrome is a common sleep disorder, but there is a paucity of large cohort studies examining the association of restless legs syndrome with clinical outcomes, including all‐cause mortality, incident coronary heart disease, stroke and chronic kidney disease. From a nationally representative prospective cohort of over 3 million US veterans [93% male, median follow‐up time of 8.1 years (interquartile range: 7.0–8.5 years)] with baseline estimated glomerular filtration rate ≥60 mL min^?1 1.73 m^?2, a propensity‐matched cohort of 7392 patients was created, and the association between incident restless legs syndrome and the following was examined: (1) all‐cause mortality; (2) incident coronary heart disease; (3) incident strokes; and (4) incident chronic kidney disease defined as estimated glomerular filtration rate <60 mL min^?1 1.73 m^?2. Associations were examined using Cox models. The mean ± SD age of the propensity‐matched cohort at baseline was 59 ± 12 years; 89 and 8% of patients were white and black, respectively; 31% of the patients were diabetic; and the mean baseline estimated glomerular filtration rate was 83.9 ± 15.1 mL min^?1 1.73 m^?2. Propensity matching resulted in a balanced cohort, with the disappearance in baseline differences in comorbidities. Compared with restless legs syndrome‐negative patients, incident restless legs syndrome was associated with 88% higher mortality risk [hazard ratio and 95% confidence interval: 1.88 (1.70–2.08)], and almost four times higher risk of coronary heart disease and stroke [hazard ratio: 3.97 (3.26–4.84) and 3.89 (3.07–4.94), respectively]. The risk of incident chronic kidney disease was also significantly higher in incident restless legs syndrome patients [hazard ratio: 3.17 (2.74–3.66)] compared with restless legs syndrome‐negative counterparts. In this large and contemporary cohort of US veterans, incident restless legs syndrome was associated with higher risk of mortality, incident coronary heart disease, stroke and chronic kidney disease.     

Stakeholders’ Perceptions Regarding the Use of Patient Photographs Integrated with Medical Imaging Studies

Integrating digital facial photographs of pediatric patients as identifiers (ID) with medical imaging (integrated photographic IDs) may increase the detection of mislabeled studies. The purpose of this study was to determine how different stakeholders would receive this novel technology. Parents or guardians of patients in a children’s hospital outpatient radiology department, radiology faculty and residents, and radiology technologists and nurses were asked to complete a survey. The perception about the anticipated use of integrated photographic ID in different clinical scenarios was investigated, and its predictors were determined using logistic regression analysis. Four hundred ninety-eight parents responded (response rate 83 %); 96 and 97 % supported the use of integrated photographic ID, if it improves the radiologist’s imaging interpretation or decreases the rate of mislabeled errors, respectively. Thirty-eight percent were worried that photographic IDs would impact patients’ privacy. Ninety-four percent believed that they should be asked for their consent prior to obtaining their child’s photograph. Seventy-eight radiologists responded (response rate 39 %); 63 and 59 % believed that the use of integrated photographic ID would result in improvement in accurate interpretation of images and identification of mislabeled patient errors, respectively. Forty-nine percent of radiologists had concern that integrated photographic ID would increase interpretation time. Fifty technologists and nurses responded (response rate 59 %); 71 and 73 % supported the technology if it resulted in more acute interpretation of images and identification of mislabeled patients, respectively. A majority of stakeholders support integrated photographic ID in order to improve safety. A majority of parents believe that consent should be obtained.     

Comprehensive characterization of a Canadian cohort of von Hippel-Lindau disease patients

Von Hippel-Lindau disease (VHL) is a heritable condition caused by pathogenic variants in VHL and is characterized by benign and malignant lesions in the central nervous system (CNS) and abdominal viscera. Due to its variable expressivity, existing efforts to collate VHL patient data do not adequately capture all VHL manifestations. We developed a comprehensive and standardized VHL database in the web-based application, REDCap, that thoroughly captures all VHL manifestation data. As an initial trial, information from 86 VHL patients from the University Health Network/Hospital for Sick Children was populated into the database. Analysis of this cohort showed missense variants occurring with the greatest frequency, with all variants localizing to the α- or β-domains of VHL. The most prevalent manifestations were central nervous system (CNS), renal, and retinal neoplasms, which were associated with frameshift variants and large deletions. We observed greater age-related penetrance for CNS hemangioblastomas with truncating variants compared to missense, while the reverse was true for pheochromocytomas. We demonstrate the utility of a comprehensive VHL database, which supports the standardized collection of clinical and genetic data specific to this patient population. Importantly, we expect that its web-based design will facilitate broader international collaboration and lead to a better understanding of VHL.