Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin

Polymorphous low‐grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of minor salivary gland (CAMSG) are low‐grade carcinomas arising most often in oral cavity and oropharynx, respectively. Controversy exists as to whether these tumors represent separate entities or variants of one spectrum, as they appear to have significant overlap, but also clinicopathologic differences. As many salivary carcinomas harbor recurrent translocations, paired‐end RNA sequencing and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs and two PLGAs. Validated rearrangements were then screened by fluorescence in situ hybridization (FISH) in 60 cases. Histologic classification was performed without knowledge of fusion status and included: 21 CAMSG, 18 classic PLGA, and 21 with “mixed/indeterminate” features. The RNAseq of 2 CAMSGs showed ARID1A‐PRKD1 and DDX3X‐PRKD1 fusions, respectively, while no fusion candidates were identified in two PLGAs. FISH for PRKD1 rearrangements identified 11 additional cases (22%), two more showing ARID1A‐PRKD1 fusions. As PRKD2 and PRKD3 share similar functions with PRKD1 in the diacylglycerol and protein kinase C signal transduction pathway, we expanded the investigation for these genes by FISH. Six additional cases each showed PRKD2 and PRKD3 rearrangements. Of the 26 (43%) fusion‐positive tumors, there were 16 (80%) CAMSGs and 9 (45%) indeterminate cases. A PRKD2 rearrangement was detected in one PLGA (6%). We describe novel and recurrent gene rearrangements in PRKD1–3 primarily in CAMSG, suggesting a possible pathogenetic dichotomy from “classic” PLGA. However, the presence of similar genetic findings in half of the indeterminate cases and a single PLGA suggests a possible shared pathogenesis for these tumor types. © 2014 Wiley Periodicals, Inc.     

Potential oral manifestations of cardiovascular drugs

Oral Diseases (2010) 16 , 769–773 Objective: The aim of this work was to determine the frequency and nature of oral manifestations secondary to use of cardiovascular drugs. Methods: Five hundred and thirty one patients attending an adult cardiology clinic in Saudi Arabia were questioned about the occurrence of oral dryness, dysgeusia, or burning sensation and were clinically evaluated for the presence of oral mucosal or gingival disease. Data were statistically analyzed with chi‐squared tests, odds ratios and Student’s t‐test. Results: Oral symptoms and/or signs were recorded in 75 (14.1%) patients with xerostomia being the most common (7.5%), followed by lichenoid (lichen planus‐like) lesions (3.6%) and dysgeusia (1.9%). Xerostomia was significantly more frequent in patients with a history of diabetes mellitus and in female patients (P < 0.05). There were no statistically significant differences (P > 0.05) between patients with or without oral manifestations when age, gender, cardiovascular risk factor, cardiac disease, type of cardiac drug used or the number of medications were assessed. There was a trend for xerostomia to be less frequent in patients receiving therapy with angiotensin converting enzyme inhibitors and a slight trend of xerostomia to be more likely with increased number of non‐cardiac and total number of agents per subject. The number of non‐cardiac and total medications taken by patients with potential oral manifestations tended to be greater than that of patients without oral manifestations. Conclusions: The frequency of potential oral manifestations in patients receiving cardiovascular agents was 14.1%. The occurrence and character of the oral manifestations had no significant relation with individual cardiac drugs, although there was a trend for oral manifestations to be likely with increasing number of drugs.     

Longitudinal Physical Activity Changes in Older Men in the Osteoporotic Fractures in Men Study

OBJECTIVES: To describe the change in physical activity (total, leisure, household, occupational) in men over a mean 5‐year follow‐up period and to identify sociodemographic and health factors associated with change in physical activity. DESIGN: Prospective cohort study; Osteoporotic Fractures in Men Study; data collected March 2000 through May 2006. SETTING: Six U.S. clinical centers. PARTICIPANTS: Volunteer sample of ambulatory community‐dwelling men aged 65 and older (N=5,161). MEASUREMENTS: Self‐reported physical activity assessed at baseline and Visit 2 (V2) (5 years apart) according to the Physical Activity Scale for the Elderly (PASE) (unitless, relative measure of physical activity). RESULTS: At baseline, PASE scores averaged 16.8±35.5 for occupational, 37.0±34.0 for leisure, 95.9±43.2 for household, and 149.7±67.6 for total physical activity. Occupational (?6.2±33.9), leisure (?3.2±37.3), household (?9.9±44.3), and total (?19.3±67.7) physical activity change scores declined, on average, from baseline to V2. On average, change in total PASE scores declined more with age: ?15.6±71.6 for men younger than 70, ?16.4±67.0 for men aged 70 to 74, ?21.4±66.9 for men aged 75 to 79, and ?29.5±60.7 for men aged 80 and older. Living alone, smoking cigarettes, poor health, and higher blood pressure were associated with greater declines in physical activity over time. Although average scores declined, some older men (1,335, 26%) reported increasing physical activity levels. Better physical and mental health, living with others, and being younger were associated with the probability of increasing physical activity over time. CONCLUSION: Over the 5‐year period, the majority of men reported declines in total physical activity. Older men in poor health who live alone have a high risk of physical activity declines and may be an important group to target for exercise interventions.     

Early surgery for biliary pancreatitis

Herein, we documented our successful experience in performing definitive biliary tract surgery on patients with biliary pancreatitis as soon as the diagnosis was made and within 48 hours of admission. Early surgery reduced the length of hospital stay and did not result in associated morbidity, death, or complications of acute pancreatitis. The results of the study support the concept that removing obstruction of the pancreatic duct prevents progression of edematous pancreatitis to hemorrhagic pancreatitis. We conclude that patients with acute pancreatitis should be evaluated urgently for the presence of biliary tract stone disease and should be operated on as soon as the diagnosis of biliary pancreatitis is made, that early definitive surgery can be performed safely on patients with biliary pancreatitis, that cholecystectomy with intraoperative cholangiography and common duct exploration as necessary should be performed in all patients, and that length of stay for patients with biliary pancreatitis is reduced and morbidity and mortality possibly may be reduced by early surgery as compared with delayed surgery.     

Predicting prognosis in patients with stroke treated with intravenous alteplase through blood pressure changes: A machine learning-based approach

The use of machine learning (ML) in predicting disease prognosis has increased, and researchers have adopted different methods for variable selection to optimize early screening for AIS to determine its prognosis as soon as possible. We aimed to improve the understanding of the predictors of poor functional outcome at three months after discharge in AIS patients treated with intravenous thrombolysis and to construct a highly effective prognostic model to improve prediction accuracy. And four ML methods (random forest, support vector machine, naive Bayesian, and logistic regression) were used to screen and recombine the features for construction of an ML prognostic model. A total of 352 patients that had experienced AIS and had been treated with intravenous thrombolysis were recruited. The variables included in the model were NIHSS on admission, age, white blood cell count, percentage of neutrophils and triglyceride after thrombolysis, tirofiban, early neurological deterioration, early neurological improvement, and BP at each time point or period. The model's area under the curve for predicting 30-day modified Rankin scale was 0.790 with random forest, 0.542 with support vector machine, 0.411 with naive Bayesian, and 0.661 with logistic regression. The random forest model was shown to accurately evaluate the prognosis of AIS patients treated with intravenous thrombolysis, and therefore they may be helpful for accurate and personalized secondary prevention. The model offers improved prediction accuracy that may reduce rates of misdiagnosis and missed diagnosis in patients with AIS.