From bench to bedside: current and future applications of molecular profiling in renal cell carcinoma

Among the adult population, renal cell carcinoma (RCC) constitutes the most prevalent form of kidney neoplasm. Unfortunately, RCC is relatively asymptomatic and there are no tumor markers available for diagnostic, prognostic or predictive purposes. Molecular profiling, the global analysis of gene and protein expression profiles, is an emerging promising tool for new biomarker identification in RCC. In this review, we summarize the existing knowledge on RCC regarding clinical presentation, treatment options, and tumor marker status. We present a general overview of the more commonly used approaches for molecular profiling at the genomic, transcriptomic and proteomic levels. We also highlight the emerging role of molecular profiling as not only revolutionizing the process of new tumor marker discovery, but also for providing a better understanding of the pathogenesis of RCC that will pave the way towards new targeted therapy discovery. Furthermore, we discuss the spectrum of clinical applications of molecular profiling in RCC in the current literature. Finally, we highlight some of the potential challenging that faces the era of molecular profiling and its transition into clinical practice, and provide an insight about the future perspectives of molecular profiling in RCC

Screening Mammograms in Alzheimer’s Disease Patients

Very little guidance exists to help clinicians and families decide whether mammograms are useful in elderly women with Alzheimer’s Disease (AD). We present a case of a patient with moderate AD who had a positive mammogram and discuss the dilemma faced by the family and clinician in deciding what was best to do for the patient. In this case, the family opted for breast conserving surgery (BCS) followed by palliative care which brought up the question of whether screening was appropriate with this treatment goal in mind. We reviewed the literature on AD and breast cancer screening and summarize these findings in our discussion

A rare case of paradoxical left sided endocarditis through patent foramen ovale.

A 36 -year old woman IV drug abuser admitted with Right-Sided Infective Endocarditis (RSIE) as demonstrated by transthoracic echocardiogram. Patient was admitted 8 weeks later with recurrence of symptoms, moreover signs of systemic embolization were noted. Transthoracic and Transesophageal Echocardiograms revealed tricuspid valve vegetation, severe tricuspid regurgitation, left atrial mass, Patent Foramen Ovale (PFO), severely dilated right atrium and prominent Chiari\u27s network. Systemic embolization included brain and Left iliacus abscesses. Patent Foramen ovale is the proposed mechanism leading to extensive systemic embolization in the present case

Vitamin D supplementation as an adjuvant therapy for patients with T2DM : an 18-month prospective interventional study

Background Vitamin D deficiency has been associated with impaired human insulin action, suggesting a role in the pathogenesis of diabetes mellitus type 2 (T2DM). In this prospective interventional study we investigated the effects of vitamin D3 supplementation on the metabolic profiles of Saudi T2DM subjects pre- and post-vitamin D supplementation over an 18-month period. Methods T2DM Saudi subjects (men, N = 34: Age: 56.6 ± 8.7 yr, BMI, 29.1 ± 3.3 kg/m2; women, N = 58: Age: 51.2 ± 10.6 yr, BMI 34.3 ± 4.9 kg/m2;) were recruited and given 2000 IU vitamin D3 daily for 18 months. Anthropometrics and fasting blood were collected (0, 6, 12, 18 months) to monitor serum 25-hydroxyvitamin D using specific ELISA, and to determine metabolic profiles by standard methods. Results In all subjects there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (32.2 ± 1.5 nmol/L) to 18 months (54.7 ± 1.5 nmol/L; p < 0.001), as well as serum calcium (baseline = 2.3 ± 0.23 mmol/L vs. 18 months = 2.6 ± 0.1 mmol/L; p = 0.003). A significant decrease in LDL- (baseline = 4.4 ± 0.8 mmol/L vs. 18 months = 3.6 ± 0.8 mmol/L, p < 0.001] and total cholesterol (baseline = 5.4 ± 0.2 mmol/L vs. 18 months = 4.9 ± 0.3 mmol/L, p < 0.001) were noted, as well as a significant improvement in HOMA-β function ( p = 0.002). Majority of the improvements elicited were more prominent in women than men. Conclusion In the Saudi T2DM population receiving oral Vitamin D3 supplementation (2000 IU/day), circulating 25-hydroxyvitamin D levels remained below normal 18 months after the onset of treatment. Yet, this “suboptimal” supplementation significantly improved lipid profile with a favorable change in HDL/LDL ratio, and HOMA-β function, which were more pronounced in T2DM females

A Case Control Study of Nutrient Intake Deficiencies in Patients Taking Warfarin

Introduction We previously published the case of a woman taking warfarin who was found to have scurvy, a disease caused by a deficiency of vitamin C. This led us to hypothesize that patients taking warfarin who consume a diet limited in vitamin K rich foods may be at risk for other nutrient deficiencies. To test our hypothesis, we studied dietary nutrient intake in patients taking warfarin compared to patients with heart disease not taking warfarin. Methods The warfarin (n=59) and control groups (n=24) comprised convenience samples of patients with heart disease over age 60 years. Patients completed a three-day food diary and reported use of supplements. Results Based on diet history, the most common deficiencies were vitamin D (100% both groups), vitamin E (93% warfarin, 92% control), vitamin A (71% warfarin, 71% control), vitamin K (66% warfarin, 58% control), vitamin C (58 % warfarin, 46% control) and pantothenic acid (69% warfarin, 71% control) with no significant differences in intake deficiencies between warfarin and control groups. Conclusion All of our patients had nutritional intake deficiencies. This may be due to Appalachian dietary habits and not the low vitamin K diet. It seems prudent to recommend multivitamins, however, universal multivitamin supplementation has not been supported by randomized controlled trials. More study is needed to determine the reason for poor nutritional intake in our Appalachian population and to determine whether similar results are evident in a larger sample

Outcomes of Transcutaneous Aortic Valve Replacement among high risk WV sample population.

Introduction:Transcatheter aortic valve replacement (TAVR) is a relatively new strategy for replacing the aortic valve. We elected to review our early experience to see if we could identify clinical characteristics at baseline or immediately following the procedure that would predict death within one year. Methods:Charts for all patients assigned to receive TAVR procedure at St Mary’s medical center, Huntington, West Virginia between April, 2013 till November, 2016 were identified and reviewed. A total of seventy-two (72) cases were included. Results: All cause mortality rate at index hospitalization, 30 days, and 12 months was 5.6%(N=4), 6.9%(N=5), 19.4%(N=14) respectively. Stroke rate at index hospitalization, 30 days, and 12 months was 2.8%(N=2), 2.8%(N=2), 8.3%(N=6) respectively. Major predictors of death were post procedure GFR, Contrast volume, and number of antiplatelet agents therapy (AUC= 0.638, 0.632, 0.637 respectively). Conclusion: We found that post procedure GFR, less number of antiplatelet agents post procedure, and contrast volume may predict mortality within first 12 months post TAVR. Further studies focused on the above factors may be warranted

MicroRNAs: exploring a new dimension in the pathogenesis of kidney cancer

Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. The role of the von-Hippel-Lindeau (VHL) tumour suppressor gene is well established in RCC with a loss of VHL protein leading to accumulated hypoxia-induced factor (HIF) and the subsequent transcriptional activation of multiple downstream targets. Recently, microRNAs (miRNAs) have been shown to be differentially expressed in RCC and their role in RCC pathogenesis is emerging. This month, in BMC Medicine, Gleadle and colleagues show that certain miRNAs are regulated by VHL in either a hypoxia-inducible factor (HIF)-dependent or HIF-independent manner in RCC. They also show that miRNA expression correlates with the survival of RCC patients

Tea and coffee consumption in relation to vitamin D and calcium levels in Saudi adolescents

Background Coffee and tea consumption was hypothesized to interact with variants of vitamin D-receptor polymorphisms, but limited evidence exists. Here we determine for the first time whether increased coffee and tea consumption affects circulating levels of 25-hydroxyvitamin D in a cohort of Saudi adolescents. Methods A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays. Results Improved lipid profiles were observed in both boys and girls, as demonstrated by increased levels of HDL-cholesterol, even after controlling for age and BMI, among those consuming 9–12 cups of coffee/week. Vitamin D levels were significantly highest among those consuming 9–12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure. Conclusion This study suggests a link between tea consumption and vitamin D levels in a cohort of Saudi adolescents, independent of age, BMI, gender, physical activity and sun exposure. These findings should be confirmed prospectively