Urologist Practice Affiliation and Intensity-modulated Radiation Therapy for Prostate Cancer in the Elderly

Background

Prostate cancer treatment is a significant source of morbidity and spending. Some men with prostate cancer, particularly those with significant health problems, are unlikely to benefit from treatment.

Assessing the efficacy of endovascular therapy in stroke treatments: updates from the new generation of trials

Introduction: For the past 20 years, intravenous recombinant tissue plasminogen activator (rt-PA) has been the only proven treatment for acute ischemic stroke. Large arteries such as the internal carotid artery, the middle cerebral artery and the basilar artery supply blood to large volumes of brain tissue. When occluded, these vessels may have low response rates to rt-PA resulting in devastating injury and death.

Areas covered: In 2013, three trials evaluating the efficacy of mechanical thrombectomy in acute stroke were neutral, however, lessons learned from these trials resulted in a second generation of five trials in 2015 and a sixth in 2016 which all demonstrated significant benefit for select patients. Here we will review the evidence behind these new trials and. introduce new questions such as models of care, techniques of thrombectomy, the role of rt-PA, modes of anesthesia, the management of late presenting and wake up strokes among other real world challenges facing stroke medicine now that the thrombectomy is an evidence based treamtnent

Expert commentary: The mechanical thrombectomy is now the new standard of care and with that comes the need to find ways to provide it to all who will benefit.     

Glycolytic metabolite methylglyoxal inhibits cold and menthol activation of the transient receptor potential melastatin type 8 channel

Methylglyoxal (MG) is a reactive dicarbonyl compound involved in protein modifications linked to diabetes mellitus. The plasma level of MG is elevated in diabetic patients, particularly those with painful diabetic neuropathy. Diabetic neuropathy is often associated with spontaneous pain and altered thermal perception. This study assesses effects of MG on TRPM8, an ion channel involved in innocuous cold sensing and cold allodynia and also in cold‐mediated analgesia. Acute treatment with MG inhibited the activation of recombinant rat and human transient receptor potential melastatin type 8 (TRPM8) by cold and chemical agonists. A similar effect was observed when native TRPM8 was investigated in cultured rat dorsal root ganglion (DRG) neurons. DRG neurons treated with MG for 16–24 hr displayed a significant reduction in the fraction of cold‐ and menthol‐sensitive neurons, most likely expressing TRPM8. The fraction of allyl isothiocyanate‐sensitive neurons was also reduced, and the coexpression among different neuronal populations was affected. The same prolonged exposure to MG significantly reduced the expression of TRPM8 at the mRNA level. Overall, our data provide evidence for decreased activity and expression level of TRPM8 in the presence of MG, which may be linked to some of the alterations in pain and temperature sensing reported by diabetic patients. © 2015 Wiley Periodicals, Inc.     

Atrial fibrillation and isolated systolic hypertension: the systolic hypertension in the elderly program and systolic hypertension in the elderly program-extension study

We performed a post hoc analysis of the Systolic Hypertension in the Elderly Program database to assess the incidence of atrial fibrillation in the elderly hypertensive population, its influence on cardiovascular events, and whether antihypertensive treatment can prevent its onset. The Systolic Hypertension in the Elderly Program was a double-blind placebo-controlled trial in 4736 subjects with isolated systolic hypertension aged >or=60 years. Atrial fibrillation was an exclusion criterion from the trial. Participants were randomly assigned to stepped care treatment with chlorthalidone and atenolol (n=2365) or placebo (n=2371). The occurrence of atrial fibrillation and cardiovascular events over 4.7 years as well as the determination of cause of death at 4.7 and 14.3 years were followed. Ninety-eight subjects (2.06%) developed atrial fibrillation over 4.7 years mean follow-up, without significant difference between treated and placebo groups. Atrial fibrillation increased the risk for: total cardiovascular events (RR 1.69; 95% CI 1.21 to 2.36), rapid death (RR 3.29; 95% CI 1.08 to 10.00), total (RR 5.10; 95% CI 3.12 to 8.37) and nonfatal left ventricular failure (RR 5.31; 95% CI 3.09 to 9.13). All-cause and total cardiovascular death were significantly increased in the atrial fibrillation group at 4.7 years (HR 3.44; 95% CI 2.18 to 5.42; HR 2.39; 95% CI 1.05 to 5.43) and 14.3 years follow-up (HR 2.33; 95% CI 1.83 to 2.98; HR 2.21; 95% CI 1.54 to 3.17). Atrial fibrillation increased the risk for total cardiovascular events, rapid death, and left ventricular failure. All-cause mortality and total cardiovascular mortality were significantly increased in hypertensives with atrial fibrillation at 4.7 and 14.3 years follow-up.     

An exercise tissue Doppler and strain rate imaging study of diastolic myocardial dysfunction after Kawasaki syndrome in childhood

OBJECTIVE: Myocardial dysfunction due to coronary arterial lesions is an important complication after Kawasaki syndrome in childhood. Tissue Doppler echocardiography, and strain rate imaging, have shown their value in detecting regional myocardial dysfunction in coronary arterial disease. We aimed to examine the diagnostic value of these methods in patients with coronary arterial lesions after Kawasaki syndrome. METHODS: We assessed regional myocardial function in 17 asymptomatic patients with coronary arterial lesions. Follow-up coronary angiographies were available in all cases. Tissue Doppler echocardiography, and strain rate imaging, were performed at rest and during bicycle exercise. Examination included peak systolic and diastolic velocities, peak systolic strain and strain rate. We enrolled 17 age- and gender-matched persons to serve as a control group. RESULTS: Segmental left ventricular longitudinal function did not significantly differ between the groups with respect to peak systolic velocity, strain, and strain rate. Diastolic abnormalities were identified in segments supplied by coronary arteries with stenotic lesions. Peak diastolic velocity decreased significantly during exercise in those areas, from 77 plus or minus 34 to 59 plus or minus 56 millimetres per second, p smaller than 0.05. Under exercise, a peak diastolic velocity value under 90 millimetres per second enabled us to identify coronary arterial stenosis with a sensitivity of 75 percent and specificity of 64 percent. CONCLUSIONS: After Kawasaki syndrome, diastolic impairment develops in segments supplied by stenotic coronary arteries before systolic dysfunction is detectable. Exercise tissue Doppler echocardiography has the potential to detect these subtle abnormalities, and help monitor progression of the disease.