Enhancement of vascular endothelial function by recombinant human thyrotropin.

CONTEXT: The cardiovascular consequences of thyroid diseases are attributed to the altered secretion of thyroid hormones. The possibility that TSH also affects the cardiovascular system has been poorly explored. Endothelial cells and vascular smooth muscle cells possess TSH receptors. OBJECTIVE: The study was designed to determine whether TSH exerts any effect on vascular homeostasis. SUBJECTS AND METHODS: Two different double-blind, controlled studies were performed, one in eight healthy volunteers and the other in six thyroidectomized patients. Recombinant human (rh) TSH (or saline) was infused intrabrachially (1 mU/min) to raise TSH to severe hypothyroidism levels (approximately 100 microU/ml). Endothelium-dependent and -independent vasodilation was tested by intraarterial infusion of acetylcholine and sodium nitroprusside, respectively, and forearm blood flow was measured by plethysmography. RESULTS: Endothelium-dependent vasodilation was potentiated by rhTSH (P < 0.05 for the treatment effect; general linear model). The dynamics of the response was also profoundly affected by rhTSH because the dose-response curve was much steeper than in controls (P < 0.02 for the interaction between TSH and acetylcholine). rhTSH had no effect on endothelium-independent vasodilation (P = NS for both treatment and interaction). During rhTSH infusion, free T(3) levels increased slowly from 2.3 +/- 0.2 to 3.6 +/- 0.2 pg/ml. In thyroidectomized patients, rhTSH potentiated endothelium-mediated vasodilation to an extent similar to that of healthy subjects (P = 0.05 for the treatment effect and P = 0.01 for the interaction), without affecting the response to nitroprusside. In these patients, thyroid hormones remained unchanged during rhTSH infusion. CONCLUSIONS: rhTSH exerts marked effects on the resistance vessels by enhancing endothelial-mediated vasodilation, independent of changes in thyroid hormone concentration.

Pre-hospital lung ultrasound for cardiac heart failure and COPD: is it worthwhile?

BACKGROUND: Pre-hospital ultrasound is a new challenge and lung ultrasound could be an interesting opportunity in the pre-hospital medical service. The aim of our study was to evaluate the efficacy of lung ultrasound in out-of-hospital non-traumatic respiratory insufficiency. METHODS: We planned a case-controlled study in the ULSS 5 ovest vicentino area (Vicenza-Italy) enrolling subjects with severe dyspnea caused by cardiac heart failure or acute exacerbation of chronic obstructive pulmonary disease. We compared drugs administration, oxygen delivery, and laboratory tests between those patients with ultrasound integrated management and those without ultrasound. RESULTS: Pre-hospital lung ultrasound had a high specificity (94.4%) and sensitivity (100%) for the correct identification of alveolar interstitial syndrome using B lines, whereas the percentages obtained with pleural effusion were lower (83.3, 53.3%, respectively). The patients with ultrasound integrated management received a more appropriate pharmacological therapy (p 0.01), as well as non-invasive ventilation (CPAP) was used more frequently in those with an acute exacerbation of chronic obstructive pulmonary disease (p 0.011). Laboratory tests and blood gases analysis were not significant different between the two study groups. In a sub-analysis of the patients with an A profile, we observed a significant lower concentration of PCO2 in those with an ultrasound integrated management (PCO2: 42.62 vs 52.23 p 0.049). According with physicians' opinion, pre-hospital lung ultrasound gave important information or changed the therapy in the 42.3% of cases, whereas it just confirmed physical examination in the 67.7% of cases. CONCLUSIONS: Pre-hospital lung ultrasound is easy and feasible, and learning curve is rapid. Our study suggests that cardiac heart failure and acute exacerbation of chronic obstructive pulmonary disease can be considered two indications for pre-hospital ultrasound, and can improve the management of patient with acute respiratory insufficiency.

Lung ultrasound for diagnosis of pneumonia in emergency department.

Lung ultrasound (LUS) in the emergency department (ED) has shown a significant role in the diagnostic workup of pulmonary edema, pneumothorax and pleural effusions. The aim of this study is to assess the reliability of LUS for the diagnosis of acute pneumonia compared to chest X-ray (CXR) study. The study was conducted from September 2013 to March 2015. 107 patients were admitted to the ED with a clinical appearance of pneumonia. All the patients underwent a CXR study, read by a radiologist, and an LUS, performed by a trained ED physician on duty. Among the 105 patients, 68 were given a final diagnosis of pneumonia. We found a sensitivity of 0.985 and a specificity of 0.649 for LUS, and a sensitivity of 0.735 and specificity of 0.595 for CXR. The positive predictive value for LUS was 0.838 against 0.7 for CXR. The negative predictive value of LUS was 0.960 versus 0.550 for CXR. This study has shown sensitivity, positive predictive value and negative predictive value of LUS compared to the CXR study for the diagnosis of acute pneumonia. These results suggest the use of bedside thoracic US first-line diagnostic tool in patients with suspected pneumonia.

Immediate versus delayed integrated point-of-care-ultrasonography to manage acute dyspnea in the emergency department.

BACKGROUND: Dyspnea is one of the most frequent complaints in the Emergency Department. Thoracic ultrasound should help to differentiate cardiogenic from non-cardiogenic causes of dyspnea. We evaluated whether the diagnostic accuracy can be improved by adding a point-of-care-ultrasonography (POC-US) to routine exams and if an early use of this technique produces any advantage. METHODS: One hundred sixty-eight patients were enrolled and randomized in two groups: Group 1 received an immediate POC-US in addition to routine laboratory and instrumental tests; group 2 received an ultrasound scan within 1 h from the admission to the Emergency Department. The concordance between initial and final diagnosis and the percentage of wrong diagnosis in the two groups were evaluated. Mortality, days of hospitalization in Emergency Medicine department and transfers to other wards were compared. Sensitivity and specificity of the routine protocol and the one including ultrasonography for the diagnosis of the causes of dyspnea were also analyzed. RESULTS: Eighty-eight patients were randomized in group 1 and 80 in group 2. The concordance rate between initial and final diagnoses was significantly different (0.94 in group 1 vs. 0.22 in group 2, p < 0.005). The percentage of wrong initial diagnosis was 5% in group 1 and 50% in group 2 (p < 0.0001). CONCLUSIONS: Adding POC-US to routine exams improves the diagnostic accuracy of dyspnea and reduces errors in the Emergency Department.

A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome.

AIM: To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome (MetS). METHODS: Sixty-four patients with MetS followed at a tertiary outpatient clinic were randomly assigned to receive either placebo or a proprietary nutraceutical combination (AP) consisting of berberine, policosanol and red yeast rice, in a prospective, double-blind, placebo-controlled study. Evaluations were performed at baseline and after 18 wk of treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) index was the primary outcome measure. Secondary endpoints included lipid panel, blood glucose and insulin fasting, after a standard mixed meal and after an oral glucose tolerance test (OGTT), flow-mediated dilation (FMD), and waist circumference. RESULTS: Fifty nine patients completed the study, 2 withdrew because of adverse effects. After 18 wk there was a significant reduction in the HOMA-IR index in the AP group compared with placebo (ΔHOMA respectively -0.6 ± 1.2 vs 0.4 ± 1.9; P < 0.05). Total and low density lipoprotein cholesterol also significantly decreased in the treatment arm compared with placebo (Δlow density lipoprotein cholesterol -0.82 ± 0.68 vs -0.13 ± 0.55 mmol/L; P < 0.001), while triglycerides, high density lipoprotein cholesterol, and the OGTT were not affected. In addition, there were significant reductions in blood glucose and insulin after the standard mixed meal, as well as an increase in FMD (ΔFMD 1.9 ± 4.2 vs 0 ± 1.9 %; P < 0.05) and a significant reduction in arterial systolic blood pressure in the AP arm. CONCLUSION: This short-term study shows that AP has relevant beneficial effects on insulin resistance and many other components of MetS.

Recombinant human thyrotropin enhances endothelial-mediated vasodilation of conduit arteries.

CONTEXT: Endothelial cells possess receptors to TSH. Their role is largely unknown. OBJECTIVES: The objective of the study was to determine whether elevated serum TSH levels, as occur in hypothyroidism, affect endothelial function of large arteries and vascular risk biomarkers. SUBJECTS AND METHODS: Thirty-four consecutively recruited patients, who had undergone thyroidectomy for thyroid carcinoma, were studied in connection with one of the monitoring procedures based on recombinant human (rh) TSH administration. Flow-mediated dilation (FMD) of the brachial artery and serum vascular risk markers were measured at baseline and for 5 d after the administration of rhTSH (0.9 mg im on d 1 and 2). Holter electrocardiogram and echocardiography were performed on d 2. RESULTS: rhTSH caused a rapid increase in flow-mediated dilation from the basal value of 10.2 to 15.6% at 6 h (P < 0.0000001), to 16.1% on d 2 (P < 0.0000001), and to 14.9% on d 6 (P = 0.0015). The results were identical when the analysis was made in a subgroup of 19 patients free of vascular risk conditions. Vascular cell adhesion molecule-1, TNFalpha, IL-6, and high sensitive C-reactive protein were unaffected by rhTSH, whereas homocysteine was decreased. Arterial blood pressure, mean 24-h heart rate, and left ventricular function were unaffected by rhTSH. CONCLUSIONS: rhTSH causes marked and persistent activation of the endothelial mediated vasodilation, independent of systemic hemodynamic changes.