Teoria della misura e teoria della probabilità

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Salt, Aldosterone, and Parathyroid Hormone: What Is the Relevance for Organ Damage?

Structured interventions on lifestyle have been suggested as a cost-effective strategy for prevention of cardiovascular disease. Epidemiologic studies demonstrate that dietary salt restriction effectively decreases blood pressure, but its influence on cardiovascular morbidity and mortality is still under debate. Evidence gathered from studies conducted in patients with primary aldosteronism, essential hypertension, or heart failure demonstrates that long-term exposure to elevated aldosterone results in cardiac structural and functional changes that are independent of blood pressure. Animal experiments and initial clinical studies indicate that aldosterone damages the heart only in the context of an inappropriately elevated salt status. Recent evidence suggests that aldosterone might functionally interact with the parathyroid hormone and thereby affect calcium homeostasis with important sequelae for bone mineral density and strength. The interaction between aldosterone and parathyroid hormone might have implications also for the heart. Elevated dietary salt is associated on the one hand with increased urinary calcium excretion and, on the other hand, could facilitate the interaction between aldosterone and parathyroid hormone at the cellular level. This review summarizes the evidence supporting the contribution of salt and aldosterone to cardiovascular disease and the possible cardiac and skeletal consequences of the mutual interplay between aldosterone, parathyroid hormone, and salt

Insulin Resistance and High Blood Pressure: Mechanistic Insight on the Role of the Kidney

The metabolic effects of insulin predominate in skeletal muscle, fat, and liver where the hormone binds to its receptor, thereby priming a series of cell-specific and biochemically diverse intracellular mechanisms. In the presence of a good secretory reserve in the pancreatic islets, a decrease in insulin sensitivity in the metabolic target tissues leads to compensatory hyperinsulinemia. A large body of evidence obtained in clinical and experimental studies indicates that insulin resistance and the related hyperinsulinemia are causally involved in some forms of arterial hypertension. Much of this involvement can be ascribed to the impact of insulin on renal sodium transport, although additional mechanisms might be involved. Solid evidence indicates that insulin causes sodium and water retention, and both endogenous and exogenous hyperinsulinemia have been correlated to increased blood pressure. Although important information was gathered on the cellular mechanisms that are triggered by insulin in metabolic tissues and on their abnormalities, knowledge of the insulin-related mechanisms possibly involved in blood pressure regulation is limited. In this review, we summarize the current understanding of the cellular mechanisms that are involved in the pro-hypertensive actions of insulin, focusing on the contribution of insulin to the renal regulation of sodium balance and body fluids

Alcohol Intake and Arterial Hypertension: Retelling of a Multifaceted Story

Alcoholic beverages are common components of diets worldwide and understanding their effects on humans’ health is crucial. Because hypertension is the leading risk factor for cardiovascular diseases and all-cause mortality, the relationship of alcohol consumption with blood pressure (BP) has been the subject of extensive investigation. For the purpose of this review, we searched the terms “alcohol”, “ethanol”, and “arterial hypertension” on Pubmed MeSH and selected the most relevant studies. Short-term studies showed a biphasic BP response after ingestion of high doses of alcohol, and sustained alcohol consumption above 30 g/day, significantly, and dose-dependently, increased the risk for hypertension. These untoward effects of alcoholic beverages on BP can be mediated by a multiplicity of neurohormonal mechanisms. In addition to the effects on BP, excess alcohol intake might contribute to cardiac and renal hypertensive organ damage, although some studies suggest possible benefits of moderate alcohol consumption on additional cardiovascular risk factors, such as diabetes and lipoprotein(a). Some intervention studies and cumulative analyses support the evidence of a benefit of the reduction/withdrawal of alcohol consumption on BP and cardiovascular outcomes. This is why guidelines of scientific societies recommend avoidance or limitation of alcohol intake below one unit/day for women and two units/day for men. This narrative article overviews all these topics, providing an update of the current knowledge on the relationship between alcohol and BP

Association of arterial stiffness with a prothrombotic state in uncomplicated nondiabetic hypertensive patients

Background and aims: Past studies reported a significant contribution of a prothrombotic state to the development and progression of target organ damage in hypertensive patients. Stiffening of arterial vessels is associated with aging and hypertension, and additional factors could contribute to this process. This study was designed to examine the relationships between arterial stiffening and the hemostatic and fibrinolytic system. Methods: In 128 middle-aged, nondiabetic, essential hypertensive patients without major cardiovascular and renal complications, we measured coagulation markers that express the spontaneous activation of the hemostatic and fibrinolytic system and assessed stiffness of the arterial tree by measurement of the carotid/femoral pulse wave velocity (cfPWV) and pulse wave analysis with calculation of the brachial augmentation index (AIx). Results: Levels of fibrinogen (FBG), D-dimer (D-d), and plasminogen activator-inhibitor 1 (PAI-1) were significantly higher in patients with PWV and AIx above the median of the distribution. FBG, D-d, and PAI-1 were significantly and directly related with both cfPWV and AIx, and multivariate regression analysis indicated that the relationships of D-d and PAI-1 with both cfPWV and AIx and of FBG with AIx, were independent of age, body mass index, severity and duration of hypertension, use of antihypertensive drugs, blood glucose, and plasma lipids. Conclusion: In middle-aged, uncomplicated, nondiabetic patients with essential hypertension, spontaneous activation of plasma hemostatic cascade and impaired fibrinolysis is significantly and independently associated with stiffening of the arterial tree

Association of non-alcoholic fatty liver disease with left ventricular changes in treatment-naive patients with uncomplicated hypertension

Background and aims: Cardiac structural and functional changes have been demonstrated in patients with non-alcoholic fatty liver disease (NAFLD). Because of the frequent association of NAFLD with hypertension, we aimed to examine the relationship of liver steatosis with left ventricular (LV) changes in patients with hypertension. Materials and methods: In a cross-sectional study, we included 360 untreated, essential hypertensive patients who were free of major cardiovascular and renal complications. Liver steatosis was assessed by three different biochemical scores (NAFLD Liver Fat Score, LFS; Fatty Liver Index, FLI; Hepatic Steatosis Index, HSI). Echocardiography was performed with standard B-mode and tissue-Doppler imaging. Results: LV hypertrophy was present in 19.4% and LV diastolic dysfunction in 49.2% of patients who had significantly higher body mass index (BMI), blood pressure (BP), and homeostatic model assessment (HOMA) index and higher frequency of the metabolic syndrome and liver steatosis that was defined by presence of 2 or more positive scores. LV mass index increased progressively across patients who had none, 1, or 2 or more liver steatosis scores, with associated progressive worsening of LV diastolic function. LV mass index was significantly and positively correlated with age, BMI, BP, HOMA-index, LFS, and HSI. Logistic regression analysis showed that age, BP, and liver steatosis scores independently predicted LV hypertrophy and diastolic dysfunction. Liver steatosis independently predicted LV dysfunction but not LV hypertrophy even after inclusion in analysis of the HOMA-index. Conclusion: NAFLD is associated with LV hypertrophy and diastolic dysfunction in untreated patients with hypertension. In hypertension, NAFLD could contribute to LV diastolic dysfunction with mechanisms unrelated to insulin resistance

Short-term cardiac outcome in survivors of COVID-19: a systematic study after hospital discharge

Background COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known.Objective To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness.Methods With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness.Results Cardiac data were collected a median of 41 days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness.Conclusions In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae.[GRAPHICS]

Short-term cardiac outcome in survivors of COVID-19: a systematic study after hospital discharge

Background: COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known. Objective: To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness. Methods: With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness. Results: Cardiac data were collected a median of 41\ua0days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness. Conclusions: In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae. Graphic abstract: [Figure not available: see fulltext.

Cyclophosphamide, Fluorouracil and subcutaneous Interleukin-2 in the treatment of advanced GIST: A Case Report

A male 68 years hold patient was admitted to surgical ward for hemorrhagic shock. After CT scan detection of 6x5 cm neoformation of first jejunal loop, he was submitted to segmental resection and pathological diagnosis was gastrointestinal stromal tumor. The patient was defined as high-risk according to Takahashi criteria, but refused Imatinib adjuvant therapy. After 15 months of disease-free interval, he developed bilobar liver metastases. After treatment with Imatinib 400 mg he reported G3 hepatotoxicity resolved with temporary suspension, he continue low dose with stable disease. After liver progression, he resumed Imatinib full dose with disease stabilization for 9 months. After liver progression, second line Sunitinib 37,5 mg/day was started for four months with stable disease. After further liver and lymph node mediastinal progression he was treated for four months with Regorafenib with disease stabilization. Patient developed slow but inexorable progression of liver disease with severe abdominal pain resistant to opioid and was treated with authorized compassionate program comprising Cyclophosphamide 300 mg/sqm and Fluorouracil 500 mg/sqm on day 1 intravenously followed by Interleukin-2 4.5 MUI subcutaneously on days 3–6 and 17–20 every four weeks. After three cycles the patients obtained a relevant subjective improvement with partial response on mediastinal lymph node and liver stabilization. A substantial increase on neutrophil, lymphocytes, monocytes, platelets, T regulator cells count, and a decrease on platelets/lymphocytes, CD8/T regulator cells ratio, CD8, NK count and C-reactive protein value were observed after treatment compared to basal value. The toxicity was mild represented by fever G1, flue-like-syndrome G1 during the treatment. After four cycle of chemo-immunotherapy, the patient demonstrated progression of disease and died five months after treatment. Noteworthy is the temporal disease control with significant symptomatic improvement achieved for the first time with this chemo-immunotherapeutic combination in a patient with very advanced pretreated GIST

Slab segmentation controls the interplate slip motion in the SW Hellenic subduction: New insight from the 2008Mw 6.8 Methoni interplate earthquake

We present an integrated approach of the seismic structure and activity along the offshore SW Hellenic subduction from combined observations of marine and land seismic stations. Our imaging of the slab top topography from teleseismic receiver function analysis at ocean bottom seismometers supports a trenchward continuation of the along-dip slab faults beneath the Peloponnesus. We further show that their morphostructural control accounts for the backstepping of the thrust contact of the Mediterranean Ridge accretionary wedge over the upper plate. Local seismic activity offshore SW Peloponnesus constrained by ocean bottom seismometer observations reveals a correlation with specific features of the forearc: the Matapan Troughs. We study the Mw6.8 14.02.2008 interplate earthquake offshore SW Peloponnesus and show that its nucleation, rupture zone, and aftershocks sequence are confined to one slab panel between two adjacent along-dip faults and are thus controlled by not only the offshore slab top segmentation but also the upper plate sea-bottom morphology