Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension.

Background and aims: A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension. Methods: In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol). Results: Plasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function. Conclusion: Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

Comprehensive Echographic Evaluation of Insulinoma, From Bedside to Endoscopic Ultrasonography: A Case Report and Brief Review of the Literature.

Insulinoma is a neuroendocrine tumor of the pancreas, and its identification with bedside ultrasonography (US) is extremely rare. With the aim of providing a comprehensive description of the main US characteristics of this rare form of neuroendocrine neoplasm, we are here describing an interesting case of a young woman with insulinoma, identified by using both bedside and endoscopic ultrasounds.

Semaglutide Treatment in Adult-Onset Autoimmune Diabetes: A Case Study With Long-Term Follow-Up and Periodic Evaluation of Beta-Cell Function.

Latent autoimmune diabetes of adults (LADA) is a form of autoimmune diabetes that typically occurs in adulthood and has intermediate characteristics between type 1 and type 2 diabetes. To optimize the diagnostic and therapeutic approach, recently, a subclassification of LADA has been proposed based on some clinical features, antibodies, and beta cellular function at onset. In this paper, we expose an interesting case showing the effectiveness of early treatment with a glucagon-like peptide receptor agonist (semaglutide) in maintaining long-term good glycemic control and associated with the preservation of beta-cell function over a five-year observation period in a young woman with LADA.

Cortisol secretion and abnormalities of glucose metabolism in nondiabetic patients with hypertension.

OBJECTIVE: Glycometabolic changes are associated with hypercortisolism in Cushing's syndrome. Because impaired glucose tolerance (IGT) and insulin resistance are frequently detected in patients with essential hypertension, we hypothesized that in these patients, early glycometabolic abnormalities might be related to differences in regulation of cortisol secretion. METHODS: In a cross-sectional study, we included 155 nondiabetic, essential hypertensive patients who were free of organ complications. The homeostasis model assessment (HOMA) index and the area under the curve of plasma glucose (AUC-glucose) and insulin (AUC-insulin) concentration following an oral glucose tolerance test were measured, together with daily plasma cortisol (8 a.m., 3 p.m. and 12 a.m.; AUC-cortisol) and 8 a.m. cortisol after 1 mg overnight dexamethasone suppression test (DST). RESULTS: IGT was present in 27% of patients who were older and had higher BMI, plasma triglycerides and uric acid, AUC-cortisol and DST-cortisol, and lower HDL-cholesterol. Frequency of IGT increased progressively across tertiles of DST-cortisol, together with levels of glycated hemoglobin, fasting insulin and C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. AUC-cortisol and DST-cortisol were directly correlated with insulin, C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. Multivariate regression analysis showed that DST-cortisol was directly and independently correlated with HOMA index, AUC-glucose, and AUC-insulin. In a logistic regression model, both AUC-cortisol and DST-cortisol independently predicted IGT. CONCLUSION: Daily cortisol and cortisol response to DST are independent determinants of IGT and insulin resistance in nondiabetic patients with hypertension, suggesting that even subtle differences in regulation of cortisol secretion might increase the risk of these patients to develop diabetes.

Lipoprotein(a): Just an Innocent Bystander in Arterial Hypertension?

Elevated plasma lipoprotein(a) [Lp(a)] is a relatively common and highly heritable trait conferring individuals time-dependent risk of developing atherosclerotic cardiovascular disease (CVD). Following its first description, Lp(a) triggered enormous scientific interest in the late 1980s, subsequently dampened in the mid-1990s by controversial findings of some prospective studies. It was only in the last decade that a large body of evidence has provided strong arguments for a causal and independent association between elevated Lp(a) levels and CVD, causing renewed interest in this lipoprotein as an emerging risk factor with a likely contribution to cardiovascular residual risk. Accordingly, the 2022 consensus statement of the European Atherosclerosis Society has suggested inclusion of Lp(a) measurement in global risk estimation. The development of highly effective Lp(a)-lowering drugs (e.g., antisense oligonucleotides and small interfering RNA, both blocking LPA gene expression) which are still under assessment in phase 3 trials, will provide a unique opportunity to reduce "residual cardiovascular risk" in high-risk populations, including patients with arterial hypertension. The current evidence in support of a specific role of Lp(a) in hypertension is somehow controversial and this narrative review aims to overview the general mechanisms relating Lp(a) to blood pressure regulation and hypertension-related cardiovascular and renal damage.

A State-of-Art Review of the Vicious Circle of Sleep Disorders, Diabetes and Neurodegeneration Involving Metabolism and Microbiota Alterations.

In the context of neurodegenerative disorders, cognitive decline is frequently reported in older population. Recently, numerous metabolic pathways have been implicated in neurodegeneration, including signaling disruption of insulin and other glucose-regulating hormones. In fact, Alzheimer's disease has now been considered as "type-3 diabetes". In this review, we tried to clarify the role of sleep impairment as the third major player in the complex relationship between metabolic and neurodegenerative diseases. Altered sleep may trigger or perpetuate these vicious mechanisms, leading to the development of both dementia and type 2 diabetes mellitus. Finally, we analyzed these reciprocal interactions considering the emerging role of the gut microbiota in modulating the same processes. Conditions of dysbiosis have been linked to circadian rhythm disruption, metabolic alterations, and release of neurotoxic products, all contributing to neurodegeneration. In a future prospective, gut microbiota could provide a major contribution in explaining the tangled relationship between sleep disorders, dementia and diabetes.

Omega-3 Fatty Acids in Arterial Hypertension: Is There Any Good News?

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are "essential" fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of "residual" cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented "pleiotropic" actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes.

Liver injury in COVID-19 patients with non-alcoholic fatty liver disease: an update.

The coronavirus disease 2019 (COVID-19) pandemic has revolutionized the priorities of the medical society worldwide. Although most patients infected with SARS-CoV-2 exhibit respiratory symptoms, other organs may also be involved, including the liver, often resulting in liver injury. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its prevalence is expected to increase together with the epidemics of type 2 diabetes and obesity. Data about liver injury during COVID-19 are numerous, while overviews of this infection in patients with NAFLD, both in terms of respiratory and liver, are emerging. In this review, we summarise the current research focusing on COVID-19 in NAFLD patients and discuss the association between liver injury in COVID-19 subjects and non-alcoholic fatty liver disease.

Effects of Monacolin K in Nondiabetic Patients with NAFLD: A Pilot Study.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies.

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.

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.

An Unusual Case of Severe Hypertension Presenting With Leg Weakness, Hypokalemia, and Hyperreninemic Aldosteronism.

Takayasu's arteritis is a rare vasculitis characterized by granulomatous inflammation of the large vessels, typically occurring in the second or third decade of life and preferentially affecting females. It commonly involves large vessels such as the aorta and its major branches (carotid and iliac arteries). Visceral arterial involvement is uncommon and reported in only a minority of patients. Clinical manifestations of Takayasu arteritis are heterogeneous and could include nonspecific symptoms such as fever of unknown origin, asthenia, myalgias, intermittent claudication, angina, and mild arterial hypertension. The rarity of this disease and the extreme heterogeneity of clinical manifestations often lead to delays in diagnosis, lasting more than three years in some patients. Improving knowledge of its diagnostic workup could help clinicians in prompt clinical suspicion and early diagnosis. Here, we aim to describe a particular case of a 40-year-old woman with severe hypertension symptomatic for dizziness, gait instability, leg weakness, and diffuse cramps caused by renovascular hypertension as the first clinical manifestation of Takayasu's arteritis involving the right renal artery.

Nutritional supplementation on wound healing in diabetic foot: What is known and what is new?

Non-healing diabetic foot ulcers (DFU) are the most notable and striking complications of diabetes mellitus. More than 25% of nonhealing DFU can ultimately lead to amputation of the lower extremity within 6-18 mo after the first manifestation of the wound. Although wound healing is complex, nutritional status is crucial in soft tissue repair. Malnutrition is highly prevalent and overlooked in patients with diabetes and chronic wounds. Moreover, to date, we do not have clear recommendations or evidence about the use of nutritional supplements for improving wound healing in patients with DFU. In this article the authors briefly analyzed the current evidence on the use of nutritional supplements of proteins or amino acids, fatty acids, probiotics, vitamins, and trace elements in the wound healing process in patients with DFU.

The impact of body composition on mortality of COVID-19 hospitalized patients: A prospective study on abdominal fat, obesity paradox and sarcopenia.

BACKGROUND & AIMS: Obesity has been described as a predisposing risk factor to severe forms of COVID-19, but conflicting results are emerging on its real impact on the mortality of COVID-19. We aimed to compare clinical outcomes and mortality among COVID-19 patients according to obesity, metabolic syndrome and adiposity distribution. METHODS: We conducted a prospective observational study of all consecutive adult patients with a confirmed diagnosis of SARS-CoV-2 infection admitted to the Infectious Diseases Clinic at Udine Hospital, Italy, from January 2021 to February 2021. At admission, the study population was submitted to specific anthropometric, laboratory and bioimpedance analysis (BIA) measurements and divided into five groups according to: 1) BMI < or >30 kg/m2; 2) waist circumference (WC) < or >98 cm for women, < or >102 cm for men; 3) presence or absence of metabolic syndrome (MS); 4) visceral adipose tissue (VAT) distribution; and 5) presence or absence of sarcopenia (SP) both based on BIA. We then compared clinical outcomes (ventilatory support, intensive care unit (ICU) admission, ICU length of stay, total hospital length of stay and mortality), immune and inflammatory makers and infectious and non-infectious acute complications within the five groups. RESULTS: A total of 195 patients were enrolled in the study. The mean age of patients was 71 years (IQR 61-80) and 64.6% (126) were male. The most common comorbidities were hypertension (55.9%) and MS (55.4%). Overall mortality was 19.5%. Abdominal adiposity, measured both with WC and with BIA, and SP were significantly associated with need for increased ventilator support (p = 0.013 for WC; p = 0.037, 0.027 and 0.009 for VAT; p = 0.004 and 0.036 for FMI; and p = 0.051 for SP), but not with ICU admission (WC p = 0.627, VAT p = 0.153, FMI p = 0.519 and SP p = 0.938), length of stay (WC p = 0.345, VAT p = 0.650, FMI p = 0.159 and SP p = 0.992) and mortality (WC p = 0.277, VAT p = 0.533, FMI p = 0.957 and SP p = 0.211). Obesity and MS did not discriminate for the intensity of ventilatory outcome (p = 0.142 and p = 0.198, respectively), ICU admission (p = 0.802 and p = 0.947, respectively), length of stay (p = 0.471 and p = 0.768, respectively) and mortality (p = 0.495 and p = 0.268, respectively). We did not find significant differences in inflammatory markers and secondary complications within the five groups. CONCLUSIONS: In patients admitted with COVID-19, increased WC, visceral abdominal fat and SP are associated with higher need for ventilatory support. However, obesity, MS, SP and abdominal adiposity are not sensitive predictive factors for mortality.

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.

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.

Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection.

Introduction: Stress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19. Methods: In a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission. Results: Patients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078-6.012) and death (OR 2.281; CI 1.049-7.369) independently of diabetes and other major confounders. Conclusions: In patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.

Effect of heparin treatment on pulmonary embolism and in-hospital death in unvaccinated COVID-19 patients without overt deep vein thrombosis.

BACKGROUND: Pulmonary embolism (PE) without overt deep vein thrombosis (DVT) was common in hospitalized coronavirus-induced disease (COVID)-19 patients and represented a diagnostic, prognostic, and therapeutic challenge. The aim of this study was to analyze the prognostic role of PE on mortality and the preventive effect of heparin on PE and mortality in unvaccinated COVID-19 patients without overt DVT. METHODS: Data from 401 unvaccinated patients (age 68 ± 13 years, 33% females) consecutively admitted to the intensive care unit or the medical ward were included in a retrospective longitudinal study. PE was documented by computed tomography scan and DVT by compressive venous ultrasound. The effect of PE diagnosis and any heparin use on in-hospital death (primary outcome) was analyzed by a classical survival model. The preventive effect of heparin on either PE diagnosis or in-hospital death (secondary outcome) was analyzed by a multi-state model after having reclassified patients who started heparin after PE diagnosis as not treated. RESULTS: Median follow-up time was 8 days (range 1-40 days). PE cumulative incidence and in-hospital mortality were 27% and 20%, respectively. PE was predicted by increased D-dimer levels and COVID-19 severity. Independent predictors of in-hospital death were age (hazards ratio (HR) 1.05, 95% confidence interval (CI) 1.03-1.08, p < 0.001), body mass index (HR 0.93, 95% CI 0.89-0.98, p = 0.004), COVID-19 severity (severe versus mild/moderate HR 3.67, 95% CI 1.30-10.4, p = 0.014, critical versus mild/moderate HR 12.1, 95% CI 4.57-32.2, p < 0.001), active neoplasia (HR 2.58, 95% CI 1.48-4.50, p < 0.001), chronic obstructive pulmonary disease (HR 2.47; 95% CI 1.15-5.27, p = 0.020), respiratory rate (HR 1.06, 95% CI 1.02-1.11, p = 0.008), heart rate (HR 1.03, 95% CI 1.01-1.04, p < 0.001), and any heparin treatment (HR 0.35, 95% CI 0.18-0.67, p = 0.001). In the multi-state model, preventive heparin at prophylactic or intermediate/therapeutic dose, compared with no treatment, reduced PE risk and in-hospital death, but it did not influence mortality of patients with a PE diagnosis. CONCLUSIONS: PE was common during the first waves pandemic in unvaccinated patients, but it was not a negative prognostic factor for in-hospital death. Heparin treatment at any dose prevented mortality independently of PE diagnosis, D-dimer levels, and disease severity.

IDegLira for the Real-World Treatment of Type 2 Diabetes in Italy: Protocol and Interim Results from the REX Observational Study.

INTRODUCTION: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). METHODS: Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2-3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients' baseline characteristics and the clinical reasons for IDegLira treatment initiation. RESULTS: Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0-20.0) units in the BOT group and 42 (30.0-52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). CONCLUSIONS: IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients' outcomes after IdegLira treatment under routine clinical care.

Differences in Regulation of Cortisol Secretion Contribute to Left Ventricular Abnormalities in Patients With Essential Hypertension.

BACKGROUND: Left ventricular (LV) abnormalities were reported in patients with overt and subclinical Cushing syndrome. The aim of this study was to investigate the relationships of daily plasma cortisol profile and cortisol response to an overnight suppression test with cardiac changes in patients with hypertension. METHODS: In a cross-sectional study, we included 136 nondiabetic, patients with essential hypertension who were free of cardiovascular and renal complications. Plasma cortisol was measured at 8 am, 3 pm, and 12 am and at 8 am after overnight suppression with 1 mg dexamethasone (dexamethasone suppression test [DST]). Echocardiography was performed with standard B-mode and tissue-Doppler imaging. RESULTS: LV hypertrophy was present in 30% and LV diastolic dysfunction in 51% of patients who were older and had significantly higher body mass index, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol. LV mass index and relative wall thickness increased progressively across tertiles of DST cortisol, together with progressive worsening of diastolic function. LV mass index was directly related to age, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol, and inversely to creatinine clearance. Multivariate regression analysis showed independent correlation of LV mass index with body mass index, systolic blood pressure, and 12 am and DST cortisol. Logistic regression showed that DST cortisol independently predicted LV hypertrophy. CONCLUSIONS: Midnight and DST plasma cortisol levels are independent determinants of LV mass and geometry in patients with essential hypertension suggesting that even minor changes in regulation of cortisol secretion could contribute to cardiac abnormalities in these patients.