White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma

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WAT to BAT transdifferentiation of omental fat in adult humans affected by pheochromocytomas

In small mammals and to some extent also in humans, White Adipose Tissue (WAT) and Brown Adipose Tissue (BAT) are contained together in discrete locations at subcutaneous or visceral level forming a multi-depots organ [1]. We have recently described paucilocular cells immunoreactive for uncoupling protein 1 (UCP1-ir) as morphological marker of WAT-BAT transformation in the adipose organ of cold-exposed mice (hyper-adrenergic stimulation) [2]. In this study, we examined biopsies of omental WAT depot, in 20 controls and in 12 patients affected by pheochromocytomas used as model of adrenergic stimulation in humans. Histological examination was performed by light microscopy, immunohistochemistry and Electron Microscopy. qPCR was carried out to asses relative expression of “brown” genes. Control tissues were all formed by unilocular UCP1-negative adipocytes. Half of the omental fat samples from pheochromocytomas showed UCP1-ir multilocular cells forming BAT-islands among WAT. Several UCP1-ir paucilocular cells were also detected. Higher density of TH-ir fibres and capillaries were found in the transformed tissues. Ultrastructural examination, highlighted poorly differentiated cells in pericapillary position with features similar to those identified in supraclavicular human BAT [3]. In light of the protective role exerted by BAT against the development of obesity and other metabolic diseases, WAT to BAT plasticity could be an important target for the development of therapeutic strategies in the treatment of obesity and type II diabetes in humans

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

Contributi per una flora vascolare di Toscana. VIII (440-506)

New localities and/or confirmations concerning 67 specific and subspecific plant taxa of Tuscan vascular flora, belonging to 59 genera and 37 families are presented: Alisma (Alismataceae), Amaranthus (Amaranthaceae), Leucojum, Sternbergia, Tristagma (Amaryllidaceae), Aloe (Asphodelaceae), Erigeron, Galinsoga, Hieracium, Rhagadiolus, Silybum, Soliva, Taraxacum (Asteraceae), Impatiens (Balsaminaceae), Berberis (Berberidaceae), Cardamine (Brassicaceae), Opuntia (Cactaceae), Cephalaria, Sixalix, Succisa (Caprifoliaceae), Silene (Caryophyllaceae), Convolvulus, Ipomoea (Convolvulaceae), Aeonium (Crassulaceae), Scirpus (Cyperaceae), Equisetum (Equisetaceae), Euphorbia (Euphorbiaceae), Astragalus, Trifolium (Fabaceae), Quercus (Fagaceae), Crocus (Iridaceae), Juncus (Juncaceae), Utricularia (Lentibulariaceae), Peplis (Lythraceae), Maclura (Moraceae), Nymphaea (Nymphaeaceae), Oenothera (Onagraceae), Anacamptis, Orchis (Orchidaceae), Orobanche (Orobanchaceae), Callitriche, Veronica (Plantaginaceae), Alopecurus, Eleusine, Glyceria, Phleum (Poaceae), Persicaria, Polygonum (Polygonaceae), Groenlandia (Potamogetonaceae), Clematis, Pulsatilla, Ranunculus (Ranunculaceae), Rhamnus (Rhamnaceae), Fragaria, Potentilla, Pyracantha (Rosaceae), Galium (Rubiaceae), Sparganium (Typhaceae), Vitis (Vitaceae). In the end, the conservation status of the units and eventual protection of the cited biotopes are discussed

Contributi per una flora vascolare di Toscana. VIII (440-506) [Contributions for a vascular flora of Tuscany. VIII (440-506)]

Contributions for a vascular flora of Tuscany. VIII (440-506). New localities and/or confirmations concerning 67 specific and subspecific plant taxa of Tuscan vascular flora, belonging to 59 genera and 37 families are presented: Alisma (Alismataceae), Amaranthus (Amaranthaceae), Leucojum, Sternbergia, Tristagma (Amaryllidaceae), Aloe (Asphodelaceae), Erigeron, Galinsoga, Hieracium, Rhagadiolus, Silybum, Soliva, Taraxacum (Asteraceae), Impatiens (Balsaminaceae), Berberis (Berberidaceae), Cardamine (Brassicaceae), Opuntia (Cactaceae), Cephalaria, Sixalix, Succisa (Caprifoliaceae), Silene (Caryophyllaceae), Convolvulus, Ipomoea (Convolvulaceae), Aeonium (Crassulaceae), Scirpus (Cyperaceae), Equisetum (Equisetaceae), Euphorbia (Euphorbiaceae), Astragalus, Trifolium (Fabaceae), Quercus (Fagaceae), Crocus (Iridaceae), Juncus (Juncaceae), Utricularia (Lentibulariaceae), Peplis (Lythraceae), Maclura (Moraceae), Nymphaea (Nymphaeaceae), Oenothera (Onagraceae), Anacamptis, Orchis (Orchidaceae), Orobanche (Orobanchaceae), Callitriche, Veronica (Plantaginaceae), Alopecurus, Eleusine, Glyceria, Phleum (Poaceae), Persicaria, Polygonum (Polygonaceae), Groenlandia (Potamogetonaceae), Clematis, Pulsatilla, Ranunculus (Ranunculaceae), Rhamnus (Rhamnaceae), Fragaria, Potentilla, Pyracantha (Rosaceae), Galium (Rubiaceae), Sparganium (Typhaceae), Vitis (Vitaceae). In the end, the conservation status of the units and eventual protection of the cited biotopes are discussed

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population