231 results on '"Settore MED/09"'
Search Results
2. Effects of COVID-19 vaccination on clinical outcomes in patients hospitalized in Internal Medicine during Omicron variant spreading
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Luca Colangeli, Gianna Aprile, Clara Carcone, Monica D’Adamo, Emanuela Medda, Paolo Sbraccia, and Valeria Guglielmi
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Omicron ,SARS-CoV-2 ,Vaccination ,Emergency Medicine ,Internal Medicine ,COVID-19 ,Settore MED/09 ,Variant - Published
- 2023
3. Bariatric surgery for metabolic unhealthy obesity (MUO) during the COVID era: short-term results of a high-volume center
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Valeria Guglielmi, Michela Campanelli, Emanuela Bianciardi, Domenico Benavoli, Luca Colangeli, Monica D’Adamo, Paolo Sbraccia, and Paolo Gentileschi
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Weight loss ,Psychiatry and Mental health ,Clinical Psychology ,Settore MED/25 ,COVID-19 ,Settore MED/09 ,Metabolically unhealthy obese ,Sleeve gastrectomy ,Laparoscopic bariatric surgery ,Settore MED/18 - Abstract
Purpose During the coronavirus disease 19 (COVID-19) outbreak, most public hospitals worldwide have been forced to postpone a major part of bariatric surgery (BS) operations with unfavorable consequences for weight and obesity complications. The aim of this study was to evaluate the effectiveness and safety of laparoscopic BS on subjects with metabolically unhealthy obesity (MUO) during COVID-19 pandemic in a high-volume Italian center. Methods Between March 2020 and January 2021, all patients with MUO submitted to laparoscopic BS (sleeve gastrectomy [SG], one anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) were enrolled according to the ATP III Guidelines, with a minimum follow-up of 3 months. Results In the study period, 210 patients with MUO underwent laparoscopic BS (77 RYGB, 85 SG and 48 OAGB) in our obesity referral center. Postoperative major complications occurred in 4 patients (1.9%) with zero mortality. At 9-month follow-up, a total weight loss (TWL) of 28.2 ± 18.4, 26.1 ± 23.1 and 24.5 ± 11.3% (p = 0.042) was observed in RYGB, OAGB and SG groups, respectively. The rate of comorbidity resolution was very similar for all type of surgeries (p = 0.871). Only two cases of postoperative SARS-CoV-2 infection were registered (0.9%) and both cases resolved with medical therapy and observation. Conclusion Among the patients studied, all surgical techniques were safe and effective for MUO during the COVID era. This group of patients is at high risk for general and SARS-CoV-2-related mortality and therefore should be prioritized for BS. Level of evidence Level III, single-center retrospective cohort study.
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- 2022
4. Metabolically healthy obesity: does it exist?
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Paolo Sbraccia
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Internal Medicine ,Settore MED/09 - Published
- 2023
5. Screening of Fabry Disease of patients in renal replacement therapy in a population from Lazio (Italy)
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Marrone, G, Angelico, R, Di Lauro, M, Sargentini, E, Manzia, Tm, Tisone, G, Mitterhofer, Ap, Della Morte Canosci, D, Tesauro, M, Di Daniele, N, and Noce, A
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Settore MED/09 ,Settore MED/18 - Published
- 2023
6. The possible role of physical activity in the modulation of gut microbiota in chronic kidney disease and its impact on cardiovascular risk: a narrative review
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Noce, A, Tranchita, E, Marrone, G, Grazioli, E, Di Lauro, M, Murri, A, Vanni, G, Della Morte Canosci, D, Di Daniele, N, Parisi, A, Tesauro, M, and Cerulli, C
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Settore MED/14 ,Settore MED/09 ,Settore MED/18 - Published
- 2023
7. Impact of Insulin Degludec/Liraglutide Fixed Combination on the Gut Microbiomes of Elderly Patients With Type 2 Diabetes: Results From A Subanalysis of A Small Non-Randomised Single Arm Study
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Rizza, S, Pietrucci, D, Longo, S, Menghini, R, Teofani, A, Piciucchi, G, Montagna, M, and Federici, M
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aging ,microbiota ,Type 2 diabetes ,Settore MED/09 ,GLP-1 RA ,Liraglutide - Published
- 2023
8. Low-density lipoprotein cholesterol levels are associated with first-phase insulin release
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Chiara M.A. Cefalo, Elena Succurro, Alessia Riccio, Maria Adelaide Marini, Teresa Vanessa Fiorentino, Maria Perticone, Angela Sciacqua, Francesco Andreozzi, and Giorgio Sesti
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Endocrinology ,β-cell function ,Endocrinology, Diabetes and Metabolism ,Insulin secretion ,Internal Medicine ,LDL-cholesterol ,Euglycemic hyperinsulinemic clamp ,Type 2 diabetes ,Settore MED/09 ,General Medicine ,Insulin sensitivity - Published
- 2023
9. The emerging role of sodium-glucose cotransporter 2 inhibitors in heart failure
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Giulio G. Stefanini, Mauro Gitto, Alessandro Villaschi, Massimo Federici, and Gianluigi Condorelli
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Pharmacology ,Drug Discovery ,Fluid overload ,Acute heart failure ,Settore MED/09 ,HFrEF ,HFpEF ,SGLT2 inhibitors ,Cardiac remodeling - Abstract
Abstract: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively novel drug class that most cardiologists are becoming familiar with. By contrasting glucose reabsorption in the proximal convoluted tubule of the nephron, SGLT2 inhibition results in glycosuria with improved glycemic control. Although originally introduced as anti-diabetic medications, the cardiovascular effects of SGLT2i have progressively emerged, leading them to become one of the four pillars for the treatment of heart failure with reduced ejection fraction (HFrEF) according to the 2021 guidelines from the European Society of Cardiology. Also, two recent randomized trials have demonstrated SGLT2i as the first compounds with proven prognostic impact in heart failure with preserved ejection fraction (HFpEF), setting a milestone in the treatment for this condition. While the exact pathogenic mechanisms mediating the substantial reduction in cardiovascular death and heart failure (HF) hospitalizations are still controversial, there is growing clinical evidence on the efficacy and safety of SGLT2i in various subsets of patients with HF. As known, heart failure is a complex and heterogeneous clinical syndrome with a magnitude of phenotypes and a variety of underlying hemodynamic and physiological aspects which cannot be fully incorporated into the traditional left ventricular ejection fraction based classification adopted in clinical trials. The aim of this review is to provide an overview of the cardiovascular benefits and indications of SGLT2i across different HF patterns and to highlight current gaps in knowledge that should be addressed by future research.
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- 2023
10. Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial
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Mauro Chiarito, Jorge Sanz-Sanchez, Raffaele Piccolo, Francesco Condello, Gaetano Liccardo, Matteo Maurina, Marisa Avvedimento, Damiano Regazzoli, Paolo Pagnotta, Hector M. Garcia-Garcia, Roxana Mehran, Massimo Federici, Gianluigi Condorelli, Jose Luis Diez Gil, Bernhard Reimers, Giuseppe Ferrante, and Giulio Stefanini
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Endocrinology, Diabetes and Metabolism ,Coronary angiography ,Settore MED/09 ,Cardiology and Cardiovascular Medicine ,Metformin ,Metformin-associated lactic acidosis ,Percutaneous coronary intervention - Abstract
Background Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. Methods In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. Results 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3–2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3–2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR − 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43–150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. Conclusions In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function. Trial registration: The study was registered at Clinicaltrials.gov (NCT04766008). Graphical Abstract
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- 2023
11. Association between Cognitive Impairment and Malnutrition in Hemodialysis Patients: Two Sides of the Same Coin
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Silverio Rotondi, Lida Tartaglione, Marzia Pasquali, Maria Josè Ceravolo, Anna Paola Mitterhofer, Annalisa Noce, Monica Tavilla, Silvia Lai, Francesca Tinti, Maria Luisa Muci, Alessio Farcomeni, and Sandro Mazzaferro
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Nutrition and Dietetics ,hemodialysis ,protein energy wasting ,mild cognitive impairment ,mis ,moca ,Settore MED/14 ,Settore MED/09 ,MIS ,Settore SECS-S/01 ,Food Science ,MoCa - Abstract
Cognitive impairment and malnutrition are prevalent in patients on hemodialysis (HD), and they negatively affect the outcomes of HD patients. Evidence suggests that cognitive impairment and malnutrition may be associated, but clinical studies to assess this association in HD patients are lacking. The aim of this study was to evaluate the association between cognitive impairment evaluated by the Montreal Cognitive Assessment (MoCA) score and nutritional status evaluated by the malnutrition inflammation score (MIS) in HD patients. We enrolled 84 HD patients (44 males and 40 females; age: 75.8 years (63.5–82.7); HD vintage: 46.0 months (22.1–66.9)). The MISs identified 34 patients (40%) as malnourished; the MoCa scores identified 67 patients (80%) with mild cognitive impairment (MCI). Malnourished patients had a higher prevalence of MCI compared to well-nourished patients (85% vs. 70%; p = 0.014). MoCa score and MIS were negatively correlated (rho:−0.317; p < 0.01). Our data showed a high prevalence of MCI and malnutrition in HD patients. Low MoCA scores characterized patients with high MISs, and malnutrition was a risk factor for MCI. In conclusion, it is plausible that MCI and malnutrition are linked by common sociodemographic, clinical, and biochemical risk factors rather than by a pathophysiological mechanism.
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- 2023
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12. Human liver microbiota modeling strategy at the early onset of fibrosis
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Camille Champion, Radu M. Neagoe, Maria Effernberger, Daniela T. Sala, Florence Servant, Jeffrey E. Christensen, Maria Arnoriaga-Rodriguez, Jacques Amar, Benjamin Lelouvier, Pascale Loubieres, Vincent Azalbert, Matthieu Minty, Charlotte Thomas, Vincent Blasco-Baque, Fabrice Gamboa, Herbert Tilg, Marina Cardellini, Massimo Federici, Jose-Manuel Fernández-Real, Jean Michel Loubes, and Rémy Burcelin
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Microbiology (medical) ,Biomathematics ,Tissue microbiota ,Microbiota ,Metabolic disease ,Settore MED/09 ,Microbiology ,Liver diseases - Abstract
Background Gut microbiota is involved in the development of liver diseases such as fibrosis. We and others identified that selected sets of gut bacterial DNA and bacteria translocate to tissues, notably the liver, to establish a non-infectious tissue microbiota composed of microbial DNA and a low frequency live bacteria. However, the precise set of bacterial DNA, and thereby the corresponding taxa associated with the early stages of fibrosis need to be identified. Furthermore, to overcome the impact of different group size and patient origins we adapted innovative statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2), to study the early stages of the disease, were collected from Romania(n = 36), Austria(n = 10), Italy(n = 19), and Spain(n = 17). The 16S rRNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences. Results Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50% of liver taxa associated with the early stage fibrosis were Enterobacteriaceae, Pseudomonadaceae, Xanthobacteriaceae and Burkholderiaceae. The Flavobacteriaceae and Xanthobacteriaceae discriminated between F0 and F1. Predicted metagenomics analysis identified that the preQ0 biosynthesis and the potential pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0. Conclusions Without demonstrating causality, our results suggest first a role of bacterial translocation to the liver in the progression of fibrosis, notably at the earliest stages. Second, our statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses. Trial registration TirguMECCH ROLIVER Prospective Cohort for the Identification of Liver Microbiota, registration 4065/2014. Registered 01 01 2014.
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- 2023
13. Recent Pharmacological Options in Type 2 Diabetes and Synergic Mechanism in Cardiovascular Disease
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Aikaterini Andreadi, Saverio Muscoli, Rojin Tajmir, Marco Meloni, Carolina Muscoli, Sara Ilari, Vincenzo Mollace, David Della Morte, Alfonso Bellia, Nicola Di Daniele, Manfredi Tesauro, and Davide Lauro
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cardiovascular risk ,Organic Chemistry ,cardiovascular complications ,Settore MED/09 ,General Medicine ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Settore MED/13 ,insulin resistance ,diabetes mellitus ,oxidative stress ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Diabetes Mellitus is a multifactorial disease with a critical impact worldwide. During prediabetes, the presence of various inflammatory cytokines and oxidative stress will lead to the pathogenesis of type 2 diabetes. Furthermore, insulin resistance and chronic hyperglycemia will lead to micro- and macrovascular complications (cardiovascular disease, heart failure, hypertension, chronic kidney disease, and atherosclerosis). The development through the years of pharmacological options allowed us to reduce the persistence of chronic hyperglycemia and reduce diabetic complications. This review aims to highlight the specific mechanisms with which the new treatments for type 2 diabetes reduce oxidative stress and insulin resistance and improve cardiovascular outcomes.
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- 2023
14. Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance
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Bellucci, E, Chiereghin, F, Pacifici, F, Donadel, G, De Stefano, A, Malatesta, G, Valente, Mg, Guadagni, F, Infante, M, Rovella, V, Noce, A, Tesauro, M, Di Daniele, N, Della Morte, D, and Pastore, D
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FMT ,Gut dysbiosis ,Settore MED/46 ,Endocannabinoid system ,NAFLD ,Polyphenols ,Insulin resistance ,Settore MED/09 ,Chinese herbs ,Settore MED/49 ,Probiot-ics ,MCJ - Published
- 2023
15. Sex-Related Differences and Factors Associated with Peri-Procedural and 1 Year Mortality in Chronic Limb-Threatening Ischemia Patients from the CLIMATE Italian Registry
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Eugenio Martelli, Matilde Zamboni, Giovanni Sotgiu, Laura Saderi, Massimo Federici, Giuseppe M. Sangiorgi, Mariangela V. Puci, Allegra R. Martelli, Teresa Messina, Paolo Frigatti, Maria Pia Borrelli, Carlo Ruotolo, Ilaria Ficarelli, Paolo Rubino, Francesco Pezzo, Luciano Carbonari, Andrea Angelini, Edoardo Galeazzi, Luca Calia Di Pinto, Franco M. Fiore, Armando Palmieri, Giorgio Ventoruzzo, Giulia Mazzitelli, Franco Ragni, Antonio Bozzani, Enzo Forliti, Claudio Castagno, Pietro Volpe, Mafalda Massara, Diego Moniaci, Elisa Pagliasso, Tania Peretti, Mauro Ferrari, Nicola Troisi, Piero Modugno, Maurizio Maiorano, Umberto M. Bracale, Marco Panagrosso, Mario Monaco, Giovanni Giordano, Giuseppe Natalicchio, Antonella Biello, Giovanni M. Celoria, Alessio Amico, Mauro Di Bartolo, Massimiliano Martelli, Roberta Munaó, Davide Razzano, Giovanni Colacchio, Francesco Bussetti, Gaetano Lanza, Antonio Cardini, Bartolomeo Di Benedetto, Mario De Laurentis, Maurizio Taurino, Pasqualino Sirignano, Pierluigi Cappiello, Andrea Esposito, Santi Trimarchi, Silvia Romagnoli, Andrea Padricelli, Giorgio Giudice, Adolfo Crinisio, Giovanni Di Nardo, Giuseppe Battaglia, Rosario Tringale, Salvatore De Vivo, Rita Compagna, Valerio S. Tolva, Ilenia D’Alessio, Ruggiero Curci, Simona Giovannetti, Giuseppe D’Arrigo, Giusi Basile, Dalmazio Frigerio, Gian Franco Veraldi, Luca Mezzetto, Arnaldo Ippoliti, Fabio M. Oddi, Alberto M. Settembrini, Martelli, Eugenio, Zamboni, Matilde, Sotgiu, Giovanni, Saderi, Laura, Federici, Massimo, Sangiorgi, Giuseppe M., Puci, Mariangela V., Martelli, Allegra R., Messina, Teresa, Frigatti, Paolo, Borrelli, Maria Pia, Ruotolo, Carlo, Ficarelli, Ilaria, Rubino, Paolo, Pezzo, Francesco, Carbonari, Luciano, Angelini, Andrea, Galeazzi, Edoardo, Di Pinto, Luca Calia Di, Fiore, Franco M., Palmieri, Armando, Ventoruzzo, Giorgio, Mazzitelli, Giulia, Ragni, Franco, Bozzani, Antonio, Forliti, Enzo, Castagno, Claudio, Volpe, Pietro, Massara, Mafalda, Moniaci, Diego, Pagliasso, Elisa, Peretti, Tania, Ferrari, Mauro, Troisi, Nicola, Modugno, Piero, Maiorano, Maurizio, Bracale, Umberto M., Panagrosso, Marco, Monaco, Mario, Giordano, Giovanni, Natalicchio, Giuseppe, Biello, Antonella, Celoria, Giovanni M., Amico, Alessio, Di Bartolo, Mauro, Martelli, Massimiliano, Munaó, Roberta, Razzano, Davide, Colacchio, Giovanni, Bussetti, Francesco, Lanza, Gaetano, Cardini, Antonio, Di Benedetto, Bartolomeo, De Laurentis, Mario, Taurino, Maurizio, Sirignano, Pasqualino, Cappiello, Pierluigi, Esposito, Andrea, Trimarchi, Santi, Romagnoli, Silvia, Padricelli, Andrea, Giudice, Giorgio, Crinisio, Adolfo, Di Nardo, Giovanni, Battaglia, Giuseppe, Tringale, Rosario, De Vivo, Salvatore, Compagna, Rita, Tolva, Valerio S., D’Alessio, Ilenia, Curci, Ruggiero, Giovannetti, Simona, D’Arrigo, Giuseppe, Basile, Giusi, Frigerio, Dalmazio, Veraldi, Gian Franco, Mezzetto, Luca, Ippoliti, Arnaldo, Oddi, Fabio M., and Settembrini, Alberto M.
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chronic limb-threatening ischemia ,age ,limb salvage ,outcome ,sex ,Medicine (miscellaneous) ,Settore MED/09 - Abstract
Background: Identifying sex-related differences/variables associated with 30 day/1 year mortality in patients with chronic limb-threatening ischemia (CLTI). Methods: Multicenter/retrospective/observational study. A database was sent to all the Italian vascular surgeries to collect all the patients operated on for CLTI in 2019. Acute lower-limb ischemia and neuropathic-diabetic foot are not included. Follow-up: One year. Data on demographics/comorbidities, treatments/outcomes, and 30 day/1 year mortality were investigated. Results: Information on 2399 cases (69.8% men) from 36/143 (25.2%) centers. Median (IQR) age: 73 (66–80) and 79 (71–85) years for men/women, respectively (p < 0.0001). Women were more likely to be over 75 (63.2% vs. 40.1%, p = 0.0001). More men smokers (73.7% vs. 42.2%, p < 0.0001), are on hemodialysis (10.1% vs. 6.7%, p = 0.006), affected by diabetes (61.9% vs. 52.8%, p < 0.0001), dyslipidemia (69.3% vs. 61.3%, p < 0.0001), hypertension (91.8% vs. 88.5%, p = 0.011), coronaropathy (43.9% vs. 29.4%, p < 0.0001), bronchopneumopathy (37.1% vs. 25.6%, p < 0.0001), underwent more open/hybrid surgeries (37.9% vs. 28.8%, p < 0.0001), and minor amputations (22% vs. 13.7%, p < 0.0001). More women underwent endovascular revascularizations (61.6% vs. 55.2%, p = 0.004), major amputations (9.6% vs. 6.9%, p = 0.024), and obtained limb-salvage if with limited gangrene (50.8% vs. 44.9%, p = 0.017). Age > 75 (HR = 3.63, p = 0.003) is associated with 30 day mortality. Age > 75 (HR = 2.14, p < 0.0001), nephropathy (HR = 1.54, p < 0.0001), coronaropathy (HR = 1.26, p = 0.036), and infection/necrosis of the foot (dry, HR = 1.42, p = 0.040; wet, HR = 2.04, p < 0.0001) are associated with 1 year mortality. No sex-linked difference in mortality statistics. Conclusion: Women exhibit fewer comorbidities but are struck by CLTI when over 75, a factor associated with short- and mid-term mortality, explaining why mortality does not statistically differ between the sexes.
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- 2023
16. Antibiotic-induced gut microbiota depletion exacerbates host hypercholesterolemia
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Ben A. Kappel, Lorenzo De Angelis, Andreas Puetz, Marta Ballanti, Rossella Menghini, Nikolaus Marx, and Massimo Federici
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Pharmacology ,vancomycin (PubChem CID: 14969) ,Hypercholesterolemia ,ursodeoxycholate (PubChem CID: 31401) ,Settore MED/09 ,Gut microbiota ,neomycin (PubChem CID: 8378) ,beta-sitosterol (PubChem CID: 222284) ,campesterol (PubChem CID: 173183) ,Antibiotics ,Cholesterol metabolism ,metronidazole (PubChem CID: 4173) ,ampicillin (PubChem CID: 6249) ,beta-muricholate (PubChem CID: 20848962) ,7-ketodeoxycholate (PubChem CID: 88292) ,cholesterol (PubChem CID: 5997) - Abstract
Hypercholesterolemia is a major driver of atherosclerosis, thus contributing to high morbidity and mortality worldwide. Gut microbiota have been identified as modulator of blood lipids including cholesterol levels. Few studies have already linked certain bacteria and microbial mechanisms to host cholesterol. However, in particular mouse models revealed conflicting results depending on genetics and experimental protocol. To gain further insights into the relationship between intestinal bacteria and host cholesterol metabolism, we first performed fecal 16S rRNA targeted metagenomic sequencing in a human cohort (n = 24) naïve for cholesterol lowering drugs. Here, we show alterations in the gut microbiota composition of hypercholesterolemic patients with depletion of Bifidobacteria, expansion of Clostridia and increased Firmicutes/Bacteroidetes ratio. To test whether pharmacological intervention in gut microbiota impacts host serum levels of cholesterol, we treated hypercholesterolemic Apolipoprotein E knockout with oral largely non-absorbable antibiotics. Antibiotics increased serum cholesterol, but only when mice were fed normal chow diet and cholesterol was measured in the random fed state. These elevations in cholesterol already occurred few days after treatment initiation and were reversible after stopping antibiotics with re-acquisition of intestinal bacteria. Gene expression analyses pointed to increased intestinal cholesterol uptake mediated by antibiotics in the fed state. Non-targeted serum metabolomics suggested that diminished plant sterol levels and reduced bile acid cycling were involved microbial mechanisms. In conclusion, our work further enlightens the link between gut microbiota and host cholesterol metabolism. Pharmacological disruption of the gut flora by antibiotics was able to exacerbate serum cholesterol and may impact cardiovascular disease.
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- 2023
17. Admission eGFR predicts in-hospital mortality independently of admission glycemia and C-peptide in patients with type 2 diabetes mellitus and COVID-19
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Marco Infante, Massimo Pieri, Santina Lupisella, Ali Mohamad, Sergio Bernardini, David Della-Morte, Andrea Fabbri, Alberto De Stefano, Marco Iannetta, Lorenzo Ansaldo, Angela Crea, Massimo Andreoni, and Maria Morello
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Settore MED/09 ,General Medicine - Abstract
Type 2 diabetes mellitus (T2DM) and impaired kidney function are associated with a higher risk of poor outcomes of coronavirus disease 2019 (COVID-19). We conducted a retrospective study in hospitalized T2DM patients with COVID-19 to assess the association between in-hospital mortality and admission values of different hematological/biochemical parameters, including estimated glomerular filtration rate (eGFR), plasma glucose and C-peptide (the latter serving as a marker of beta-cell function). The study included T2DM patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were consecutively admitted to our Institution between 1 October 2020 and 1 April 2021. Patients (n = 74) were categorized into survivors (n = 55) and non-survivors (n = 19). Non-survivors exhibited significantly higher median white blood cell (WBC) count, D-dimer, neutrophil-to-lymphocyte ratio, high-sensitivity C-reactive protein (hsCRP), and procalcitonin levels, as well as significantly lower median serum 25-hydroxyvitamin D [25(OH)D] levels compared to survivors. Non-survivors exhibited significantly higher median admission plasma glucose (APG) values compared to survivors (210 vs. 166 mg/dL; p = .026). There was no statistically significant difference in median values of (random) plasma C-peptide between non-survivors and survivors (3.55 vs. 3.24 ng/mL; p = .906). A significantly higher percentage of patients with an eGFR < 60 mL/min/1.73 m2 was observed in the non-survivor group as compared to the survivor group (57.9% vs. 23.6%; p = .006). A multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, sex, body mass index, major comorbidities) showed a significant inverse association between admission eGFR values and risk of in-hospital mortality (OR, 0.956; 95% CI, 0.931-0.983; p = .001). We also found a significant positive association between admission WBC count and risk of in-hospital mortality (OR, 1.210; 95% CI, 1.043–1.404; p = .011). Admission eGFR and WBC count predict in-hospital COVID-19 mortality among T2DM patients, independently of traditional risk factors, APG and random plasma C-peptide. Hospitalized patients with COVID-19 and comorbid T2DM associated with impaired kidney function at admission should be considered at high risk for adverse outcomes and death.
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- 2023
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18. Beyond Weight Loss: Added Benefits Could Guide the Choice of Anti-Obesity Medications
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Valeria Guglielmi, Silvia Bettini, Paolo Sbraccia, Luca Busetto, Massimo Pellegrini, Volkan Yumuk, Anna Maria Colao, Marwan El Ghoch, and Giovanna Muscogiuri
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Anti-obesity drugs ,Comorbidities ,Liraglutide ,Naltrexone/bupropion ,Semaglutide ,Tirzepatide ,Settore MED/09 ,General Medicine - Abstract
Purpose of Review To highlight the added benefits of approved and upcoming, centrally-acting, anti-obesity drugs, focusing not only on the most common metabolic and cardiovascular effects but also on their less explored clinical benefits and drawbacks, in order to provide clinicians with a tool for more comprehensive, pharmacological management of obesity. Recent Findings Obesity is increasingly prevalent worldwide and has become a challenge for healthcare systems and societies. Reduced life expectancy and cardiometabolic complications are some of the consequences of this complex disease. Recent insights into the pathophysiology of obesity have led to the development of several promising pharmacologic targets, so that even more effective drugs are on the horizon. The perspective of having a wider range of treatments increases the chance to personalize therapy. This primarily has the potential to take advantage of the long-term use of anti-obesity medication for safe, effective and sustainable weight loss, and to concomitantly address obesity complications/comorbidities when already established. Summary The evolving scenario of the availability of anti-obesity drugs and the increasing knowledge of their added effects on obesity complications will allow clinicians to move into a new era of precision medicine.
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- 2023
19. The role of MTHFR polymorphisms in the risk of lipedema
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Gualtieri, P, Al-Wadart, M, de Santis, Gl, Alwadart, N, della Morte, D, Clarke, C, Best, T, Salimei, C, Bigioni, G, Cianci, R, Lorenzo, Ade, and Renzo, Ldi
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Settore MED/09 - Published
- 2023
20. Dynapenia, muscle quality, and hepatic steatosis in patients with obesity and sarcopenic obesity
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Francesco Frigerio, Maria De Marinis, Francesca Camardella, Vito Cantisani, Alessandro Pinto, Marco Bernardi, Carla Lubrano, Lucio Gnessi, Massimo Federici, Lorenzo Maria Donini, and Eleonora Poggiogalle
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handgrip strength ,NAFLD ,hepatic steatosis ,insulin resistance ,Medicine (miscellaneous) ,fatty liver disease ,Settore MED/09 ,dynapenia ,muscle quality ,sarcopenic obesity ,General Biochemistry, Genetics and Molecular Biology - Abstract
Accumulating evidence supports a connection between sarcopenic obesity (SO) and NAFLD. The extent to which fatty liver contributes to impaired muscle contractility is not yet well established. The aim of our study was to investigate the effect of NAFLD on dynapenia in patients with SO. In this study, 71 non-diabetic subjects (age 55 (7.8) years, BMI 35.2 kg/m2 (32.6–38.8)) were classified as having SO and non-sarcopenic obesity (NSO). SO patients displayed worse serum lipid profiles, higher body fat, and lower skeletal muscle mass (both total and appendicular) than NSO patients, despite the absence of any significant differences in body weight, glycometabolic parameters, and hepatic steatosis prevalence. A positive correlation between disposition index and muscle quality index (MQI) (r = 0.393, p = 0.013) emerged after controlling for menopause and body fat percentage. Based on multiple linear regression analysis, MQI was significantly positively associated with the disposition index (β: 0.059, SE: 0.002, p = 0.006) after adjustment for menopause, body fat percentage, and the presence of hepatic steatosis according to the hepatorenal index (HRI). Similar findings emerged when including liver enzyme levels in place of hepatic steatosis. Muscle quality was positively associated with β-cell function corrected for insulin resistance among patients with obesity and sarcopenic obesity, irrespective of the presence of fatty liver disease.
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- 2023
21. Liver lipopolysaccharide binding protein prevents hepatic inflammation in physiological and pathological non-obesogenic conditions
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Edward Milbank, Ramon Díaz-Trelles, Nathalia Dragano, Jèssica Latorre, Rajesh Mukthavaram, Jordi Mayneris-Perxachs, Francisco Ortega, Massimo Federici, Remy Burcelin, Priya P. Karmali, Kiyoshi Tachikawa, Pad Chivukula, Miguel López, José Manuel Fernández-Real, and José María Moreno-Navarrete
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Pharmacology ,Liver inflammation ,Lipid nanoparticles ,NASH ,LPS-binding protein ,Settore MED/09 ,SiRNAs - Abstract
Lipopolysaccharide binding protein (LBP) knockout mice models are protected against the deleterious effects of major acute inflammation but its possible physiological role has been less well studied. We aimed to evaluate the impact of liver LBP downregulation (using nanoparticles containing siRNA- Lbp) on liver steatosis, inflammation and fibrosis during a standard chow diet (STD), and in pathological non-obesogenic conditions, under a methionine and choline deficient diet (MCD, 5 weeks). Under STD, liver Lbp gene knockdown led to a significant increase in gene expression markers of liver inflammation (Itgax, Tlr4, Ccr2, Ccl2 and Tnf), liver injury (Krt18 and Crp), fibrosis (Col4a1, Col1a2 and Tgfb1), endoplasmic reticulum (ER) stress (Atf6, Hspa5 and Eif2ak3) and protein carbonyl levels. As expected, the MCD increased hepatocyte vacuolation, liver inflammation and fibrosis markers, also increasing liver Lbp mRNA. In this model, liver Lbp gene knockdown resulted in a pronounced worsening of the markers of liver inflammation (also including CD68 and MPO activity), fibrosis, ER stress and protein carbonyl levels, all indicative of non-alcoholic steatohepatitis (NASH) progression. At cellular level, Lbp gene knockdown also increased expression of the proinflammatory mediators (Il6, Ccl2), and markers of fibrosis (Col1a1, Tgfb1) and protein carbonyl levels. In agreement with these findings, liver LBP mRNA in humans positively correlated with markers of liver damage (circulating hsCRP, ALT activity, liver CRP and KRT18 gene expression), and with a network of genes involved in liver inflammation, innate and adaptive immune system, endoplasmic reticulum stress and neutrophil degranulation (all with q-value0.05). In conclusion, current findings suggest that a significant downregulation in liver LBP levels promotes liver oxidative stress and inflammation, aggravating NASH progression, in physiological and pathological non-obesogenic conditions.
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- 2023
22. Metabolic characteristics in patients with COVID-19 and no-COVID-19 interstitial pneumonia with mild-to-moderate symptoms and similar radiological severity
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Gianluca Vanni, Alfonso Bellia, Francesca Davato, Marcello Chiocchi, Luca Coppeta, Daniele Mereu, Marta Ballanti, Giovanni Di Cola, Romualdo Gervasi, Marina Cardellini, Davide Lauro, Alessandro Nucera, Massimo Federici, Claudio Oreste Buonomo, Stefano Rizza, and Gianluigi Ferrazza
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,Medicine (miscellaneous) ,Settore MED/09 ,Severity of Illness Index ,Article ,chemistry.chemical_compound ,Settore MED/13 ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Severity of illness ,Diabetes Mellitus ,Humans ,Medicine ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,Glycated Hemoglobin ,education.field_of_study ,Nutrition and Dietetics ,diabetes ,SARS-CoV-2 ,business.industry ,Mortality rate ,Case-control study ,COVID-19 ,Retrospective cohort study ,Pneumonia ,Middle Aged ,medicine.disease ,chemistry ,Case-Control Studies ,Female ,Glycated hemoglobin ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background and aims It is known that the highest COVID-19 mortality rates are among patients who develop severe COVID-19 pneumonia. However, despite the high sensitivity of chest CT scans for diagnosing COVID-19 in a screening population, the appearance of a chest CT is thought to have low diagnostic specificity. The aim of this retrospective case–control study is based on evaluation of clinical and radiological characteristics in patients with COVID-19 (n = 41) and no-COVID-19 interstitial pneumonia (n = 48) with mild-to-moderate symptoms. Methods and results To this purpose we compared radiological, clinical, biochemical, inflammatory, and metabolic characteristics, as well as clinical outcomes, between the two groups. Notably, we found similar radiological severity of pneumonia, which we quantified using a disease score based on a high-resolution computed tomography scan (COVID-19 = 18.6 ± 14.5 vs n-COVID-19 = 23.2 ± 15.2, p = 0.289), and comparable biochemical and inflammatory characteristics. However, among patients without diabetes, we observed that COVID-19 patients had significantly higher levels of HbA1c than n-COVID-19 patients (COVID-19 = 41.5 ± 2.6 vs n-COVID-19 = 38.4 ± 5.1, p = 0.012). After adjusting for age, sex, and BMI, we found that HbA1c levels were significantly associated with the risk of COVID-19 pneumonia (odds ratio = 1.234 [95%CI = 1.051–1.449], p = 0.010). Conclusions In this retrospective case–control study, we found similar radiological and clinical characteristics in patients with COVID-19 and n-COVID-19 pneumonia with mild-to-moderate symptoms. However, among patients without diabetes HbA1c levels were higher in COVID-19 patients than in no-COVID-19 individuals. Future studies should assess whether reducing transient hyperglycemia in individuals without overt diabetes may lower the risk of SARS-CoV-2 infection.
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- 2021
23. Insulin Resistance and Acne: The Role of Metformin as Alternative Therapy in Men
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Aikaterini Andreadi, Saverio Muscoli, Rojin Tajmir, Marco Meloni, Alessandro Minasi, Carolina Muscoli, Sara Ilari, Vincenzo Mollace, David Della Morte, Alfonso Bellia, Elena Campione, Nicola Di Daniele, and Davide Lauro
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drug efficacy evaluation ,Settore MED/13 ,insulin resistance ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Settore MED/09 ,metformin ,acne ,Settore MED/49 - Abstract
The association between acne and insulin resistance has not been investigated as thoroughly in males as it has been in women, despite the fact that in adult men, acne prevalence has grown. On the face, sebaceous glands produce and secrete sebum, which lubricates the skin and protects it from friction. Metformin, an insulin-sensitizing medication, may modify the association between acne vulgaris and insulin resistance (IR). Individuals with IR, metabolic syndrome or with impaired glucose tolerance are sometimes treated ‘off label’ with Metformin. In these conditions, IR may be a leading factor in the pathogenesis of acne, and in men, Metformin treatment may reduce the Global Acne Grading System (GAGS) score by enhancing insulin sensitivity. However, additional clinical studies are required to corroborate these assumptions.
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- 2022
24. Bariatric surgery-induced weight loss and associated genome-wide DNA-methylation alterations in obese individuals
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Fazlur Rahman Talukdar, David Israel Escobar Marcillo, Ruhina Shirin Laskar, Alexei Novoloaca, Cyrille Cuenin, Paolo Sbraccia, Lorenza Nisticò, Valeria Guglielmi, Tarik Gheit, Massimo Tommasino, Eugenia Dogliotti, Paola Fortini, and Zdenko Herceg
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Bariatric surgery ,Weight loss ,DNA methylation ,Epigenetic clock ,Genetics ,Epigenetics ,Settore MED/09 ,Obesity ,Molecular Biology ,Genetics (clinical) ,Developmental Biology - Abstract
BackgroundObesity is a multifactorial and chronic condition of growing universal concern. It has recently been reported that bariatric surgery is a more successful treatment for severe obesity than other noninvasive interventions, resulting in rapid significant weight loss and associated chronic disease remission. The identification of distinct epigenetic patterns in patients who are obese or have metabolic imbalances has suggested a potential role for epigenetic alterations in causal or mediating pathways in the development of obesity-related pathologies. Specific changes in the epigenome (DNA methylome), associated with metabolic disorders, can be detected in the blood. We investigated whether such epigenetic changes are reversible after weight loss using genome-wide DNA methylome analysis of blood samples from individuals with severe obesity (mean BMI ~ 45) undergoing bariatric surgery.ResultsOur analysis revealed 41 significant (Bonferronip p p SMAD6andPFKFB3genes were the top hypermethylated and hypomethylated regions, respectively. Pathway enrichment analysis of the DMR-associated genes showed that functional pathways related to immune function and type 1 diabetes were significant. Weight loss due to bariatric surgery also significantly decelerated epigenetic age 12 months after the intervention (mean = − 4.29;p = 0.02).ConclusionsWe identified weight loss-associated DNA-methylation alterations targeting immune and inflammatory gene pathways in blood samples from bariatric-surgery patients. The top hits were replicated in samples from an independent cohort of BMI-discordant monozygotic twins following a hypocaloric diet. Energy restriction and bariatric surgery thus share CpGs that may represent early indicators of response to the metabolic effects of weight loss. The analysis of bariatric surgery-associated DMRs suggests that epigenetic regulation of genes involved in endothelial and adipose tissue function is key in the pathophysiology of obesity.
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- 2022
25. Investigating the potential non-authorized use of two different formulations of liraglutide in Europe: A real-world drug utilization study
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Paolo Sbraccia, Jens Aberle, Anne Helene Olsen, Naveen Rathor, and Atheline Major‐Pedersen
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GLP-1 analogue ,liraglutide ,Endocrinology ,Endocrinology, Diabetes and Metabolism ,obesity therapy ,Internal Medicine ,Antiobesity drug ,incretin therapy ,Settore MED/09 - Abstract
Liraglutide is marketed in Europe as Victoza® (1.2 mg/1.8 mg), indicated for glycaemic control in type 2 diabetes, and Saxenda® (3.0 mg), indicated for weight management in adults with obesity. We performed a post-authorization safety study (PASS) to assess the in-market use of Saxenda® and Victoza® according to approved indications and posology.This retrospective, non-interventional study was conducted at 41 sites between December 2016 and May 2019. Via medical record review, physicians at each site identified patients who had been prescribed Saxenda® (Italy) or Victoza® (Italy/Germany) within the 24 months following launch in each country. Pseudonymized data were abstracted on patient and site characteristics, indication for the prescription, posology and duration of usage. Adherence to the approved indications and posology, and to the Saxenda® stopping rule, were assessed. No formal statistical analysis was performed.A total of 440 patients were pre-screened and 225 (51.1%) were enrolled (Saxenda®: N=75, all in Italy; Victoza®: N=75 in Italy; N=75 in Germany). In all, 96% (72/75) of Saxenda® prescriptions, and 98.7% (148/150) of Victoza®, were in accordance with the approved indications. Among the 40 patients treated with Saxenda® for ≥16 weeks, only two (5.0%) were confirmed as non-adherent to the stopping rule. Adherence could not be assessed in 23 (57.5%) patients owing to missing body weight measurements.This retrospective, real-world PASS provides reassurance that Saxenda® and Victoza® are primarily used according to the approved European label, thus their real-world utilization does not raise safety concerns.gov identifier: NCT02967757. This article is protected by copyright. All rights reserved.
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- 2022
26. DPP9 as a Potential Novel Mediator in Gastrointestinal Virus Infection
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Ángela del Castillo-Izquierdo, José María Moreno-Navarrete, Jessica Latorre, María Arnoriaga-Rodríguez, Marta Ballanti, Giovanni Monteleone, Omero Alessandro Paoluzi, Geltrude Mingrone, Josep Puig, Rafael Ramos, Josep Garre-Olmo, Mariona Jové, Reinald Pamplona, Manuel Portero-Otín, Joaquim Sol, Philippe Lefebvre, Bart Staels, Massimo Federici, José Manuel Fernández-Real, and Jordi Mayneris-Perxachs
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viral infection ,gastrointestinal tract ,transcriptomics ,metabolomics ,SARS-CoV-2 ,Physiology ,Clinical Biochemistry ,Settore MED/09 ,Cell Biology ,Gastrointestinal system ,Biochemistry ,Gastrointestinal tract ,Viral infection ,Tracte gastrointestinal ,Metabolomics ,Intestines -- Infections ,Transcriptomics ,Molecular Biology ,Intestins -- Infeccions - Abstract
Dipeptidyl peptidase 9 (DPP9) is a member of the dipeptidyl peptidase IV family. Inhibition of DPP9 has recently been shown to activate the nucleotide-binding domain leucine-rich repeat 1 (NLRP1) inflammasome. NLRP1 is known to bind nucleic acids with high affinity and directly interact with double stranded RNA, which plays a key role in viral replication. DPP9 has also recently emerged as a key gene related to lung-inflammation in critical SARS-CoV-2 infection. Importantly, DPP9 activity is strongly dependent on the oxidative status. Here, we explored the potential role of DPP9 in the gastrointestinal tract. We performed transcriptomics analyses of colon (microarray, n = 37) and jejunal (RNA sequencing, n = 31) biopsies from two independent cohorts as well as plasma metabolomics analyses in two independent cohorts (n = 37 and n = 795). The expression of DPP9 in the jejunum, colon, and blood was significantly associated with circulating biomarkers of oxidative stress (uric acid, bilirubin). It was also associated positively with the expression of transcription factors (NRF-2) and genes (SOD, CAT, GPX) encoding for antioxidant enzymes, but negatively with that of genes (XDH, NOX) and transcription factors (NF-KB) involved in ROS-generating enzymes. Gene co-expression patterns associated with DPP9 identified several genes participating in antiviral pathways in both tissues. Notably, DPP9 expression in the colon and plasma was strongly positively associated with several circulating nucleotide catabolites (hypoxanthine, uric acid, 3-ureidopropionic acid) with important roles in the generation of ROS and viral infection, as well as other metabolites related to oxidative stress (Resolvin D1, glutamate-containing dipeptides). Gene-drug enrichment analyses identified artenimol, puromycin, anisomycin, 3-phenyllactic acid, and linezolid as the most promising drugs targeting these DPP9-associated genes. We have identified a novel potential pathogenic mechanism of viral infection in the digestive tract and promising existing drugs that can be repositioned against viral infection This work was partially supported by Fundació Marató de TV3 research grant number 201612-31 and by Instituto de Salud Carlos III (ISCIII, Madrid, Spain) through the project PI20/01090 (co-funded by the European Union under the European Regional Development Fund (FEDER). “A way to make Europe”) to J.M.-P. Á.d.C.-I. is funded by Girona Biomedical Research Institute (Girona, Spain) through the Horizon 2020 Framework Programme of the European Union under the Marie Skłodowska-Curie Innovative Training Network grant agreement No 859890. M.A.-R. is funded by Instituto de Salud Carlos III (Madrid, Spain) through a predoctoral Río Hortega contract CM19/00190 (co-funded by European Regional Development Fund “Investing in your future”). J.M.-P. is funded by Instituto de Salud Carlos III (Madrid, Spain) through the Miguel Servet Program CP18/00009 (co-funded by European Regional Development Fund “Investing in your future”)
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- 2022
27. Staphylococcal scalded skin syndrome in adults with obesity and type 2 diabetes: A case series
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Carolina Vitale, Valentina Spinozzi, Luca Colangeli, Paolo Sbraccia, and Valeria Guglielmi
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obesity ,staphylococcal scalded skin syndrome ,case report ,Settore MED/09 ,type 2 diabetes ,General Medicine ,immune system dysregulation ,immunodepression - Published
- 2022
28. Obesity is a chronic progressive relapsing disease of particular interest for internal medicine
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Paolo Sbraccia and Dror Dicker
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Emergency Medicine ,Internal Medicine ,Settore MED/09 - Published
- 2022
29. Correction: Advice of General Practitioner, of Surgeon, of Endocrinologist, and Self-Determination: the Italian Road to Bariatric Surgery
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Antonio E. Pontiroli, Geltrude Mingrone, Annamaria Colao, Luigi Barrea, Giulia Cannavale, Ferdinando Pinna, Valerio Ceriani, Stefano Maria De Carli, Giovanni Cesana, Stefano Olmi, Gloria Scolari, Simonetta Sarro, Giuliano Sarro, Claudia Procopio, Alessandro Giovanelli, Lelio Morricone, Giancarlo Micheletto, Alexis Malavazos, Valerio Panizzo, Laura Plebani, Marco Antonio Zappa, Igor Tubazio, Diego Foschi, Silvia Capogrossi, Caterina Conte, Alessandro Saibene, Carlo Socci, Martina Gozza, Sara Testa, Giuseppe Marinari, Stefano Maccatrozzo, Marina Croci, Enrico Mozzi, Ornella Verrastro, Esmeralda Capristo, Marco Raffaelli, Vincenzo Bruni, Andrea Soare, Giuseppe Spagnolo, Silvia Manfrini, Ida Gallo, Giovanni Casella, Lidia Castagneto Gissey, Mikiko Watanabe, Simona Frontoni, Massimiliano Di Paola, Benedetta Russo, Patrizia Bigarelli, James R. Casella Mariolo, Franca Filippi, Frida Leonetti, Alberto Di Biasio, Gianfranco Silecchia, Valeria Guglielmi, Claudio Arcudi, Paolo Gentileschi, Paolo Sbraccia, Antonio Vitiello, Mario Musella, Rita Schiano, Cristiano Giardiello, Michele Giuseppe Iovino, Maurizio De Palma, Salvatore Tolone, Ludovico Docimo, Michele Renzulli, Vincenzo Pilone, Maria Police, Luigi Angrisani, and Elena Tagliabue
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Nutrition and Dietetics ,Settore MED/13 ,Endocrinology, Diabetes and Metabolism ,Surgery ,Settore MED/09 ,Settore MED/18 - Published
- 2022
30. A Call to Action by the Italian Mesotherapy Society on Scientific Research
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Domenico Russo, Teresa Paolucci, Silvia Natoli, Carmen Pediliggieri, Cristiana Di Campli, Gianpaolo Ronconi, Maria Chiara Collina, Raffaele Di Marzo, Renato Vellucci, Massimo Mammucari, Stefano Brauneis, Bartolomeo Violo, Umberto Massafra, Enrica Maggiori, Barbara Bifarini, Paola Emilia Ferrara, Fabio Gori, Rocco Domenico Mediati, and Alberto Migliore
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medicine.medical_specialty ,Technology Assessment, Biomedical ,Injections, Intradermal ,Pain medicine ,medicine.medical_treatment ,Pharmaceutical Science ,Settore MED/09 ,RM1-950 ,Review ,law.invention ,Randomized controlled trial ,law ,Drug Discovery ,medicine ,Humans ,Intensive care medicine ,intradermal therapy ,Randomized Controlled Trials as Topic ,Pharmacology ,Analgesics ,Rehabilitation ,business.industry ,Health technology ,Call to action ,Mesotherapy ,Clinical research ,mesotherapy ,Italy ,Settore MED/41 ,research plan ,Therapeutics. Pharmacology ,Venous disease ,business ,Societies - Abstract
Mesotherapy (local intradermal therapy, LIT) is a technique used to slowly spread drugs in tissues underlying the site of injection to prolong the pharmacological effect with respect to intramuscular injection. Recommendations for proper medical use of this technique have been made for pain medicine and rehabilitation, chronic venous disease, sport medicine, musculoskeletal disorders, several dermatological conditions, skin ageing, and immune-prophylaxis. Although mesotherapy is considered a valid technique, unresolved questions remain, which should be answered to standardize methodology and dosing regimen as well as to define the right indications in clinical practice. New randomized controlled trials are needed to test single products (dose, frequency of administration, efficacy and safety). Even infiltration of substances for dermo-cosmetic purposes must be guided by safety and efficacy tests before being proposed by mesotherapy. In this article, we put forth a preclinical and clinical research plan and a health technology assessment as a call to action by doctors, researchers and scientific societies to aid national health authorities in considering mesotherapy for prevention, treatment and rehabilitation paths., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/bIuRhGQsUjs
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- 2021
31. Evaluation of dental demands and needs of people experiencing homelessness in the city of Rome, Italy
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G, Palaia, F, Semprini, F, De-Giorgio, M, Ralli, M, Bossù, A, Arcangeli, L, Ercoli, and A, Polimeni
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Adult ,Aged, 80 and over ,Male ,Adolescent ,Rome ,Oral Health ,Settore MED/09 ,Middle Aged ,Health Services Accessibility ,Young Adult ,Ill-Housed Persons ,Humans ,Female ,Child ,Aged ,Retrospective Studies - Abstract
Poor oral health and oral diseases are common among people experiencing homelessness. The aim of this study was to evaluate the dental demands and needs of a population of homeless persons in the city of Rome, Italy.The clinical records of 165 homeless patients admitted between October 2020 and October 2021 to the dental service of the Primary Care Services of the Eleemosynaria Apostolica, Vatican City, were retrospectively reviewed. The service employed dentists to evaluate dental needs and oral conditions in patients experiencing homelessness. The main dental and oral pathological conditions were noted.One hundred and sixty-five records of homeless patients were included in the study. The sample consisted in 138 males (76.97%) and 27 females (23.03%) with a mean age of 46.9 years (range 7-85 years). Acute tooth pain was reported by 132 (80%) patients, 42 (25.45%) had edentulism or missing teeth and 18 (10.91%) patients had oral lesions. Both dental and oral pathologies were intercepted and managed in secondary healthcare facilities.Given the specific peculiarities of this vulnerable population, it is important to implement strategies that facilitate the access of persons experiencing homelessness to dental evaluation with a preventive and curative perspective.
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- 2022
32. How the First Year of the COVID-19 Pandemic Impacted Patients' Hospital Admission and Care in the Vascular Surgery Divisions of the Southern Regions of the Italian Peninsula
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Eugenio Martelli, Giovanni Sotgiu, Laura Saderi, Massimo Federici, Giuseppe Sangiorgi, Matilde Zamboni, Allegra R. Martelli, Giancarlo Accarino, Giuseppe Bianco, Francesco Bonanno, Umberto M. Bracale, Enrico Cappello, Giovanni Cioffi, Giovanni Colacchio, Adolfo Crinisio, Salvatore De Vivo, Carlo Patrizio Dionisi, Loris Flora, Giovanni Impedovo, Francesco Intrieri, Luca Iorio, Gabriele Maritati, Piero Modugno, Mario Monaco, Giuseppe Natalicchio, Vincenzo Palazzo, Fernando Petrosino, Francesco Pompeo, Raffaele Pulli, Davide Razzano, Maurizio R. Ruggieri, Carlo Ruotolo, Paolo Sangiuolo, Gennaro Vigliotti, Pietro Volpe, Antonella Biello, Pietro Boggia, Michelangelo Boschetti, Enrico M. Centritto, Flavia Condò, Lucia Cucciolillo, Amodio S. D’Amodio, Mario De Laurentis, Claudio Desantis, Daniela Di Lella, Giovanni Di Nardo, Angelo Disabato, Ilaria Ficarelli, Angelo Gasparre, Antonio N. Giordano, Alessandro Luongo, Mafalda Massara, Vincenzo Molinari, Andrea Padricelli, Marco Panagrosso, Anna Petrone, Serena Pisanello, Roberto Prunella, Michele Tedesco, Alberto M. Settembrini, Martelli, Eugenio, Sotgiu, Giovanni, Saderi, Laura, Federici, Massimo, Sangiorgi, Giuseppe, Zamboni, Matilde, Martelli, Allegra R., Accarino, Giancarlo, Bianco, Giuseppe, Bonanno, Francesco, Bracale, Umberto M., Cappello, Enrico, Cioffi, Giovanni, Colacchio, Giovanni, Crinisio, Adolfo, De Vivo, Salvatore, Dionisi, Carlo Patrizio, Flora, Lori, Impedovo, Giovanni, Intrieri, Francesco, Iorio, Luca, Maritati, Gabriele, Modugno, Piero, Monaco, Mario, Natalicchio, Giuseppe, Palazzo, Vincenzo, Petrosino, Fernando, Pompeo, Francesco, Pulli, Raffaele, Razzano, Davide, Ruggieri, Maurizio R., Ruotolo, Carlo, Sangiuolo, Paolo, Vigliotti, Gennaro, Volpe, Pietro, Biello, Antonella, Boggia, Pietro, Boschetti, Michelangelo, Centritto, Enrico M., Condò, Flavia, Cucciolillo, Lucia, D’Amodio, Amodio S., De Laurentis, Mario, Desantis, Claudio, Di Lella, Daniela, Di Nardo, Giovanni, Disabato, Angelo, Ficarelli, Ilaria, Gasparre, Angelo, Giordano, Antonio N., Luongo, Alessandro, Massara, Mafalda, Molinari, Vincenzo, Padricelli, Andrea, Panagrosso, Marco, Petrone, Anna, Pisanello, Serena, Prunella, Roberto, Tedesco, Michele, and Settembrini, Alberto M.
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carotid stenosi ,chronic limb-threatening ischemia ,abdominal aortic aneurysm ,amputation ,Medicine (miscellaneous) ,COVID-19 ,carotid stenosis ,deep venous thrombosis ,Settore MED/09 - Abstract
Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia.
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- 2022
33. A multi-marker integrative analysis reveals benefits and risks of bariatric surgery
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Simonetta Palleschi, Valeria Guglielmi, Lorenza Nisticò, Carla Ferreri, Claudio Tabolacci, Francesco Facchiano, Egidio Iorio, Alessandro Giuliani, Sonia Brescianini, Emanuela Medda, Corrado Fagnani, Barbara Rossi, Anna Minoprio, Mattea Chirico, Maria Elena Pisanu, Federica Di Nolfo, Paola Fortini, Valeria Simonelli, Sara Baccarini, Serena Laterza, Tiziana Morretti, Ambra Dell’Orso, Federico Manganello, Paolo Gentileschi, Paolo Sbraccia, and Eugenia Dogliotti
- Subjects
Multidisciplinary ,Weight Loss ,Humans ,Bariatric Surgery ,Settore MED/09 ,Obesity ,Morbid ,Weight Gain ,Risk Assessment ,Obesity, Morbid - Abstract
Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success.
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- 2022
34. Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department
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Emanuela Sozio, Francesco Curcio, Silvia Angeletti, Carlo Tascini, Jacopo M. Legramante, Stephen Poole, Kordo Saeed, Juan González del Castillo, and Iria Miguens
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0301 basic medicine ,emergency department ,Coronavirus disease 2019 (COVID-19) ,MR-proADM ,Settore MED/09 ,Context (language use) ,Infections ,Severity of Illness Index ,Pathology and Forensic Medicine ,Adrenomedullin ,Hospital ,03 medical and health sciences ,0302 clinical medicine ,Diagnostic Tests ,Severity of illness ,Genetics ,Humans ,Medicine ,Routine ,In patient ,Hospital Mortality ,Protein Precursors ,Molecular Biology ,admission ,ICU ,triage tool ,Emergency Service ,Diagnostic Tests, Routine ,business.industry ,COVID-19 ,Emergency department ,medicine.disease ,Anti-Bacterial Agents ,030104 developmental biology ,030220 oncology & carcinogenesis ,Expert opinion ,Critical Pathways ,Molecular Medicine ,Mid regional pro adrenomedullin ,Medical emergency ,Emergency Service, Hospital ,business ,Algorithms ,Biomarkers ,Healthcare system - Abstract
INTRODUCTION: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians' decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature.AREAS COVERED: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients' clinical pathways in an ED setting.EXPERT OPINION: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician's decision making and recognizing the 'ill looking well' and the 'well looking ill' sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally.
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- 2021
35. Mechanisms of SGLT2 (Sodium-Glucose Transporter Type 2) Inhibition-Induced Relaxation in Arteries From Human Visceral Adipose Tissue
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Nicola Di Daniele, Alessandro De Stefano, Giuseppina Vizioli, Manfredi Tesauro, Carmine Cardillo, and Francesca Schinzari
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Adipose tissue ,Settore MED/09 ,Prostacyclin ,Intra-Abdominal Fat ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Obesity ,Canagliflozin ,Enzyme Inhibitors ,Sodium-Glucose Transporter 2 Inhibitors ,biology ,Liraglutide ,Chemistry ,catalase ,Settore MED/09 - MEDICINA INTERNA ,Glucose transporter ,Vasodilation ,Nitric oxide synthase ,Arterioles ,NG-Nitroarginine Methyl Ester ,030104 developmental biology ,Endocrinology ,biology.protein ,Endothelium, Vascular ,Nitric Oxide Synthase ,Perfusion ,medicine.drug ,Myograph - Abstract
As novel drug treatments for diabetes have shown favorable cardiovascular effects, interest has mounted with regard to their possible vascular actions, particularly in relation to visceral adipose tissue perfusion and remodeling in obesity. The present study tested the vasorelaxing effect of the SGLT2 (sodium-glucose transporter type 2) inhibitor canagliflozin in arteries from visceral adipose tissue of either nonobese or obese humans and investigated the underlying mechanisms. Also, the vasorelaxing effect of canagliflozin and the GLP-1 (glucagon-like peptide 1) agonist liraglutide were compared in arteries from obese patients. To these purposes, small arteries (116–734 μm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. Canagliflozin elicited a higher concentration-dependent vasorelaxation in arterioles from obese than nonobese individuals ( P =0.02). The vasorelaxing response to canagliflozin was not modified ( P =0.93) by inhibition of nitric oxide synthase (L-NAME) or prostacyclin (indomethacin), or by H 2 O 2 scavenging (catalase); also, canagliflozin-induced relaxation was similar ( P =0.23) in endothelium-intact or -denuded arteries precontracted with high potassium concentration, thereby excluding an involvement of endothelium-derived hyperpolarizing factors. The vasorelaxing response to canagliflozin was similar to that elicited by the Na + /H + exchanger 1 inhibitor BIX ( P =0.67), but greater than that to the Na + /Ca ++ exchanger inhibitor SEA 0400 ( P =0.001), hinting a role of Na + /H + exchanger inhibition in canagliflozin-induced relaxation. In arterioles from obese patients, the vasorelaxing response to canagliflozin was greater than that to liraglutide ( P =0.004). These findings demonstrate that canagliflozin induces endothelium-independent vasorelaxation in arterioles from human visceral adipose tissue, thereby suggesting that SGLT2 inhibition might favorably impact the processes linking visceral adipose burden to vascular disease in obesity.
- Published
- 2021
36. Upregulation of serum and glucocorticoid-regulated kinase 1 exacerbates brain injury and neurological deficits after cardiac arrest
- Author
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Reggie Hui-Chao Lee, Hung Wen Lin, Garrett A. Clemons, Celeste Yin-Chieh Wu, Davide Lauro, Alexandre Couto e Silva, Jake T. Neumann, Har Lee E. Possoit, Cristiane T. Citadin, Mychal S. Grames, Chih Feng Lien, David Della-Morte, and Donatella Pastore
- Subjects
Male ,medicine.medical_specialty ,Physiology ,cerebral blood flow ,Ischemia ,Hippocampus ,Settore MED/09 ,Protein Serine-Threonine Kinases ,Benzoates ,Neuroprotection ,cerebral ischemia ,Immediate-Early Proteins ,neuroinflammation ,Rats, Sprague-Dawley ,Brain ischemia ,Settore MED/13 ,Memory ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Protein Kinase Inhibitors ,Neuroinflammation ,Asphyxia ,serum and glucocorticoid-regulated kinase ,Rapid Report ,urogenital system ,business.industry ,neuronal cell death ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,Heart Arrest ,Rats ,Up-Regulation ,Neuroprotective Agents ,Endocrinology ,Cerebral blood flow ,Brain Injuries ,Cerebrovascular Circulation ,SGK1 ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Cardiopulmonary arrest (CA) is the leading cause of death and disability in the United States. CA-induced brain injury is influenced by multifactorial processes, including reduced cerebral blood flow (hypoperfusion) and neuroinflammation, which can lead to neuronal cell death and functional deficits. We have identified serum and glucocorticoid-regulated kinase-1 (SGK1) as a new target in brain ischemia previously described in the heart, liver, and kidneys (i.e., diabetes and hypertension). Our data suggest brain SGK1 mRNA and protein expression (i.e., hippocampus), presented with hypoperfusion (low cerebral blood flow) and neuroinflammation, leading to further studies of the potential role of SGK1 in CA-induced brain injury. We used a 6-min asphyxia cardiac arrest (ACA) rat model to induce global cerebral ischemia. Modulation of SGK1 was implemented via GSK650394, a SGK1-specific inhibitor (1.2 μg/kg icv). Accordingly, treatment with GSK650394 attenuated cortical hypoperfusion and neuroinflammation (via Iba1 expression) after ACA, whereas neuronal survival was enhanced in the CA1 region of the hippocampus. Learning/memory deficits were observed 3 days after ACA but ameliorated with GSK650394. In conclusion, SGK1 is a major contributor to ACA-induced brain injury and neurological deficits, while inhibition of SGK1 with GSK650394 provided neuroprotection against CA-induced hypoperfusion, neuroinflammation, neuronal cell death, and learning/memory deficits. Our studies could lead to a novel, therapeutic target for alleviating brain injury following cerebral ischemia. NEW & NOTEWORTHY Upregulation of SGK1 exacerbates brain injury during cerebral ischemia. Inhibition of SGK1 affords neuroprotection against cardiac arrest-induced hypoperfusion, neuroinflammation, neuronal cell death, and neurological deficits.
- Published
- 2020
37. Autoantibodies against the glial glutamate transporter GLT1/EAAT2 in Type 1 diabetes mellitus-Clues to novel immunological and non-immunological therapies
- Author
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Carla Perego, Eliana S. Di Cairano, Alessandra Galli, Stefania Moretti, Elena Bazzigaluppi, Victoria Frolich Centonze, Amalia Gastaldelli, Emma Assi, Paolo Fiorina, Massimo Federici, Ottavia Porzio, Federico Bertuzzi, Alberto M. Davalli, and Franco Folli
- Subjects
Pharmacology ,Amino Acid Transport System X-AG ,Settore BIO/12 ,Glutamic Acid ,Type 1 diabetes mellitus ,Settore MED/09 ,Complement pathway ,Glutamate toxicity ,Diabetes Mellitus, Type 1 ,Autoantibody ,Humans ,Neuroglia ,EAAT2/GLT1 ,Autoantibodies - Abstract
Islet cell surface autoantibodies were previously found in subjects with type 1 diabetes mellitus (T1DM), but their target antigens and pathogenic mechanisms remain elusive. The glutamate transporter solute carrier family 1, member 2 (GLT1/EAAT2) is expressed on the membrane of pancreatic β-cells and physiologically controls extracellular glutamate concentrations thus preventing glutamate-induced β-cell death. We hypothesized that GLT1 could be an immunological target in T1DM and that autoantibodies against GLT1 could be pathogenic. Immunoprecipitation and ELISA experiments showed that sera from T1DM subjects recognized GLT1 expressed in brain, pancreatic islets, and GLT1-transfected COS7-cell extracts. We validated these findings in two cohorts of T1DM patients by quantitative immunofluorescence assays. Analysis of the combined data sets indicated the presence of autoantibodies against GLT1 in 32 of the 87 (37%) T1DM subjects and in none of healthy controls (n = 64) (p 0.0001). Exposure of pancreatic βTC3 cells and human islets to purified IgGs from anti-GLT1 positive sera supplemented with complement resulted in plasma membrane ruffling, cell lysis and death. The cytotoxic effect was prevented when sera were depleted from IgGs. Furthermore, in the absence of complement, 6 out of 16 (37%) anti-GLT1 positive sera markedly reduced GLT1 transport activity in βTC3 cells by inducing GLT1 internalization, also resulting in β-cell death. In conclusion, we provide evidence that GLT1 is a novel T1DM autoantigen and that anti-GLT1 autoantibodies cause β-cell death through complement-dependent and independent mechanisms. GLT1 seems an attractive novel therapeutic target for the prevention of β-cell death in individuals with diabetes and prediabetes.
- Published
- 2022
38. Updating obesity management strategies: an audit of Italian specialists
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Luca Busetto, Maria Grazia Carbonelli, Antonio Caretto, Annamaria Colao, Claudio Cricelli, Maurizio De Luca, Francesco Giorgino, Lucio Gnessi, Gerardo Medea, Giovanni Pappagallo, Ferruccio Santini, Paolo Sbraccia, and Marco Antonio Zappa
- Subjects
Bariatric surgery ,Adult ,Consensus ,Adipose tissue ,Settore MED/09 ,Obesity Management ,Psychiatry and Mental health ,Clinical Psychology ,Italy ,Risk Factors ,Cardio-metabolic risk ,Humans ,Adult obesity ,Obesity comorbidities ,Obesity management ,Obesity - Abstract
Obesity negatively affects physical and psychological health and increases health care costs. Although there is increasing interest in early diagnosis and timely intervention, there are several principles of care included in the current guidelines for clinical management of obesity that can potentially be updated and improved to address the “clinical inertia” and, consequently, to optimize the management of adult obesity. Using an online Delphi-based process, an Italian board of experts involved in the management of obesity discussed the usefulness of a pro-active approach to the care of patients with obesity, providing a consensus document with practical indications to identify risk factors for morbidity and death and raise awareness throughout the treatment continuum, including the early stages of the disease. In clinical practice, it seems inappropriate to delay an intervention that could avoid progression to a more severe level of obesity and/or prevent the onset of obesity-related comorbidities.Level of evidence Level V, report of expert committee.
- Published
- 2022
39. Cluster analysis of weather and pollution features and its role in predicting acute cardiac or cerebrovascular events
- Author
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Alberto TESTA, Giuseppe BIONDI-ZOCCAI, Sabrina ANTICOLI, Francesca R. PEZZELLA, Marilena MANGIARDI, Alessandro DI GIOSA, Giada MARCHEGIANI, Giacomo FRATI, Sebastiano SCIARRETTA, Armando PERROTTA, Mariangela PERUZZI, Elena CAVARRETTA, Achille GASPARDONE, Enrica MARIANO, Massimo FEDERICI, Rocco A. MONTONE, Angela DEI GIUDICI, Benedetta VERSACI, and Francesco VERSACI
- Subjects
myocardial infarction ,weather ,air pollution ,Settore MED/09 ,General Medicine ,climate ,stroke - Abstract
Despite mounting evidence, the impact of the interplay between weather and pollution features on the risk of acute cardiac and cerebrovascular events has not been entirely appraised. The aim of this study was to perform a comprehensive cluster analysis of weather and pollution features in a large metropolitan area, and their association with acute cardiac and cerebrovascular events.Anonymized data on acute myocardial infarction (AMI) and acute cerebrovascular events were obtained from 3 tertiary care centers from a single large metropolitan area. Weather and pollution data were obtained averaging measurements from several city measurement stations managed by the competent regional agency for enviromental protection, and from the Metereological Center of Italian Military Aviation. Unsupervised machine learning was performed with hierarchical clustering to identify specific days with distinct weather and pollution features. Clusters were then compared for rates of acute cardiac and cerebrovascular events with Poisson models.As expected, significant pairwise correlations were found between weather and pollution features. Building upon these correlations, hierarchical clustering, from a total of 1169 days, generated 4 separate clusters: mostly winter days with low temperatures and high ozone concentrations (cluster 1, N.=60, 5.1%), days with moderately high temperatures and low pollutants concentrations (cluster 2, N.=419, 35.8%), mostly summer and spring days with high temperatures and high ozone concentrations (cluster 3, N.=673, 57.6%), and mostly winter days with low temperatures and low ozone concentrations (cluster 4, N.=17, 1.5%). Overall cluster-wise comparisons showed significant differences in adverse cardiac and cerebrovascular events (P0.001), as well as in cerebrovascular events (P0.001) and strokes (P=0.001). Between-cluster comparisons showed that cluster 1 was associated with an increased risk of any event, cerebrovascular events, and strokes in comparison to cluster 2, cluster 3 and cluster 4 (all P0.05), as well as AMI in comparison to cluster 3 (P=0.047). In addition, cluster 2 was associated with a higher risk of strokes in comparison to cluster 4 (P=0.030). Analysis adjusting for season confirmed the increased risk of any event, cerebrovascular events and strokes for cluster 1 and cluster 2.Unsupervised machine learning can be leveraged to identify specific days with a unique clustering of adverse weather and pollution features which are associated with an increased risk of acute cardiovascular events, especially cerebrovascular events. These findings may improve collective and individual risk prediction and prevention.
- Published
- 2022
40. ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids
- Author
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Rossella Menghini, Lesley Hoyles, Marina Cardellini, Viviana Casagrande, Arianna Marino, Paolo Gentileschi, Francesca Davato, Maria Mavilio, Ivan Arisi, Alessandro Mauriello, Manuela Montanaro, Manuel Scimeca, Richard H. Barton, Francesca Rappa, Francesco Cappello, Manlio Vinciguerra, José Maria Moreno-Navarrete, Wifredo Ricart, Ottavia Porzio, José-Manuel Fernández-Real, Rémy Burcelin, Marc-Emmanuel Dumas, Massimo Federici, Menghini R., Hoyles L., Cardellini M., Casagrande V., Marino A., Gentileschi P., Davato F., Mavilio M., Arisi I., Mauriello A., Montanaro M., Scimeca M., Barton R.H., Rappa F., Cappello F., Vinciguerra M., Moreno-Navarrete J.M., Ricart W., Porzio O., Fernandez-Real J.-M., Burcelin R., Dumas M.-E., Federici M., Nottingham Trent University, Università degli Studi di Roma Tor Vergata [Roma], University of Rome TorVergata, European Brain Research Institute [Rome, Italy] (EBRI), Cardiff Business School, Cardiff University, Euro-Mediterranean Institute of Science and Technology (IEMEST), Università degli studi di Palermo - University of Palermo, Section of Diabetes, Endocrinology and Nutrition, University Hospital of Girona-Biomedical Research Institute 'Dr Josep Trueta'-CIBERobn Fisiopatología de la Obesidad y Nutrición, Hospital Dr Josep Trueta de Girona, Universitat de Girona (UdG), Instituto de Salud Carlos III [Madrid] (ISC), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London, ANR-16-IDEX-0004,ULNE,ULNE(2016), and ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018)
- Subjects
Mice, Knockout ,BCAAm Metabolomic, NAFLD, Transcriptomics ,Ubiquitin-Protein Ligases ,[SDV]Life Sciences [q-bio] ,Liver Neoplasms ,Down-Regulation ,BCAA ,Metabolomics ,NAFLD ,Transcriptomics ,Settore MED/09 ,Cell Biology ,Mice ,Non-alcoholic Fatty Liver Disease ,otorhinolaryngologic diseases ,Animals ,Humans ,Female ,Obesity ,skin and connective tissue diseases ,Molecular Biology ,Amino Acids, Branched-Chain - Abstract
Objective: Metabolic syndrome, obesity, and steatosis are characterized by a range of dysregulations including defects in ubiquitin ligase tagging proteins for degradation. The identification of novel hepatic genes associated with fatty liver disease and metabolic dysregulation may be relevant to unravelling new mechanisms involved in liver disease progression Methods: Through integrative analysis of liver transcriptomic and metabolomic obtained from obese subjects with steatosis, we identified itchy E ubiquitin protein ligase (ITCH) as a gene downregulated in human hepatic tissue in relation to steatosis grade. Wild-type or ITCH knockout mouse models of non-alcoholic fatty liver disease (NAFLD) and obesity-related hepatocellular carcinoma were analyzed to dissect the causal role of ITCH in steatosis Results: We show that ITCH regulation of branched-chain amino acids (BCAAs) degradation enzymes is impaired in obese women with grade 3 compared with grade 0 steatosis, and that ITCH acts as a gatekeeper whose loss results in elevation of circulating BCAAs associated with hepatic steatosis. When ITCH expression was specifically restored in the liver of ITCH knockout mice, ACADSB mRNA and protein are restored, and BCAA levels are normalized both in liver and plasma Conclusions: Our data support a novel functional role for ITCH in the hepatic regulation of BCAA metabolism and suggest that targeting ITCH in a liver-specific manner might help delay the progression of metabolic hepatic diseases and insulin resistance.
- Published
- 2022
41. Risk factors for diabetic foot ulcers: an Albanian retrospective study of inpatients with type 2 diabetes
- Author
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Pastore, D, Deja-Simoni, A, De Stefano, A, Pacifici, F, Cela, E, Infante, M, Coppola, A, Di Daniele, N, Lauro, D, Della-Morte, D, and Donadel, G
- Subjects
Adult ,Male ,Inpatients ,Type 2 diabetes ,Settore MED/09 ,Lower-extremity amputations ,Middle Aged ,Settore MED/04 ,Diabetic peripheral neu-ropathy ,Settore MED/49 ,Albanian inpa-tients ,Diabetic Foot ,Settore MED/46 ,Settore MED/13 ,Diabetes Mellitus, Type 2 ,Risk Factors ,Therapeutic adherence ,Case-Control Studies ,Diabetic foot ulcers ,Humans ,T2D ,Female ,Glucose con-trol ,Aged ,Retrospective Studies - Abstract
The aim of this study was to assess the impact of glucose control, diabetes-related complications and cardiometabolic risk factors on the risk of diabetic foot ulcers (DFUs) and DFU complications in Albanian adult inpatients with T2D.We conducted a retrospective case-control study on 482 Albanian adult inpatients with T2D. DFU was defined as a full-thickness skin lesion requiring ≥14 days for healing and was classified at the time of hospital admission. Demographic and biochemical parameters of the study participants, the presence of comorbidities and diabetes-related complications at the time of hospital admission were evaluated through a retrospective chart review.Mean age of study participants was 54.8±10.7 years. Participants (284 males and 198 females) were divided into two groups: DFU (cases; n=104) and non-DFU (controls; n=378). Multivariate analysis (performed by a logistic regression model) revealed that the most relevant independent variables associated with DFU were BMI [OR=0.62; p=0.007], HDL-cholesterol [OR=0.00; p0.0001], triglycerides [OR=7.48; p=0.0004], cigarette smoking [OR=26.46; p=0.005], duration of diabetes [OR=1.53; p0.0001], fasting plasma glucose (FPG) [OR=1.06; p0.0001], systolic blood pressure (SBP) [OR=1.13; p=0.0004] and insulin therapy alone [OR=0.11; p=0.02]. ROC curve analysis showed that FPG (AUC=0.83), glycated hemoglobin (HbA1c) (AUC=0.75), triglycerides (AUC=0.78) and HDL-cholesterol (AUC=0.82) were the most reliable biomarkers able to detect DFU. In the DFU group, the most relevant independent variables associated with previous minor lower-extremity amputations (LEAs) were represented by HbA1c [OR=1.47; p=0.03], age55 years [OR=0.12; p=0.05] and female sex [OR=4.18; p=0.03]; whereas the most relevant independent variables associated with diabetic peripheral neuropathy (DPN) were HbA1c [OR=1.70; p=0.006], SBP [OR=1.08; p=0.05], BMI [OR=1.20; p=0.03] and lack of cigarette smoking [OR=0.07; p=0.01]. Correlation analysis (performed through the nonparametric Spearman's rank correlation test or through the parametric Pearson test, as appropriate) revealed a significant positive relationship between HbA1c and FPG (r=0.58; p0.0001), ulcer surface area (r=0.50; p0.0001), ulcer grade (r=0.23; p=0.02), minor LEAs (r=0.20; p=0.04), DPN (r=0.41; p0.0001), and metformin therapy alone (r=0.72; p0.0001). There was a significant inverse correlation between HbA1c and insulin therapy alone (r=-0.31; p=0.01) and combined metformin and insulin therapy (r=-0.60; p0.0001). Both DFU and non-DFU groups exhibited suboptimal mean LDL-cholesterol levels (100 mg/dl) and mean HbA1c values7.5%. Moreover, in DFU group HbA1c values were markedly elevated (≥10%) particularly in patients with a grade 3 ulcer and an ulcer surface area ≥4 cm2, as well as in patients with history of minor LEAs and in patients affected by DPN.The present study suggested that longer duration of diabetes, cigarette smoking, lower HDL-cholesterol levels, poor glucose control, and elevated triglyceride and SBP values may all represent major risk factors for the development of DFU in Albanian patients with T2D. Thus, community interventions and health policies aimed to improve the management of diabetes and related cardiometabolic risk factors should be urgently implemented in Albania, in order to prevent DFUs and other diabetes complications in patients with T2D.
- Published
- 2022
42. Sex-differences in insulin sensitivity and insulin secretion in subjects with impaired fasting glucose and impaired glucose tolerance
- Author
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Elena Succurro, Maria Adelaide Marini, Alessia Riccio, Teresa Vanessa Fiorentino, Maria Perticone, Angela Sciacqua, Francesco Andreozzi, and Giorgio Sesti
- Subjects
insulin secretion ,Endocrinology ,impaired glucose tolerance ,impaired fasting glucose ,Endocrinology, Diabetes and Metabolism ,insulin sensitivity ,prediabetes ,sex-differences ,Internal Medicine ,Settore MED/09 ,General Medicine - Abstract
To assess sex-related differences in whole-body insulin sensitivity and insulin secretion in a group of Caucasian subjects with varying degrees of glucose tolerance.Sex-related differences in insulin sensitivity using the hyperinsulinemic-euglycemic clamp technique and insulin secretion using validated indexes obtained during an oral glucose tolerance test were examined among 570 non-diabetic offspring individuals having only one parent with type 2 diabetes. Participants were classified as having with NGT, isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG/IGT.Isolated IFG, isolated IGT, and combined IFG/IGT women exhibited greater relative differences in BMI, waist circumference, and insulin-stimulated glucose disposal than their male counterparts. Formal tests for glucose tolerance status × sex interaction were statistically significant for BMI (P = 0.05) waist circumference (P = 0.04), and insulin-stimulated glucose disposal (P = 0.01) suggesting a sex-specific association. By contrast, tests for glucose tolerance status × sex interaction regarding both insulinogenic and disposition indexes were not significant.This study suggests that deterioration of glucose homeostasis in women is associated with a greater fat accumulation and worsening in insulin sensitivity as compared with men.
- Published
- 2022
43. Sex-specific differences in prevalence of nonalcoholic fatty liver disease in subjects with prediabetes and type 2 diabetes
- Author
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Elena Succurro, Maria Adelaide Marini, Teresa Vanessa Fiorentino, Maria Perticone, Angela Sciacqua, Francesco Andreozzi, and Giorgio Sesti
- Subjects
nonalcoholic fatty liver disease ,Endocrinology, Diabetes and Metabolism ,adult ,prevalence ,non-alcoholic fatty liver disease ,Settore MED/09 ,General Medicine ,prediabetes ,Endocrinology ,prediabetic state ,female ,Diabetes Mellitus, Type 2 ,type 2 ,male ,c-reactive protein ,diabetes mellitus ,Internal Medicine ,risk factors ,odds ratio ,type 2 diabetes ,glucose ,humans ,sex-differences - Abstract
To characterize the prevalence of NAFLD among subjects with NGT, prediabetes and type 2 diabetes (T2DM) by sex in adults with one or more cardio-metabolic risk factors, and to assess whether cardio-metabolic factors explained sex-related differences in NAFLD prevalence.The study sample encompasses 742 individuals with NGT, 553 with prediabetes, and 431 with T2DM.Women with prediabetes and T2DM exhibited greater relative differences in waist circumference, HOMA-IR, hsCRP, and lipid profile than prediabetic and diabetic men when compared with their NGT counterparts. Formal tests for glucose tolerance status × sex interaction were statistically significant for waist circumference (P = 0.008), HOMA-IR (P = 0.03), total cholesterol (P = 0.003), LDL (P = 0.001), HDL (P = 0.006), triglycerides (P 0.0001), and hsCRP (P 0.05). In a logistic regression analysis, prediabetic and diabetic women exhibited a higher OR for NAFLD than their male counterparts with test for glucose tolerance status × sex interaction being statistically significant.Prediabetic and diabetic women have higher OR of having NAFLD than men. Deterioration of glucose homeostasis in women is associated with a greater worsening in metabolic risk factors than men, which may explain the stronger impact of prediabetes and T2DM on NAFLD in women.
- Published
- 2022
44. One-hour post-load glucose is associated with severity of hepatic fibrosis risk
- Author
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Ram, Jagannathan, Teresa Vanessa, Fiorentino, Maria Adelaide, Marini, Giorgio, Sesti, and Michael, Bergman
- Subjects
Endocrinology, Diabetes and Metabolism ,liver cirrhosis ,1-h post load glucose ,cross-sectional studies ,Settore MED/09 ,General Medicine ,oral glucose tolerance test ,cardiovascular diseases ,Endocrinology ,Diabetes Mellitus, Type 2 ,glucose intolerance ,type 2 ,FIB-4 ,hepatic fibrosis ,blood glucose ,glucose ,humans ,diabetes mellitus, type 2 ,diabetes mellitus ,Internal Medicine - Abstract
Individuals with high 1-hour post-load glucose (1-h PG 155 mg/dl; 8.6 mmol/l) during an oral glucose tolerance test are at increased risk of type 2 diabetes (T2D) and cardiovascular complications, hepatic steatosis, and mortality. However,the clinical relevance of 1-h PG for the severity of hepatic fibrosis risk remains undefined.Cross-sectional data of the CATAMERI study (n = 2335) were analyzed. Participants underwent anthropometric measurements, liver enzyme determinations, cardiometabolic profiling, and a75-gram oral glucose tolerance test, including fasting, 1-h and 2-h PG determinations and measurement of FIB-4 score to assess degree of hepatic fibrosis. Multivariable logistic regression analysis was performed to evaluate risk of advanced hepatic fibrosis with worsening glycemic status.We stratifiedthe study group into 6 categories based on glycemic status: normal glucose tolerance (NGT) 1h-PG Low, NGT 1h-PG High, iIFG 1h-PG Low, iIFG 1h-PG High, IGT, and newly detected T2D. Anthropometric and cardiometabolic profiles worsened gradually with glycemic status. Moreover, compared to NGT-1h-PG Low group, worsening glycemic status was significantly associated with the severity of fibrosis, independent of other significant clinical risk factors.1-PG is a valuable tool for stratifying subjects with NGT or IFG at heightened risk of hepatic fibrosis requiring further evaluation with elastography.
- Published
- 2022
45. Editorial: Hyperglycemia and Coronary Artery Diseases: Physio-Pathological Findings and Therapeutic Implications
- Author
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Raffaele, Marfella, Massimo, Federici, Giuseppe, Paolisso, Marfella, Raffaele, Federici, Massimo, and Paolisso, Giuseppe
- Subjects
Pharmacology ,atheroclerosis ,coronary artery diseas ,Pharmacology (medical) ,Settore MED/09 ,hyperglycemia ,type 2 diabetes ,macro-angiopathy - Published
- 2022
46. Inflammation, underweight, malignancy and a marked catabolic state as predictors for worse outcomes in COVID-19 patients with moderate-to-severe disease admitted to Internal Medicine Unit
- Author
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Valeria Guglielmi, Luca Colangeli, Valeria Scipione, Simona Ballacci, Martina Di Stefano, Lauren Hauser, Michela Colella Bisogno, Monica D’Adamo, Emanuela Medda, and Paolo Sbraccia
- Subjects
Aged, 80 and over ,Inflammation ,Multidisciplinary ,SARS-CoV-2 ,COVID-19 ,Settore MED/09 ,Comorbidity ,Middle Aged ,Hospitalization ,COVID-19 Testing ,Thinness ,Neoplasms ,Humans ,Pandemics ,Aged ,Retrospective Studies - Abstract
Introduction During COVID-19 pandemic, Internal Medicine Units (IMUs) accounted for about 70% of patients hospitalized. Although a large body of data has been published regarding the so-called first wave of the pandemic, little is known about the characteristics and predictors of worse outcomes of patients managed in IMUs during the second wave. Methods We prospectively assessed demographics, comorbidities, treatment and outcomes, including ventilation support (VS) and death, in patients admitted to our IMU for SARS-CoV-2 between October 13th, 2020 and January 21st, 2021. Clinical evolution and biochemical testing 1, 7 and 14 days after COVID-19 diagnosis were recorded. Results We studied 120 patients (M/F 56/64, age 71±14.5 years) admitted to our IMU. Most of them had at least one comorbidity (80%). Patients who died were older, more frequently underweight, affected by malignant neoplasms and on statin therapy compared to patients eventually discharged. Both worse outcome groups (VS and death) presented higher neutrophils, ferritin, IL-6 and lower total proteins levels than controls. Age was significantly associated with mortality but not with VS need. The multivariate analysis showed age and gender independent association of mortality with underweight, malignancy and antibiotics use at the admission. With regard to biochemical parameters, both unfavourable outcomes were positively associated with high WBC count, neutrophils, blood urea nitrogen and low serum total proteins. Conclusions Our study identified inflammation, underweight, malignancy and a marked catabolic state as the main predictors for worse outcomes in COVID-19 patients admitted to IMU during the so-called second wave of the pandemic.
- Published
- 2022
47. The Protective Effect of a Unique Mix of Polyphenols and Micronutrients against Neurodegeneration Induced by an In Vitro Model of Parkinson’s Disease
- Author
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Francesca Pacifici, Chiara Salimei, Donatella Pastore, Gina Malatesta, Camillo Ricordi, Giulia Donadel, Alfonso Bellia, Valentina Rovella, Marco Tafani, Enrico Garaci, Manfredi Tesauro, Davide Lauro, Nicola Di Daniele, and David Della-Morte
- Subjects
Dopaminergic Neurons ,Organic Chemistry ,Parkinson Disease ,Settore MED/09 ,General Medicine ,Settore MED/49 ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Disease Models, Animal ,Mice ,SIRT1 ,Settore MED/46 ,inflammation ,Parkinson’s disease ,Animals ,oxidative stress ,Micronutrients ,Physical and Theoretical Chemistry ,polyphenols ,Oxidopamine ,Molecular Biology ,Spectroscopy - Abstract
Parkinson’s disease (PD) is second-most common disabling neurological disorder worldwide, and unfortunately, there is not yet a definitive way to prevent it. Polyphenols have been widely shown protective efficacy against various PD symptoms. However, data on their effect on physio-pathological mechanisms underlying this disease are still lacking. In the present work, we evaluated the activity of a mixture of polyphenols and micronutrients, named A5+, in the murine neuroblastoma cell line N1E115 treated with 6-Hydroxydopamine (6-OHDA), an established neurotoxic stimulus used to induce an in vitro PD model. We demonstrate that a pretreatment of these cells with A5+ causes significant reduction of inflammation, resulting in a decrease in pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, and CXCL1), a reduction in ROS production and activation of extracellular signal-regulated kinases (ERK)1/2, and a decrease in apoptotic mechanisms with the related increase in cell viability. Intriguingly, A5+ treatment promoted cellular differentiation into dopaminergic neurons, as evident by the enhancement in the expression of tyrosine hydroxylase, a well-established dopaminergic neuronal marker. Overall, these results demonstrate the synergic and innovative efficacy of A5+ mixture against PD cellular pathological processes, although further studies are needed to clarify the mechanisms underlying its beneficial effect.
- Published
- 2022
48. Obesity management: at the forefront against disease stigma and therapeutic inertia
- Author
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Roberto Vettor, Luca Busetto, and Paolo Sbraccia
- Subjects
medicine.medical_specialty ,Social Stigma ,Judgement ,Bariatric Surgery ,Stigma (botany) ,Therapeutic inertia ,Settore MED/09 ,030209 endocrinology & metabolism ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Intervention (counseling) ,Health care ,medicine ,Humans ,Narrative ,030212 general & internal medicine ,Obesity ,Psychiatry ,Life Style ,business.industry ,Body Weight ,Evidence-based medicine ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,Stigma ,Chronic diseases ,business - Abstract
Obesity is a complex chronic relapsing disease, resulting from the interaction between multiple environmental, genetic and epigenetic causes, and supported by changes in the neuroendocrine mechanisms regulating energy balance and body weight. Adipose tissue dysfunction contributes to obesity-related complications. However, the prevalent narrative about the causes and mechanisms of obesity remains a much more simplistic one, based on the false assumption that individuals can fully control their body weight through appropriate behavioural choices. According to this narrative, obesity is simply reversible “persuading” the patient to follow healthier and more virtuous individual behaviours (moral judgement). This persistent narrative forms the deep root of the stigmatisation of people with obesity at the individual level and creates a clear discrepancy on how obesity prevention and cure are designed in comparison with the case of other non-communicable chronic diseases (clinical stigma). The promotion of systemic preventive measures against obesity is not supported at a political and social level by the persistence of a narrative of obesity as the simple consequence of individual failures and lack of willpower. The simplistic narrative of obesity as a self-imposed condition with an easy way-out (“eat less and move more”) creates a clear discrepancy on how obesity is managed by health care systems in comparison with other NCDs. The over-estimation of the efficacy of therapeutic intervention solely based on patients education and lifestyle modification is responsible of therapeutic inertia in health care professionals and in clinical guidelines, limiting or delaying the adoption of more effective therapeutic strategies, like anti-obesity medications and bariatric surgery. In conclusion, the persistence of a narrative describing obesity as a self-induced easily reversible condition has profound consequences on how obesity prevention and management are build, including the design and implementation of obesity management guidelines and a tendency to therapeutic inertia.Level of evidence: No level of evidence.
- Published
- 2022
49. Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings
- Author
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Marco Valerio Mariani, Massimo Galli, Nazzareno Galiè, Marco Schiavone, Francesca Salghetti, Firat Duru, Ardan M. Saguner, Antonio Lanfranchi, Davide Fabbricatore, Spinello Antinori, Mattia Busana, Alfonso Bellia, Chiara Cogliati, Pierluigi Viale, Alessio Gasperetti, Gianfranco Mitacchione, Mauro Biffi, Claudio Tondo, Marco Tocci, Matteo Ziacchi, Giovanni B. Forleo, Carlo Lavalle, Giacomo Casalini, Gasperetti A., Biffi M., Duru F., Schiavone M., Ziacchi M., Mitacchione G., Lavalle C., Saguner A., Lanfranchi A., Casalini G., Tocci M., Fabbricatore D., Salghetti F., Mariani M.V., Busana M., Bellia A., Cogliati C.B., Viale P., Antinori S., Galli M., Galie N., Tondo C., Forleo G.B., and University of Zurich
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Male ,QT interval ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Settore MED/09 ,610 Medicine & health ,Clinical settings ,Arrhythmias ,030204 cardiovascular system & hematology ,2705 Cardiology and Cardiovascular Medicine ,law.invention ,Electrocardiography ,03 medical and health sciences ,Settore MED/13 ,2737 Physiology (medical) ,0302 clinical medicine ,Clinical Research ,law ,Physiology (medical) ,Internal medicine ,Intensive care ,Humans ,Medicine ,AcademicSubjects/MED00200 ,cardiovascular diseases ,030212 general & internal medicine ,SARS-CoV-2 ,business.industry ,COVID-19 ,Arrhythmias, Cardiac ,Hydroxychloroquine ,Middle Aged ,Intensive care unit ,COVID-19 Drug Treatment ,3. Good health ,Regimen ,Italy ,10209 Clinic for Cardiology ,Cardiology ,Qtc interval prolongation ,Female ,Cardiology and Cardiovascular Medicine ,business ,Arrhythmia ,medicine.drug - Abstract
Aims The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings. Methods and results COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36–72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9–16) ms]. Baseline QT/QTc length and presence of fever (P = 0.001) at admission represented the most important determinants of QT/QTc prolongation. No arrhythmic-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), with all events found not to be related to QT or HCQ therapy at a centralized event evaluation. No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non-QT-related arrhythmias being more common in the intensive care setting. Conclusion HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths.
- Published
- 2020
50. Carotid intimal medial thickness in rotating night shift is related to IL1β/IL6 axis
- Author
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Rizza, S, Longo, S, Giacomo, P, Daniele, R, Maria, M, Martina, M, Coppeta, L, Eugenio, M, Magrini, A, Federici, M, and Coppetta, L
- Subjects
Carotid Artery Diseases ,Male ,Carotid atherosclerosis ,Time Factors ,Future studies ,Endocrinology, Diabetes and Metabolism ,Interleukin-1beta ,rotating-night shift workers ,Medicine (miscellaneous) ,Settore MED/09 ,030204 cardiovascular system & hematology ,Carotid Intima-Media Thickness ,0302 clinical medicine ,Risk Factors ,Subclinical infection ,common ,Nutrition and Dietetics ,Shift Work Schedule ,Middle Aged ,Cardiology ,sleep disorders ,Female ,IL6/IL-1β ,Inflammation Mediators ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,circadian rhythm ,Adult ,medicine.medical_specialty ,Carotid Artery, Common ,Cardiovascular risk factors ,030209 endocrinology & metabolism ,Inflammation ,Anthropometric parameters ,03 medical and health sciences ,Predictive Value of Tests ,Sleep Disorders, Circadian Rhythm ,Internal medicine ,medicine ,Humans ,carotid artery ,Interleukin-6 ,business.industry ,inflammation ,intimal-medial-thickness ,adult ,biomarkers ,carotid artery diseases ,carotid artery, common ,cross-sectional studies ,female ,humans ,inflammation mediators ,interleukin-1beta ,interleukin-6 ,male ,middle aged ,predictive value of tests ,risk factors ,sleep ,sleep disorders, circadian rhythm ,time factors ,carotid intima-media thickness ,shift work schedule ,Cross-Sectional Studies ,Sleep ,business ,Biomarkers ,Night Shift Work - Abstract
Sleep disturbances may promote glucose abnormalities and inflammatory burden among shift workers. Therefore, precocious subclinical atherosclerotic process might develop in healthy shift workers even without known metabolic and cardiovascular risk factors.We measured anthropometric parameters, glucose, lipids, inflammation and common carotid Intimal Medial Thickness (cIMT) in rotating-night shift workers (r-NSW, n = 88, age = 40.3 ± 7.8 y) in comparison with former-night shift workers (f-NSW, n = 35, age = 44.2 ± 6.4 y) and with day-only workers (DW, n = 64, age = 44.1 ± 8.9 y). R-NSW and f-NSW showed significantly higher cIMT and high sensitivity C-Reactive Protein (hs-CRP) respect to DW (p = 0.043 and p = 0.025, respectively). IL-1β levels were higher in r-NSW than in DW and f-NSW (p = 0.043) and significantly correlated with IL6 (r = 0.365, p 0.001). In addition, r-NSW and f-NSW had higher HbA1c levels in comparison with DW (p = 0.047). Carotid-IMT was significantly related to night shift work (p = 0.023), with age (p 0.001), with HOMA IR (p = 0.009), with insulin (p = 0.006) with HbA1c (p = 0.002), with LDL cholesterol (p 0.001), with diastolic BP (p 0.001), with WBC (p = 0.002) and with IL6 (p = 0.004). After performing a multivariate analysis night shift work remained statistically related to cIMT (B = 2.633, 95%CI = 0.489-4.776, p = 0.016).Our result described a possible link bridging night shift work, inflammation and carotid Intimal Medial Thickness. Future studies are warranted to understand if carotid atherosclerosis process should be mainly driven by the IL1β/IL6 citokine axis connected to sleep disturbances.
- Published
- 2020
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