Publications by authors named "Marco Rossato"

76 Publications

Machine learning-based analysis of alveolar and vascular injury in SARS-CoV-2 acute respiratory failure.

J Pathol 2021 Feb 24. Epub 2021 Feb 24.

Department of Cardiac, Thoracic, Vascular Sciences, and Public Health, University of Padua Medical School, Padua, Italy.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumopathy is characterized by a complex clinical picture and heterogeneous pathological lesions, both involving alveolar and vascular components. The severity and distribution of morphological lesions associated with SARS-CoV-2 and how they relate to clinical, laboratory, and radiological data have not yet been studied systematically. The main goals of the present study were to objectively identify pathological phenotypes and factors that, in addition to SARS-CoV-2, may influence their occurrence. Lungs from 26 patients who died from SARS-CoV-2 acute respiratory failure were comprehensively analysed. Robust machine learning techniques were implemented to obtain a global pathological score to distinguish phenotypes with prevalent vascular or alveolar injury. The score was then analysed to assess its possible correlation with clinical, laboratory, radiological, and tissue viral data. Furthermore, an exploratory random forest algorithm was developed to identify the most discriminative clinical characteristics at hospital admission that might predict pathological phenotypes of SARS-CoV-2. Vascular injury phenotype was observed in most cases being consistently present as pure form or in combination with alveolar injury. Phenotypes with more severe alveolar injury showed significantly more frequent tracheal intubation; longer invasive mechanical ventilation, illness duration, intensive care unit or hospital ward stay; and lower tissue viral quantity (p < 0.001). Furthermore, in this phenotype, superimposed infections, tumours, and aspiration pneumonia were also more frequent (p < 0.001). Random forest algorithm identified some clinical features at admission (body mass index, white blood cells, D-dimer, lymphocyte and platelet counts, fever, respiratory rate, and PaCO ) to stratify patients into different clinical clusters and potential pathological phenotypes (a web-app for score assessment has also been developed; https://r-ubesp.dctv.unipd.it/shiny/AVI-Score/). In SARS-CoV-2 positive patients, alveolar injury is often associated with other factors in addition to viral infection. Identifying phenotypical patterns at admission may enable a better stratification of patients, ultimately favouring the most appropriate management. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014445PMC
February 2021

Prostate specific antigen in COVID-19 patients.

Andrology 2021 Feb 13. Epub 2021 Feb 13.

Clinica Medica 3, Department of Medicine - DIMED, University-Hospital of Padova, Padova, Italy.

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http://dx.doi.org/10.1111/andr.12987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014206PMC
February 2021

Human white-fat thermogenesis: Experimental and meta-analytic findings.

Temperature (Austin) 2020 Jun 5;8(1):39-52. Epub 2020 Jun 5.

FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece.

White adipose tissue (WAT) thermogenic activity may play a role in whole-body energy balance and two of its main regulators are thought to be environmental temperature (T) and exercise. Low T may increase uncoupling protein one (UCP1; the main biomarker of thermogenic activity) in WAT to regulate body temperature. On the other hand, exercise may stimulate UCP1 in WAT, which is thought to alter body weight regulation. However, our understanding of the roles (if any) of T and exercise in WAT thermogenic activity remains incomplete. Our aim was to examine the impacts of low T and exercise on WAT thermogenic activity, which may alter energy homeostasis and body weight regulation. We conducted a series of four experimental studies, supported by two systematic reviews and meta-analyses. We found increased UCP1 mRNA (p = 0.03; but not protein level) in human WAT biopsy samples collected during the cold part of the year, a finding supported by a systematic review and meta-analysis (PROSPERO review protocol: CRD42019120116). Additional clinical trials (NCT04037371; NCT04037410) using Positron Emission Tomography/Computed Tomography (PET/CT) revealed no impact of low T on human WAT thermogenic activity (p > 0.05). Furthermore, we found no effects of exercise on UCP1 mRNA or protein levels (p > 0.05) in WAT biopsy samples from a human randomized controlled trial (Clinical trial: NCT04039685), a finding supported by systematic review and meta-analytic data (PROSPERO review protocol: CRD42019120213). Taken together, the present experimental and meta-analytic findings of UCP1 and SUV, demonstrate that cold and exercise may play insignificant roles in human WAT thermogenic activity. : WAT:White adipose tissue; T: Environmental temperature; UCP1: Uncoupling protein one; BAT: Brown adipose tissue; BMI:Body mass index; mRNA: Messenger ribonucleic acid; RCT: Randomized controlled trial; WHR: Waist-to-hip ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; PET/CT: Positron Emission Tomography and Computed Tomography; REE: Resting energy expenditure; F-FDG: F fludeoxyglucose; VOpeak:Peak oxygen consumption; 1RM: One repetition maximum; SUV: Maximum standardized uptake value; Std: Standardized mean difference.
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http://dx.doi.org/10.1080/23328940.2020.1769530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849687PMC
June 2020

Cigarette smoking and COVID-19.

Pulmonology 2021 Jan 20. Epub 2021 Jan 20.

Clinica Medica 3, Department of Medicine - DIMED, University - Hospital of Padova, Italy.

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http://dx.doi.org/10.1016/j.pulmoe.2020.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817467PMC
January 2021

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: the Multicenter Italian CORIST Study.

Authors:
Augusto Di Castelnuovo Simona Costanzo Andrea Antinori Nausicaa Berselli Lorenzo Blandi Marialaura Bonaccio Roberto Cauda Giovanni Guaraldi Lorenzo Menicanti Marco Mennuni Giustino Parruti Giuseppe Patti Francesca Santilli Carlo Signorelli Alessandra Vergori Pasquale Abete Walter Ageno Antonella Agodi Piergiuseppe Agostoni Luca Aiello Samir Al Moghazi Rosa Arboretti Marinella Astuto Filippo Aucella Greta Barbieri Alessandro Bartoloni Paolo Bonfanti Francesco Cacciatore Lucia Caiano Laura Carrozzi Antonio Cascio Arturo Ciccullo Antonella Cingolani Francesco Cipollone Claudia Colomba Crizia Colombo Francesca Crosta Gian Battista Danzi Damiano D'Ardes Katleen de Gaetano Donati Francesco Di Gennaro Giuseppe Di Tano Gianpiero D'Offizi Massimo Fantoni Francesco Maria Fusco Ivan Gentile Francesco Gianfagna Elvira Grandone Emauele Graziani Leonardo Grisafi Gabriella Guarnieri Giovanni Larizza Armando Leone Gloria Maccagni Ferruccio Madaro Stefano Maitan Sandro Mancarella Massimo Mapelli Riccardo Maragna Rossella Marcucci Giulio Maresca Silvia Marongiu Claudia Marotta Lorenzo Marra Franco Mastroianni Maria Mazzitelli Alessandro Mengozzi Francesco Menichetti Marianna Meschiari Jovana Milic Filippo Minutolo Beatrice Molena Arturo Montineri Cristina Mussini Maria Musso Daniela Niola Anna Odone Marco Olivieri Antonella Palimodde Roberta Parisi Emanuela Pasi Raffaele Pesavento Francesco Petri Biagio Pinchera Venerino Poletti Claudia Ravaglia Andrea Rognoni Marco Rossato Marianna Rossi Vincenzo Sangiovanni Carlo Sanrocco Laura Scorzolini Raffaella Sgariglia Paola Giustina Simeone Eleonora Taddei Carlo Torti Roberto Vettor Andrea Vianello Marco Vinceti Alexandra Virano Laura Vocciante Raffaele De Caterina Licia Iacoviello

Thromb Haemost 2021 Jan 7. Epub 2021 Jan 7.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy.

Introduction:  A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.

Aim:  We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.

Methods:  In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.

Results:  Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.

Conclusion:  In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.
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http://dx.doi.org/10.1055/a-1347-6070DOI Listing
January 2021

COVID-19 and smoking habits: a smoky situation!

Monaldi Arch Chest Dis 2020 Nov 23;90(4). Epub 2020 Nov 23.

Clinica Medica 3, Department of Medicine (DIMED), University-Hospital of Padua.

Dear Editor, the issues recently raised by Carratù et al. on the role of smoking/former smoking in patients hospitalized for COVID-19 all around the world as widely reported in many different published papers, are important for different reasons...
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http://dx.doi.org/10.4081/monaldi.2020.1539DOI Listing
November 2020

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.

Authors:
Augusto Di Castelnuovo Marialaura Bonaccio Simona Costanzo Alessandro Gialluisi Andrea Antinori Nausicaa Berselli Lorenzo Blandi Raffaele Bruno Roberto Cauda Giovanni Guaraldi Ilaria My Lorenzo Menicanti Giustino Parruti Giuseppe Patti Stefano Perlini Francesca Santilli Carlo Signorelli Giulio G Stefanini Alessandra Vergori Amina Abdeddaim Walter Ageno Antonella Agodi Piergiuseppe Agostoni Luca Aiello Samir Al Moghazi Filippo Aucella Greta Barbieri Alessandro Bartoloni Carolina Bologna Paolo Bonfanti Serena Brancati Francesco Cacciatore Lucia Caiano Francesco Cannata Laura Carrozzi Antonio Cascio Antonella Cingolani Francesco Cipollone Claudia Colomba Annalisa Crisetti Francesca Crosta Gian B Danzi Damiano D'Ardes Katleen de Gaetano Donati Francesco Di Gennaro Gisella Di Palma Giuseppe Di Tano Massimo Fantoni Tommaso Filippini Paola Fioretto Francesco M Fusco Ivan Gentile Leonardo Grisafi Gabriella Guarnieri Francesco Landi Giovanni Larizza Armando Leone Gloria Maccagni Sandro Maccarella Massimo Mapelli Riccardo Maragna Rossella Marcucci Giulio Maresca Claudia Marotta Lorenzo Marra Franco Mastroianni Alessandro Mengozzi Francesco Menichetti Jovana Milic Rita Murri Arturo Montineri Roberta Mussinelli Cristina Mussini Maria Musso Anna Odone Marco Olivieri Emanuela Pasi Francesco Petri Biagio Pinchera Carlo A Pivato Roberto Pizzi Venerino Poletti Francesca Raffaelli Claudia Ravaglia Giulia Righetti Andrea Rognoni Marco Rossato Marianna Rossi Anna Sabena Francesco Salinaro Vincenzo Sangiovanni Carlo Sanrocco Antonio Scarafino Laura Scorzolini Raffaella Sgariglia Paola G Simeone Enrico Spinoni Carlo Torti Enrico M Trecarichi Francesca Vezzani Giovanni Veronesi Roberto Vettor Andrea Vianello Marco Vinceti Raffaele De Caterina Licia Iacoviello

Nutr Metab Cardiovasc Dis 2020 10 31;30(11):1899-1913. Epub 2020 Jul 31.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy; Department of Medicine and Surgery, University of Insubria, Varese, Italy. Electronic address:

Background And Aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death.

Methods And Results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses.

Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.
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http://dx.doi.org/10.1016/j.numecd.2020.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833278PMC
October 2020

COVID-19 and Orchi-epididymitis.

Pediatr Infect Dis J 2020 11;39(11):e385

Clinica Medica 3, Department of Medicine - DIMED, University-Hospital of Padova, Padova, Italy.

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http://dx.doi.org/10.1097/INF.0000000000002869DOI Listing
November 2020

Infrapatellar Fat Pad Gene Expression and Protein Production in Patients with and without Osteoarthritis.

Int J Mol Sci 2020 08 21;21(17). Epub 2020 Aug 21.

Rheumatology Unit, Department of Medicine-DIMED, University-Hospital of Padova, Via Giustiniani, 2, 35128 Padova, Italy.

Osteoarthritis (OA) is one of the most common joint disorders. Evidence suggests that the infrapatellar fat pad (IFP) is directly involved in OA pathology. However, a comparison between OA versus non-OA IFP is still missing. Thus, the aim of this study was to compare IFP molecular, adipocytes and extracellular matrix characteristics of patients affected by OA, and patients undergoing anterior cruciate ligament (ACL) reconstruction. We hypothesized that not only inflammation but also changes in adipocytes and extracellular matrix (ECM) composition might be involved in OA pathogenesis. Fifty-three patients were enrolled. IFP biopsies were obtained, evaluating: (a) lymphocytic infiltration and vascularization; (b) adipocytes area and number; (c) adipo-cytokines and extracellular matrix gene expression levels; (d) IL-6 and VEGF protein production; (e) collagen fibers distribution. OA IFP was more inflamed and vascularized compared to ACL IFP. OA IFP adipocytes were larger and numerically lower (1.3-fold) than ACL IFP adipocytes. An increase of gene expression of typical white adipose tissue genes was observed in OA compared to ACL IFP. Collagen-types distribution was different in the OA IFP group compared to controls, possibly explaining the change of the biomechanical characteristics found in OA IFP. Statistical linear models revealed that the adipocyte area correlated with BMI in the OA group. In conclusion, inflammation and fibrotic changes of OA IFP could represent novel therapeutic targets to counteract OA.
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http://dx.doi.org/10.3390/ijms21176016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503946PMC
August 2020

Smoking and Angiotensin-converting Enzyme Inhibitor/Angiotensin Receptor Blocker Cessation to Limit Coronavirus Disease 2019.

Eur Cardiol 2020 Feb 14;15:e54. Epub 2020 Jul 14.

Clinica Medica 3, Department of Medicine - DIMED, University Hospital of Padova Italy.

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http://dx.doi.org/10.15420/ecr.2020.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387891PMC
February 2020

The hazard of (sub)therapeutic doses of anticoagulants in non-critically ill patients with Covid-19: The Padua province experience.

J Thromb Haemost 2020 Oct 24;18(10):2629-2635. Epub 2020 Aug 24.

Department of Medicine, University of Padua, Padua, Italy.

Background: Coronavirus Disease 2019 (COVID-19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality. The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID-19 patients. Information on the benefit/risk ratio of this approach is still lacking.

Objective: To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug.

Methods: Consecutive COVID-19 patients admitted between February and April 2020 were included in a retrospective analysis. Major bleedings (MB) and clinically relevant non-major bleeding (CRNMB) were obtained from patient medical records and were adjudicated by an independent committee.

Results: Of the 324 patients who were recruited, 240 had been treated with prophylactic doses and 84 with higher doses of anticoagulants. The rate of the composite endpoint of MB or CRNMB was 6.9 per 100-person/months in patients who had been given prophylactic doses, and 26.4 per 100-person/months in those who had been prescribed higher doses (hazard ratio, 3.89; 95% confidence interval, 1.90-7.97). The corresponding rates for overall mortality were 12.2 and 20.1 per 100-person/months, respectively.

Conclusions: The rate of relevant bleeding events was high in patients treated with (sub)therapeutic doses of anticoagulants. In the latter group, overall mortality did not differ from that of patients treated with standard prophylactic doses and was even higher. Our result does not support a strategy of giving (sub)therapeutic doses of anticoagulants in non-critically ill patients with COVID-19.
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http://dx.doi.org/10.1111/jth.15022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404507PMC
October 2020

Comment on: Outcome of bariatric surgery on hypothyroidism: experience from a tertiary care center in India.

Authors:
Marco Rossato

Surg Obes Relat Dis 2020 09 22;16(9):1302-1303. Epub 2020 May 22.

Clinica Medica 3, Department of Medicine - DIMED, University-Hospital of Padova, Padova, Italy.

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http://dx.doi.org/10.1016/j.soard.2020.04.053DOI Listing
September 2020

What are we talking about when we talk of steroid in COVID-19?

Authors:
Marco Rossato

Minerva Anestesiol 2020 11 29;86(11):1249. Epub 2020 May 29.

Department of Medicine (DIMED), Clinica Medica 3, University Hospital of Padua, Padua, Italy -

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http://dx.doi.org/10.23736/S0375-9393.20.14810-7DOI Listing
November 2020

Obesity and COVID-19: An Italian Snapshot.

Obesity (Silver Spring) 2020 09 9;28(9):1600-1605. Epub 2020 Aug 9.

Department of Medicine, University of Padova, Padova, Italy.

Objective: The clinical manifestations of coronavirus disease (COVID-19) run from asymptomatic disease to severe acute respiratory syndrome. Older age and comorbidities are associated to more severe disease. A role of obesity is suspected.

Methods: Patients hospitalized in the medical COVID-19 ward with severe acute respiratory syndrome coronavirus 2-related pneumonia were enrolled. The primary outcome of the study was to assess the relationship between the severity of COVID-19 and obesity classes according to BMI.

Results: A total of 92 patients (61.9% males; age 70.5 [13.3] years) were enrolled. Patients with overweight and obesity were younger than patients with normal weight (68.0 [12.6] and 67.0 [12.6] years vs. 76.1 [13.0] years, P < 0.01). A higher need for assisted ventilation beyond pure oxygen support (invasive mechanical ventilation or noninvasive ventilation) and a higher admission to intensive or semi-intensive care units were observed in patients with overweight and obesity (P < 0.01 and P < 0.05, respectively) even after adjusting for sex, age, and comorbidities (P < 0.05 and P < 0.001, respectively) or when patients with dementia or advanced cancer were removed from the analysis (P < 0.05).

Conclusions: Patients with overweight and obesity admitted in a medical ward for severe acute respiratory syndrome coronavirus 2-related pneumonia, despite their younger age, required more frequently assisted ventilation and access to intensive or semi-intensive care units than normal weight patients.
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http://dx.doi.org/10.1002/oby.22918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283686PMC
September 2020

Regulation of energy intake and mechanisms of metabolic adaptation or maladaptation after caloric restriction.

Rev Endocr Metab Disord 2020 Sep;21(3):399-409

Department of Medicine - DIMED, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.

Despite their critical role in susceptibility to metabolic diseases such as obesity and type 2 diabetes, mechanisms regulating energy balance are extremely complex and far from being fully understood. Both central and peripheral feedback circuits are involved and, despite it was traditionally thought that the energy balance of an organism depends on the equality between calorie intake within the system and energy expenditure, the regulation of energy content in biological systems oversteps the classical physical laws of thermodynamics. The fine-tuned mechanism for body weight and energy storage regulation is aimed to preserve survival chances in response to the variations of energy availability, as expressed by the metabolic flexibility of this system adapting subjects to both starvation and overfeeding. However, these mechanisms can lose their flexibility, with consequent maladaptation to both increased energy intake and calorie restriction leading to the development of several metabolic disturbances.
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http://dx.doi.org/10.1007/s11154-020-09565-6DOI Listing
September 2020

A rationale for targeting the P2X7 receptor in Coronavirus disease 19.

Br J Pharmacol 2020 11 26;177(21):4990-4994. Epub 2020 Jul 26.

Department of Medicine, University of Padova, Padova, Italy.

Severe pneumonia which shares several of the features of acute respiratory distress syndrome (ARDS) is the main cause of morbidity and mortality in Coronavirus disease 19 (Covid-19) for which there is no effective treatment, so far. ARDS is caused and sustained by an uncontrolled inflammatory activation characterized by a massive release of cytokines (cytokine storm), diffuse lung oedema, inflammatory cell infiltration, and disseminated coagulation. Macrophage and T lymphocyte dysfunction plays a central role in this syndrome. In several experimental in vitro and in vivo models, many of these pathophysiological changes are triggered by stimulation of the P2X7 receptor. We hypothesize that this receptor might be an ideal candidate to target in Covid-19-associated severe pneumonia. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.
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http://dx.doi.org/10.1111/bph.15138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280564PMC
November 2020

Limiting treatment plan complexity by applying a novel commercial tool.

J Appl Clin Med Phys 2020 Aug 21;21(8):27-34. Epub 2020 May 21.

Medical Physics Department, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.

Purpose: A recently introduced commercial tool is tested to assess whether it is able to reduce the complexity of a treatment plan and improve deliverability without compromising overall quality.

Methods: Ten prostate and ten oropharynx plans of previously treated patients were reoptimized using the aperture shape controller (ASC) tool recently introduced in Eclipse TPS (Varian Medical Systems, Palo Alto, CA). The performance of ASC was assessed in terms of the overall plan quality using a plan quality metric, the reduction in plan complexity through the analysis of 14 of the most common plan complexity metrics, and the change in plan deliverability through 3D dosimetric measurements. Similarly, plans optimized limiting the total number of delivered monitor units was assessed and compared. The two strategies were also combined to assess their potential combination.

Results: The plans optimized by exploiting the ASC generally show a reduced number of total Monitor Units, a more constant gantry rotation and a MLC modulation characterized by larger and less complicated shapes with leaves traveling shorter overall lengths.

Conclusions: This first experience suggests that the ASC is an effective tool to reduce the unnecessary complexity of a plan. This turns into an increased plan deliverability with no loss of plan quality.
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http://dx.doi.org/10.1002/acm2.12908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484888PMC
August 2020

Current smoking is not associated with COVID-19.

Eur Respir J 2020 06 4;55(6). Epub 2020 Jun 4.

Clinica Medica 3, Dept of Medicine - DIMED, University-Hospital of Padova, Padova, Italy.

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http://dx.doi.org/10.1183/13993003.01290-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191113PMC
June 2020

The P2X7 Receptor and NLRP3 Axis in Non-Alcoholic Fatty Liver Disease: A Brief Review.

Cells 2020 04 22;9(4). Epub 2020 Apr 22.

Clinica Medica 3, Department of Medicine - DIMED, University of Padova, 35128 Padova, Italy.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and its prevalence is reaching epidemic characteristics both in adults and in children. The increase of NAFLD prevalence parallels that of obesity, now representing the major cause of liver inflammation, increasing the risk of cirrhosis and hepatocarcinoma. Furthermore, NAFLD is a risk factor for cardiovascular diseases and type 2 diabetes, two of the major leading causes of morbidity and mortality in western countries. Thus a significant amount of studies have dealt with the evaluation of the possible molecular mechanisms leading to NAFLD and its inflammatory consequences within the liver, the non-alcoholic steatohepatitis, and cirrhosis. The inflammasome is a key player in the inflammation and fibrogenic responses in many different tissues, including the liver. The activation of the NLRP3 inflammasome requires the activation by extracellular adenosine tri-phosphate (ATP) of a specific purinergic receptor named P2X7 located in the target cells, although other pathways have been described. To this regard, extracellular ATP acts as an internal danger signal coming from damaged cells participating in the activation of the inflammatory process, a signaling pathway common to many different tissues. Here, we briefly review the involvement of the P2X7 receptor/inflammasome NLRP3 axis in the pathophysiological events leading to NAFLD and its inflammatory and fibrotic evolutions, reporting the possible therapeutical strategies targeting the P2X7 receptor/NLRP3 inflammasome.
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http://dx.doi.org/10.3390/cells9041047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226571PMC
April 2020

Relationship between Heart Disease and Liver Disease: A Two-Way Street.

Cells 2020 02 28;9(3). Epub 2020 Feb 28.

Internal Medicine 3, Department of Medicine - DIMED, University of Padova, Via Giustiniani2, 35100 Padova, Italy.

In clinical practice, combined heart and liver dysfunctions coexist in the setting of the main heart and liver diseases because of complex cardiohepatic interactions. It is becoming increasingly crucial to identify these interactions between heart and liver in order to ensure an effective management of patients with heart or liver disease to provide an improvement in overall prognosis and therapy. In this review, we aim to summarize the cross-talk between heart and liver in the setting of the main pathologic conditions affecting these organs. Accordingly, we present the clinical manifestation, biochemical profiles, and histological findings of cardiogenic ischemic hepatitis and congestive hepatopathy due to acute and chronic heart failure, respectively. In addition, we discuss the main features of cardiac dysfunction in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and those following liver transplantation.
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http://dx.doi.org/10.3390/cells9030567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140474PMC
February 2020

Testicular function and sexuality in adult patients with anorectal malformation.

J Pediatr Surg 2020 Sep 29;55(9):1839-1845. Epub 2020 Jan 29.

Pediatric Surgery, Ca' Foncello Hospital, Treviso, Italy. Electronic address:

Purpose: To collect data on sexual and fertility issues in adult male patients with history of anorectal malformations (ARM).

Materials And Methods: Thirty adult males born with ARM, cared for at the Pediatric Surgery of Treviso and Padua Hospitals, were enrolled and interviewed about sexual habits and relationships. Testicular ultrasound, evaluation of male sex hormones and semen analysis were performed to assess testicular function and compare data with 15 fertile controls. Presence of erectile dysfunction was evaluated with IIEF-5 questionnaire.

Results: Cryptorchidism and recurrent orchiepididymitis were reported in 33% and 40% of patients, respectively. Average testicular volume resulted significantly lower than fertile controls (11.1 vs 14.3 mL, p = 0.002) and 53.5% presented testicular hypotrophy (<10 mL). Erectile dysfunction was reported by a single patient and ejaculatory anomalies by 46.5%. Thirteen patients were azoospermic/cryptozoospermic; 6 of them presented a reduced peripheral sensitivity to androgens (ASI > 139). Coital debut resulted delayed at 18 years old (vs 15 years in the control group). Overall 63.5% reported their condition did not affect their sexual sphere.

Conclusions: Evaluation of testicular function is recommended in ARM patients to detect and treat possible infertility disorders, to recognize the clinical conditions which could affect the spermatogenesis since childhood, and to guarantee psychological support.

Level Of Evidence Rating: Prognosis study. Level III (case-control study).
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http://dx.doi.org/10.1016/j.jpedsurg.2019.12.028DOI Listing
September 2020

Effects of Surgical and Non-surgical Weight Loss on Migraine Headache: a Systematic Review and Meta-Analysis.

Obes Surg 2020 06;30(6):2173-2185

Department of Medicine, University of Padua, via Giustiniani 2, 35128, Padova, Italy.

Background: The aim of this study was to perform a meta-analysis on the effect of weight loss obtained by bariatric surgery or behavioral intervention on migraine frequency and indices of severity.

Materials And Methods: A search through Pubmed/Medline, ISI-web of knowledge, and Google Scholar retrieved 10 studies (n = 473). Selected outcomes were Headache Frequency, Pain Severity, Disability, and Attack Duration while BMI, BMI change, type of intervention (bariatric vs. behavioral), and type of population (adult vs. pediatric) were used for moderators and meta-regression analysis.

Results: Random effect meta-analysis shows that weight loss yields significant reductions in Headache Frequency (ES - 0.78, p < 0.0001), Pain Severity (ES - 1.04, p < 0.0001), Disability (ES -0.68, p < 0.0001), and Attack Duration (ES - 0.25, p = 0.017). Improvement in migraine was not correlated either to the degree of obesity at baseline or the degree of weight reduction. The effect on migraine was similar when weight reduction was obtained with bariatric surgery or behavioral intervention and was comparable in adult and pediatric populations.

Conclusions: Weight loss improves characteristics of migraine headache in patients who have obesity independently of the type of intervention and the amount of weight loss. The mechanisms underlying the link between obesity, weight loss, and migraine headache may include chronic inflammation, obesity comorbidities, and overlapping behavioral and psychological risk factors.
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http://dx.doi.org/10.1007/s11695-020-04429-zDOI Listing
June 2020

Infrapatellar Fat Pad Stem Cells Responsiveness to Microenvironment in Osteoarthritis: From Morphology to Function.

Front Cell Dev Biol 2019 10;7:323. Epub 2019 Dec 10.

Department of Neurosciences, Institute of Human Anatomy, University of Padova, Padua, Italy.

Recently, infrapatellar fat pad (IFP) has been considered as a source of stem cells for cartilage regeneration in osteoarthritis (OA) due to their ability for differentiation into chondrocytes. However, stressful conditions, like that related to OA, may induce a pathogenic reprograming. The aim of this study was to characterize the structural and functional properties of a new population of stem cells isolated from osteoarthritic infrapatellar fat pad (OA-IFP). Nine OA patients undergoing total knee arthroplasty (TKA) were enrolled in this study [median age = 74 years, interquartile range (IQR) = 78.25-67.7; median body mass index = 29.4 Kg/m, IQR = 31.7-27.4]. OA-IFP stem cells were isolated and characterized for morphology, stemness, metabolic profile and multi-differentiative potential by transmission electron microscopy, flow cytometric analysis, gene expression study and cytochemistry. OA-IFP stem cells displayed a spindle-like morphology, self-renewal potential and responsiveness (CD44, CD105, VEGFR2, FGFR2, IL1R, and IL6R) to microenvironmental stimuli. Characterized by high grade of stemness (, , , and ), the cells showed peculiar immunophenotypic properties (CD73/CD39/CD90/CD105/CD44/CD45). The expression of HLA-DR, CD34, Fas and FasL was indicative of a possible phenotypic reprograming induced by inflammation. Moreover, the response to mechanical stimuli together with high expression level of gene, suggested their possible protective response against mechanical overloading. Conversely, the low expression of was indicative of their inability to counteract NAD-mediated OA inflammation. Based on the ultrastructural, immunophenotypic and functional characterization, OA-IFP stem cells were hypothesized to be primed by the pathological environment and to exert incomplete protective activity from OA inflammation.
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http://dx.doi.org/10.3389/fcell.2019.00323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914674PMC
December 2019

Sudden death with massive hemoptysis from aortobronchial fistula.

Cardiovasc Pathol 2020 Jan - Feb;44:107158. Epub 2019 Oct 24.

Cardiovascular Pathology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy. Electronic address:

Aortobronchial fistula is an uncommon clinical entity, with unpredictable clinical course and significant mortality. Here, we describe a case of fistulous tract between a descending aortic graft and a branch of the left upper lobar bronchus leading to massive hemoptysis causing death for hemorrhagic shock in a 72-year-old man.
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http://dx.doi.org/10.1016/j.carpath.2019.107158DOI Listing
March 2020

Obstructive Sleep Apnea in Acromegaly and the Effect of Treatment: A Systematic Review and Meta-Analysis.

J Clin Endocrinol Metab 2020 03;105(3)

Department of Medicine, University of Padua, via Giustiniani 2, Padova, Italy.

Background: Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway collapse requiring nocturnal ventilatory assistance. Multiple studies have investigated the relationship between acromegaly and OSA, reporting discordant results.

Aim: To conduct a meta-analysis on the risk for OSA in acromegaly, and in particular to assess the role of disease activity and the effect of treatments.

Methods And Study Selection: A search through literature databases retrieved 21 articles for a total of 24 studies (n = 734). Selected outcomes were OSA prevalence and apnea-hypopnea index (AHI) in studies comparing acromegalic patients with active (ACT) vs inactive (INACT) disease and pretreatment and posttreatment measures. Factors used for moderator and meta-regression analysis included the percentage of patients with severe OSA, patient sex, age, body mass index, levels of insulin-like growth factor 1, disease duration and follow-up, and therapy.

Results: OSA prevalence was similar in patients with acromegaly who had ACT and INACT disease (ES = -0.16; 95% CI, -0.47 to 0.15; number of studies [k] = 10; P = 0.32). In addition, AHI was similar in ACT and INACT acromegaly patients (ES = -0.03; 95% CI, -0.49 to 0.43; k = 6; P = 0.89). When AHI was compared before and after treatment in patients with acromegaly (median follow-up of 6 months), a significant improvement was observed after treatment (ES = -0.36; 95% CI, -0.49 to -0.23; k = 10; P < 0.0001). In moderator analysis, the percentage of patients with severe OSA in the populations significantly influenced the difference in OSA prevalence (P = 0.038) and AHI (P = 0.04) in ACT vs INACT patients.

Conclusion: Prevalence of OSA and AHI is similar in ACT and INACT patients in cross-sectional studies. However, when AHI was measured longitudinally before and after treatment, a significant improvement was observed after treatment.
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http://dx.doi.org/10.1210/clinem/dgz116DOI Listing
March 2020

Antioxidant, Anti-Inflammatory, and Metabolic Properties of Tocopherols and Tocotrienols: Clinical Implications for Vitamin E Supplementation in Diabetic Kidney Disease.

Int J Mol Sci 2019 Oct 15;20(20). Epub 2019 Oct 15.

Department of Medicine-DIMED, Clinica Medica 3, Center for the Study and Integrated Management of Obesity, University-Hospital of Padova, 35100 Padova, Italy.

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.
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http://dx.doi.org/10.3390/ijms20205101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834186PMC
October 2019

Aging, fat mass, and prostate cancer: is it the time to reconsider testosterone?

Aging Clin Exp Res 2020 02 15;32(2):357-359. Epub 2019 Oct 15.

Clinica Medica 3, Department of Medicine - DIMED, University-Hospital of Padova, Via Giustiniani 2, 35128, Padua, Italy.

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http://dx.doi.org/10.1007/s40520-019-01372-7DOI Listing
February 2020

Psoriatic arthritis and obesity: the role of anti-IL-12/IL-23 treatment.

Clin Rheumatol 2019 Sep 28;38(9):2355-2362. Epub 2019 Jun 28.

Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Naples, Naples, Italy.

Patients with psoriatic arthritis (PsA) have an increased prevalence of obesity, but mechanisms underlying this association remain unknown and it is unclear if obesity is the cause or effect of PsA. For PsA patients, comorbid obesity may influence their clinical response to systemic treatment, and especially targeted immunomodulators such as anti-tumor necrosis factor (TNF)α. Weight gain has also been associated with anti-TNFα treatment. Consequently, modification of the therapeutic approach may be needed for patients with an inadequate response to TNFα inhibitors. In recent years, interleukin (IL)-12/IL-23 inhibitors have entered clinical practice as a new class of drug for the treatment of PsA, with some data suggesting a lower effect of body weight on their effectiveness. Recent findings demonstrate effective and sustained responses in patients with PsA to ustekinumab, an IL-12/IL-23 inhibitor. This narrative review critically discusses the link between PsA, obesity, and response to therapy. The current role of ustekinumab in this setting is also discussed.
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http://dx.doi.org/10.1007/s10067-019-04663-6DOI Listing
September 2019

Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease.

Int J Mol Sci 2019 May 6;20(9). Epub 2019 May 6.

Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.

With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.
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http://dx.doi.org/10.3390/ijms20092215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539803PMC
May 2019

Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain.

Biomed Res Int 2019 31;2019:6390182. Epub 2019 Mar 31.

Institute of Human Anatomy, Department of Neuroscience, University of Padova, Italy.

Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA.
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http://dx.doi.org/10.1155/2019/6390182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462341PMC
August 2019