Publications by authors named "P Rovere Querini"

7 Publications

  • Page 1 of 1

Role of blood pressure dysregulation on kidney and mortality outcomes in COVID-19. Kidney, blood pressure and mortality in SARS-CoV-2 infection.

J Nephrol 2021 Apr 3;34(2):305-314. Epub 2021 Mar 3.

Nephrology and Dialysis Unit, Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.

Background: In February 2020 the corona virus disease 2019 (COVID-19) infection started spreading throughout Italy, hitting the Lombardy region very hard. Despite the high diffusion, only a subset of patients developed severe COVID-19: around 25% of them developed acute kidney injury (AKI) and one-third of them died. Elderly patients and patients with high comorbidities were identified as being at higher risk of severe COVID-19.

Methods: Our prospective observational cohort study includes 392 consecutive patients hospitalized for COVID-19 in Milan (median age 67 years, 75% male). We evaluated the relationship between blood pressure at presentation, presence of AKI at Emergency Department admission and during hospitalization, and total in-hospital mortality (24%).

Results: Although 58% of our study patients reported a history of hypertension (HYP) (86% on treatment), 30% presented with low blood pressure levels. Only 5.5% were diagnosed with AKI on admission; 75% of hypertensive patients discontinued therapy during hospitalization (only 20% were on treatment at discharge). Gender and hypertension were strongly associated with AKI at admission (odds ratio 11). Blood pressure was inversely correlated with increased risk of AKI upon admission, regardless of the severity of respiratory distress. Age over 65, history of hypertension, and severity of respiratory distress were the main predictors of AKI, which developed in 34.7% of cases during hospitalization. AKI was associated with increased in-hospital mortality. Hypertension and low blood pressure at presentation were the main predictors of in-hospital mortality, together with age over 65, baseline pulmonary involvement, and severity of illness.

Conclusions: In patients hospitalized for COVID-19, hypertension and low blood pressure at presentation are important risk factors for AKI and mortality. Early reduction of antihypertensive therapy may improve outcomes in patients with SARS-CoV-2 infection.
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http://dx.doi.org/10.1007/s40620-021-00997-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926195PMC
April 2021

Viral clearance after early corticosteroid treatment in patients with moderate or severe covid-19.

Sci Rep 2020 12 4;10(1):21291. Epub 2020 Dec 4.

Unit of Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, Milan, Italy.

The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO/FiO ≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO/FiO > 200 mmHg, and a lymphocyte count at admission > 1.0 × 10/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.
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http://dx.doi.org/10.1038/s41598-020-78039-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718220PMC
December 2020

Incidence of deep venous thrombosis in COVID-19 hospitalized patients during the first peak of the Italian outbreak.

Phlebology 2020 Nov 26:268355520975592. Epub 2020 Nov 26.

Division of Vascular Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Objectives: A high rate of thrombotic events has been reported in COVID-19 population. The study aims to assess the incidence of deep vein thrombosis (DVT) in COVID-19 patients admitted to a single tertiary hospital.

Methods: From April 2nd to April 18th, 2020, hospitalized patients with SARS-CoV-2 infection were screened by lower limb duplex ultrasound (DUS). Patients were on (low molecular weight heparin) LMWH prophylaxis in medical wards, and on therapeutic anticoagulation in intensive care unit (ICU). DVT risk factors, reported by the Padua prediction score and blood tests, were retrieved from institutional electronic charts. The study primary endpoint was the incidence of DVT in the in-hospital COVID-19 population and its association with clinical and laboratory risk factors. The secondary endpoint was the association of DVT with mortality.

Results: Two hundred patients (median age 62 years, 72% male, 40 in ICU) received DUS screening. DVT was observed in 29 patients (14.5%), with proximal extension in 16 patients, and in association with symptoms in four patients. The DVT rate was similar in ICU (12.5%) and non-ICU patients (15%). Eighty-seven patients underwent a computed tomography angiography (CTA) that showed pulmonary embolism in 35 patients (40.2%) not associated with DVT in 25/35 cases (71.4%). DVT in the ten patients with pulmonary embolism were symptomatic in four and with a proximal localization in eight cases. A D-dimer level ≥5 mg/l at admission was predictive of DVT (OR 1.02; IC95% 1.03-1.16; p  = .003). At the multivariate analysis in-hospital mortality was predicted by age (OR 1.06; 95% CI 0.02-1.15; p  = .004) and by being an ICU patient (OR 1.23; 95% CI 0.30-2.25; p  = .01).

Conclusions: Despite LMWH prophylaxis or full anticoagulant therapy, the incidence of DVT, mainly asymptomatic, in hospitalized COVID-19 patients was 14.5%. Further research should focus on the appropriate antithrombotic therapy for COVID-19 patients.
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http://dx.doi.org/10.1177/0268355520975592DOI Listing
November 2020

Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway.

Cell Death Differ 2014 Apr 6;21(4):507-20. Epub 2013 Dec 6.

Unit of Clinical Pharmacology, National Research Council Institute of Neuroscience, Department of Biomedical and Clinical Sciences, University Hospital L. Sacco, Università di Milano, Milan, Italy.

Melanoma is a rapidly growing and highly metastatic cancer with high mortality rates, for which a resolutive treatment is lacking. Identification of novel therapeutic strategies and biomarkers of tumour stage is thus of particular relevance. We report here on a novel biomarker and possible candidate therapeutic target, the sphingolipid metabolising enzyme acid sphingomyelinase (A-SMase). A-SMase expression correlates inversely with tumour stage in human melanoma biopsies. Studies in a mouse model of melanoma and on cell lines derived from mouse and human melanomas demonstrated that A-SMase levels of expression actually determine the malignant phenotype of melanoma cells in terms of pigmentation, tumour progression, invasiveness and metastatic ability. The action of A-SMase is mediated by the activation of the extracellular signal-regulated kinase, the subsequent proteasomal degradation of the Microphtalmia-associated transcription factor (Mitf) and inhibition of cyclin-dependent kinase 2, Bcl-2 and c-Met, downstream targets of Mitf involved in tumour cell proliferation, survival and metastatisation.
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http://dx.doi.org/10.1038/cdd.2013.173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950316PMC
April 2014

The nitric oxide-donor molsidomine modulates the innate inflammatory response in a mouse model of muscular dystrophy.

Eur J Pharmacol 2013 Sep 23;715(1-3):296-303. Epub 2013 May 23.

Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milano, Italy.

Inflammation plays a crucial role in muscle remodeling and repair after acute and chronic damage, in particular in muscular dystrophies, a heterogeneous group of genetic diseases leading to muscular degeneration. Defect of nitric oxide (NO) generation is a key pathogenic event in muscular dystrophies, thus NO donors have been explored as new therapeutics for this disease. We have investigated the immune-modulating effect of one of such drugs, molsidomine, able to slow the progression of muscular dystrophy in the α-Sarcoglican-null mice, a model for the limb girdle muscular dystrophy 2D, sharing several hallmarks of muscle degeneration with other muscular dystrophies. α-Sarcoglican-null mice were treated with molsidomine and drug effects on the inflammatory infiltrates and on muscle repair were assessed at selected time points. We found that molsidomine treatment modulates effectively the characteristics of the inflammatory infiltrate within dystrophic muscles, enhancing its healing function. Initially molsidomine amplified macrophage recruitment, promoting a more efficient clearance of cell debris and effective tissue regeneration. At a later stage molsidomine decreased significantly the extent of the inflammatory infiltrate, whose persistence exacerbates muscle damage: most of the remaining macrophages displayed characteristics of the transitional population, associated with reduced fibrosis and increased preservation of the muscle tissue. The dual action of molsidomine, the already known NO donation and the immunomodulatory function we now identified, suggests that it has a unique potential in tissue healing during chronic muscle damage. This, alongside its already approved use in human, makes molsidomine a drug with a significant therapeutic potential in muscular dystrophies.
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http://dx.doi.org/10.1016/j.ejphar.2013.05.007DOI Listing
September 2013

Anti-beta2 glycoprotein I antibodies cause inflammation and recruit dendritic cells in platelet clearance.

Thromb Haemost 2001 Nov;86(5):1257-63

Immunopathology Unit-Cancer Immunotherapy and Gene Therapy Programme, Istituto Scientifico H S. Raffaele, Milano, Italy.

Scavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite proinflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the beta2 Glycoprotein I (beta2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se intemalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1beta, TNF-alpha, or IL-10, beta2GPI bound to activated platelets and was required for their recognition by anti-beta2GPI antibodies. DCs internalised platelets opsonised by anti-beta2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-alpha and IL-1beta by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-10. We conclude that anti-beta2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.
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November 2001

PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation.

Arthritis Rheum 2001 Dec;44(12):2841-50

Istituto Scientifico H San Raffaele and Università, Milan, Italy.

Objective: To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis.

Methods: Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples.

Results: Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions.

Conclusion: PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis.
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http://dx.doi.org/10.1002/1529-0131(200112)44:12<2841::aid-art472>3.0.co;2-6DOI Listing
December 2001