Clinica Medica

Monza, Italy

Clinica Medica

Monza, Italy
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Schmieder R.E.,Friedrich - Alexander - University, Erlangen - Nuremberg | Redon J.,University of Valencia | Grassi G.,Clinica Medica | Grassi G.,Instituto Of Ricerche A Carattere Ccientifico Irccs Multimedica | And 7 more authors.
Journal of Hypertension | Year: 2012

Experts from the European Society of Hypertension prepared this position paper in order to summarize current evidence, unmet needs and practical recommendations on the application of percutaneous transluminal ablation of renal nerves [renal denervation (RDN)] as a novel therapeutic strategy for the treatment of resistant hypertension. The sympathetic nervous activation to the kidney and the sensory afferent signals to the central nervous system represent the targets of RND. Clinical studies have documented that catheter-based RDN decreases both efferent sympathetic and afferent sensory nerve traffic leading to clinically meaningful systolic and diastolic blood pressure (BP) reductions in patients with resistant hypertension. This position statement intends to facilitate a better understanding of the effectiveness, safety, limitations and issues still to be addressed with RDN. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Corrao G.,Unit of Biostatistics and Epidemiology | Corrao G.,University of Milan Bicocca | Nicotra F.,Unit of Biostatistics and Epidemiology | Parodi A.,Unit of Biostatistics and Epidemiology | And 6 more authors.
Hypertension | Year: 2011

Guidelines recommend a combination of 2 drugs to be used as first-step treatment strategy in high-risk hypertensive individuals to achieve timely blood pressure control and avoid early events. The evidence that this is associated with cardiovascular (CV) benefits compared with initial monotherapy is limited, however. The objective of this study was to assess whether, compared with antihypertensive monotherapy, a combination of antihypertensive drugs provides a greater CV protection in daily clinical practice. A population-based, nested case-control study was carried out by including the cohort of 209 650 patients from Lombardy (Italy) aged 40 to 79 years who were newly treated with antihypertensive drugs between 2000 and 2001. Cases were the 10 688 patients who experienced a hospitalization for CV disease from initial prescription until 2007. Three controls were randomly selected for each case. Logistic regression was used to model the CV risk associated with starting on and/or continuing with combination therapy. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients starting on combination therapy had an 11% CV risk reduction with respect to those starting on monotherapy (95% CI: 5% to 16%). Compared with patients who maintained monotherapy also during follow-up, those who started on combination therapy and kept it along the entire period of observation had 26% reduction of CV risk (95% CI: 15% to 35%). In daily life practice, a combination of antihypertensive drugs is associated with a great reduction of CV risk. The indication for using combination of blood pressure drugs should be broadened. © 2011 American Heart Association, Inc.


Olivieri J.,Marche Polytechnic University | Manfredi L.,Marche Polytechnic University | Postacchini L.,Marche Polytechnic University | Tedesco S.,Marche Polytechnic University | And 6 more authors.
The Lancet Haematology | Year: 2015

Background: Consensus recommendations are used to improve the methodology of research about rare disorders, but their uptake is unknown. We studied the uptake of consensus recommendations in steroid-refractory chronic graft-versus-host disease (SR-cGVHD). Although in 2006 the National Institutes of Health (NIH) cGVHD consensus project produced recommendations for clinical trials, guidelines have emphasised the scarcity of valuable evidence for all tested interventions. Methods: We searched Medline (PubMed) between Jan 1, 1998, and Oct 1, 2013, for non-randomised studies of systemic treatment for SR-cGVHD. To measure adherence to NIH recommendations, we applied a 61 item checklist derived from the NIH consensus document. We did a meta-analysis to measure pooled effect size for overall response rate (ORR) and meta-regression analyses to measure the effect of deviations from NIH recommendations on pooled effect size. Findings: We included 82 studies related to nine interventions. Conformity to NIH recommendations was evenly low across the analysed timeframe (1998-2013), and did not change significantly after publication of NIH recommendations. The pooled effect size for ORR for systemic treatment of SR-cGVHD was 0·66 (95% CI 0·62-0·70). Increased adherence to NIH recommendations in a score of items defining correct response assessment was associated with a significant reduction in ORR (-4·2%, 95% CI -6·6 to -1·9; p=0·001). We recorded no significant association between ORR and sets of items related to correct diagnostic definition of SR-cGVHD (change in ORR -3·1%, 95% CI -7·7 to 1·5), specification of primary intervention (0, -3·8 to 3·6), or concomitant treatments (-1·6%, -5·4 to 2·3). The score of items defining correct response assessment increased after publication of NIH recommendations. Interpretation: Our findings show evidence of bias in the reported efficacy of treatment of SR-cGVHD. The overall effect of NIH recommendations in scientific literature is scarce; however, NIH recommendations improved assessment of response, possibly reducing the overestimation bias. Better implementation of NIH recommendations might reduce false expectations about new interventions, and thus prevent clinical studies with ineffective treatments. Funding: None. © 2015 Elsevier Ltd.


Grassi G.,Clinica Medica | Grassi G.,Instituto Auxologico Italiano | Seravalle G.,Instituto Auxologico Italiano | Quarti-Trevano F.,Clinica Medica
Experimental Physiology | Year: 2010

Data collected in experimental animals and in humans support the hypothesis that sympathetic neural mechanisms are involved in the development and progression of hypertension. Direct approaches to assess human adrenergic cardiovascular drive have shown that sympathetic activation occurs in hypertensive patients, the magnitude of which is proportional to the degree of elevation of the blood pressure. Evidence has also been obtained that sympathetic activation participates in the development of hypertension-related target organ damage, such as left ventricular diastolic dysfunction, left ventricular hypertrophy and arterial remodelling and hypertrophy. Despite the large amount of information collected on the main features of the hypertension-related neurogenic abnormality, the causes of the sympathetic activation remain undefined, although alterations in the reflex modulation of adrenergic drive and/or participation of metabolic factors are likely candidates. This paper will provide background information on the behaviour of the sympathetic nervous system in experimental hypertension, followed by a review of the main features, mechanisms and effects of the sympathetic overdrive in human hypertension. Finally, the new frontiers of research in the area of therapeutic intervention aimed at reducing the adrenergic overdrive will be highlighted. © 2010 The Physiological Society.


Gallerani M.,Internal Medicine | Reverberi R.,Immunohematological and Transfusional Service | Salmi R.,Internal Medicine | Smolensky M.H.,University of Texas at Austin | Manfredini R.,Clinica Medica
European Journal of Medical Research | Year: 2013

Background: Since available data are not univocal, the aim of this study was to explore the existence of a seasonal variation in platelet count. Methods. The study was based on the database of the Italian Association of Blood Volunteers (AVIS), section of Ferrara, Italy, 2001-2010. Hematological data (170,238 exams referring to 16,422 donors) were categorized into seasonal and monthly intervals, and conventional and chronobiological analyses were applied. Results: Platelets and plateletcrit were significantly higher in winter-autumn, with a main peak in December-February (average +3.4% and +4.6%, respectively, P <0.001 for both). Conclusions: Although seasonal variations have been reported for several acute cardiovascular diseases, it is extremely unlikely that such a slight increase in platelet count in winter alone may be considered as a risk factor. © 2013 Gallerani et al.; licensee BioMed Central Ltd.


Mancia G.,Clinica Medica | Grassi G.,University of Milan Bicocca
Handbook of Clinical Neurology | Year: 2013

The sympathetic nervous system participates in the development and progression of the essential hypertensive state, as shown by increased circulating plasma levels of the adrenergic neurotransmitter norepinephrine, elevated norepinephrine spillover rate, and augmented sympathetic nerve traffic discharge detected in the high blood pressure state. In addition, the sympathetic overdrive participates in the development of the metabolic disarray as well as target organ damage frequently detected in this condition. The above mentioned sympathetic abnormalities explain why adrenergic overdrive represents an important therapeutic target in the treatment of hypertension. © 2013 Elsevier B.V.


De Giorgi A.,Clinica Medica | Mallozzi Menegatti A.,Clinica Medica | Fabbian F.,Clinica Medica | Portaluppi F.,Hypertension Unit | Manfredini R.,Clinica Medica
European Journal of Internal Medicine | Year: 2013

Background Chronobiology is devoted to the study of biological rhythms. It is possible that a given medication may be therapeutic and safe when administered at some time, but subtherapeutic or poorly tolerated at another. Methods We focused on some classes of drugs, widely used by the internists, performing a PubMed search with the single drugs associated with the MeSH terms "Chronotherapy", "Circadian rhythm", and "Chronobiology, phenomena". Among the studies found, we considered only those provided with discrete numerosity or clearly stated methodological characteristics. Results The results of available studies were given, along with a series of short take-home messages at the end of each mini-chapter devoted to: antihypertensives, statins, anticoagulants, analgesics, drugs for acid-related disorders, and anti-asthmatic drugs. In particular, evidence of morning vs. evening administration, when applicable, was given for each medication. Conclusions Adequate evidence seems to support that at least ACE-inhibitors or angiotensin receptor blockers, simvastatin, corticosteroids (slow-release formulation) for arthritic patients, and ranitidine should preferably be administered in the evening. Morning dosing could be better for proton pump inhibitors, whereas time of administration is not crucial for asthma inhalation drugs. Studies are available for other drugs, but not so strong enough to draw definite conclusions. For now, we need prospective intervention trials specifically designed to investigate the long-term effects of a temporal approach to medical therapy. However, since switching to morning-evening administration or vice versa is simple and inexpensive, in some cases it could be considered, remembering that, in any case, adherence remains the crucial point. © 2013 European Federation of Internal Medicine.


Grassi G.,Clinica Medica
Expert Opinion on Pharmacotherapy | Year: 2012

Current guidelines on antihypertensive treatment emphasize the importance of combination drug treatment for achieving a full blood pressure control. The TALENT Study, involving more than 400 high-risk hypertensive patients, aimed to evaluate the efficacy and safety profile of nifedipine gastrointestinal therapeutic system (GITS) 20 mg/telmisartan 80 mg combination, as compared to the single monotherapies. After 8 weeks, ambulatory blood pressure values were significantly more reduced by the combination treatment than by single monotherapies. These potentiated blood-pressure-lowering effects were mirrored by a higher trough-to-peak ratio and smoothness index. They were also accompanied by: i) significantly greater blood pressure (particularly systolic) control; ii) a greater ability of combination drug treatment to achieve a controlled blood pressure at a time earlier than that found in single monotherapies; and iii) a better side-effects profile. © 2012 Informa UK, Ltd.


Grassi G.,Clinica Medica | Quarti-Trevano F.,Clinica Medica | Dell'Oro R.,Clinica Medica | Mancia G.,Clinica Medica
Current Hypertension Reports | Year: 2010

This paper critically addresses the issue of the "J-curve" paradox-the finding described in studies performed about 30 years ago indicating that treatment-induced systolic blood pressure values below 120 or 125 mm Hg and diastolic blood pressure values below 75 mm Hg are characterized by an increase, rather than a reduction, in the incidence of coronary events. This paper focuses on four major subjects: 1) the benefits of a lower blood pressure target during treatment; 2) the historical background of the "J-curve" phenomenon; 3) the evidence collected in recent clinical trials regarding the existence of a "J-curve" in treated hypertensive patients; and 4) the recent recommendations by the Task Force Committee of the European Society of Hypertension on blood pressure goals to be achieved during treatment. © 2010 Springer Science+Business Media, LLC.


Common variable immunodeficiency is the most common symptomatic primary immunodeficiency in adulthood. Pregnant women with common variable immunodeficiency have different needs from other patients with the same disease. Because of immature state of the fetal and neonatal immune system, transplacental transfer of immunoglobulin G (IgG) has a relevant role in protecting the infant. We here report on a high-risk pregnant woman with common variable immunodeficiency with adverse reactions to intravenous immunoglobulin that was successfully rescued with a new Ig human intravenous, 10% liquid preparation. The treatment was tailored to the health status and characteristics of the patient. The new product was safe and well tolerated. The mother did not report any infections during pregnancy and the baby had a healthy course with 'protective' serum IgG levels. Our case is a further demonstration that intravenous immunoglobulin tolerability in patients with immunodeficiency could be linked to a product's characteristics.

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