Publications by authors named "Alessandro Galluzzo"

25 Publications

  • Page 1 of 1

Identification of novel circulating microRNAs in advanced heart failure by next-generation sequencing.

ESC Heart Fail 2021 May 2. Epub 2021 May 2.

Department of Oncology, University of Turin, Turin, Italy.

Aims: Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF-specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients.

Methods And Results: We performed a global miRNome analysis using next-generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real-time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty-two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR-210-3p, miR-22-5p, miR-22-3p, miR-21-3p, miR-339-3p, and miR-125a-5p) significantly correlated with HF biomarkers, among which N-terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR-125a-5p, miR-10b-5p, and miR-9-5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio-HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82).

Conclusions: This discovery study has characterized, for the first time, the advanced chronic HF-specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations.
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http://dx.doi.org/10.1002/ehf2.13371DOI Listing
May 2021

The Management of Psychomotor Agitation Associated with Schizophrenia or Bipolar Disorder: A Brief Review.

Int J Environ Res Public Health 2021 04 20;18(8). Epub 2021 Apr 20.

Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", National Health Service (NHS), ASL 4 Teramo, 64100 Teramo, Italy.

The early and correct assessment of psychomotor agitation (PMA) is essential to ensure prompt intervention by healthcare professionals to improve the patient's condition, protect healthcare staff, and facilitate future management. Proper training for recognizing and managing agitation in all care settings is desirable to improve patient outcomes. The best approach is one that is ethical, non-invasive, and respectful of the patient's dignity. When deemed necessary, pharmacological interventions must be administered rapidly and avoid producing an excessive state of sedation, except in cases of severe and imminent danger to the patient or others. The purpose of this brief review is to raise awareness about best practices for the management of PMA in emergency care situations and consider the role of new pharmacological interventions in patients with agitation associated with bipolar disorder or schizophrenia.
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http://dx.doi.org/10.3390/ijerph18084368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074323PMC
April 2021

Effectiveness and safety of antithrombotic strategies in elderly patients with acute myocardial infarction.

World J Cardiol 2020 Nov;12(11):513-525

Cardiology Department, St. Andrea Hospital, Vercelli 13100, Italy.

Background: Elderly patients represent a rapidly growing part of the population more susceptible to acute coronary syndromes and their complications. However, literature evidence is lacking in this clinical setting.

Aim: To describe the clinical features, in-hospital management and outcomes of "elderly" patients with myocardial infarction treated with antiplatelet and/or anticoagulation therapy.

Methods: This study was a retrospective analysis of all consecutive patients older than 80 years admitted to the Division of Cardiology of St. Andrea Hospital of Vercelli from January 2018 to December 2018 due to ST-elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI). Clinical and laboratory data were collected for each patient, as well as the prevalence of previous or in-hospital atrial fibrillation (AF). In-hospital management, consisting of an invasive or conservative strategy, and the anti-thrombotic therapy used are described. Outcomes evaluated at 1 year follow-up included an efficacy ischemic endpoint and a safety bleeding endpoint.

Results: Of the 105 patients enrolled (mean age 83.9 ± 3.6 years, 52.3% males), 68 (64.8%) were admitted due to NSTEMI and 37 (35.2%) due to STEMI. Among the STEMI patients, 34 (91.9%) underwent coronary angiography and all of them were treated with percutaneous coronary intervention (PCI); among the NSTEMI patients, 42 (61.8%) were assigned to an invasive strategy and 16 (38.1%) of them underwent a PCI. No significant difference between the groups was found concerning the prevalence of previous or in-hospital de-novo AF. 10.5% of the whole population received triple antithrombotic therapy and 9.5% single antiplatelet therapy plus oral anticoagulation (OAC), with no significant difference between the subgroups, although a higher number of STEMI patients received dual antiplatelet therapy without OAC as compared with NSTEMI patients. A low rate of in-hospital death (5.7%) and 1-year cardiovascular death (3.3%) was registered. Seven (7.8%) patients experienced major adverse cardiovascular events, while the rate of minor and major bleeding at 1-year follow-up was 10% and 2.2%, respectively, with no difference between NSTEMI and STEMI patients.

Conclusion: In this real-world study, a tailored evaluation of an invasive strategy and antithrombotic therapy resulted in a low rate of adverse events in elderly patients hospitalized with acute myocardial infarction.
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http://dx.doi.org/10.4330/wjc.v12.i11.513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701903PMC
November 2020

Reduction in heart failure hospitalization rate during coronavirus disease 19 pandemic outbreak.

ESC Heart Fail 2020 Oct 23. Epub 2020 Oct 23.

Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161, Italy.

Aims: The recent coronavirus disease 19 (COVID-19) pandemic outbreak forced the adoption of restraint measures, which modified the hospital admission patterns for several diseases. The aim of the study is to investigate the rate of hospital admissions for heart failure (HF) during the early days of the COVID-19 outbreak in Italy, compared with a corresponding period during the previous year and an earlier period during the same year.

Methods And Results: We performed a retrospective analysis on HF admissions number at eight hospitals in Italy throughout the study period (21 February to 31 March 2020), compared with an inter-year period (21 February to 31 March 2019) and an intra-year period (1 January to 20 February 2020). The primary outcome was the overall rate of hospital admissions for HF. A total of 505 HF patients were included in this survey: 112 during the case period, 201 during intra-year period, and 192 during inter-year period. The mean admission rate during the case period was 2.80 admissions per day, significantly lower compared with intra-year period (3.94 admissions per day; incidence rate ratio, 0.71; 95% confidence interval [CI], 0.56-0.89; P = 0.0037), or with inter-year (4.92 admissions per day; incidence rate ratio, 0.57; 95% confidence interval, 0.45-0.72; P < 0.001). Patients admitted during study period were less frequently admitted in New York Heart Association (NYHA) Class II compared with inter-year period (P = 0.019). At covariance analysis NYHA class was significantly lower in patients admitted during inter-year control period, compared with patients admitted during case period (P = 0.014).

Conclusions: Admissions for HF were significantly reduced during the lockdown due to the COVID-19 pandemic in Italy.
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http://dx.doi.org/10.1002/ehf2.13043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754919PMC
October 2020

Correction to: Spot urinary sodium in acute decompensation of advanced heart failure and dilutional hyponatremia: insights from DRAIN trial.

Clin Res Cardiol 2020 Oct;109(10):1260

Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Torino, Italy.

The original version of this article unfortunately contained a mistake.
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http://dx.doi.org/10.1007/s00392-020-01644-7DOI Listing
October 2020

Urinary sodium evaluation: the missing target for diuretic treatment optimization in acute heart failure patients? Letter regarding the article 'Clinical importance of urinary sodium excretion in acute heart failure'.

Eur J Heart Fail 2020 10 1;22(10):1933. Epub 2020 Apr 1.

Division of Cardiology, Città della Salute e della Scienza University Hospital of Turin, Turin, Italy.

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http://dx.doi.org/10.1002/ejhf.1814DOI Listing
October 2020

Spot urinary sodium in acute decompensation of advanced heart failure and dilutional hyponatremia: insights from DRAIN trial.

Clin Res Cardiol 2020 Oct 6;109(10):1251-1259. Epub 2020 Mar 6.

Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Torino, Italy.

Background: Diuretic resistance portends a poor prognosis in acute heart failure, especially in advanced stages. Early identification of a poor response to diuretics may help to improve treatment and outcomes. Spot natriuresis (UNa) at 2 h from the start of intravenous furosemide has been proposed as an early indicator of diuretic response. Our paper aimed to determine the role of early natriuresis in patients hospitalized with advanced chronic heart failure (ACHF) and high risk of diuretic resistance.

Methods And Results: We performed a sub-analysis of the DRAIN trial, a randomized clinical trial on 80 patients with acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with low systolic blood pressure (≤ 110 mmHg) and dilutional hyponatremia (sodium ≤ 135 mMol/L) at admission. Patients were divided into two groups according to spot urinary sodium excretion (high: UNa  > 50 or low: ≤ 50 mEq/L) at 2 h from furosemide administration. Twenty-eight patients (35%) showed a low natriuretic response. As compared to the other patients, this group showed lower daily urinary output (2275 ± 790 vs 3849 ± 2034 mL, p < 0.001), lower body weight reduction after 48 h (1.55 ± - 1.66 vs - 3.55 ± - 2.93 kg, p < 0.001), higher incidence of worsening renal function (32% vs 10%, p 0.02) and increasing rather than reducing NT-proBNP at 72 h (p 0.02).

Conclusions: In patients with ACHF and dilutional hyponatremia, low natriuresis after furosemide is an early marker of poor diuretic response and correlates with higher NT-proBNP and higher incidence of worsening renal function at 72 h.
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http://dx.doi.org/10.1007/s00392-020-01617-wDOI Listing
October 2020

Diuretic treatment in high-risk acute decompensation of advanced chronic heart failure-bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial.

Clin Res Cardiol 2020 Apr 29;109(4):417-425. Epub 2019 Jun 29.

Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy.

Background: Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance.

Methods: In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients' care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h.

Results: 80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of < 8 cm, with no orthopnea and with trace peripheral edema or no edema) occurred more in the continuous infusion than in the bolus arm (48% vs. 25%, p = 0.04), while total urinary output after 72 h was 8612 ± 2984 ml in the bolus arm and 10,020 ± 3032 ml in the continuous arm (p = 0.04). Treatment failure occurred less in the continuous-infusion group (15% vs. 38%, p = 0.02), while there was no significant difference between groups in the incidence of worsening of renal function.

Conclusion: Among patients with acute decompensation of ACHF and high risk of diuretic resistance, continuous infusion of intravenous furosemide was associated with better decongestion.

Drain Trial: ClinicalTrials.gov number NCT03592836.
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http://dx.doi.org/10.1007/s00392-019-01521-yDOI Listing
April 2020

Prognostic impact of MitraClip in patients with left ventricular dysfunction and functional mitral valve regurgitation: A comprehensive meta-analysis of RCTs and adjusted observational studies.

Int J Cardiol 2019 09 10;290:70-76. Epub 2019 May 10.

Cardiology Department, Città della Salute e della Scienza, Molinette Hospital, Turin, Italy.

The real prognostic impact of MitraClip in patients with significant functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction remains to be elucidated. Two randomized controlled trials (RCTs) with conflicting results have been recently published. We conducted a comprehensive meta-analysis of all RCTs and adjusted observational studies to evaluate the clinical impact of percutaneous mitral valve repair when compared with optimal medical therapy (OMT) alone, in patients with symptomatic FMR and LV dysfunction. Death from any cause and heart failure rehospitalizations at the longest available follow-up were the primary endpoints. Cardiac death, one year and short-term death were the secondary ones. 2255 patients (1207 for MitraClip and 1048 for OMT-only) from 8 studies (2 RCTs and 6 observational studies) were included. At a median (mid-term) follow-up of 438 days (IQR 360-625) MitraClip was associated with a significant reduction of all-cause death (odds Ratio [OR] 0.55, 95%CI 0.41-0.73, p < 0.001; [ORadj] 0.66, 95%CI 0.49-0.90, p = 0.009) and rehospitalization (OR 0.49, 95%CI 0.24-1.00, p = 0.05 and ORadj 0.63, 95%CI 0.43-0.94, p = 0.02). At one year, adjusted analysis demonstrated a trend favoring the experimental cohort (ORadj 0.73, 95%CI 0.53-1.02, p = 0.07). Meta-regression suggested that benefit of MitraClip on mid-term survival persists even after accounting for the prevalence of implanted CRT, burden of comorbidities, NYHA class, cardiomyopathy etiology and LV function and dimensions. In conclusion, MitraClip for FMR in patients with LV dysfunction is associated with a considerable reduction of death and HF hospitalization at mid-term follow-up. Further ongoing RCTs are needed to strengthen present results.
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http://dx.doi.org/10.1016/j.ijcard.2019.05.015DOI Listing
September 2019

Effectiveness of Cognitive Remediation in Early Versus Chronic Schizophrenia: A Preliminary Report.

Front Psychiatry 2019 11;10:236. Epub 2019 Apr 11.

Department of Mental Health and Addiction Services, ASST Spedali Civili, Brescia, Italy.

Many evidences have demonstrated the effectiveness of cognitive remediation on cognition and functioning in patients with schizophrenia. Some researchers speculate that cognitive deficits are more amenable to remediation during earlier phases of illness than in chronicity. Therefore, cognitive rehabilitation should be used as an early intervention, seeking to produce durable functional changes in the early course of schizophrenia. Although there is strong evidence that cognitive remediation is effective in adult schizophrenia, there is little evidence about its efficacy and long-term generalized effectiveness in the early course of the disease. In this paper, we intended to investigate the possibility that cognitive remediation may produce more beneficial effects when applied in the early phase of the illness compared to chronic patients. Data were gathered from a database used for a previous study performed by our group, in which 56 patients with schizophrenia received a cognitive remediation intervention. In a analysis, patients with a duration of illness shorter than 5 years were defined as "early course" patients, while patients with a duration of illness longer than 5 years were defined as "chronic." Clinical, neuropsychological, and functional outcome variables were assessed at baseline and after treatment. Of the 56 patients included in the study, 11 were "early course" and 45 were "chronic." Both the early course group and the chronic group showed significant improvements in all the clinical, neurocognitive, and functional parameters analyzed. A significantly greater improvement in early course patients compared with chronic patients emerged in clinical and functional measures. No differential change was observed between early course patients and chronic patients in the cognitive composite score. Our study confirms the effectiveness of cognitive remediation in improving clinical, cognitive, and functional parameters in patients with schizophrenia, both in patients in the early course and in chronic patients. However, patients in the early course showed a differential, greater change in clinical and functional parameters compared to chronic patients. Although this study has some limitations, it confirms the effectiveness of cognitive remediation interventions, particularly if applied in the early course of the illness.
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http://dx.doi.org/10.3389/fpsyt.2019.00236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470279PMC
April 2019

Calcific tendinopathy of the shoulder: clinical perspectives into the mechanisms, pathogenesis, and treatment.

Orthop Res Rev 2018 3;10:63-72. Epub 2018 Oct 3.

Department of Orthopaedics, University of Milan,

Calcific tendinopathy (CT) of the shoulder is a common, painful condition characterized by the presence of calcium deposits in the rotator cuff tendons. Current theories indicate that CT may be the result of a cell-mediated process in which, after a stage of calcium deposition, calcifications are spontaneously resorbed. However, in a minority of cases, this self-healing process is somehow disrupted, resulting in symptoms. Recent literature shows an emerging role of biological and genetic factors underlying CT. This new evidence could supplement the classic mechanical theory of rotator cuff tendinopathy complicated by calcium precipitation, and it may also explain why the majority of the therapies currently in use are only able to provide partially satisfactory outcomes. This review aims to summarize the current knowledge about the pathological processes underlying CT of the shoulder and thereby justify the quest for advanced biological treatments of this condition when it becomes symptomatic.
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http://dx.doi.org/10.2147/ORR.S138225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209365PMC
October 2018

Factors Associated With Response and Resistance to Cognitive Remediation in Schizophrenia: A Critical Review.

Front Pharmacol 2018 10;9:1542. Epub 2019 Jan 10.

Department of Mental Health and Addiction Services, ASST Spedali Civili, Brescia, Italy.

Cognitive impairment is a central feature of schizophrenia and has shown to play a crucial role in the psychosocial function of the disorder. Over the past few years, several cognitive remediation (CR) interventions have been developed for schizophrenia, whose effectiveness has also been widely demonstrated by systematic reviews and meta-analysis studies. Despite these evidences, many questions remain open. In particular, the identification of CR response predictors in patients with schizophrenia is still a topic with equivocal findings and only a few studies have looked for the relationship between CR response or resistance and the biological, socio-demographic, clinical and cognitive features in schizophrenia. The current knowledge on positive or negative response predictors to CR treatment in schizophrenia include: age, duration of illness, premorbid adjustment, baseline cognitive performance, intrinsic motivation, hostility, disorganized symptoms, neurobiological reserve, genetic polymorphisms, the amounts of antipsychotics, the type of CR, etc. The aim of this review is to identify neurobiological, psychopathological, cognitive, and functional predictors of CR response or resistance in schizophrenia, taking into account both cognitive and functional outcome measures. The information obtained could be very useful in planning integrated and personalized interventions, also with a better use of the available resources.
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http://dx.doi.org/10.3389/fphar.2018.01542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335346PMC
January 2019

Advances in medical therapy for pericardial diseases.

Expert Rev Cardiovasc Ther 2018 Sep 21;16(9):635-643. Epub 2018 Aug 21.

a University Cardiology, AOU Città della Salute e della Scienza di Torino , Torino , Italy.

Introduction: Medical therapy of pericardial diseases is moving forward to the road of evidence-based medicine and has improved in the last years because of the first randomized clinical trials in the area as well as new therapeutic options for recurrent pericarditis. Areas covered: The present review will focus on more recent advances with a special emphasis on the treatment of pericarditis, the area with more significant improvements in the last years. Medline/Pubmed Library were systematically screened with two specific key searches: 'pericarditis AND therapy' and 'pericardial effusion AND therapy'. The search was restricted to articles published in the last 5 years, in order to select the latest novelties in medical treatment and was restricted to 'human' studies and papers in English. Expert commentary: The anti-inflammatory therapy of pericarditis has been now well defined with first-line agents represented by nonsteroidal anti-inflammatory drugs plus colchicine, low-dose corticosteroids with slow tapering as second-line agents and for specific indications (e.g. specific systemic inflammatory diseases, renal failure, pregnancy, patients with interfering therapies such as oral anticoagulants), and third-line options in case of multiple recurrences (e.g. azathioprine, intravenous immunoglobulins, and especially anakinra).
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http://dx.doi.org/10.1080/14779072.2018.1510315DOI Listing
September 2018

Prognostic incremental role of right ventricular function in acute decompensation of advanced chronic heart failure.

Eur J Heart Fail 2016 05 16;18(5):564-72. Epub 2016 Mar 16.

Division of Cardiology, Città della Salute e della Scienza University Hospital of Torino, Italy.

Aims: The purpose of this study was to evaluate the additional prognostic value of echocardiography in acute decompensation of advanced chronic heart failure (CHF), focusing on right ventricular (RV) dysfunction and its interaction with loading conditions. Few data are available on the prognostic role of echocardiography in acute HF and on the significance of pulmonary hypertension in patients with severe RV failure.

Methods And Results: A total of 265 NYHA IV patients admitted for acute decompensation of advanced CHF (EF 22 ± 7%, systolic blood pressure 107 ± 20 mmHg) were prospectively enrolled. Fifty-nine patients met the primary composite endpoint of cardiac death, urgent heart transplantation, and urgent mechanical circulatory support implantation at 90 days. Pulmonary hypertension failed to predict events, while patients with a low transtricuspid systolic gradient (TR gradient <20 mmHg) showed a worse outcome [hazard ratio (HR) 2.37, 95% confidence interval (CI) 1.12-5.00, P = 0.02]. RV dysfunction [tricuspid annular plane systolic excursion (TAPSE) ≤14 mm] in the presence of a low TR gradient identified patients at higher risk of events (HR 2.97, 95% CI 1.19-7.41, P = 0.02). Multivariate analysis showed as best predictors of outcome low RV contraction pressure index (RVCPI), defined as TAPSE × TR gradient, and high estimated right atrial pressure (eRAP). Adding RVCPI (<400 mm*mmHg) and eRAP (≥20 mmHg) to conventional clinical (ADHERE risk tree and NT-proBNP) and echocardiographic risk evaluation resulted in an increase in net reclassification improvement of +19.1% and +20.1%, respectively (P = 0.01) and in c-statistic from 0.59 to 0.73 (P < 0.01).

Conclusions: In acute decompensation of advanced CHF, pulmonary hypertension failed to predict events. The in-hospital and short-term prognosis can be better predicted by eRAP and RVCPI.
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http://dx.doi.org/10.1002/ejhf.504DOI Listing
May 2016

Prolonged QT interval in ST-elevation myocardial infarction: predictors and prognostic value in medium-term follow-up.

J Cardiovasc Med (Hagerstown) 2016 Jun;17(6):440-5

Division of Cardiology, Department of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Italy.

Aims: The prognostic role of corrected QT interval in ST-elevation myocardial infarction is still unknown. This study aims to identify the prognostic value of corrected QT interval prolongation (≥480 ms) in acute coronary syndrome.

Methods: One hundred and eighty-five consecutive patients with ST-elevation myocardial infarction were prospectively enrolled and electrocardiographic monitoring of corrected QT interval was performed during the hospitalization.

Results: Over a mean period of 17.6 ± 11 months, 16 (8.6%) patients died because of cardiovascular diseases, 6 (3.2%) patients experienced aborted sudden cardiac death, 3 (1.6%) cerebral ischemic strokes, 11 (6%) recurrent myocardial ischemia and 6 (3.2%) acute heart failure. At univariate analysis a corrected QT interval peak of at least 480 ms relates to cardiovascular death (P < 0.001), aborted sudden cardiac death (P = 0.037), cerebral ischemic stroke (P = 0.016) and recurrences of myocardial infarction (P = 0.032). Multivariate analysis confirms its role an independent predictor of cardiovascular death [odds ratio 6.38, 95% confidence interval (CI) 1.77-22.92, P = 0.004], together with an ejection fraction of 35% or less (odds ratio 4.20, 95% CI 1.24-14.16, P = 0.021). The presence of either corrected QT of at least 480 ms or ejection fraction of 35% or less increases the sensitivity and the accuracy to correctly predict cardiovascular death without a significant reduction in specificity (sensitivity 88%, specificity 69%, accuracy 88%, area under curve 0.83, 95% CI 0.72-0.94, P < 0.01).

Conclusion: A corrected QT interval peak of at least 480 ms in the acute phase of ST-elevation myocardial infarction is an independent predictor of cardiovascular death. Its association with reduced ejection fraction (≤35%) increases risk stratification accuracy.
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http://dx.doi.org/10.2459/JCM.0000000000000317DOI Listing
June 2016

Schizophrenia susceptibility and NMDA-receptor mediated signalling: an association study involving 32 tagSNPs of DAO, DAOA, PPP3CC, and DTNBP1 genes.

BMC Med Genet 2013 Mar 9;14:33. Epub 2013 Mar 9.

Psychiatric Unit, University of Brescia, School of Medicine, Viale Europa 11, 25123 Brescia, Italy.

Background: Recent studies supported associations between four NMDA-receptor-mediated signalling genes (D-amino acid oxidase, DAO; D-amino acid oxidase activator, DAOA; protein phosphatase 3 catalytic subunit gamma isoform, PPP3CC; dystrobrevin-binding protein 1, DTNBP1) and schizophrenia susceptibility, even though with contrasting results.

Methods: In an attempt to replicate these findings for the first time in an Italian population, a panel of 32 tagSNPs was analysed in a representative case-control sample involving 879 subjects.

Results: An association in the allele frequency was observed for the estimated PPP3CC CAG triplotype in the SNP window rs4872499 T/C-rs11780915 A/G-rs13271367 G/A (pcorrect = 0.001). Similarly, the clustered genotype frequencies of the estimated/phased CAG triplotype differed between cases and controls (p = 0.004), with the carriers having a higher frequency in the control population (p = 0.002, odd ratio OR = 0.59, 95% confident interval CI: 0.43-0.82).Following the phenotypic dissection strategy, the analysis of single SNPs evidenced a protective effect in males of rs11780915 and rs13271367 in PPP3CC gene (pcorrect = 0.02, pcorrect = 0.04 respectively). Moreover the estimated/phased GT diplotype (rs2070586A/G-rs3741775G/T) carriers of the DAO gene were more highly represented in female controls (p = 0.017, OR = 0.58, 95% CI: 0.37-0.90), as were the estimated/phased CAG triplotype carriers of the PPP3CC gene in females (p = 0.01, OR = 0.53, 95% CI: 0.32-0.87). In addition, we performed an interaction analysis, and a 66% (p = 0.003, OR = 0.34, 95% CI: 0.17-0.70) lower risk of developing schizophrenia for female (CAG + GT) carriers versus non-CAG or -GT carriers was observed. For DTNBP1, we found a protective effect in males for the rs6459409 (pcorrect = 0.02) and the estimated/phased CT diplotype (rs6459409-rs9476886) carriers (p = 3x10-4, OR = 0.46, 95% CI: 0.30-0.70).In relation to diagnostic subtypes, the estimated/phased DAO GT diplotype and PPP3CC CAG triplotype female carriers were found to show relative risk ratio (RRR) values of 0.52 and 0.54 lower risk for a paranoid phenotype respectively.

Conclusions: Although the results are preliminary and needed replication in a larger sample, this study suggests that NMDA receptor-mediated signalling genes (DAO, PPP3CC, DTNBP1) might be involved in schizophrenia pathogenic mechanisms related to gender.
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http://dx.doi.org/10.1186/1471-2350-14-33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599832PMC
March 2013

Oral ziprasidone in the treatment of patients with bipolar disorders: a critical review.

Expert Rev Clin Pharmacol 2011 Mar;4(2):163-79

Department of Psychiatry, Brescia University School of Medicine, Brescia, Italy.

Ziprasidone, a benzisothiazolyl piperazine derivative of tiospirone, is a second-generation antipsychotic with high-affinity antagonism for 5-hydroxytryptophan (5HT)(2A), 5HT(2C), 5HT(1D) and D(2) receptors, pre- and post-synaptic agonism for 5HT(1A) receptors, and inhibition of reuptake for serotonin and norepinephrine. Initially approved for the treatment of adults with schizophrenia, ziprasidone has more recently received supplementary indications for acute manic and mixed episodes and as maintenance therapy for people affected by bipolar disorder. Based on MEDLINE citations up to November 2010 and hand-searched references, this article relating to ziprasidone addresses its short- and long-term efficacy and safety, according to the results of randomized clinical trials, open-label studies and real-world experiences. Emerging evidence indicates that in patients with bipolar disorder, ziprasidone provides valid efficacy and remarkable safety when administered alone for the treatment of manic and mixed episodes. The same applies when ziprasidone is administered in combination with lithium or valproate for the prevention of affective relapses and recurrences. Any conclusion on the potential of ziprasidone as an antidepressant should be postponed because of insufficient evidence.
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http://dx.doi.org/10.1586/ecp.10.139DOI Listing
March 2011

Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study.

Schizophr Res 2009 Aug;113(1):112-21

Chair of Psychiatry, Brescia University School of Medicine, Brescia, Italy.

This 18-week, randomized, flexible-dose, double-blind, double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients. Patients had a DSM-IV diagnosis of schizophrenia, a history of resistance and/or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses, PANSS score >or= 80, and CGI-S score >or= 4. Patients were randomized to ziprasidone (80-160 mg/day, n = 73) or clozapine (250-600 mg/day, n = 74). On the primary ITT-LOCF analysis, baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone (- 25.0 +/- 22.0, 95% CI - 30.2 to - 19.8) and clozapine (- 24.5 +/- 22.5, 95% CI - 29.7 to - 19.2) groups. A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms. There were also significant improvements on PANSS subscales, CGI-S, CG-I, CDSS, and GAF, without between-drug differences. The two treatment groups had similar rates of early discontinuations due to AEs. AEs were mostly of similar mild-moderate severity in the two groups. There were also no detrimental effects on prolactin, renal and liver function, hematology, and cardiovascular parameters. However, ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores. Moreover, when compared with clozapine, ziprasidone also had a more favorable metabolic profile, with significant endpoint differences in weight, fasting glucose, total cholesterol, LDL cholesterol, and triglycerides. In conclusion, this trial indicates that both ziprasidone and clozapine, having comparable efficacy coupled with satisfactory general safety and tolerability, may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and/or intolerance to antipsychotics. The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians, at least in the presence of patients at high risk for metabolic disorders.
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http://dx.doi.org/10.1016/j.schres.2009.05.002DOI Listing
August 2009

Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study.

Schizophr Res 2009 May 9;110(1-3):80-9. Epub 2009 Mar 9.

Brescia University School of Medicine, Brescia, Italy.

This 18-week, randomized, flexible-dose, double-blind, double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients. Patients had a DSM-IV diagnosis of schizophrenia, a history of resistance and/or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses, PANSS score >or=80, and CGI-S score >or=4. Patients were randomized to ziprasidone (80-160 mg/day, n=73) or clozapine (250-600 mg/day, n=74). On the primary ITT-LOCF analysis, baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone (-25.0+/-22.0, 95% CI -30.2 to -19.8) and clozapine (-24.5+/-22.5, 95% CI -29.7 to -19.2) groups. A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms. There were also significant improvements on PANSS subscales, CGI-S, CG-I, CDSS, and GAF, without between-drug differences. The two treatment groups had similar rates of early discontinuations due to AEs. AEs were mostly of similar mild-moderate severity in the two groups. There were also no detrimental effects on prolactin, renal and liver function, hematology, and cardiovascular parameters. However, ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores. Moreover, when compared with clozapine, ziprasidone also had a more favorable metabolic profile, with significant endpoint differences in weight, fasting glucose, total cholesterol, LDL cholesterol, and triglycerides. In conclusion, this trial indicates that both ziprasidone and clozapine, having comparable efficacy coupled with satisfactory general safety and tolerability, may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and/or intolerance to antipsychotics. The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians, at least in the presence of patients at high risk for metabolic disorders.
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http://dx.doi.org/10.1016/j.schres.2009.02.017DOI Listing
May 2009

Reduced fractional anisotropy of corpus callosum in first-contact, antipsychotic drug-naive patients with schizophrenia.

Schizophr Res 2009 Mar 21;108(1-3):41-8. Epub 2008 Dec 21.

Department of Diagnostic Imaging, Neuroradiology Unit, Brescia University School of Medicine and Brescia Spedali Civili, Brescia, Italy.

Background: Corpus callosum is the most important commissure of the brain and therefore represents a first-choice candidate to challenge hypotheses of disrupted inter-hemispheric connectivity and white matter pathology in patients with schizophrenia. Recent studies on diffusion tensor imaging (DTI) of corpus callosum yielded promising but equivocal evidence of reduced fractional anisotropy (FA) in schizophrenia patients who were, for the most part, chronic cases on medication for a lengthy period of time. To exclude potentially confounding effects of the course of the disorder and its treatment, we compared callosal FA of first-contact, antipsychotic drug-naive schizophrenia patients (n=21) and healthy controls (n=21).

Methods: Splenium and genu FA were obtained by two independent observers utilizing large, rectangular, tractography-guided regions of interest outlined on directional color-coded maps. Inter-observer agreement on FA was evaluated by means of the Bland and Altman and the Passing and Bablok procedures together with an estimate of the intra-class correlation coefficient.

Results: Strong inter-observer agreement of FA values emerged from each of the three statistical approaches utilized. ANCOVA showed a significant effect on FA for the interaction between patient-control membership and callosal region (F=5.354; p=0.026); post hoc multiple comparisons demonstrated that, when compared to the controls, the patients had lower mean FA values (p=0.005) in the splenium but not in the genu and that this difference tended to be more evident in males (p=0.090).

Conclusions: Lowered mean FA values in the splenium of first-contact, antipsychotic drug-naive patients with respect to healthy controls strongly support the hypothesis that processes operant at least since the earliest phases of the disorder and independent from exposition to antipsychotic drugs contribute to reduced anisotropy in schizophrenia.
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http://dx.doi.org/10.1016/j.schres.2008.11.015DOI Listing
March 2009

Self-ordered pointing and visual conditional associative learning tasks in drug-free schizophrenia spectrum disorder patients.

BMC Psychiatry 2008 Jan 23;8. Epub 2008 Jan 23.

Department of Psychiatry, Brescia University School of Medicine, Brescia, Italy.

Background: There is evidence of a link between schizophrenia and a deficit of working memory, but this has been derived from tasks not specifically developed to probe working memory per se. Our aim was to investigate whether working memory deficits may be detected across different paradigms using the self-ordered pointing task (SOPT) and the visual conditional associative learning task (VCALT) in patients with schizophrenia spectrum disorders and healthy controls. The current literature suggests deficits in schizophrenia spectrum disorder patients versus healthy controls but these studies frequently involved small samples, broad diagnostic criteria, inclusion of patients on antipsychotic medications, and were not controlled for symptom domains, severity of the disorder, etc. To overcome some of these limitations, we investigated the self-monitoring and conditional associative learning abilities of a numerically representative sample of healthy controls and a group of non-deteriorated, drug-free patients hospitalized for a schizophrenia spectrum disorder with florid, mainly positive psychotic symptoms.

Methods: Eighty-five patients with a schizophrenia spectrum disorder (DSM-IV-TR diagnosis of schizophrenia (n = 71) or schizophreniform disorder (n = 14)) and 80 healthy controls entered the study. The clinical picture was dominated by positive symptoms. The healthy control group had a negative personal and family history of schizophrenia or mood disorder and satisfied all the inclusion and exclusion criteria other than variables related to schizophrenia spectrum disorders.

Results: Compared to controls, patients had worse performances on SOPT, VCALT and higher SOPT/VCALT ratios, not affected by demographic or clinical variables. ROC curves showed that SOPT, VCALT, and SOPT/VCALT ratio had good accuracy in discriminating patients from controls. The SOPT and VCALT scores were inter-correlated in controls but not in patients.

Conclusion: The selection of a clinically homogeneous group of patients, controlled for a number of potential confounding factors, and the high level of significance found in the different analyses confirm the presence of SOPT and VCALT abnormalities in a large preponderance of patients with schizophrenia spectrum disorder with positive symptoms. SOPT, VCALT, and SOPT/VCALT ratio showed good accuracy in discriminating patients from healthy controls. These conclusions cannot be extended to schizophrenia spectrum disorder patients with a different clinical profile from our patient population.
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http://dx.doi.org/10.1186/1471-244X-8-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2245938PMC
January 2008

A randomized double-blind comparison of ziprasidone vs. clozapine for cognition in patients with schizophrenia selected for resistance or intolerance to previous treatment.

Schizophr Res 2008 Oct 20;105(1-3):138-43. Epub 2008 Feb 20.

Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30032, United States.

Background: Recent data have suggested few differences in the cognitive effects of antipsychotic medications. However, assessment of such effects can be complex, due to a number of factors. Clozapine has previously shown greater clinical and lesser cognitive benefits than other atypicals. This study compared the cognitive benefits of clozapine and ziprasidone in schizophrenia patients (n=130) with a history of either failure to respond to or intolerance of previous adequate antipsychotic treatments.

Methods: Patients were randomized (double-blind) to either clozapine or ziprasidone in a single country (Italy), multi-site trial. The cognitive assessments examined episodic memory (RAVLT), executive functioning (Stroop test), and processing speed (Trail-making test (TMT) Parts A and B).

Results: Analyses found statistically significant within-group improvements for ziprasidone in learning and delayed recall on the RAVLT and on TMT Parts A and B. Clozapine-treated patients improved on the RAVLT, but not on the TMT. A composite cognitive score improved from baseline in both groups, but the improvements were significantly larger in the ziprasidone group (p=.029).

Implications: These results indicated that cognitive functioning improved following treatment with ziprasidone in patients with a history of either treatment resistance or intolerance, and that the effects are comparable or greater than those observed with clozapine. One interpretation of these findings is that clozapine treatment interferes with the performance benefits associated with practice.
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http://dx.doi.org/10.1016/j.schres.2007.11.014DOI Listing
October 2008

Cytokine profiles in schizophrenic patients treated with risperidone: a 3-month follow-up study.

Prog Neuropsychopharmacol Biol Psychiatry 2002 Jan;26(1):33-9

Association for the Research on Schizophrenia, Fondazione Legrenzi, Milan, Italy.

An increasing body of evidence suggests a role for the immune system in the pathogenesis of schizophrenia. The information concerning the effects of antipsychotics on cytokine profiles are limited and often controversial in particular regarding novel antipsychotics. The authors first investigated the production of various cytokines [interleukin (IL)-2, IL-4, IL-10, interferon (INF)-gamma] in drug-free (n = 12) and drug-naive (n = 3) schizophrenic patients and in healthy controls (n = 33) and then the modifications of cytokines values during a 3-month period of treatment with risperidone. In the baseline condition, the production of IL-2 and INF-gamma was significantly higher (P = .023 and .026, respectively) in patients than in controls. In the same patients, the use of risperidone was associated with augmented IL-10 (a suppressor of Type I cytokines) and decreased INF-gamma production. This modification suggests that clinical improvement is associated with a reduction in the inflammatory-like situation present in not currently treated schizophrenic patients.
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http://dx.doi.org/10.1016/s0278-5846(01)00221-4DOI Listing
January 2002