Ciro Maiello - Academia.edu (original) (raw)

Papers by Ciro Maiello

Drugs in context, 2014

Although several treatment options are available to reduce hyperglycemia, only about half of indi... more Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM) achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM). The renal sodium-glucose co-transporter 2 (SGLT2) is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic ...

Transplant Immunology, Aug 1, 2021

Heart transplantation (HTx) is considered the gold-standard therapy for the treatment of advanced... more Heart transplantation (HTx) is considered the gold-standard therapy for the treatment of advanced heart failure (HF). The long-term survival in HTx is hindered by graft failure which represents one of the major limitations of the long-term efficacy of HTx. Endomyocardial biopsy (EMB) and the evaluation of donor-specific antibodies (DSA) are currently considered the essential diagnostic tools for surveillance of graft rejection. Recently, new molecular biomarkers (including cell-free DeoxyriboNucleic Acid, exosome, gene profiling microarray, nanostring, reverse transcriptase multiplex ligation-dependent probe amplification, proteomics and immune profiling by quantitative multiplex immunofluorescence) provide useful information on mechanisms of graft rejection. The ambitious role of a similar change of perspective is aimed at a better and longer graft preservation.

Journal of Heart and Lung Transplantation, Jul 1, 2011

We report the successful implantation of dual Jarvik 2000 biventricular assist devices (BiVAD; Ja... more We report the successful implantation of dual Jarvik 2000 biventricular assist devices (BiVAD; Jarvik Heart Inc, New York, NY). A 27-year-old woman with arrhythmogenic right ventricular (RV) cardiomyopathy was referred to our hospital and approved for heart transplantation. Her body size was small (body surface area, 1.38 m 2) due to cardiac cachexia. Her left ventricular (LV) ejection fraction 845 Comment and Opinion

Transplantation Reviews, Apr 1, 2021

The lack of a precise stratification algorithm for predicting patients at high risk of graft reje... more The lack of a precise stratification algorithm for predicting patients at high risk of graft rejection challenges the current solid organ transplantation (SOT) clinical setting. In fact, the established biomarkers for transplantation outcomes are unable to accurately predict the onset time and severity of graft rejection (acute or chronic) as well as the individual response to immunosuppressive drugs. Thus, identifying novel molecular pathways underlying early immunological responses which can damage transplant integrity is needed to reach precision medicine and personalized therapy of SOT. Direct epigenetic-sensitive mechanisms, mainly DNA methylation and histone modifications, may play a relevant role for immune activation and long-term effects (e.g., activation of fibrotic processes) which may be translated in new non-invasive biomarkers and drug targets. In particular, the measure of DNA methylation by using the blood-based "epigenetic clock" system may be an added value to the donor eligibility criteria providing an estimation of the heart biological age as well as a predictive biomarkers. Besides, monitoring of DNA methylation changes may aid to predict acute vs chronic graft damage in kidney transplantation (KT) patients. For example, hypermethylation of genes belonging to the Notch and Wnt pathways showed a higher predictive value for chronic injury occurring at 12 months post-KT with respect to established clinical parameters. Detecting higher circulating cell-free DNA (cfDNA) fragments carrying hepatocyte-specific unmethylated loci in the inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), insulin like growth factor 2 receptor (IGF2R), and vitronectin (VTN) genes may be useful to predict acute graft injury after liver transplantation (LT) in serum samples. Furthermore, hypomethylation in the forkhead box P3 (FOXP3) gene may serve as a marker of infiltrating natural Treg percentage in the graft providing the ability to predict acute rejection events after heart transplantation (HTx). We aim to update on the possible clinical relevance of DNA methylation changes regulating immune-related pathways underlying acute or chronic graft rejection in KT, LT, and HTx which might be useful to prevent, monitor, and treat solid organ rejection at personalized level.

Transplant Immunology, 2021

PubMed, Dec 1, 2017

Steinert's disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic diso... more Steinert's disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure. We report the case of a patient with Steinert disease showing an early onset ventricular dysfunction due to chronic right ventricular apical pacing, in which an epicardial left ventricular lead implantation was performed following the failure of the percutaneous attempt. As no relief in symptoms of heart failure, nor an improvement of left ventricular ejection fraction and reverse remodelling was observed six months later, the patient was addressed to the heart transplantation.

Transplant Infectious Disease, Dec 21, 2017

Direct-acting antiviral agents (DAAs) are a safe and effective treatment for chronic hepatitis C ... more Direct-acting antiviral agents (DAAs) are a safe and effective treatment for chronic hepatitis C (CHC). This may be particularly valuable for patients with severe comorbidities or baseline conditions, including non-liver solid organ transplant. We report cases of two heart transplant recipients with CHC treated with DAA (sofosbuvir and daclatasvir) achieving sustained virological response. Treatment was well tolerated and no relevant side effects were observed. The drug-drug interactions and graft function were carefully monitored.

Transplant Infectious Disease, Mar 18, 2021

Background: The aim of this study was to assess the effect of continuing immune suppressive thera... more Background: The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID-19). Methods: Systematic review and meta-analysis of data on 202 SOTR with COVID-19, published as case reports or case series. We extracted clinical, hemato-chemical, imaging, treatment, and outcome data. Results: Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57 years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID-19 disease. Age (OR 1.07, 95% CI 1-1.11, P = .001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2-8.5, P = .013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008-0.558, P = .012) and tacrolimus continuation (OR 0.3, 95% CI 0.1-0.7, P = .013) were independent predictors of survival. Conclusions: Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID-19. Specifically, receiving tacrolimus could be beneficial for COVID-19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID-19 can be derived from our data.

Transplant Infectious Disease, May 10, 2016

Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flare... more Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients. In this prospective, observational study, we assessed outcomes of therapy with tenofovir (TDF), entecavir (ETV), and telbivudine (LdT) in 13 heart transplant recipients (HTR) with CHB. Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus (HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0-4). Glomerular filtration rate (GFR) was <50 mL/min in 7 patients (54%). Two patients were started on de novo ETV before transplant. Eleven previously treated patients were switched to TDF (n = 9) or LdT (n = 2). Median treatment duration was 33 months (range 1-71). HBV DNA remained suppressed in 6 patients and became undetectable in 5. Aminotransferases went down to the normal range in all patients, with a single flare in 1 patient. One patient lost hepatitis B surface antigen. No cases occurred of hepatic decompensation, hepatocellular carcinoma, or liver-related death. The GFR remained largely stable, and no cases of TDF-related hyper-phosphaturia were observed. This study indicates that newer antivirals are effective and safe in HTR with CHB.

Vascular Health and Risk Management, May 1, 2021

Despite the current reductionist approach providing an optimal indication for diagnosis and treat... more Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy ("epidrugs") is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF.

International Journal of Medical Informatics, Aug 1, 2023

Pharmacological Research, Oct 1, 2022

Journal of Cardiothoracic Surgery, Oct 29, 2022

Big Data, and the derived analysis techniques, such as artificial intelligence and machine learni... more Big Data, and the derived analysis techniques, such as artificial intelligence and machine learning, have been considered a revolution in the modern practice of medicine. Big Data comes from multiple sources, encompassing electronic health records, clinical studies, imaging data, registries, administrative databases, patient-reported outcomes and OMICS profiles. The main objective of such analyses is to unveil hidden associations and patterns. In cardiac surgery, the main targets for the use of Big Data are the construction of predictive models to recognize patterns or associations better representing the individual risk or prognosis compared to classical surgical risk scores. The results of these studies contributed to kindle the interest for personalized medicine and contributed to recognize the limitations of randomized controlled trials in representing the real world. However, the main sources of evidence for guidelines and recommendations remain RCTs and meta-analysis. The extent of the revolution of Big Data and new analytical models in cardiac surgery is yet to be determined.

Tumori Journal, Jun 1, 1989

European Journal of Internal Medicine, May 1, 2008

To evaluate the clinical characteristics and outcomes of in-hospital adult patients who had cardi... more To evaluate the clinical characteristics and outcomes of in-hospital adult patients who had cardiopulmonary arrest and received cardiopulmonary resuscitation (CPR). Methods: Retrospective, observational study of 133 consecutive patients, experiencing 143 episodes of in-hospital cardiopulmonary arrest over a 24month period. Primary end-points include return of spontaneous circulation (ROSC), survival to hospital discharge, 30-day survival and 1-year survival. Results: 133 patients with a mean age 70 (range 24-92) years; female: male 72 (54%): 61 (46%). 133 (93%) episodes were cardiopulmonary arrests whereas 10 (7%) were primary respiratory arrests. 98 episodes were witnessed, 27 unwitnessed and no record was available for 18 episodes. On initial assessment, majority (73%) of the patients had non-shockable rhythm. The mean number of CPR cycles were 3 (median 3, range 1-12). 65 (45%) patients were intubated during CPR. 49 (34%) patients received defibrillation, 112 (78%) had adrenaline, 80 (60%) had atropine, 13 (9%) had amiodarone and 1 received sodium bicarbonate. 14 patients underwent postmortem following failed CPR. 53 (37%) patients were successfully resuscitated, of which 27 (51%) were discharged from the hospital. 30-day survival following cardiopulmonary resuscitation was 20% and 1-year survival was 13%. It was noted that in patients with primary respiratory arrest, successful resuscitation was achieved in 90% cases, and 1-year survival was 60%. Conclusions: Inspite of effective advanced life support training and early identification of critically ill patients, the overall outcome following in-hospital cardiorespiratory arrest remains poor

Tumori Journal, Jun 1, 1989

DBA/2N is a genetically non responsive inbred strain of mice in which administration of polycycli... more DBA/2N is a genetically non responsive inbred strain of mice in which administration of polycyclic aromatic hydrocarbons (PAHs) does not induce microsomal monooxygenase activity. DBA/2N mouse liver cytosol contains a polycyclic aromatic hydrocarbon-binding protein that sediments, in a sucrose gradient, at 4S (« 4S » PAH-BP). Its binding kinetic and physicochemical properties indicate that this protein is practically indistinguishable from the « 4S " PAH-BP identified and characterized in liver cytosol of rats and other PAH responsive rodents including C57 B1/6J mice. « 4S » PAH-BP was purified to homogeneity from DBA/2N mouse liver by ammonium sulfate fractionation of the cytosol, followed by Sephadex G-200

Internal and Emergency Medicine, Apr 4, 2018

Background: Multiple hormonal deficiency syndrome (MHDS) is common in heart failure (HF). To date... more Background: Multiple hormonal deficiency syndrome (MHDS) is common in heart failure (HF). To date, no large observational study has unequivocally demonstrated that MHDS impacts on HF progression. Aim of the T.O.S.CA. Registry (NCT02335801) was to test whether MHDS affects morbidity and mortality in a large cohort of HF patients. Methods: The T.O.S.CA. Registry is a prospective, observational study involving 19 Italian centers. Thyroid hormones, insulin-like growth factor-1, testosterone, dehydropianoandrosterone, and insulin were measured at baseline and every year for a patient-average follow-up of 3 years. MHDS was defined as the presence of 2 or more hormonal deficiency (HD). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Results: A total of 526 consecutive patients was enrolled with a median follow-up of 36 months. MHDS was diagnosed in 405 patients (75%). A total of 276 events (98 death and 176 cardiovascular hospitalizations) were recorded; respectively 42.7% in MHDS-and 62.2 % in MHDS (p:0.001). MHDS was independently associated with the occurrence of the primary endpoint [HR 95% (CI), p-value: 1.58 (1.16-2.15), p:0.001] (Panel A). Further, MHDS identified a group of patients with higher mortality (χ2=9.2, p=0.03). Moreover a graded relation between HD and cumulative events were found (p:0.01) (Panel B). Conclusion: MHDS is a common finding in CHF and is independently associated with increased all-cause mortality and CV hospitalization.

Circulation, Nov 22, 2011

Journal of Clinical Virology, Nov 1, 2017

Background: Occult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,ab... more Background: Occult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,absence of serum HBsAg, low/undetectable serum HBVDNA. Reactivation of HBV infection may occur during immunosuppression, but few data are available in heart transplant. Objectives: We followed-up heart recipients with or without markers of previous HBV infection,evaluating prevalence of HBV markers, incidence of HBV reactivation and its virological and clinical features. Study design: Heart failure patients listed for heart transplant (2007-2013) were screened for current or past HBV infection. Transplanted patients with past HBV infection (anti-HBc+/ ± anti-HBs+/HBVDNA−) were followed up as cases, and an equal number of HBV negative patients as controls. Virological reactivation was detected by standard real-time and home-made highly sensitive PCR (surface/core HBVDNA regions). Clinical status and progression were assessed by liver histology, ultrasound or elastography. Results: 67 patients underwent heart transplant, including 4 (5.9%) HBsAg+ subjects. Cases were 11/67 (16.4%). During a median follow-up of 30 months, only one of these 11 patients presented viral reactivation (HBVDNA 209 IU/mL) at month 22, and started antiviral treatment. Four other recipients showed virological events of uncertain significance (sensitive PCR-only intermittently positive). Clinical signs of liver disease were observed in only one case at the last follow-up. A nonsignificant difference in survival was observed between cases and all other heart recipients without prior HBV contact (death rate 5/11 vs 15/52, respectively; p = 0.097). Conclusions: HBV genotypic reactivation in HBsAg−/anti-HBc+/HBVDNA− heart recipients is uncommon. Virological events of uncertain significance occur more frequently; their clinical impact seems to be negligible.

Drugs in context, 2014

Although several treatment options are available to reduce hyperglycemia, only about half of indi... more Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM) achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM). The renal sodium-glucose co-transporter 2 (SGLT2) is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic ...

Transplant Immunology, Aug 1, 2021

Heart transplantation (HTx) is considered the gold-standard therapy for the treatment of advanced... more Heart transplantation (HTx) is considered the gold-standard therapy for the treatment of advanced heart failure (HF). The long-term survival in HTx is hindered by graft failure which represents one of the major limitations of the long-term efficacy of HTx. Endomyocardial biopsy (EMB) and the evaluation of donor-specific antibodies (DSA) are currently considered the essential diagnostic tools for surveillance of graft rejection. Recently, new molecular biomarkers (including cell-free DeoxyriboNucleic Acid, exosome, gene profiling microarray, nanostring, reverse transcriptase multiplex ligation-dependent probe amplification, proteomics and immune profiling by quantitative multiplex immunofluorescence) provide useful information on mechanisms of graft rejection. The ambitious role of a similar change of perspective is aimed at a better and longer graft preservation.

Journal of Heart and Lung Transplantation, Jul 1, 2011

We report the successful implantation of dual Jarvik 2000 biventricular assist devices (BiVAD; Ja... more We report the successful implantation of dual Jarvik 2000 biventricular assist devices (BiVAD; Jarvik Heart Inc, New York, NY). A 27-year-old woman with arrhythmogenic right ventricular (RV) cardiomyopathy was referred to our hospital and approved for heart transplantation. Her body size was small (body surface area, 1.38 m 2) due to cardiac cachexia. Her left ventricular (LV) ejection fraction 845 Comment and Opinion

Transplantation Reviews, Apr 1, 2021

The lack of a precise stratification algorithm for predicting patients at high risk of graft reje... more The lack of a precise stratification algorithm for predicting patients at high risk of graft rejection challenges the current solid organ transplantation (SOT) clinical setting. In fact, the established biomarkers for transplantation outcomes are unable to accurately predict the onset time and severity of graft rejection (acute or chronic) as well as the individual response to immunosuppressive drugs. Thus, identifying novel molecular pathways underlying early immunological responses which can damage transplant integrity is needed to reach precision medicine and personalized therapy of SOT. Direct epigenetic-sensitive mechanisms, mainly DNA methylation and histone modifications, may play a relevant role for immune activation and long-term effects (e.g., activation of fibrotic processes) which may be translated in new non-invasive biomarkers and drug targets. In particular, the measure of DNA methylation by using the blood-based "epigenetic clock" system may be an added value to the donor eligibility criteria providing an estimation of the heart biological age as well as a predictive biomarkers. Besides, monitoring of DNA methylation changes may aid to predict acute vs chronic graft damage in kidney transplantation (KT) patients. For example, hypermethylation of genes belonging to the Notch and Wnt pathways showed a higher predictive value for chronic injury occurring at 12 months post-KT with respect to established clinical parameters. Detecting higher circulating cell-free DNA (cfDNA) fragments carrying hepatocyte-specific unmethylated loci in the inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), insulin like growth factor 2 receptor (IGF2R), and vitronectin (VTN) genes may be useful to predict acute graft injury after liver transplantation (LT) in serum samples. Furthermore, hypomethylation in the forkhead box P3 (FOXP3) gene may serve as a marker of infiltrating natural Treg percentage in the graft providing the ability to predict acute rejection events after heart transplantation (HTx). We aim to update on the possible clinical relevance of DNA methylation changes regulating immune-related pathways underlying acute or chronic graft rejection in KT, LT, and HTx which might be useful to prevent, monitor, and treat solid organ rejection at personalized level.

Transplant Immunology, 2021

PubMed, Dec 1, 2017

Steinert's disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic diso... more Steinert's disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure. We report the case of a patient with Steinert disease showing an early onset ventricular dysfunction due to chronic right ventricular apical pacing, in which an epicardial left ventricular lead implantation was performed following the failure of the percutaneous attempt. As no relief in symptoms of heart failure, nor an improvement of left ventricular ejection fraction and reverse remodelling was observed six months later, the patient was addressed to the heart transplantation.

Transplant Infectious Disease, Dec 21, 2017

Direct-acting antiviral agents (DAAs) are a safe and effective treatment for chronic hepatitis C ... more Direct-acting antiviral agents (DAAs) are a safe and effective treatment for chronic hepatitis C (CHC). This may be particularly valuable for patients with severe comorbidities or baseline conditions, including non-liver solid organ transplant. We report cases of two heart transplant recipients with CHC treated with DAA (sofosbuvir and daclatasvir) achieving sustained virological response. Treatment was well tolerated and no relevant side effects were observed. The drug-drug interactions and graft function were carefully monitored.

Transplant Infectious Disease, Mar 18, 2021

Background: The aim of this study was to assess the effect of continuing immune suppressive thera... more Background: The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID-19). Methods: Systematic review and meta-analysis of data on 202 SOTR with COVID-19, published as case reports or case series. We extracted clinical, hemato-chemical, imaging, treatment, and outcome data. Results: Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57 years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID-19 disease. Age (OR 1.07, 95% CI 1-1.11, P = .001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2-8.5, P = .013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008-0.558, P = .012) and tacrolimus continuation (OR 0.3, 95% CI 0.1-0.7, P = .013) were independent predictors of survival. Conclusions: Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID-19. Specifically, receiving tacrolimus could be beneficial for COVID-19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID-19 can be derived from our data.

Transplant Infectious Disease, May 10, 2016

Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flare... more Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients. In this prospective, observational study, we assessed outcomes of therapy with tenofovir (TDF), entecavir (ETV), and telbivudine (LdT) in 13 heart transplant recipients (HTR) with CHB. Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus (HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0-4). Glomerular filtration rate (GFR) was <50 mL/min in 7 patients (54%). Two patients were started on de novo ETV before transplant. Eleven previously treated patients were switched to TDF (n = 9) or LdT (n = 2). Median treatment duration was 33 months (range 1-71). HBV DNA remained suppressed in 6 patients and became undetectable in 5. Aminotransferases went down to the normal range in all patients, with a single flare in 1 patient. One patient lost hepatitis B surface antigen. No cases occurred of hepatic decompensation, hepatocellular carcinoma, or liver-related death. The GFR remained largely stable, and no cases of TDF-related hyper-phosphaturia were observed. This study indicates that newer antivirals are effective and safe in HTR with CHB.

Vascular Health and Risk Management, May 1, 2021

Despite the current reductionist approach providing an optimal indication for diagnosis and treat... more Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy ("epidrugs") is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF.

International Journal of Medical Informatics, Aug 1, 2023

Pharmacological Research, Oct 1, 2022

Journal of Cardiothoracic Surgery, Oct 29, 2022

Big Data, and the derived analysis techniques, such as artificial intelligence and machine learni... more Big Data, and the derived analysis techniques, such as artificial intelligence and machine learning, have been considered a revolution in the modern practice of medicine. Big Data comes from multiple sources, encompassing electronic health records, clinical studies, imaging data, registries, administrative databases, patient-reported outcomes and OMICS profiles. The main objective of such analyses is to unveil hidden associations and patterns. In cardiac surgery, the main targets for the use of Big Data are the construction of predictive models to recognize patterns or associations better representing the individual risk or prognosis compared to classical surgical risk scores. The results of these studies contributed to kindle the interest for personalized medicine and contributed to recognize the limitations of randomized controlled trials in representing the real world. However, the main sources of evidence for guidelines and recommendations remain RCTs and meta-analysis. The extent of the revolution of Big Data and new analytical models in cardiac surgery is yet to be determined.

Tumori Journal, Jun 1, 1989

European Journal of Internal Medicine, May 1, 2008

To evaluate the clinical characteristics and outcomes of in-hospital adult patients who had cardi... more To evaluate the clinical characteristics and outcomes of in-hospital adult patients who had cardiopulmonary arrest and received cardiopulmonary resuscitation (CPR). Methods: Retrospective, observational study of 133 consecutive patients, experiencing 143 episodes of in-hospital cardiopulmonary arrest over a 24month period. Primary end-points include return of spontaneous circulation (ROSC), survival to hospital discharge, 30-day survival and 1-year survival. Results: 133 patients with a mean age 70 (range 24-92) years; female: male 72 (54%): 61 (46%). 133 (93%) episodes were cardiopulmonary arrests whereas 10 (7%) were primary respiratory arrests. 98 episodes were witnessed, 27 unwitnessed and no record was available for 18 episodes. On initial assessment, majority (73%) of the patients had non-shockable rhythm. The mean number of CPR cycles were 3 (median 3, range 1-12). 65 (45%) patients were intubated during CPR. 49 (34%) patients received defibrillation, 112 (78%) had adrenaline, 80 (60%) had atropine, 13 (9%) had amiodarone and 1 received sodium bicarbonate. 14 patients underwent postmortem following failed CPR. 53 (37%) patients were successfully resuscitated, of which 27 (51%) were discharged from the hospital. 30-day survival following cardiopulmonary resuscitation was 20% and 1-year survival was 13%. It was noted that in patients with primary respiratory arrest, successful resuscitation was achieved in 90% cases, and 1-year survival was 60%. Conclusions: Inspite of effective advanced life support training and early identification of critically ill patients, the overall outcome following in-hospital cardiorespiratory arrest remains poor

Tumori Journal, Jun 1, 1989

DBA/2N is a genetically non responsive inbred strain of mice in which administration of polycycli... more DBA/2N is a genetically non responsive inbred strain of mice in which administration of polycyclic aromatic hydrocarbons (PAHs) does not induce microsomal monooxygenase activity. DBA/2N mouse liver cytosol contains a polycyclic aromatic hydrocarbon-binding protein that sediments, in a sucrose gradient, at 4S (« 4S » PAH-BP). Its binding kinetic and physicochemical properties indicate that this protein is practically indistinguishable from the « 4S " PAH-BP identified and characterized in liver cytosol of rats and other PAH responsive rodents including C57 B1/6J mice. « 4S » PAH-BP was purified to homogeneity from DBA/2N mouse liver by ammonium sulfate fractionation of the cytosol, followed by Sephadex G-200

Internal and Emergency Medicine, Apr 4, 2018

Background: Multiple hormonal deficiency syndrome (MHDS) is common in heart failure (HF). To date... more Background: Multiple hormonal deficiency syndrome (MHDS) is common in heart failure (HF). To date, no large observational study has unequivocally demonstrated that MHDS impacts on HF progression. Aim of the T.O.S.CA. Registry (NCT02335801) was to test whether MHDS affects morbidity and mortality in a large cohort of HF patients. Methods: The T.O.S.CA. Registry is a prospective, observational study involving 19 Italian centers. Thyroid hormones, insulin-like growth factor-1, testosterone, dehydropianoandrosterone, and insulin were measured at baseline and every year for a patient-average follow-up of 3 years. MHDS was defined as the presence of 2 or more hormonal deficiency (HD). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Results: A total of 526 consecutive patients was enrolled with a median follow-up of 36 months. MHDS was diagnosed in 405 patients (75%). A total of 276 events (98 death and 176 cardiovascular hospitalizations) were recorded; respectively 42.7% in MHDS-and 62.2 % in MHDS (p:0.001). MHDS was independently associated with the occurrence of the primary endpoint [HR 95% (CI), p-value: 1.58 (1.16-2.15), p:0.001] (Panel A). Further, MHDS identified a group of patients with higher mortality (χ2=9.2, p=0.03). Moreover a graded relation between HD and cumulative events were found (p:0.01) (Panel B). Conclusion: MHDS is a common finding in CHF and is independently associated with increased all-cause mortality and CV hospitalization.

Circulation, Nov 22, 2011

Journal of Clinical Virology, Nov 1, 2017

Background: Occult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,ab... more Background: Occult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,absence of serum HBsAg, low/undetectable serum HBVDNA. Reactivation of HBV infection may occur during immunosuppression, but few data are available in heart transplant. Objectives: We followed-up heart recipients with or without markers of previous HBV infection,evaluating prevalence of HBV markers, incidence of HBV reactivation and its virological and clinical features. Study design: Heart failure patients listed for heart transplant (2007-2013) were screened for current or past HBV infection. Transplanted patients with past HBV infection (anti-HBc+/ ± anti-HBs+/HBVDNA−) were followed up as cases, and an equal number of HBV negative patients as controls. Virological reactivation was detected by standard real-time and home-made highly sensitive PCR (surface/core HBVDNA regions). Clinical status and progression were assessed by liver histology, ultrasound or elastography. Results: 67 patients underwent heart transplant, including 4 (5.9%) HBsAg+ subjects. Cases were 11/67 (16.4%). During a median follow-up of 30 months, only one of these 11 patients presented viral reactivation (HBVDNA 209 IU/mL) at month 22, and started antiviral treatment. Four other recipients showed virological events of uncertain significance (sensitive PCR-only intermittently positive). Clinical signs of liver disease were observed in only one case at the last follow-up. A nonsignificant difference in survival was observed between cases and all other heart recipients without prior HBV contact (death rate 5/11 vs 15/52, respectively; p = 0.097). Conclusions: HBV genotypic reactivation in HBsAg−/anti-HBc+/HBVDNA− heart recipients is uncommon. Virological events of uncertain significance occur more frequently; their clinical impact seems to be negligible.