Publications by authors named "Carlo Torti"

186 Publications

Therapy with RAS inhibitors during the COVID-19 pandemic.

J Cardiovasc Med (Hagerstown) 2021 05;22(5):329-334

Division of Cardiology, University Magna Graecia, Catanzaro.

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus first identified in Wuhan, China. The global number of confirmed cases of COVID-19 has surpassed 28,285,700 with mortality that appears higher than for seasonal influenza. About 20% of COVID-19 patients have experienced cardiac involvement and myocardial infarction in patients infected with SARS-CoV-2 had a worse prognosis. Furthermore, the widespread use of antiviral drugs can be linked to a worsening of heart function. Arrhythmias and hypertension have also been reported in patients with Covid-19. On the other hand, previous cardiac diseases are present in 30% of patients infected with SARS-CoV-2. There is uncertainty in the use of ace inhibitors and angiotensin II (Ang II) antagonists in the COVID-19 era. The mechanism of action of SARS-CoV-2 has been elucidated. It has been demonstrated that angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the new coronavirus SARS-CoV-2 and it is required for host cell entry and subsequent viral replication. The effect of the SARS-CoV-2 infection is the downregulation of ACE2 that may contribute to the severity of lung pathologies as well as the cardiac function. ACE2, a homolog of ACE, is a monocarboxypeptidase that converts Ang II into angiotensin 1-7 (Ang 1-7) that with its vasodilatory, antifibrotic, antihypertrophic effects counterbalances the negative effects of Ang II. On the other hand, angiotensin-converting enzyme inhibitors (ACEi) and AT1R blockers have been shown to upregulate the expression of ACE2. Based on the mechanism of action of SARS-CoV-2, the use of renin angiotensin system (RAS) inhibitors was questioned although all scientific societies did not recommend discontinuation when clinically recommended. The BRACE CORONA, a phase 4, randomized study tested two strategies: temporarily stopping the ACE inhibitor/angiotensin receptor blockers (ARB) for 30 days versus continuing ACE inhibitors/ARBs in patients who were taking these medications chronically and were hospitalized with a confirmed diagnosis of COVID-19 was also discussed. Therefore, the goal of this review is to summarize recent laboratory and clinical investigations concerning the use of ACEi and ARBs during the COVID-19 pandemic. The available data, based also on a randomized trial, suggest that ACEIs or ARBs, when clinically indicated, should be regularly used in the COVID-19 era.
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http://dx.doi.org/10.2459/JCM.0000000000001160DOI Listing
May 2021

What Every Reader Should Know About Studies Using Electronic Health Record Data but May Be Afraid to Ask.

J Med Internet Res 2021 03 2;23(3):e22219. Epub 2021 Mar 2.

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Coincident with the tsunami of COVID-19-related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field.
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http://dx.doi.org/10.2196/22219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927948PMC
March 2021

Combined lymphocyte/monocyte count, D-dimer and iron status predict COVID-19 course and outcome in a long-term care facility.

J Transl Med 2021 02 17;19(1):79. Epub 2021 Feb 17.

Center of Interdepartmental Services (CIS), "Magna Graecia" University of Catanzaro, Catanzaro, Italy.

Background: The Sars-CoV-2 can cause severe pneumonia with multiorgan disease; thus, the identification of clinical and laboratory predictors of the progression towards severe and fatal forms of this illness is needed. Here, we retrospectively evaluated and integrated laboratory parameters of 45 elderly subjects from a long-term care facility with Sars-CoV-2 outbreak and spread, to identify potential common patterns of systemic response able to better stratify patients' clinical course and outcome.

Methods: Baseline white blood cells, granulocytes', lymphocytes', and platelets' counts, hemoglobin, total iron, ferritin, D-dimer, and interleukin-6 concentration were used to generate a principal component analysis. Statistical analysis was performed by using R statistical package version 4.0.

Results: We identified 3 laboratory patterns of response, renamed as low-risk, intermediate-risk, and high-risk, strongly associated with patients' survival (p < 0.01). D-dimer, iron status, lymphocyte/monocyte count represented the main markers discriminating high- and low-risk groups. Patients belonging to the high-risk group presented a significantly longer time to ferritin decrease (p: 0.047). Iron-to-ferritin-ratio (IFR) significantly segregated recovered and dead patients in the intermediate-risk group (p: 0.012).

Conclusions: Our data suggest that a combination of few laboratory parameters, i.e. iron status, D-dimer and lymphocyte/monocyte count at admission and during the hospital stay, can predict clinical progression in COVID-19.
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http://dx.doi.org/10.1186/s12967-021-02744-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887565PMC
February 2021

International Comparisons of Harmonized Laboratory Value Trajectories to Predict Severe COVID-19: Leveraging the 4CE Collaborative Across 342 Hospitals and 6 Countries: A Retrospective Cohort Study.

medRxiv 2021 Feb 5. Epub 2021 Feb 5.

Beth Israel Deaconess Medical Center, Surgery.

Objectives: To perform an international comparison of the trajectory of laboratory values among hospitalized patients with COVID-19 who develop severe disease and identify optimal timing of laboratory value collection to predict severity across hospitals and regions.

Design: Retrospective cohort study.

Setting: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), an international multi-site data-sharing collaborative of 342 hospitals in the US and in Europe.

Participants: Patients hospitalized with COVID-19, admitted before or after PCR-confirmed result for SARS-CoV-2. Primary and secondary outcome measures: Patients were categorized as ″ever-severe″ or ″never-severe″ using the validated 4CE severity criteria. Eighteen laboratory tests associated with poor COVID-19-related outcomes were evaluated for predictive accuracy by area under the curve (AUC), compared between the severity categories. Subgroup analysis was performed to validate a subset of laboratory values as predictive of severity against a published algorithm. A subset of laboratory values (CRP, albumin, LDH, neutrophil count, D-dimer, and procalcitonin) was compared between North American and European sites for severity prediction.

Results: Of 36,447 patients with COVID-19, 19,953 (43.7%) were categorized as ever-severe. Most patients (78.7%) were 50 years of age or older and male (60.5%). Longitudinal trajectories of CRP, albumin, LDH, neutrophil count, D-dimer, and procalcitonin showed association with disease severity. Significant differences of laboratory values at admission were found between the two groups. With the exception of D-dimer, predictive discrimination of laboratory values did not improve after admission. Sub-group analysis using age, D-dimer, CRP, and lymphocyte count as predictive of severity at admission showed similar discrimination to a published algorithm (AUC=0.88 and 0.91, respectively). Both models deteriorated in predictive accuracy as the disease progressed. On average, no difference in severity prediction was found between North American and European sites.

Conclusions: Laboratory test values at admission can be used to predict severity in patients with COVID-19. Prediction models show consistency across international sites highlighting the potential generalizability of these models.
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http://dx.doi.org/10.1101/2020.12.16.20247684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872369PMC
February 2021

Analysis of the persistence time of the SARS-CoV-2 virus in the cadaver and the risk of passing infection to autopsy staff.

Med Leg J 2021 Mar 21;89(1):40-53. Epub 2021 Jan 21.

Clinical Microbiology Unit, Department of Health Sciences, University "Magna Graecia" of Catanzaro, Italy.

The activity of the SARS-CoV-2 virus has not yet been studied in a post-mortem setting. The absence of these data has led to the prohibition of exposure of infected corpses during burial procedures. Our aim was to assess the virus's persistence and the possibility of transmission in the post-mortem phase including autopsy staff. The sample group included 29 patients who were admitted to our Covid-19 Centre who died during hospitalisation and the autopsy staff. All the swabs were subjected to a one-step real-time reverse transcription polymerase chain reaction with cycle threshold (Ct) values. Swab collection was performed at 2 h, 4 h, 6 h, 12 h, over 24 since death. The following were the analysis of patients' swabs: 10 cases were positive 2 h after death; 10 cases positive 4 h after death; 9 cases were found positive 6 h after death; 7 cases positive 12 h after death; 9 cases remained positive 24 h after death. The swabs performed on all the forensic pathologist staff on duty who performed the autopsies were negative. The choice to avoid rituals and the display of corpses before and at the burial procedures given appears cautiously valid due to the persistence of the SARS-CoV-2 virus in the post-mortem period. Although the caution in choosing whether or not to perform an autopsy on infected corpses is acceptable, not to perform autopsies is not biologically supported.
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http://dx.doi.org/10.1177/0025817220980601DOI Listing
March 2021

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

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

Thromb Haemost 2021 Jan 7. Epub 2021 Jan 7.

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

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

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

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

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

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

Late-onset myocardial infarction and autoimmune haemolytic anaemia in a COVID-19 patient without respiratory symptoms, concomitant with a paradoxical increase in inflammatory markers: a case report.

J Med Case Rep 2020 Dec 18;14(1):246. Epub 2020 Dec 18.

Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy.

Background: In December 2019, a new coronavirus (named severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) spread from China, causing a pandemic in a very short time. The main clinical presentation of SARS-CoV-2 infection (COVID-19, coronavirus disease-2019) is pneumonia, but several cardiovascular complications may also occur (e.g., acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure and cardiogenic shock). Direct or indirect mechanisms induced by SARS-CoV-2 could be implicated in the pathogenesis of these events.

Case Presentation: We report herein the third case of COVID-19 autoimmune haemolytic anaemia (AIHA) reported so far, which occurredwithout any other possible explanations in a Caucasian patient. The patient also suffered from ST-elevation myocardial injury.

Conclusions: Both complications occurred quite late after COVID-19 diagnosis and were probably precipitated by systemic inflammation, as indicated by a significant delayed increase in inflammatory markers, including interleukin-6 (IL-6).
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http://dx.doi.org/10.1186/s13256-020-02595-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746982PMC
December 2020

Clinical characteristics and predictors of mortality associated with COVID-19 in elderly patients from a long-term care facility.

Sci Rep 2020 11 30;10(1):20834. Epub 2020 Nov 30.

Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy.

Since December 2019, coronavirus disease 2019 (COVID-19) pandemic has spread from China all over the world and many COVID-19 outbreaks have been reported in long-term care facilities (LCTF). However, data on clinical characteristics and prognostic factors in such settings are scarce. We conducted a retrospective, observational cohort study to assess clinical characteristics and baseline predictors of mortality of COVID-19 patients hospitalized after an outbreak of SARS-CoV-2 infection in a LTCF. A total of 50 patients were included. Mean age was 80 years (SD, 12 years), and 24/50 (57.1%) patients were males. The overall in-hospital mortality rate was 32%. At Cox regression analysis, significant predictors of in-hospital mortality were: hypernatremia (HR 9.12), lymphocyte count < 1000 cells/µL (HR 7.45), cardiovascular diseases other than hypertension (HR 6.41), and higher levels of serum interleukin-6 (IL-6, pg/mL) (HR 1.005). Our study shows a high in-hospital mortality rate in a cohort of elderly patients with COVID-19 and hypernatremia, lymphopenia, CVD other than hypertension, and higher IL-6 serum levels were identified as independent predictors of in-hospital mortality. Given the small population size as major limitation of our study, further investigations are necessary to better understand and confirm our findings in elderly patients.
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http://dx.doi.org/10.1038/s41598-020-77641-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705720PMC
November 2020

Oxygen therapy via high flow nasal cannula in severe respiratory failure caused by Sars-Cov-2 infection: a real-life observational study.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620963016

Department of Health Sciences, 'Magna Graecia' University of Catanzaro, Catanzaro, Italy.

The worldwide spread of coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020. According to clinical studies carried out in China and Italy, most patients experience mild or moderate symptoms; about a fifth of subjects develop a severe and critical disease, and may suffer from interstitial pneumonia, possibly associated with acute respiratory distress syndrome (ARDS) and death.In patients who develop respiratory failure, timely conventional oxygen therapy through nasal catheter plays a crucial role, but it can be used only in mild forms. Continuous positive airway pressure (CPAP) support or non-invasive mechanical ventilation (NIV) are uncomfortable, and require significant man-machine cooperation. Herein we describe our experience of five patients with COVID-19, who were treated with high-flow nasal cannula (HFNC) after failure of CPAP or NIV, and discuss the role of HFNC in COVID-19 patients. Our findings suggest that HFNC can be used successfully in selected patients with COVID-19-related ARDS..
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http://dx.doi.org/10.1177/1753466620963016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580191PMC
October 2020

Evidence of Low Prevalence of Cystic Echinococcosis in the Catanzaro Province, Calabria Region, Italy.

Am J Trop Med Hyg 2020 11;103(5):1951-1954

Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University, Catanzaro, Italy.

Cystic echinococcosis (CE) is one of the neglected tropical diseases recognized by the WHO. affects more than 1 million people worldwide and is responsible for high costs in the healthcare system. A clear knowledge of the prevalence of CE and its clinical characteristics could have an important impact on the approach to its diagnosis and to the public health planning of treatment and control interventions. We performed a prevalence study in four municipalities of Catanzaro Province, South Italy. This area is considered to be at high risk of CE because of ovine breeding. We screened by abdominal ultrasound 2,426 volunteers, four of whom had abdominal CE. Given the need for prevention and control programs for CE in endemic areas of Italy, a detailed mapping of prevalence of CE, to complement data obtained through hospital discharge records, appears imperative.
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http://dx.doi.org/10.4269/ajtmh.20-0119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646790PMC
November 2020

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

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

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

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

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

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

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

Spontaneous and Severe Haematomas in Patients with COVID-19 on Low- Molecular-Weight Heparin for Paroxysmal Atrial Fibrillation.

Mediterr J Hematol Infect Dis 2020 1;12(1):e2020054. Epub 2020 Jul 1.

Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Catanzaro, Italy.

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http://dx.doi.org/10.4084/MJHID.2020.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340243PMC
July 2020

Histopathological findings in a COVID-19 patient affected by ischemic gangrenous cholecystitis.

World J Emerg Surg 2020 07 2;15(1):43. Epub 2020 Jul 2.

Digestive Surgery Unit, Department of Science of Health, "Magna Graecia" University, Catanzaro, Italy.

Background: Since its first documentation, a novel coronavirus (SARS-CoV-2) infection has emerged worldwide, with the consequent declaration of a pandemic disease (COVID-19). Severe forms of acute respiratory failure can develop. In addition, SARS-CoV-2 may affect organs other than the lung, such as the liver, with frequent onset of late cholestasis. We here report the histological findings of a COVID-19 patient, affected by a tardive complication of acute ischemic and gangrenous cholecystitis with a perforated and relaxed gallbladder needing urgent surgery.

Case Presentation: A 59-year-old Caucasian male, affected by acute respiratory failure secondary to SARS-CoV-2 infection was admitted to our intensive care unit (ICU). Due to the severity of the disease, invasive mechanical ventilation was instituted and SARS-CoV-2 treatment (azithromycin 250 mg once-daily and hydroxychloroquine 200 mg trice-daily) started. Enoxaparin 8000 IU twice-daily was also administered subcutaneously. At day 8 of ICU admission, the clinical condition improved and patient was extubated. At day 32, patient revealed abdominal pain without signs of peritonism at examination, with increased inflammatory and cholestasis indexes at blood tests. At a first abdominal CT scan, perihepatic effusion and a relaxed gallbladder with dense content were detected. The surgeon decided to wait and see the evolution of clinical conditions. The day after, conditions further worsened and a laparotomic cholecystectomy was performed. A relaxed and perforated ischemic gangrenous gallbladder, with a local tissue inflammation and perihepatic fluid, was intraoperatively met. The gallbladder and a sample of omentum, adherent to the gallbladder, were also sent for histological examination. Hematoxylin-eosin-stained slides display inflammatory infiltration and endoluminal obliteration of vessels, with wall breakthrough, hemorrhagic infarction, and nerve hypertrophy of the gallbladder. The mucosa of the gallbladder appears also atrophic. Omentum vessels also appear largely thrombosed. Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels. All these findings define a histological diagnosis of vasculitis of the gallbladder.

Conclusions: Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19, and it is characterized by a dysregulated host inflammatory response and thrombosis of medium-size vessels.
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http://dx.doi.org/10.1186/s13017-020-00320-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330255PMC
July 2020

Potential implications of SARS-CoV-2 epidemic in Africa: where are we going from now?

BMC Infect Dis 2020 Jun 15;20(1):412. Epub 2020 Jun 15.

Department of Infectious Diseases, Kiruddu National Referral Hospital, Kampala, Uganda.

The SARS-CoV-2, which emerged from East Asia in December 2019, has rapidly evolved into a global pandemic infecting close to 7 million people. The current uncertainties regarding its impact on Africa calls for critical monitoring of the evolution of the pandemic and correlation of factors that influence the burden of the disease. We herein discuss possible implications of SARS-CoV-2 on the African continent.
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http://dx.doi.org/10.1186/s12879-020-05147-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293889PMC
June 2020

Listeria infection after treatment with alemtuzumab: a case report and literature review. Would antibiotic prophylaxis be considered?

Infez Med 2020 Jun;28(2):258-262

Department of Medical and Surgical Sciences, Infectious and Tropical Diseases Unit, "Magna Graecia" University, Catanzaro, Italy.

Few cases of complicated infections with Listeria monocytogenes (LM) have been reported to date in patients with multiple sclerosis (MS) treated with alemtuzumab. Primary prevention strategies may be suggested in such patients to avoid infections. However, these may be ineffective because patients may already be carriers of LM. We report herein a case of bloodstream infection due to LM in a 25-year-old woman with MS treated with alemtuzumab. We searched the UMC/WHO Vigibase system for all reported cases of LM in patients treated with alemtuzumab and found 29 cases overall up to 21 July 2019. We also performed a literature review of MS cases with LM on alemtuzumab, in order to evaluate epidemiology, clinical characteristics, and outcome of this complication. Since the published cases (N=8) were mainly reported in recent years but more cases were found in the UMC/WHO Vigibase system (although not necessarily in patients with MS), we hypothesize that this complication is more frequent than currently believed and may become even more important in the future. Therefore, it is worth reaching a consensus on appropriate algorithms to stratify individuals by risk so as to implement targeted prevention strategies (whether primary or secondary).
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June 2020

Risk factors for hepatitis B and C among healthy population: a community-based survey from four districts of Southern Italy.

Infez Med 2020 Jun;28(2):223-226

Department of Medical and Surgical Sciences, Infectious and Tropical Diseases Unit, "Magna Graecia" University, Catanzaro, Italy.

In Southern Italy, viral hepatitis B and C still represent an important public health problem, with a serious social impact, and significant economic consequences. The objective of our community-based study was to assess the prevalence of risk factors and access to the test for viral hepatitis to get information for guiding prevention and screening strategies in our setting. The study was conducted among population of four selected districts in Southern Italy during May 2019. An anonymous structured questionnaire consisting of multiple-choice questions was administered by trained research assistants in order to assess any possible risk factor for HCV or HBV acquisition, and if any screening was previously performed. Six-hundred participants were included: 367 (61.2%) were females, with a mean age of 51 years (standard deviation, SD: 18 years). The three most frequent risk factors were: dental treatments in 425/600=70.8% (of whom 76/425=17.8% were previously tested), unprotected sexual intercourses in 340/600=56.6% (of whom 54/340=15.8% were previously tested), and injections with glass syringes in 162/600=27% (of whom 32/162=19.7% were previously tested). Only 47/502 (9.3%) patients who were never been tested, did not report any risk factors for HCV or HBV acquisition, while 433 (86.2%) reported at least one risk factor, 293 (58.3%) at least two, 97 (19.3%) at least three, 16 (3.1%) at least four, and 2 reported to have at least five risk factors for HBV/HCV acquisition.
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June 2020

Is There Any Opportunity to Provide an HBV Vaccine Booster Dose Before Anti-Hbs Titer Vanishes?

Vaccines (Basel) 2020 May 16;8(2). Epub 2020 May 16.

Department of Health Sciences, University of Catanzaro "Magna Græcia", Campus Universitario "Salvatore Venuta", Viale Europa, 88100 Catanzaro, Italy.

Whether the primary Hepatitis B vaccination confers lifelong protection is debated. The aim of the study was to assess the effectiveness of booster doses in mounting a protective HBV immune response in subjects vaccinated 18-20 years earlier. The study population consisted of vaccinated students attending medical and healthcare professions schools. A booster dose was offered to subjects with a <10 mIU/mL anti-HBs titer. The post-booster anti-HBs titer was evaluated after four weeks. The subjects with a <10 mIU/mL post-booster anti-HBs titer, received a second and third dose of the vaccine and after one month they were retested. A <10 mIU/mL anti-HBs titer was found in 35.1% of the participants and 92.2% of subjects that were boosted had a ≥10 mIU/mL post-booster anti-HBs titer, whereas 7.8% did not mount an anamnestic response. A low post-booster response (10-100 mIU/mL anti-HBs) was significantly more likely in subjects with a <2.00 mIU/mL pre-booster titer compared to those with a 2.00-9.99 mIU/mL pre-booster titer. The anamnestic response was significantly related to the baseline anti-HBs levels. A booster dose of the HBV vaccine may be insufficient to induce an immunological response in subjects with undetectable anti-HBs titers. A booster dose might be implemented when an anamnestic response is still present.
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http://dx.doi.org/10.3390/vaccines8020227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349749PMC
May 2020

Use of subcutaneous tocilizumab in patients with COVID-19 pneumonia.

J Med Virol 2021 01 30;93(1):32-34. Epub 2020 Sep 30.

Department of Medical and Surgical Sciences, Infectious and Tropical Disease Unit, "Magna Graecia" University of Catanzaro, Catanzaro, Italy.

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http://dx.doi.org/10.1002/jmv.26016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272953PMC
January 2021

Enhanced Immunological Recovery With Early Start of Antiretroviral Therapy During Acute or Early HIV Infection-Results of Italian Network of ACuTe HIV InfectiON (INACTION) Retrospective Study.

Pathog Immun 2020 24;5(1):8-33. Epub 2020 Feb 24.

Infectious Diseases Unit; Department of Internal Medicine; IRCCS Ca' Granda Foundation Maggiore Hospital; Milan, Italy.

Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation.

Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers.

Methods: This was an observational, retrospective, and multicenter study. We investigated the effect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virological suppression, optimal immunological recovery (defined as CD4 count ≥500/µL, CD4 ≥30%, and CD4/CD8 ≥1), and first-line ART regimen discontinuation by Cox regression analysis.

Results: There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log copies/mL and the median CD4 count was 456 cells/µL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associated with a shorter time to virological suppression. Early ART emerged as an independent predictor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percentage count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs.

Conclusions: In a large cohort of well-characterized patients with AEHI, we confirmed the beneficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunological markers associated with virological control.
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http://dx.doi.org/10.20411/pai.v5i1.341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104556PMC
February 2020

Virological and Clinical Outcome of DAA Containing Regimens in a Cohort of Patients in Calabria Region (Southern Italy).

Medicina (Kaunas) 2020 Feb 28;56(3). Epub 2020 Feb 28.

Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, 88100 Catanzaro, Italy.

In Italy, Hepatitis C Virus (HCV) infections are most prevalent in people older than 50 years of age, who often experience multi-morbidities, take co-medications, and have a long history of liver disease. These characteristics could potentially affect tolerability of HCV treatments and adherence in this subgroup. After achievement of sustained virological response (SVR), retention into care is very important both to detect the onset of possible complications and prevent further infections. In this study, SVR rates and retention into care of patients treated with directly acting antivirals (DAAs) of a single-center cohort in Southern Italy were evaluated. Patients treated with directly acting antivirals from 2014 to 2018 were included. Patients were stratified by age (i.e., <65 vs. ≥65 years) and by cirrhosis presence (i.e., liver stiffness >14.6 KPa or clinical/ultrasound cirrhosis vs. absence of these criteria). Primary outcome was availability of SVR at Weeks 12-24 after the end of treatment. Inter- and intra-group comparisons were performed along the follow-up for significant laboratory parameters. In total, 212 patients were treated; 184 (87%) obtained SVR after the first treatment course and 4 patients after retreatment. Twenty-two (10.4%) patients were lost to follow-up before assessment of SVR, and two patients died before the end of treatment for liver decompensation. Considering only the first treatment episode, per protocol analysis (i.e., excluding patients lost to follow-up) showed the following rates of SVR: 97% (overall), 97% (older age group), 96% (age group <65 years), 94% (cirrhotics), and 100% (non-cirrhotics). By contrast, at the intention to treat analysis (i.e., patients lost were computed as failures), SVR percentages were significantly lower for patients <65 years of age (80%) and for non-cirrhotics (85%). High rates of SVR were obtained. However, younger patients and those without cirrhosis displayed an apparent high risk of being lost to follow-up. This may have important implications: since those who are lost may transmit HCV in case SVR is not achieved, these subpopulations should receive appropriate counselling during treatment.
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http://dx.doi.org/10.3390/medicina56030101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142984PMC
February 2020

Identification of pmrB mutations as putative mechanism for colistin resistance in A. baumannii strains isolated after in vivo colistin exposure.

Microb Pathog 2020 Feb 11;142:104058. Epub 2020 Feb 11.

Department of Health Sciences, Unit of Clinical Microbiology, "Magna Graecia" University, 88100, Catanzaro, Italy.

Colistin resistance among extensively-resistant Acinetobacter baumannii isolates is a serious health-care problem. Alterations in PmrA-PmrB two-component system have been associated with resistance to colistin. We investigated three pairs of colistin-susceptible and colistin-resistant A. baumannii, sequentially isolated from three patients before and after colistin treatment, respectively. The pmrA and pmrB genes were sequenced by Sanger method. Amino acidic positions and their effect on protein were predicted by InterPro and PROVEAN tools. Expression of pmrA, pmrB and pmrC genes was assessed by semi-quantitative reverse transcription-PCR (qRT-PCR). We found three different nonsynonymous substitutions P233T, E301G and L168K in pmrB coding region, each one in a different colistin resistance strain. The E301G and L168K substitutions represent novel mutations in pmrB, not previously described. Relative expression of pmrA, pmrB and pmrC mRNA increased in all colistin resistant strains. In our study, pmrB substitutions were associated with pmrC over-expression and colistin resistance. Further studies are necessary to understand their impact on modification of lipid A components.
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http://dx.doi.org/10.1016/j.micpath.2020.104058DOI Listing
February 2020

Ceftolozane/tazobactam for difficult-to-treat Pseudomonas aeruginosa infections: A systematic review of its efficacy and safety for off-label indications.

Int J Antimicrob Agents 2020 Mar 8;55(3):105891. Epub 2020 Jan 8.

Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples 'Federico II', via Sergio Pansini, 5, I-80131 Naples, Italy.

Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor combination targeting Enterobacteriaceae and Pseudomonas aeruginosa (PA). It is approved in adult patients for complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) as well as for nosocomial pneumonia. It displays excellent activity against PA, even multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The aim of this systematic review (PROSPERO protocol no. CRD42019117350) was to summarise the available evidence from observational studies regarding the efficacy and safety of off-label use of C/T when administered to treat MDR- or XDR-PA infections. The MEDLINE and Embase databases were screened from inception up to 30 June 2019. Studies were deemed eligible if they described real-life use of C/T in the case of MDR- or XDR-PA infections for non-approved indications. Exclusion criteria were cIAIs, cUTIs, pneumonia (unless occurring in a paediatric population) and infections by non-MDR/XDR-PA. Thirty articles fulfilled the inclusion criteria. In total, 130 cases of MDR- or XDR-PA infections treated with C/T in 128 patients were described. The most relevant off-label uses were skin and soft-tissue infection (49/30; 37.7%), bone and joint infection (42/130; 32.3%) and bloodstream infection (23/130; 17.7%). Five cases involved paediatric patients. The overall clinical success rate was 76.2%. The most common adverse event was hypokalaemia (4.2%, in 48 evaluable cases). C/T may be a useful therapeutic option for difficult-to-treat infections by PA even outside the framework of approved indications. Further studies are necessary to better define new indications for the drug.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.105891DOI Listing
March 2020

Severe myocarditis due to influenza A(H1N1)pdm09 viral infection in a young woman successfully treated with intravenous zanamivir: A case report.

Clin Case Rep 2019 Dec 21;7(12):2336-2340. Epub 2019 Oct 21.

Department of Medical and Surgical Sciences Unit of Intensive Care, "Magna Graecia" University Catanzaro Italy.

In patients with influenza-related myocarditis, prompt diagnosis and treatment are important. Intravenous zanamivir can be an alternative to oral oseltamivir, especially in severe cases and when drug intestinal malabsorption is suspected or proven.
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http://dx.doi.org/10.1002/ccr3.2499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935647PMC
December 2019

Clinical outcomes of patients treated with intravenous zanamivir for severe influenza A(H1N1)pdm09 infection: a case report series.

BMC Infect Dis 2019 Oct 16;19(1):858. Epub 2019 Oct 16.

Department of Medical and Surgical Sciences, Unit of Intensive Care, "Magna Graecia" University, Catanzaro, Italy.

Background: Intravenous (IV) zanamivir could be a suitable alternative for the treatment of severe influenza A(H1N1)pdm09 infection in patients who are unable to take oral or inhaled medication, for example, those on mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, data on the clinical outcomes of such patients is limited.

Case Presentation: We report the clinical outcomes of four patients who were admitted at the intensive care unit during the 2017-2018 influenza season with severe sepsis (SOFA score > 11) and acute respiratory distress syndrome requiring ECMO and mechanical ventilation. Two patients were immune-compromised. The A(H1N1)pdm09 genome was confirmed by polymerase chain reaction (PCR) on nasopharyngeal specimen swabs prior to administration of IV zanamivir at a dose of 600 mg twice daily. Weekly qualitative PCR analysis was done to monitor viral clearance, with zanamivir treatment being discontinued upon receipt of negative results. In addition, the patients were managed for concomitant multidrug-resistant bacterial infections, with infection resolution confirmed with blood cultures. The median time for zanamivir treatment was 10 days (IQR 10-17). The clinical outcome was favourable with all four patients surviving and improving clinically. All four patients achieved viral clearance of A(H1N1)pdm09 genome, and resolution of multidrug-resistant bacterial infections.

Conclusions: IV zanamivir could be a good therapeutic option in patients with severe influenza A(H1N1)pdm09 infection who are unable to take oral or aerosolised antiviral medication. We recommend prospective randomized control trials to support this hypothesis.
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http://dx.doi.org/10.1186/s12879-019-4530-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796355PMC
October 2019

[Good practices for the surveillance and control of antimicrobial resistance].

Epidemiol Prev 2019 Mar-Jun;43(2-3):185-193

Dipartimento di scienze della sanità pubblica e pediatriche, Università di Torino.

Italy is one of the European Countries with the highest level of antimicrobial consumption, both in the community and in hospital settings, and with the highest prevalence of antimicrobial resistant microorganisms. In 2015, the Project "Good practices for the surveillance and control of antimicrobial resistance" was funded by the Italian National Centre for Disease Prevention and Control (CCM): the aim was to promote integrated actions at national level to control antimicrobial resistance, favouring the transfer of existing good practices. The principal objectives of the project were: to describe the Italian scenario of good practices based on literature review; to improve the capacity of surveillance, through achieving consensus on a core set of indicators, including paediatrics, and through the strengthening of the national surveillance system of antimicrobial resistance coordinated by the Italian National Institute of Health; to define tools useful for priority setting; to evaluate the efficacy of intervention programme aimed at promoting the appropriate use of antibiotics among children for upper respiratory tract infections in the community; to set up training programmes on the prudent use of antibiotics in veterinary medicine. Seven regions were enrolled in the project (Emilia-Romagna with the role of programme coordinator, Campania, Calabria, Lazio, Lombardy, Piedmont, Tuscany) and the Italian National Health Institute. The project allowed to document: the scarce spread of control practices at national level (out of 277 studies reviewed, only 6.1% of the cases were targeted to evaluating the effectiveness of intervention programmes); a significant variability among regions both in relation to antimicrobial consumption and antimicrobial resistance prevalence, with a worrying spread in some regions of several antimicrobial resistant organisms responsible for "critical" infections with great potential health impact; the effectiveness of an intervention aimed at promoting appropriate use of antibiotics in frequent infections for children in the community, such as pharingotonsillitis and acute otitis media (35% reduction of antimicrobial consumption between 2010 and 2017 in Emilia-Romagna; an inversion of the ratio amoxicillin/amoxicillin-clavulanate); the need for new indicators to monitor antimicrobial consumption in hospital paediatric wards and of a new national system for timely identification of new antimicrobial resistance profiles; a positive evaluation of the training programme for veterinary physicians. In conclusion, the project has contributed to identify the most critical areas for antimicrobial resistance control and to select appropriate solutions, potentially transferable to the national level.
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http://dx.doi.org/10.19191/EP19.2-3.P185.058DOI Listing
January 2020

Use of colistin in adult patients: A cross-sectional study.

J Glob Antimicrob Resist 2020 03 15;20:43-49. Epub 2019 Jun 15.

Department of Health Sciences, University of Genoa, Genoa, Italy; Ospedale Policlinico San Martino-IRCCS, Genoa, Italy.

Objectives: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB).

Methods: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed.

Results: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P =  0.024) was associated with use of colistin monotherapy.

Conclusion: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.
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http://dx.doi.org/10.1016/j.jgar.2019.06.009DOI Listing
March 2020

Clinical, Virological Characteristics, and Outcomes of Treatment with Sofosbuvir/Ledipasvir in Two Pediatric Patients Infected by HCV Genotype 4.

Cells 2019 05 5;8(5). Epub 2019 May 5.

Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University, 88100 Catanzaro, Italy.

Direct-acting antiviral drugs to cure infections with Hepatitis C virus (HCV) achieve a sustained virological response (SVR) in more than 90% of adult patients. At present, clinical trials are ongoing and real-life data are still limited in children. Herein, we report two cases of pediatric patients treated with fixed-dose combination of sofosbuvir/ledipasvir, already approved to treat HCV4 genotype. Both young girls achieved SVR even though HCV4 isolates carried L28M and M31L NS5A resistance-associated substitutions (RASs). Therefore, possible effects of these RASs merit further study, especially in children.
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http://dx.doi.org/10.3390/cells8050416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562692PMC
May 2019

Discussion on critical points for a tailored therapy to cure hepatitis C virus infection.

Clin Mol Hepatol 2019 03 23;25(1):30-36. Epub 2019 Jan 23.

Department of Health Sciences, Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, Magna Graecia University, Catanzaro, Italy.

Hepatitis C virus (HCV) infects around 71 million people worldwide and in 2018 it is still a major health problem. Since 2011, anti-HCV therapy with availability of direct-acting antiviral drugs has revolutionized the clinical response and paved the way to eradication strategies. However, despite the high rate of sustained virological response, treatment failure may occur in a limited percentage of patients, possibly due to resistance-associated substitutions (RASs), either emergent or pre-existent even in minority viral populations. Clearly this problem may impair success of eradication strategies. With this background, several questions marks still exist around HCV treatment, including whether pan-genotypic treatments with complete effectiveness in any clinical conditions really exist outside clinical trials, the actual cost-effectiveness of genotyping testing, and utility of RAS detection in viral quasispecies by next generation sequencing approach. In this review, we describe these critical points by discussing recent literature data and our research experience.
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http://dx.doi.org/10.3350/cmh.2018.0061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435970PMC
March 2019