Publications by authors named "Massimo Ciccozzi"

324 Publications

Viral community acquired pneumonia at the emergency department: Report from the pre COVID-19 age.

J Med Virol 2021 Mar 30. Epub 2021 Mar 30.

Department of Public Health and Infectious Diseases, University of Rome Sapienza, Rome, Italy.

The role of viruses in community acquired pneumonia (CAP) has been largely underestimated in the pre-coronavirus disease 2019 age. However, during flu seasonal early identification of viral infection in CAP is crucial to guide treatment and in-hospital management. Though recommended, the routine use of nasopharyngeal swab (NPS) to detect viral infection has been poorly scaled-up, especially in the emergency department (ED). This study sought to assess the prevalence and associated clinical outcomes of viral infections in patients with CAP during peak flu season. In this retrospective, observational study adults presenting at the ED of our hospital (Rome, Italy) with CAP from January 15th to February 22th, 2019 were enrolled. Each patient was tested on admission with Influenza rapid test and real time multiplex assay. Seventy five consecutive patients were enrolled. 30.7% (n = 23) tested positive for viral infection. Of these, 52.1% (n = 12) were H1N1/FluA. 10 patients had multiple virus co-infections. CAP with viral infection did not differ for any demographic, clinic and laboratory features by the exception of CCI and CURB-65. All intra-ED deaths and mechanical ventilations were recorded among CAP with viral infection. Testing only patients with CURB-65 score ≥2, 10 out of 12 cases of H1N1/FluA would have been detected saving up to 40% tests. Viral infection occurred in one-third of CAP during flu seasonal peak 2019. Since not otherwise distinguishable, NPS is so far the only reliable mean to identify CAP with viral infection. Testing only patients with moderate/severe CAP significantly minimize the number of tests.
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http://dx.doi.org/10.1002/jmv.26980DOI Listing
March 2021

Animal Hosts and Experimental Models of SARS-CoV-2 Infection.

Chemotherapy 2021 Mar 26:1-9. Epub 2021 Mar 26.

National HIV/AIDS Research Center, Istituto Superiore di Sanità, Rome, Italy.

Viruses arise through cross-species transmission and can cause potentially fatal diseases in humans. This is the case of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which recently appeared in Wuhan, China, and rapidly spread worldwide, causing the outbreak of coronavirus disease 2019 (COVID-19) and posing a global health emergency. Sequence analysis and epidemiological investigations suggest that the most likely original source of SARS-CoV-2 is a spillover from an animal reservoir, probably bats, that infected humans either directly or through intermediate animal hosts. The role of animals as reservoirs and natural hosts in SARS-CoV-2 has to be explored, and animal models for COVID-19 are needed as well to be evaluated for countermeasures against SARS-CoV-2 infection. Experimental cells, tissues, and animal models that are currently being used and developed in COVID-19 research will be presented.
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http://dx.doi.org/10.1159/000515341DOI Listing
March 2021

Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection.

Chemotherapy 2021 Mar 23:1-9. Epub 2021 Mar 23.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.
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http://dx.doi.org/10.1159/000515344DOI Listing
March 2021

SARS-CoV-2 Infection and the COVID-19 Pandemic Emergency: The Importance of Diagnostic Methods.

Chemotherapy 2021 Mar 19:1-7. Epub 2021 Mar 19.

Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.

Background: Currently, a pandemic of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is underway, resulting in high morbidity and mortality across the globe.

Summary: A prompt and effective diagnosis is crucial to identify infected individuals, to monitor the infection, to perform contact tracing, and to limit the spread of the virus. Since the announcement of this public health emergency, several diagnostic methods have been developed including molecular and serological assays, and more recently biosensors. Here, we present the use of these assays as well as their main technical features, advantages, and limits. Key Messages: The development of reliable diagnostic assays is crucial not only for a correct diagnosis and containment of COVID-19 pandemic, but also for the decision-making process that is behind the clinical decisions, eventually contributing to the improvement of patient management. Furthermore, with the advent of vaccine and therapeutic monoclonal antibodies against SARS-CoV-2, serological assays will be instrumental for the validation of these new therapeutic options.
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http://dx.doi.org/10.1159/000515343DOI Listing
March 2021

SARS-CoV-2 Lineages and Sub-Lineages Circulating Worldwide: A Dynamic Overview.

Chemotherapy 2021 Mar 18:1-5. Epub 2021 Mar 18.

Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil,

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China, in early December 2019 has rapidly widespread worldwide, becoming one of the major global public health issues of the last centuries. Key Messages: Over the course of the pandemic, due to the advanced whole-genome sequencing technologies, an unprecedented amount of genomes have been generated, providing invaluable insights into the ongoing evolution and epidemiology of the virus during the pandemic. Therefore, this large amount of data played an important role in the SARS-CoV-2 mitigation and control strategies. Key Messages: The active monitoring and characterization of the SARS-CoV-2 lineages circulating worldwide is useful for a more specific diagnosis, better care, and timely treatment. In this review, a concise characterization of all the lineages and sub-lineages circulating and co-circulating across the world has been presented in order to determine the magnitude of the SARS-CoV-2 threat and to better understand the virus genetic diversity and its dispersion dynamics.
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http://dx.doi.org/10.1159/000515340DOI Listing
March 2021

Analysis of Three Mutations in Italian Strains of SARS-CoV-2: Implications for Pathogenesis.

Chemotherapy 2021 Mar 18:1-5. Epub 2021 Mar 18.

Institute of Human Virology and Global Virus Network Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA,

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus initially detected in Wuhan in December 2019, responsible for coronavirus disease 2019 (COVID-19), a respiratory syndrome currently affecting >220 countries around the world, with >80 million cases registered and >1.8 million deaths.

Objective: As several vaccines are still being developed and 2 have been approved, it is particularly important to perform evolutionary surveillance to identify mutations potentially affecting vaccine efficacy.

Methods: DynaMut server has been used to evaluate the impact of the mutation found on SARS-CoV-2 isolates available on GISAID.

Results: In this article, we analyze whole genomes sequenced from Italian patients, and we report the characterization of 3 mutations, one of which presents in the spike protein.

Conclusion: The mutations analyzed in this article can be useful to evaluate the evolution of SARS-CoV-2.
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http://dx.doi.org/10.1159/000515342DOI Listing
March 2021

The Bayesian reconstruction and the evolutionary history of Salivirus type 1 and type 2: the worldwide spreading.

J Infect Dev Ctries 2021 Mar 7;15(2):280-288. Epub 2021 Mar 7.

Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Italy.

Introduction: Salivirus (SalV) represents an emerging problem in public health especially during the recent years. In this study, the Bayesian evolutionary history and the spread of the virus through the different countries have been reported.

Methodology: a database of 81 sequences of SalV structural VP1 fragment were downloaded from GenBank, aligned and manually edited by Bioedit Software. ModelTest v. 3.7 software was used to estimate the simplest evolutionary model fitting the sequence dataset. A Maximum-Likelihood tree has been generated using MEGA-X to test the "clockliness" signal using TempEst 1.5.1. The Bayesian phylogenetic tree was built by BEAST. Homology modelling was performed by SWISS-Model and protein variability evaluated by ConSurf server.

Results: the phylogenetic tree showed a clade of SalV A2 and three main clades of SalV A1, revealing several infections in humans in South Korea, India, Tunisia, China, Nigeria, Ethiopia and USA. The Bayesian maximum clade credibility tree and the time of the most common recent ancestor dated back the root of the tree to the year 1788 with the probable origin in USA. Selective pressure analysis revealed two positive selection sites, His at 100th and Leu at 116th positions that at the homology modelling resulted important to guarantee protein stability and variability. This could contribute to the development of new mutations modifying the clinical features of this evolving virus.

Conclusions: Bayesian phylogenetic and phylodynamic represented a useful tool to follow the transmission dynamic of SalV and to prevent new epidemics worldwide.
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http://dx.doi.org/10.3855/jidc.12141DOI Listing
March 2021

Time and Mode of Epidemic HCV-2 Subtypes Spreading in Europe: Phylodynamics in Italy and Albania.

Diagnostics (Basel) 2021 Feb 17;11(2). Epub 2021 Feb 17.

Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157 Milan, Italy.

Hepatitis C virus (HCV) genotype 2 causes about 10% of global infections and has the most variable circulation profile in Europe. The history of "endemic" HCV-2 subtypes has been satisfactorily reconstructed, instead there is little information about the recent spread of the "epidemic" subtypes, including HCV-2c. To investigate the origin and dispersion pathways of HCV-2c, 245 newly characterized Italian and Albanian HCV-2 NS5B sequences were aligned with 247 publicly available sequences and included in phylogeographic and phylodynamic analyses using the Bayesian framework. Our findings show that HCV-2c was the most prevalent subtype in Italy and Albania. The phylogeographic analysis suggested an African origin of HCV-2c before it reached Italy about in the 1940s. Phylodynamic analysis revealed an exponential increase in the effective number of infections and Re in Italy between the 1940s and 1960s, and in Albania between the 1990s and the early 2000s. It seems very likely that HCV-2c reached Italy from Africa at the time of the second Italian colonization but did not reach Albania until the period of dramatic migration to Italy in the 1990s. This study contributes to reconstructing the history of the spread of epidemic HCV-2 subtypes to Europe.
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http://dx.doi.org/10.3390/diagnostics11020327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922790PMC
February 2021

SARS-CoV-2 infection affects the lower urinary tract and male genital system: A systematic review.

J Med Virol 2021 May 1;93(5):3133-3142. Epub 2021 Mar 1.

Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy.

PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems in COVID-19. Sixteen studies involving a total of 575 patients (538 males and 37 females) were included in this systematic review. The COVID-19 phase was available for 479 patients: 426 in the acute and 53 in the recovery phase. De novo lower urinary tract symptoms (LUTS) were observed in 43 patients and deterioration of pre-existing LUTS in 7. Bladder hemorrhage was observed in three patients and acute urinary retention in one. Regarding the male genital system, scrotal discomfort was observed in 8 patients, swelling in 14, pain in 16, and erythema in 1; low flow priapism was observed in 2 patients. Ultrasound examination identified acute orchitis in 10 patients, acute epididymitis in 7, and acute epididymo-orchitis in 16. A case-control study reported that patients with moderate COVID-19 show a significant reduction in sperm concertation, the total number of sperms per ejaculate, progressive motility, and complete motility. In contrast to what is known from the first studies on the subject, this review also includes subsequent studies that give evidence of the involvement of the lower urinary tract and male genital system in COVID-19.
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http://dx.doi.org/10.1002/jmv.26883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013185PMC
May 2021

On the misuse of the reproduction number in the COVID-19 surveillance system in Italy.

J Med Virol 2021 05 19;93(5):2569-2570. Epub 2021 Feb 19.

Laboratory of Biostatistics and Computational Epidemiology, Department of Biosciences, University of Molise, Campobasso, Italy.

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http://dx.doi.org/10.1002/jmv.26881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014213PMC
May 2021

Malaria in an asylum seeker paediatric liver transplant recipient: diagnostic challenges for migrant population.

J Infect Dev Ctries 2021 Jan 31;15(1):172-178. Epub 2021 Jan 31.

Migrant and global Health Research Organization (Mi-HeRO) Rome, Italy.

Transplanted patients are particularly exposed to a major risk of infectious diseases due to prolonged immunosuppressive treatment. Over the last decade, the growing migration flows and the transplant tourism have led to increasing infections caused by geographically restricted organisms. Malaria is an unusual event in organ transplant recipients than can be acquired primarily or reactivation following immunosuppression, by transfusion of blood products or through the transplanted organ. We report a rare case of Plasmodium falciparum infection in a liver transplanted two years-old African boy who presented to one Italian Asylum Seeker Center on May 2019. We outlined hereby diagnostic challenges, possible aetiologies of post-transplantation malaria and finally we summarized potential drug interactions between immunosuppressive agents and antimalarials. This report aims to increase the attention to newly arrived migrants, carefully evaluating patients coming from tropical areas and taking into consideration also rare tropical infections not endemic in final destination countries.
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http://dx.doi.org/10.3855/jidc.12541DOI Listing
January 2021

Epidemiology of Posterior Cruciate Ligament Reconstructions in Italy: A 15-Year Study.

J Clin Med 2021 Feb 1;10(3). Epub 2021 Feb 1.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, Trigoria, 00128 Rome, Italy.

Background: The posterior cruciate ligament (PCL) is an essential element in knee stability. PCL reconstructions represent an under-investigated topic in the literature due to the rarity of this type of knee injury. This study aims to investigate the incidence of PCL reconstructive surgeries in Italy, following their trend during a 15-year period.

Methods: The National Hospital Discharge records (SDO) collected by the Italian Ministry of Health between January 2001 and October 2015 were analyzed. The database reports anonymous data comprising patients' ages, genders, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for diagnosis and intervention, census regions, regions of hospitalization, lengths of hospitalization and types of reimbursement.

Results: The overall incidence of PCL reconstructions in the Italian population during the study period was 0.46 surgeries per 100,000 inhabitants/year, ranging from 0.32 to 0.54. The median patient's age was 30 years old, and the male:female ratio was 5.3. PCL lesions were isolated in 39.7% of patients, while anterior cruciate ligament injuries were the most frequently associated lesions (31.1%).

Conclusions: The incidence of PCL reconstruction in Italy was low and stable during the study period. Young men are the category at the highest risk for these procedures. Given the paucity of epidemiological data on PCL reconstructions, this data may represent a reference for the current and foreseeable needs in PCL surgeries for countries sharing similar cultural context.
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http://dx.doi.org/10.3390/jcm10030499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867089PMC
February 2021

Emotional trauma in migrants: A vulnerability to listen to.

Int J Soc Psychiatry 2021 Jan 28:20764020988580. Epub 2021 Jan 28.

Psychiatric Service Psychiatry Unit rather than "Psychiatric Service", Campus Bio-Medico University, Rome, Italy.

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http://dx.doi.org/10.1177/0020764020988580DOI Listing
January 2021

Rescue Therapy of Refractory Diffuse Large B-Cell Lymphomas BCL2 with Venetoclax: Case Report.

Chemotherapy 2020 21;65(5-6):161-165. Epub 2021 Jan 21.

Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy.

Eleven years ago, a 64-year-old Caucasian man had LNH Follicular 3a, IV A stage, FLIPI 2 as a prognostic index of follicular lymphoma. He received 8 cycles of RCHOP followed by rituximab maintenance, with complete remission. Due to a systemic recurrence, a new treatment schedule (RCOMP, 6 cycles) was introduced with partial remission persisting during a long-term maintenance treatment with rituximab. Three years ago, LNH Follicular 3a progressed into GC type diffuse large B-cell lymphomas (DLBCL); 6 cycles of rituximab and bendamustine were followed by R-ICE and R OXALI DHAP treatments without beneficial effect. Due to the worse general condition (ECOG 3-4), the patient was treated with pixantrone (6 cycles) until July 10, 2019, with a partial response. On Jan 13, 2020, an extreme compassioned treatment with venetoclax alone was started; this drug was well tolerated and provided a satisfactory clinical and laboratory improvement. In June 2020, however, he developed bone marrow toxicity and septic fever. Nasal and pharyngeal secretions were SARS-CoV-2 RNA negative. Blood cultures for mycotic agents and Gram-positive, Gram-negative, and anaerobic bacteria were negative, but few days later, the patients died of sepsis due to unidentified agents. The use of venetoclax as a single drug to treat DLBCL BCL2 patients deserves further investigation.
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http://dx.doi.org/10.1159/000512541DOI Listing
March 2021

First detection of SARS-CoV-2 spike protein N501 mutation in Italy in August, 2020.

Lancet Infect Dis 2021 Jan 12. Epub 2021 Jan 12.

Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(21)00007-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836831PMC
January 2021

Role of BRCA Mutation and HE4 in Predicting Chemotherapy Response in Ovarian Cancer: A Retrospective Pilot Study.

Biomedicines 2021 Jan 8;9(1). Epub 2021 Jan 8.

Department of Obstetrics and Gynecology, University ''Campus Bio-Medico'' of Rome, Via Alvaro del Portillo, 200-00128 Rome, Italy.

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in mutated patients and in wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to mutation test, patients were further divided into wild-type (53 patients), and mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence < 12 months). Thus, in the total population, HE4 performed as a marker of chemosensitivity with a sensibility of 79% and a specificity of 97%. In the WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios.
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http://dx.doi.org/10.3390/biomedicines9010055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827362PMC
January 2021

Epidemiology of Anterior Cruciate Ligament Reconstruction Surgery in Italy: A 15-Year Nationwide Registry Study.

J Clin Med 2021 Jan 10;10(2). Epub 2021 Jan 10.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, Trigoria, 00128 Rome, Italy.

There remains little information on the epidemiology of anterior cruciate ligament reconstruction (ACL-R), therefore, we performed an epidemiological evaluation on the ACL-R procedures performed in Italy from 2001 to 2015 to highlight potential disparities in access to healthcare. The National Hospital Discharge records (SDO) maintained at the Italian Ministry of Health were analyzed from 2001 to 2015; 248,234 ACL-Rs were performed in Italy over the 15-year study period in the adult population (starting from 15 years old), and the incidence rate per year in 100,000 persons ranged from 21.70 to 33.60 over the study period. The overall male/female ratio was 4.54. The length of hospitalization ranged from four days in 2001 to two days in 2015. Italy is historically divided into north, center, and south regions, and more than half of ACL-R surgery was performed in the north (67.2%); 95.2% of ACL-Rs were underwent in public institutions. The predicted model projected a slight growth in the number of ACL-Rs in the next 10 years (2016-2025). The number of ACL-R procedures increased in the adult population from 2001 to 2015. The ACL-R procedures were concentrated in the north of Italy, suggesting that efforts on regionalization of ACL-Rs should turn toward improving quality in hospitals in the south of Italy.
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http://dx.doi.org/10.3390/jcm10020223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826510PMC
January 2021

The use of an implemented infection prevention bundle reduces the incidence of surgical site infections after colorectal surgery: a retrospective single center analysis.

Updates Surg 2021 Jan 5. Epub 2021 Jan 5.

Department of Surgery, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy.

Background: Surgical-site infections (SSIs) represent the most common complications after colorectal surgery (CS). Role of preoperative administration of oral antibiotic prophylaxis (OAP) and mechanical bowel preparation (MBP), alone or in combination, in the prevention of SSIs after CS is debated. Aim of this study was to assess the effect of the introduction of an Implemented Infection Prevention Bundle (IIPB) in preventing SSIs in CS.

Methods: A group of 251 patients (Group 1) who underwent CS receiving only preoperative intravenous antibiotic prophylaxis (IAP) was compared to a Group of 107 patients (Group 2) who also received the IIPB. The IIPB consisted of the combination of oral administrations of three doses of Rifaximin 400 mg and MBP the day before surgery and in the administration of a cleansing enema the day of the surgical procedure.

Results: At the univariate analysis, Group 2 showed significant lower rates of wound infection (WI) (2.8% vs. 9.9%; p = 0.021) and anastomotic leakage (AL) (2.8% vs. 14.7%; p = 0.001) with shorter hospital stay (5 vs. 6 days; p < 0.0001). The probability of postoperative AL was lower in Group 2; patients in this Group resulted protected from AL; a statistically significant Odds ratio of 0.16 (CI 0.05-0.55 p = 0.0034) was found. In diabetic patients, that were at higher risk of WI (OR 3.53, CI 1.49-8.35 p = 0.002), despite having any impact on anastomotic dehiscence, the use of IIPB significantly reduced the rate of WI (0% vs 28.1%; p = 0.01).

Conclusion: The use of an IIPB significantly reduces rates of SSIs and post-operative hospital stay after CS.
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http://dx.doi.org/10.1007/s13304-020-00960-xDOI Listing
January 2021

Molecular Epidemiology of HIV-1 in African Countries: A Comprehensive Overview.

Pathogens 2020 Dec 21;9(12). Epub 2020 Dec 21.

National HIV/AIDS Research Center, Istituto Superiore di Sanità, 00162 Rome, Italy.

The human immunodeficiency virus type 1 (HIV-1) originated in non-human primates in West-central Africa and continues to be a major global public health issue, having claimed almost 33 million lives so far. In Africa, it is estimated that more than 20 million people are living with HIV/Acquired Immunodeficiency Syndrome (AIDS) and that more than 730,000 new HIV-1 infections still occur each year, likely due to low access to testing. The high genetic variability of HIV-1, due to a fast replication cycle and high mutation rate, may cause the generation of many viral variants in a single infected patient during a single day. Therefore, the active monitoring and characterization of the HIV-1 subtypes and recombinant forms circulating through African countries poses a significant challenge to more specific diagnoses, treatments, care, and intervention strategies. In this review, a concise characterization of all the subtypes and recombinant forms circulating in Africa is presented to highlight the magnitude of the HIV-1 threat among the African countries and to understand virus genetic diversity and dispersion dynamics better.
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http://dx.doi.org/10.3390/pathogens9121072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766877PMC
December 2020

SARS-Cov-2 ORF3a: Mutability and function.

Int J Biol Macromol 2021 Feb 8;170:820-826. Epub 2021 Jan 8.

Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, 00185 Rome, Italy. Electronic address:

In this study, analysis of changes of SARS-CoV-2 ORF3a protein during pandemic is reported. ORF3a, a conserved coronavirus protein, is involved in virus replication and release. A set of 70,752 high-quality SARS-CoV-2 genomes available in GISAID databank at the end of August 2020 have been scanned. All ORF3a mutations in the virus genomes were grouped according to the collection date interval and over the entire data set. The considered intervals were: start of collection-February, March, April, May, June, July and August 2020. The top five most frequent variants were examined within each collection interval. Overall, seventeen variants have been isolated. Ten of the seventeen mutant sites occur within the transmembrane (TM) domain of ORF3a and are in contact with the central pore or side tunnels. The other variant sites are in different places of the ORF3a structure. Within the entire sample, the five most frequent mutations are V13L, Q57H, Q57H + A99V, G196V and G252V. The same analysis identified 28 sites identically conserved in all the genome isolates. These sites are possibly involved in stabilization of monomer, dimer, tetramerization and interaction with other cellular components. The results here reported can be helpful to understand virus biology and to design new therapeutic strategies.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836370PMC
February 2021

The Pregnancy Outcomes Among Newly Arrived Asylum-Seekers in Italy: Implications of Public Health.

J Immigr Minor Health 2021 Apr 5;23(2):232-239. Epub 2020 Dec 5.

Department of Public Health and Infectious Diseases, Policlinico Umberto I Hospital. University of Rome Sapienza, Rome, Italy.

Background: Migration has a significant impact on overall health and pregnancy outcome. Despite the fact that growing volume of migration flows significantly engaging the public health system of European host countries, there is a lack of evidence concerning pregnancy outcomes of newly arrived asylum-seeking women.

Methods: Data about pregnant asylum seekers hosted in the Italian Reception Centers between the 1 st June 2016 and the 1st June 2018 were retrospectively collected and analysed in the present study. We examined the following pregnancy outcomes: miscarriage, self-induced abortion, voluntary pregnancy termination, live-birth; and studied potentially related socio-demographic factors.

Results: Out of the 110 pregnant women living in the reception centers, 44 (40%) had eutocic delivery, 8 (7.3%) dystocic delivery, 15 (13.6%) miscarriage, 17 (15.5%) self-induced abortion and 26 (23.6%) underwent voluntary pregnancy termination. Nigerian women were at a significantly higher risk of abortive outcomes for voluntary pregnancy termination (p < 0.001), miscarriage (p = 0.049) and self-induced abortion (p < 0.001). Being unmarried was significantly associated with voluntary pregnancy termination and self-induced abortion. Women who chose to undergo unsafe abortion did not result to have significantly lower educational levels, compared to women who preferred medical abortion.

Conclusion: This study offers first insights into pregnancy outcomes among asylum-seeking women in Italy. The country of origin and marital status seem to significantly impact on pregnancy outcome. We identified sub-groups of migrant women at increased risk of abortive outcomes, and highlight the need to improve care in order to promote migrant women's reproductive health.
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http://dx.doi.org/10.1007/s10903-020-01126-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914189PMC
April 2021

High value of mid-regional proadrenomedullin in COVID-19: A marker of widespread endothelial damage, disease severity, and mortality.

J Med Virol 2021 05 19;93(5):2820-2827. Epub 2021 Feb 19.

Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy.

The widespread endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi-organs dysfunction. The aim of this study was to evaluate the role of mid-regional proadrenomedullin (MR-proADM) as a marker of SARS-CoV2 related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS-CoV-2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR-proADM cut-off values for ARDS development and mortality prediction were 3.04 and 2 nmol/L, respectively. Patients presenting with MR-proADM values ≥2 nmol/L showed a significantly higher mortality risk. In conclusion, MR-proADM values ≥2 nmol/L identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach.
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http://dx.doi.org/10.1002/jmv.26676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753433PMC
May 2021

Evolution patterns of SARS-CoV-2: Snapshot on its genome variants.

Biochem Biophys Res Commun 2021 01 6;538:88-91. Epub 2020 Nov 6.

Medical Statistic and Molecular Epidemiology Unit, University of Biomedical Campus, Rome, Italy. Electronic address:

An acute respiratory syndrome (COVID-19), caused by a novel coronavirus (SARS-CoV-2) with a high rate of morbidity and elevate mortality, has emerged as one of the most important threats to humankind in the last centuries. Rigorous determination of SARS-CoV-2 infectivity is very difficult owing to the continuous evolution of the virus, with its single nucleotide polymorphism (SNP) variants and many lineages. However, it is urgently necessary to study the virus in depth, to understand the mechanism of its pathogenicity and virulence, and to develop effective therapeutic strategies. The present contribution summarizes in a succinct way the current knowledge on the evolutionary and structural features of the virus, with the aim of clarifying its mutational pattern and its possible role in the ongoing pandemic.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836704PMC
January 2021

Correction to: Epidemiology of Achilles tendon surgery in Italy: a nationwide registry study, from 2001 through 2015.

BMC Musculoskelet Disord 2020 Nov 10;21(1):728. Epub 2020 Nov 10.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, Trigoria, 00128, Rome, Italy.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12891-020-03746-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653848PMC
November 2020

Cost-effectiveness analysis of O-Ring wound retractor in elective laparoscopic colorectal surgery.

Ann Ital Chir 2020 Nov 2;9. Epub 2020 Nov 2.

Introduction: Surgical site infections (SSIs) are a feared complication following colorectal surgery and have a sizeable economic impact on the healthcare system. The aim of this study is to assess the clinical effectiveness and cost-effectiveness of O-Ring wound protector/retractor in elective laparoscopic colorectal surgery.

Methods: Data were analyzed from a retrospective colorectal database from January 2015 to June 2018. SSI was defined according to the criteria published by the European Centre for Disease Prevention and Control (ECDC). An economic evaluation was conducted comparing the group in which Alexis® device was used during surgery (Group A) with a control group (Group B) in which Alexis® device was not used.

Results: Two hundred fifty-eight consecutive patients were enrolled in our study. Among them, the intervention group (Group A, 154 patients) was compared with the control group (Group B, 94 patients). A total of 8 (5.2%) and 14 (15%) patients with SSIs were identified in groups A and B, respectively (p = 0.008). The economic evaluation showed that there was no difference in terms of costs and returns on comparing both groups.

Conclusion: The final costs and profit are similar in both groups, but the use of O-Ring protector reduces SSI rates and may significantly improve patient's quality of life.

Key Words: Colorectal surgery, Cost-effectiveness, Surgical site infection, Length of stay, Wound protector/retractor.
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November 2020

High Seroprevalence of Hepatitis E Virus Infection Among East Balkan Swine () in Bulgaria: Preliminary Results.

Pathogens 2020 Nov 3;9(11). Epub 2020 Nov 3.

Unit of Medical Statistics and Molecular Epidemiology, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy.

The East Balkan swine () is the only aboriginal pig breed in Bulgaria, and it is indigenous to the eastern part of the country. The aim of the present study was to investigate East Balkan swine (EBS) in Bulgaria for serological evidence of hepatitis E virus (HEV). Sera from 171 swine from two parts of the country (northeastern and southeastern) were tested for anti-HEV IgG antibodies. The overall HEV seroprevalence was 82.5% (141/171), and for weaners it was 77.2% (44/57), for fattening pigs 79.0% (45/57), and for adults 91.2% (52/57). HEV positivity was higher in fattening pigs and adults compared to weaners: OR = 1.108 (95% CI: 0.456-2.692) and OR = 3.073 (95% CI: 1.016-9.294), respectively. This study provides the first evidence of exposure to HEV in EBS from Bulgaria.
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http://dx.doi.org/10.3390/pathogens9110911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693706PMC
November 2020

Epidemiology of Achilles tendon surgery in Italy: a nationwide registry study, from 2001 through 2015.

BMC Musculoskelet Disord 2020 Oct 17;21(1):687. Epub 2020 Oct 17.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy.

Background: This study aims (1) to estimate the yearly number of Achilles tendon (AT) surgeries in Italy from 2001 to 2015 based on official hospitalization records; (2) to investigate the eventual presence of geographical variation in equity in access to AT surgery between three macroregions of Italy (North, Center and South); (3) to perform statistical projections of the number of AT procedure volumes and rates based on these data.

Methods: We analysed the National Hospital Discharge records (SDO) maintained at the Italian Ministry of Health for a 15-year period, from 2001 through 2015. These data are anonymous and include the patient's age (evaluated in the class of age), sex, census region, the region of hospitalization, length of the hospitalization, public or private reimbursement and diagnosis.

Results: During the 15-year study period, 118,652 AT repair were performed in Italy, whose peak of incidence was in 2010. More than half of AT repairs was performed in the North of Italy (52.1%), while 27.2% was performed in the South of Italy and 20.6% Center of Italy. The projection model predicted a slight growth of 2.65% in 2025 in comparison with 2015.

Conclusion: The current study provides detailed information about the national population-weighted incidence of AT surgery, distribution and projection. The peak of average age was 35-45 year. The majority of AT procedures was performed in the North of Italy. The projection model predicts a slight growth of AT surgery by 2025. Furthermore, this 15-year nationwide registry study shows that the age of incidence of AT injuries shifted from 30 to 40 to 35-45 years compared to the available literature. The higher prevalence of AT surgery was found in men during the working age. Moreover, a low rate of procedures in pediatric and elder age classes was observed.
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http://dx.doi.org/10.1186/s12891-020-03688-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568369PMC
October 2020

A Coinfection on a COVID-19 Pneumonia in a Breast Cancer Patient.

Int J Gen Med 2020 30;13:729-733. Epub 2020 Sep 30.

Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy.

Introduction: Coronavirus disease 19 (COVID-19), due to (SARS-CoV2), comprises a broad spectrum of clinical presentation ranging from flu-like syndrome to organ failure. The risk of coinfections is high and responsible for a worse prognosis, mainly in the case of bacterial involvement and in the presence of particular comorbidity. We present the clinical, laboratory, radiologic characteristic along with therapeutic management of a patient with COVID-19 and coinfection.

Case Presentation: A 55-year-old Caucasian woman was admitted to our hospital due to a two-day history of fever and acute dyspnea with severe respiratory failure worsened after the administration of atezolizumab and nab-paclitaxel. Her medical history comprehended a triple negative, -related, PD-L1 positive right breast cancer with multiple bone metastasis, causing bone marrow infiltration-related severe pancytopenia. Her physical examination revealed scattered wheezes, rales, and bilateral dry crackles in the middle and lower lung fields and lower limb paresis. The body mass index was 30 kg/m and arterial blood gas evaluation revealed a stage III acute respiratory distress syndrome. Microbiological specimens revealed a positivity from endotracheal aspirate. The chest computed tomography (CT) scan showed the presence of large areas of parenchymal consolidation and aerial bronchogram, bilateral "ground glass" areas reaching the highest extension on the upper and middle zones. The high clinical and radiological suspicion of COVID-19 along with the negative result of nasopharyngeal specimen make necessary an endotracheal aspirate resulting positive for SARS-CoV2. Patient started an antimicrobial treatment and lopinavir-ritonavir plus hydroxychloroquine but, unfortunately, died five days after hospital admission.

Conclusion: The high risk of mortality of our patient was due to viral-bacterial coinfection, advanced cancer status with active immunotherapy. This case highlights the need for a prompt clinical, laboratory, and radiological evaluation to allow a correct diagnosis and start a specific therapy.
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http://dx.doi.org/10.2147/IJGM.S261760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533271PMC
September 2020

Outbreak of acute hepatitis A associated with men who have sex with men (MSM) in North Sardinia 2017-2018.

J Infect Dev Ctries 2020 09 30;14(9):1065-1070. Epub 2020 Sep 30.

Infectious Diseases Unit, Department of Medical, Surgical, and Experimental Sciences, University of Sassari, Sassari, Italy.

Introduction: We describe an outbreak of hepatitis A among men who have sex with men (MSM) which evolved in Sassari (Italy), between January 2017 and December 2018, close to a contextual of large concurrent hepatitis A outbreak reported in Europe and recently, in Italy.

Methodology: HAV RNA detection and molecular characterization was performed from serum samples and/or stool by RT - PCR of VP1/2A junction region that ranges from nt. 2,873 to nt. 3,376. The phylogenetic correlation of the circulating hepatitis A strains was assessed by sequencing method according to the HAVNET protocol.

Results: 10 Acute Hepatitis A virus (AHA)-positive cases, 8 of which were among men who have sex with men (MSM) were identified. All patients were tested at the time of hospitalization for the presence of anti-HIV antibodies, only two MSM resulted co-infected by HIV. No differences were observed in median age (37 years vs. 41 years, P-value = 0.14), severity or duration of hospitalization between seropositive and HIV-negative men. Phylogenetic analysis was conducted in 2 cases and revealed two distinct sequences of genotype IA linking to clusters recognized in MSM in other European countries in 2016.

Conclusion: Our study reported a recent increase of notified hepatitis A cases attributable to cases in the European interconnectedness of MSM in Sassari, a small locality. Hepatitis A vaccination for MSM in Sardinia region is recommended; however, our data emphasize the need of hepatitis A screening and vaccination not only for MSM with occasional partners but also for those in monogamous relationships.
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http://dx.doi.org/10.3855/jidc.12184DOI Listing
September 2020

Procalcitonin in the Assessment of Ventilator Associated Pneumonia: A Systematic Review.

Adv Exp Med Biol 2021 ;1323:103-114

Azienda Policlinico Umberto I, Rome, Italy.

Background: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infection, associated with considerable mortality and morbidity in critically ill patients; however, its diagnosis and management remain challenging since clinical assessment is often poorly reliable. The aim of this systematic review was to evaluate the role of PCT in the diagnosis and management of critical ill patients affected by VAP.

Methods: We performed a systematic review of the evidence published over the last 10 years and currently available in medical literature search databases (Pubmed, Embase, Web of Knowledge, Cochrane Libraries) and searching clinical trial registries. We regarded as predefined outcomes the role of PCT in diagnosis, therapeutic monitoring, antibiotic discontinuation and prognosis. The Open Science Framework Registration number was doi.org/10.17605/OSF.

Io/zgfkq Results: 761 articles were retrieved and a total of 18 studies (n° of patients = 1774) were selected and analyzed according to inclusion criteria. In this 2020 update, the systematic review showed that currently, conflicting and inconclusive data are available about the role of PCT in the diagnosis of VAP and in the prediction (i) of the efficacy of antibiotic therapy, and (ii) of the clinical outcome. These studies, instead, seem to agree on the utility of PCT in the management of antibiotic therapy discontinuation.

Conclusions: Currently there is insufficient evidence to support the role of PCT in the routine assessment of patients with VAP. The value of the results published appears to be limited by the deep methodological differences that characterize the various studies available at the present being.
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http://dx.doi.org/10.1007/5584_2020_591DOI Listing
January 2021