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1.
Artigo em Inglês | MEDLINE | ID: mdl-32390320

RESUMO

AIM: Human papillomavirus (HPV) is the etiologic agent of the majority of cervical intraepithelial lesions (CIN) and cervical cancers. While prophylactic HPV vaccines prevent infections from the main high-risk HPV types associated with cervical cancer, alternative nonsurgical and nonablative therapeutics to treat HPV infection and preinvasive HPV diseases have been experimentally investigated. Therapeutic vaccines are an emerging investigational strategy. This review aims to introduce the results of the main clinical trials on the use of therapeutic vaccines for treating HPV infection and -related CIN, reporting the ongoing studies on this field. METHODS: Data research was conducted using MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library querying for all articles related to therapeutic vaccines for the treatment of HPV-related CIN. Selection criteria included randomized clinical trials, nonrandomized controlled studies and review articles. RESULTS: Preliminary data are available on the evaluation of therapeutic vaccines for treating cervical HPV infections and CIN. Despite having in vitro demonstrated to obtain humoral and cytotoxic responses, therapeutic vaccines have not yet clinically demonstrated consistent success; moreover, each class of therapeutic vaccines has advantages and limitations. Early clinical data are available in the literature for these compounds, except for MVA E2, which reached the phase III clinical trial status, obtaining positive clinical outcomes. CONCLUSION: Despite promising results, to date many obstacles are still present before hypothesize an introduction in the clinical practice within the next years. Further studies will draw a definitive conclusion on the role of therapeutic vaccines in this setting.

2.
Minerva Med ; 111(2): 120-132, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338841

RESUMO

BACKGROUND: The aim of this study was to describe the population of patients arriving in several Italian Emergency Departments (EDs) complaining of chest pain suggestive of acute coronary syndrome (ACS) in order to evaluate the incidence of ACS in this cohort and the association between ACS and different clinical parameters and risk factors. METHODS: This is an observational prospective study, conducted from the 1st January to the 31st December 2014 in 11 EDs in Italy. Patients presenting to ED with chest pain, suggestive of ACS, were consecutively enrolled. RESULTS: Patients with a diagnosis of ACS (N.=1800) resulted to be statistically significant older than those without ACS (NO ACS; N.=4630) (median age: 70 vs. 59, P<0.001), and with a higher prevalence of males (66.1% in ACS vs. 57.5% in NO ACS, P<0.001). ECG evaluation, obtained at ED admission, showed new onset alterations in 6.2% of NO ACS and 67.4% of ACS patients. Multiple logistic regression analysis showed that the following parameters were predictive for ACS: age, gender, to be on therapy for cardio-vascular disease (CVD), current smoke, hypertension, hypercholesterolemia, heart rate, ECG alterations, increased BMI, reduced SaO2. CONCLUSIONS: Results from this observational study strengthen the importance of the role of the EDs in ruling in and out chest pain patients for the diagnosis of ACS. The analysis put in light important clinical and risk factors that, if promptly recognized, can help Emergency Physicians to identify patients who are more likely to be suffering from ACS.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Dor no Peito/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Síndrome Coronariana Aguda/diagnóstico , Fatores Etários , Idoso , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Fatores Sexuais
3.
Mycoses ; 63(4): 361-368, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954083

RESUMO

AIM: During the last decade a continuous increase in non-albicans species isolation has been observed with Candida parapsilosis being one of the leading species. Aim of this study was to describe the epidemiology of candidemia, particularly of C parapsilosis, its predictors and clinical outcome. MATERIALS AND METHODS: Incidences of candidemia was evaluated analyzing data from both a prospective collection (2012-2016) and a retrospective one (2008-2011). Predictors and outcome were based only on the prospective phase. C parapsilosis potential clusters were analysed by randomly amplified polymorphic DNA (RAPD) technique. RESULTS: 1240 episodes were identified. Incidences of candidemia increased from 1.97 episodes/10 000 patient-days in 2008 to 4.59/10 000 patient-days in 2016 (P < .001), mainly due to an increase of C parapsilosis (incidence rate ratio, IRR: 1.04, P < .001). 33.0% of C parapsilosis strains were resistant to fluconazole; no resistance to echinocandins was found. Independent predictors of C parapsilosis candidemia were time of infection (P = .007), previous use of echinocandins (P < .0001) and year in which the episode was registered (P < .0001). 30 days mortality was 32.4% for C parapsilosis, with a significant difference compared to C non-parapsilosis. Potential clonal C parapsilosis strains were detected by genetic analyses, showing RAPD profile A as the most represented (72.6% of isolates). DISCUSSION: C parapsilosis candidemia is an emerging issue in our center, possibly attributed to some extent to horizontal transmission of the pathogen, as confirmed by the analysis of isolates similarities. Further microbiological and epidemiological investigations are needed in order to identify the most effective measures to reduce the rate of this infection.

4.
Expert Rev Vaccines ; 19(1): 115-122, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31875483

RESUMO

Objectives: The authors conducted an in-depth phylogenetic analysis of the hemagglutinin (HA) gene of A(H3N2) identified during the 2016-2017 season to compare the circulating strains with both the egg-derived and cell-derived 2016-2017 candidate vaccine virus (CVV).Methods: 162 HA1 sequences of H3N2 viruses identified during the 2016-2017 season were phylogenetically analyzed and compared with egg-/cell-derived CVV. The predicted vaccine efficacy (pVE) of egg-/cell-derived CVV against field strains was quantified by Pepitope model.Results: All H3N2 belonged to 3C.2a genetic clade, most (80.2%) to 3C.2a1 sub-clade. Several H3N2 variants circulated in the 2016-2017 season. HA sequences of field H3N2 strains displayed greater identity with cell-derived CVV than with egg-derived CVV. The amino acid substitutions in positions 160 and 194 identified in egg-derived CVV affected the pVE, which was lower for egg-derived CVV than for cell-derived CVV.Conclusions: The results suggested that reduced vaccine effectiveness observed in 2016-2017 season was probably due to changes in the HA of vaccine strains acquired upon adaptation in eggs, which are the basis of most manufacturing systems currently used globally. Egg-free vaccine manufacturing systems would be advisable to improve the effectiveness of influenza vaccines.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31505743

RESUMO

Hepatitis B Virus (HBV) is a significant public health challenge. Around 250 million people live with chronic HBV infection. With a global approach to this issue, we focus on new perspective in diagnosis, management and prevention of HBV chronic infection. Precise diagnosis of HBV status is crucial to guide patient management. Although available drugs reduce the risk of liver disease progression, they are not able to definitely eradicate HBV, and new therapeutic options are urgently needed. Thus, prevention of HBV infection is still the most effective strategy to achieve the control of the disease. Key aspects of prevention programs include surveillance of viral hepatitis, screening programs and immunization strategies. In spite of the high success rate of licensed HBV vaccines, a need for improved vaccine persists, especially in order to provide coverage of current non-responders.


Assuntos
Hepatite B Crônica , Antivirais/uso terapêutico , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/prevenção & controle , Humanos , Imunização , Imunocompetência
6.
Euro Surveill ; 24(37)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31530343

RESUMO

We recently isolated Candida auris from a blood culture and cutaneous swabs of a patient in her mid-70s. Our routine phenotypic methods failed to identify the microorganism, but it was identified by molecular tests and MALDI-TOF MS analysis. Our report, the first from Italy, further underlines the geographically wide distribution of C. auris and the need to confirm species identification of any suspicious colony as soon as possible to stop its spread.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31561963

RESUMO

BACKGROUND: From January 2017 to June 2018 more than 7000 measles cases were reported in Italy, of which more than 400 among unvaccinated healthcare workers. We described a measles outbreak occurred in Western Liguria, Italy, characterized by a high involvement of healthcare workers and hospital visitors. METHODS: Suspected measles cases and data regarding vaccination status and clinical management of the patients were collected by reviewing 3 different surveillance systems: the routine mandatory notification system, the National Integrated Surveillance System for Measles and Rubella and the regional reference laboratory for measles diagnosis. RESULTS: Thirty-six cases were reported, with a median age of 31 years and >95% in unvaccinated subjects. One death occurred, 15 cases were hospitalized. Hospital transmission was confirmed or suspected in 12 cases; amongst this cases, 5 were healthcare workers (a gynaecologist, an obstetric nurse, a radiologist, a physiotherapist and a nurse working in an infectious disease ward), all certified unvaccinated. Phylogenetic analysis revealed the circulation of a single B3 genotype variant. CONCLUSIONS: Our experience highlighted the key role of nosocomial transmission and the need for targeted strategies, in particular (i) to implement a measles catch-up immunization campaign in susceptible groups, especially in healthcare workers, (ii) to intensify the check of immunisation status of healthcare workers and to offer vaccination for those who need it, (iii) to improve timeliness and completeness of surveillance systems. Efforts are needed to guarantee the safety of the hospital and the reliability of the healthcare workers. Only high vaccination coverage among HCWs can prevent the diffusion of measles in the hospital setting.

8.
BMC Health Serv Res ; 19(1): 585, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426795

RESUMO

BACKGROUND: Influenza-like illnesses (ILIs) and lower respiratory tract infections (LRTIs) cause substantial morbidity and mortality worldwide. The study assessed the health and economic burden of ILI and LRTI according to age and comorbidities, since available evidence is limited and heterogeneous. METHOD: The prevalence of comorbidities, the seasonal incidence rates and the mean and per capita direct costs of ED accesses for ILI/LRTI, whether followed by hospitalization or not, recorded in adults aged ≥50 years over the last 6 years, in the referral hospitals located in the Genoese metropolitan area (Liguria, Italy) where the syndromic surveillance system is active, were evaluated through a retrospective observational study. Comorbidities were estimated through the Chronic Condition Data Warehouse that integrates multiple Medicare data sources. A comparison with the administrative healthcare International Classification of Diseases-9th revision-Clinical Modification (ICD-9-CM)-based data was also conducted. RESULTS: The prevalence of subjects with ≥1 comorbidity ranged from 23.49 to 59.92%. The most prevalent all-age comorbidities were cardiovascular diseases and cancer. The overall ILI/LRTI incidence rate was 6.73/1000 person-years, almost double the value derived from routine data, and increased with age. The highest rates were observed in patients with renal failure and bronchopneumopathies. The mean cost of ED accesses/hospitalization for ILI/LRTI was €3353 and was almost twice as high in the ≥85 years as in the youngest age-group. The highest mean costs were observed in patients with renal failure and cancer. The per capita costs increased from €4 to €71 with age, and were highest in patients with renal failure and bronchopneumopathy. CONCLUSION: The burden of ILIs/LRTIs in terms of ED accesses and hospitalizations in adults aged ≥50 years is heavy, and is related to increasing age and, especially, to specific comorbidities. These results could contribute to revising age- and risk-based anti-influenza and -pneumococcus immunization strategies.


Assuntos
Efeitos Psicossociais da Doença , Influenza Humana/economia , Infecções Respiratórias/economia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Imunização , Vacinas contra Influenza , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Morbidade , Prevalência , Encaminhamento e Consulta/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Estudos Retrospectivos , Vigilância de Evento Sentinela , Vacinação/economia , Vacinação/estatística & dados numéricos
9.
ACS Omega ; 4(7): 12841-12847, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31460409

RESUMO

We report the site-specific and covalent bioconjugation of fluorescent polymer chains to proteins in live cells using the HaloTag technology. Polymer chains bearing a Halo-ligand precisely located at their α-chain-end were synthesized in a controlled manner owing to the RAFT polymerization process. They were labeled in lateral position by several organic fluorophores such as AlexaFluor 647. The resulting Halo-ligand polymer probe was finally shown to selectively recognize and label HaloTag proteins present at the membrane of live cells using confocal fluorescence microscopy. Such a polymer bioconjugation approach holds great promises for various applications ranging from cell imaging to cell surface functionalization.

10.
Expert Rev Vaccines ; 18(6): 671-679, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31159616

RESUMO

Background: Evidence on influenza vaccine effectiveness (VE) in preventing mortality and morbidity in the elderly is weak. Our aim was to measure the VE against severe outcomes in the elderly. Methods: We conducted a multicentre hospital-based test-negative design (TND) case-control study, during the 2017/18 season, in four Italian hospitals. The study population included individuals aged ≥65 years hospitalized with Severe Acute Respiratory Infections (SARI). Patients were classified as cases and controls based on the results of the PCR influenza testing. We estimated VE by virus subtypes and specific VE for the trivalent adjuvanted vaccine (TIVadj). Results: 502 patients with SARI were enrolled: 118 (23.5%) tested positive (cases) and 384 (76.5%) tested negative (controls) for influenza. The adjusted VE of 48.5% for all vaccines was comparable to the adjusted VE for the TIVadj vaccine (48.3%). Adjusted VE for the TIVadj vaccine was 67.5% for A(H1N1)pdm09 and 44.5% for B viruses. Conclusion: We show a moderate adjusted VE of the TIVadj against all viruses, a good adjusted VE against A(H1N1)pdm09 strains and a moderate adjusted VE against B strains, despite a mismatch between the B circulating lineage and the lineage included in the vaccine. This is likely due to the cross-protection among B strains induced by the TIVadj in elderly patients.

11.
Expert Opin Biol Ther ; 19(7): 671-683, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30957589

RESUMO

INTRODUCTION: Influenza occurs worldwide and causes significant disease burden in terms of morbidity, associated complications, hospitalizations, and deaths. Vaccination constitutes the primary approach for controlling influenza. Current influenza vaccines elicit a strain-specific response yet occasionally exhibit suboptimal effectiveness. This review describes the limits of available immunization tools and the future prospects and potentiality of universal influenza vaccines. AREAS COVERED: New 'universal' vaccines, which are presently under development, are expected to overcome the problems related to the high variability of influenza viruses, such as the need for seasonal vaccine updates and re-vaccination. Here, we explore vaccines based on the highly conserved epitopes of the HA, NA, or extracellular domain of the influenza M2 protein, along with those based on the internal proteins such as NP and M1. EXPERT OPINION: The development of a universal influenza vaccine that confers protection against homologous, drifted, and shifted influenza virus strains could obviate the need for annual reformulation and mitigate disease burden. The scientific community has long been awaiting the advent of universal influenza vaccines; these are currently under development in laboratories worldwide. If such vaccines are immunogenic, efficacious, and able to confer long-lasting immunity, they might be integrated with or supplant traditional influenza vaccines.

12.
Elife ; 82019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30869076

RESUMO

How endoplasmic reticulum (ER) stress leads to cytotoxicity is ill-defined. Previously we showed that HeLa cells readjust homeostasis upon proteostatically driven ER stress, triggered by inducible bulk expression of secretory immunoglobulin M heavy chain (µs) thanks to the unfolded protein response (UPR; Bakunts et al., 2017). Here we show that conditions that prevent that an excess of the ER resident chaperone (and UPR target gene) BiP over µs is restored lead to µs-driven proteotoxicity, i.e. abrogation of HRD1-mediated ER-associated degradation (ERAD), or of the UPR, in particular the ATF6α branch. Such conditions are tolerated instead upon removal of the BiP-sequestering first constant domain (CH1) from µs. Thus, our data define proteostatic ER stress to be a specific consequence of inadequate BiP availability, which both the UPR and ERAD redeem.

13.
Sci Adv ; 4(5): eaar5770, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29732408

RESUMO

Upon engagement of tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases release H2O2 in the extracellular space. We reported previously that aquaporin-8 (AQP8) transports H2O2 across the plasma membrane and is reversibly gated during cell stress, modulating signal strength and duration. We show that AQP8 gating is mediated by persulfidation of cysteine 53 (C53). Treatment with H2S is sufficient to block H2O2 entry in unstressed cells. Silencing cystathionine ß-synthase (CBS) prevents closure, suggesting that this enzyme is the main source of H2S. Molecular modeling indicates that C53 persulfidation displaces a nearby histidine located in the narrowest part of the channel. We propose that H2O2 molecules transported through AQP8 sulfenylate C53, making it susceptible to H2S produced by CBS. This mechanism tunes H2O2 transport and may control signaling and limit oxidative stress.


Assuntos
Aquaporinas/metabolismo , Sulfetos/metabolismo , Sequência de Aminoácidos , Aquaporinas/química , Transporte Biológico , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular , Peróxido de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/metabolismo , Modelos Biológicos , Conformação Molecular , Oxirredução , Estresse Fisiológico , Sulfetos/química
14.
Ital J Pediatr ; 44(1): 50, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728106

RESUMO

BACKGROUND: Human respiratory syncytial virus (hRSV) is ubiquitous and causes respiratory diseases in both children and adults. Worldwide, hRSV pneumonia is the second cause of postnatal infant death after malaria. Given the high impact in terms of morbidity, mortality and costs, especially in the pediatric population, hRSV is recognized as a global health problem and the WHO, in view of the availability of new vaccines, has urged an active surveillance program of virus-related infections. The aim of this study has been to evaluate the impact of hRSV infections in the Italian population, particularly the pediatric one, in terms of hospitalizations. METHODS: In the period 2001-2014, Hospital Discharge Records (HDRs) with the following diagnosis codes included in the primary diagnosis were evaluated: 466.11 (hRSV bronchiolitis), 480.1 (hRSV pneumonia) and 796 (hRSV). HDRs were supplied by the National Archive of HDRs data, Ministry of Health. RESULTS: During the period 2001-2014, 57,656 hospital admissions due to hRSV pathologies were performed. Most hospitalizations (88.8%) involved patients with less than 1 year of age. Considering only primary diagnosis, 93% of the admissions were due to bronchiolitis, 5% to pneumonia and 2% to not otherwise specified hRSV infections. In the period 2001-2014, the hospitalization rate in 0-2 years old children, was equal to 224.8, 9.6 and 4.6/100,000 for hRSV bronchiolitis, hRSV pneumonia and not otherwise specified hRSV infection, respectively. CONCLUSIONS: This study confirms the high impact of hRSV on the pediatric population in the age class 0-4 years, with a peak in the first 12 months of life. Most hospitalizations were urgent, although the duration of the hospital stay was for the most part less than a week, with ordinary discharge at home. Pending the conclusion of ongoing clinical trials on different hRSV vaccine types, it is extremely important to have updated data on the impact of hRSV-related pathologies in the various age groups.


Assuntos
Hospitalização/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Estudos Retrospectivos
15.
Cell Rep ; 23(5): 1387-1398, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29719252

RESUMO

Selenof (15-kDa selenoprotein; Sep15) is an endoplasmic reticulum (ER)-resident thioredoxin-like oxidoreductase that occurs in a complex with UDP-glucose:glycoprotein glucosyltransferase. We found that Selenof deficiency in mice leads to elevated levels of non-functional circulating plasma immunoglobulins and increased secretion of IgM during in vitro splenic B cell differentiation. However, Selenof knockout animals show neither enhanced bacterial killing capacity nor antigen-induced systemic IgM activity, suggesting that excess immunoglobulins are not functional. In addition, ER-to-Golgi transport of a target glycoprotein was delayed in Selenof knockout embryonic fibroblasts, and proteomic analyses revealed that Selenof deficiency is primarily associated with antigen presentation and ER-to-Golgi transport. Together, the data suggest that Selenof functions as a gatekeeper of immunoglobulins and, likely, other client proteins that exit the ER, thereby supporting redox quality control of these proteins.


Assuntos
Apresentação do Antígeno , Linfócitos B/imunologia , Retículo Endoplasmático/imunologia , Complexo de Golgi/imunologia , Imunoglobulina M/imunologia , Selenoproteínas/imunologia , Animais , Linfócitos B/citologia , Linhagem Celular , Retículo Endoplasmático/genética , Fibroblastos/citologia , Fibroblastos/imunologia , Complexo de Golgi/genética , Imunoglobulina M/genética , Camundongos , Camundongos Knockout , Selenoproteínas/genética , Baço/citologia , Baço/imunologia
16.
G Ital Cardiol (Rome) ; 19(2 Suppl 1): 1S-95S, 2018 Feb.
Artigo em Italiano | MEDLINE | ID: mdl-29531376

RESUMO

Cardiovascular prevention represents a cornerstone of modern strategies to reduce the burden of cardiovascular disease. It is of key importance to prevent cardiovascular diseases and associated events, not only to reduce morbidity and mortality, but also to increase the years of wellness in the aging population and to make the growing socio-economic burden imposed by cardiovascular events more sustainable.The current approach to prevention is based on an integrated use of effective lifestyle measures and, whenever appropriate, of antihypertensive and antidiabetic drugs, lipid-lowering agents and antiplatelet drugs.Given that population characteristics, in terms of ethnicity, demography and lifestyle habits, and healthcare system organizations differ among countries, international guidelines are not always applicable to specific countries and, often, are difficult to translate into daily clinical practice.In order to afford the specific features of Italy, 10 Scientific Societies and Research Institutions, mostly involved in preventive strategies, contributed to the present Italian consensus document, which includes brief, practical recommendations to support the preventive actions within the physician community and the general practice setting.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Estilo de Vida , Idoso , Anti-Hipertensivos/administração & dosagem , Doenças Cardiovasculares/etiologia , Humanos , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Itália , Inibidores da Agregação de Plaquetas/administração & dosagem , Fatores de Risco , Fatores Socioeconômicos
17.
J Infect Public Health ; 11(2): 171-177, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28668656

RESUMO

In the last decade, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has become endemic in several countries, including Italy. In the present study, we assessed the differences in epidemiology, management, and mortality of CR-Kp bloodstream infection (BSI) in the three main adult acute-care hospitals of the metropolitan area of Genoa, Italy. From January 2013 to December 2014, all patients with CR-Kp BSI were identified through the computerized microbiology laboratory databases of the three hospitals. The primary endpoints of the study were incidence and characteristics of CR-Kp BSI in hospitals within the same endemic metropolitan area. Secondary endpoints were characteristics of CR-Kp BSI in hospitals with and without internal infectious diseases consultants (IDCs) and 15-day mortality. During the study period, the incidence of healthcare-associated CR-Kp BSI in the entire study population was 1.35 episodes per 10,000 patient-days, with substantial differences between the three hospitals. Patients admitted to the two hospital with internal IDCs were more likely to receive post-susceptibility test combined therapy including carbapenems (77% vs. 26%, p<0.001), adequate post-susceptibility test therapies (86% vs. 52%, p<0.001), and post-susceptibility therapies prescribed by an infectious diseases specialist (84% vs. 14%, p<0.001). Overall, the crude 15-days mortality was 26%. In the final multivariable model, only septic shock at BSI presentation was unfavorably and independently associated with 15-days mortality (odds ratio [OR] 6.7, 95% confidence intervals [CI] 2.6-17.6, p<0.001), while a protective effect was observed for post-susceptibility test combined therapies including a carbapenem (OR 0.11, 95% CI 0.03-0.43, p=0.002). Mortality of CR-Kp remains high. Differences in the incidence of CR-Kp BSI were detected between acute-care centers within the same endemic metropolitan area. Efforts should be made to improve the collaboration and coordination between centers, to prevent further diffusion of CR-Kp.


Assuntos
Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Idoso , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Carbapenêmicos/uso terapêutico , Cidades , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Gerenciamento Clínico , Feminino , Hospitais/estatística & dados numéricos , Humanos , Incidência , Itália/epidemiologia , Infecções por Klebsiella/sangue , Infecções por Klebsiella/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
18.
Hum Vaccin Immunother ; 14(3): 523-531, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-28708953

RESUMO

Influenza A and B viruses are responsible for respiratory infections, representing globally seasonal threats to human health. The 2 viral types often co-circulate and influenza B plays an important role in the spread of infection. A 6-year retrospective surveillance study was conducted between 2010 and 2016 in 2 large administrative regions of Italy, located in the north (Liguria) and in the south (Sicily) of the country, to describe the burden and epidemiology of both B/Victoria and B/Yamagata lineages in different healthcare settings. Influenza B viruses were detected in 5 of 6 seasonal outbreaks, exceeding influenza A during the season 2012-2013. Most of influenza B infections were found in children aged ≤ 14 y and significant differences were observed in the age-groups infected by the different lineages. B/Victoria strains prevailed in younger population than B/Yamagata, but also were more frequently found in the community setting. Conversely, B/Yamagata viruses were prevalent among hospitalized cases suggesting their potential role in the development of more severe disease. The relative proportions of viral lineages varied from year to year, resulting in different lineage-level mismatch for the B component of trivalent influenza vaccine. Our findings confirmed the need for continuous virological surveillance of seasonal epidemics and bring attention to the adoption of universal influenza immunization program in the childhood. The use of tetravalent vaccine formulations may be useful to improve the prevention and control of the influenza burden in general population.


Assuntos
Vírus da Influenza B/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Criança , Pré-Escolar , Surtos de Doenças , Epidemias , Feminino , Humanos , Vírus da Influenza A/imunologia , Influenza Humana/virologia , Masculino , Estudos Retrospectivos , Estações do Ano , Sicília/epidemiologia , Vacinação/métodos
19.
Hum Vaccin Immunother ; 14(3): 772-789, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-28787234

RESUMO

Influenza imposes a significant burden worldwide from the healthcare and socio-economic standpoints. This is also due to suboptimal vaccination coverage among the target population, even though immunization is recommended since many years and still remains the fundamental tool for its prevention. Healthcare workers (HCWs) are at increased risk of exposure to respiratory pathogens compared with the general population, including flu, with potential threat for their health and for patients' safety. Nevertheless, despite recommendation for immunization of this work-category in most of Western Countries, inadequate flu vaccine uptake is reported during the last decade in the European area. According to recent systematic reviews on this topic, the main determinants of vaccine acceptance among HCWs have been largely investigated and include desire for self-protection and to protect family rather than absolute disease risk or desire to protect patients, among the main drivers. On the other hand, concerns regarding safety of the vaccines resulted in decreased vaccine uptake. Moreover, influenza vaccine hesitancy among HCWs was also associated with several issues such as low risk perception, denial of the social benefit of influenza vaccination, low social pressure, lack of perceived behavioral control, negative attitude toward vaccines, not having been previously vaccinated against influenza, not having previously had influenza, lack of adequate influenza-specific knowledge, lack of access to vaccination facilities, and socio-demographic variables. The topic of influenza vaccination among HCWs is challenging, full of ethical issues. Systematic reviews of randomized controlled trials (RCTs) investigating the effectiveness of interventions for improving vaccine uptake among HCWs found that combined strategies were more effective than isolate approaches. Mandatory policies are currently under debate in several countries. High quality studies would help policy-makers and stake-holders to shape evidence-based initiatives and programs to improve the control of influenza.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Humanos , Imunização/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinação/métodos
20.
Elife ; 62017 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-29251598

RESUMO

Insufficient folding capacity of the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) to restore homeostasis. Yet, how the UPR achieves ER homeostatic readjustment is poorly investigated, as in most studies the ER stress that is elicited cannot be overcome. Here we show that a proteostatic insult, provoked by persistent expression of the secretory heavy chain of immunoglobulin M (µs), is well-tolerated in HeLa cells. Upon µs expression, its levels temporarily eclipse those of the ER chaperone BiP, leading to acute, full-geared UPR activation. Once BiP is in excess again, the UPR transitions to chronic, submaximal activation, indicating that the UPR senses ER stress in a ratiometric fashion. In this process, the ER expands about three-fold and becomes dominated by BiP. As the UPR is essential for successful ER homeostatic readjustment in the HeLa-µs model, it provides an ideal system for dissecting the intricacies of how the UPR evaluates and alleviates ER stress.


Assuntos
Proteínas de Choque Térmico/metabolismo , Imunoglobulina M/metabolismo , Transdução de Sinais , Resposta a Proteínas não Dobradas , Células Epiteliais/metabolismo , Células HeLa , Humanos
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