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1.
Gut ; 73(10): 1737-1748, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39033025

RESUMEN

OBJECTIVE: Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on. DESIGN: 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs. Serum hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels as well as peripheral blood NK cell phenotype and function and HBV-specific T cell responses upon in vitro stimulation with overlapping HBV peptides were measured longitudinally before, during and after pegIFN-α therapy. RESULTS: Two cohorts of pegIFN-α treated patients were identified according to HBsAg decline greater or less than 0.5 log at week 24 post-treatment. PegIFN-α add-on did not significantly improve HBV-specific T cell responses during therapy but elicited a significant multispecific and polyfunctional T cell improvement at week 24 post-pegIFN-α treatment compared with baseline. This improvement was maximal in patients who had a higher drop in serum HBsAg levels and a lower basal HBcrAg values. CONCLUSIONS: PegIFN-α treatment can induce greater functional T cell improvement and HBsAg decline in patients with lower baseline HBcrAg levels. Thus, HBcrAg may represent an easily and reliably applicable parameter to select patients who are more likely to achieve better response to pegIFN-α add-on to virally suppressed patients.


Asunto(s)
Antivirales , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Interferón-alfa , Células Asesinas Naturales , Polietilenglicoles , Proteínas Recombinantes , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/sangre , Interferón-alfa/uso terapéutico , Antivirales/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Femenino , Adulto , Masculino , Polietilenglicoles/uso terapéutico , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de los fármacos , Persona de Mediana Edad , Antígenos e de la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos del Núcleo de la Hepatitis B/sangre , Quimioterapia Combinada , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Resultado del Tratamiento , Nucleósidos/uso terapéutico
2.
Liver Int ; 44(2): 603-613, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38100128

RESUMEN

OBJECTIVES: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. PRIMARY END-POINT: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5). CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.


Asunto(s)
Carcinoma Hepatocelular , Coinfección , Consumidores de Drogas , Infecciones por VIH , Hepatitis C , Hepatitis D , Neoplasias Hepáticas , Abuso de Sustancias por Vía Intravenosa , Masculino , Humanos , Femenino , Virus de la Hepatitis Delta/genética , Antígenos de Superficie de la Hepatitis B , Carcinoma Hepatocelular/epidemiología , Coinfección/epidemiología , Neoplasias Hepáticas/epidemiología , Abuso de Sustancias por Vía Intravenosa/complicaciones , Hepatitis D/complicaciones , Hepatitis D/epidemiología , Anticuerpos Antihepatitis , Prevalencia , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , ARN , Hepatitis C/complicaciones , Virus de la Hepatitis B/genética
3.
Eur J Clin Microbiol Infect Dis ; 41(9): 1203-1206, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35915273

RESUMEN

Objective of this study was to assess the appropriate treatment duration for enterococcal central line-associated bloodstream infections (CLABSIs). This observational, retrospective, multicenter study conducted between 2011 and 2019 enrolled all hospitalized patients with monomicrobial enterococcal CLABSI. Those with infective endocarditis and non-survivors at least 7 days from index blood culture (BC) were excluded. Primary endpoint was 30-day mortality. We enrolled 113 patients, of whom 59% were male, median age was 64 (SD ± 15) and median Charlson's index score 5 (IQR 3-8). Enterococcus faecalis and Enterococcus faecium were found in 51% and 44% of cases, respectively. Median treatment duration was 11 days (IQR 6-17), and 32% of patients (n = 36) received ≤ 7 days. Characteristics of patients receiving more or less than 7 days of treatment were similar. Central line was removed in 82% (n = 93) of cases within a median of 3 days (1-8). At both uni- and multivariate analysis, duration of antibiotic treatment > 7 days was not associated with 30-day mortality [HR 0.41 (95% CI, 0.13-1.24), p = 0.12] even after adjustment with propensity score [HR 0.47 (95% CI 0.17-1.26), p = 0.13]. A 7-day treatment course appears to be safe in non-complicated enterococcal CLABSIs.


Asunto(s)
Bacteriemia , Infecciones por Bacterias Grampositivas , Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Duración de la Terapia , Enterococcus , Enterococcus faecalis , Femenino , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
4.
Monaldi Arch Chest Dis ; 90(4)2020 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-33372741

RESUMEN

We report the case of a man affected by cystic fibrosis who developed a severe SARS-CoV-2 related pneumonia in March 2020. In addition to lopinavir/ritonavir and hydroxychloroquine, he was treated with two doses of tocilizumab, displaying a significant clinical improvement. This is the first case described in the literature of an adult patient affected by cystic fibrosis who received tocilizumab for COVID-19, with documented total recovery, also assessed by a spirometry.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Tratamiento Farmacológico de COVID-19 , COVID-19 , Fibrosis Quística , Hidroxicloroquina/administración & dosificación , Lopinavir/administración & dosificación , Neumonía Viral , Infecciones del Sistema Respiratorio/microbiología , Ritonavir/administración & dosificación , SARS-CoV-2/aislamiento & purificación , Adulto , Antivirales/administración & dosificación , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/fisiopatología , Fibrosis Quística/complicaciones , Fibrosis Quística/inmunología , Fibrosis Quística/fisiopatología , Combinación de Medicamentos , Humanos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Masculino , Terapia por Inhalación de Oxígeno/métodos , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/etiología , Receptores de Interleucina-6/antagonistas & inhibidores , Pruebas de Función Respiratoria/métodos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/etiología , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
5.
Viruses ; 16(5)2024 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-38793565

RESUMEN

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.


Asunto(s)
Antivirales , Carcinoma Hepatocelular , Hepacivirus , Hepatitis C Crónica , Neoplasias Hepáticas , Puntaje de Propensión , Respuesta Virológica Sostenida , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Masculino , Antivirales/uso terapéutico , Femenino , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/virología , Persona de Mediana Edad , Anciano , Incidencia , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/virología , Cirrosis Hepática/epidemiología , Estudios Prospectivos , Italia/epidemiología , Factores de Riesgo , Estudios de Cohortes , Adulto
6.
J Clin Med ; 13(19)2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39407867

RESUMEN

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug-drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit.

7.
Int J Infect Dis ; 146: 107115, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38801968

RESUMEN

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.


Asunto(s)
Hepatitis D Crónica , Virus de la Hepatitis Delta , Humanos , Femenino , Masculino , Italia/epidemiología , Hepatitis D Crónica/epidemiología , Adulto , Persona de Mediana Edad , Estudios Transversales , Virus de la Hepatitis Delta/inmunología , Virus de la Hepatitis Delta/genética , Estudios de Cohortes , Cirrosis Hepática/epidemiología , Cirrosis Hepática/virología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Comorbilidad , Anciano , Antígenos de Superficie de la Hepatitis B/sangre , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/virología , Interferones/uso terapéutico , Antivirales/uso terapéutico
8.
Antibiotics (Basel) ; 12(1)2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36671327

RESUMEN

After the onset of COVID-19 pandemic, a decrease in antibiotic consumption in the out-of-hospital setting was observed. However, data about the impact of this reduction on antimicrobial resistance are lacking. The aim of this study was to assess antibiotic consumption and antibiotic resistance at the community level in an Italian province before and after the beginning of the COVID-19 pandemic. We carried out an observational study, comparing antibiotic consumption in the community during 2019 and 2020 and the antibiotic resistance patterns of Enterobacterales cultured from urine samples from the out-of-hospital setting during the first semester of 2020 and 2021. Overall, antibiotic consumption decreased by 28% from 2019 to 2020 (from 13.9 to 9.97 DDD/1000 inhabitants/day). The main reductions involved penicillins (ATC J01C, from 6.9 to 4.8 DDD/1000 inhabitants/day, −31%), particularly amoxicillin/clavulanate (ATC J01CR02, −30%) and amoxicillin (J01CA04, −35.2%). Overall, 6445 strains of Enterobacterales were analyzed; in 2020, the susceptibility rate of amoxicillin/clavulanate increased from 57.5% to 87% among isolates from the primary care setting (p < 0.001) and from 39% to 72% (p < 0.001) among isolates from LTCF. The reduction in the community use of antibiotics observed in 2020 was followed by a change in the antimicrobial resistance patterns of urinary isolates.

9.
J Glob Antimicrob Resist ; 29: 386-389, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35569757

RESUMEN

OBJECTIVES: Conditions favouring persistent enterococcal bacteraemia (p-EB) have not been fully investigated yet. The aim of our study is to analyse risk factors for p-EB and its impact on mortality. METHODS: International two-centre retrospective study of all hospitalised adults with enterococcal bacteraemia managed with follow-up blood cultures (BCs) during the period 2011-2019. Exclusion criteria were: (1) death within 72 hours from index BCs and (2) polymicrobial bacteraemia. Primary endpoint was p-EB, defined as further isolation of the same species of Enterococcus spp. from BCs after at least 72 hours of appropriate antibiotic therapy. Multivariable logistic regression model was performed to assess risk factors for p-EB. The impact of p-EB on 30-day mortality was assessed by Kaplan-Meier survival curve and Cox regression multivariable model. RESULTS: During the study period, 244 enterococcal bacteraemia were diagnosed. P-EB were 13.5% (33/244). At multivariable analysis, factors independently associated with p-EB were hematologic malignancy (OR 4.60 [95% CI 1.32-16.00], P = 0.01), infective endocarditis (OR 7.99 [95% CI 2.20-28.9], P = 0.002), and use of daptomycin as initial treatment (OR 4.50 [95% CI 1.29-15.61], P = 0.018). Mortality rate was higher in the p-EB group (32% vs. 18%). Kaplan-Meier survival curve showed that patients with p-EB were less likely to survive at 30 days from index BCs (log-rank P = 0.002). Using a Cox regression model, independent predictors of 30-day mortality were hematologic malignancy (HR 2.30 [95% CI 1.02-4.11], P = 0.043), p-EB (HR 1.93 [95% CI 0.92-4.04], P = 0.08), and septic shock (HR 5.92 [95% CI 2.17-16.30], P = 0.001). CONCLUSION: P-EB was diagnosed mainly in very fragile patients and in those receiving daptomycin as frontline therapy. P-EB may have an impact on mortality.


Asunto(s)
Bacteriemia , Daptomicina , Infecciones por Bacterias Grampositivas , Neoplasias Hematológicas , Adulto , Bacteriemia/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Factores de Riesgo
10.
Clin Microbiol Infect ; 27(3): 364-371, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33152537

RESUMEN

BACKGROUND: Enterococcal bacteraemia (EB) is common, particularly in the nosocomial setting, and its management poses a challenge for clinicians and microbiologists. OBJECTIVES: The aim was to summarize the more relevant features of EB and to provide a practical state-of-the-art on the topics that more directly affect its management. SOURCES: Pubmed articles from inception to 31 May 2020. CONTENT: The following topics are covered: epidemiological, clinical and microbiological characteristics and factors associated with prognosis of EB; diagnosis and work-up, including the use of echocardiography to rule out endocarditis; antibiotic management with special focus on antimicrobial resistance and complicated EB; and the role of infectious disease consultation and the use of bundles in EB. In addition, three clinical vignettes are presented to illustrate the practical application of the guidance provided, and major gaps in the current evidence supporting EB management are discussed. IMPLICATIONS: EB is associated with large burdens of morbidity and mortality, particularly among fragile and immunosuppressed patients presenting complicated bacteraemia due to multidrug-resistant enterococci. Most cases of EB are caused by Enterococcus faecalis, followed by E. faecium. EB often presents as polymicrobial bacteraemia. Rapidly identifying patients at risk of EB is crucial for timely application of diagnostic techniques and empiric therapy. Early alert systems and rapid diagnostic techniques, such as matrix-assisted desorption ionization-time of flight mass spectrometry, especially if used together with infectious disease consultation within bundles, appear to improve management and prognosis of EB. Echocardiography is also key in the work-up of EB and should probably be more extensively used, although its exact indications in EB are still debated. Multidisciplinary approaches are warranted due to the complexity and severity of EB.


Asunto(s)
Bacteriemia/microbiología , Bacteriemia/terapia , Enterococcus/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/terapia , Humanos
11.
J Clin Med ; 10(21)2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34768474

RESUMEN

BACKGROUND: People who inject drugs (PWID) and homeless people represent now a large reservoir of Hepatitis C virus (HCV) infection. However, Hepatis C elimination programs can barely reach these subgroups of patients. We aimed to evaluate and compare the retention in care among these difficult-to-treat patients when managed for HCV in hospital or in an out-of-hospital setting. METHODS: In our retrospective study, we categorized the included patients (PWID and homeless persons) into two groups according to whether anti-HCV treatment was offered and provided in a hospital or an out-of-hospital setting. We run logistic regressions to evaluate factors associated with retention in care (defined as the completion of direct antiviral agents (DAAs) therapy). RESULTS: We included 56 patients in our study: 27 were in the out-of-hospital group. Overall, 33 patients completed DAAs therapy. A higher rate of retention in care was observed in the out-of-hospital group rather than in-hospital group (p = 0.001). At the univariate analysis, retention in care was associated with the out-of-hospital management (p = 0.002) and with a shorter time between the first visit and the scheduled start of DAAs (p = 0.003). CONCLUSIONS: The choice of treatment models that can better adapt to difficult-to-treat populations, such as an out-of-hospital approach, will be important for achieving the eradication of HCV infection.

12.
AIDS ; 35(12): 1967-1972, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34101631

RESUMEN

OBJECTIVES: Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population. DESIGN: We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017. METHODS: We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer. RESULTS: During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P < 0.001) and CD4+ cell count nadir greater than 350 cells/µl (P = 0.001), whereas antiretroviral therapy (ART) was associated to a lower rate of cancer (P = 0.02). At multivariable analysis CPT score and a history of HCC remained independently associated with HCC after DAAs (P = 0.003 and P < 0.001, respectively), and ART administration maintained its protective role (P = 0.047), regardless of HIV RNA at baseline. CONCLUSION: Our study highlights the importance of a long-lasting follow-up for HCC after HCV eradication, mostly in those patients with advanced cirrhosis and history of HCC. Furthermore, our data showed a potential role of ART itself (and not of undetectable HIV RNA) in reducing the risk for HCC development.


Asunto(s)
Carcinoma Hepatocelular , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Estudios Retrospectivos , Respuesta Virológica Sostenida
13.
Eur J Endocrinol ; 183(4): 389-397, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32674071

RESUMEN

OBJECTIVE: Specific comorbidities and old age create a greater vulnerability to severe Coronavirus Disease 19 (COVID-19). While obesity seems to aggravate the course of disease, the actual impact of the BMI and the cutoff which increases illness severity are still under investigation. The aim of the study was to analyze whether the BMI represented a risk factor for respiratory failure, admission to the intensive care unit (ICU) and death. RESEARCH DESIGN AND METHODS: A retrospective cohort study of 482 consecutive COVID-19 patients hospitalised between March 1 and April 20, 2020. Logistic regression analysis and Cox proportion Hazard models including demographic characteristics and comorbidities were carried out to predict the endpoints within 30 days from the onset of symptoms. RESULTS: Of 482 patients, 104 (21.6%) had a BMI ≥ 30 kg/m2. At logistic regression analysis, a BMI between 30 and 34.9 kg/m2 significantly increased the risk of respiratory failure (OR: 2.32; 95% CI: 1.31-4.09, P = 0.004) and admission to the ICU (OR: 4.96; 95% CI: 2.53-9.74, P < 0.001). A significantly higher risk of death was observed in patients with a BMI ≥ 35 kg/m2 (OR: 12.1; 95% CI: 3.25-45.1, P < 0.001). CONCLUSIONS: Obesity is a strong, independent risk factor for respiratory failure, admission to the ICU and death among COVID-19 patients. A BMI ≥ 30 kg/m2 identifies a population of patients at high risk for severe illness, whereas a BMI ≥ 35 kg/m2 dramatically increases the risk of death.


Asunto(s)
Betacoronavirus , Índice de Masa Corporal , Infecciones por Coronavirus/epidemiología , Obesidad/epidemiología , Neumonía Viral/epidemiología , Insuficiencia Respiratoria/epidemiología , Adulto , Anciano , COVID-19 , Comorbilidad , Infecciones por Coronavirus/complicaciones , Femenino , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Italia/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/virología , Pandemias , Neumonía Viral/complicaciones , Modelos de Riesgos Proporcionales , Insuficiencia Respiratoria/virología , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2
14.
Open Forum Infect Dis ; 6(12): ofz473, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32128323

RESUMEN

OBJECTIVE: In this study, we evaluated the effectiveness of a management bundle for Enterococcus spp bloodstream infection (E-BSI). METHOD: This was a single-center, quasi-experimental (pre/post) study. In the prephase (January 2014 to December 2015), patients with monomicrobial E-BSI were retrospectively enrolled. During the post- or intervention phase (January 2016 to December 2017), all patients with incident E-BSI were prospectively enrolled in a nonmandatory intervention arm comprising infectious disease consultation, echocardiography, follow-up blood cultures, and early targeted antibiotic treatment. Patients were followed up to 1 year after E-BSI. The primary outcome was 30-day mortality. RESULTS: Overall, 368 patients were enrolled, with 173 in the prephase and 195 in the postphase. The entire bundle was applied in 15% and 61% patients during the pre- and postphase, respectively (P < .001). Patients enrolled in the postphase had a significant lower 30-day mortality rate (20% vs 32%, P = .0042). At multivariate analysis, factors independently associated to mortality were age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00-1.05), intensive care unit admission (HR, 2.51; 95% CI, 1.18-3.89), and healthcare-associated (HR, 2.32; 95% CI, 1.05-5.16) and hospital-acquired infection (HR, 2.85; 95% CI, 1.34-4.76), whereas being enrolled in the postphase period (HR, 0.49; 95% CI, 0.32-0.75) was associated with improved survival. Results were consistent also in the subgroups with severe sepsis (HR, 0.37; 95% CI, 0.16-0.90) or healthcare-associated infections (HR, 0.53; 95% CI, 0.31-0.93). A significantly lower 1-year mortality was observed in patients enrolled in the postphase period (50% vs 68%, P < .001). CONCLUSIONS: The introduction of a bundle for the management of E-BSI was associated with improved 30-day and 1-year survival.

15.
J Chemother ; 30(5): 304-309, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30843776

RESUMEN

Candidemia is a major cause of in-hospital mortality. Antifungal stewardship programme (AFSP) providing infectious diseases consultation (IDC) might improve the outcome. We evaluate the impact on candidemia mortality of IDC as part of AFSP restricting the use of all antifungals with exception of fluconazole. We retrospectively reviewed the charts of patients with documented candidemia in our hospital during the period 2012-2014 evaluating the impact of several variables on 30-days in-hospital mortality. We reviewed data on 276 patients with documented candidemia: 200 (72%) were treated without IDC and 76 (28%) with IDC. In the group without IDC, 52 patients (26%) received no antifungal therapy. Antifungals used for treating candidemia were (no IDC/IDC): azoles (74%/42%); echinocandins (0%/46%); liposomal and lipidic complex amphotericin B (0%/12%). The 30-day in-hospital mortality was respectively (no IDC/IDC) 37% vs. 20% (p = 0.011). The multivariate analysis confirmed IDC as independent factor protecting from death (OR 0.511, 95% CI 0.251-0.994; p = 0.046), together with fungemia due to non-albicans Candida (OR 0.565, 95% CI 0.327-0.977; p = 0.042). Age >65 years was associated with a higher risk of death (OR 1.989, 95% CI 1.055-3.895; p = 0.038). The additional cost for the use of echinocandins driven by IDC in the study period was €207,000. IDC, as a part of a restrictive front-end antimicrobial stewardship programme (ASP), providing a timely right choice of antifungal therapy, increases the cost of antifungal drugs but might be a contributing protective factor from mortality due to candidemia. Efforts to increase the number of IDC in patients with candidemia seems to be warranted.


Asunto(s)
Antifúngicos/uso terapéutico , Candidemia/tratamiento farmacológico , Enfermedades Transmisibles/tratamiento farmacológico , Anciano , Programas de Optimización del Uso de los Antimicrobianos/métodos , Candida/efectos de los fármacos , Femenino , Fluconazol/uso terapéutico , Hospitales Universitarios , Humanos , Italia , Masculino , Derivación y Consulta , Estudios Retrospectivos
16.
HIV Clin Trials ; 18(3): 110-117, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28420298

RESUMEN

BACKGROUND: The combination antiretroviral therapy (cART) has dramatically improved the life expectancy of patients with HIV infection, but may lead to several long-term metabolic abnormalities. However, data about the frequency of metabolic syndrome (MS) in HIV-infected people vary considerably across different observational studies. METHODS: The prevalence of MS among HIV-infected patients was evaluated by a cross-sectional study conducted among subjects naive to cART or receiving the first antiretroviral regimen and referring to our Clinics from January 2015 to December 2015. The diagnosis of MS was made based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. RESULTS: The study recruited 586 patients: 98 naive to cART and 488 under the first antiretroviral treatment. The prevalence of MS, according to NCEP-ATP III criteria, was significantly higher among treated patients than among naive ones (20.9% vs. 7.1%; p = 0.014). The most frequently reported components of MS among treated patients were high triglycerides (44.3%), low high-density lipoprotein cholesterol (41.1%), and hypertension (19.7%). On multivariate analysis, long duration of HIV infection, low nadir of CD4 lymphocytes, high body mass index, current use of one protease inhibitor, and long duration of cART were significantly associated with a higher risk of MS, while current use of one integrase inhibitor was significantly associated with a lower risk of MS. CONCLUSIONS: The non-negligible prevalence of MS among HIV-infected patients under cART requires a careful and periodic monitoring of its components, with particular attention to dyslipidemia and hypertension.


Asunto(s)
Infecciones por VIH/complicaciones , Enfermedades Metabólicas/epidemiología , Adolescente , Adulto , Anciano , Antirretrovirales/uso terapéutico , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Adulto Joven
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