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OBJECTIVES: This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals. STUDY DESIGN: We retrospectively analysed data from the COVID-19 Italian integrated surveillance system (14 September 2020 to 17 October 2021). METHODS: We used multivariable Cox proportional hazards models to estimate the hazard ratio (HR) of infection and, among cases, the HRs of death, hospitalisation and subsequent admission to intensive care unit in non-Italian nationals relative to Italian nationals. Estimates were adjusted for differences in sociodemographic characteristics and in the week and region of diagnosis. RESULTS: Of 4,111,067 notified cases, 336,265 (8.2%) were non-Italian nationals. Compared with Italian nationals, non-Italians showed a lower incidence of SARS-CoV-2 infection (HR = 0.81, 95% confidence interval [CI]: 0.80-0.81). However, once diagnosed, they were more likely to be hospitalised (HR = 1.90, 95% CI: 1.87-1.92) and then admitted to intensive care unit (HR = 1.08, 95% CI: 1.04-1.13), with differences larger in those coming from countries with a lower human development index. Compared with Italian cases, an increased rate of death was observed in non-Italian cases from low-human development index countries (HR = 1.41, 95% CI: 1.23-1.62). The HRs of SARS-CoV-2 infection and severe outcomes slightly increased after the start of the vaccination campaign. CONCLUSIONS: Underdiagnosis and delayed diagnosis in non-Italian nationals could explain their lower incidence compared with Italians and, among cases, their higher probability to present clinical conditions leading to worse outcomes. Facilitating early access to vaccination, diagnosis and treatment would improve the control of SARS-CoV-2 transmission and health outcomes in this vulnerable group.
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COVID-19 , COVID-19/epidemiología , Hospitalización , Humanos , Incidencia , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVES: Switching from tenofovir (TDF) to tenofovir alafenamide (TAF) affects lipid profile. The aim of this study was to evaluate whether this results in an increased frequency of patients with low-density lipoprotein (LDL) above their cardiovascular-related target. METHODS: All HIV patients switching from TDF to TAF, with no changes of the anchor drug, and with plasma lipids available within 6 months before and after the switch, were included. Demographic, HIV-related parameters, cardiovascular (CV) risk factors and lipid profile on both TDF and TAF were collected. The CV risk score and the relative target of LDL for each patient were calculated according to 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidaemias. Modifications in lipid profiles and in the prevalence of patients with LDL above their CV-related target were evaluated after switch to TAF. RESULTS: Overall, 221 HIV patients were included, according to CV risk: 55% at low risk, 34% at moderate risk, and 11% at high/very high risk. By analysing lipid profiles according to CV risk, 38% of patients on TDF had LDL above their CV target; this prevalence increases to 60% after switching to TAF (P < 0.0001). The presence of cobicistat in the combination antiretroviral therapy (cART) regimen was associated with an increased risk of LDL above the CV-related target after switch to TAF [adjusted odds ratio (aOR) = 2.4, 95% confidence interval (CI): 1-5.1], P = 0.03) and with an increased prescription of lifestyle/therapeutic intervention (OR = 3.0, 95% CI: 1.7-5.3, P < 0.0001). DISCUSSION: Switching from TDF to TAF affects lipid parameters, and data from real life suggest a clinical relevance of this worsening that often leads clinicians to implement lifestyle/therapeutic interventions.
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Dislipidemias , Infecciones por VIH , Alanina/uso terapéutico , Dislipidemias/inducido químicamente , Infecciones por VIH/tratamiento farmacológico , Humanos , Tenofovir/efectos adversos , Tenofovir/análogos & derivadosRESUMEN
OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.
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Fármacos Anti-VIH/uso terapéutico , Enfermedades del Sistema Nervioso Central/etiología , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Enfermedad Aguda , Adulto , Fármacos Anti-VIH/farmacología , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Italia , Masculino , Persona de Mediana Edad , ARN Viral/genética , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND AND PURPOSE: The involvement of protein C (PC) pathway components in multiple sclerosis (MS) has scarcely been explored. The aim was to investigate their levels in relation to clinical and neurodegenerative magnetic resonance imaging (MRI) outcomes in patients. METHODS: In all, 138 MS patients and 42 healthy individuals were studied. PC, protein S (PS) and soluble endothelial protein C receptor (sEPCR) were evaluated by multiplex assays and enzyme-linked immunosorbent assay. Regression analyses between 3 T MRI outcomes and PC pathway components were performed. ancova was used to compare MRI volumes based on protein level quartiles. Partial correlation was assessed amongst levels of PC pathway components and hemostasis protein levels, including soluble thrombomodulin (sTM), heparin cofactor II (HCII), plasminogen activator inhibitor 1 (PAI-1) and factor XII (FXII). The variation of PC concentration across four time points was evaluated in 32 additional MS patients. RESULTS: There was an association between PC concentration, mainly reflecting the zymogen PC, and MRI measures for volumes of total gray matter (GM) (P = 0.003), thalamus (P = 0.007), cortex (P = 0.008), deep GM (P = 0.009) and whole brain (P = 0.026). Patients in the highest PC level quartile were characterized by the lowest GM volumes. Correlations of PC-HCII, PC-FXII and sEPCR-sTM values were detectable in MS patients, whilst PC-PS and PS-PAI-1 correlations were present in healthy individuals only. CONCLUSIONS: Protein C plasma concentrations might be associated with neurodegenerative MRI outcomes in MS. Several differences in correlation amongst protein plasma levels suggest dysregulation of PC pathway components in MS patients. The stability of PC concentration over time supports a PC investigation in relation to GM atrophy in MS.
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Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Proteína C/análisis , Adulto , Estudios Transversales , Progresión de la Enfermedad , Receptor de Proteína C Endotelial/genética , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Proteína S/análisis , Transducción de Señal , Resultado del TratamientoRESUMEN
HBV eradication in chronic hepatitis B (CHB) subjects is rarely achieved with either nucleos(t)ide analogues (NA) or pegylated interferon (Peg-IFN), which both have a limited effect in restoring immune responses. Thirty CHB subjects on long-term treatment with tenofovir (TDF) and HBV suppression were enrolled and randomized 1:2 to either receive Peg-IFN-α-2a add-on therapy or continue TDF alone. We studied γδ T and iNKT frequency and function (by flow cytometry) at baseline, at 12 weeks and 12 weeks after the end of treatment. A higher reduction in qHBsAg occurred in the add-on group compared with the NA group at W12 (P = .016) and at W24 (P = .012). A decline of qHBsAg ≥0.5 log10 at week 24 occurred in 4 of 10 patients in the add-on arm and 1 of 20 in the NA arm, respectively (P = .03). HBsAg loss was seen in 20% of subjects in the add-on group and in none of the NA group. Compared to HBV negative, CHB on TDF showed lower frequency of iNKT (P = .03) and γδ T cells (P = .03) as well as fewer γδ T cells expressing Vδ2 T-cell receptors (P = .005). No changes in unconventional T-cell frequency and function were shown in both add-on and NA patients nor were differences detected between the two treatment groups. We report persistent impairment of unconventional T cells in CHB. Despite a greater qHBsAg decline of add-on patients, our data failed to detect any effect of Peg-IFN treatment on unconventional T cells.
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Antivirales/administración & dosificación , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Subgrupos de Linfocitos T/inmunología , Tenofovir/administración & dosificación , Adulto , Anciano , Citometría de Flujo , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: The aim was to investigate the plasma levels of hemostasis components in multiple sclerosis (MS) and their association with clinical and magnetic resonance imaging (MRI) outcomes. METHODS: In all, 138 MS patients [85 with relapsing-remitting MS (RR-MS) and 53 with progressive MS (P-MS) with a mean age of 54 years; 72.5% female; median Expanded Disability Status Scale 3.5; mean disease duration 21 years] and 42 age- and sex-matched healthy individuals (HI) were studied. All subjects were examined with 3 T MRI and clinical examinations. Plasma levels of hemostasis factors [procoagulant, factor XII (FXII)] and inhibitors [tissue factor pathway inhibitor (TFPI), thrombomodulin, heparin cofactor II, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and plasminogen activator inhibitor 1 (PAI-1)] were evaluated by magnetic Luminex assays and enzyme-linked immunosorbent assay. Associations between hemostasis plasma levels and clinical and MRI outcomes were assessed. RESULTS: Lower ADAMTS13 levels were found in MS patients compared to HI (P = 0.008) and in MS patients presenting with cerebral microbleeds compared to those without (P = 0.034). Higher PAI-1 levels were found in MS patients compared to HI (P = 0.02). TFPI levels were higher in the P-MS subgroup compared to RR-MS patients (P = 0.011) and compared to HI (P = 0.002). No significant associations between hemostasis plasma levels and clinical or MRI outcomes were found. CONCLUSIONS: Decreased ADAMTS13, particularly in MS patients with cerebral microbleeds, which deserves further investigation, and increased PAI-1 and TFPI levels were observed in MS patients, which deserves further investigation. No relationship between hemostasis plasma levels and measures of disease severity was detected.
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Biomarcadores/sangre , Hemostasis , Esclerosis Múltiple/sangre , Proteína ADAMTS13/sangre , Mapeo Encefálico , Estudios de Casos y Controles , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Femenino , Glicoproteínas/sangre , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/diagnóstico por imagen , Inhibidor 1 de Activador Plasminogénico/sangreRESUMEN
OBJECTIVES: The aim of this study was to evaluate the clinical impact of including lateral spine X-ray in the screening of bone diseases in HIV-positive patients. METHODS: A total of 194 HIV-positive patients underwent dual-energy X-ray absorptiometry (DEXA), lateral spine X-ray and bone biochemical analysis. Vertebral fractures were identified using a morphometric analysis of X-rays and classified using the semiquantitative scoring system of Genant et al. For each patient, a spine deformity index (SDI) score was calculated by summing the grades of vertebral deformities. Reductions in vertebral body height of > 25% were considered vertebral fractures, and those < 25% were considered vertebral deformities. Risk factors associated with vertebral fractures were evaluated by univariate and multivariate analysis. RESULTS: Vertebral fractures were detected in 24 patients (12.4%) and vertebral deformities in 17 patients (8.7%); 153 patients (78.9%) did not show any vertebral deformity. Among patients with fractures, only two with SDI > 10 reported lumbar pain; the remaining were asymptomatic. Patients over 50 years old showed a higher prevalence of vertebral fracture [24.4% versus 11.8% in patients 41-50 years old (P = 0.05) and 1.9% in patients ≤ 40 years old (P = 0.04)]. No significant increase in the prevalence according to bone mineral density (BMD) reduction was observed, and 70% of fractures were diagnosed in nonosteoporotic patients. Older age [adjusted odds ratio 1.09; 95% confidence interval (CI) 1.03-1.13; P = 0.001] and steroid use (adjusted odds ratio 3.64; 95% CI 1.29-10.3; P = 0.01) were independently associated with vertebral fracture; no association was found with HIV- or highly active antiretroviral therapy (HAART)-related variables. CONCLUSIONS: A prevalence of vertebral fractures of 12.4% was observed in our HIV-positive cohort. Given that two-thirds of fractures occurred in nonosteoporotic patients, spine X-ray may be considered in patients at increased risk, irrespective of BMD; that is, in elderly patients and/or patients using steroids.
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Infecciones por VIH/complicaciones , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Absorciometría de Fotón/métodos , Adulto , Densidad Ósea , Femenino , Infecciones por VIH/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoAsunto(s)
Infecciones por VIH , VIH-1 , Recuento de Linfocito CD4 , Infecciones por VIH/genética , VIH-1/genética , HumanosRESUMEN
Mycobacterium avium ssp. paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic contagious bacterial disease primarily affecting dairy cattle. Paratuberculosis represents a dual problem for the milk production chain: in addition to economic losses to affected herds, MAP may have zoonotic potential. Infected herds must be identified in order to implement programs designed to reduce the incidence of disease within and between herds and to prevent MAP from entering the food chain. The objective of this study was to evaluate the sensitivity and specificity of a screening sampling plan (SSP) to detect MAP-positive dairy herds by repetitive analysis of bulk tank milk (BTM) samples by ELISA and in-line milk filter (ILMF) samples by PCR. Samples from BTM and ILMF were collected twice from 569 dairy herds in southern Italy. Additionally, 12,016 individual milk samples were collected: 9,509 from 102 SSP-positive herds (SSP MAP-positive) and 2,507 from 21 randomly selected SSP-negative herds (SSP MAP-negative). There was a total of 126 SSP MAP-positive herds (i.e., 21.3% SSP MAP-positive herds; 95% confidence interval=18.0-24.9); the within-herd apparent prevalence (AP) ranged between 0.00 and 22.73% (mean 6.07%). A significant difference in within-herd AP was shown between SSP MAP-positive herds and SSP MAP-negative herds. A highly significant association was shown between the median AP herd status (>5%) and positivity to at least one ILMF or BTM sample. The SSP detected a minimum of 56.25% of low AP herds (AP ≤ 2.0%) up to a maximum of 100% of herds with a within-herd AP ≥ 8.0%. Overall, the SSP detected 85.57% of herds in which at least one individual milk sample was positive by ELISA. The proposed SSP was an inexpensive and useful tool to detect MAP-positive herds with a higher risk of infection diffusion and milk contamination. Although the SSP cannot be used for MAP-free certification of herds, it could be useful to prioritize appropriate control measures aimed at reducing the prevalence of infection in dairy herds and milk contamination.
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Enfermedades de los Bovinos/epidemiología , Bovinos/microbiología , Mycobacterium avium subsp. paratuberculosis/aislamiento & purificación , Paratuberculosis/epidemiología , Animales , Enfermedades de los Bovinos/microbiología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Filtración , Contaminación de Alimentos/análisis , Microbiología de Alimentos , Italia/epidemiología , Leche/microbiología , Paratuberculosis/microbiología , Reacción en Cadena de la Polimerasa , Prevalencia , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND OBJECTIVES: Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP). METHODS: A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements. RESULTS: The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502). CONCLUSIONS: Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited.
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A case of primary adenocarcinoma of the rectovaginal septum (PARVS) is reported with clinical and pathological findings. A 37-year-old Caucasian woman with a history of sterility and small posterior leiomyoma, a few months after a cesarean section, was admitted because of vaginal spotting, abdominal pain and constipation. Her previous history did not reveal exposure to diethylstil bestrol (DES). Pelvic computed tomography showed a heterogeneous pelvic mass in the Douglas pouch, measuring 9 cm in diameter, located in the rectovaginal septum, involving the rectal and vaginal wall. Histological examination of neoplastic tissue revealed solid sheet structures, occasional tubular lumen, extensive necrotic areas and clear cells. The neoplastic elements showed immunoreactivity for Mullerian markers (cytokeratin 7, CA-125 and vimentin). Because, the present case of PARVS cannot be due to DES exposure, the clear appearance of the neoplastic elements could represent only one differentiation of Mullerian rests. Moreover, because no foci of endometriosis were identified in several sections of the neoplasm, uterine and cervical wall, and tissues nearby the neoplasm could represent a rare subtype of PARVS arising in the absence of endometriosis.
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Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Complicaciones Neoplásicas del Embarazo/patología , Neoplasias del Recto/patología , Neoplasias Vaginales/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Carboplatino/administración & dosificación , Femenino , Humanos , Histerectomía , Ovariectomía , Paclitaxel/administración & dosificación , Embarazo , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Complicaciones Neoplásicas del Embarazo/cirugía , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Resultado del Tratamiento , Neoplasias Vaginales/tratamiento farmacológico , Neoplasias Vaginales/cirugíaRESUMEN
Empyema is defined as pus in the thoracic cavity due to pleural space infection and has a multifactorial underlying cause, although the majority of cases are post-bacterial pneumonia. Despite treatment with antibiotics, patients with empyema have a considerable morbidity and mortality due at least in part to inappropriate management of the effusion. Timely diagnosis of pleural space infection and rapid initiation of effective pleural drainage represent fundamental principles for managing patients with empyema. Ultrasound is particularly useful to identify early fibrin membranes and septations in the pleural cavity conditioning treatment strategy. Empyema and large or loculated effusion with a pH < 7.20 need to be drained. Thoracoscopy has largely been used in pleural effusion due to lung infection. Whereas the efficacy of video-assisted thoracic surgery (VATS) in empyema management has been evaluated in several retrospective studies showing favourable results, less is known about the role of medical thoracoscopy (MT) in pleural infection. MT, appears to be safe and successful in multiloculated empyema treatment. It is also lower in cost and in frail patients is better tolerated than VATS which requires tracheal intubation.
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Empiema Pleural/cirugía , Antibacterianos/uso terapéutico , Tubos Torácicos , Terapia Combinada , Drenaje , Empiema Pleural/tratamiento farmacológico , Empiema Pleural/fisiopatología , Humanos , Cirugía Torácica Asistida por VideoRESUMEN
BACKGROUND: We hypothesized that there may be a correlation between the interleukin-7 (IL-7)/IL-7 receptor (IL-7R) regulatory system and parameters of T-cell homeostasis in HIV-infected long-term nonprogressors (LTNPs) as compared with patients with disease progression. METHODS: The possibility of a correlation between T-cell homeostatic parameters and IL-7/IL-7R was investigated in 22 LTNPs (CD4 count > or =500 cells/microL for >10 years) vs. HIV-positive patients at different disease stages [12 early: CD4 count > or =400 cells/microL ; 15 late (AIDS-presenters): CD4 count < or =150 cells/microL ]. RESULTS: Compared with early-stage HIV-positive patients, LTNPs displayed a higher circulating IL-7 concentration (P=0.05), which was positively associated with higher IL-7Ralpha expression and a higher T-cell receptor excision circle (TREC) content specifically within CD4 cells (P<0.05). Compared with late-stage disease patients, early-stage disease patients displayed a lower IL-7 concentration (P<0.01) and higher percentages of IL-7Ralpha+ CD4 and CD8 cells (P=0.05). IL-7 was positively correlated with the percentage of TREC+ CD4 cells (P<0.01), which translated into a higher percentage of naïve CD4 cells in early-stage disease patients than in late-stage disease patients; however, the CD4 cells in early-stage disease patients were less enriched in recent thymic emigrants (RTEs) compared with LTNPs (P<0.05). In late-stage AIDS-developing patients, substantially increased IL-7 was correlated with a decreased percentage of IL-7Ralpha+ CD4 cells (P=0.01), which resulted in these patients having a significantly lower percentage of naïve T cells (P<0.01) and a significantly lower content of TREC (P<0.01) than the other patients. CONCLUSIONS: The maintenance of high CD4 cell counts in LTNPs was associated with a specific IL-7/IL-7R pattern characterized by increased IL-7 and highest IL-7Ralpha-expressing CD4 cells relative to other patients. Compared with patients with late-stage disease, LTNPs displayed a phenotypically naïve, less activated CD4 cell pool highly enriched in RTEs, suggesting the existence of a compensatory IL-7-mediated pathway specifically sustaining peripheral CD4 counts.
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Infecciones por VIH/sangre , Sobrevivientes de VIH a Largo Plazo , Homeostasis , Interleucina-7/sangre , Receptores de Interleucina-7/sangre , Linfocitos T/inmunología , Adulto , Anciano , Recuento de Linfocito CD4 , Estudios Transversales , Regulación hacia Abajo , Femenino , Reordenamiento Génico de Linfocito T , Infecciones por VIH/inmunología , Homeostasis/inmunología , Humanos , Interleucina-7/inmunología , Antígeno Ki-67/metabolismo , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Receptores de Interleucina-7/inmunología , Linfocitos T/metabolismo , Timo/citologíaRESUMEN
Fluvastatin showed anti-hepatitis C virus (HCV) activity in vitro, through the inhibition of geranylgeranylation of cellular proteins, and a synergistic effect with interferon (IFN)-alpha. Nevertheless statins up-regulate low-density lipoprotein (LDL) receptor, required for HCV cell entry, and the closely related scavenger receptors SRBI and CD36; moreover they reduce class II major histocompatibility complex expression on antigen presenting cell, modulating T-cell activation. In vivo LDL levels have been identified as prognostic indicator of sustained viral response to IFN in patients with HCV infection, suggesting that lipid-lowering agents might conversely favour HCV entry into the hepatocytes and translate into higher viral replication. We evaluated the effect of fluvastatin on HCV-RNA levels, CD36 expression and T-cell homeostasis in HCV-RNA positive patients. HCV-RNA was measured at baseline and after 4 weeks in 42 HCV/HIV-1 co-infected patients, randomized to receive either fluvastatin 80 mg qd or no treatment. CD36 expression and markers of T-cell activation were evaluated by means of flow cytometry. Plasma interleukin (IL)-10, IFN-gamma and IL-7 were measured by ELISA. Serum cholesterol and LDL decreased significantly in the treatment group (P = 0.0001 and 0.01, respectively). Surprisingly a significant increase of HCV-RNA levels was seen after 4 weeks of fluvastatin (P = 0.03). The percentages of naive/activated/apoptotic cells and CD36 expression remained unchanged. Fluvastatin did not inhibit HCV-RNA replication in vivo; conversely we observed a significant increase of HCV-RNA levels. CD36 expression on monocytes were not up-regulated by statins as previously reported in vitro. The correlation between HCV infectivity, oxidized-LDL receptor and statins in HCV infection need further evaluation.
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Antivirales/uso terapéutico , Ácidos Grasos Monoinsaturados/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/crecimiento & desarrollo , Hepatitis C Crónica/complicaciones , Indoles/uso terapéutico , Replicación Viral/efectos de los fármacos , Adulto , Antígenos CD36/análisis , Células Cultivadas , Colesterol/sangre , LDL-Colesterol/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Fluvastatina , Hepacivirus/efectos de los fármacos , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-7/sangre , Masculino , Persona de Mediana Edad , Proyectos Piloto , ARN Viral/sangre , Linfocitos T/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: Adiponectin has antisteatosis-anti-inflammatory properties and its circulating levels are reduced in nonalcoholic steatohepatitis (NASH). METHODS: To assess the role of adiponectin in NASH, we measured expression of adiponectin gene (APM1) and receptors (AdipoR1/AdipoR2) in liver and subcutaneous and visceral fat in subjects with biopsy-proven NASH or pure steatosis (PS). In 103 subjects undergoing gastric bypass or elective abdominal surgery (17 with normal liver histology (C), 52 with PS, and 34 with NASH), RNA was extracted from tissue samples, and quantification of APM1, AdipoR1, and AdipoR2 was carried out by real-time polymerase chain reaction. RESULTS: In NASH vs C, circulating adiponectin levels (3.6[2.4] vs 5.3[4.3] microg/ml, median[interquartile range], p < 0.05) and adiponectin concentrations, APM1, AdipoR1, and AdipoR2 expression in visceral fat were all reduced (p < or = 0.03). These differences disappeared when adjusting for obesity. In contrast, liver AdipoR1 (1.40 [0.46] vs 1.00 [0.32] of controls) and AdipoR2 expression (1.20 [0.41] vs 0.78 [0.43]) were increased in NASH, and group differences were statistically significant (p < 0.0001 for AdipoR1 and p = 0.0001 for AdipoR2). Results for PS were generally intermediate between NASH and C. Liver receptor expression was reciprocally related to circulating adiponectin (rho = -0.42, p < 0.003 for AdipoR1 and rho = -0.26, p < 0.009 for AdipoR2). In multivariate models adjusting for sex, age, fasting plasma glucose, and obesity, liver enzymes levels were directly related to both AdipoR1 and AdipoR2 expression in liver. CONCLUSION: In obese patients with NASH, adiponectin receptors are underexpressed in visceral fat-as a likely correlate of obesity-but overexpressed in liver, possibly as a compensatory response to hypoadiponectinemia, and positively associated with liver damage.
Asunto(s)
Hígado Graso/metabolismo , Hígado/metabolismo , Receptores de Adiponectina/metabolismo , Adiponectina/metabolismo , Adulto , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Grasa Intraabdominal/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/metabolismoRESUMEN
This paper reports the results of a joint project carried out by three regional environmental agencies of Italy to evaluate long-range mercury (Hg) transport from the abandoned Mt. Amiata Hg district in southern Tuscany (the third largest worldwide site for Hg production) to the fluvial ecosystems of the Paglia and Tiber rivers. Most of the work focused on stream sediments, surface waters and soils. A preliminary survey of Hg0 content in air was also conducted. Data obtained by public health authorities on Hg in vegetables and fish were also included. The highest Hg concentrations (up to thousands of µg/g Hg) were observed in stream sediments and soils directly impacted by Hg mine runoff. Although progressive Hg dilution was observed from north to south along the river, sediments and soils show anomalous Hg levels for over 200â¯km downstream of Mt. Amiata, testifying to an extreme case of long-range Hg contamination. A pervasive redistribution of Hg is observed in all sediment compartments. Presumably, the width of the impacted fluvial corridor corresponds to the entire alluvial plains of the rivers. The floodplains can be considered new sources for downstream Hg redistribution, especially during large flood events. On the other hand, results from water, air, and vegetable sampling indicate low potential for human exposure to Hg. The extent and distribution of the contamination make remediation not viable. Therefore, people and human activities must coexist with such an anomaly. On the technical side, the most urgent action to be taken is a better definition of the exact extent of the contaminated area. On the management side, it is necessary to identify which public institution(s) can best deal with such a widespread phenomenon. According to the precautionary principle, the impact of the contamination on human activities in the affected areas should be considered.
Asunto(s)
Monitoreo del Ambiente/estadística & datos numéricos , Sedimentos Geológicos/química , Mercurio/análisis , Ríos/química , Suelo/química , Contaminantes Químicos del Agua/análisis , Animales , Conservación de los Recursos Naturales , Ecosistema , Exposición a Riesgos Ambientales/estadística & datos numéricos , Peces , Humanos , ItaliaRESUMEN
Synovial Sarcoma (SS) is an aggressive neoplasm commonly affecting deep soft tissues of the extremities. In rare instances SS can arise in large veins of the lower extremities or trunk. We report the first case of intravascular synovial sarcoma (IVSS) occurring in a male patient. A biphasic tumor was diagnosed by histology and immunohistochemistry. Molecular analysis at RNA level confirmed the diagnosis demonstrating the chromosomal translocation t(X;18) (p11.2;q11.2) in the tumor. Although extremely rare, IVSS should be considered in the differential diagnosis of primary intravascular neoplasms and as a potential cause of deep vein thrombosis and thromboembolism.