Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.Universidade Estadual Paulista (UNESP) Botucatu School of MedicineUniversidade Federal do Rio de JaneiroUniversidade Estadual de CampinasUniversidade Federal de São Paulo (UNIFESP)Pontificia Universidade Catolica de São PauloUNIFESPSciEL

Correlação da intensidade do sinal em FLAIR e os níveis de mediadores inflamatórios no hipocampo de pacientes com epilepsia do lobo temporal e esclerose mesial temporal

We investigated a relationship between the FLAIR signal found in mesial temporal sclerosis (MTS) and inflammation. Twenty nine patients were selected through clinical and MRI analysis and submitted to cortico-amygdalo-hippocampectomy to seizure control. Glutamate, TNF&#945;, IL1, nitric oxide (NO) levels and immunostaining against IL1&#946; and CD45 was performed. Control tissues (n=10) were obtained after autopsy of patients without neurological disorders. The glutamate was decreased in the temporal lobe epilepsy (TLE) -MTS group (p<0.001), suggesting increased release of this neurotransmitter. The IL1&#946; and TNF&#945; were increased in the hippocampus (p<0.05) demonstrating an active inflammatory process. A positive linear correlation between FLAIR signal and NO and IL1&#946; levels and a negative linear correlation between FLAIR signal and glutamate concentration was found. Lymphocytes infiltrates were present in hippocampi of TLE patients. These data showed an association between hippocampal signal alteration and increased inflammatory markers in TLE-MTS.Este estudo foi delineado para investigar a presença de relação entre a intensidade de sinal em FLAIR e níveis de citocinas, óxido nítrico (NO) e glutamato no hipocampo de pacientes com epilepsia do lobo temporal refratária, associada com esclerose mesial (TLE-MTS). Vinte e nove pacientes foram selecionados através de análise clínica e de ressonância magnética (RM) que foram submetidos a cortico-amigdalo-hipocampectomia para o controle das crises. Os níveis de glutamato foram avaliados por HPLC, as citocinas TNF&#945; e IL1&#946; por ELISA e os níveis de NO via NO system. Avaliamos também por imuno-histoquímica a expressão de IL1&#946; e CD45 em tecidos controles e com esclerose. Tecido controle foi obtido após autópsia de indivíduos mortos sem disfunções inflamatórias e neurológicas (n=10). A concentração de glutamato se mostrou reduzida no tecido TLE-MTS (p<0,001) sugerindo aumento na liberação desse neurotransmissor. TNF&#945; e IL1&#946; também apresentaram níveis elevados no hipocampo dos pacientes (p<0,05), demonstrando um processo inflamatório crônico. Houve uma correlação linear positiva entre a intensidade do sinal em FLAIR e os níveis de NO e IL1&#946;. Em contraste, uma correlação linear negativa foi encontrada entre a intensidade do sinal em FLAIR e níveis de glutamato no hipocampo com esclerose. Infiltrado linfocitário hipocampal também foi visualizado pela imuno-marcação com CD45 em pacientes com TLE-MTS. Esses dados mostraram uma associação entre alteração de sinal na RM e marcadores inflamatórios em pacientes com TLE-MTS.FAPESP - CInNAPCeCNPqMCT - Instituto Nacional de Neurociência Translaciona

SLAM Project - Long Term Ecological Study of the Impacts of Climate Change in the natural forests of Azores: V - New records of terrestrial arthropods after ten years of SLAM sampling

BACKGROUND: A long-term study monitoring arthropods (Arthropoda) is being conducted since 2012 in the forests of Azorean Islands. Named "SLAM - Long Term Ecological Study of the Impacts of Climate Change in the natural forest of Azores", this project aims to understand the impact of biodiversity erosion drivers in the distribution, abundance and diversity of Azorean arthropods. The current dataset represents arthropods that have been recorded using a total of 42 passive SLAM traps (Sea, Land and Air Malaise) deployed in native, mixed and exotic forest fragments in seven Azorean Islands (Flores, Faial, Pico, Graciosa, Terceira, São Miguel and Santa Maria). This manuscript is the fifth data-paper contribution, based on data from this long-term monitoring project. NEW INFORMATION: We targeted taxa for species identification belonging to Arachnida (excluding Acari), Chilopoda, Diplopoda, Hexapoda (excluding Collembola, Lepidoptera, Diptera and Hymenoptera (but including only Formicidae)). Specimens were sampled over seven Azorean Islands during the 2012-2021 period. Spiders (Araneae) data from Pico and Terceira Islands are not included since they have been already published elsewhere (Costa and Borges 2021, Lhoumeau et al. 2022). We collected a total of 176007 specimens, of which 168565 (95.7%) were identified to the species or subspecies level. For Araneae and some Hemiptera species, juveniles are also included in this paper, since the low diversity in the Azores allows a relatively precise species-level identification of this life-stage. We recorded a total of 316 named species and subspecies, belonging to 25 orders, 106 families and 260 genera. The ten most abundant species were mostly endemic or native non-endemic (one Opiliones, one Archaeognatha and seven Hemiptera) and only one exotic species, the Julida Ommatoiulus moreleti (Lucas, 1860). These ten species represent 107330 individuals (60%) of all sampled specimens and can be considered as the dominant species in the Azorean native forests for the target studied taxa. The Hemiptera were the most abundant taxa, with 90127 (50.4%) specimens. The Coleoptera were the most diverse with 30 (28.6%) families. We registered 72 new records for many of the islands (two for Flores, eight for Faial, 24 for Graciosa, 23 for Pico, eight for Terceira, three for São Miguel and four for Santa Maria). These records represent 58 species. None of them is new to the Azores Archipelago. Most of the new records are introduced species, all still with low abundance on the studied islands. This publication contributes to increasing the baseline information for future long-term comparisons of the arthropods of the studied sites and the knowledge of the arthropod fauna of the native forests of the Azores, in terms of species abundance, distribution and diversity throughout seasons and years.AMCS is supported by the Ramón y Cajal program (RYC2020-029407-I), financed by the Spanish Ministerio de Ciencia e Innovación. IRA and MB were funded by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., under the Norma Transitória – DL 57/2016/CP1375/CT0003 and DL 57/2016/CP1375/CT0001, respectively. Several projects supported the acquisition of traps during the last ten years, namely: EUFCT-NETBIOME –ISLANDBIODIV grant 0003/2011 (between 2012 and 2015); Portuguese National Funds, through FCT – Fundação para a Ciência e Tecnologia, within the project UID/BIA/00329/2013-2020; Direcção Regional do Ambiente - PRIBES (LIFE17 IPE/PT/ 000010) (2019); Direcção Regional do Ambiente – LIFE-BETTLES (LIFE18 NAT_PT_000864) (2020); AZORESBIOPORTAL – PORBIOTA (ACORES-01-0145- FEDER-000072) (2019); (FCT) - MACRISK-Trait-based prediction of extinction risk and invasiveness for Northern Macaronesian arthropods (FCT-PTDC/BIA-CBI/0625/2021) (2021-2022). Data curation and open Access of this manuscript were supported by the project MACRISK-Trait-based prediction of extinction risk and invasiveness for Northern Macaronesian arthropods (FCT-PTDC/BIA-CBI/0625/2021).info:eu-repo/semantics/publishedVersio

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10;

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%,

Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment:interim analysis from a phase II clinical trial

BACKGROUND: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. METHODS: PBMCs were obtained from 10 HIV(+) individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient’s HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients’ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4(+) and CD8(+) T-cells. RESULTS: The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4(+) and CD8(+) T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4(+) T-cells. The number of candidates that increased in vitro the cytokine levels in CD4(+) and CD8(+) T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. CONCLUSIONS: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829, posted November 11th, 2016) SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-021-00426-z