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BACKGROUND: Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. METHODS: Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. RESULTS: Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%-5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. CONCLUSIONS: The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.
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To date, former research about the impact of HIV infection on mpox poor outcomes is still limited and controversial. Therefore, the aim of this study was to assess the impact of HIV on the clinical course of mpox, in a large population of patients from Spain. Nationwide case-series study. Patients from 18 Spanish hospitals, with PCR-confirmed mpox from April 27, 2022 to June 30, 2023 were included in this study. The main outcome was the development of long or complicated (LC) mpox, defined as: (i) duration of the clinical course ≥ 28 days, or; (ii) disseminated disease, or: (iii) emergence of severe complications. One thousand eight hundred twenty-three individuals were included. Seven hundred eighty-six (43%) were people living with HIV (PLWH), of whom 11 (1%) had a CD4 cell count < 200 cells/mm3 and 33 (3%) <350 cells/mm3 . HIV viral load ≥ 1000 cp/mL was found in 27 (3%) PLWH, none of them were on effective ART. Fifteen (60%) PLWH with HIV-RNA ≥ 1000 cp/mL showed LC versus 182 (29%) PLWH with plasma HIV-RNA load < 1000 copies/mL and 192 (24%) individuals without HIV infection (p < 0.001). In multivariate analysis, adjusted by age, sex, CD4 cell counts and HIV viral load at the time of mpox, only plasma HIV-RNA ≥ 1000 cp/mL was associated with a greater risk of developing LC mpox [adjusted OR = 4.06 (95% confidence interval 1.57-10.51), p = 0.004]. PLWH with uncontrolled HIV infection, due to lack of ART, are at a greater risk of developing LC mpox. Efforts should be made to ensure HIV testing is carried out in patients with mpox and to start ART without delay in those tested positive.
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Infecções por HIV , Mpox , Humanos , Contagem de Linfócito CD4 , Progressão da Doença , RNARESUMO
Tomatoes are well known for their impressive nutritional value among vegetables. However, the industrial processing of tomatoes generates a significant amount of waste. Specifically, 10% to 18% of the raw materials used in tomato processing become waste. This waste can seriously affect ecosystems, such as freshwater bodies, wetlands, rivers, and other natural environments, if not properly managed. Interestingly, tomato waste, specifically the skin, contains lycopene, a potent antioxidant and antimutagenic that offers a range of health benefits. This makes it a valuable ingredient in industries such as food and cosmetics. In addition, researchers are exploring the potential of lycopene in the treatment of various types of cancer. This systematic review, guided by the PRISMA 2020 methodology, examined studies exploring the possibility of tomato peel as a source of lycopene and carotenoids for cancer treatment. The findings suggest that tomato peel extracts exhibit promising anticancer properties, underscoring the need for further investigation of possible therapeutic applications. The compiled literature reveals significant potential for using tomato peel to create new cancer treatments, which could potentially revolutionize the field of oncology. This underscores the importance of continued research and exploration, emphasizing the urgency and importance of the scientific community's contribution to this promising area of study.
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Licopeno , Neoplasias , Solanum lycopersicum , Solanum lycopersicum/química , Licopeno/química , Licopeno/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Carotenoides/uso terapêutico , Carotenoides/química , Carotenoides/farmacologia , AnimaisRESUMO
Cancer stands as one of the deadliest diseases in human history, marked by an inferior prognosis. While traditional therapeutic methods like surgery, chemotherapy, and radiation have demonstrated success in inhibiting tumor cell growth, their side effects often limit overall benefits and patient acceptance. In this regard, three different graphene oxides (GO) with variations in their degrees of oxidation were studied chemically and tissue-wise. The accuracy of the synthesis of the different GO was verified by robust techniques using X-ray photoelectron spectroscopy (XPS), as well as conventional techniques such as infrared spectroscopy (FTIR), RAMAN spectroscopy, and X-ray diffraction (XRD). The presence of oxygenated groups was of great importance. It affected the physicochemical properties of each of the different graphene oxides demonstrated in the presence of new vibrational modes related to the formation of new bonds promoted by the graphitization of the materials. The toxicity analysis in the Hep-2 cell line of graphene oxide formulations at 250 µg/mL on the viability and proliferation of these tumor cells showed low activity. GO formulations did not show high antibacterial activity against Staphylococcus aureus and Escherichia coli strains. However, the different graphene oxides showed biocompatibility in the subdermal implantation model for 30, 60, and 90 days in the biomodels. This allowed healing by restoring hair and tissue architecture without triggering an aggressive immune response.
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Grafite , Neoplasias do Colo do Útero , Humanos , Feminino , Grafite/farmacologia , Antibacterianos/farmacologia , Escherichia coli , Óxidos/farmacologiaRESUMO
OBJECTIVES: HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials. METHODS: The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts. RESULTS: Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (Pâ=â1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use. CONCLUSIONS: G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.
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Coinfecção , Infecções por HIV , Hepatite C Crônica , Humanos , Antivirais/farmacologia , Coinfecção/tratamento farmacológico , Coinfecção/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos como Assunto , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)<â50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VLâ<â50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAFâ+âdarunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.
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Fármacos Anti-HIV , Infecções por HIV , Adulto , Feminino , Humanos , Masculino , Adenina/uso terapêutico , Alanina/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/uso terapêutico , Cobicistat/uso terapêutico , Darunavir/uso terapêutico , DNA/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , Espectrometria de Massas em TandemRESUMO
The aim of this study was to assess the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among people living with HIV (PLWH) with severe immunosuppression, after a booster dose. The design was a case-control study nested in a prospective cohort of PLWH. All patients with CD4 cell count <200 cells/mm3 who had received additional dose of messenger RNA (mRNA) COVID-19 vaccine, after a standard immunization scheme were included. Control group: patients age- and sex-matched, with CD4 ≥ 200 cells/mm3 , in the ratio of 2:1. Antibody response to a booster dose (anti-S levels 33.8 ≥ BAU/mL) and neutralizing activity against SARS-CoV-2 B.1, B.1.617.2, and Omicron BA.1, BA.2, and BA.5 strains were assessed after the booster shot. Fifty-four PLWH were included, 18 with CD4 counts < 200 cells/mm3 . Fifty-one (94%) showed response to a booster dose. Response was less frequent in PLWH with CD4 < 200 cells/mm3 than in those with CD4 counts ≥ 200 cells/mm3 (15 [83%] vs. 36 [100%], p = 0.033). In the multivariate analysis, CD4 counts ≥ 200 cells/mm3 [incidence rate ratio (IRR) = 18.1 (95% confidence interval [CI]: 16.8-19.5), p < 0.001] was associated with a higher probability of showing antibody response. Neutralization activity against SARS-CoV-2 B.1, B.1.617, BA.1, and BA.2 strains was significantly inferior among individuals with CD4 counts < 200 cells/mm3 . In conclusion, among PLWH with CD4 counts < 200 cells/mm3 , the immune response elicited by mRNA additional vaccine dose is reduced.
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COVID-19 , Infecções por HIV , Humanos , Vacinas contra COVID-19 , Anticorpos Neutralizantes , Formação de Anticorpos , Estudos de Casos e Controles , Estudos Prospectivos , COVID-19/prevenção & controle , SARS-CoV-2 , Terapia de Imunossupressão , RNA Mensageiro , Anticorpos AntiviraisRESUMO
BACKGROUND AND AIMS: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.
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Técnicas de Imagem por Elasticidade , Infecções por HIV , Hipertensão Portal , Humanos , Cirrose Hepática , Prognóstico , Baço/diagnóstico por imagem , Plaquetas , Fígado/diagnóstico por imagem , Fígado/patologia , Hipertensão Portal/complicações , Infecções por HIV/complicaçõesRESUMO
BACKGROUND: People living with HIV have an increased risk of anal cancer. OBJECTIVE: To estimate anal cancer incidence and related risk factors in a national cohort of HIV-infected patients. DESIGN: Prospective multicenter cohort study. SETTINGS: Multicenter study including patients from the Spanish HIV Research Network. PATIENTS: We collected data from 16,274 HIV-infected treatment-naive adults recruited from January 2004 to November 2020. MAIN OUTCOMES MEASURES: The primary outcome measures of this study were the incidence and prevalence of anal carcinoma. The secondary outcome measures included the associations between baseline and time-dependent covariables and the primary end point. RESULTS: Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29 of 100,000 person-years, which was stable during the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), were mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), had a median age of 43 years (interquartile range, 35-51), were more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16,248; 15%), and had lower nadir CD4 cell counts (115 vs 303 µL). About a third (34.6%, 9/26) were younger than 35 years. In multivariable analysis, men who have sex with men and patients with previous AIDS-defining illness had an 8.3-fold (95% CI, 1.9-36.3) and 2.7-fold (95% CI, 1.1-6.6) increased HR for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI, 41%-22%). LIMITATIONS: Lack of information on some potential risk factors, screening, and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period. CONCLUSIONS: Although the overall incidence in our study was low, there was a significant number of patients younger than 35 years with anal cancer. In addition to age, other factors, such as men who have sex with men and patients with severe immunosuppression (current or past), should be prioritized for anal cancer screening. INCIDENCIA DEL CNCER DE ANO Y LOS FACTORES DE RIESGO RELACIONADOS CON PACIENTES INFECTADOS POR VIH INCLUIDOS EN LA COHORTE PROSPECTIVA NACIONAL ESPAOLA CORIS: ANTECEDENTES:Las personas portadoras del virus de la inmunodeficiencia humana tienen un mayor riesgo de cáncer anal.OBJETIVO:Nosotros queremos estimar la incidencia de cáncer anal y los factores de riesgo relacionados en una cohorte nacional española de pacientes infectados por VIH.DISEÑO:Estudio de cohortes de tipo multicéntrico y prospectivo.ÁMBITO:Se incluyeron pacientes de la Red Española de Investigación en VIH.PACIENTES:Recolectamos los datos de 16,274 adultos infectados por el VIH que nunca habían recibido tratamiento, reclutados desde enero de 2004 hasta noviembre de 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las medidas de resultado primarias de este estudio fueron la incidencia y la prevalencia del carcinoma anal. Las medidas de resultado secundarias incluyeron las asociaciones entre las covariables basales y dependientes del tiempo y el criterio principal de valoración.RESULTADOS:Se diagnosticaron 26 casos de cáncer anal, de los cuales 22 fueron casos incidentales resultando con una incidencia acumulada de 22,29/100.000 personas-año que se mantuvo estable durante el período de estudio.Al final de nuestro estudio, 20 de los 43 centros referentes tenían programas de detección de displasia anal de alto grado. Los pacientes con cáncer anal eran hombres (26/26; 100% vs 13 833/16 248; 85,1%), en su mayoría hombres que mantenían sexo con otros hombres (23/26; 88,5% vs 10 017/16 248; 61,6%), la mediana de edad fue de 43 años (IQR: 3 -51), 34,6% (9/26) < 35 años, previa y frecuentemente diagnosticados con una enfermedad definitoria de SIDA (9/26; 34,6% vs 2429/16248; 15%) y que tenían un punto opuesto mucho más bajo en el recuentos de células CD4 (115 µL frente a 303 µL).En el análisis multivariable, los hombres que tenían relaciones sexuales con otros hombres y los pacientes con enfermedades definitorias de sida anteriores, tenían un aumento de 8,3 veces (IC del 95%: 1,9 a 36,3) y de 2,7 veces (IC del 95%: 1,1 a 6,6) en el cociente de riesgos instantáneos para desarrollar cáncer anal, respectivamente. Los pacientes con recuentos de células CD4 más altos durante el seguimiento mostraron un riesgo 28 % menor por cada 100 células CD4/µl adicionales (95% IC: 41%- 22%).LIMITACIONES:La falta de información sobre algunos factores potenciales de riesgo, la detección y el tratamiento de la displasia anal de alto grado no se iniciaron uniformemente en todos los centros durante el período de estudio.CONCLUSIONES:Si bien la incidencia general en nuestro estudio fue baja, hubo un número significativo de pacientes de <35 años con cáncer anal. Además de la edad, otros factores como los hombres que tienen sexo con hombres y los pacientes con inmunosupresión severa (actual o pasada) deben priorizarse para la detección del cáncer anal. ( Traducción-Dr. Xavier Delgadillo ).
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Síndrome da Imunodeficiência Adquirida , Neoplasias do Ânus , Carcinoma , Minorias Sexuais e de Gênero , Adulto , Masculino , Humanos , Feminino , Incidência , Estudos de Coortes , Homossexualidade Masculina , Estudos Prospectivos , Neoplasias do Ânus/epidemiologia , Fatores de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group). METHODS: We performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log-link) adjusted by significant variables and sex. RESULTS: 13 ICs (BTLA, CD137(4-1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, and TIM-3) and 13 SASP proteins (EGF, Eotaxin, IL-1alpha, IL-1RA, IL-8, IL-13, IL-18, IP-10, SDF-1alpha, HGF, beta-NGF, PLGF-1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After stratifying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD-L2 was significantly higher in SC women, and no differences in SASP were found. CONCLUSIONS: Higher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non-hepatic diseases.
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Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 R)-5α-spirost-3,5,6-triol (1), a diosgenin derivative, ketones 2, 3, 4, and 9 were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (2, 3, 4, and 9) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42-96% yield. Also, a new spirostanic α, ß-unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation.
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Antineoplásicos , Diosgenina , Humanos , Cianocetona , Diosgenina/farmacologia , Esteroides/farmacologia , Antineoplásicos/farmacologia , Oximas/farmacologia , Cetonas/farmacologiaRESUMO
Gastric adenocarcinoma is associated with Helicobacter pylori infection. The transition to a carcinogenic process is preceded by glandular atrophy and serum levels of pepsinogen I and II (PGI and PGII) correlate with this type of gastric lesions. Possible associations of serum PG levels in relation to the frequency of serological activity against H. pylori antigens were studied. Serum samples from patients with gastric pathology associated with H. pylori (n=26) and asymptomatic individuals as controls (n=37) were used. Seroactive antigens were identified by immunoblot using a protein extract of H. pylori. The antibody titers anti-H. pylori and the concentration of PGs in serum was determined by ELISA. Thirty-one seroactive antigens were identified, nine of which exhibited a differential frequency between both groups (116.7, 68.8, 61.9, 54.9, 45.6, 38.3, 36.5, 33.8 and 30.1kDa) and only 3 were related to altered levels of PGs in serum. In the control group, the seropositivity of the 33.8kDa antigen was related to an increase in PGII, while the 68.8kDa antigen was related to normal PG values (decreased PGII and elevated PGI/PGII levels) indicating that seropositivity to this antigen could be a protective factor to gastric pathology. The seropositivity of the 54.9kDa antigen was related to altered values of PGs indicative of inflammation and gastric atrophy (increased in PGII and decreased in PGI/PGII). The identification of serum alterations in pepsinogen levels related to seropositivity to H. pylori 33.8, 54.9 and 68.8kDa antigens sets a precedent for further study as possible prognostic serological biomarkers.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Pepsinogênio A , Infecções por Helicobacter/complicações , Estômago , Pepsinogênio C , Atrofia/complicaçõesRESUMO
BACKGROUND: The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). METHODS: Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. RESULTS: In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]: .08-.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5-24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01-1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01-1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11-.85). CONCLUSIONS: Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.
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Carcinoma Hepatocelular , Infecções por HIV , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Estudos Prospectivos , Resposta Viral SustentadaRESUMO
BACKGROUND: In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. METHODS: This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. RESULTS: Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. CONCLUSIONS: After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.
Assuntos
Coinfecção , Varizes Esofágicas e Gástricas , Infecções por HIV , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Varizes Esofágicas e Gástricas/tratamento farmacológico , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/tratamento farmacológico , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Estudos Prospectivos , Resultado do TratamentoRESUMO
Elbasvir/grazoprevir (EBR/GZR) use in drug users on opiate agonist therapy (OAT) is supported by the C-EDGE Co-STAR trial. SVR rates in this study were within those found in the rest of patients included by the EBR/GZR development programme. In clinical practice, however, efficacy could theoretically be lower. Thus, we aimed at evaluating the SVR rates of EBR/GZR among people who injected drugs (PWID) with and without OAT in clinical practice. Patients starting EBR/GZR included in the HEPAVIR-DAA (NCT02057003), recruiting HIV/HCV-coinfected patients or the GEHEP-MONO (NCT02333292), including HCV-monoinfected individuals, prospective cohorts were analysed. Overall SVR12 (ITT), discontinuations due to adverse effects and drop-outs were evaluated. The same analysis was carried out for PWID with and without OAT. 336 patients had started EBR/GZR and reached the SVR12 evaluation date. 318 [95%, 95% confidence interval (95% CI): 92%-98%] patients achieved SVR12. SVR12 was 97% (95% CI: 93%-99%, n/N = 141/145) among people who never used injecting drugs, 94% (95% CI: 88%-97%, n/N = 117/125) among PWIDs without OAT and 91% (95% CI: 81%-97%, n/N = 60/66) among PWIDs with OAT (p = 0.134). Five (1.5%) patients showed relapses, and two (0.6%) individuals showed viral breakthrough. The SVR12 rate for recent drug users was 69% (n/N = 18/26) compared with 97% (n/N = 276/284) for individuals without recent drug use (in the prior year) (p < 0.001). Among recent drug users, three (12%) showed relapses, and five (19%) were lost-to-follow-up. The SVR rates achieved with EBR/GZR were high in real-world conditions of use. However, PWID with recent drug use reach suboptimal response rates with EBR/GZR.
Assuntos
Hepatite C , Preparações Farmacêuticas , Amidas , Analgésicos Opioides , Antivirais/efeitos adversos , Benzofuranos , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Humanos , Imidazóis , Estudos Prospectivos , Quinoxalinas/efeitos adversos , SulfonamidasRESUMO
BACKGROUND: Hepatitis C Virus (HCV) is a leading cause for chronic liver diseases worldwide. The European Union and World Health Organization aspire to eliminate HCV by 2030. However, among at-risk populations, including, homeless people, prisoners and People Who Inject Drugs, access to diagnosis and treatment is challenging. Hepcare Europe is an integrated model of care developed to address this by assessing potential reasons for these restrictions and determining measures needed to improve HCV diagnosis, treatment and access to care within different communities. OBJECTIVES: HepCare Europe is an EU-supported project involving collaboration between five institutions in: Ireland, United Kingdom, Spain and Romania. We aim to explore the journey of care experienced by those living with HCV with a focus on previous care disruptions (loss to follow up) and the new HepCare Europe Programme. METHODS: Research teams conducted semi-structured interviews with patients who accessed services through HepCare Europe thus, patients were recruited by purposeful sampling. Patients interviewed had received, or were in the final weeks of receiving, treatment. The interviews were audio recorded, transcribed and translated into English, and sent to the Dublin team for inductive thematic analysis. Researchers from the HepCare Europe research team coded the data separately, then together. RESULTS: Common themes are introduced to present similarities, following individual site themes to highlight the importance of tailored interventions for each country. Key themes are: 1) Hepatitis C patients lost to follow up 2) HepCare improved access to treatment and 3) the need for improved HCV education. Individual themes also emerged for each site. These are: Ireland: New opportunities associated with achieving Sustained Virologic Responses (SVR). Romania: HCV is comparatively less crucial in light of Human Immunodeficiency Viruses (HIV) coinfections. UK: Patients desire support to overcome social barriers and Spain: Improved awareness of HCV, treatment and alcohol use. CONCLUSION: This study identified how the tailored HepCare interventions enabled improved HCV testing and linkage to care outcomes for these patients. Tailored interventions that targeted the needs of patients, increased the acceptability and success of treatment by patients. HepCare demonstrated the need for flexibility in treatment delivery, and provided additional supports to keep patients engaged and educated on new treatment therapies.
Assuntos
Atenção à Saúde , Hepatite C/diagnóstico , Hepatite C/terapia , Adulto , Usuários de Drogas , Europa (Continente) , Feminino , Hepacivirus , Pessoas Mal Alojadas , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Prisioneiros , Romênia , Espanha , Resposta Viral Sustentada , Reino UnidoRESUMO
Exosomes are vesicles, ranging of 30-150 nm in diameter, which are released by different cell types into the extracellular space. Exosomes are capable of transporting several biomolecules such as proteins, lipids, DNA, mRNA, and non-coding RNA, including microRNAs (miRs). miRs signatures have been linked to the development of non-communicable diseases and their classification into various subtypes and/or stages. Interestingly, the miRs contained in exosomes (exomiRs) are suitable candidates as non-invasive biomarkers due to their stability in body fluids and harsh conditions, as well as they are considered critical players involved in intercellular communication; so that they can be a promising diagnostic tool for several diseases. Besides, exomiRs allow discrimination between different stages of the disease and could be a valuable strategy for the early detection of several pathologies in a non-invasive approach. This review aims to describe exomiRs present in biologic fluids that can be used as a tool for the diagnosis and prognosis of non-communicable diseases such as cancer, cardiovascular, kidney, and neurodegenerative disease.
Assuntos
Doenças Cardiovasculares/genética , Exossomos/química , Nefropatias/genética , MicroRNAs/genética , Neoplasias/genética , Doenças Neurodegenerativas/genética , Transporte Biológico , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Exossomos/metabolismo , Regulação da Expressão Gênica , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/patologia , MicroRNAs/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/patologia , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/patologia , PrognósticoRESUMO
In order to survive in a hostile habitat, plants have to manage the available resources to reach a delicate balance between development and defense processes, setting up what plant scientists call a trade-off. Most of these processes are basically responses to stimuli sensed by plant cell receptors and are influenced by the environmental features, which can incredibly modify such responses and even cause changes upon both molecular and phenotypic level. Therefore, significant differences can be detected between plants of the same species living in different environments. The comprehension of plant growth-defense trade-offs from the molecular basis to the phenotypic expression is one of the fundamentals for developing sustainable agriculture, so with this review we intend to contribute to the increasing of knowledge on this topic, which have a great importance for future development of agricultural crop production.
Assuntos
Desenvolvimento Vegetal/fisiologia , Animais , Produtos Agrícolas/fisiologia , Ecossistema , HumanosRESUMO
The objective was to evaluate the risk of presenting an alcohol use disorder (AUD) in outpatient psychiatric units and compare it with drug addiction outpatient units and with healthy controls in the same administrative health area. An observational, descriptive, multicenter study was carried out in which a total of 1054 participants were evaluated. Data were obtained by means of the camouflaged CAGE questionnaire, which consists of 4 basic questions camouflaged with 8 other questions about healthy lifestyle habits. Cut-off points 1 and 2 were considered.Of the total number of participants, 588 were psychiatric outpatients, 153 outpatients from addiction centers and 313 healthy individuals. The mean age of the total sample was 45.8 years and the percentage of men was 53.2%. Of the total sample, 38.3% scored ≥1, as did 34.2% of psychiatric patients, 72.5% of drug addicts and 29.4% of healthy people. The ≥2 cut-off was reached by 26.6% of the total sample, 22.6% of psychiatric patients, 64.7% of drug addicts and 15.3% of healthy subjects. The participants with the highest percentage of ≥1 scores were men (48.8%), those younger than 30 years (50%), those with a diagnosis of alcohol use disorder (95.9%) and ADHD (83.3%).Psychiatric patients are at a higher risk of having an AUD than the healthy subjects, although lower than those who are drug addicts, and the CAGE questionnaire is a simple and useful tool to detect the risk patients have to suffer the condition under study.
El objetivo fue evaluar el riesgo de presentar un trastorno por uso de alcohol (TUA) en las consultas psiquiátricas ambulatorias y compararlo con las consultas de drogodependencias y con individuos sanos de la misma zona de salud. Se realizó un estudio observacional, descriptivo, multicéntrico, en el que fueron incluidos un total de 1054 participantes. Se utilizó el cuestionario CAGE camuflado para la obtención de los datos, que consta de 4 preguntas básicas camufladas con otras 8 preguntas sobre hábitos de vida saludables. Se consideraron los puntos de corte de 1 y 2.Del total de participantes, 588 eran pacientes psiquiátricos ambulatorios, 153 de los centros de drogodependencias ambulatorios y 313 sanos. La edad media de la muestra fue de 45,8 años y el porcentaje de hombres fue del 53,2%. El 38,3% de los participantes presentaron una puntuación ≥1, el 34,2% en las consultas psiquiátricas, el 72,5% en las de drogodependencias y el 29,4% en sanos. El 26,6% presentaron una puntuación ≥2, el 22,6% en las consultas psiquiátricas, el 64,7% en las de drogodependencias y el 15,3% en sanos. Los que presentaron mayor porcentaje de puntuación ≥1 fueron los hombres (48,8%), los menores de 30 años (50%), y los que tenían un diagnóstico de trastorno por uso de alcohol (95,9%) y de TDAH (83,3%).Los pacientes psiquiátricos presentan un mayor riesgo de presentar un TUA que los individuos sanos, aunque menor que los drogodependientes, siendo el cuestionario CAGE una herramienta sencilla y útil para detectar el riesgo de presentarlos.
Assuntos
Alcoolismo , Usuários de Drogas , Transtornos Relacionados ao Uso de Substâncias , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Populacionais , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: People living with human immunodeficiency virus (PLWH) are at increased risk of cirrhosis and esophageal varices. Baveno VI criteria, based on liver stiffness measurement (LSM) and platelet count, have been proposed to avoid unnecessary esophagogastroduodenoscopy (EGD) screening for esophageal varices needing treatment (EVNT). This approach has not been validated in PLWH. METHODS: PLWH from 8 prospective cohorts were included if they fulfilled the following criteria: (1) compensated advanced chronic liver disease (LSM >10 kPa); (2) availability of EGD within 6 months of reliable LSM. Baveno VI (LSM <20 kPa and platelets >150 000/µL), expanded Baveno VI (LSM <25 kPa and platelets >110 000/µL), and Estudio de las Hepatitis Víricas (HEPAVIR) criteria (LSM <21 kPa) were applied to identify patients not requiring EGD screening. Criteria optimization was based on the percentage of EGDs spared, while keeping the risk of missing EVNT <5%. RESULTS: Five hundred seven PLWH were divided into a training (n = 318) and a validation set (n = 189). EVNT were found in 7.5%. In the training set, Baveno VI, expanded Baveno VI, and HEPAVIR criteria spared 10.1%, 25.5%, and 28% of EGDs, while missing 0%, 1.2%, and 2.2% of EVNT, respectively. The best thresholds to rule out EVNT were platelets >110 000/µL and LSM <30 kPa (HIV cirrhosis criteria), with 34.6% of EGDs spared and 0% EVNT missed. In the validation set, HEPAVIR and HIV cirrhosis criteria spared 54% and 48.7% of EGDs, while missing 4.9% and 2.2% EVNT, respectively. CONCLUSIONS: Baveno VI criteria can be extended to HEPAVIR and HIV cirrhosis criteria while sparing a significant number of EGDs, thus improving resource utilization for PLWH with compensated advanced chronic liver disease.