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We evaluated the safety and viral rebound, after analytical treatment interruption (ATI), of vedolizumab and ART in recent HIV-1 infection. We used this model to analyze the impact of α4ß7 on the HIV-1 reservoir size. Participants started ART with monthly Vedolizumab infusions and ATI was performed at week 24. Biopsies were obtained from ileum and caecum at baseline and week 24. Vedolizumab levels, HIV-1 reservoir, flow cytometry and cell-sorting and antibody competition experiments were assayed. Vedolizumab was safe and well-tolerated. No participant achieved undetectable viremia off ART 24 weeks after ATI. Only a modest effect on the time to achieve >1000 HIV-RNA copies/mL and the proportion of participants off ART was observed, being higher compared to historical controls. Just before ATI, α4ß7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of α4ß7 was observed on peripheral CD4+ T-cells but not in gut (ileum and caecum), where α4ß7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA. Our findings support α4ß7 as an important determinant in HIV-1 reservoir size, suggesting the complete α4ß7 blockade in tissue as a promising tool for HIV-cure combination strategies.
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Objectives: Precise HDV-RNA detection and quantification are pivotal for diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three HDV RNA detection and quantification assays. Methods: Hepatitis Delta RT-PCR system kit, EurobioPlex HDV assay, and RoboGene HDV RNA Quantification kit 2.0 were used for testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. All HDV-RNA positive samples were genotyped using a next-generation sequencing strategy. Results: Qualitative results indicated a 100% concordance between tests. Quantitative results correlated well, r2 = 0.703 (Vircell-vs-Eurobio), r2 = 0.833 (Vircell-vs-RoboGene), r2 = 0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results for correlation and bias. Conclusion: This study underscores the necessity of using reliable HDV-RNA detection and quantification assays, as evidenced by the high concordance rates in qualitative detection and the observed variability in quantitative results. These findings highlight the importance of consistent assay use in clinical practice to ensure accurate diagnosis and effective treatment monitoring of HDV infection.
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Genotipo , Hepatitis D , Virus de la Hepatitis Delta , ARN Viral , Carga Viral , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/aislamiento & purificación , Humanos , ARN Viral/genética , Carga Viral/métodos , Hepatitis D/diagnóstico , Hepatitis D/virología , Juego de Reactivos para Diagnóstico/normas , Sensibilidad y Especificidad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Técnicas de Diagnóstico Molecular/métodosRESUMEN
OBJECTIVES: Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) with multidrug resistance (MDR; confirmed resistance to three or more [or resistance to two or more plus contraindication to one or more] core ART classes) and limited treatment options (LTOs) in Spain. METHODS: This was an observational, retrospective, multicentre, cross-sectional chart review study undertaken in five reference Spanish centres. Participants were people with HIV on ART with MDR and LTOs (detectable viral load [HIV-RNA >200 copies/mL], treatment-limiting drug-drug interaction [DDI], or intolerance precluding the use of one or more ART classes). Prevalence, demographic/clinical characteristics, and treatment options were assessed. Logistic regression analyses were used to identify MDR-associated variables. RESULTS: Of 14 955 screened people with HIV, 69 (0.46%) presented with MDR and 23 (0.15%) had LTOs. The population analysed was 73.9% male with a median age of 54.0 years; the median time since HIV diagnosis was 26.5 years, and median CD4+ cell count was 511.0 cells/µL. The only factor significantly associated with MDR (univariate analysis) was CD4+ cell count. Injection drug use was the most common transmission route. Comorbidities (mainly endocrine and cardiovascular disorders; 34.8% affecting HIV management) and concomitant treatments were frequent. No recent opportunistic infections were reported. Patients had been exposed to the following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease inhibitors (95.6%), non-nucleoside analogue reverse transcriptase inhibitors (87.0%), and integrase strand transfer inhibitors (82.6%). The available fully active drugs were dolutegravir (39.1%), bictegravir (30.4%), and raltegravir (21.7%). CONCLUSIONS: The prevalence of people with HIV with MDR and LTOs in Spain is very low, with approximately half of those studied not exhibiting virological suppression. Low CD4+ cell counts were associated with MDR. These findings may help address the impact and treatment needs of these patients and prevent clinical progression and transmission of MDR HIV.
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Farmacorresistencia Viral Múltiple , Infecciones por VIH , Humanos , Masculino , España/epidemiología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Estudios Transversales , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto , Fármacos Anti-VIH/uso terapéutico , Carga Viral , Recuento de Linfocito CD4RESUMEN
The mpox outbreak, caused by monkeypox virus (MPXV), accelerated the development of molecular diagnostics. In this study, we detail the evaluation of the Research Use Only (RUO) NeuMoDx MPXV assay by multiple European and US sites. The assay was designed and developed by Qiagen for the NeuMoDx Molecular Systems. Primers and probes were tested for specificity and inclusivity in silico. The analytical sensitivity of the assay was determined by testing dilutions of synthetic and genomic MPXV DNA. A total of 296 clinical samples were tested by three sites; the Johns Hopkins University (US), UZ Gent (Belgium, Europe), and Hospital Universitario San Cecilio (Spain, Europe). The analytical sensitivity of the assay was 50 copies/mL for both clades I and II. The assay showed 100% in silico identity for 80 clade I and 99.98% in silico identity for 5,162 clade II genomes. Clade II primers and probes showed 100% in silico specificity; however, identity of at least one of the two sets of clade I primers and probes with variola, cowpox, camelpox, and vaccinia viruses was noticed. The clinical validation showed sensitivity of 99.21% [95% confidence interval (CI): 95.66-99.98%] and specificity of 96.64% (95% CI: 91.62-99.08%) for lesion swab samples. The NeuMoDx MPXV Test shows acceptable analytical and clinical performance. The assay improves the laboratory's workflow as it consolidates nucleic acid extraction, PCR, data analysis, and interpretation and can be interfaced. The Test Strip can differentiate clades I and II, which has important laboratory safety implications. IMPORTANCE: In this manuscript, we provide detailed in silico analysis and clinical evaluation of the assay using a large cohort of clinical samples across three academic centers in Europe and the United States. Because the assay differentiates MPXV clades I and II, this manuscript is timely due to the current need to rule out the regulated clade I by diagnostic clinical laboratories. In December 2023, and due to first report of cases of sexually transmitted clade I infections in the Democratic Republic of the Congo, when generic assays that do not differentiate the clades are used, samples are considered regulated. The assay meets the need of full automation and has a marked positive impact on the laboratory workflow.
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Técnicas de Diagnóstico Molecular , Monkeypox virus , Mpox , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Humanos , Monkeypox virus/genética , Monkeypox virus/aislamiento & purificación , Monkeypox virus/clasificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Mpox/diagnóstico , Mpox/virología , Técnicas de Diagnóstico Molecular/métodos , Europa (Continente) , Estados Unidos , Automatización de Laboratorios/métodos , Cartilla de ADN/genética , BélgicaRESUMEN
In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm1 and emm12; emm12 predominated in 2022 but was surpassed by emm1 in 2023. Spread of M1UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm1, but also important representativeness of emm12 and emm89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the speA gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/emm1, ST36-ST425/emm12, ST242/emm12.37, ST39/emm4, and ST101-ST1295/emm89 isolates. IMPORTANCE: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.
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Neumonía , Infecciones Estreptocócicas , Niño , Humanos , Streptococcus pyogenes , España/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antígenos Bacterianos/genética , Proteínas de la Membrana Bacteriana Externa/genética , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiologíaRESUMEN
Background and Aim: Until the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain. Methods: Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Results: Whole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment.
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Objetivo. Se estima que la prevalencia de infección activa por el virus de la hepatitis C (VHC) en España es de un 0,2%, pero un gran número de personas desconocen su estado de infección. Por ello, se requiere aumentar las estrategias de diagnóstico precoz dirigidas a población vulnerable y con escaso vínculo con el sistema sanitario. El objetivo es evaluar el impacto de un programa de cribado oportunista del VHC en los pacientes atendidos en el servicio de urgencias (SU) de un hospital universitario. Método. Se realizó un cribado oportunista entre agosto de 2021 y abril de 2023 a los pacientes de 18 a 69 años atendidos en el SU que no se habían realizado la prueba del VHC el año anterior, y que requerían un análisis de sangre dentro de la práctica clínica habitual por cualquier motivo. Resultados. Durante el periodo de estudio se atendieron 110.267 pacientes en el SU, fueron candidatos a realizar el cribado 22.712 (20,6%), y finalmente se realizó una serología frente al VHC a 11.368 pacientes (50,1%). Se identificaron 43 casos (0,4% de los test efectuados) de infección activa por VHC (viremia), de los cuales, 24 (56%) desconocían previamente su estado. La media de edad del total de pacientes virémicos fue de 57 (DE: 6 años), 34 (79,1%) eran hombres y 5 (11,6%) tenían nacionalidades distintas a la española. No se identificaron factores de riesgo relacionados con la infección por VHC en 22 (51,2%) de los pacientes, y 41 (95,3%) habían tenido oportunidades de diagnóstico en visitas previas al sistema de salud. De los 18 pacientes analizados mediante elastografía transitoria, 7 (38,8%) presentaban cirrosis en el momento del diagnóstico. Se logró vincular a la atención médica posterior a 33 (77%) de los pacientes con infección activa. Conclusiones. Las tasas de infección activa por VHC detectadas en el programa de cribado fueron más altas que la prevalencia estimada en la población general... (AU)
Background and objective. The prevalence of active hepatitis C virus (HCV) infection in Spain is estimated to be 0.2%, but a large number of persons are unaware of their infection status. Additional approaches to early diagnosis of HCV infection in vulnerable populations with scarce contact with the national health care system are therefore needed. Our aim was to evaluate the impact of an opportunistic screening program to detect HCV-infected patients attended in our university hospital emergency department (ED). Methods. Opportunistic screening was implemented from August 2021 to April 2023 in ED patients aged 18 to 69 years. The test was ordered if HCV screening had not been done in the last year and blood extraction for testing was indicated for any reason as part of routine ED care. Results. A total of 110 267 patients were seen; 22 712 of them (20.6%) were eligible for screening. Serology for HCV was done for 11 368 of the eligible patients (50.1%). Forty-three cases (in 0.4% of tested samples) of active HCV infection (viremia) were found. In 24 of these cases (56%) the patients had not been aware that they were infected. Their mean (SD) age was 57 (6) years, 34 (79.1%) were men, and 5 (11.6%) were citizens of countries other than Spain. No risk factors related to HCV infection could be found for 22 of the patients (51.2%), and 41 (95.3%) could have been diagnosed during previous contact with the health care system. Of the 18 patients evaluated by transient elastography (FibroScan), 7 (38.8%) had signs of cirrhosis at the time of diagnosis. Thirty-three of the patients with active infections (77%) were subsequently able to access care. Conclusions. The rate of active HCV infection in the screening program was higher than the prevalence estimated for the general population. Opportunistic screening for HCV during ED visits is useful for increasing the number of diagnoses and should be considered as a tool for eradicating this disease. (AU)
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Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Tamizaje Masivo , Servicios Médicos de Urgencia , Hepatitis C/diagnóstico , Hepatitis C/prevención & control , Hepacivirus , EspañaRESUMEN
Objetivo. Se estima que la prevalencia de infección activa por el virus de la hepatitis C (VHC) en España es de un 0,2%, pero un gran número de personas desconocen su estado de infección. Por ello, se requiere aumentar las estrategias de diagnóstico precoz dirigidas a población vulnerable y con escaso vínculo con el sistema sanitario. El objetivo es evaluar el impacto de un programa de cribado oportunista del VHC en los pacientes atendidos en el servicio de urgencias (SU) de un hospital universitario. Método. Se realizó un cribado oportunista entre agosto de 2021 y abril de 2023 a los pacientes de 18 a 69 años atendidos en el SU que no se habían realizado la prueba del VHC el año anterior, y que requerían un análisis de sangre dentro de la práctica clínica habitual por cualquier motivo. Resultados. Durante el periodo de estudio se atendieron 110.267 pacientes en el SU, fueron candidatos a realizar el cribado 22.712 (20,6%), y finalmente se realizó una serología frente al VHC a 11.368 pacientes (50,1%). Se identificaron 43 casos (0,4% de los test efectuados) de infección activa por VHC (viremia), de los cuales, 24 (56%) desconocían previamente su estado. La media de edad del total de pacientes virémicos fue de 57 (DE: 6 años), 34 (79,1%) eran hombres y 5 (11,6%) tenían nacionalidades distintas a la española. No se identificaron factores de riesgo relacionados con la infección por VHC en 22 (51,2%) de los pacientes, y 41 (95,3%) habían tenido oportunidades de diagnóstico en visitas previas al sistema de salud. De los 18 pacientes analizados mediante elastografía transitoria, 7 (38,8%) presentaban cirrosis en el momento del diagnóstico. Se logró vincular a la atención médica posterior a 33 (77%) de los pacientes con infección activa. Conclusiones. Las tasas de infección activa por VHC detectadas en el programa de cribado fueron más altas que la prevalencia estimada en la población general... (AU)
Background and objective. The prevalence of active hepatitis C virus (HCV) infection in Spain is estimated to be 0.2%, but a large number of persons are unaware of their infection status. Additional approaches to early diagnosis of HCV infection in vulnerable populations with scarce contact with the national health care system are therefore needed. Our aim was to evaluate the impact of an opportunistic screening program to detect HCV-infected patients attended in our university hospital emergency department (ED). Methods. Opportunistic screening was implemented from August 2021 to April 2023 in ED patients aged 18 to 69 years. The test was ordered if HCV screening had not been done in the last year and blood extraction for testing was indicated for any reason as part of routine ED care. Results. A total of 110 267 patients were seen; 22 712 of them (20.6%) were eligible for screening. Serology for HCV was done for 11 368 of the eligible patients (50.1%). Forty-three cases (in 0.4% of tested samples) of active HCV infection (viremia) were found. In 24 of these cases (56%) the patients had not been aware that they were infected. Their mean (SD) age was 57 (6) years, 34 (79.1%) were men, and 5 (11.6%) were citizens of countries other than Spain. No risk factors related to HCV infection could be found for 22 of the patients (51.2%), and 41 (95.3%) could have been diagnosed during previous contact with the health care system. Of the 18 patients evaluated by transient elastography (FibroScan), 7 (38.8%) had signs of cirrhosis at the time of diagnosis. Thirty-three of the patients with active infections (77%) were subsequently able to access care. Conclusions. The rate of active HCV infection in the screening program was higher than the prevalence estimated for the general population. Opportunistic screening for HCV during ED visits is useful for increasing the number of diagnoses and should be considered as a tool for eradicating this disease. (AU)
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Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Tamizaje Masivo , Servicios Médicos de Urgencia , Hepatitis C/diagnóstico , Hepatitis C/prevención & control , Hepacivirus , EspañaRESUMEN
OBJECTIVES: The prevalence of active hepatitis C virus (HCV) infection in Spain is estimated to be 0.2%, but a large number of persons are unaware of their infection status. Additional approaches to early diagnosis of HCV infection in vulnerable populations with scarce contact with the national health care system are therefore needed. Our aim was to evaluate the impact of an opportunistic screening program to detect HCV-infected patients attended in our university hospital emergency department (ED). MATERIAL AND METHODS: Opportunistic screening was implemented from August 2021 to April 2023 in ED patients aged 18 to 69 years. The test was ordered if HCV screening had not been done in the last year and blood extraction for testing was indicated for any reason as part of routine ED care. RESULTS: A total of 110 267 patients were seen; 22 712 of them (20.6%) were eligible for screening. Serology for HCV was done for 11 368 of the eligible patients (50.1%). Forty-three cases (in 0.4% of tested samples) of active HCV infection (viremia) were found. In 24 of these cases (56%) the patients had not been aware that they were infected. Their mean (SD) age was 57 (6) years, 34 (79.1%) were men, and 5 (11.6%) were citizens of countries other than Spain. No risk factors related to HCV infection could be found for 22 of the patients (51.2%), and 41 (95.3%) could have been diagnosed during previous contact with the health care system. Of the 18 patients evaluated by transient elastography (FibroScan), 7 (38.8%) had signs of cirrhosis at the time of diagnosis. Thirty-three of the patients with active infections (77%) were subsequently able to access care. CONCLUSION: The rate of active HCV infection in the screening program was higher than the prevalence estimated for the general population. Opportunistic screening for HCV during ED visits is useful for increasing the number of diagnoses and should be considered as a tool for eradicating this disease.
OBJETIVO: Se estima que la prevalencia de infección activa por el virus de la hepatitis C (VHC) en España es de un 0,2%, pero un gran número de personas desconocen su estado de infección. Por ello, se requiere aumentar las estrategias de diagnóstico precoz dirigidas a población vulnerable y con escaso vínculo con el sistema sanitario. El objetivo es evaluar el impacto de un programa de cribado oportunista del VHC en los pacientes atendidos en el servicio de urgencias (SU) de un hospital universitario. METODO: Se realizó un cribado oportunista entre agosto de 2021 y abril de 2023 a los pacientes de 18 a 69 años atendidos en el SU que no se habían realizado la prueba del VHC el año anterior, y que requerían un análisis de sangre dentro de la práctica clínica habitual por cualquier motivo. RESULTADOS: Durante el periodo de estudio se atendieron 110.267 pacientes en el SU, fueron candidatos a realizar el cribado 22.712 (20,6%), y finalmente se realizó una serología frente al VHC a 11.368 pacientes (50,1%). Se identificaron 43 casos (0,4% de los test efectuados) de infección activa por VHC (viremia), de los cuales, 24 (56%) desconocían previamente su estado. La media de edad del total de pacientes virémicos fue de 57 (DE: 6 años), 34 (79,1%) eran hombres y 5 (11,6%) tenían nacionalidades distintas a la española. No se identificaron factores de riesgo relacionados con la infección por VHC en 22 (51,2%) de los pacientes, y 41 (95,3%) habían tenido oportunidades de diagnóstico en visitas previas al sistema de salud. De los 18 pacientes analizados mediante elastografía transitoria, 7 (38,8%) presentaban cirrosis en el momento del diagnóstico. Se logró vincular a la atención médica posterior a 33 (77%) de los pacientes con infección activa. CONCLUSIONES: Las tasas de infección activa por VHC detectadas en el programa de cribado fueron más altas que la prevalencia estimada en la población general. El cribado oportunista de VHC en los SU puede ser de utilidad para aumentar el diagnóstico y debe ser considerado como una herramienta para la eliminación de la hepatitis C.
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Hepacivirus , Hepatitis C , Masculino , Humanos , Femenino , España/epidemiología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Factores de Riesgo , Servicio de Urgencia en HospitalRESUMEN
Introducción: La carga viral es un marcador muy útil para realizar el seguimiento de los pacientes infectados por VHB y VHC. Este trabajo compara ensayos basados en amplificación mediada por transcripción y en PCR a tiempo real con el objetivo de comprobar si pueden ser intercambiables. Material y métodos: Estudio bicéntrico en el que se analizó la carga viral de 147 muestras de plasma de pacientes infectados por VHB y 229 por VHC, mediante ensayos basados en amplificación mediada por transcripción (Aptima® HBV Quant y Aptima® HCV Quant Dx, que utilizan el sistema Panther (Hologic®)) y PCR a tiempo real (COBAS® AmpliPrep / COBAS® TaqMan® y COBAS® 6800), calculando el grado de concordancia entre ellos. Resultados: Se detectó carga viral en ambos equipos en 60 (40,82%) muestras de VHB (mediana del log de la carga viral: COBAS®: 2,51UI/mL (RIC 2,20-3,17), Panther: 2,71UI/mL (RIC 2,21-3,22)) y en 39 (16,96%) muestras de VHC (mediana del log de la carga viral: COBAS®: 3,93UI/mL (RIC 2,24-6,01), Panther: 3,80UI/mL (RIC 1,99-6,14)). La concordancia entre ambos equipos fue de κ=0,943 para VHB y κ=0,925 para VHC. La comparación de las muestras con carga viral detectada mediante los 2 ensayos mostró una correlación alta tanto para VHB (R2=0,86) como para VHC (R2=0,97). Conclusiones: Los ensayos basados tanto en amplificación mediada por transcripción como en PCR a tiempo real pueden ser intercambiables para el manejo de pacientes infectados con VHB y VHC.(AU)
Introduction: Viral load is a very useful marker for monitoring patients infected with HBV and HCV. This work compares assays based on transcription-mediated amplification and on real-time PCR to verify whether they can be interchangeable. Material and methods: a bicentric study, in which 147 plasma samples from patients infected with HBV and 229 with HCV were analyzed, was carried out. Transcription-mediated amplification-based assays (Aptima® HBV Quant and Aptima® HCV Quant Dx, employing Panther system (Hologic®)) and on real-time PCR (COBAS® AmpliPrep / COBAS® TaqMan® and COBAS® 6800) were used and the degree of concordance between them was calculated. Results: Viral load was detected in both systems in 60 (40.82%) HBV samples (median log viral load: COBAS®: 2.51IU/mL (IQR 2.20-3.17), Panther: 2.71IU/mL (IQR 2.21-3.22)) and in 39 (16.96%) HCV samples (median log viral load: COBAS®: 3.93IU/mL (IQR 2.24-6.01), Panther: 3.80IU/mL (IQR 1.99-6.14)). The agreement between both systems was κ=0.943 for HBV and κ=0.925 for HCV. Comparison of viral load samples detected by both assays showed a hight correlation for HBV (R2=0.86) and for HCV (R2=0.97). Conclusions: Both transcription-mediated amplification and on real-time PCR based assays may be interchangeable for the management of patients infected with HBV and HCV.(AU)
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Humanos , Masculino , Femenino , Virus de la Hepatitis B , Hepacivirus/genética , Plasma/virología , Carga Viral , Reacción en Cadena en Tiempo Real de la Polimerasa , Microbiología , Técnicas Microbiológicas , Reacción en Cadena de la PolimerasaRESUMEN
INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease is a major public health problem considering its high prevalence and its strong association with extrahepatic diseases. Implementing strategies based on an intermittent fasting approach and supervised exercise may mitigate the risks. This study aims to investigate the effects of a 12-week time-restricted eating (TRE) intervention combined with a supervised exercise intervention, compared with TRE or supervised exercise alone and with a usual-care control group, on hepatic fat (primary outcome) and cardiometabolic health (secondary outcomes) in adults with obesity. METHODS AND ANALYSIS: An anticipated 184 adults with obesity (50% women) will be recruited from Granada (south of Spain) for this parallel-group, randomised controlled trial (TEMPUS). Participants will be randomly designated to usual care, TRE alone, supervised exercise alone or TRE combined with supervised exercise, using a parallel design with a 1:1:1:1 allocation ratio. The TRE and TRE combined with supervised exercise groups will select an 8-hour eating window before the intervention and will maintain it over the intervention. The exercise alone and TRE combined with exercise groups will perform 24 sessions (2 sessions per week+walking intervention) of supervised exercise combining resistance and aerobic high-intensity interval training. All participants will receive nutritional counselling throughout the intervention. The primary outcome is change from baseline to 12 weeks in hepatic fat; secondary outcomes include measures of cardiometabolic health. ETHICS AND DISSEMINATION: This study was approved by Granada Provincial Research Ethics Committee (CEI Granada-0365-N-23). All participants will be asked to provide written informed consent. The findings will be disseminated in scientific journals and at international scientific conferences. TRIAL REGISTRATION NUMBER: NCT05897073.
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Enfermedades Cardiovasculares , Hígado Graso , Adulto , Femenino , Humanos , Masculino , Ejercicio Físico , Caminata , Obesidad/complicaciones , Obesidad/terapia , Enfermedades Cardiovasculares/prevención & control , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Limited data are available regarding the susceptibility of the reverse transcriptase V106 polymorphism to doravirine. METHODS: Doravirine susceptibility was measured in site-directed mutants (SDMs) containing V106I, V106A, V106M, and Y188L mutations in subtype B (NL4-3, HXB2) and CRF02_AG background and in recombinant viruses with RT harboring V106I alone derived from 50 people with HIV. RESULTS: HIV-1 B subtype was detected in 1523 of 2705 cases. Prevalence of V106I was 3.2% in B and 2.5% in non-B subtypes, and was higher in subtype F (8.1%) and D (14.3%). Fold-changes (FC) in susceptibility for SDMs were below doravirine biological cutoff (3.0) for V106I, but not for V106A, V106M, and Y188L. Clinically derived viruses tested included 22 B (median FC, 1.2; interquartile range [IQR], 0.9-1.6) and 28 non-B subtypes (median FC, 1.8; IQR, 0.9-3.0). Nine (18%) viruses showed FC values equal or higher than the doravirine biological FC cutoff. CONCLUSIONS: The prevalence of the HIV-1 RT V106I polymorphism in MeditRes HIV consortium remains low, but significantly more prevalent in subtypes D and F. V106I minimally decreased the susceptibility to doravirine in SDMs and most clinical isolates. Reduced susceptibility seems to occur at increased frequency in subtype F1; however, the clinical impact remains to be investigated. CLINICAL TRIALS REGISTRATION: NCT04894357.
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Fármacos Anti-VIH , Farmacorresistencia Viral , Infecciones por VIH , Transcriptasa Inversa del VIH , VIH-1 , Piridonas , Triazoles , Humanos , VIH-1/genética , VIH-1/efectos de los fármacos , VIH-1/clasificación , VIH-1/enzimología , Transcriptasa Inversa del VIH/genética , Infecciones por VIH/virología , Infecciones por VIH/epidemiología , Piridonas/farmacología , Farmacorresistencia Viral/genética , Fármacos Anti-VIH/farmacología , Triazoles/farmacología , Polimorfismo Genético , Prevalencia , Masculino , Femenino , Inhibidores de la Transcriptasa Inversa/farmacología , Adulto , Genotipo , Fenotipo , Persona de Mediana EdadRESUMEN
INTRODUCTION: Viral load is a very useful marker for monitoring patients infected with HBV and HCV. This work compares assays based on transcription-mediated amplification (TMA) and on real-time PCR (RT-PCR) to verify whether they can be interchangeable. MATERIAL AND METHODS: A bicentric study, in which 147 plasma samples from patients infected with HBV and 229 with HCV were analyzed, was carried out. TMA-based assays (Aptima® HBV Quant and Aptima® HCV Quant Dx, employing Panther system (Hologic®)) and RT-PCR (COBAS® AmpliPrep/COBAS® TaqMan® and COBAS® 6800) were used and the degree of concordance between them was calculated. RESULTS: Viral load was detected in both systems in 60 (40.82%) HBV samples (median log viral load: COBAS: 2.51IU/mL (IQR 2.20-3.17), Panther: 2.71IU/mL (IQR 2.21-3.22)) and in 39 (16.96%) HCV samples (median log viral load: COBAS: 3.93IU/mL (IQR 2.24-6.01), Panther: 3.80IU/mL (IQR 1.99-6.14)). The agreement between both systems was κ=0.943 for HBV and κ=0.925 for HCV. Comparison of viral load samples detected by both assays showed a hight correlation for HBV (R2=0.86) and for HCV (R2=0.97). CONCLUSIONS: Both TMA and RT-PCR based assays may be interchangeable for the management of patients infected with HBV and HCV.
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Virus de la Hepatitis B , Hepatitis C , Humanos , Virus de la Hepatitis B/genética , Carga Viral , Reacción en Cadena en Tiempo Real de la Polimerasa , Hepatitis C/diagnósticoRESUMEN
BACKGROUND AND IMPORTANCE: The rates of hidden infection and late diagnosis of HIV still remain high in Western countries. Missed diagnostic opportunities represent the key point in changing the course of the epidemic. OBJECTIVE: To evaluate the feasibility and results of implementation of a selective strategy to test for HIV in the emergency department (ED) in patients with six pre-defined medical situations: sexually transmitted infections, herpes zoster, community-acquired pneumonia, mononucleosis syndrome, practice of chemsex (CS) or request of post-exposure prophylaxis. DESIGN: This quasi-experimental longitudinal study evaluated the pre- and post-implementation results of HIV testing in the six aforementioned clinical scenarios. SETTINGS AND PARTICIPANTS: Patients attended 34 Spanish EDs. INTERVENTION OR EXPOSURE: The intervention was an intensive educational program and pathways to facilitate and track orders and results were designed. We collected and compared pre- and post-implementation ED census and diagnoses, and HIV tests requested and results. OUTCOME MEASURES AND ANALYSIS: The main outcome was adherence to the recommendations. Secondary outcomes were to evaluate the effectiveness of the program by the rate of positive test and the new HIV diagnoses. Differences between first and second periods were assessed. The magnitude of changes (absolute and relative) was expressed with the 95% confidence interval (CI). MAIN RESULTS: HIV tests increasing from 7080 (0.42% of ED visits) to 13 436 (relative increase of 75%, 95% CI from 70 to 80%). The six conditions were diagnosed in 15 879 and 16 618 patients, and HIV testing was ordered in 3393 (21%) and 7002 (42%) patients (increase: 97%; 95% CI: 90-104%). HIV testing significantly increased for all conditions except for CS. The positive HIV test rates increased from 0.92 to 1.67%. Detection of persons with undiagnosed HIV increased from 65 to 224, which implied a 220% (95% CI: 143-322%) increase of HIV diagnosis among all ED comers and a 71% (95% CI: 30-125%) increase of positive HIV tests. CONCLUSION: Implementation of a strategy to test for HIV in selective clinical situations in the ED is feasible and may lead to a substantial increase in HIV testing and diagnoses.
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Infecciones por VIH , Humanos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Estudios Controlados Antes y Después , Estudios de Factibilidad , Estudios Longitudinales , Tamizaje Masivo/métodos , Prueba de VIH , Servicio de Urgencia en HospitalRESUMEN
BACKGROUND: In response to the pandemic, the International Hepato-Pancreato-Biliary Association (IHPBA) developed the IHPBA-COVID Registry to capture data on HPB surgery outcomes in COVID-positive patients prior to mass vaccination programs. The aim was to provide a tool to help members gain a better understanding of the impact of COVID-19 on patient outcomes following HPB surgery worldwide. METHODS: An online registry updated in real time was disseminated to all IHPBA, E-AHPBA, A-HPBA and A-PHPBA members to assess the effects of the pandemic on the outcomes of HPB procedures, perioperative COVID-19 management and other aspects of surgical care. RESULTS: One hundred twenty-five patients from 35 centres in 18 countries were included. Seventy-three (58%) patients were diagnosed with COVID-19 preoperatively. Operative mortality after pancreaticoduodenectomy and major hepatectomy was 28% and 15%, respectively, and 2.5% after cholecystectomy. Postoperative complication rates of pancreatic procedures, hepatic interventions and biliary interventions were respectively 80%, 50% and 37%. Respiratory complication rates were 37%, 31% and 10%, respectively. CONCLUSION: This study reveals a high risk of mortality and complication after HPB surgeries in patient infected with COVID-19. The more extensive the procedure, the higher the risk. Nonetheless, an increased risk was observed across all types of interventions, suggesting that elective HPB surgery should be avoided in COVID positive patients, delaying it at distance from the viral infection.
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Procedimientos Quirúrgicos del Sistema Biliar , COVID-19 , Humanos , COVID-19/epidemiología , Pancreaticoduodenectomía/efectos adversos , Hepatectomía , Sistema de RegistrosRESUMEN
Introduction: Cytomegalovirus (CMV) is a common herpesvirus with a high prevalence worldwide. After the acute infection phase, CMV can remain latent in several tissues. CD8 T cells in the lungs and salivary glands mainly control its reactivation control. White adipose tissue (WAT) contains a significant population of memory T cells reactive to viral antigens, but CMV specificity has mainly been studied in mouse WAT. Therefore, we obtained blood, omental WAT (oWAT), subcutaneous WAT (sWAT), and liver samples from 11 obese donors to characterize the human WAT adaptive immune landscape from a phenotypic and immune receptor specificity perspective. Methods: We performed high-throughput sequencing of the T cell receptor (TCR) locus to analyze tissue and blood TCR repertoires of the 11 donors. The presence of TCRs specific to CMV epitopes was tested through ELISpot assays. Moreover, phenotypic characterization of T cells was carried out through flow cytometry. Results: High-throughput sequencing analyses revealed that tissue TCR repertoires in oWAT, sWAT, and liver samples were less diverse and dominated by hyperexpanded clones when compared to blood samples. Additionally, we predicted the presence of TCRs specific to viral epitopes, particularly from CMV, which was confirmed by ELISpot assays. Remarkably, we found that oWAT has a higher proportion of CMV-reactive T cells than blood or sWAT. Finally, flow cytometry analyses indicated that most WAT-infiltrated lymphocytes were tissue-resident effector memory CD8 T cells. Discussion: Overall, these findings postulate human oWAT as a major reservoir of CMV-specific T cells, presumably for latent viral reactivation control. This study enhances our understanding of the adaptive immune response in human WAT and highlights its potential role in antiviral defense.
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Infecciones por Citomegalovirus , Citomegalovirus , Animales , Ratones , Humanos , Receptores de Antígenos de Linfocitos T/genética , Epítopos , Tejido AdiposoRESUMEN
To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , España/epidemiología , Filogenia , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/farmacología , Antirretrovirales/uso terapéutico , Integrasas/genética , Integrasas/uso terapéutico , Mutación , Farmacorresistencia Viral/genética , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , PrevalenciaRESUMEN
To evaluate molecular assays for Mpox diagnosis available in various clinical microbiology services in Spain through a quality control (QC) approach. A total of 14 centers from across Spain participated in the study. The Reference Laboratory dispatched eight serum samples and eight nucleic acid extracts to each participating center. Some samples were spiked with Mpox or Vaccinia virus to mimic positive samples for Mpox or other orthopox viruses. Participating centers provided information on the results obtained, as well as the laboratory methods used. Among the 14 participating centers seven different commercial assays were employed, with the most commonly used kit being LightMix Modular Orthopox/Monkeypox (Mpox) Virus (Roche®). Of the 12 centers conducting Mpox determinations, concordance ranged from 62.5% (n = 1) to 100% (n = 11) for eluates and from 75.0% (n = 1) to 100% (n = 10) for serum. Among the 10 centers performing Orthopoxvirus determinations, a 100% concordance was observed for eluates, while for serum, concordance ranged from 87.5% (n = 6) to 100% (n = 4). Repeatedly, 6 different centers reported a false negative in serum samples for Orthopoxvirus diagnosis, particularly in a sample with borderline Ct = 39. Conversely, one center, using the TaqMan™ Mpox Virus Microbe Detection Assay (Thermo Fisher), reported false positives in Mpox diagnosis for samples spiked with vaccinia virus due to cross-reactions. We observed a positive correlation of various diagnostic assays for Mpox used by the participating centers with the reference values. Our results highlight the significance of standardization, validation, and ongoing QC in the microbiological diagnosis of infectious diseases, which might be particularly relevant for emerging viruses.