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Flavobacterium strains exert a substantial influence on roots and leaves of plants. However, there is still limited understanding of how the specific interactions between Flavobacterium and their plant hosts are and how these bacteria thrive in this competitive environment. A crucial step in understanding Flavobacterium - plant interactions is to unravel the structure of bacterial envelope components and the molecular features that facilitate initial contact with the host environment. Here, we have revealed structure and properties of the exopolysaccharides (EPS) produced by Flavobacterium sp. Root935. Chemical analyses revealed a complex and interesting branched heptasaccharidic repeating unit, containing a variety of sugar moieties, including Rha, Fuc, GlcN, Fuc4N, Gal, Man and QuiN and an important and extended substitution pattern, including acetyl and lactyl groups. Additionally, conformational analysis using molecular dynamics simulation showed an extended hydrophobic interface and a distinctly elongated, left-handed helicoidal arrangement. Furthermore, properties of the saccharide chain, and likely the huge substitution pattern prevented interaction and recognition by host lectins and possessed a low immunogenic potential, highlighting a potential role of Flavobacterium sp. Root935 in plant-microbial crosstalk.
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Flavobacterium , Polissacarídeos Bacterianos , Flavobacterium/química , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/isolamento & purificação , Simulação de Dinâmica Molecular , Raízes de Plantas/microbiologia , Raízes de Plantas/químicaRESUMO
The transition from MIRU-VNTR-based epidemiology studies in tuberculosis (TB) to genomic epidemiology has transformed how we track transmission. However, short-read sequencing is poor at analyzing repetitive regions such as the MIRU-VNTR loci. This causes a gap between the new genomic data and the large amount of information stored in historical databases. Long-read sequencing could bridge this knowledge gap by allowing analysis of repetitive regions. However, the feasibility of extracting MIRU-VNTRs from long reads and linking them to historical data has not been evaluated. In our study, an in silico arm, consisting of inference of MIRU patterns from long-read sequences (using MIRUReader program), was compared with an experimental arm, involving standard amplification and fragment sizing. We analyzed overall performance on 39 isolates from South Africa and confirmed reproducibility in a sample enriched with 62 clustered cases from Spain. Finally, we ran 25 consecutive incident cases, demonstrating the feasibility of correctly assigning new clustered/orphan cases by linking data inferred from genomic analysis to MIRU-VNTR databases. Of the 3,024 loci analyzed, only 11 discrepancies (0.36%) were found between the two arms: three attributed to experimental error and eight to misassigned alleles from long-read sequencing. A second round of analysis of these discrepancies resulted in agreement between the experimental and in silico arms in all but one locus. Adjusting the MIRUReader program code allowed us to flag potential in silico misassignments due to suboptimal coverage or unfixed double alleles. Our study indicates that long-read sequencing could help address potential chronological and geographical gaps arising from the transition from molecular to genomic epidemiology of tuberculosis. IMPORTANCE: The transition from molecular epidemiology in tuberculosis (TB), based on the analysis of repetitive regions (VNTR-based genotyping), to genomic epidemiology transforms in the precision with which we track transmission. However, short-read sequencing, the most common method for performing genomic analysis, is poor at analyzing repetitive regions. This means that we face a gap between the new genomic data and the large amount of information stored in historical databases, which is also an obstacle to cross-national surveillance involving settings where only molecular data are available. Long-read sequencing could help bridge this knowledge gap by allowing analysis of repetitive regions. Our study demonstrates that MIRU-VNTR patterns can be successfully inferred from long-read sequences, allowing the correct assignment of new cases as clustered/orphan by linking new data extracted from genomic analysis to historical MIRU-VNTR databases. Our data may provide a starting point for bridging the knowledge gap between the molecular and genomic eras in tuberculosis epidemiology.
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BACKGROUND: Carboplatin and paclitaxel (CP) have been the standard of care for advanced/recurrent endometrial cancer (EC) for many years. However, this chemotherapy combination shows limited efficacy and recurrences often occur in less than 12 months. ABTL0812 is a novel drug that selectively kill cancer cells by cytotoxic autophagy and has shown anticancer efficacy in preclinical models of EC in combination with CP. METHODS: ENDOLUNG was an open-label, phase 1/2 clinical trial designed to determine the safety and efficacy of Ibrilatazar (ABTL0812) with CP in patients with advanced/recurrent EC and non-irradiable stage III and IV squamous non-small cell lung cancer (sq-NSCLC). The phase 1 part consisted of a 3 + 3 de-escalation design followed by an expansion cohort with 12 patients. The primary endpoint was safety. ABTL0812 starting dose was 1300 mg tid combined with carboplatin at area under the curve (AUC) 5 and paclitaxel at 175 mg/m2 both administered every 21 days for up to 8 cycles. The phase 2 part included a total of 51 patients. The primary endpoint was overall response rate (ORR) and the secondary endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival (OS). RESULTS: During the phase 1 only one dose limiting toxicity (DLT), a grade 4 neutropenia, was observed in 1 out of 6 patients, thus no de-escalation was applied. One additional DLT, a grade 3 febrile neutropenia, was observed in the expansion cohort, thus the recommended phase 2 dose (RP2D) for ABTL0812 was established at 1300 mg tid. Most frequent hematological adverse events (AE) of the combination were neutropenia (52.9%), anemia (37.3%) and thrombocytopenia (19.6%). Nausea (66.7%), asthenia (66.7%), diarrhea (54.9%) and vomiting (54.9%) were the most frequent non-hematological adverse events (AEs). The combination of ABTL0812 plus CP showed an ORR of 65.8% (13.2% complete response and 52.6% partial response) with a median DOR of 7.4 months (95% CI: 6.3-10.8 months). Median PFS was 9.8 months (95% CI: 6.6-10.6) and median OS 23.6 months (95% CI 6.4-ND). Pharmacokinetic parameters were compatible with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation during, at least, 28 days after starting the treatment. CONCLUSIONS: This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC. Our data warrant further confirmation in prospective randomized trials. TRIAL REGISTRATION: EU Clinical Trial Register, EudraCT number 2016-001352-21 and National Clinical Trials Number, NCT03366480. Registration on 19 September 2016.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Neoplasias do Endométrio , Recidiva Local de Neoplasia , Paclitaxel , Feminino , Humanos , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Pessoa de Meia-Idade , Idoso , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Autofagia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologiaRESUMO
Patients with chronic hypoxia show a higher tumor incidence; however, no primary common cause has been recognized. Given the similarities between cellular reprogramming and oncogenic transformation, we directly compared these processes in human cells subjected to hypoxia. Mouse embryonic fibroblasts were employed as controls to compare transfection and reprogramming efficiency; human adipose-derived mesenchymal stem cells were employed as controls in human cells. Easily obtainable human peripheral blood mononuclear cells (PBMCs) were chosen to establish a standard protocol to compare cell reprogramming (into induced pluripotent stem cells (iPSCs)) and oncogenic focus formation efficiency. Cell reprogramming was achieved for all three cell types, generating actual pluripotent cells capable for differentiating into the three germ layers. The efficiencies of the cell reprogramming and oncogenic transformation were similar. Hypoxia slightly increased the reprogramming efficiency in all the cell types but with no statistical significance for PBMCs. Various PBMC types can respond to hypoxia differently; lymphocytes and monocytes were, therefore, reprogrammed separately, finding a significant difference between normoxia and hypoxia in monocytes in vitro. These differences were then searched for in vivo. The iPSCs and oncogenic foci were generated from healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). Although higher iPSC generation efficiency in the patients with COPD was found for lymphocytes, this increase was not statistically significant for oncogenic foci. Remarkably, a higher statistically significant efficiency in COPD monocytes was demonstrated for both processes, suggesting that physiological hypoxia exerts an effect on cell reprogramming and oncogenic transformation in vivo in at least some cell types.
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Transformação Celular Neoplásica , Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Humanos , Reprogramação Celular/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Animais , Camundongos , Hipóxia Celular , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/citologia , Masculino , Feminino , Pessoa de Meia-Idade , Fibroblastos/metabolismo , Fibroblastos/patologia , Diferenciação Celular/genética , IdosoRESUMO
The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.
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Cuidados Críticos , Hiperemia , Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Hiperemia/metabolismo , Humanos , Cuidados Críticos/métodos , Oxigênio/metabolismo , Oxigênio/sangue , Consumo de Oxigênio/fisiologia , Oximetria/métodos , Oximetria/instrumentação , Músculo Esquelético/metabolismo , Músculo Esquelético/irrigação sanguínea , Microcirculação/fisiologia , Microvasos/metabolismo , Saturação de Oxigênio/fisiologiaRESUMO
The aim of this meta-analysis was to determine the effects of low-load blood flow restriction training (LL-BFRT) on muscle anabolism and thrombotic biomarkers compared with the effects of traditional LL training and to analyse the changes in these biomarkers in the short and medium term (acute/immediate and after at least 4 weeks of the training programme, respectively). A search was conducted in the following electronic databases from inception to 1 March 2024: MEDLINE, CENTRAL, Web of Science, PEDro, Science Direct, CINHAL, and Scopus. A total of 13 randomized controlled trials were included, with a total of 256 healthy older adults (mean (min-max) age 68 (62-71) years, 44.53% female). The outcome measures were muscle anabolism biomarkers and thrombosis biomarkers. The standardized mean difference (SMD) was calculated to compare the outcomes reported by the studies. The overall meta-analysis showed that LL-BFRT produces a large increase in muscle anabolism biomarkers compared with traditional LL training (eight studies; SMD = 0.88 [0.39; 1.37]) and compared with a passive control (four studies; SMD = 0.91 [0.54; 1.29]). LL-BFRT does not produce an increase in thrombotic biomarkers compared with traditional LL training (four studies; SMD = -0.02 [-0.41; 0.36]) or compared with a passive control (two studies; SMD = 0.20 [-0.41; 0.80]). The increase in muscle anabolism biomarkers was large after applying a single session (four studies; SMD = 1.29 [0.18; 2.41]) and moderate after applying a training programme (four studies; SMD = 0.58 [0.09; 1.06]). In conclusion, LL-BFRT increases muscle anabolism biomarkers to a greater extent than traditional LL training (low-quality evidence) or a passive control (moderate-quality evidence) in healthy older adults. This superior anabolic potential of LL-BFRT compared with LL training is sustained in the short to medium term. LL-BFRT is a safe training methodology for older adults, showing moderate-quality evidence of no increase in thrombotic biomarkers compared with traditional LL training.
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Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.
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Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Macrolídeos , Filogenia , Infecção Persistente , Reinfecção , Farmacorresistência Bacteriana/genética , Genômica , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND/OBJECTIVES: To assess the methodological quality of Clinical Practice Guidelines (CPG) for the diagnosis and management of Retinal Vein Occlusion (RVO). METHODS: A systematic review of CPGs for the diagnosis and management of RVO was carried out with a search in databases, metasearch engines, CPG development institutions, ophthalmology associations and CPG repositories until April 2022. Search update was performed on April 2023, with no new record available. Five CPGs published in the last 10 years in English/Spanish were selected, and 5 authors evaluated them independently, using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument. An individual assessment of each CPG by domain (AGREE-II), an overall assessment of the guide, and its use with or without modifications were performed. Additionally, a meta-synthesis of the recommendations for the most relevant outcomes was carried out. RESULTS: The lowest score (mean 18.8%) was for domain 5 'applicability', and the highest score (mean 62%) was for domain 4 'clarity of presentation'. The 2019 American guideline (PPP) presented the best score (40.4%) in domain 3 'rigour of development'. When evaluating the overall quality of the CPGs analysed, all CPGs could be recommended with modifications. In the meta-synthesis, anti-VEGF therapy is the first-choice therapy for macular oedema associated with RVO, but there is no clear recommendation about the type of anti-VEGF therapy to choose. Recommendations for diagnosis and follow-up are similar among the CPGs appraised. CONCLUSION: Most CPGs for the diagnosis and management of RVO have a low methodological quality assessed according to the AGREE-II. PPP has the higher score in the domain 'rigour of development'. Among the CPGs appraised, there is no clear recommendation on the type of anti-VEGF therapy to choose.
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Inibidores da Angiogênese , Guias de Prática Clínica como Assunto , Oclusão da Veia Retiniana , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/terapia , Humanos , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Injeções Intravítreas , Gerenciamento Clínico , Oftalmologia/normasRESUMO
Hepatic focal lesions are a heterogeneous group of lesions that can be either benign or malignant in nature. They are typically diagnosed through ultrasound in all cases needing to rule out a metastatic nature. We present the case of a 51-year-old male from Morocco diagnosed with hepatic SOLs in the context of abdominal pain and constitutional syndrome.
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INTRODUCTION AND OBJECTIVES: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. PATIENTS AND METHODS: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. RESULTS: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). CONCLUSIONS: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.
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Vacinas contra COVID-19 , COVID-19 , Recidiva , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Vacinas contra COVID-19/efeitos adversos , Estudos Retrospectivos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Estudos Prospectivos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , SARS-CoV-2 , Idoso , Adulto , Imunização Secundária , Fatores de Risco , Transplante de Fígado , Imunossupressores/efeitos adversosRESUMO
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 Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Programas de Rastreamento , Serviços Médicos de Emergência , Hepatite C/diagnóstico , Hepatite C/prevenção & controle , Hepacivirus , EspanhaRESUMO
Regulating the transition of bacteria from motile to sessile lifestyles is crucial for their ability to compete effectively in the rhizosphere environment. Pseudomonas are known to rely on extracellular matrix (ECM) components for microcolony and biofilm formation, allowing them to adapt to a sessile lifestyle. Pseudomonas ogarae F113 possesses eight gene clusters responsible for the production of ECM components. These gene clusters are tightly regulated by AmrZ, a major transcriptional regulator that influences the cellular levels of c-di-GMP. The AmrZ-mediated transcriptional regulation of ECM components is primarily mediated by the signaling molecule c-di-GMP and the flagella master regulator FleQ. To investigate the functional role of these ECM components in P. ogarae F113, we performed phenotypic analyses using mutants in genes encoding these ECM components. These analyses included assessments of colony morphology, dye-staining, static attachment to abiotic surfaces, dynamic biofilm formation on abiotic surfaces, swimming motility, and competitive colonization assays of the rhizosphere. Our results revealed that alginate and PNAG polysaccharides, along with PsmE and the fimbrial low molecular weight protein/tight adherence (Flp/Tad) pilus, are the major ECM components contributing to biofilm formation. Additionally, we found that the majority of these components and MapA are needed for a competitive colonization of the rhizosphere in P. ogarae F113.
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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 , Hepatite C , Masculino , Humanos , Feminino , Espanha/epidemiologia , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Fatores de Risco , Serviço Hospitalar de EmergênciaRESUMO
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)
Assuntos
Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Programas de Rastreamento , Serviços Médicos de Emergência , Hepatite C/diagnóstico , Hepatite C/prevenção & controle , Hepacivirus , EspanhaRESUMO
PURPOSE: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFß receptor II (a TGFß "trap") fused to a human IgG1 mAb blocking programmed death-ligand 1 (PD-L1), was evaluated as treatment in patients with locally advanced or persistent, recurrent, or metastatic (P/R/M) cervical cancer. PATIENTS AND METHODS: In this multicenter, open-label, phase Ib trial (NCT04551950), patients with P/R/M cervical cancer received bintrafusp alfa 2,400 mg once every 3 weeks plus cisplatin or carboplatin plus paclitaxel with (Cohort 1A; n = 8) or without (Cohort 1B; n = 9) bevacizumab; patients with locally advanced cervical cancer received bintrafusp alfa 2,400 mg every 3 weeks plus cisplatin plus radiation, followed by bintrafusp alfa monotherapy maintenance (Cohort 2; n = 8). The primary endpoint was safety; secondary endpoints included efficacy (including objective response rate) and pharmacokinetics. RESULTS: At the data cutoff of April 27, 2022, patients in Cohorts 1A, 1B, and 2 had received bintrafusp alfa for a median duration of 37.9, 31.1, and 16.7 weeks, respectively. Two dose-limiting toxicities (grade 4 amylase elevation and grade 3 menorrhagia) unrelated to bintrafusp alfa were observed in Cohort 1B and none in other cohorts. Most treatment-emergent adverse events of special interest were grades 1-2 in severity, most commonly anemia (62.5%-77.8%) and bleeding events (62.5%-77.8%). Objective response rate was 75.0% [95% confidence interval (CI), 34.9-96.8], 44.4% (95% CI, 13.7-78.8), and 62.5% (95% CI, 24.5-91.5) in Cohorts 1A, 1B, and 2, respectively. CONCLUSIONS: Bintrafusp alfa had manageable safety and demonstrated clinical activity, further supporting the investigation of TGFß/PD-L1 inhibition in human papillomavirus-associated cancers, including cervical cancer.
Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Antígeno B7-H1 , Cisplatino/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Fatores Imunológicos , Paclitaxel/efeitos adversos , Fator de Crescimento Transformador betaAssuntos
Adenocarcinoma Mucinoso , Neoplasias Gástricas , Humanos , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Haemophilia is a haematological disease, although most haemorrhages occur in the locomotor system. Patients are physically disabled from an early age and have a poorer perception of quality of life. In the day-to-day lives of patients and their families, psychosocial well-being, the disease's physical, personal, and social impact, as well as work-related problems are the most complicated aspects of the disease that need to be addressed. OBJECTIVE: To identify the role of occupational therapy in managing patients with haemophilia and to analyse the therapeutic potential of occupational therapy in treating these patients. METHODS: A scoping review was conducted to identify the role of occupational therapy in managing patients with haemophilia and to analyse the therapeutic potential of occupational therapy in treating these patients. The review was registered in the international registry PROSPERO (Id: CRD42022319637). The databases consulted were SCOPUS, PubMed, PsycINFO, Web of Science and Science Direct, including all studies published until 14 August 2023. RESULTS: No single study was found that specifically developed an occupational therapy intervention for patients with haemophilia. Measurement instruments have been identified, specific for patients with haemophilia and generic, that can be useful for the functional evaluation of these patients in the occupational therapy approach. Different studies showed the importance of multidisciplinary treatment, including occupational therapy. CONCLUSIONS: The use of occupational therapy could be effective in improving autonomy and quality of life in haemophilia patients. Therefore, it is of paramount importance to conduct research studies within the field of occupational therapy.