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OBJECTIVES: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe. METHODS: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders). RESULTS: Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates. CONCLUSION: Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status.
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Anticuerpos Monoclonales Humanizados , Espondiloartritis Axial , Humanos , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Adulto , Resultado del Tratamiento , Europa (Continente) , Persona de Mediana Edad , Espondiloartritis Axial/tratamiento farmacológico , Espondiloartritis Axial/etiología , Antirreumáticos/uso terapéutico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Medición de Resultados Informados por el Paciente , Radiografía , Inducción de RemisiónRESUMEN
INTRODUCTION: Autoimmune diseases are known to be associated with an elevated risk of cardiovascular diseases; however, there exists a lack of awareness regarding this increased risk among patients. OBJECTIVE: This study aimed to assess the prevalence of cardiovascular risk factors and events in various systemic autoimmune diseases, including Systemic Sclerosis (SSc), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren's syndrome (SS), matched by age, sex, and disease duration. Additionally, the study aimed to evaluate the perceived and actual risks of cardiovascular disease among patients. METHODS: A cross-sectional self-reported survey on the patient's perspective of cardiovascular risk was conducted between January and June 2023. Sociodemographic and clinical data, including disease activity, were collected through medical records and questionnaires. Traditional cardiovascular risk factors and events were assessed, alongside the perceived cardiovascular risk. The SCORE calculation and Charlson Comorbidity Index (CCI) were employed for cardiovascular risk assessment. RESULTS: Survey responses from 180 patients (45 patients each with SSc, SLE, RA, and SS) with systemic autoimmune diseases revealed that 20% perceived a low risk, 23% perceived neither lower nor higher, and 56% perceived a higher risk of developing cardiovascular diseases in the next ten years. Only 45% agreed that their autoimmune disease could increase the risk of a heart attack, even in the absence of other risk factors, and 46.7% were unaware that NSAIDs pose a cardiovascular risk. An association between cardiovascular risk measured by SCORE, comorbidities, and risk perception was observed in RA, SSc, and SS patients, with no association found in SLE patients (p=0.27). Except for SS patients (p=0.02), no association between CCI and disease activity level was found. Regarding the influence of age, working status, and education in CVD risk perception, an association between CVD risk perception and age was observed (p=0.01), with patients over 40 years exhibiting a higher perception of CVD risk. No differences were found regarding working status (p=0.19) nor education level (p=0.06). CONCLUSIONS: Patients with SS, RA, and SSc displayed a heightened perception of cardiovascular risk, correlating with their actual risk and preexisting comorbidities. However, patients exhibited unawareness of certain cardiovascular risk behaviors. This underscores the need for tailored education programs on cardiovascular risk for autoimmune disease patients, to be implemented at the time of diagnosis and during follow-up in outpatient clinics.
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Enfermedades Autoinmunes , Enfermedades Cardiovasculares , Humanos , Masculino , Femenino , Estudios Transversales , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Persona de Mediana Edad , Adulto , Anciano , Factores de Riesgo de Enfermedad Cardiaca , Autoinforme , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/epidemiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/epidemiología , Medición de Riesgo , Prevalencia , Autoimagen , Factores de RiesgoRESUMEN
OBJECTIVE: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. METHODS: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). RESULTS: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. CONCLUSION: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.
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Artritis Psoriásica , Sistema de Registros , Inducción de Remisión , Índice de Severidad de la Enfermedad , Humanos , Artritis Psoriásica/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Estudios Prospectivos , Inducción de Remisión/métodos , Adulto , Antirreumáticos/uso terapéutico , Europa (Continente) , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Anciano , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Alamandine is a peptide hormone belonging to the renin-angiotensin system (RAS). It acts through the Mas-related G-protein coupled receptor type D, MrgD, which is expressed in different tissues, including the brain. In the present study, we hypothesize that a lack of alamandine, through MrgD, could cause the anxiety-like behavior in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)680]. Adult male transgenic rats exhibited a significant increase in the latency to feeding time in the novelty suppressed feeding test and a decrease in the percentage of time and entries in the open arms in the elevated plus maze. These effects were reversed by intracerebroventricular infusion of alamandine. Pretreatment with D-Pro7-Ang-(1-7), a Mas and MrgD receptor antagonist, prevented the anxiolytic effects induced by this peptide. However, its effects were not altered by the selective Mas receptor antagonist, A779. In conclusion, our data indicates that alamandine, through MrgD, attenuates anxiety-like behavior in male TGR(ASrAOGEN)680, which reinforces the importance of the counter-regulatory RAS axis as promising target for the treatment of neuropsychiatric disorders.
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Angiotensinógeno , Ansiolíticos , Ansiedad , Encéfalo , Ratas Transgénicas , Receptores Acoplados a Proteínas G , Animales , Masculino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Ratas , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Ansiolíticos/farmacología , Angiotensinógeno/metabolismo , Angiotensinógeno/genética , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Receptores de la Hormona Gastrointestinal/metabolismo , Oligopéptidos/farmacología , Proteínas del Tejido NerviosoRESUMEN
The renin-angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity-associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein-coupled receptor (MasR) and Mas-related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity-associated metabolic effects.
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Tejido Adiposo , Proto-Oncogenes Mas , Receptores Acoplados a Proteínas G , Sistema Renina-Angiotensina , Animales , Humanos , Tejido Adiposo/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Metabolismo Energético , Obesidad/metabolismo , Obesidad/patología , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/fisiología , Transducción de SeñalRESUMEN
OBJECTIVE: Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.
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Espondiloartritis Axial , Sedimentación Sanguínea , Proteína C-Reactiva , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante , Humanos , Proteína C-Reactiva/análisis , Masculino , Femenino , Espondilitis Anquilosante/sangre , Espondilitis Anquilosante/diagnóstico , Adulto , Persona de Mediana Edad , Espondiloartritis Axial/sangre , Espondiloartritis Axial/diagnóstico , Sistema de RegistrosRESUMEN
Consistent condom use is recognized as one of the most effective strategies to prevent unwanted pregnancies and sexually transmitted infections. Despite their effectiveness, condoms remain fairly well used among younger people. The conception of appropriate measures to change behaviors needs a deep understanding of the factors underlying poor adherence to condom use. This study aims to identify the predictors of condom use among college students. A cross-sectional, correlational, and predictive study was conducted involving a convenience sample of 1946 university students, with an average age of 21 years (20.74 ± 2.32). Pender's Health Promotion Model (HPM) was used as a conceptual and methodological framework to understand the relationship between the predictors of condom use. An explanatory theoretical model of condom use behavior was established using path analysis. Condom use among young people is infrequent, with only 39.4% of respondents reporting consistent use. Perceived benefits, positive feelings, and interpersonal influences emerged as variables with the most explicitly positive influence on the commitment to condom use, a trend confirmed for both sexes. Commitment was the strongest predictor of condom use behavior (ß = 0.580; p < 0.001). Pender's HPM is effective in explaining the relationships between the predictors of condom use.
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Condones , Estudiantes , Humanos , Condones/estadística & datos numéricos , Femenino , Masculino , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Adulto Joven , Estudios Transversales , Universidades , Adolescente , Adulto , Conducta Sexual/estadística & datos numéricosRESUMEN
OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.
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Angiotensina I , Lipopolisacáridos , Pulmón , Ovalbúmina , Fragmentos de Péptidos , Animales , Angiotensina I/uso terapéutico , Angiotensina I/farmacología , Angiotensina I/administración & dosificación , Fragmentos de Péptidos/farmacología , Fragmentos de Péptidos/uso terapéutico , Fragmentos de Péptidos/administración & dosificación , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/inmunología , Ovalbúmina/inmunología , Ratones , Masculino , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Ratones Endogámicos BALB C , Inflamación/tratamiento farmacológico , Eosinofilia/tratamiento farmacológico , Eosinofilia/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citologíaRESUMEN
We report the complete genome sequence of deformed wing virus and black queen cell virus isolated from Argentinean's honeybees. These sequence data will be valuable for future research on the viral variants present in the country and the development of strategies to control the spread of these viruses in apiaries.
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STUDY QUESTION: Are there cell lineage-related differences in the apoptotic rates and differentiation capacity of human blastocysts diagnosed as euploid, mosaic, and aneuploid after preimplantation genetic testing for aneuploidy (PGT-A) based on concurrent copy number and genotyping analysis? SUMMARY ANSWER: Trophectoderm (TE) cells of mosaic and aneuploid blastocysts exhibit significantly higher levels of apoptosis and significantly reduced differentiation capacity compared to those of euploid blastocysts. WHAT IS KNOWN ALREADY: Embryos diagnosed as mosaic after PGT-A can develop into healthy infants, yet understanding the reasons behind their reproductive potential requires further research. One hypothesis suggests that mosaicism can be normalized through selective apoptosis and reduced proliferation of aneuploid cells, but direct evidence of these mechanisms in human embryos is lacking. Additionally, data interpretation from studies involving mosaic embryos has been hampered by retrospective analysis methods and the high incidence of false-positive mosaic diagnoses stemming from the use of poorly specific PGT-A platforms. STUDY DESIGN, SIZE, DURATION: Prospective cohort study performing colocalization of cell-lineage and apoptotic markers by immunofluorescence (IF). We included a total of 64 human blastocysts donated to research on Day 5 or 6 post-fertilization (dpf) by 43 couples who underwent in vitro fertilization treatment with PGT-A at IVI-RMA Valencia between September 2019 and October 2022. A total of 27 mosaic blastocysts were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study consisted of two phases: Phase I (caspase-3, n = 53 blastocysts): n = 13 euploid, n = 22 mosaic, n = 18 aneuploid. Phase II (terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), n = 11 blastocysts): n = 2 euploid, n = 5 mosaic, n = 4 aneuploid. Following donation for research, vitrified blastocysts were warmed, cultured until re-expansion, fixed, processed for IF, and imaged using confocal microscopy. For each blastocyst, the following cell counts were conducted: total cells (DAPI+), TE cells (GATA3+), inner cell mass (ICM) cells (GATA3-/NANOG+), and apoptotic cells (caspase-3+ or TUNEL+). The incidence of apoptosis was calculated for each blastocyst by dividing the number of caspase-3+ cells (Phase I) or TUNEL+ cells (Phase II) by the number of TE or ICM cells. Statistical analysis was performed according to data type and distribution (P < 0.05 was considered statistically significant). MAIN RESULTS AND THE ROLE OF CHANCE: Phase I: Mosaic blastocysts displayed a similar number of total cells (49.6 ± 15 cells at 5 dpf; 58.8 ± 16.9 cells at 6 dpf), TE cells (38.8 ± 13.7 cells at 5 dpf; 49.2 ± 16.2 cells at 6 dpf), and ICM cells (10.9 ± 4.2 cells at 5 dpf; 9.7 ± 7.1 cells at 6 dpf) compared to euploid and aneuploid blastocysts (P > 0.05). The proportion of TE cells retaining NANOG expression increased gradually from euploid blastocysts (9.7% = 63/651 cells at 5 dpf; 0% = 0/157 cells at 6 dpf) to mosaic blastocysts (13.1% = 104/794 cells at 5 dpf; 3.4% = 12/353 cells at 6 dpf) and aneuploid blastocysts (27.9% = 149/534 cells at 5 dpf; 4.6% = 19/417 cells at 6 dpf) (P < 0.05). At the TE level, caspase-3+ cells were frequently observed (39% = 901/2310 cells). The proportion of caspase-3+ TE cells was significantly higher in mosaic blastocysts (44.1% ± 19.6 at 5 dpf; 43% ± 16.8 at 6 dpf) and aneuploid blastocysts (45.9% ± 16.1 at 5 dpf; 49% ± 15.1 at 6 dpf) compared to euploid blastocysts (26.6% ± 16.6 at 5 dpf; 17.5% ± 14.8 at 6 dpf) (P < 0.05). In contrast, at the ICM level, caspase-3+ cells were rarely observed (1.9% = 11/596 cells), and only detected in mosaic blastocysts (2.6% = 6/232 cells) and aneuploid blastocysts (2.5% = 5/197 cells) (P > 0.05). Phase II: Consistently, TUNEL+ cells were only observed in TE cells (32.4% = 124/383 cells). An increasing trend was identified toward a higher proportion of TUNEL+ cells in the TE of mosaic blastocysts (37.2% ± 21.9) and aneuploid blastocysts (39% ± 41.7), compared to euploid blastocysts (23% ± 32.5), although these differences did not reach statistical significance (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: The observed effects on apoptosis and differentiation may not be exclusive to aneuploid cells. Additionally, variations in aneuploidies and unexplored factors related to blastocyst development and karyotype concordance may introduce potential biases and uncertainties in the results. WIDER IMPLICATIONS OF THE FINDINGS: Our findings demonstrate a cell lineage-specific effect of aneuploidy on the apoptotic levels and differentiation capacity of human blastocysts. This contributes to unravelling the biological characteristics of mosaic blastocysts and supports the concept of clonal depletion of aneuploid cells in explaining their reproductive potential. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by grants from Centro para el Desarrollo Tecnológico Industrial (CDTI) (20190022) and Generalitat Valenciana (APOTIP/2019/009). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
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Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Diagnóstico Preimplantación/métodos , Caspasa 3/metabolismo , Estudios Retrospectivos , Estudios Prospectivos , Blastocisto/metabolismo , Pruebas Genéticas/métodos , AneuploidiaRESUMEN
BACKGROUND: Pain is a complex experience that interferes with the well-being of youth who experience it. We aimed to assess whether recurrent pain sites in childhood can predict later recurrent pain sites prospectively. METHODS: Pain was assessed using the Luebeck Pain Screening Questionnaire at ages 7, 10, and 13 from the Generation XXI cohort. We used multinomial regression to assess the association of recurrent pain sites at ages 7 and 10 with those at age 13. RESULTS: We included 3833 participants. Boys with recurrent abdominal/pelvic pain at age 7 were more likely to report headaches (OR 2.81; 95%CI 1.48-5.34), abdominal/pelvic (OR 2.92; 95%CI 1.46-5.84), and musculoskeletal pain (OR 1.55; 95%CI 1.02-2.34) at age 13. Girls with recurrent abdominal/pelvic pain at age 7 were more likely to report both musculoskeletal (OR 1.62; 95%CI 1.10-2.40) and abdominal/pelvic pain (OR 1.74; 95%CI 1.15-2.65). At age 10, all pain sites were associated with pain in the same site at age 13. CONCLUSION: Recurrent abdominal/pelvic pain at age 7 may be related to the development of various pains in adolescence. Pain at a given site at age 10 can be associated with pain at that same site at age 13. IMPACT: Recurrent abdominal or pelvic pain during childhood was distinctively associated with an increased risk of recurrent pain in other sites during adolescence. Recurrent pain during childhood was associated with pain in the same sites at age 13, and this persistence seemed to emerge between the ages of 7 and 10 for both boys and girls. Studying early pain sites may add to the understanding of the etiology of chronic pain.
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Dolor Abdominal , Recurrencia , Humanos , Masculino , Femenino , Niño , Adolescente , Estudios Prospectivos , Dolor Abdominal/etiología , Encuestas y Cuestionarios , Dolor Pélvico/etiología , Dolor Musculoesquelético , Dimensión del Dolor , CefaleaRESUMEN
Uveitis is a heterogeneous collection of infrequent diseases, which poses significant challenges to cost-effective research in the field. Medical registries are being increasingly recognized as crucial tools to provide high-quality data, thus enabling prospective clinical research. This paper describes the design and technical structure development of an innovative countrywide electronic medical record for uveitis, Uveite.pt, and gives an overview of the cohort registered since its foundation, March 2020.Uveite.pt is an electronic medical record platform developed by the Portuguese Ocular Inflammation Group (POIG), a scientific committee of the Portuguese Ophthalmology Society. This is a nationwide customized web-based platform for uveitis patients useful for both clinical practice and real-world-based research, working as a central repository and reporting tool for uveitis. This paper describes the technical principles, the design and the development of a web-based interoperable registry for uveitis in Portugal and provides an overview of more than 400 patients registered in the first 18 months since inception.In infrequent diseases, the existence of registries enables to gather evidence and increase research possibilities to clinicians. The adoption of this platform enables standardization and improvement of clinical practice in uveitis. It is useful to apprehend the repercussion of medical and surgical treatments in uveitis and scleritis, supporting clinicians in the strict monitoring of drug adverse reactions and surgical outcomes.
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Uveítis , Humanos , Portugal/epidemiología , Estudios Prospectivos , Uveítis/diagnóstico , Uveítis/epidemiología , Sistema de Registros , Trastornos de la Visión , Inflamación , InternetRESUMEN
Bovine respiratory syncytial virus (BRSV) affects both beef and dairy cattle, reaching morbidity and mortality rates of 60-80% and 20%, respectively. The aim of this study was to obtain a recombinant MVA expressing the BRSV F protein (MVA-F) as a vaccine against BRSV and to evaluate the immune response induced by MVA-F after systemic immunization in homologous and heterologous vaccination (MVA-F alone or combined with a subunit vaccine), and after intranasal immunization of mice. MVA-F administered by intraperitoneal route in a homologous scheme elicited levels of neutralizing antibodies similar to those obtained with inactivated BRSV as well as better levels of IFN-γ secretion. In addition, nasal administration of MVA-F elicited local and systemic immunity with a Th1 profile. This study suggests that MVA-F is a good candidate for further evaluations combining intranasal and intramuscular routes, in order to induce local and systemic immune responses, to improve the vaccine efficacy against BRSV infection.
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Administración Intranasal , Ratones Endogámicos BALB C , Virus Sincitial Respiratorio Bovino , Animales , Virus Sincitial Respiratorio Bovino/inmunología , Ratones , Femenino , Bovinos , Proteínas Virales de Fusión/inmunología , Proteínas Virales de Fusión/genética , Proteínas Virales de Fusión/administración & dosificación , Vacunas contra Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Vectores Genéticos , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/veterinaria , Virus Vaccinia/inmunología , Virus Vaccinia/genética , Anticuerpos Antivirales/sangre , Inmunidad Mucosa , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Inmunización/métodos , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificaciónRESUMEN
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a heterogeneous group of rare diseases characterized by necrotizing inflammation predominantly of small vessels and the presence of these circulating antibodies. AAV comprises three important diseases, namely granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, which affect multiple organ systems, significantly affecting patients' quality of life and survival. The diagnosis is established according to the clinical manifestations, detectable ANCA, and histopathology findings. Primary treatment strategies are adapted to the severity of the disease and based on immunosuppression with corticosteroids and cyclophosphamide, with increasing adoption of new, less toxic agents aimed at sustained remission of the disease, such as rituximab, methotrexate, and mycophenolate mofetil. Several international medical organizations have proposed recommendations for diagnosing and managing these diseases to standardize the procedures. In this study, we provide an up-to-date European perspective on AAV management, compiling current and relevant information regarding its epidemiology, symptoms, diagnosis, treatment strategies, and prognosis.
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PURPOSE: Does vitrification/warming affect the mitochondrial DNA (mtDNA) content and the gene expression profile of blastocysts? METHODS: Prospective cohort study in which 89 blastocysts were obtained from 50 patients between July 2017 and August 2018. mtDNA was measured in a total of 71 aneuploid blastocysts by means of real-time polymerase chain reaction (RT-PCR). Transcriptomic analysis was performed by RNA sequencing (RNA-seq) in an additional 8 aneuploid blastocysts cultured for 0 h after warming, and 10 aneuploid blastocysts cultured for 4-5 h after warming. RESULTS: A significant decrease in mtDNA content just during the first hour after the warming process in blastocysts was found (P < 0.05). However, mtDNA content experimented a significantly increased along the later culture hours achieving the original mtDNA levels before vitrification after 4-5 h of culture (P < 0.05). Gene expression analysis and functional enrichment analysis revealed that such recovery was accompanied by upregulation of pathways associated with embryo developmental capacity and uterine embryo development. Interestingly, the significant increase in mtDNA content observed in blastocysts just after warming also coincided with the differential expression of several cellular stress response-related pathways, such as apoptosis, DNA damage, humoral immune responses, and cancer. CONCLUSION: To our knowledge, this is the first study demonstrating in humans, a modulation in blastocysts mtDNA content in response to vitrification and warming. These results will be useful in understanding which pathways and mechanisms may be activated in human blastocysts following vitrification and warming before a transfer.
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Transcriptoma , Vitrificación , Humanos , Transcriptoma/genética , ADN Mitocondrial/genética , Estudios Prospectivos , Blastocisto/fisiología , Aneuploidia , Criopreservación/métodos , Técnicas de Cultivo de EmbrionesAsunto(s)
Reumatología , Humanos , Reumatólogos/historia , Reumatología/historia , Portugal , Historia del Siglo XX , Historia del Siglo XXIRESUMEN
Objectives: Juvenile systemic sclerosis is a rare childhood disease. Three disease activity indices have been published for adult patients with systemic sclerosis: the European Scleroderma Study Group Index, a modified version of the European Scleroderma Study Group Index and the revised European Scleroderma Trials and Research index. The objective of this study was to determine the feasibility and performance of the three disease activity indices in a prospectively followed cohort of patients with juvenile systemic sclerosis. Methods: The analysis cohort was selected from the prospective international inception cohort enrolling juvenile systemic sclerosis patients. The correlation of the disease activity indices with the physicians' and the patients' global assessment of disease activity was determined. The disease activity indices were compared between patients with active and inactive disease. Sensitivity to change between 6- and 12-month follow-up was investigated by mixed models. Results: Eighty percent of the 70 patients had a diffuse cutaneous subtype. The revised European Scleroderma Trials and Research index was highly correlated with the physician-reported global disease activity/parents-reported global disease activity (r = 0.74/0.64), followed by the European Scleroderma Study Group activity index (r = 0.61/0.55) and the modified version of the European Scleroderma Study Group activity index (r = 0.51/0.43). The disease activity indices significantly differed between active and inactive patients. The disease activity indices showed sensitivity to change between 6- and 12-month follow-up among patients who improved or worsened according to the physician-reported global disease activity and the parents-reported global disease activity. Conclusion: Overall, no disease activity score is superior to the other, and all three scores have limitations in the application in juvenile systemic sclerosis patients. Furthermore, research on the concept of disease activity and suitable scores to measure disease activity in patients with juvenile systemic sclerosis is necessary in future.
RESUMEN
BACKGROUND: Juvenile idiopathic arthritis (JIA) treatment is aimed at inducing remission to prevent joint destruction and disability. However, it is unclear what is the long-term impact on health-related outcomes of the timing of biological disease-modifying antirheumatic drug (bDMARD) initiation in JIA. Our aim was to evaluate the long-term impact of the time between JIA onset and the initiation of a bDMARD in achieving clinical remission, on physical disability and health-related quality of life (HRQoL). METHODS: Adult JIA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) and ever treated with bDMARD were included. Data regarding socio-demographic, JIA-related characteristics, disease activity, physical disability (HAQ-DI), HRQoL (SF-36), and treatments were collected at the last visit. Patients were divided into 3 groups (≤ 2 years, 2-5 years, or > 5 years), according to the time from disease onset to bDMARD initiation. Regression models were obtained considering remission on/off medication, HAQ-DI, SF-36, and joint surgeries as outcomes and time from disease onset to bDMARD start as an independent variable. RESULTS: Three hundred sixty-one adult JIA patients were evaluated, with a median disease duration of 20.3 years (IQR 12.1; 30.2). 40.4% had active disease, 35.1% were in remission on medication, and 24.4% were in drug-free remission; 71% reported some degree of physical disability. Starting a bDMARD > 5 years after disease onset decreased the chance of achieving remission off medication (OR 0.24; 95% CI 0.06, 0.92; p = 0.038). Patients who started a bDMARD after 5 years of disease onset had a higher HAQ and worse scores in the physical component, vitality, and social function domains of SF-36, and more joint surgeries when compared to an earlier start. CONCLUSION: Later initiation of bDMARDs in JIA is associated with a greater physical disability, worse HRQoL, and lower chance of drug-free remission in adulthood.
Asunto(s)
Antirreumáticos , Artritis Juvenil , Enfermedades Reumáticas , Adulto , Humanos , Artritis Juvenil/tratamiento farmacológico , Calidad de Vida , Antirreumáticos/uso terapéutico , CogniciónRESUMEN
OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with 1) treatment line (second and third TNFi-series) and 2) reason for withdrawal from the preceding TNFi (lack of efficacy (LOE) versus adverse events (AE)). METHODS: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission (Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)) were assessed in second and third TNFi-series and stratified by withdrawal reason. RESULTS: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE versus LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE < 26 versus ≥26 weeks) (58% versus 71%, p< 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) versus LOE (17%), p< 0.001, while similar for the third TNFi (19% versus 13%, p= 0.20). CONCLUSION: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE versus LOE.