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1.
Clin Rheumatol ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210206

RESUMEN

Systemic sclerosis (SSc) is a progressive autoimmune disorder that mainly affects the skin. There are other clinical manifestations as renal, pulmonary, cardiovascular, and gastrointestinal tract involvements. Based on the skin involvement there are two subtypes of SSc, as limited cutaneous SSc (lSSc) which involves the acral part of the body and diffuse cutaneous SSc (dSSc) resulting in significant skin thickening of the body. Despite of the extensive research the pathomechanism is not fully clarified, how Ssc develops, moreover identifying biomarkers to predict the clinical outcome and prognosis still remains challenging. Circulating biomarkers can be crucial to define the diagnosis, to predict the prognosis and monitor the clinical course. However, only some patients are responsive to the therapy in SSc, and there is a need to reach the ideal therapy for any individual to prevent or slow down the progression in early stages of the disease. In this narrative review, our purpose was to summarize the potential biomarkers in Ssc, describe their role in the diagnosis, pathomechanism, clinical course, organ manifestations, as well as the response to the therapy. Biomarkers assessment aids in the evaluation of disease progression, and disease outcome.

2.
Clin Exp Rheumatol ; 38(5): 858-863, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31820730

RESUMEN

OBJECTIVES: Until now, glucocorticoids (GCs) with their anti-inflammatory and immune suppressive effects are one of the most effective agents in therapy of several autoimmune disorders including rheumatoid arthritis (RA). Glucocorticoid receptor (GR) polymorphisms may result in variable sensitivity to glucocorticoids playing an important role in the development and control of symptoms in RA. We aimed to test whether the functional polymorphisms of the GR encoding gene (NR3C1) are associated with susceptibility to RA and with various clinical signs and symptoms. METHODS: 146 patients were enrolled at the National Institute of Reumatology. Clinical diagnosis was based on the criteria of the American College of Rheumatism (ACR) 2010. Complex clinical, routine laboratory and immunlaboratory evaluations were performed. For genotyping of the GR polymorphisms N363S (rs6195), BclI (rs41423247) and 9ß (rs6198) peripheral blood DNA was used, extracted with commercially available reagents. Genotyping was performed with routine molecular biological methods. Genetic data were compared to those obtained in a healthy control group (n=160) using Chi square or Fisher tests. Associations between GR genotypes and clinical and immunological parameters were determined with ANOVA. RESULTS: The main finding of the present study is the lower frequency of the BclI in RA patients. Furthermore, regarding the laboratory and immunoserological parameters, the level of anti-DNA antibody was significantly higher in homozygous BclI carriers compared to heterozygous carriers, irrespective of the anti-TNF-alpha therapy. CONCLUSIONS: Our results reveal that although GR polymorphisms are not key players in development or clinical course of RA, they might affect glucocorticoid action and, together with other endogenous and exogenous factors, interfere with the pathomechanism of RA. Our results reveal some possible factors (including BclI polymorphism), and therefore contribute to elucidate the implication of the combination of GR functional variants.


Asunto(s)
Artritis Reumatoide , Receptores de Glucocorticoides , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Genotipo , Glucocorticoides/uso terapéutico , Humanos , Polimorfismo Genético , Receptores de Glucocorticoides/genética , Factor de Necrosis Tumoral alfa
4.
Clin Rheumatol ; 38(7): 1979-1984, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30850964

RESUMEN

BACKGROUND: SLE is a systemic autoimmune disorder with multiple organ manifestations. Despite of the innovations glucocorticoids (GC) have still remained the first-line therapy in SLE. Besides HSD11B enzymes, intracellular glucocorticoid receptors (GR) affect tissue-specific cortisol effect and the consequent signalisation pathway. SNPs of the glucocorticoid receptor gene (NR3C1) modulate individual sensitivity to glucocorticoids. Our aim was to determine the allele frequency of the three, clinically most important SNPs in a SLE patient population in comparison to healthy volunteers and to find association with particular manifestations of SLE. METHODS: We analysed results of 104 SLE patients compared to 160 healthy subjects. All patients were genotyped for the functional GR polymorphisms BclI, N363S, and A3669G. The GR gene polymorphisms were determined using allele-specific PCR and Taqman allelic discrimination assays. RESULTS: The BclI allele frequency was lower in the SLE group compared to the healthy control group. The central nervous system and especially psychiatric symptoms developed more frequently in the BclI carriers compared to none carriers. The prevalence of theA3669G polymorphism was the same in both groups, but showed a negative association with the psychiatric symptoms. CONCLUSION: The increased and decreased sensitivity associated with GR BclI and A3669G polymorphisms could have a pathogenic significance in SLE especial with the central nervous system and psychiatric symptoms. Improving our knowledge on the importance of GR polymorphisms may reveal their pathophysiologic and therapeutic consequences.


Asunto(s)
Lupus Eritematoso Sistémico/genética , Polimorfismo de Nucleótido Simple , Receptores de Glucocorticoides/genética , Adulto , Anciano , Autoanticuerpos/sangre , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad
5.
Orv Hetil ; 156(41): 1653-60, 2015 Oct 11.
Artículo en Húngaro | MEDLINE | ID: mdl-26551168

RESUMEN

The authors review the nomenclature of vasculitides and the classification of antineutrophil cytoplasm antibody associated vasculitides and present the method of measuring disease activity (Five-factor Score, Birmingham Vasculitis Activity Score) and its role in defining therapeutical needs. They discuss the treatment algorithm of antineutrophil cytoplasm antibody associated vasculitides, present the sometimes equipotential medications used during the induction therapy followed by a maintenance regimen, and outline their usage and possible side-effects that may require medical attention. They point out the importance of plasmapheresis as an adjunctive treatment in some cases, as well as indications and possible outcome of kidney transplantation in therapy-resistant cases. Finally, they review several ongoing clinical studies, as their outcome will probably influence therapeutical opportunities of antineutrophil cytoplasm antibody associated vasculitides in the next few years.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Inmunosupresores/uso terapéutico , Algoritmos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/clasificación , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Azatioprina/uso terapéutico , Ensayos Clínicos como Asunto , Granulomatosis con Poliangitis/terapia , Humanos , Trasplante de Riñón , Metotrexato/uso terapéutico , Poliangitis Microscópica/terapia , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Plasmaféresis , Pronóstico , Rituximab/uso terapéutico , Índice de Severidad de la Enfermedad , Terminología como Asunto
6.
Mediators Inflamm ; 2015: 657907, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26339139

RESUMEN

Psoriasis is a systemic immune-inflammatory disease characterized by chronic or recurrent skin symptoms, psoriatic arthritis, enthesopathy, and uveitis. Psoriasis has recently been published to appear with various autoimmune disorders, but the coexistence has been systematically reviewed by only few studies until now. In the present study, charts and electronic database of 4344 patients with various systemic autoimmune disorders, under regular medical control at our department, were reviewed retrospectively searching for association with psoriasis. Hereby, we demonstrate 25 psoriatic patients coinciding with various systemic autoimmune diseases. The coexistence of psoriasis and autoimmune diseases resulted in the worsening of the clinical outcome of the autoimmune diseases as indicated by higher frequency and dosages of glucocorticoid use, need for biologicals, and other comorbidities. These results suggest common environmental and genetic background as well as therapeutic possibilities in the future.


Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Psoriasis/diagnóstico , Enfermedades Reumáticas/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/patología , Glucocorticoides/uso terapéutico , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/patología
7.
Autoimmun Rev ; 14(4): 349-51, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25526806

RESUMEN

The therapeutic management of systemic lupus erythaematosus (SLE) is still a great debate. Despite the latest innovation agents or developing trials, there is not an integrated and common approach for treating SLE. For decades, natural and synthetic glucocorticoids (GCs) have been the first and most frequently used immune suppressive agents in SLE. Therefore, GCs are the most important therapy in SLE in daily routine, however the response to GCs differs widely and long-term therapy is associated with side-effects. Still now, clinicians and physicians are unable to predict the exact and ideal dose and term of therapy for patients suffering from various symptoms and degree of disease activity of SLE. The biological mechanism of GCs is regulated through activation of glucocorticoid receptors (GRs). There are two major isoforms of GRs: GRα and GRß; however, the GRα is the predominant one which binds steroids and activates target genes. In the present review, we summarise the anti-inflammatory and immune suppressive effects of GCs via GRs to regulate the target genes.


Asunto(s)
Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/metabolismo , Receptores de Glucocorticoides/metabolismo , Antiinflamatorios/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Transducción de Señal
8.
Immunol Res ; 61(1-2): 172-6, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25407648

RESUMEN

A strong connection between spondylarthropathies and inflammatory bowel diseases (IBD) is well established. About 10-15% of IBD are associated with different forms of spondylarthritis. Arthritis can be manifested as axial, peripheral form or both. The primary functions of the gastrointestinal tract are digestion and absorption of nutrients, electrocytes and maintenance of water homoeostasis. The anatomic and functional lesions could lead to the development of IBD based on molecular mimicry and bystander effects. The mechanism of the macromolecules is uptaken may affect intestinal and extraintestinal manifestation in genetically susceptible individuals by gut-associated lymphoid tissue, the interplay between innate and adaptive immunity and the neuroendocrine network.


Asunto(s)
Artritis/etiología , Microambiente Celular , Mucosa Intestinal/metabolismo , Inmunidad Adaptativa , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/microbiología , Humanos , Inmunidad Innata , Enfermedades Inflamatorias del Intestino/complicaciones , Intestinos/inmunología , Intestinos/microbiología , Microbiota , Espondiloartropatías/etiología
10.
Rheumatology (Oxford) ; 50(7): 1337-40, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21372001

RESUMEN

OBJECTIVE: To report the efficacy and safety of TNF-α inhibitors (etanercept and adalimumab) in a cohort of patients with JIA treated in a single paediatric rheumatological centre. METHODS: Patients with JIA under the age of 18 years, treated with TNF-α blockers at the Paediatric Rheumatologic Centre of the National Institute of Rheumatology and Physiotherapy (Budapest, Hungary) from 2002, were enrolled in an open, observational study. At baseline, patient and disease characteristics were registered. Disease activity was evaluated (before the start of the treatment and after every 3 months) according to the JIA core set of the ACR paediatric definition of improvement (ACR Pedi). Adverse events (AEs) were documented. RESULTS: In all, 72 patients were evaluated. Mean (S.D.) age at onset was 5.5 (3.8) years, mean disease duration was 7.4 (3.9) years. All disease activity parameters improved significantly in the first 3 months of treatment. After 3 and 12 months of treatment, 88 and 76% of patients, respectively, achieved the criteria of the ACR Pedi 30. AEs were uncommon. After 12 months, >85% of patients continued the therapy. CONCLUSION: Anti-TNF-α agents (etanercept and adalimumab) are effective, safe and well tolerated in JIA patients. Extension of this study for a longer follow-up period and to the patients with JIA after the age of 18 years (with validated and comparable disease activity parameters) is needed to evaluate the long-term effectiveness and safety of the TNF-α inhibitors.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adolescente , Análisis de Varianza , Antirreumáticos/uso terapéutico , Artritis Juvenil/diagnóstico , Niño , Preescolar , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Etanercept , Femenino , Estudios de Seguimiento , Humanos , Hungría , Masculino , Dimensión del Dolor , Rango del Movimiento Articular/fisiología , Sistema de Registros , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
11.
Rheumatol Int ; 31(5): 695-8, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-20676642

RESUMEN

Hereby, we report the case of a 12-year-old girl developing oligoarthritis and progressing into a polyarticular form. Rheumatoid factor was positive, and juvenile idiopathic arthritis (JIA) was diagnosed. After a poor response to DMARDs, an anti-TNF agent (infliximab) was initiated, but to be discontinued due to an allergic reaction. The same complication was observed with the fully human derivative, adalimumab. At the age of 22, the patient presented septicemia with severe anemia and subsequent development of leukopenia, myocarditis with heart failure, and ANA, aSm, aSS-A, aCL positives, and nephrotic syndrome. These new clinical manifestations fulfilled the classification criteria for the diagnosis of systemic lupus erythematosus. Due to the poor therapeutic responses for both diseases, alternative medical options have to be considered, such as targeted therapy with anti-CD20 or interleukin-6 receptor antagonist monoclonal antibodies. This patient may also be a candidate for autologous hemopoietic stem cell transplantation.


Asunto(s)
Artritis Juvenil/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Antirreumáticos/uso terapéutico , Artritis Juvenil/diagnóstico , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/inmunología , Productos Biológicos/efectos adversos , Niño , Hipersensibilidad a las Drogas/etiología , Femenino , Humanos , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Recurrencia , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto Joven
12.
Clin Exp Rheumatol ; 28(3): 424-33, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20497629

RESUMEN

OBJECTIVES: To evaluate change over time and level of agreement of renal-specific and multi-dimensional measures in juvenile systemic lupus erythematosus (SLE) with renal disease. METHODS: An analysis was made of 205/557 children with baseline 24-hour proteinuria >or=0.5 g. Data were collected at baseline, 6-, 12- and 24-month intervals. Using the Systemic Lupus International Collaborating Clinics (SLICC) renal index (change in proteinuria and urine sediment) as gold standard, responsiveness and discriminative ability analyses were used to identify key renal and multi-dimensional disease activity and damage measures for the evaluation of response to therapy. We also evaluated the kappa agreement between SLICC renal index and PRINTO/ACR juvenile SLE criteria (change in proteinuria, physician and parents evaluations, disease activity, health related quality of life [HRQOL]). RESULTS: Children with renal disease compared to children without renal disease, had a lower female rate and higher disease activity/response rate (p-values <0.01) but similar damage levels. Large responsiveness (standardised response mean >or=0.8) and statistical significant discriminative ability with the SLICC renal index 4 levels of response (improved, partially improved, stable and worsened) were observed for renal specific measures (proteinuria, urine sediment, renal sub-scores, p<0.0001) and for multi-dimensional variables (disease activity level and physician evaluation p<0.001). Agreement between the SLICC renal index and PRINTO/ACR criteria was moderate (0.57; 95% confidence intervals: 0.44-0.71). CONCLUSIONS: We propose to incorporate multi-dimensional measures (physician and parents' evaluations, disease activity and HRQOL), in addition to renal specific measures, in future clinical trials in juvenile SLE with renal involvement.


Asunto(s)
Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/fisiopatología , Proteinuria/diagnóstico , Proteinuria/fisiopatología , Índice de Severidad de la Enfermedad , Biomarcadores , Niño , Ensayos Clínicos como Asunto/métodos , Ensayos Clínicos como Asunto/normas , Bases de Datos Factuales , Monitoreo de Drogas/métodos , Monitoreo de Drogas/normas , Estado de Salud , Humanos , Riñón/fisiología , Estudios Longitudinales , Lupus Eritematoso Sistémico/tratamiento farmacológico , Proteinuria/tratamiento farmacológico , Calidad de Vida , Estándares de Referencia , Orina
13.
Orv Hetil ; 151(18): 735-40, 2010 May 02.
Artículo en Húngaro | MEDLINE | ID: mdl-20410000

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune disorder involving different organs and organ systems with consequent characteristic clinical and serologic symptoms. Despite of the improvement in lupus survival, approximately 10-20% of patients do not respond to traditional immune suppressive therapies. Relapses are more frequent; e.g. after cyclophosphamide therapy diffuse proliferative nephritis flares in 1/3 of patients. Different immune competent cells and inflammatory mediators participate in the pathogenesis of SLE involving both the adaptive and innate immunity. Several pathogenic elements and mechanisms may serve as therapeutic targets, consequently. Authors summarize novel therapeutic possibilities and their mechanisms regarding the pathogenesis of SLE. Immune modulation of B and T cells, co-stimulatory pathways, cytokine network, soluble mediators and autologous hemopoietic stem cell transplantation are discussed.


Asunto(s)
Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Citocinas/efectos de los fármacos , Citocinas/inmunología , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lupus Eritematoso Sistémico/cirugía , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Trasplante Autólogo
14.
Arthritis Rheum ; 61(5): 658-66, 2009 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-19405003

RESUMEN

OBJECTIVE: To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS). METHODS: The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on >4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0-101), 27-joint (range 0-57), or 10-joint (range 0-40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI). RESULTS: The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change. CONCLUSION: The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.


Asunto(s)
Artritis Juvenil/fisiopatología , Evaluación de la Discapacidad , Articulaciones/fisiopatología , Índice de Severidad de la Enfermedad , Adolescente , Antiinflamatorios no Esteroideos/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/diagnóstico , Artritis Juvenil/tratamiento farmacológico , Sedimentación Sanguínea , Niño , Preescolar , Estudios Transversales , Humanos , Meloxicam , Metotrexato/uso terapéutico , Naproxeno/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Pronóstico , Tiazinas/uso terapéutico , Tiazoles/uso terapéutico , Resultado del Tratamiento
15.
Orv Hetil ; 150(23): 1083-7, 2009 Jun 07.
Artículo en Húngaro | MEDLINE | ID: mdl-19470424

RESUMEN

In the present report the authors describe four cases with megacolon and arthritis. The etiology of these unique associations is known in only one case. The musculoskeletal pictures belong to the group of seronegative spondyloarthritis. A huge resistance with great scibalas was detected in the left iliac region by physical examination in all cases. Surgical procedures of the colon resulted in complete remission of arthritis in one case, in the others, chronic obstipation with intermittent relapse of arthritis persisted.


Asunto(s)
Artritis/complicaciones , Megacolon/complicaciones , Adulto , Artritis/diagnóstico por imagen , Enfermedad Crónica , Estreñimiento/etiología , Humanos , Masculino , Megacolon/diagnóstico por imagen , Megacolon/cirugía , Radiografía
16.
J Rheumatol ; 36(1): 183-90, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19208532

RESUMEN

OBJECTIVE: To develop and test reduced joint counts in children with juvenile idiopathic arthritis (JIA). METHODS: Four reduced joint counts including 45, 35, 27, and 10 joints were devised by a panel of experienced pediatric rheumatologists, who selected the joints to be included based on the ease of technical assessment, functional relevance, and frequency of involvement. Three large samples of patients with JIA (total n=4353) who had a detailed joint assessment available were used to develop and test reduced joint counts. Performance of reduced counts was examined by comparing their Spearman correlation with the standard (i.e., complete) joint count. Construct validity was evaluated by calculating Spearman correlation with other JIA outcome measures. Responsiveness to clinical change was determined through the standardized response mean (SRM). RESULTS: Spearman correlations of reduced joint counts with the whole joint count and with the other JIA outcome measures were comparable, revealing that they had similar ability to serve as surrogate for the whole joint count and construct validity. Responsiveness to clinical change was also comparable across reduced counts (SRM 0.83-1.09 for active joint counts and 0.63-0.81 for restricted joint counts). Based on these results and considering the relative feasibility of the different counts, the 27-joint reduced count is proposed for use in JIA. This joint count includes the cervical spine and the elbow, wrist, metacarpophalangeal (from first to third), proximal interphalangeal, hip, knee, and ankle joints. CONCLUSION: Reduced joint counts appear to be as reliable as standard joint counts in assessment of the severity of joint disease and its change over time in children with JIA.


Asunto(s)
Artritis Juvenil/patología , Articulaciones/patología , Examen Físico/normas , Índice de Severidad de la Enfermedad , Adolescente , Niño , Preescolar , Estudios Transversales , Bases de Datos Factuales , Estado de Salud , Humanos , Reproducibilidad de los Resultados
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