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Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with myelodysplastic syndrome (MDS). Despite this, the role of TP53 gene aberrations in MDS with isolated deletion of chromosome 5 [MDS-del(5q)] remains unclear. This study aimed to assess the impact of TP53 gene mutations and their allelic state in patients with MDS-del(5q). To that end, a comprehensive analysis of TP53 abnormalities, examining both TP53 mutations and allelic imbalances, in 682 patients diagnosed with MDS-del(5q) was conducted. Twenty-four percent of TP53-mutated patients exhibited multihit alterations, while the remaining patients displayed monoallelic mutations. TP53 multihit alterations were predictive of an increased risk of leukemic transformation. The impact of monoallelic alterations was dependent on the variant allele frequency (VAF); patients with TP53 monoallelic mutations and VAF <20% exhibited behavior similar to TP53 wild type, and those with TP53 monoallelic mutations and VAF ≥20% presented outcomes equivalent to TP53 multihit patients. This study underscores the importance of considering TP53 allelic state and VAF in the risk stratification and treatment decision-making process for patients with MDS-del(5q).
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Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN. We propose a germline-augmented somatic panel (GASP), combining MN predisposition genes with a myeloid somatic panel for timely germline variant identification when initial testing is not indicated. Out of our 133 whole-exome-sequenced MN cases aged over 50 years, 9% had pathogenic/likely variants. GASP detected 92%, compared to 50% with somatic-only panel. Our study highlights the relevance of germline screening in MN, particularly for alloHSCT candidates without established germline-testing recommendations.
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Mutação em Linhagem Germinativa , Transplante de Células-Tronco Hematopoéticas , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Testes Genéticos/métodos , Predisposição Genética para Doença , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/diagnóstico , Sequenciamento do Exoma , Transplante HomólogoRESUMO
Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS-MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS-MDS accurately predicted overall survival (OS) and leukaemia-free survival (LFS), outperforming the Revised-IPSS score. Similarly, in the Taiwanese cohort, the AIPSS-MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS-MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision-making in CMML enables clinicians to identify high-risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS-MDS to further refine risk stratification in CMML and improve patient outcomes.
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Leucemia Mielomonocítica Crônica , Leucemia , Síndromes Mielodisplásicas , Humanos , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Prognóstico , Inteligência Artificial , Síndromes Mielodisplásicas/terapia , Síndromes Mielodisplásicas/tratamento farmacológico , Medição de RiscoRESUMO
OBJECTIVES: Multiple sclerosis (MS) is a neurodegenerative chronic inflammatory. Mutations in the vitamin D receptor (VDR) gene can substantially affect serum vitamin D levels or alter its functionality, and can consequently increase susceptibility to developing MS. The objective of this study was to evaluate the association between polymorphisms in the VDR gene and risk of MS in a (Spanish) Caucasian population. PATIENTS AND METHODS: We conducted a retrospective case-control study comprising 209 patients with relapsing-remitting multiple sclerosis (RRMS) and 836 controls of Caucasian origin from southern Spain. The ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms were determined by allelic discrimination real-time PCR using TaqMan probes. RESULTS: The recessive logical regression model, adjusted for age and sex, revealed that the TT genotype for VDR FokI (rs2228570) polymorphism was associated with higher risk of MS (P = 0.0150; OR = 1.82; 95% CI = 1.12-2.94; TT vs. CT + CC). No association between the other polymorphisms and development of MS was found in any of the models analyzed. The haplotype analysis, adjusted for age, smoking, and sex, did not find any statistically significant association between the haplotypes analyzed and risk of MS. CONCLUSIONS: The VDR FokI (rs2228570) polymorphism was significantly associated with developing MS. We found no influence of the ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms on the risk of developing MS in our patients.
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Estudos de Associação Genética , Predisposição Genética para Doença , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Calcitriol/genética , Adulto , Alelos , Feminino , Genótipo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/patologia , Fatores de Risco , Espanha/epidemiologia , População Branca/genéticaRESUMO
OBJECTIVES: To identify recommendations on the diagnosis and management of rheumatoid arthritis (RA) supported by low recommendation grades, to study the causes of this low grading, and to propose solutions. METHODS: A group of six rheumatologists, with extensive experience in the development of systematic reviews, reviewed national and international RA recommendations and practice guidelines. They identified all recommendations with a low level of evidence or recommendation grade (levels equivalent to 4, 5, or grades C or D of the Oxford Levels of Evidence), classified them by areas (diagnosis, follow-up, treatment, others), and analyzed plausible causes of low graduation. A Delphi was used to select 10 recommendations where it was most important to obtain quality evidence to support them. Subsequently, actions were proposed to improve evidence and recommendation grading. RESULTS: Fourteen documents were analyzed, in which 192 recommendations with low evidence/grade of recommendation were identified, most of which were on treatment. The two most frequent causes of this low level are the absence of studies and the discrepancy between the wording of the recommendation and the evidence used. Finally, the proposed solution to the critical recommendations is a list of unanswered research questions and possible designs to answer them. CONCLUSIONS: We propose to design and promote research that truly supports or rectifies clinical practice and, thus, bridges the gap between existing evidence and critical recommendations.
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Artrite Reumatoide/terapia , Medicina Baseada em Evidências/normas , Reumatologia/normas , Artrite Reumatoide/diagnóstico , Humanos , Guias de Prática Clínica como Assunto , Revisões Sistemáticas como AssuntoRESUMO
Objectives: The aims were to evaluate the prevalence of anti-drug antibodies (ADA) in patients with RA or SpA experiencing secondary failure to anti-TNF therapy and to correlate ADA presence with anti-TNF concentration and clinical response. Methods: This was a cross-sectional, observational study of patients with active RA or SpA experiencing secondary failure to etanercept (ETN), infliximab (INF) or adalimumab (ADL). Concomitant non-biologic DMARDs were permitted. Serum anti-TNF and ADA levels were measured with two-site ELISA. Results: Among 570 evaluable patients, those with RA (n = 276) were mostly female (80 vs 39%), older (56 vs 48 years), received concomitant DMARDs (83 vs 47%) and had maintained good clinical disease control for longer (202 vs 170 weeks) compared with patients with SpA (n = 294). ADA were found in 114/570 (20.0%) patients; 51/188 (27.1%) against INF and 63/217 (29.0%) against ADL; none against ETN. Of these 114 patients, 92 (81%) had no detectable serum drug concentrations. Proportionately more patients with SpA (31.3%) had anti-INF antibodies than those with RA (21.1%; P = 0.014). A significantly lower proportion of patients receiving concomitant DMARDs (16.5%) developed ADA than those on monotherapy (26.4%; P < 0.05). Conclusion: In patients with RA or SpA and secondary failure, the development of ADA against ADL or INF, but not ETN, appears to be one of the main reasons for secondary treatment failure, but not the only one. Further investigations are needed to determine other causes of anti-TNF failure.
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Adalimumab/imunologia , Anticorpos/imunologia , Artrite Reumatoide/tratamento farmacológico , Etanercepte/imunologia , Infliximab/imunologia , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/administração & dosagem , Anticorpos/sangue , Antirreumáticos/administração & dosagem , Antirreumáticos/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Estudos Transversais , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Etanercepte/administração & dosagem , Feminino , Humanos , Infliximab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/sangue , Espondilite Anquilosante/imunologia , Falha de Tratamento , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: To establish feasible and practical recommendations for the management of the psychological needs of patients with rheumatoid arthritis (RA) from the moment of diagnosis through the course of the disease. METHODS: A nominal group meeting was held with an RA expert team including rheumatologists and psychologists, at which a guided discussion addressed the most important psychological and emotional needs in RA. Based on the comments collected, and a literature review, a matrix document of recommendations for telematics discussion was prepared, as well as a Delphi survey to test agreement with these recommendations. Agreement was defined if at least 80% of participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grading of recommendations was established following the Oxford criteria, and the degree of agreement through the Delphi. RESULTS: Thirteen recommendations were established, addressing several key processes: (1) identification of psychological problems and needs in patients with RA, and a guideline for their management in daily practice; (2) communication with patients; (3) referral criteria to mental health professionals. CONCLUSIONS: These recommendations are intended to help health care professionals openly address the psychological aspects of patients in daily practice to follow and treat them properly.
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Adaptação Psicológica , Artrite Reumatoide/terapia , Efeitos Psicossociais da Doença , Emoções , Serviços de Saúde Mental/normas , Psiquiatria/normas , Psicologia/normas , Reumatologia/normas , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/psicologia , Consenso , Técnica Delphi , Humanos , Comunicação Interdisciplinar , Saúde Mental , Equipe de Assistência ao Paciente , Reumatologistas/normasRESUMO
In the context of psychological treatment, a sudden gain is a large and enduring improvement in symptom severity that occurs between two single therapy sessions. The influence of sudden gains on long-term outcomes and functional impairment in anxiety disorders is not well understood, and little is known with regard to panic disorder in particular. In addition, previous research on patients with anxiety disorders has produced inconsistent results regarding the relationship between sudden gains and cognitive change. We examined the incidence of sudden gains in a large sample (n = 116) of panic disorder patients undergoing exposure-focused cognitive-behavioral group therapy, and compared panic severity, functional impairment, and cognitive change in patients with and without sudden gains at posttreatment and 6-month follow-up. Participants who experienced sudden gains displayed lower levels of panic severity and functional impairment at posttreatment and 6-month follow-up than those who did not experience sudden gains. However, we observed no difference in cognitive changes between groups, either at posttreatment or at follow-up. Our results demonstrate that the beneficial effects of sudden gains on therapeutic outcomes not only extend to long-term and functional outcome measures but are also evident in less cognitive (i.e., exposure-focused) forms of psychological treatment. KEY PRACTITIONER MESSAGE: Sudden gains are common in panic disorder patients undergoing exposure-based cognitive-behavioral group therapy. Sudden gains during exposure-focused therapy are linked to greater improvement in panic disorder severity and functional impairment. The positive impact of sudden gains on panic disorder severity and functional impairment is maintained in the long term.
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Terapia Cognitivo-Comportamental/métodos , Terapia Implosiva/métodos , Transtorno de Pânico/psicologia , Transtorno de Pânico/terapia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Espanha , Resultado do Tratamento , Adulto JovemRESUMO
The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0-3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist-MCP-ankle-MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist-hand-ankle-MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Articulações/efeitos dos fármacos , Articulações/diagnóstico por imagem , Metotrexato/uso terapêutico , Tendões/efeitos dos fármacos , Tendões/diagnóstico por imagem , Ultrassonografia Doppler , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Avaliação da Deficiência , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Indução de Remissão , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Tenossinovite/diagnóstico , Tenossinovite/diagnóstico por imagem , Fatores de Tempo , Resultado do TratamentoAssuntos
Cromossomos Humanos , Amplificação de Genes , Neoplasias Hematológicas , Micronúcleos com Defeito Cromossômico , Transtornos Mieloproliferativos , Proteínas Proto-Oncogênicas c-myc , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos/genética , Cromossomos Humanos/metabolismo , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Masculino , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismoRESUMO
OBJECTIVE: To investigate the predictive value of synovitis detected by Doppler US in relation to failed tapering of biologic therapy (BT) in RA patients in sustained clinical remission. METHODS: A total of 77 RA patients (52 women, 25 men) in sustained clinical remission, treated with a stable dosage of BT were prospectively recruited. BT was tapered according to an agreed strategy implemented in clinical practice (i.e. increasing the interval between doses for s.c. BT and reducing the dose for i.v. BT). BT tapering failure was assessed at 6 and 12 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy and synovial power Doppler signal (i.e. Doppler synovitis) was performed at baseline by a rheumatologist blinded to clinical and laboratory data. Hand and foot radiographs were obtained at baseline and at 12-month follow-up. RESULTS: Of the 77 patients, 46 (59.7%) were on s.c. BT and 31 (40.3%) on i.v. BT. At 12 months, 35 patients (45.5%) presented BT tapering failure, 23 of them (29.9% of all patients) in the first 6 months of BT tapering. In logistic regression analysis, the baseline DAS28 and the global score of Doppler synovitis were identified as independent predictors of BT tapering failure at 12 and 6 months. The presence of Doppler synovitis was the strongest predictor for BT tapering failure. No patient showed radiographic progression. CONCLUSION: Our results suggest that the presence of Doppler-detected synovitis may predict BT tapering failure in RA patients in sustained clinical remission.
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Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Membrana Sinovial/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Articulações do Pé/diagnóstico por imagem , Articulação da Mão/diagnóstico por imagem , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Radiografia , Sinovite/diagnóstico , Fatores de Tempo , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to investigate the influence of the pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in RA patients. METHODS: Fifty RA patients were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment with s.c. anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)] and US assessment at two time points, i.e. at peak plasma drug concentration and at trough plasma drug concentration. US assessments were performed blindly to the anti-TNF agent, the administration time and the clinical and laboratory data. Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode synovitis and synovial power Doppler signal. Global indices for B-mode synovitis (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist-hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. RESULTS: There were no significant differences between the clinical, laboratory and B-mode and Doppler US parameters at peak time and trough time (P = 0.132-0.986). There were no significant differences between the proportion of patients with active disease and those in remission according to DAS28, SDAI, B-mode US and Doppler US at peak time and trough time assessments (P = 0.070-1). CONCLUSION: Our results suggested that s.c. anti-TNF pharmacokinetics do not significantly influence US-scored synovitis in RA patients.
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Antirreumáticos/farmacocinética , Artrite Reumatoide/tratamento farmacológico , Sinovite/diagnóstico por imagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Artrite Reumatoide/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Sinovite/tratamento farmacológico , Sinovite/etiologia , Ultrassonografia Doppler , Adulto JovemRESUMO
OBJECTIVE: The goal of the study was to assess the psychometric properties and the factor structure of the Spanish self-report version of the Panic Disorder Severity Scale (PDSS-SR). METHOD: One hundred and twenty four patients meeting DSM-IV criteria for panic disorder were assessed with the Spanish PDSS-SR, the Anxiety Sensitivity Index-3 (ASI-3), the Sheehan Disability Inventory (SDI) and the Beck Depression Inventory-II (BDI-II). Cronbach's alpha was used to evaluate internal consistency. Pearson correlations were used to evaluate test-retest reliability, convergent and divergent validity. Sensitivity to change data was obtained for 91 patients that had completed a cognitive behavioural therapy. The factor structure was analysed using a confirmatory factor analysis (CFA). RESULTS: The Spanish PDSS-SR showed excellent internal consistency, good test-retest reliability and adequate convergent validity. Regarding divergent validity, the correlation with the BDI-II was larger than expected. The Spanish PDSS-SR was sensitive to change. Our CFA suggested a two-factor model for the scale. CONCLUSIONS: The Spanish PDSS-SR has similar psychometric properties as the previous versions of the PDSS-SR and it can become a useful instrument to assess panic symptoms in clinical and research settings in Spanish-speaking countries.
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Transtorno de Pânico/diagnóstico , Transtorno de Pânico/psicologia , Autorrelato/normas , Adulto , Idoso , Terapia Cognitivo-Comportamental , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/terapia , Escalas de Graduação Psiquiátrica , Psicometria , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Espanha , Inquéritos e Questionários/normasRESUMO
Cutaneous polyarteritis nodosa (CPAN) is a form of necrotizing vasculitis of small and medium-sized arteries. It is limited to the skin and has a recurrent and chronic course, possibly associated with fever, arthralgia, myalgia and neuropathy, but without visceral involvement. We report the clinical case of a 7-year-old male patient with CPAN refractory to treatment with high doses of corticoids and cyclophosphamide, who was successfully treated with the TNF-α (tumor necrosis factor-alpha) inhibitor, etanercept, in monotherapy.
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Imunoglobulina G/uso terapêutico , Fatores Imunológicos/uso terapêutico , Poliarterite Nodosa/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Dermatopatias/tratamento farmacológico , Criança , Etanercepte , Humanos , Masculino , Resultado do TratamentoRESUMO
Purpose: To evaluate the characteristics, efficacy, and retention of tofacitinib monotherapy in patients with rheumatoid arthritis using data from randomized controlled trials (RCTs) and real-world data (RWD). Patients and Methods: Three patient groups receiving tofacitinib 5 mg twice daily (BID) monotherapy were defined for post hoc RCT/long-term extension (LTE) analyses: (1) disease-modifying antirheumatic drug (DMARD)-inadequate responder patients from phase 3/3b/4 RCTs; (2) methotrexate-naïve patients from a phase 3 RCT; and (3) index study patients continuing in an LTE study. Outcomes included low disease activity (LDA)/remission rates defined by Clinical Disease Activity Index (CDAI); Disease Activity Score in 28 joints (DAS28-4), erythrocyte sedimentation rate; DAS28-4, C-reactive protein (DAS28-4[CRP]); and rates of/time to discontinuation due to lack of efficacy/adverse events. RWD were identified by non-systematic literature searches of PubMed, Embase, and American College of Rheumatology/European Alliance of Associations for Rheumatology congress abstracts (2012-2022). Results: RCT/LTE analyses included 1000/498 patients receiving tofacitinib 5 mg BID monotherapy. Baseline disease activity was high; patients tended to receive concomitant glucocorticoids; most were biologic DMARD-naïve. CDAI LDA rates were 32.2-62.2% for Groups 1/2 (months 3-12) and 64.0-70.7% for Group 3 (months 12-72). In Groups 1, 2, and 3, 4.0%, 15.6%, and 27.7% of patients, respectively, discontinued tofacitinib monotherapy due to lack of efficacy/adverse events. From 11 RWD publications, 16.6-66.1% received tofacitinib monotherapy. Consistent with clinical data, tofacitinib monotherapy effectiveness (month 6 CDAI LDA, 30.2%; month 3 DAS28-4[CRP] remission, 53.4%) and persistence were observed in RWD, with retention comparable to tofacitinib combination therapy. Conclusion: Tofacitinib monotherapy demonstrated clinically significant responses/persistence in RCT/LTE analyses, with effectiveness observed and persistence comparable to combination therapy in RWD. Trial Registration: NCT00814307, NCT02187055, NCT01039688, NCT00413699, NCT00661661 (ClinicalTrials.gov).
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While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34+ progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS.
Assuntos
Antígenos CD34 , Deleção Cromossômica , Cromossomos Humanos Par 5 , Células-Tronco Hematopoéticas , Lenalidomida , Síndromes Mielodisplásicas , Análise de Célula Única , Humanos , Lenalidomida/farmacologia , Lenalidomida/uso terapêutico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/metabolismo , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Antígenos CD34/metabolismo , Cromossomos Humanos Par 5/genética , Masculino , Feminino , Idoso , Redes Reguladoras de Genes/efeitos dos fármacos , Pessoa de Meia-Idade , Hematopoese/efeitos dos fármacos , Hematopoese/genética , Transcriptoma , Idoso de 80 Anos ou mais , RNA-Seq , Perfilação da Expressão GênicaRESUMO
OBJECTIVE: The objective of this study was to compare disease activity assessed by the patient, the physician and musculoskeletal US in patients with RA in clinical remission. METHODS: We evaluated 69 patients with RA in clinical remission according to their attending rheumatologist. Tenderness and swelling in 28 joints were blindly assessed by patients and physicians. The presence of B-mode and Doppler synovitis was blindly investigated in the above joints. The DAS28 and Simplified Disease Activity Index (SDAI) were calculated. RESULTS: The percentage of patients in remission according to the self-derived DAS28 (26.1%) was significantly less than that according to the physician-derived DAS28 (52.2%) (P < 0.0005). There was no significant difference in the percentage of patients in remission according to the self-derived SDAI (14.5%) and the physician-derived SDAI (11.6%) (P = 0.172). We found moderate agreement between the patient-derived and physician-derived DAS28 and SDAI [intraclass correlation coefficient (ICC) = 0.620 and ICC = 0.678, respectively]. Agreement between patient and physician was better for the tender joint count (TJC; ICC = 0.509) than for the swollen joint count (SJC; ICC = 0.279). The mean (S.D.) count for B-mode synovitis [4.09 (3.25)] was significantly greater than the SJC assessed by both the patient and physician [2 (3.71) and 1.42 (2.03), respectively] (P < 0.0005 and P = 0.033, respectively). We found moderate agreement between the physician-assessed SJC and the joint count for Doppler synovitis (ICC = 0.528). CONCLUSION: Patient-assessed and physician-assessed overall RA activity showed acceptable agreement. Patient self-assessment overestimated disease activity determined by the DAS28. At the patient level, physician-assessed joint swelling showed an acceptable concordance with Doppler US synovitis.
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Artrite Reumatoide/diagnóstico , Autoavaliação Diagnóstica , Exame Físico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Indução de Remissão , Índice de Gravidade de Doença , Sinovite/diagnóstico , Sinovite/diagnóstico por imagem , UltrassonografiaRESUMO
Cutaneous polyarteritis nodosa (CPAN) is a form of necrotizing vasculitis of small and medium-sized arteries. It is limited to the skin and has a recurrent and chronic course, possibly associated with fever, arthralgia, myalgia and neuropathy, but without visceral involvement. We report the clinical case of a 7-year-old male patient with CPAN refractory to treatment with high doses of corticoids and cyclophosphamide, who was successfully treated with the TNF-α (tumor necrosis factor-alpha) inhibitor, etanercept, in monotherapy.
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[This corrects the article DOI: 10.3389/fmicb.2022.814448.].
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INTRODUCTION: The management of specific clinical scenarios is not adequately addressed in national and international guidelines for axial spondyloarthritis (axSpA). Expert opinions could serve as a valuable complement to these documents. METHODS: Seven expert rheumatologists identified controversial areas or gaps of current recommendations for the management of patients with axSpA. A systematic literature review (SLR) was performed to analyze the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs (csDMARDs, b/tsDMARDs) in axSpA regarding controversial areas or gaps. In a nominal group meeting, the results of the SLR were discussed and a set of statements were proposed. A Delphi process inviting 150 rheumatologists was followed to define the final statements. Agreement was defined as if at least 70% of the participants voted ≥ 7 (from 1, totally disagree, to 10, totally agree). RESULTS: Three overarching principles and 17 recommendations were generated. All reached agreement. According to them, axSpA care should be holistic and individualized, taking into account objective findings, comorbidities, and patients' opinions and preferences. Integrating imaging and clinical assessment with biomarker analysis could also help in decision-making. Connected to treatments, in refractory enthesitis, b/tsDMARDs are recommended. If active peripheral arthritis, csDMARD might be considered before b/tsDMARDs. The presence of significant structural damage, long disease duration, or HLA-B27-negative status do not contraindicate for the use of b/tsDMARDs. CONCLUSIONS: These recommendations are intended to complement guidelines by helping health professionals address and manage specific groups of patients, particular clinical scenarios, and gaps in axSpA.