Influence of TP53 Gene Mutations and its Allelic Status in Myelodysplastic Syndromes with Isolated 5q Deletion.

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).

Germline assessment for alloHSCT candidates over 50 years: A 'Fast-Track' screening in myeloid neoplasms.

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.

Validation of the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes in chronic myelomonocytic leukaemia: A novel approach for improved risk stratification.

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.

Tofacitinib Monotherapy in Rheumatoid Arthritis: Clinical Trials and Real-World Data Contextualization of Patients, Efficacy, and Treatment Retention.

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).

Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide.

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.

Influencia del entrenamiento vibratorio en el dolor y la calidad de vida de mujeres mayores de 65 años / Influence of vibration training on pain and quality of life in women older than 65 years old

El objetivo de nuestro estudio fue evaluar los efectos de un programa de ejercicio físico complementado con entrenamiento vibratorio sobre el dolor y la calidad de vida en mujeres mayores de 65 años. 52 mujeres físicamente activas e independientes, mayores de 65 años, fueron distribuidas aleatoriamente en dos grupos: ejercicio físico (n= 26) y este mismo programa complementado con entrenamiento vibratorio (n= 26). Ambos grupos realizaron dos sesiones semanales durante 12 semanas. Se evaluaron el dolor, mediante la escala verbal numérica, y la calidad de vida relacionada con la salud con el cuestionario SF-12. La diferencia estadística se estableció en p < .05. Tras la intervención hubo cambios significativos en el dolor en el grupo experimental frente al control, así como en la calidad de vida relacionada con la salud, tanto en su dimensión mental como física, a favor del grupo implementado con vibraciones. Los resultados sugieren que un entrenamiento vibratorio de tres meses como complemento del ejercicio físico disminuye el dolor y aumenta la calidad de vida de mujeres mayores de 65 años

The objective of our study was to evaluate the effects of an exercise program supplemented with vibration training on pain and quality of life in women over 65 years. 52 physically active and independent women, 65 and older, were randomized into two groups: exercise (n = 26) and the same supplemented with vibration training program (n = 26). Both groups performed two sessions per week for 12 weeks. Pain through verbal numeric scale and quality of life related to health with the SF-12 questionnaire were evaluated. Statistical signifficance was set at p < .05. After the intervention there were signifficant changes in pain in the experimental group compared to control and quality of life related to health, both mental and physical dimensions in favor of the group implemented vibrations. The results suggest that a three-month vibration training as a complement to physical exercise reduces pain and improves quality of life for women over 65

El entrenamiento vibratorio como intervención en la sarcopenia: repercusiones en el sistema neuromuscular de los adultos mayores / The vibration training as sarcopenia intervention: impact on the neuromuscular system of the elderly

Introducción: el envejecimiento se acompaña de una reducción progresiva de la masa muscular que contribuye al desarrollo de limitaciones funcionales, donde el entrenamiento vibratorio puede ser una opción de intervención óptima en la prevención y tratamiento de la sarcopenia. Objetivo: comprobar la efectividad del entrenamiento de vibraciones de cuerpo completo en el sistema neuromuscular de los adultos mayores. Métodos: revisión sistemática en las bases de datos Medline, CINAHL, WOS y PEDro, mediante la combinación de los descriptores del Medical Subjects Headings (MeSH) referentes a entrenamiento vibratorio, fuerza muscular, masa muscular y personas mayores. Resultados: fueron encontrados un total de 214 estudios sobre el entrenamiento vibratorio en personas mayores, bien como única intervención o en combinación con otros ejercicios, de los cuales 45 cumplían los criterios de selección. De ellos, 30 artículos fueron eliminados por no superar los 5 puntos según la escala de PEDro. Se incluyeron para el análisis final 15 ensayos clínicos. Conclusión: el entrenamiento con plataformas vibratorias demuestra ser un método de entrenamiento de la fuerza seguro, adecuado y eficaz para la población de mayor edad, pero con resultados similares al ejercicio de resistencia convencional, en la prevención y tratamiento de la sarcopenia (AU)

Introduction: aging is accompanied by a progressive reduction of muscle mass that contributes to the development of functional limitations, and where vibration training may be an option for optimal intervention in the prevention and treatment of sarcopenia. Objective: to assess the effectiveness of whole-body vibration in the neuromuscular system of the elderly. Methods: systematic review in Medline, CINAHL, WOS and PEDro data by combining the descriptors of Medical Subject Headings concerning vibration training, muscle strength, muscle mass and older adults. Results: a total of 214 studies were found on the vibration training in older people as either the only intervention or in combination with other exercises, of which 45 met the selection criteria. Of these, 30 items were eliminated by not more than 5 points according to the PEDro scale. They were included 15 clinical trials for final analysis. Conclusion: WBV training proves to be a safe, adequate and effective strength training method in the elderly population, but results are similar to conventional resistance exercise in the prevention and treatment of sarcopenia (AU)

Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study / Dosis efectiva mínimas de anti-TNF en artritis reumatoide: un estudio transversal

Aims: To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Patients and methods: Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. Main variables: dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. Results: 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). Conclusions: RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients

Objetivos: Avaluar dosis modificadas de anti-TNF en el control de actividad de la enfermedad en la artritis reumatoide (AR) medida por DAS28-VSG. Pacientes y métodos: Estudio transversal: pacientes con AR tratados con etanercept (ETN), adalimumab (ADA) o infliximab (IFX), en dosis estándar o modificada. Principales variables: dosis, enfermedad concomitante, fármacos modificadores (DMARDs), DAS28-VSG. Resultados: 195 pacientes con AR fueron incluidos (79% mujeres, edad media 58,1 años): ETN = 81, ADA = 56, IFX = 58. La duración de la enfermedad y el tiempo medio hasta el primer tratamiento biológico fue mayor en el grupo con IFX (p = 0,01). Distribución de los pacientes por dosis estándar: ETN (72,8%), ADA (69,6%), IFX (27,6%); incremento: IFX (69%), ADA (5,4%), ETN (0%), reducción: ETN (27,1%), ADA (25%), IFX (3,4%). Uso concomitante DMARD fue menor en ETN (58,2%) que ADA (66,07%) e IFX (79,31%). La mayor proporción de respondedores (DAS28 ≤ 3,2) se vio en ADA (65,3%) y ETN (61,7%) que en IFX (48,3%). Conclusiones: El control clínico de la AR se puede preservar con dosis modificadas de anti-TNF. Estudios prospectivos controlados deben realizarse para definir cuando la terapia se puede adaptar y en que pacientes (AU)

Estándares de calidad en una Unidad de Hospitalización de Día reumatológica. Propuesta del Grupo de Trabajo de Hospitales de Día de la Sociedad Española de Reumatología / Quality standards in a rheumatology day-care hospital unit. The proposal of the Spanish Society of Rheumatology Day Hospitals’ Working Group

Antecedentes. En los últimos años, las Unidades de Hospitalización de Día (UHdD) en Reumatología han experimentado un amplio desarrollo. Sin embargo, existe escasa documentación respecto a estándares de calidad, que mayoritariamente se limita a la estructura y no incluye aspectos específicos de la especialidad. Objetivo. Desarrollar estándares de calidad específicos para las UHdD en Reumatología. Métodos. Tras una revisión sistemática de la literatura y de documentos relacionados, un grupo de trabajo (GT) de 8 reumatólogos, bajo la supervisión de un metodólogo experto, elaboró una primera propuesta de estándares de calidad. Se realizó una segunda ronda para su revisión y sugerencias por todo el GT. Consensuado el contenido, se realizó un informe final. Resultados. Se definieron 17 estándares de estructura, 25 de proceso y 10 de resultados, con especial énfasis en aspectos específicos de una UHdD de Reumatología. La propuesta incluye: 1) estándares imprescindibles; 2) estándares de excelencia; 3) cartera de servicios de una UHdD reumatológica, y 4) criterios de funcionamiento. Conclusiones. Los estándares de calidad propuestos son la base para la elaboración de indicadores y de otras herramientas de gestión para las UHdD reumatológicas que garanticen una práctica homogénea, centrada en el paciente y basada en la evidencia y en la experiencia (AU)

Background. In recent years, the Rheumatology Day-Care Hospital Units (DHUs) have undergone extensive development. However, the quality standards are poorly documented and mainly limited to structure items rather than including broad and specific areas of this specialty. Objective. To develop specific quality standards for Rheumatology DHUs. Methods. After a systematic review of the literature and related documents, a working group (WG) involving 8 DHU-experienced rheumatologists developed an initial proposal of the quality standards, under the supervision of an expert methodologist. A second round was held by the WG group to review the initial proposal and to consider further suggestions. Once the content was agreed upon by consensus, a final report was prepared. Results. Seventeen structure standards, 25 process standards and 10 results standards were defined, with special emphasis on specific aspects of the Rheumatology DHU. The proposal includes: (1) essential standards to (2) excellent standards, (3) a Rheumatology DHU services portfolio and (4) performance criteria. Conclusions. The proposed quality standards are the basis for developing the indicators and other management tools for Rheumatology DHU, thereby ensuring a patient-oriented practice based on both the evidence and the experience (AU)