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.

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1ß release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1ß release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers.

Evaluation of right ventricular function after cardiac surgery: The importance of tricuspid annular plane systolic excursion and right ventricular ejection fraction.

OBJECTIVE: The evaluation of right ventricular systolic function is essential to the hemodynamic management of critically ill cardiac patients. Nevertheless, assessment of right ventricular function remains problematic. We sought to analyze the correlation between tricuspid annular plane systolic excursion (TAPSE) and right ventricular ejection fraction (RVEF) in the assessment of global and regional right ventricular function, respectively. METHODS: This was a prospective study of 61 cardiac surgical patients. TAPSE was measured with transthoracic echocardiography and RVEF was obtained by a thermodilution pulmonary artery catheter. Both measurements were estimated simultaneously during the early postoperative period. Patients with previously identified severe tricuspid insufficiency were excluded from the study to avoid confounding results. RESULTS: The etiologies for cardiac surgery were surgical pulmonary thromboendarterectomy in 19 patients, valve replacement in 17 patients, heart transplant in 13 patients, and coronary artery bypass graft in 9 patients. Mean RVEF and TAPSE were 26.2% ± 9.7% and 11.4 ± 4 mm, respectively. RVEF and TAPSE showed a significant correlation (r = 0.73, P < .001). Weak reverse relationships between TAPSE or RVEF with afterload hemodynamic parameters, mean pulmonary artery pressure, or pulmonary vascular resistance were elucidated. CONCLUSIONS: TAPSE is a robust measure of right ventricular function that correlates with RVEF assessed by pulmonary artery catheter. A noninvasive method such as echocardiography can guide and support invasive monitoring of right ventricular function in cardiac surgical patients.

Lacosamida: una nueva generación en el tratamiento de la epilepsia / Lacosamide: a new generation in the treatment of epilepsy

Resumen. A pesar de los numerosos fármacos antiepilépticos (FAE) disponibles, más del 30% de los pacientes con epilepsia no alcanza un control adecuado de sus crisis. Para estos pacientes, la administración de los recientes FAE puede ser una alternativa, previa a la cirugía o cuando ésta se contraindica. Los FAE de tercera generación proporcionan mecanismos de acción diferentes y perfiles de tolerabilidad más favorables que los de primera y segunda generación. La lacosamida ha recibido recientemente autorización de las agencias del medicamento europea (EMEA) y estadounidense (FDA) como FAE adyuvante en las crisis de inicio parcial en adultos mayores de 16 años, convirtiéndose en una novedosa opción en el tratamiento de la epilepsia (AU)

Summary. Despite the large number of antiepileptic drugs (AED) available today, more than 30% of patients with epilepsy do not manage to achieve adequate control over their seizures. For patients, the administration of the latest AED can be a good alternative, prior to surgery or when there are contraindications against it. Third generation AED offer different mechanisms of action and tolerability profiles that are more favourable than those of the first and second generations. Lacosamide has recently been approved by the European Medicines Agency (EMEA) and its United States counterpart (FDA) as an adjuctive AED in partial onset seizures in adults over the age of 16, thus making it a novel option in the treatment of epilepsy (AU)