Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Does physical activity improve motor function and gait in huntington disease? A systematic review and meta-analysis. / ¿La actividad física mejora la función motora y la marcha en la enfermedad de Huntington? Una revisión sistemática y metaanálisis.

INTRODUCTION: Huntington's disease (HD) is a degeneration of the brain. OBJECTIVE: To assess the evidence of the physical activity (PA) to improve motor function, gait speed, and walking endurance in individuals with HD. MATERIALS AND METHODS: Two reviewers independently screened references and selected relevant studies to identify randomized controlled trials (RCT), from MEDLINE/PubMed, CENTRAL, PEDro, Scopus, CINAHL, Web of Science databases from inception to September 2021. Two reviewers evaluated risk of bias by the PEDro scale. The primary outcome was assessed motor function, gait speed and walking endurance as a secondary outcome was evaluated activities of daily living (ADL), lower limb functionality strenght, balance, mobility and cognition function in HD. RESULTS: Eight RCT were finally included (231 individuals). Forest plots showed a positive effect for gait endurance, the mean difference (MD) was 17.40 (95% CI from 5.40 to 29.35; p = 0.004), the MD lower limb functionality strength was 1.76 (95% CI from 0.18 to 3.33; p = 0.03) favoring PA group and the MD cognition function was 1.83 (95% CI from 0.50 to 3.16; p = 0.007). No benefits were found for motor function, gait speed, ADL, balance and mobility. CONCLUSIONS: Positive effects of programs PA were observed for walking endurance lower limb functionality strenght and cognition function in low and moderate stage of HD. However, no benefits were found for motor function, gait speed, ADL, balance and mobility. All authors included aerobic exercises in their programs but is unclear if vigorous and intensive PA is optimal for individuals with HD.

TITLE: ¿La actividad física mejora la función motora y la marcha en la enfermedad de Huntington? Una revisión sistemática y metaanálisis.Introducción. La enfermedad de Huntington (EH) es una degeneración del cerebro. Objetivos. Evaluar la evidencia de la actividad física (AF) para mejorar la función motora y la marcha en las personas con EH. Materiales y métodos. Dos revisores examinaron de forma independiente las referencias y seleccionaron ensayos controlados aleatorizados en Medline/PubMed, CENTRAL, PEDro, Scopus, CINAHL y Web of Science desde el inicio hasta septiembre de 2021 y evaluaron el riesgo de sesgo mediante la escala PEDro. Las variables principales fueron la función motora y la marcha, y las secundarias, las actividades de la vida diaria (AVD), la funcionalidad (extremidades inferiores), el equilibrio, la movilidad y la función cognitiva en la EH. Resultados. Se incluyeron ocho ensayos controlados aleatorizados (231 individuos). Se observó un efecto positivo para la resistencia en la marcha, la diferencia de medias fue de 17,4 (intervalo de confianza al 95%: 5,4-29,35; p = 0,004), la diferencia de medias para la funcionalidad (extremidades inferiores) fue de 1,76 (intervalo de confianza al 95%: 0,18-3,33; p = 0,03) y la diferencia de medias para la función cognitiva fue de 1,83 (intervalo de confianza al 95%: 0,5-3,16; p = 0,007) a favor del grupo de AF. No se encontraron beneficios para la función motora, la velocidad de marcha, las AVD, el equilibrio y la movilidad. Conclusiones. Los programas de AF mejoran la resistencia en la marcha, la función cognitiva y la funcionalidad (extremidades inferiores) en la EH. Sin embargo, no se observaron efectos positivos para la función motora, la velocidad de la marcha, las AVD, el equilibrio y la movilidad. Todos los autores incluyeron ejercicios aeróbicos en sus programas, pero no está claro si la AF vigorosa e intensiva es óptima para las personas con EH.

Exploring insect biodiversity: the parasitic Hymenoptera, chiefly Chalcidoidea, associated with seeds of asphodels (Xanthorrhoeaceae), with the description of nine new species belonging to Eurytomidae and Torymidae.

An account is given of the communities of Chalcidoidea, mostly based upon species of Bruchophagus Ashmead (Eurytomidae), which feed as larvae in seeds of Asphodelus and Asphodeline (Xanthorrhoeaceae). Eight new species of Eurytomidae, namely B. abscedus Askew sp. n., B. asphodelinae Askew Stojanova sp. n., B. gijswijti Askew Ribes sp. n., B. insulare Delvare sp. n., B. lecomtei Delvare sp. n., B. ribesi Askew sp. n., Eurytoma genale Askew Stojanova sp. n., and Aximopsis balajasi Delvare sp. n., are described together with the new species Idiomacromerus asphodeli Ribes sp. n. (Torymidae). Eurytoma setigera Mayr, 1878 is again synonymized with E. pistaciae Rondani, 1877 syn. rev. Puklina dillerae Doganlar, 1993 and P. asphodelinae Boyadzhiev, 2003 are synonymized with P. depilata Graham, 1987 syn n. The use, respectively of the mitochondrial genes COI and Cyt B and of the nuclear gene EF1-α, allowed us to discriminate pairs of sibling species in the three genera of Eurytomidae and to circumscribe the limits of the hypervariable Eurytoma asphodeli Hedqvist, 1976. The trophic webs associated with five species/subspecies of asphodels are fully described and illustrated, the distributions of the chalcid wasps involved are figured, and the phenology of the most common species is quoted and figured.

Type A ganglion cysts of the radiocapitellar joint may involve compression of the superficial radial nerve.

INTRODUCTION: Two types of ganglion cysts at the elbow have been described depending on their anatomic location. Type A ganglion cyst is located proximal to the arcade of Frohse, and type B distal to it. Compressive neuropathies of the radial nerve at the level of the radial tunnel may lead to two different clinical entities with different clinical manifestations. These different conditions depend on which branch is involved. Although compression of the deep motor branch due to a ganglion cyst has been previously described, affection of the superficial sensory branch is considered much rarer. The aim of this study was to describe a series of patients in which painful and dysesthetic symptoms arose from superficial radial nerve compression due to type A ganglion cysts coming from the radiocapitellar joint. METHODS: A review of currently available literature about the disease was carried out. The clinical, histological and radiological records of a series of eight cases (seven patients) with compression of the superficial radial nerve diagnosed and treated between 2008 and 2011 were retrospectively reviewed. All patients complained of pain and dysesthesia at the lateral aspect of the elbow. All patients were initially diagnosed and managed as lateral epicondylitis. Persistence of the symptoms was evidenced in all patients after a course of six months of non-operative management. Magnetic resonance imaging was performed and revealed the presence of a mass compatible with a ganglion cyst coming from the radiocapitellar joint, pushing up the superficial sensory branch of the radial nerve and compressing it against the extensor carpi radialis brevis. Surgical excision was performed in all cases. RESULTS: Histology confirmed the diagnosis of ganglion cysts. Histological findings consisted of dense fibrous tissue, with no synovial or epithelial lining and mucoid material with foamy macrophages. The mean follow-up after surgical excision was 28months (range 24-30). The symptoms subsided in all cases. No complications were registered during the follow-up. CONCLUSION: Type A ganglion cysts of the radiocapitellar joint may involve compression of the superficial radial nerve. Our series of eight cases may suggest that this pathology might not be as rare as it was thought before. This evidence may be useful for the orthopaedic population, who may have another differential diagnosis when managing cases of painful symptoms located in the lateral aspect of the elbow. TYPE OF STUDY: Therapeutic study. LEVEL OF EVIDENCE: IV.