Эффективность и безопасность препарата нусинерсен в рамках программы расширенного доступа в России

Introduction. Spinal muscular atrophy is a severe neuromuscular disease characterized by rapid progression of muscle weakness and early death. Pathogenetic therapy with nusinersen can significantly change the course of the disease and enable the patient to acquire new skills. The study of the efficacy and safety of nusinersen therapy in patients with type 1 spinal muscular atrophy should be continued. The aim of the study was to assess the safety and efficacy of nusinersen therapy in patients with type 1 spinal muscular atrophy for 6 months as part of an expanded access program at federal and regional healthcare facilities. Materials and methods. Patients with type 1 spinal muscular atrophy received nusinersen therapy under the expanded access program (NCT02865109). Patients were evaluated before starting treatment and 6 months after starting treatment. Overall motor development and motor function was assessed using the Hammersmith Infant Neurological Status Scale Part 2 and the Philadelphia Pediatric Hospital Neonatal Motor Scale. Results. 41 children aged 6 to 38 months received nusinersen therapy between July 2019 and March 2020. At the time of analysis, all patients were alive and continued treatment. The average improvement on the Hammersmith Hospital Neurological Status Scale was 3.7 points after 6 months of therapy compared to baseline (n = 39, p <0.001). The mean improvement on the Children’s Hospital of Philadelphia Scale for the Diagnosis of Motor Function in Newborns was 9.8 after 6 months of therapy from baseline (n = 30, p <0.001). Conclusion. The efficacy and safety of nusinersen have been demonstrated in real clinical practice in Russia in the treatment of early-onset spinal muscular atrophy.Введение. Спинальная мышечная атрофия – тяжелое нервно-мышечное заболевание, характеризующееся быстрым прогрессированием мышечной слабости, ранним летальным исходом. Применение патогенетической терапии нусинерсеном может существенно изменить течение болезни и дать возможность пациенту приобрести новые навыки. Изучение эффективности и безопасности терапии нусинерсеном у пациентов со спинальной мышечной атрофией 1-го типа неообходимо продолжать. Цель исследования – оценить безопасность и эффективность терапии нусинерсеном пациентов со спинальной мышечной атрофией 1-го типа в течение 6 мес в рамках клинической практики в лечебно-профилактических учреждениях федерального и регионального уровней. Материалы и методы. Пациенты со спинальной мышечной атрофией 1-го типа получали терапию препаратом нусинерсен в рамках программы расширенного доступа (NCT02865109). Оценка пациентов проводилась до начала лечения и через 6 мес после начала лечения. Оценивали общее двигательное развитие, моторную функцию – с помощью Шкалы оценки неврологического статуса больницы Хаммерсмит у детей раннего возраста, часть 2, и Шкалы детской больницы Филадельфии для диагностики двигательных функций у новорожденных. Результаты. Терапию препаратом нусинерсен получил 41 ребенок в возрасте от 6 до 38 мес в период с июля 2019 по март 2020 г. На момент анализа все пациенты были живы и продолжали лечение. Среднее улучшение по Шкале оценки неврологического статуса больницы Хаммерсмит составило 3,7 балла через 6 мес терапии по сравнению с исходным уровнем (n = 39, р <0,001). Среднее улучшение по Шкале детской больницы Филадельфии для диагностики двигательных функций у новорожденных составило 9,8 балла через 6 мес терапии по сравнению с исходным уровнем (n = 30, р <0,001). Заключение. Продемонстрированы эффективность и безопасность нусинерсена в условиях реальной клинической практики в России при терапии спинальной мышечной атрофии 1-го типа с ранним началом

UTERINE CANCER IN OLDER WOMEN: WHAT ARE ITS DISTINGUISHING CHARACTERISTICS?

Endometrial cancer (EC) is one of the most common pathologies among gynecologic cancer patients: It ranks the 3rd in the structure of oncological diseases in women in Russia. Early manifestation of various bleedings and good tumor visualization with ultrasound therapy allow to detect uterine cancer at stages I–II in almost 80 % of patients. Moreover, mortality due to progression has remained stable in the last 10 years. In this regard, detailed study of prognostic factors affecting the course and prognosis of the disease is timely and important for improvement of long-term results. One of the factors of unfavorable prognosis is old age. In this article, characteristics of the clinical course of uterine cancer in women after 70 with concomitant extragenital pathology are considered, and possible improvements for treatment quality of these patients are proposed based on literature results.The objective is to advance methods of treatment of uterine cancer in older patients and to obtain proven facts of improved prognosis for inclusion into clinical guidelines

The efficacy and safety of nusinersen within the expanded access program in Russia

Introduction. Spinal muscular atrophy is a severe neuromuscular disease characterized by rapid progression of muscle weakness and early death. Pathogenetic therapy with nusinersen can significantly change the course of the disease and enable the patient to acquire new skills. The study of the efficacy and safety of nusinersen therapy in patients with type 1 spinal muscular atrophy should be continued. The aim of the study was to assess the safety and efficacy of nusinersen therapy in patients with type 1 spinal muscular atrophy for 6 months as part of an expanded access program at federal and regional healthcare facilities. Materials and methods. Patients with type 1 spinal muscular atrophy received nusinersen therapy under the expanded access program (NCT02865109). Patients were evaluated before starting treatment and 6 months after starting treatment. Overall motor development and motor function was assessed using the Hammersmith Infant Neurological Status Scale Part 2 and the Philadelphia Pediatric Hospital Neonatal Motor Scale. Results. 41 children aged 6 to 38 months received nusinersen therapy between July 2019 and March 2020. At the time of analysis, all patients were alive and continued treatment. The average improvement on the Hammersmith Hospital Neurological Status Scale was 3.7 points after 6 months of therapy compared to baseline (n = 39, p <0.001). The mean improvement on the Children’s Hospital of Philadelphia Scale for the Diagnosis of Motor Function in Newborns was 9.8 after 6 months of therapy from baseline (n = 30, p <0.001). Conclusion. The efficacy and safety of nusinersen have been demonstrated in real clinical practice in Russia in the treatment of early-onset spinal muscular atrophy

Fluid‐Enhanced Annealing in the Subcontinental Lithospheric Mantle Beneath the Westernmost Margin of the Carpathian‐Pannonian Extensional Basin System

Mantle xenoliths from the Styrian Basin Volcanic Field (Western Pannonian Basin, Austria) are mostly coarse granular amphibole-bearing spinel lherzolites with microstructures attesting for extensive annealing. Olivine and pyroxene CPO (crystal-preferred orientation) preserve nevertheless the record of coeval deformation during a preannealing tectonic event. Olivine shows transitional CPO symmetry from [010]-fiber to orthogonal type. In most samples with [010]-fiber olivine CPO symmetry, the [001] axes of the pyroxenes are also dispersed in the foliation plane. This CPO patterns are consistent with lithospheric deformation accommodated by dislocation creep in a transpressional tectonic regime. The lithospheric mantle deformed most probably during the transpressional phase after the Penninic slab breakoff in the Eastern Alps. The calculated seismic properties of the xenoliths indicate that a significant portion of shear wave splitting delay times in the Styrian Basin (0.5 s out of approximately 1.3 s) may originate in a highly annealed subcontinental lithospheric mantle. Hydroxyl content in olivine is correlated to the degree of annealing, with higher concentrations in themore annealed textures. Based on the correlation between microstructures and hydroxyl content in olivine, we propose that annealing was triggered by percolation of hydrous fluids/melts in the shallow subcontinental lithospheric mantle. A possible source of these fluids/melts is the dehydration of the subducted Penninic slab beneath the Styrian Basin. The studied xenoliths did not record the latest large-scale geodynamic events in the region—the Miocene extension then tectonic inversion of the Pannonian Basin