المؤلفون: Anna Łusakowska, Adrianna Wójcik, Anna Frączek, Karolina Aragon-Gawińska, Anna Potulska-Chromik, Paweł Baranowski, Ryszard Nowak, Grzegorz Rosiak, Krzysztof Milczarek, Dariusz Konecki, Zuzanna Gierlak-Wójcicka, Małgorzata Burlewicz, Anna Kostera-Pruszczyk

المصدر: Orphanet Journal of Rare Diseases, Vol 18, Iss 1, Pp 1-13 (2023)

مصطلحات موضوعية: Patient global impression – improvement, Computed tomography–guided lumbar puncture, Functional tests, Nusinersen, Scoliosis, SMN2 gene, Medicine

الوصف: Abstract Background Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a biallelic mutation in the SMN1 gene, resulting in progressive muscle weakness and atrophy. Nusinersen is the first disease-modifying drug for all SMA types. We report on effectiveness and safety data from 120 adults and older children with SMA types 1c-3 treated with nusinersen. Methods Patients were evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE; n = 73) or the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; n = 47). Additionally, the Revised Upper Limb Module (RULM) and 6-minute walk test (6MWT) were used in a subset of patients. Patients were followed for up to 30 months of nusinersen treatment (mean, SD; 23, 14 months). Subjective treatment outcomes were evaluated with the Patients Global Impression–Improvement (PGI-I) scale used in all patients or caregivers at each follow-up visit. Results An increase in the mean HFMSE score was noted at month 14 (T14) (3.9 points, p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-1172Test

الوصول الحر: https://doaj.org/article/caba915b35344630ab47436ccc08a777Test

المؤلفون: Claudia A. Chiriboga, Claudio Bruno, Tina Duong, Dirk Fischer, Eugenio Mercuri, Janbernd Kirschner, Anna Kostera-Pruszczyk, Birgit Jaber, Ksenija Gorni, Heidemarie Kletzl, Imogen Carruthers, Carmen Martin, Francis Warren, Renata S. Scalco, Kathryn R. Wagner, Francesco Muntoni, the JEWELFISH Study Group

المصدر: Neurology and Therapy, Vol 12, Iss 2, Pp 543-557 (2023)

مصطلحات موضوعية: Evrysdi, Pharmacodynamics, Risdiplam, Safety, Spinal muscular atrophy, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Introduction Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1–3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam. Methods Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment. Results A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1–60 years) and 39.1 kg (9.2–108.9 kg), respectively. About 63% of patients aged 2–60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2193-8253Test; https://doaj.org/toc/2193-6536Test

الوصول الحر: https://doaj.org/article/cf9aa173befd4087b4e4bc7cce3e9e84Test

المؤلفون: Claudia A. Chiriboga, Claudio Bruno, Tina Duong, Dirk Fischer, Eugenio Mercuri, Janbernd Kirschner, Anna Kostera-Pruszczyk, Birgit Jaber, Ksenija Gorni, Heidemarie Kletzl, Imogen Carruthers, Carmen Martin, Francis Warren, Renata S. Scalco, Kathryn R. Wagner, Francesco Muntoni, the JEWELFISH Study Group

المصدر: Neurology and Therapy, Vol 12, Iss 5, Pp 1799-1801 (2023)

مصطلحات موضوعية: Neurology. Diseases of the nervous system, RC346-429

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2193-8253Test; https://doaj.org/toc/2193-6536Test

الوصول الحر: https://doaj.org/article/258bc786e54b4365b79dbe9dd14b5d86Test

المؤلفون: Jacek Jakubowski, Anna Potulska-Chromik, Jolanta Chmielińska, Monika Nojszewska, Anna Kostera-Pruszczyk

المصدر: Bulletin of the Polish Academy of Sciences: Technical Sciences, Vol 71, Iss 2 (2023)

مصطلحات موضوعية: image processing, medical diagnosis, parkinson’s disease, finger tapping test, Technology, Technology (General), T1-995

الوصف: Finger tapping is one of the standard tests for Parkinson's disease diagnosis performed to assess the motor function of patients' upper limbs. In clinical practice, the assessment of the patient's ability to perform the test is carried out visually and largely depends on the experience of clinicians. This article presents the results of research devoted to the objectification of this test. The methodology was based on the proposed measurement method consisting in frame processing of the video stream recorded during the test to determine the time series representing the distance between the index finger and the thumb. Analysis of the resulting signals was carried out in order to determine the characteristic features that were then used in the process of distinguishing patients with Parkinson's disease from healthy cases using methods of machine learning. The research was conducted with the participation of 21 patients with Parkinson's disease and 21 healthy subjects. The results indicate that it is possible to obtain the sensitivity and specificity of the proposed method at the level of approx. 80 %. However, the patients were in the so-called ON phase when symptoms are reduced due to medication, which was a much greater challenge compared to analyzing signals with clearly visible symptoms as reported in related works.

وصف الملف: electronic resource

العلاقة: https://journals.pan.pl/Content/126606/PDF/BPASTS_2023_71_2_3211.pdfTest; https://doaj.org/toc/2300-1917Test

الوصول الحر: https://doaj.org/article/ad3957b8f1354bf6a8428fc78b595ae7Test

المؤلفون: Dominika Krupa, Marcin Czech, Ewa Chudzyńska, Beata Koń, Anna Kostera-Pruszczyk

المصدر: Healthcare, Vol 11, Iss 10, p 1515 (2023)

مصطلحات موضوعية: spinal muscular atrophy, real-world evidence, nusinersen, therapy costs, budget impact, Medicine

الوصف: Background: Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease resulting in children’s mortality and disability. Nusinersen is available to all SMA patients in Poland since 2019. Aim: To compare mortality or disease progression to mechanical ventilation in two patient cohorts before and after the program’s introduction. Additionally, to describe the patient population treated with nusinersen and costs incurred by the public payer. Methods: We used the National Health Fund (NHF) database to identify patients born in either 2014 or 2019, who received at least two health services with an ICD10 G12 diagnosis. Outcomes were time to event: death or first mechanical ventilation. We identified all benefits received by nusinersen-treated patients, between 1 January 2019 and 31 May 2022. Results: Children with SMA born in 2019 had significantly lower mortality in the first years of their lives than children born in 2014. Approximately 875 patients (all age groups) were treated with nusinersen in the analysis period. The cost of causal drugs in this period amounted to €51.4 million. The cost of healthcare benefits amounted to €14.9 million. Conclusions: The drug program to treat SMA improved patient care in Poland. The NHF database was a reliable source to monitor resource-intensive therapies’ costs, demography, and selected patient outcomes.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2227-9032/11/10/1515Test; https://doaj.org/toc/2227-9032Test

الوصول الحر: https://doaj.org/article/6966662795aa4d848ce8436aa8a4f220Test

المؤلفون: Anna Lusakowska, Maria Jedrzejowska, Anna Kaminska, Katarzyna Janiszewska, Przemysław Grochowski, Janusz Zimowski, Janusz Sierdzinski, Anna Kostera-Pruszczyk

المصدر: Orphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-9 (2021)

مصطلحات موضوعية: Spinal muscular atrophy (SMA), Neuromuscular disease, Registry, TREAT-NMD, SMN2 copy number, Type 3 SMA, Medicine

الوصف: Abstract Background Spinal muscular atrophy (SMA) is one of the most frequent and severe genetic diseases leading to premature death or severe motor disability. New therapies have been developed in recent years that change the natural history of the disease. The aim of this study is to describe patients included in the Polish Registry of SMA, with a focus on the course of type 3 SMA (SMA3) before the availability of disease-modifying treatments. Results 790 patients with SMA were included in the registry (173 with type 1 [SMA1], 218 with type 2 [SMA2], 393 with SMA3, and six with type 4 SMA [SMA4]), most (52%) of whom were adults. Data on SMN2 gene copy number were available for 672 (85%) patients. The mean age of onset was 5 months for SMA1, 11.5 months for SMA2, and 4.5 years for SMA3. In patients with SMA3, the first symptoms occurred earlier in those with three copies of SMN2 than in those with four copies of SMN2 (3.2 years vs. 6.7 years). The age of onset of SMA3 was younger in girls than in boys (3.1 years vs. 5.7 years), with no new cases observed in women older than 16 years. Male patients outnumbered female patients, especially among patients with SMA3b (49 female vs. 85 male patients) and among patients with SMA3 with four copies of SMN2 (30 female vs. 69 male patients). 44% of patients with SMA3 were still able to walk; in those who were not still able to walk, the mean age of immobilization was 14.0 years. Patients with SMA3a (age of onset

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-1172Test

الوصول الحر: https://doaj.org/article/675fa2b2c04f498a88188b85b100dd84Test

المؤلفون: Małgorzata Łukawska, Anna Potulska-Chromik, Marta Lipowska, Dorota Hoffman-Zacharska, Beata Olchowik, Magdalena Figlerowicz, Karolina Kanabus, Edyta Rosiak, Anna Kostera-Pruszczyk

المصدر: Frontiers in Neurology, Vol 12 (2022)

مصطلحات موضوعية: chronic inflammatory demyelinating polyneuropathy, childhood CIDP, IVIg, atypical CIDP, CIDP criteria, Neurology. Diseases of the nervous system, RC346-429

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fneur.2021.784144/fullTest; https://doaj.org/toc/1664-2295Test

الوصول الحر: https://doaj.org/article/155442a6133a4994bb511fc4f017b414Test

المؤلفون: Kalina Andrysiak, Alicja Martyniak, Anna Potulska-Chromik, Anna Kostera-Pruszczyk, Jacek Stępniewski, Józef Dulak

المصدر: Stem Cell Research, Vol 57, Iss , Pp 102563- (2021)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disease caused by mutations inSMN1 gene encoding survival motor neuron (SMN) protein. Lack of this protein leads to progressive loss of motor neurons and therefore to gradual loss of signal transmission between motor neurons and skeletal muscle cells. As a consequence, patients develop muscle atrophy and lose the ability to move independently, what is also related to problems with breathing and swallowing. Here, we describe the generation of human induced pluripotent stem cells (hiPSC) from peripheral blood mononuclear cells (PBMC) of adult SMA type 3 patient with a use of Sendai virus vectors.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1873506121004104Test; https://doaj.org/toc/1873-5061Test

الوصول الحر: https://doaj.org/article/7bc2e014b8df4854b25bfcb570300c17Test

المؤلفون: Agnieszka Cieniewicz, Janusz Trzebicki, Ewa Mayzner-Zawadzka, Anna Kostera-Pruszczyk, Radosław Owczuk

المصدر: Anaesthesiology Intensive Therapy, Vol 51, Iss 3, Pp 169-177 (2019)

مصطلحات موضوعية: Anesthesiology, RD78.3-87.3, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9

وصف الملف: electronic resource

العلاقة: https://www.termedia.pl/Malignant-hyperthermia-what-do-we-know-in-2019-,118,37560,1,1.htmlTest; https://doaj.org/toc/1642-5758Test; https://doaj.org/toc/1731-2531Test

الوصول الحر: https://doaj.org/article/f0b395a428d044f2962b2c88f47f3916Test

المؤلفون: Anna Macias, Jakub Piotr Fichna, Malgorzata Topolewska, Maria J. Rȩdowicz, Anna M. Kaminska, Anna Kostera-Pruszczyk

المصدر: Frontiers in Neuroscience, Vol 15 (2021)

مصطلحات موضوعية: LGMD, CAPN3, non-coding, enhancer, silencer, calpain-3, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Limb–girdle muscular dystrophy type R1 (LGMDR1) is caused by mutations in CAPN3 and is the most common type of recessive LGMD. Even with the use of whole-exome sequencing (WES), only one mutant allele of CAPN3 is found in a significant number of LGMDR patients. This points to a role of non-coding, intronic or regulatory, sequence variants in the disease pathogenesis. Targeted sequencing of the whole CAPN3 gene including not only intronic, 3′ and 5′ UTRs but also potential regulatory regions was performed in 27 patients suspected with LGMDR1. This group included 13 patients with only one mutated CAPN3 allele detected previously with exome sequencing. A second rare variant in the non-coding part of CAPN3 was found in 11 of 13 patients with previously identified single mutation. Intronic mutations were found in 10 cases, with c.1746-20C>G variant present in seven patients. In addition, a large deletion of exons 2–8 was found in one patient. In the patients with no causative mutation previously found, we detected rare CAPN3 variants in 5 out of 10 patients and in two of them in a compound heterozygous state. Rare variants within putative regulatory sequences distant from the CAPN3 gene were found in 15 patients, although in 11 of these cases, other variants are deemed causative. The results indicate that intronic mutations are common in Polish LGMDR patients, and testing for non-coding mutations in CAPN3 should be performed in apparently single heterozygous patients.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnins.2021.692482/fullTest; https://doaj.org/toc/1662-453XTest

الوصول الحر: https://doaj.org/article/337ad31ac4cd4a9d8166ab21a5852521Test