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Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

Polyglucosan body myopathy-1 (PGBM1) is an extremely rare glycogen storage diseases that leads to muscle weakness and cardiomyopathy due to the accumulation of polyglucosan bodies. The clinical presentation appears to be partially dependent on the genetic mutation, but no clear genotype/phenotype correlation is currently possible.We describe a 7 year old patient, who initially presented with recurrent vomiting and respiratory infections until her first year of life. Diagnostic workup revealed an achalasia and the whole exome sequencing revealed an homozygous RBCK1 (RANBP2-type and C3HC4-type zinc finger containing 1) variant (c.896_899delAGTG) located in exon 7 (mid-domain), which has also been described in 4 patients with PGBM1.The unusual presentation with gastrointestinal and respiratory symptoms before the development of progressive muscle weakness expands the phenotype of this disease.

IntroductionChildhood obesity has become an important topic, not only of increasing relevance during the COVID-19 pandemic but specifically enhanced by it. Restrictions implemented to mitigate further outbreaks led to major constraints on daily physical activity, leading to a severe increase in body weight among children. This study highlights changes in BMI and weight development in children during and (in particular) after the COVID-19 restrictions in Austria, focusing on various socioeconomic factors.MethodsWeight development throughout the pandemic and socioeconomic factors were evaluated by anonymous cross-sectional surveys filled out by parents at a pediatric practice.ResultsThis study included 388 children. The rate of obesity increased by 88.5%, from 6.4 to 12.1%, throughout the pandemic, reaching a maximum of 15.2% during the restrictions. Overall, age-adapted BMI z-scores increased significantly by 0.22 during the restrictions and remained increased by 0.19 compared to pre-pandemic levels. With the exception of obese children, all children in the study population experienced significant weight loss after the restrictions were lifted. Obese children continued to gain weight without any sign of the onset of normalization. Socioeconomic factors, such as participation in regular activity in the form of organized sport or the availability of an outdoor area, were associated with relevant differences before the pandemic but had no protective effect against intra-pandemic weight gain. A higher level of parental education was the only factor associated with less weight gain in children during the early phase of the pandemic.DiscussionAustrian COVID-19 restrictions have had concerning effects on pediatric BMI, with very little effect of socioeconomic background. After restrictions were loosened, measurable weight loss occurred, but the significant increase in children's BMI percentiles persisted. No weight loss was observed among children who were obese prior to the pandemic. There is a need for broad projects tackling childhood obesity, as obese children are the most vulnerable group with the strongest and most severe long-term effects.

Abstract Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.

Ante la presencia del COVID-19, se identificó que en Paraguay la información de generación propia es escasa y en ocasiones, falsa; aun así, es diseminada por los medios de comunicación, a ello se suma que, en poblaciones rurales, la información sobre como el coronavirus afecta la salud es insuficiente y los comunicadores de estas zonas no están capacitados en la difusión de este tipo de noticias. La investigación se desarrolló en dos comunidades rurales y una comunidad indígena del distrito de Alto Vera, Itapúa, Paraguay. El objetivo principal fue elaborar un diagnóstico participativo para determinar la percepción de las comunidades de Poncho, Caraguata y Mberu Pirapo’i sobre la pandemia del COVID-19. Se aplicó una investigación con enfoque mixto, en lo cuantitativo se trabajó con un diseño no experimental, transaccional descriptivo, en lo cualitativo con grupos focales (personal de salud, líderes/referentes comunitarios y autoridades). Al concluir la investigación, se comprobó que la población accede a informaciones sobre el COVID-19 principalmente a través de medios radiales, seguido de la televisión y las redes sociales; sin embargo, no pueden confirmar si la información recibida a través de esta última es real o no. Además, se identificó una disminución en la implementación de medidas sanitarias en el área; la información obtenida es insumo necesario para establecer una estrategia comunicativa utilizando tecnologías existentes en la comunidad, a fin de permitir una comunicación fluida y real sobre la pandemia del COVID-19 a ser implementada en el área de estudio y con posibilidad de ser replicada.

Cada año la Reserva para Parque Nacional San Rafael (RPNSR) se ve afectada por incendios forestales que ocasionan daños a extensas superficies tanto de bosques como pastizales naturales y otros componentes de la biodiversidad. Esto puede resultar en un inconveniente si no se toman las medidas correspondientes en la gestión de estos fenómenos. Por ello, el objetivo principal fue analizar la dinámica de los incendios forestales en la RPNSR, mediante un análisis multitemporal en el periodo 2007-2017, con el registro detallado de los focos de calor captados por el sensor MODIS y análisis con sistemas de información geográfica. Comparación y análisis con los datos de precipitaciones mensuales. Los mismos dieron como resultado que indistintamente del régimen pluviométrico dado a lo largo del periodo de análisis, se registraron ocurrencia de incendios. Con relación a la cantidad de focos de calor registrados mensualmente, los meses de mayor registro de focos de calor van de junio a noviembre, siendo los meses de julio y agosto los que más repetidamente presentan los picos más elevados. En base a estos resultados y analizando los antecedentes de acciones en gestión de incendios forestales, ya emprendidas por organizaciones e instituciones en la RPNSR, se propuso un Plan de Prevención y Control de Incendios Forestales con los puntos más resaltantes.

Abstract Background New-generation, cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD). Objective To describe systematically the CSF profile in children with MOG-EM. Material and methods Cytological and biochemical findings (including white cell counts [WCC] and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgM/IgA fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster [MRZ] reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF l-lactate) from 108 lumbar punctures in 80 pediatric patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively. Results Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in 89% of samples (N = 96), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 29). If present at all, intrathecal IgG synthesis was low, often transient and mostly restricted to acute attacks. Intrathecal IgM synthesis was present in 21% and exclusively detectable during acute attacks. CSF WCC were elevated in 54% of samples (median 40 cells/μl; range 6–256; mostly lymphocytes and monocytes; > 100/μl in 11%). Neutrophils were present in 71% of samples; eosinophils, activated lymphocytes, and plasma cells were seen only rarely (all

Abstract Interspecific variation in life‐history traits and physiological limits can be linked to the environmental conditions species experience, including climatic conditions. As alpine environments are particularly vulnerable under climate change, we focus on the montane‐alpine fly Drosophila nigrosparsa. Here, we characterized some of its life‐history traits and physiological limits and compared these with those of other drosophilids, namely Drosophila hydei, Drosophila melanogaster, and Drosophila obscura. We assayed oviposition rate, longevity, productivity, development time, larval competitiveness, starvation resistance, and heat and cold tolerance. Compared with the other species assayed, D. nigrosparsa is less fecund, relatively long‐living, starvation susceptible, cold adapted, and surprisingly well heat adapted. These life‐history characteristics provide insights into invertebrate adaptations to alpine conditions which may evolve under ongoing climate change.

This article, published in the journal Neuropediatrics, discusses the use of A20 (TNFAIP3) as a potential biomarker to distinguish relapse from remission in pediatric patients with monophasic MOGAD (MOG-IgG-associated disorders). MOGAD is a type of acquired demyelinating syndrome associated with antibodies against myelin oligodendrocyte glycoprotein. The study found that A20 levels were significantly lower during clinical events compared to remission in monophasic MOGAD patients. However, there was no significant difference in A20 levels between clinical events and remission in multiphasic MOGAD patients. The authors suggest that further research is needed to investigate the diagnostic, prognostic, and therapeutic implications of A20 in pediatric MOGAD patients. [Extracted from the article]

5q-associated spinal muscular atrophy is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by the European Medicines Agency and Food and Drug Administration for the treatment of spinal muscular atrophy patients, however, long-term experience is still scarce. In contrast to clinical trial data with restricted patient populations and short observation periods, we report here real-world evidence on a broad spectrum of patients with early-onset spinal muscular atrophy treated with nusinersen focusing on effects regarding motor milestones, and respiratory and bulbar insufficiency during the first years of treatment. Within the SMArtCARE registry, all patients under treatment with nusinersen who never had the ability to sit independently before the start of treatment were identified for data analysis. The primary outcome of this analysis was the change in motor function evaluated with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders and motor milestones considering World Health Organization criteria. Further, we evaluated data on the need for ventilator support and tube feeding, and mortality. In total, 143 patients with early-onset spinal muscular atrophy were included in the data analysis with a follow-up period of up to 38 months. We observed major improvements in motor function evaluated with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders. Improvements were greater in children >2 years of age at start of treatment than in older children. 24.5% of children gained the ability to sit independently. Major improvements were observed during the first 14 months of treatment. The need for intermittent ventilator support and tube feeding increased despite treatment with nusinersen. Our findings confirm the increasing real-world evidence that treatment with nusinersen has a dramatic influence on disease progression and survival in patients with early-onset spinal muscular atrophy. Major improvements in motor function are seen in children younger than 2 years at the start of treatment. Bulbar and respiratory function needs to be closely monitored, as these functions do not improve equivalent to motor function. [ABSTRACT FROM AUTHOR]