RESUMO
AIM: To evaluate the long-term clinical effectiveness of computed tomography (CT)-guided transforaminal cervical epidural steroid injection using an anterolateral approach for the treatment of cervical radiculopathy (CR) using well-established robust clinical scoring systems for neck pain and neck disability. Despite its widespread use, evidence to support the long-term benefit of routine cervical epidural steroid injection is currently very limited. MATERIALS AND METHODS: This study included 113 patients with magnetic resonance imaging (MRI)-confirmed CR who underwent a steroid injection at a single cervical level via a unilateral transforaminal anterolateral approach. Pain was assessed quantitatively at pre-injection, 15 minutes post-injection, 1 month, 3 months, and at 1 year. Neck disability was assessed using the Oswestry Neck Disability Index (NDI) at pre-injection, 1 month, 3 months, and 1 year time points. RESULTS: Eighty patients completed the study. Sixty per cent reported reduced neck pain (mean pain reduction, 55%), which was clinically significant in 45% cases. Furthermore, 66% reported an improvement in neck disability (mean improvement, 51%), which was clinically significant for 56% patients. Clinically significant good outcomes in both neck pain and neck disability were evident from as early as 1-month, and importantly, were independent both of pre-treatment CR characteristics (including severity of pre-injection neck pain or disability) and of findings on pre-injection MRI imaging. CONCLUSION: Transforaminal anterolateral approach CT-guided epidural steroid injection resulted in a clinically significant long-term improvement in both neck pain and disability for half of the present cohort of patients with unilateral single-level CR. This improvement was independent of the severity of the initial symptoms and pre-injection MRI findings.
Assuntos
Radiculopatia , Humanos , Radiculopatia/diagnóstico por imagem , Radiculopatia/tratamento farmacológico , Cervicalgia/diagnóstico por imagem , Cervicalgia/tratamento farmacológico , Injeções Epidurais/métodos , Resultado do Tratamento , Esteroides/uso terapêutico , Tomografia Computadorizada por Raios X/métodosRESUMO
Calcium-dependent activator protein for secretion 1 (CAPS1) is a SNARE accessory protein that facilitates formation of the SNARE complex to enable neurotransmitter release. Messenger RNAs encoding CAPS1 are subject to a site-specific adenosine-to-inosine (A-to-I) editing event resulting in a glutamate-to-glycine (E-to-G) substitution in the C-terminal domain of the encoded protein product. The C-terminal domain of CAPS1 is necessary for its synaptic enrichment and Cadps RNA editing has been shown previously to enhance the release of neuromodulatory transmitters. Using mutant mouse lines engineered to solely express CAPS1 protein isoforms encoded by either the non-edited or edited Cadps transcript, primary neuronal cultures from mouse hippocampus were used to explore the effect of Cadps editing on neurotransmission and CAPS1 synaptic localization at both glutamatergic and GABAergic synapses. While the editing of Cadps does not alter baseline evoked neurotransmission, it enhances short-term synaptic plasticity, specifically short-term depression, at inhibitory synapses. Cadps editing also alters spontaneous inhibitory neurotransmission. Neurons that solely express edited Cadps have a greater proportion of synapses that contain CAPS1 than neurons that solely express non-edited Cadps for both glutamatergic and GABAergic synapses. Editing of Cadps transcripts is regulated by neuronal activity, as global network stimulation increases the extent of transcripts edited in wild-type hippocampal neurons, whereas chronic network silencing decreases the level of Cadps editing. Taken together, these results provide key insights into the importance of Cadps editing in modulating its own synaptic localization, as well as the modulation of neurotransmission at inhibitory synapses in hippocampal neurons.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/fisiologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Edição de RNA/genética , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia , Adenosina Desaminase/metabolismo , Animais , Sistemas CRISPR-Cas , Fenômenos Eletrofisiológicos , Ácido Glutâmico/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Hipocampo/citologia , Hipocampo/metabolismo , Camundongos , Mutação , Plasticidade Neuronal/genética , Plasticidade Neuronal/fisiologia , Cultura Primária de Células , Edição de RNA/fisiologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
BACKGROUND: Educational capacity building in pediatric ophthalmology is necessary to address the burden of childhood blindness in Ethiopia. Residency and fellowship training at Addis Ababa University (AAU) have been enhanced with support from the University of Toronto (UofT), following the established Toronto Addis Ababa Academic Collaboration (TAAAC). Our aim was to assess the feasibility of implementing a pediatric ophthalmology fellowship at AAU with support from UofT, modeled by successful postgraduate medical education within TAAAC. METHODS: A situational analysis, including a needs assessment, was conducted at Menelik II Hospital, Addis Ababa. Staff expertise, equipment and infrastructure were compared to International Council of Ophthalmology fellowship guidelines. Patient volumes were assessed through medical chart review. Local training needs were evaluated. A strategic working meeting facilitated program specification. RESULTS: The faculty consisted of 11 ophthalmologists, including 2 pediatric specialists. Fourteen thousand six hundred twenty-seven medical and three thousand six hundred forty-one surgical pediatric cases were seen in the previous year. A 2-year fellowship incorporating anterior segment, retinoblastoma, strabismus, and retinopathy of prematurity modules was developed. Research collaborations, didactic teaching, and surgical supervision were identified as priorities requiring support. Quality standard indicators included faculty feedback, case log review and formal examination. Telemedicine, development of a larger eye hospital and partnerships to support equipment maintenance were identified as strategies to manage implementation barriers. CONCLUSIONS: The situational analysis provided a way forward for the development of a pediatric ophthalmology fellowship, the first of its kind in Eastern Africa. Learning outcomes are feasible given high patient volumes, qualified staff supervision and sufficient equipment. Strategic partnerships may ensure resource sustainability.
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Educação Médica , Oftalmologia , Canadá , Criança , Etiópia , Bolsas de Estudo , Humanos , Recém-Nascido , Oftalmologia/educaçãoRESUMO
Purpose: Little is known regarding differences in childhood growth between somatic and heritable retinoblastoma (Rb) populations. We aimed to compare childhood growth parameters between somatic and heritable Rb cohorts at birth and at time of diagnosis with Rb. Methods: A multinational, longitudinal cohort study was conducted with patients from 11 centers in 10 countries who presented with treatment naïve Rb from January to December 2019. Variables of interest included age, sex, and size characteristics at birth and at time of presentation, as well as germline mutation status. After Bonferroni correction, results were statistically significant if the P value was less than 0.005. Results: We enrolled 696 patients, with 253 analyzed after exclusion criteria applied. Between somatic (n = 39) and heritable (n = 214) Rb cohorts, with males and females analyzed separately, there was no significant difference in birth weight percentile, weight percentile at time of diagnosis, length percentile at time of diagnosis, weight-for-length percentile at time of diagnosis, or change of weight percentile from birth to time of diagnosis. Patients with heritable Rb had a smaller mean weight percentile at birth and smaller mean weight and length percentiles at time of diagnosis with Rb, although this difference was not statistically significant. All cohorts experienced a slight negative change of weight percentile from birth to time of diagnosis. No cohort mean percentiles met criteria for failure to thrive, defined as less than the 5th percentile. Conclusions: Children with Rb seem to have normal birth and childhood growth patterns. There is no definitive evidence that somatic or heritable Rb has a biological or environmental impact on childhood growth parameters.
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Peso ao Nascer , Neoplasias da Retina , Retinoblastoma , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estatura/genética , Peso Corporal , Desenvolvimento Infantil/fisiologia , Mutação em Linhagem Germinativa , Estudos Longitudinais , Neoplasias da Retina/genética , Retinoblastoma/genética , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate in a large global sample of patients with retinoblastoma whether sex predilection exists for this childhood eye cancer. METHODS: A cross-sectional analysis including 4351 treatment-naive retinoblastoma patients from 153 countries who presented to 278 treatment centers across the world in 2017. The sex ratio (male/female) in the sample was compared to the sex ratio at birth by means of a two-sided proportions test at global level, country economic grouping, continent, and for selected countries. RESULTS: For the entire sample, the mean retinoblastoma sex ratio, 1.20, was higher than the weighted global sex ratio at birth, 1.07 (p < 0.001). Analysis at economic grouping, continent, and country-level demonstrated differences in the sex ratio in the sample compared to the ratio at birth in lower-middle-income countries (n = 1940), 1.23 vs. 1.07 (p = 0.019); Asia (n = 2276), 1.28 vs. 1.06 (p < 0.001); and India (n = 558), 1.52 vs. 1.11 (p = 0.008). Sensitivity analysis, excluding data from India, showed that differences remained significant for the remaining sample (χ2 = 6.925, corrected p = 0.025) and for Asia (χ2 = 5.084, corrected p = 0.036). Excluding data from Asia, differences for the remaining sample were nonsignificant (χ2 = 2.205, p = 0.14). CONCLUSIONS: No proof of sex predilection in retinoblastoma was found in the present study, which is estimated to include over half of new retinoblastoma patients worldwide in 2017. A high male to female ratio in Asian countries, India in specific, which may have had an impact on global-level analysis, is likely due to gender discrimination in access to care in these countries, rather than a biological difference between sexes.