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OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.
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BACKGROUND: To clarify the relationship between the PaO2/FiO2 and 28-day mortality in patients with sepsis. METHODS: This was a retrospective cohort study regarding MIMIC-IV database. Nineteen thousand two hundred thirty-three patients with sepsis were included in the final analysis. PaO2/FiO2 was exposure variable, 28-day mortality was outcome variable. PaO2/FiO2 was log-transformed as LnPaO2/FiO2. Binary logistic regression was used to explore the independent effects of LnPaO2/FiO2 on 28-day mortality using non-adjusted and multivariate-adjusted models. A generalized additive model (GAM) and smoothed curve fitting was used to investigate the non-linear relationship between LnPaO2/FiO2 and 28-day mortality. A two-piecewise linear model was used to calculate the OR and 95% CI on either side of the inflection point. RESULTS: The relationship between LnPaO2/FiO2 and risk of 28-day death in sepsis patients was U-shape. The inflection point of LnPaO2/FiO2 was 5.30 (95%CI: 5.21-5.39), which indicated the inflection point of PaO2/FiO2 was 200.33 mmHg (95%CI: 183.09 mmHg-219.20 mmHg). On the left of inflection point, LnPaO2/FiO2 was negatively correlated with 28-day mortality (OR: 0.37, 95%CI: 0.32-0.43, p < 0.0001). On the right of inflection point, LnPaO2/FiO2 was positively correlated with 28-day mortality in patients with sepsis (OR: 1.53, 95%CI: 1.31-1.80, p < 0.0001). CONCLUSIONS: In patients with sepsis, either a high or low PaO2/FiO2 was associated with an increased risk of 28-day mortality. In the range of 183.09 mmHg to 219.20 mmHg, PaO2/FiO2 was associated with a lower risk of 28-day death in patients with sepsis.
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Sepsis , Humanos , Estudios Retrospectivos , Modelos LogísticosRESUMEN
OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS: For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.
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Miastenia Gravis , Tacrolimus , Humanos , Niño , Prednisona/efectos adversos , Tacrolimus/efectos adversos , Estudios Retrospectivos , Actividades Cotidianas , Inmunosupresores/efectos adversos , Miastenia Gravis/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Ácido Micofenólico/efectos adversosRESUMEN
BACKGROUND: Thiamine metabolism dysfunction syndrome 5 (THMD5) is a rare inherited metabolic disorder due to thiamine pyrophosphokinase 1(TPK1) deficiency, caused by mutations in TPK1. The core symptoms of the disease is acute or subacute onset encephalopathy, ataxia, muscle hypotonia, and regression of developmental milestones in early infancy, repeatedly triggered by acute infectious illness. However, we report two brothers of THMD5 with compound heterozygous for the mutations c.614-1G > A,c.224 T > A p.(Ile75Asn), but the prognosis is quite different if thiamine suppled. According to our current knowledge, the missense variant c.224 T > A p.(Ile75Asn) was not published previously. CASE PRESENTATION: Here, we describe two affected siblings in a Chinese family, after an uneventful pregnancy to non-consanguineous and healthy parents. The older brother presented with normal development during the first 6 months of life, but developed regression of developmental milestones after, accompanied with muscle hypotonia, and chronic encephalopathy, and died at 1 year and 6 months old. The younger brother presented with acute onset encephalopathy, ataxia, muscle hypotonia, repeatedly triggered by acute infectious illness. He was compound heterozygous for the mutations c.614-1G > A,c.224 T > A p.(Ile75Asn) identified by whole exome sequencing. He was diagnosed of THMD5 when he was 11 month. Oral supplementation of thiamine 100 mg/day, the symptoms gradually disappeared. At the age of 2 years and 4 months, he stoped thiamine, his symptoms returned and were once again relieved by oral supplementation of thiamine 100 mg/day. CONCLUSIONS: THMD5 is a rare, but treatable neurodegenerative disease, the clinical phenotype ranges from mild to severe. Massive-dose of thiamine supplementation may ameliorate the course of TPK1 deficiency. When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis. Treatment with thiamine while awaiting the outcome of diagnostic tests may be a good choice.
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Encefalopatías , Enfermedades Neurodegenerativas , Ataxia/tratamiento farmacológico , Humanos , Masculino , Hipotonía Muscular , Mutación/genética , Hermanos , Tiamina Pirofosfoquinasa/genética , Tiamina/genética , Tiamina/metabolismo , Tiamina/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVES: To investigate the Intensivists' cognizance of nutritional management and its determinants, and to provide evidence for standardizing nutritional therapy with protocols. METHODS AND STUDY DESIGN: From April to July 2021, a multi-stage sampling method was used to investigate the nutritional cognizance of critical care physicians in secondary and tertiary hospitals in Guizhou Province, China; Questionnaires and scales were used as survey tools. The questionnaires sought general information about the respondents and documented their nutrition cognizance and practice. Five scalar dimensions explored nutritional management, with answers scored for 1-5 points, 3 points being the pass score. RESULTS: 322 respondents from 147 hospitals were surveyed. The average score was passable, but not good at 3.37±0.71 (p<0.01 with 3.0 as reference). Among the five dimensions, evaluation and monitoring of nutritional status had the highest score (3.79±0.67, p<0.01), the understanding of nutritional preparations had the lowest (3.09±0.86, p>0.05), and the scores of other dimensions ranged from 3.21 to 3.49. Almost 70% of intensivists said that they would give priority to other than nutritional therapeutic measures in actual clinical practice. But 96% thought it necessary to strengthen and emphasise nutritional management. CONCLUSIONS: Critical care physicians' knowledge and understanding of nutritional therapy are limited, especially in the use of supportive preparations; Recourse to protocols and standardized nutritional management of assistance may depend on training, assigned role, peer expectations and health system policy, each of which has the potential for advancement in the interest of better nutritional care in provincial Guizhou.
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Cuidados Críticos , Unidades de Cuidados Intensivos , China , Cuidados Críticos/métodos , Hospitales , Humanos , Apoyo Nutricional/métodos , Encuestas y CuestionariosRESUMEN
PURPOSE: To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders. METHODS: De-identified chromosomal microarray (CMA) data from 10,026 pediatric patients with developmental disorders were collected for re-evaluating the pathogenic CNV (pCNV) yields of different medical conditions and for comparing the frequency and phenotypic variability of genomic disorders between the Chinese and Western patient populations. RESULTS: The overall yield of pCNVs in the Chinese pediatric patient cohort was 21.37%, with variable yields for different disorders. Yields of pCNVs were positively associated with phenotypic complexity and intellectual disability/developmental delay (ID/DD) comorbidity for most disorders. The genomic burden and pCNV yield in neurodevelopmental disorders supported a female protective effect. However, the stratification analysis revealed that it was seen only in nonsyndromic ID/DD, not in nonsyndromic autism spectrum disorders or seizure. Furthermore, 15 known genomic disorders showed significantly different frequencies in Chinese and Western patient cohorts, and profiles of referred clinical features for 15 known genomic disorders were also significantly different in the two cohorts. CONCLUSION: We defined the pCNV yields and profiles of the Chinese pediatric patients with different medical conditions and uncovered differences in the frequency and phenotypic diversity of genomic disorders between Chinese and Western patients.
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Discapacidades del Desarrollo , Discapacidad Intelectual , Niño , China/epidemiología , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN/genética , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/genética , Femenino , Humanos , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/genéticaRESUMEN
BACKGROUND: Hemiplegic migraine (HM) is an uncommon subtype of migraine with aura including motor weakness. The core symptoms of HM are headache and motor weakness. However, we report a rare case of atypical HM with nonheadache onset in a Chinese child who was misdiagnosed several times. CASE PRESENTATION: We report a Chinese boy whose onset was sudden when he was 3 years old. He presented with a variety of phenotypes, including fever, vomiting, alternating hemiplegia, and drowsiness, but no headache in the initial stages. Magnetic resonance imaging (MRI) demonstrated unilateral cerebral oedema during the initial episode of hemiplegia. These symptoms recurred many times. As the disease progressed, the patient developed episodic headache. The patient was misdiagnosed several times with encephalitis, alternating hemiplegia of childhood (AHC) and mitochondrial encephalopathy. Whole-exome next-generation sequencing revealed a de novo heterozygous missense mutation in the ATP1A2 gene(p.Gly715Arg) classified as pathogenic and eventually led to a diagnosis of HM when he was 11 years old. Flunarizine was subsequently administered, and no recurrence was found during follow-up. CONCLUSIONS: HM in children may be atypical in the initial stage of the disease, which could manifest as fever, alternating hemiplegia and drowsiness but no headache at the onset. This could easily lead to misdiagnosis. With age, it may eventually manifest as typical HM. Therefore, attention should be given to differentiation in clinical practice.When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment.
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Hemiplejía , Migraña con Aura , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Preescolar , China , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Febrile seizures are the most common nervous system disease in childhood, and most children have a good prognosis. However, some epilepsy cases are easily induced by fever and are characterized by "fever sensitivity", and it is difficult to differentiate such cases from febrile seizures. Epilepsy related to fever sensitivity includes hereditary epilepsy with febrile seizures plus, Dravet syndrome, and PCDH19 gene-related epilepsy. This article mainly describes the clinical manifestations of these three types of epilepsy and summarizes their clinical features in the early stage of disease onset, so as to achieve early identification, early diagnosis, and early intervention to improve prognosis.
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Epilepsia , Síndromes Epilépticos , Convulsiones Febriles , Cadherinas/genética , Niño , Epilepsia/etiología , Epilepsia/genética , Humanos , Mutación , Protocadherinas , Convulsiones Febriles/etiología , Convulsiones Febriles/genéticaRESUMEN
Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous conditions. We launched a nationwide study to determine the frequency of CMD in the Chinese population and assess the status of diagnosis and disease management for CMD in China. Cases were chosen from databases in 34 tertiary academic hospitals from 29 first-level administrative divisions (provinces, municipalities, autonomous regions, and special administrative regions), and medical records were reviewed to confirm the diagnoses. The study included 409 patients, of those patients who consented to genetic testing (n = 340), mutations were identified in 286 of them. The most common forms identified were LAMA2-related CMD (36.4%), followed by COL6-related CMD (23.2%) and α-dystroglycanopathy (21.0%). The forms of CMD related to mutations in LMNA and SEPN1 were less frequent (12.5% and 2.4%, respectively). We also recorded a significant difference in the diagnostic capabilities and disease management of CMD, with this being relatively backward in research centers from less developed regions. We provide, for the first time, comprehensive epidemiologic information of CMD in a large cohort of Chinese people. To our knowledge, this is the largest sample size of its kind so far highlighting the prevalence of CMD in China.
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Distrofias Musculares/epidemiología , Distrofias Musculares/genética , Alelos , China/epidemiología , Diagnóstico Diferencial , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Masculino , Distrofias Musculares/diagnóstico , Mutación , Fenotipo , Vigilancia de la Población , PrevalenciaRESUMEN
BACKGROUND: Chromosomal duplication at the Xq28 region including the MECP2 gene, share consistent clinical phenotypes and a distinct facial phenotype known as MECP2 duplication syndrome. The typical clinical features include infantile hypotonia , mild dysmorphic features, a broad range of neurodevelopmental disorders, recurrent infections, and progressive spasticity. METHODS: This Chinese MECP2 duplication syndrome family includes six patients (five males and one female), and four asymptomatic female carriers. Two kinds of chips including 4x180K CNV + SNP chip and custom 8x60K CNV chip were used to detect MECP2 duplication, and then fluorescent in situ hybridization (FISH) analysis was performed to identify the exact copy number of MECP2. X-chromosome inactivation (XCI) analysis on AR gene was detected for all female family members, and the m icrosatellite analysis on MECP2 was used to validate the recombination event on MECP2 region. RESULTS: The affected male subjects presented with a broad range of neurodevelopmental symptoms (severe intellectual disability, developmental delay, seizure, language deficit, and autism spectrum disorder) as well as facial dysmorphism and other symptoms which were consistent with that of Western patients previous reported. Seizure is reported in Chinese patients for the first time. In addition, we validated three recombination events for the MECP2-duplication allele during maternal transmission due to X homologous recombination. CONCLUSIONS: We provided the largest known Chinese pedigree with MECP2 duplication syndrome. The detailed clinical description and molecular genetic characterization in all affected family members further delineate the typical phenotype of this genomic disorder in Chinese population.
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Pueblo Asiatico/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Adolescente , Adulto , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/genética , Niño , Preescolar , Duplicación Cromosómica , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Proteína 2 de Unión a Metil-CpG/genética , Linaje , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Convulsiones/diagnóstico , Convulsiones/genéticaRESUMEN
OBJECTIVE: To investigate the immunological mechanism of prednisone in the treatment of infantile spasm (IS) by evaluating the immune function of IS children before and after treatment. METHODS: Thirty children with IS were enrolled as IS group. Thirty healthy infants who underwent physical examination were enrolled as healthy control group. Fasting venous blood was collected for both groups before and after prednisone treatment. Chemiluminescence was used to measure serum levels of interleukin-1B (IL-1B), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Immunoturbidimetric assay was used to measure serum levels of immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG). Flow cytometry was used to measure the percentages of T lymphocyte subsets (CD3+, CD4+, and CD8+). The clinical outcome and electroencephalographic findings were evaluated for all IS children after prednisone treatment. RESULTS: The IS group had significantly higher serum levels of IL-2R, IL-8, and TNF-α than the healthy control group before treatment (P<0.05). The mean number of daily ictal clusters was positively correlated with the levels of IL-2R, IL-8, and TNF-α in IS children, the mean number of total daily seizures was positively correlated with IL-8 level, and any two indices out of IL-2R, IL-8, and TNF-α were positively correlated with each other (P<0.05). Among the 30 IS children treated with prednisone, 19 achieved seizure control; electroencephalography showed that 18 children achieved complete remission of hyperarrhythmia. After treatment, the IS group had significant reductions in the numbers of daily ictal clusters and total daily seizures, significant improvement in developmental quotient (P<0.05), and significant reductions in serum levels of IL-2R, L-8, and TNF-α, the percentage of CD4+ T lymphocytes, and CD4+/CD8+ ratio (P<0.05), as well as a significant increase in the percentage of CD8+ T lymphocytes (P<0.05). CONCLUSIONS: IS children have immune dysfunction. Prednisone can control seizures in IS children, possibly by regulating and improving immune dysfunction.
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Prednisona/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Relación CD4-CD8 , Citocinas/sangre , Electroencefalografía , Femenino , Humanos , Lactante , Masculino , Espasmos Infantiles/inmunologíaRESUMEN
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a new category of severe, potentially treatable autoimmune encephalitis and can appear in patients of all ages, but more frequently in children. It is a highly characteristic syndrome evolving in five stages: the prodromal phase (viral infection-like symptoms), psychotic phase, unresponsive phase, hyperkinetic phase, and gradual recovery phase. The treatment for this disorder includes first-line immunotherapy (steroids, intravenous immunoglobulin, plasmapheresis), second-line immunotherapy (rituximab, cyclophosphamide), and tumor removal. Hereby the progresses, selections and shortcomings of the treatment protocols for this disease are introduced.
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Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Niño , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Inmunoterapia , Plasmaféresis , Pronóstico , RituximabRESUMEN
METTL23 belongs to a family of protein lysine methyltransferases that methylate non-histone proteins. Recently, the METTL23 gene has been reported to be related to an intellectual developmental disorder, autosomal recessive 44. Patients present with developmental delay, intellectual disability (ID), and variable dysmorphic features. Here, we report on a Chinese girl who presented with global developmental delay, abnormal brain structure, and multiple facial deformities, including a short/upturned nose with a sunken bridge, thin lips, and flat occiput. Whole-exome sequencing identified a novel variant (NM_001080510.5: c.322+1del) on the METTL23 gene. This variant was not collected on public human variants databases such as gnomAD, predicted to influence the splicing as a classical splicing variant, and classified as Pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Since patients with METTL23-related ID are rare, we summarize and compare the clinical phenotype of reported patients with METTL23 variants. Our report further expands the METTL23 variants and provides new evidence for clinical diagnosis of METTL23-related ID.
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BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, inherited disorder that causes epilepsy, intellectual disorders, and early onset macrocephaly. MLC1 has been identified as a main pathogenic gene. METHODS: Clinical data such as magnetic resonance imaging (MRI), routine blood tests, and physical examinations were collected from proband. Trio whole-exome sequencing (WES) of the family was performed, and all variants with a minor allele frequency (<0.01) in the exon and canonical splicing sites were selected for further pathogenic evaluation. Candidate variants were validated using Sanger sequencing. RESULTS: Here, we report a new homozygous variant identified in two children from the same family in the MLC1 gene [NM_015166.4: c.838_843delinsATTTTA, (p.Ser280_Phe281delinsIleLeu)]. This variant is classified as variant of uncertain significance (VUS) according to the ACMG guidelines. Further experiments demonstrate that the newly identified variant causes a decrease of MLC1 protein levels when expressed in a heterologous expression system. CONCLUSION: Our case expands on this genetic variation and provides new evidence for the clinical diagnosis of MLC1-related MLC.
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Quistes , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias , Megalencefalia , Niño , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/diagnóstico por imagen , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/genéticaRESUMEN
PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.
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Epilepsias Parciales , Epilepsia , Convulsiones Febriles , Humanos , Anticonvulsivantes/uso terapéutico , Convulsiones Febriles/genética , Convulsiones Febriles/tratamiento farmacológico , Epilepsias Parciales/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Recurrencia , Expresión Génica , Cadherinas/genéticaRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients. METHODS: Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results. RESULTS: As of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4-5.4) and 4.1 (2.8-5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7-3.1) and 2.3 (1.2-3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5-5.3) and 4.3 (2.6-6.0) in HFMSE, and 2.1 (1.2-3.0) and 1.5 (0.0-3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae. CONCLUSIONS: These data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance.
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Oligonucleótidos , Sistema de Registros , Atrofias Musculares Espinales de la Infancia , Humanos , Masculino , Femenino , Oligonucleótidos/administración & dosificación , Oligonucleótidos/farmacología , Oligonucleótidos/efectos adversos , China , Preescolar , Lactante , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Atrofias Musculares Espinales de la Infancia/fisiopatología , Niño , Estudios Retrospectivos , Resultado del Tratamiento , Estudios Longitudinales , Adolescente , Estudios ProspectivosRESUMEN
Background: Reversible splenial lesion syndrome (RESLES) is a new clinico-radiological syndrome. We retrospectively analyzed the clinical features of 130 children with RESLES in China, which is the largest case series available in the literature. Methods: The clinical data of children diagnosed as RESLES in Jiangxi Provincial Children's Hospital between 2017 and 2023 were retrospectively analyzed. The 130 cases were divided into two groups: ≤ 3 years old group (group A) (n = 83) and > 3 years old group (group B) (n = 47). The chi-squared test or Fisher's test was used to evaluate the data. Results: The vast majority of patients (127/130 cases, 97.7%) had prodromal symptoms of infection. Preceding infections of the gastrointestinal tract were statistically more significant in group A (60/83, 72.3%) than in group B (11/47, 23.4%) (P < 0.05). Preceding infections of the respiratory tract were statistically more significant in group B (33/47, 70.2%) than in group A (17/83, 20.5%) (P < 0.05). Seizures were statistically more significant in group A (82/83, 98.8%) than in group B (24/47,51.1%) (P < 0.05). The disturbance of consciousness and headache/dizziness were statistically more significant in group B (27/47, 57.4%; 37/47, 78.7%) than in group A (3/83, 3.6%; 1/83, 1.2%), respectively (P < 0.05). Convulsions with mild gastroenteritis (CwG) were statistically more significant in group A (50/83, 60.2%) than in group B (8/47, 17.0%) (P < 0.05). However, encephalitis/encephalopathy was statistically more significant in group B (20/47, 42.6%) than in group A (10/83, 12.0%) (P < 0.05). MRI showed cytotoxic edema in typical locations (RESLES type-1 limited to the splenium of the corpus callosum and RESLES type-2 spread to the entire corpus callosum, adjacent white matter, or both). There was full recovery of the lesions of MRI in all cases from 3 days to 50 days after the initial examinations. All the children showed normal neurodevelopment. Conclusion: Infection was the most common cause of RESLES. Infections of the gastrointestinal tract are common in ≤ 3 years old children, while infections of the respiratory tract are common in >3 years old children. Younger patients are more likely to develop convulsions, and older children were more likely to have symptoms with disturbance of consciousness and headache/dizziness. RESLES has characteristic MRI manifestations and a good prognosis.
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PURPOSE: PHF21A has been associated with intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Here, we report a new patient with IDDBCS and review previously reported patients. METHODS: We reviewed the phenotypic and genetic spectrum of the newly diagnosed patient and previously reported patients with IDDBCS. RESULTS: Among 12 patients (11 whose cases were previously reported and the patient whose case we report here), all patients (100%) had intellectual disability (ID) and motor development delay. Three of 8 patients (37.5%) for whom information on cognition was available had severe ID; ID was moderate in two patients (25%) and mild in three patients (37.5%). Seven of the 12 patients (58.33%) had an epileptic phenotype, and the majority (5/7, 71.42%) of affected individuals developed developmental and epileptic encephalopathy (DEE). Of the 5 patients with DEE, three developed infantile epileptic spasm syndrome (IESS). The seizures of 2 patients (2/5, 40%) were controlled by antiseizure medications. Overgrowth, ADHD, hypotonia, ASD, and sleep disorders were observed in 100%, 77.78%, 70%, 50%, and 33.33% of patients, respectively. All of the variants (100%) were de novo heterozygous variants. Three of the 12 patients (25%) had the same variant (p.Arg580*). The most common types of variants were frameshift variants (7/12, 58.33%), followed by nonsense variants (4/12, 33.33%) and missense variants (1/12, 8.33%). Genotype-phenotype relationships for IDDBCS were uncertain, as phenotypic variability was observed among patients with the same variant (p.Arg580*). The patient whose case we report here had a novel PHF21A gene variant (p.Gln97fs*20), which caused neurodevelopmental delay, macrocephaly, and IESS. CONCLUSION: The core phenotypes of IDDBCS include neurodevelopmental delay (intellectual disability and impaired motor skills), craniofacial abnormalities, and overgrowth. ADHD, hypotonia, epilepsy, ASD, and sleep disorders are common symptoms of IDDBCS. Notably, DEE is the dominant phenotype of epilepsy, especially IESS. PHF21A may be a candidate gene for DEE. De novo variants are the main mode of inheritance. The most common types of variants are frameshift variants, and the variant p.Arg580* in PHF21A is located at a mutation hot spot.
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OBJECTIVE: To investigate the prevalence, risk factors, duration and outcome of delirium in intensive care unit (ICU) patients. METHODS: A prospective observational study was conducted for critically ill patients admitted to the department of critical care medicine, the Affiliated Hospital of Guizhou Medical University from September to November 2021. Delirium assessments were performed twice daily using the Richmond agitation-sedation scale (RASS) and confusion assessment method of ICU (CAM-ICU) for patients who met the inclusions and exclusion criteria. Patient's age, gender, body mass index (BMI), underlying disease, acute physiologic assessment and chronic health evaluation (APACHE) at ICU admission, sequential organ failure assessment (SOFA) at ICU admission, oxygenation index (PaO2/FiO2), diagnosis, type of delirium, duration of delirium, outcome, etc. were recorded. Patients were divided into delirium and non-delirium groups according to whether delirium occurred during the study period. The clinical characteristics of the patients in the two groups were compared, and risk factors for the development of delirium were screened using univariate analysis and multivariate Logistic regression analysis. RESULTS: A total of 347 ICU patients were included, and delirium occurred in 57.6% (200/347) patients. The most common type was hypoactive delirium (73.0% of the total). Univariate analysis showed statistically significant differences in age, APACHE score and SOFA score at ICU admission, history of smoking, hypertension, history of cerebral infarction, immunosuppression, neurological disease, sepsis, shock, glucose (Glu), PaO2/FiO2 at ICU admission, length of ICU stay, and duration of mechanical ventilation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.045, 95% confidence interval (95%CI) was 1.027-1.063, P < 0.001], APACHE score at ICU admission (OR = 1.049, 95%CI was 1.008-1.091, P = 0.018), neurological disease (OR = 5.275, 95%CI was 1.825-15.248, P = 0.002), sepsis (OR = 1.941, 95%CI was 1.117-3.374, P = 0.019), and duration of mechanical ventilation (OR = 1.005, 95%CI was 1.001-1.009, P = 0.012) were all independent risk factors for the development of delirium in ICU patients. The median duration of delirium in ICU patients was 2 (1, 3) days. Delirium was still present in 52% patients when they discharged from the ICU. CONCLUSIONS: The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.
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Cuidados Críticos , Sepsis , Humanos , Prevalencia , Factores de Riesgo , Unidades de Cuidados IntensivosRESUMEN
Nutritive symbiosis between bacteria and ticks is observed across a range of ecological contexts; however, little characterization on the molecular components responsible for this symbiosis has been done. Previous studies in our lab demonstrated that Rickettsia monacensis str. Humboldt (strain Humboldt) can synthesize folate de novo via the folate biosynthesis pathway involving folA, folC, folE, folKP, and ptpS genes. In this study, expression of the strain Humboldt folA gene within a folA mutant Escherichia coli construct was used to functionally characterize the strain Humboldt folA folate gene in vivo. The strain Humboldt folA folate gene was subcloned into a TransBac vector and transformed into a folA mutant E. coli construct. The mutant containing strain Humboldt folA subclone and a pFE604 clone of the knocked-out folA gene was cured of pFE604. Curing of the folA mutant E. coli construct was successful using acridine orange and 43.5 °C incubation temperature. The plasmid curing assay showed curing efficiency of the folA mutant at 100%. Functional complementation was assessed by growth phenotype on minimal media with and without IPTG between strain Humboldt folA and E. coli folA. Large and homogenous wild-type colony growth was observed for both strain Humboldt and E. coli folA on minimal media with 0.1 mM IPTG, wild-type growth for strain Humboldt folA and pin-point growth for E. coli folA on 0.01 mM IPTG, and pin-point growth without IPTG for both strain Humboldt and E. coli folA. This study provides evidence substantiating the in vivo functionality of strain Humboldt folA in producing functional gene products for folate biosynthesis.