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Spinal muscular atrophy (SMA) is a congenital neuromuscular disorder characterized by motor neuron loss, resulting in progressive weakness. SMA is notable in the health care community because it accounts for the most common cause of infant death resulting from a genetic defect. SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from SMN1 gene mutations or deletions. However, patients always harbor various copies of SMN2, an almost identical but functionally deficient copy of the gene. A genotype-phenotype correlation suggests that SMN2 is a potent disease modifier for SMA, which also represents the primary target for potential therapies. Increasing comprehension of SMA pathophysiology, including the characterization of SMN1 and SMN2 genes and SMN protein functions, has led to the development of multiple therapeutic approaches. Until the end of 2016, no cure was available for SMA, and management consisted of supportive measures. Two breakthrough SMN-targeted treatments, either using antisense oligonucleotides (ASOs) or virus-mediated gene therapy, have recently been approved. These two novel therapeutics have a common objective: to increase the production of SMN protein in MNs and thereby improve motor function and survival. However, neither therapy currently provides a complete cure. Treating patients with SMA brings new responsibilities and unique dilemmas. As SMA is such a devastating disease, it is reasonable to assume that a unique therapeutic solution may not be sufficient. Current approaches under clinical investigation differ in administration routes, frequency of dosing, intrathecal versus systemic delivery, and mechanisms of action. Besides, emerging clinical trials evaluating the efficacy of either SMN-dependent or SMN-independent approaches are ongoing. This review aims to address the different knowledge gaps between genotype, phenotypes, and potential therapeutics.
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Terapia Combinada/métodos , Atrofia Muscular Espinal/patología , Atrofia Muscular Espinal/terapia , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Animales , Predisposición Genética a la Enfermedad , Terapia Genética , Genotipo , Humanos , Inyecciones Espinales , Terapia Molecular Dirigida , Atrofia Muscular Espinal/genética , Oligonucleótidos Antisentido/uso terapéutico , Fenotipo , Proteína 2 para la Supervivencia de la Neurona Motora/genéticaRESUMEN
Facioscapulohumeral muscular dystrophy (FSHD)-the worldwide third most common inherited muscular dystrophy caused by the heterozygous contraction of a 3.3 kb tandem repeat (D4Z4) on a chromosome with a 4q35 haplotype-is a progressive genetic myopathy with variable onset of symptoms, distribution of muscle weakness, and clinical severity. While much is known about the clinical course of adult FSHD, data on the early-onset infantile phenotype, especially on the progression of the disease, are relatively scarce. Contrary to the classical form, patients with infantile FSHD more often have a rapid decline in muscle wasting and systemic features with multiple extramuscular involvements. A rough correlation between the phenotypic severity of FSHD and the D4Z4 repeat size has been reported, and the majority of patients with infantile FSHD obtain a very short D4Z4 repeat length (one to three copies, EcoRI size 10-14 kb), in contrast to the classical, slowly progressive, form of FSHD (15-38 kb). With the increasing identifications of case reports and the advance in genetic diagnostics, recent studies have suggested that the infantile variant of FSHD is not a genetically separate entity but a part of the FSHD spectrum. Nevertheless, many questions about the clinical phenotype and natural history of infantile FSHD remain unanswered, limiting evidence-based clinical management. In this review, we summarize the updated research to gain insight into the clinical spectrum of infantile FSHD and raise views to improve recognition and understanding of its underlying pathomechanism, and further, to advance novel treatments and standard care methods.
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Distrofia Muscular Facioescapulohumeral/etiología , Distrofia Muscular Facioescapulohumeral/terapia , Edad de Inicio , Humanos , Distrofia Muscular Facioescapulohumeral/patología , Retina/fisiopatologíaAsunto(s)
COVID-19 , Niño , Tracto Gastrointestinal , Humanos , SARS-CoV-2 , Síndrome , Síndrome de Respuesta Inflamatoria SistémicaRESUMEN
BACKGROUND: Fetal akinesia deformation sequence (FADS) refers to a broad spectrum of disorder with the absent fetal movement as the unifying feature. The etiology of FADS is heterogeneous, and the majority remains unknown. Prenatal diagnosis of FADS because of neuromuscular origin has relied on clinical features and fetal muscle pathology, which can be unrevealing. The recent advance of next-generation sequencing (NGS) can provide definitive molecular diagnosis effectively. METHODS AND RESULTS: An 18-week-old fetus presented with akinesia and multiple contractures of joints. The mother had two previously aborted similarly affected fetuses. Clinical diagnosis of FADS was made. Molecular diagnosis using cord blood by NGS of genes related to neuromuscular diseases revealed two compound heterozygous mutations; c.602G > A(p.W201*) and c.1516A > C(p.T506P), in the Kelch-like 40 (KLHL40) gene. Based on this information, prenatal diagnosis was performed on the CVS of the subsequent pregnancy that resulted in an unaffected female baby, heterozygous for the c.1516A > C(p.T506P) mutation. CONCLUSION: Identification of KLHL40 mutations in one of the aborted fetuses provided a confirmative diagnosis of FADS, facilitating the prenatal diagnosis of the subsequent pregnancy. This report underscores the importance of target NGS in providing FADS families with an affordable, precise molecular diagnosis for genetic counseling and options of prenatal diagnosis. © 2016 John Wiley & Sons, Ltd.
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Artrogriposis/genética , Proteínas Musculares/genética , Adulto , Artrogriposis/diagnóstico , Muestra de la Vellosidad Coriónica , Femenino , Sangre Fetal , Movimiento Fetal , Heterocigoto , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Linaje , Embarazo , Segundo Trimestre del Embarazo , Diagnóstico PrenatalRESUMEN
Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of SMN1 is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, Mir34 family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.
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OBJECTIVE: To identify the prevalence and risk factors of feeding and swallowing problems in patients with type II and type III spinal muscular atrophy (SMA). STUDY DESIGN: Cross-sectional data from 108 genetically confirmed patients with SMA (age range, 3-45 years; 60 with type II and 48 with type III) were analyzed. The questionnaire survey included demographic data, current motor function and respiratory status, feeding and swallowing difficulties, and consequences. The risk factors were analyzed via logistic regression. RESULTS: The 3 most common feeding and swallowing difficulties in patients with type II and III SMA were choking (30.6%), difficulty conveying food to the mouth (20.4%), and difficulty chewing (20.4%). Current motor function status was an independent risk factor for feeding and swallowing difficulties (sitters vs walkers: OR, 7.59; 95% CI, 1.22-47.46). All 4 nonsitters (ie, patients with type II SMA who had lost their sitting ability) had feeding and swallowing difficulties. Patients with feeding and swallowing difficulties had significantly higher rates of underweight and aspiration pneumonia than those without these problems. CONCLUSION: Patients with type II and III SMA have a high prevalence of risk factors for feeding and swallowing difficulties, suggesting that an individualized treatment plan should depend on current motor function status.
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Trastornos de Deglución/etiología , Ingestión de Alimentos , Atrofias Musculares Espinales de la Infancia/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía por Aspiración/etiología , Factores de Riesgo , Atrofias Musculares Espinales de la Infancia/complicaciones , Adulto JovenRESUMEN
Clear cell renal cell carcinoma (ccRCC) accounts for 80% of renal cell carcinomas (RCCs), and its morbidity and prognosis are unfavorable. Surgical resection is the first-line treatment for ccRCC, but the oncogenesis of ccRCC is very complex. With the development of high-throughput sequencing technology, it is necessary to analyze the transcriptome to determine more effective treatment methods. The tumor microenvironment (TME) is composed of tumor cells, various immune-infiltrating cells, fibroblasts, many cytokines, and catalysts. It is a complex system with a dynamic balance that plays an essential role in tumor growth, invasion, and metastasis. Previous studies have confirmed that potassium channels can affect the immune system, especially T lymphocytes that require potassium channel activation. However, the effect of potassium channels on the TME of ccRCC remains to be studied. Therefore, this study aims to construct a prognostic signature for ccRCC patients based on potassium ion channel-related genes (PCRGs), assess patient risk scores, and divide patients into high- and low-risk groups based on the cutoff value. In addition, we investigated whether there were differences in immune cell infiltration, immune activator expression, somatic mutations, and chemotherapeutic responses between the high- and low-risk groups. Our results demonstrate that the PCRG signature can accurately assess patient prognosis and the tumor microenvironment and predict chemotherapeutic responses. In summary, the PCRG signature could serve as an auxiliary tool for the precision treatment of ccRCC.
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The coronavirus disease 2019 (COVID-19) pandemic has prompted a rapid and unprecedented reorganization of medical institutions, affecting clinical care for patients with chronic neurological diseases. Although there is no evidence that patients with neuromuscular disorders (NMD) confer a higher infection risk of COVID-19, NMD and its associated therapies may affect the patient's ability to cope with infection or its systemic effects. Moreover, there is a concern that patients with chronic NMD may be at increased risk of manifesting severe symptoms of COVID-19. In particular, as respiratory compromises account for the major cause of mortality and morbidity in NMD patients, newly emerging data also show that the risk of exacerbation caused by COVID-19 accumulates in this particular patient group. For example, patients with motor neuron disease and dystrophinopathies often have ventilatory muscle weakness or cardiomyopathy, which may increase the risk of severe COVID-19 infection. Thus, the COVID-19 pandemic may severely affect NMD patients. Several neurological associations and neuromuscular networks have recently guided the impact of COVID-19 on patients with NMD, especially in managing cardiopulmonary involvements. It is recommended that patients with moderate- to high-risk NMD be sophisticatedly monitored to reduce the risk of rapid decline in cardiopulmonary function or potential deterioration of the underlying NMD. However, limited neuromuscular-specific recommendations for NMD patients who contract COVID-19 and outcome data are lacking. There is an urgent need to properly modify the respiratory care method for NMD patients, especially during the COVID-19 pandemic. Conclusively, COVID-19 is a rapidly evolving field, and the practical guidelines for the management of NMD patients are frequently revised. There must be a close collaboration in a multidisciplinary care team that should support their hospital to define a standardized care method for NMD patients during the COVID pandemic. This article reviews evidence-based practical guidelines regarding care delivery, modification, and education, highlighting the need for team-based and interspecialty collaboration.
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Posterior reversible encephalopathy syndrome (PRES) is a novel clinicoradiological syndrome characterized by convulsions, headache, altered mentality, and impaired vision, which are usually accompanied by hypertension. As its nomination, PRES is usually diagnosed according to the presence of typical neuroimage showing vasogenic edema predominately involving the posterior brain area. With the widespread utilization of magnetic resonance imaging (MRI), PRES is becoming more perceptible in different medical fields. Compared to adult cases, childhood PRES seems to have a broader clinical and neuroradiological spectrum. PRES can be associated with various underlying comorbidities, medication use, and therapeutic modalities in children with diverse neurological manifestations. Moreover, pediatric patients with PRES have a more significant propensity for atypical MRI findings beyond the typically posterior cerebral areas. The knowledge of typical and atypical presentations in children is essential to avoid misdiagnosing or missing PRES, which is a potentially treatable entity. Early supportive care is the mainstay of treatment, with particular attention to the treatment of hypertension with rigorous attention to all body systems. Prompt identification and symptom-directed management are imperative to achieve a reversible prognosis in childhood PRES. Future studies specially designed for the child population are required to determine potential outcome predictors, and further, to develop novel strategies of neuroprotection in childhood PRES.
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Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is a neurodegenerative disease characterized by the selective loss of particular groups of motor neurons (MNs) in the anterior horn of the spinal cord with progressive muscle wasting. SMA is caused by a deficiency of the survival motor neuron (SMN) protein due to a homozygous deletion or mutation of the SMN1 gene. However, the molecular mechanisms whereby the SMN complex regulates MN functions are not fully elucidated. Emerging studies on SMA pathogenesis have turned the attention of researchers to RNA metabolism, given that increasingly identified SMN-associated modifiers are involved in both coding and non-coding RNA (ncRNA) processing. Among various ncRNAs, microRNAs (miRNAs) are the most studied in terms of regulation of posttranscriptional gene expression. Recently, the discovery that miRNAs are critical to MN function and survival led to the study of dysregulated miRNAs in SMA pathogenesis. Circulating miRNAs have drawn attention as a readily available biomarker due to their property of being clinically detectable in numerous human biofluids through non-invasive approaches. As there are recent promising findings from novel miRNA-based medicines, this article presents an extensive review of the most up-to-date studies connecting specific miRNAs to SMA pathogenesis and the potential applications of miRNAs as biomarkers and therapeutic targets for SMA.
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Children with neuromuscular disorder (NMD) usually have pulmonary involvement characterized by weakened respiratory muscles, insufficient coughing, and inability to clear airway secretions. When suffering from community-acquired pneumonia, these patients are more likely to develop acute respiratory failure (ARF). Therefore, recurrent pneumonias leading to acute on chronic respiratory failure accounts for a common cause of mortality in children with NMD. For many years, noninvasive ventilation (NIV) has been regarded as a life-prolonging tool and has been used as the preferred intervention for treating chronic hypoventilation in patients with advanced NMD. However, an increasing number of studies have proposed the utility of NIV as first-line management for acute on chronic respiratory failure in NMD patients. The benefits of NIV support in acute settings include avoiding invasive mechanical ventilation, shorter intensive care unit or hospital stays, facilitation of extubation, and improved overall survival. As the difficulty in clearing respiratory secretions is considered a significant risk factor attributing to NIV failure, combined coughing assistance of mechanical insufflator-exsufflator (MI-E) with NIV has been recommended the treatment of acute neuromuscular respiratory failure. Several recent studies have demonstrated the feasibility and effectiveness of combined NIV and MI-E in treating ARF of children with NMD in acute care settings. However, to date, only one randomized controlled study has investigated the efficacy of NIV in childhood ARF, but subjects with underlying NMD were excluded. It reflects the need for more studies to elaborate evidence-based practice, especially the combined NIV and MI-E use in children with acute neuromuscular respiratory failure. In this article, we will review the feasibility, effectiveness, predictors of outcome, and perspectives of novel applications of combined NIV and MI-E in the treatment of ARF in NMD children.
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The reviews of this paper are available via the supplemental material section.
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Manejo de la Vía Aérea/métodos , Infecciones por Coronavirus/epidemiología , Enfermedades Neuromusculares/terapia , Pandemias/estadística & datos numéricos , Neumonía Viral/epidemiología , Síndrome Respiratorio Agudo Grave/terapia , COVID-19 , Diseño de Equipo , Femenino , Humanos , Masculino , Evaluación de Necesidades , Enfermedades Neuromusculares/epidemiología , Posicionamiento del Paciente , Impresión Tridimensional , Posición Prona , Respiración Artificial/instrumentación , Respiración Artificial/métodos , Terapia Respiratoria/métodos , Ventiladores Mecánicos/estadística & datos numéricosRESUMEN
Spinal muscular atrophy (SMA), the main genetic cause of infant death, is a neurodegenerative disease characterized by the selective loss of motor neurons in the anterior horn of the spinal cord, accompanied by muscle wasting. Pathomechanically, SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from the loss of the SMN1 gene. However, emerging research extends the pathogenic effect of SMN deficiency beyond motor neurons. A variety of metabolic abnormalities, especially altered fatty acid metabolism and impaired glucose tolerance, has been described in isolated cases of SMA; therefore, the impact of SMN deficiency in metabolic abnormalities has been speculated. Although the life expectancy of these patients has increased due to novel disease-modifying therapies and standardization of care, understanding of the involvement of metabolism and nutrition in SMA is still limited. Optimal nutrition support and metabolic monitoring are essential for patients with SMA, and a comprehensive nutritional assessment can guide personalized nutritional therapy for this vulnerable population. It has recently been suggested that metabolomics studies before and after the onset of SMA in patients can provide valuable information about the direct or indirect effects of SMN deficiency on metabolic abnormalities. Furthermore, identifying and quantifying the specific metabolites in SMA patients may serve as an authentic biomarker or therapeutic target for SMA. Here, we review the main epidemiological and mechanistic findings that link metabolic changes to SMA and further discuss the principles of metabolomics as a novel approach to seek biomarkers and therapeutic insights in SMA.
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Atrofia Muscular Espinal/metabolismo , Terapia Nutricional/métodos , Fenómenos Fisiológicos de la Nutrición/genética , Proteínas del Complejo SMN/deficiencia , Proteína 1 para la Supervivencia de la Neurona Motora , Biomarcadores/metabolismo , Humanos , Metaboloma , Metabolómica/métodos , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/terapia , Evaluación NutricionalRESUMEN
Background: Acute gastroenteritis (AGE) accompanied by seizures is not a rare scenario in childhood. We investigated the clinical features of children with febrile or afebrile seizures during AGE and aimed to identify the impact of fever in this situation-related seizure. Methods: We retrospectively reviewed the medical charts of children admitted due to seizures associated with mild AGE between January 2008 and December 2017. These consecutive patients were divided into two groups: an "afebrile group" whose diagnosis was compatible with "benign convulsion with mild gastroenteritis (CwG)" and a "febrile group" who had a fever within 24 h of the onset of an AGE-related seizure. We compared the two groups' clinical and laboratory characteristics, electroencephalograms (EEG), neuroimaging, and outcomes. Results: Of the children suffering from AGE and seizures, 41 were afebrile and 30 were febrile, with a mean age of 32.2 ± 27.6 months. The gender, seizure semiology, frequency, duration of seizures, the time interval between AGE symptoms onset and first seizure, and levels of serum sodium, and hepatic enzymes were significantly different between the two groups. The most frequently identified enteropathogen was rotavirus (33%), especially in the male and febrile subjects. Afebrile patients had more EEG abnormalities initially, but all returned to normal later. All cases had an uneventful outcome. Of note, seizure clusters (≥2 episodes) occurred more frequently in the afebrile patients who had a duration of AGE symptoms lasting 2 days or more, or white blood cell counts ≥ 10,000/µL (p-values: 0.05 and 0.04, respectively). In comparison with seven similar studies, all showed more seizure clusters, partial seizures, and a shorter interval between AGE onset and seizures in afebrile patients than in febrile patients. Contrarily, afebrile patients had longer seizure duration and lower serum hepatic transaminases than febrile patients. Conclusion: Although fever partially influenced the clinical features of AGE-related seizures, febrile CwG might have pathophysiology distinctly different from that of febrile seizures. Comprehensive knowledge in discerning febrile and afebrile CwG can help to avoid unnecessary diagnostics tests, and anticonvulsants use.
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Aicardi syndrome (AS) is a rare neuro-ophthalmic disorder first described by Jean Aicardi in 1965 with a characteristic triad of corpus callosal agenesis (CCA), chorioretinal lacunae (CRL), and infantile spasms (IS). All known cases of AS have been sporadic and a responsible gene has not been identified. With 5 exceptional males, potential X-linked dominant genetic mutation characterizes AS occurring almost exclusively in girls. Most of male AS cases were still debatable in diagnosis either for their 46 XY karyotype or too atypical presentations to fit the formerly stricter diagnostic criteria. We report a 47, XXY male neonate presenting some undisputable, but otherwise some regarded as atypical features in AS. We compare his distinctively clinical pictures with previously reported male cases and find CRL is less pathognomonic and lissencephaly appears frequently among male AS. Because of insufficient genetic and biochemical markers for definite diagnosis at this moment, we suggest the experience of a relatively rare male case would help to shed light on the underlying genetic pathogenesis of AS.
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Anomalías Múltiples , Síndrome Acrocallosal , Holoprosencefalia , Lisencefalia , Aberraciones Cromosómicas Sexuales , Síndrome Acrocallosal/genética , Síndrome Acrocallosal/patología , Encéfalo/patología , Electroencefalografía , Holoprosencefalia/genética , Holoprosencefalia/patología , Humanos , Recién Nacido , Lisencefalia/genética , Lisencefalia/patología , Imagen por Resonancia Magnética , Masculino , Síndrome de Dificultad Respiratoria del Recién Nacido , Convulsiones , Espasmos Infantiles , SíndromeRESUMEN
Our study evaluates the usefulness and the limitations of using the medical records of a central referral hospital to develop a child injury surveillance system in northern Malawi. The most prevalent types of injury were falls (29.6%), road traffic injuries (22.0%), burns (21.4%) and poisoning (15.1%). Older children (aged 5-14 years), in the cool-dry season (May to August) and the hot-dry season (September to October), were significant predictors for total injury admissions. Our study indicated that hospital medical records are a valuable component of a child injury surveillance system and can illustrate the trends and patterns of moderate to severe injuries as well as suggest potential prevention strategies for local settings. Combined with a specially designed trauma registry form, it is possible for developing countries at local level to combat the emerging public health issues.
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Accidentes por Caídas/estadística & datos numéricos , Accidentes de Tránsito/estadística & datos numéricos , Quemaduras/epidemiología , Registros Médicos , Intoxicación/epidemiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Malaui/epidemiología , Masculino , Sistema de RegistrosRESUMEN
Two crucial questions in neuroscience are how neurons establish individual identity in the developing nervous system and why only specific neuron subtypes are vulnerable to neurodegenerative diseases. In the central nervous system, spinal motor neurons serve as one of the best-characterized cell types for addressing these two questions. In this review, we dissect these questions by evaluating the emerging role of regulatory microRNAs in motor neuron generation in developing embryos and their potential contributions to neurodegenerative diseases such as spinal muscular atrophy (SMA). Given recent promising results from novel microRNA-based medicines, we discuss the potential applications of microRNAs for clinical assessments of SMA disease progression and treatment.
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Sistema Nervioso Central/crecimiento & desarrollo , Sistema Nervioso Central/fisiopatología , Regulación de la Expresión Génica , MicroARNs/metabolismo , Neuronas Motoras/fisiología , Atrofia Muscular Espinal/fisiopatología , Animales , HumanosRESUMEN
BACKGROUND: No previous studies have explored emergency medical care for children with chronic neuromuscular disorders (NMDs). We aimed to determine the major reasons for the emergency room (ER) readmission of pediatric patients with NMDs and suggest changes to the care plan to decrease readmissions. METHODS: Children with chronic NMDs (aged <18 years) who visited a medical center-based ER between January 2005 and January 2015 were included. The following data were extracted from the patient's ER records: presentations; demographic data, including sex and age; NMD diagnosis; triage classification; emergency examination; initial management and outcomes. The outcomes were death inside or outside the ER, admission to the ward or pediatric intensive care unit (PICU), uneventful discharge, and repeated ER visits. RESULTS: In 10 years, 44 children with heterogeneous NMDs (boys/girls: 30/14, mean age: 9.9 years) visited the ER for a total of 204 times. Repeated ER visits and readmissions occurred in 56.8% and 55.6% of the patients, respectively. Most NMD children belonged to triage class 3 (35.3%), with underlying congenital hereditary muscular dystrophy (44.1%). The major symptoms were usually multiple and concurrent, and primarily respiratory (62.3%) or gastrointestinal (28.9%). The most common causes of hospitalization were pneumonia (48.5%) or acute gastritis (20.4%), and approximately half of the ER visits required further hospitalization, of which 28.2% involved PICU admission. Twenty of the 36 children admitted to the ER required readmission. The most commonly prescribed examinations were complete blood count (38%) and C-reactive protein (38%), and the most common therapy was intravenous fluid administration (34%). Although respiratory compromise caused most ER visits and admissions, pulmonary assessments, including chest films (28%), pulse oximetry (15%), and blood gas analysis (11%), were performed in a relatively small proportion. CONCLUSION: The ER staff must recognize patients' unmet needs for respiratory and gastrointestinal care related to underlying NMDs.
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Servicio de Urgencia en Hospital/estadística & datos numéricos , Enfermedades Gastrointestinales/epidemiología , Hospitalización/estadística & datos numéricos , Enfermedades Neuromusculares/epidemiología , Enfermedades Respiratorias/epidemiología , Adolescente , Niño , Preescolar , Resfriado Común/epidemiología , Femenino , Fiebre/epidemiología , Gastritis/epidemiología , Hemorragia Gastrointestinal/epidemiología , Insuficiencia Cardíaca/epidemiología , Humanos , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Masculino , Atrofia Muscular Espinal/epidemiología , Distrofias Musculares/epidemiología , Readmisión del Paciente/estadística & datos numéricos , Neumonía/epidemiología , Insuficiencia Respiratoria/epidemiología , Convulsiones/epidemiología , Taiwán/epidemiología , TriajeRESUMEN
BACKGROUND: To determine the effectiveness of combined noninvasive ventilation (NIV) and mechanical insufflator-exsufflator (MI-E) for acute respiratory failure (ARF) in patients with neuromuscular disease (NMD), and outcome predictors. METHODS: A prospectively observational study of patients with ARF was conducted in a pediatric intensive care unit (PICU). All received combined NIV/MI-E during PICU stays between 2007 and 2017. Pertinent clinical variables of heart rate (HR), respiratory rate (RR), pH, PaCO2, and PaO2/FiO2 ratio were collected at baseline and at 2 h, 4-8 h, and 12-24 h after initiating use of NIV/MI-E. Treatment success was defined as avoiding intubation. RESULTS: A total of 62 ARF episodes in 56 patients with NMD (median age, 13 years) were enrolled. The most frequent underlying NMD was spinal muscular atrophy (32/62, 52%). ARF was primarily due to pneumonia (65%). The treatment success rate was 86%. PICU stay and hospitalization were shorter in the success group (9.4 ± 6.1 vs. 21.9 ± 13.9 days and 16.3 ± 7.8 vs. 33.6 ± 17.9 days, respectively; both p < 0.05). HR, RR, pH, and PaCO2 showed a progressive improvement, particularly after 4 h following successful NIV/MI-E treatment. RR decrease at 4 h, and pH increase and PaCO2 decrease at 4-8 h might predict success of NIV/MI-E treatment. The multivariate analysis identified PaCO2 at 4-8 h of 58.0 mmHg as an outcome predictor of NIV/MI-E treatment. CONCLUSIONS: Applying combined NIV/MI-E in the acute care setting is an efficient means of averting intubation in NMD patients with ARF. Clinical features within 8 h of the institution may predict treatment outcome. The reviews of this paper are available via the supplemental material section.