Objetivos: Determinar a acurácia do estridor em predizer a ocorrência de estenose subglótica (ESG) por intubação em pacientes pediátricos quando comparado ao seu diagnóstico por endoscopia de via aérea. Delineamento: Coorte Prospectiva. Métodos: Foram elegíveis todas as crianças de 28 dias a quatro anos de idade internadas na Unidade de Terapia Intensiva Pediátrica do Hospital de Clínicas de Porto Alegre que necessitaram de intubação endotraqueal por mais de 24 horas. Foram excluídas as com história de intubação, doença laríngea prévia, presença de traqueostomia atual ou no passado, presença de malformações craniofaciais e aquelas consideradas portadoras de doença terminal. Foram acompanhadas diariamente e, após a extubação, submetidas à fibronasolaringoscopia (FNL). Novo exame era realizado em sete a dez dias naquelas com alterações moderadas a graves no primeiro. Se essas persistissem ou surgissem sintomas, independentemente da FNL inicial, realizava-se laringoscopia sob anestesia geral. Após a extubação, verificou-se diariamente a ocorrência de estridor, classificado como presente ou ausente. Resultados: Foram acompanhados, de novembro de 2005 a agosto de 2012, 194 pacientes. A incidência de estridor pós-extubação foi de 43,81%. O estridor apresentou uma sensibilidade de 77,78% (IC 95%: 51,9 – 92,6) e especificidade de 59,66% (IC 95%: 52,0 – 66,9) em detectar ESG nessa amostra, o valor preditivo positivo (VPP) foi de 16,47% (IC 95%: 9,6 – 26,4) e o valor preditivo negativo (VPN) foi de 96,33% (IC 95%: 90,3 – 98,8). O estridor quando presente por mais de 72 horas ou quando esse surgiu após as primeiras 72 horas da extubação apresentou uma sensibilidade de 66,67% (IC 95%: 41,2 – 85,6) e especificidade de 88,5% (IC 95%: 83,1 – 93,1). O VPP foi de 38,8% (IC 95%: 22,4 – 57,7) e o VPN foi de 96,23 (IC 95%: 91,6 – 98,5). A área da curva ROC foi 0,78 (IC 95%: 0,65 – 0,91). Conclusões: A ausência de estridor mostrou-se adequada para afastar o diagnóstico de ESG por intubação em pacientes pediátricos após o período neonatal. Melhor especificidade foi encontrada quando o estridor ocorreu por mais de 72 horas após a extubação ou quando teve o início depois desse período. A partir desse estudo, parece adequado indicar endoscopia de via aérea, para a confirmação de ESG, apenas naqueles pacientes que apresentarem estridor após 72 horas da extubação. / Objective: To determine the accuracy of stridor in predicting the occurrence of postintubation subglottic stenosis (SGS) in pediatric patients when compared with endoscopy airway diagnosis. Design: Prospective cohort. Methods: Children aged 28 days to four years admitted to the Pediatric Intensive Care Unit of Hospital de Clinicas de Porto Alegre who required endotracheal intubation for more than 24 hours were eligible for study. Patients with previous intubation, history of laryngeal disease, current or past tracheostomy, presence of craniofacial malformations and those considered terminal by the staff were excluded from the study. Children were monitored daily and underwent flexible fiberoptic laryngoscopy (FFL) after extubation. Those who presented moderate to severe abnormalities in this first examination underwent another FFL between 7 and 10 days later. If these lesions persisted or symptoms developed, regardless of the findings in initial examination, laryngoscopy under general anesthesia was warranted. Occurrence of stridor was verified daily after extubation and classified as either present or absent. Results: We followed 194 children between November 2005 and August 2012. The incidence of post-extubation stridor was 43.81 per cent. Stridor had a sensitivity of 77.78% (CI 95%: 51.9 – 92.6) and specificity of 59.66% (CI 95%: 52.0 – 66.9) to detect SGS in this sample. The positive predictive value (PPV) was 16.47% (CI 95%: 9.6 – 26.4) and the negative predictive value was 96.33% (CI 95%: 90.3 – 98.8). Stridor, when present more than 72 hours or when started after these first 72 hours after extubation, showed a sensitivity of 66.67% (CI 95%: 41.2 – 85.6), specificity of 88.5% (CI 95%: 83.1 – 93.1), PPV of 38.8% (CI 95%: 22.4 – 57.7) and NPV of 96.23% (CI 95%: 91,6 – 98,5). ROC curve area was 0,78 (CI 95%: 0.65 – 0.91). Conclusions: Absence of stridor proved to be adequate to rule out the diagnosis of post-intubation SGS in pediatric patients. Improved specificity was found when stridor occurred for more than 72 hours after extubation or when started after that. From this study, it seems appropriate to indicate airway endoscopy under general anesthesia for the confirmation of SGS only in those patients who present stridor after 72 hours following extubation.

Objetivos: Determinar a acurácia do estridor em predizer a ocorrência de estenose subglótica (ESG) por intubação em pacientes pediátricos quando comparado ao seu diagnóstico por endoscopia de via aérea. Delineamento: Coorte Prospectiva. Métodos: Foram elegíveis todas as crianças de 28 dias a quatro anos de idade internadas na Unidade de Terapia Intensiva Pediátrica do Hospital de Clínicas de Porto Alegre que necessitaram de intubação endotraqueal por mais de 24 horas. Foram excluídas as com história de intubação, doença laríngea prévia, presença de traqueostomia atual ou no passado, presença de malformações craniofaciais e aquelas consideradas portadoras de doença terminal. Foram acompanhadas diariamente e, após a extubação, submetidas à fibronasolaringoscopia (FNL). Novo exame era realizado em sete a dez dias naquelas com alterações moderadas a graves no primeiro. Se essas persistissem ou surgissem sintomas, independentemente da FNL inicial, realizava-se laringoscopia sob anestesia geral. Após a extubação, verificou-se diariamente a ocorrência de estridor, classificado como presente ou ausente. Resultados: Foram acompanhados, de novembro de 2005 a agosto de 2012, 194 pacientes. A incidência de estridor pós-extubação foi de 43,81%. O estridor apresentou uma sensibilidade de 77,78% (IC 95%: 51,9 – 92,6) e especificidade de 59,66% (IC 95%: 52,0 – 66,9) em detectar ESG nessa amostra, o valor preditivo positivo (VPP) foi de 16,47% (IC 95%: 9,6 – 26,4) e o valor preditivo negativo (VPN) foi de 96,33% (IC 95%: 90,3 – 98,8). O estridor quando presente por mais de 72 horas ou quando esse surgiu após as primeiras 72 horas da extubação apresentou uma sensibilidade de 66,67% (IC 95%: 41,2 – 85,6) e especificidade de 88,5% (IC 95%: 83,1 – 93,1). O VPP foi de 38,8% (IC 95%: 22,4 – 57,7) e o VPN foi de 96,23 (IC 95%: 91,6 – 98,5). A área da curva ROC foi 0,78 (IC 95%: 0,65 – 0,91). Conclusões: A ausência de estridor mostrou-se adequada para afastar o diagnóstico de ESG por intubação em pacientes pediátricos após o período neonatal. Melhor especificidade foi encontrada quando o estridor ocorreu por mais de 72 horas após a extubação ou quando teve o início depois desse período. A partir desse estudo, parece adequado indicar endoscopia de via aérea, para a confirmação de ESG, apenas naqueles pacientes que apresentarem estridor após 72 horas da extubação. / Objective: To determine the accuracy of stridor in predicting the occurrence of postintubation subglottic stenosis (SGS) in pediatric patients when compared with endoscopy airway diagnosis. Design: Prospective cohort. Methods: Children aged 28 days to four years admitted to the Pediatric Intensive Care Unit of Hospital de Clinicas de Porto Alegre who required endotracheal intubation for more than 24 hours were eligible for study. Patients with previous intubation, history of laryngeal disease, current or past tracheostomy, presence of craniofacial malformations and those considered terminal by the staff were excluded from the study. Children were monitored daily and underwent flexible fiberoptic laryngoscopy (FFL) after extubation. Those who presented moderate to severe abnormalities in this first examination underwent another FFL between 7 and 10 days later. If these lesions persisted or symptoms developed, regardless of the findings in initial examination, laryngoscopy under general anesthesia was warranted. Occurrence of stridor was verified daily after extubation and classified as either present or absent. Results: We followed 194 children between November 2005 and August 2012. The incidence of post-extubation stridor was 43.81 per cent. Stridor had a sensitivity of 77.78% (CI 95%: 51.9 – 92.6) and specificity of 59.66% (CI 95%: 52.0 – 66.9) to detect SGS in this sample. The positive predictive value (PPV) was 16.47% (CI 95%: 9.6 – 26.4) and the negative predictive value was 96.33% (CI 95%: 90.3 – 98.8). Stridor, when present more than 72 hours or when started after these first 72 hours after extubation, showed a sensitivity of 66.67% (CI 95%: 41.2 – 85.6), specificity of 88.5% (CI 95%: 83.1 – 93.1), PPV of 38.8% (CI 95%: 22.4 – 57.7) and NPV of 96.23% (CI 95%: 91,6 – 98,5). ROC curve area was 0,78 (CI 95%: 0.65 – 0.91). Conclusions: Absence of stridor proved to be adequate to rule out the diagnosis of post-intubation SGS in pediatric patients. Improved specificity was found when stridor occurred for more than 72 hours after extubation or when started after that. From this study, it seems appropriate to indicate airway endoscopy under general anesthesia for the confirmation of SGS only in those patients who present stridor after 72 hours following extubation.

Objetivos: Determinar a acurácia do estridor em predizer a ocorrência de estenose subglótica (ESG) por intubação em pacientes pediátricos quando comparado ao seu diagnóstico por endoscopia de via aérea. Delineamento: Coorte Prospectiva. Métodos: Foram elegíveis todas as crianças de 28 dias a quatro anos de idade internadas na Unidade de Terapia Intensiva Pediátrica do Hospital de Clínicas de Porto Alegre que necessitaram de intubação endotraqueal por mais de 24 horas. Foram excluídas as com história de intubação, doença laríngea prévia, presença de traqueostomia atual ou no passado, presença de malformações craniofaciais e aquelas consideradas portadoras de doença terminal. Foram acompanhadas diariamente e, após a extubação, submetidas à fibronasolaringoscopia (FNL). Novo exame era realizado em sete a dez dias naquelas com alterações moderadas a graves no primeiro. Se essas persistissem ou surgissem sintomas, independentemente da FNL inicial, realizava-se laringoscopia sob anestesia geral. Após a extubação, verificou-se diariamente a ocorrência de estridor, classificado como presente ou ausente. Resultados: Foram acompanhados, de novembro de 2005 a agosto de 2012, 194 pacientes. A incidência de estridor pós-extubação foi de 43,81%. O estridor apresentou uma sensibilidade de 77,78% (IC 95%: 51,9 – 92,6) e especificidade de 59,66% (IC 95%: 52,0 – 66,9) em detectar ESG nessa amostra, o valor preditivo positivo (VPP) foi de 16,47% (IC 95%: 9,6 – 26,4) e o valor preditivo negativo (VPN) foi de 96,33% (IC 95%: 90,3 – 98,8). O estridor quando presente por mais de 72 horas ou quando esse surgiu após as primeiras 72 horas da extubação apresentou uma sensibilidade de 66,67% (IC 95%: 41,2 – 85,6) e especificidade de 88,5% (IC 95%: 83,1 – 93,1). O VPP foi de 38,8% (IC 95%: 22,4 – 57,7) e o VPN foi de 96,23 (IC 95%: 91,6 – 98,5). A área da curva ROC foi 0,78 (IC 95%: 0,65 – 0,91). Conclusões: A ausência de estridor mostrou-se adequada para afastar o diagnóstico de ESG por intubação em pacientes pediátricos após o período neonatal. Melhor especificidade foi encontrada quando o estridor ocorreu por mais de 72 horas após a extubação ou quando teve o início depois desse período. A partir desse estudo, parece adequado indicar endoscopia de via aérea, para a confirmação de ESG, apenas naqueles pacientes que apresentarem estridor após 72 horas da extubação. / Objective: To determine the accuracy of stridor in predicting the occurrence of postintubation subglottic stenosis (SGS) in pediatric patients when compared with endoscopy airway diagnosis. Design: Prospective cohort. Methods: Children aged 28 days to four years admitted to the Pediatric Intensive Care Unit of Hospital de Clinicas de Porto Alegre who required endotracheal intubation for more than 24 hours were eligible for study. Patients with previous intubation, history of laryngeal disease, current or past tracheostomy, presence of craniofacial malformations and those considered terminal by the staff were excluded from the study. Children were monitored daily and underwent flexible fiberoptic laryngoscopy (FFL) after extubation. Those who presented moderate to severe abnormalities in this first examination underwent another FFL between 7 and 10 days later. If these lesions persisted or symptoms developed, regardless of the findings in initial examination, laryngoscopy under general anesthesia was warranted. Occurrence of stridor was verified daily after extubation and classified as either present or absent. Results: We followed 194 children between November 2005 and August 2012. The incidence of post-extubation stridor was 43.81 per cent. Stridor had a sensitivity of 77.78% (CI 95%: 51.9 – 92.6) and specificity of 59.66% (CI 95%: 52.0 – 66.9) to detect SGS in this sample. The positive predictive value (PPV) was 16.47% (CI 95%: 9.6 – 26.4) and the negative predictive value was 96.33% (CI 95%: 90.3 – 98.8). Stridor, when present more than 72 hours or when started after these first 72 hours after extubation, showed a sensitivity of 66.67% (CI 95%: 41.2 – 85.6), specificity of 88.5% (CI 95%: 83.1 – 93.1), PPV of 38.8% (CI 95%: 22.4 – 57.7) and NPV of 96.23% (CI 95%: 91,6 – 98,5). ROC curve area was 0,78 (CI 95%: 0.65 – 0.91). Conclusions: Absence of stridor proved to be adequate to rule out the diagnosis of post-intubation SGS in pediatric patients. Improved specificity was found when stridor occurred for more than 72 hours after extubation or when started after that. From this study, it seems appropriate to indicate airway endoscopy under general anesthesia for the confirmation of SGS only in those patients who present stridor after 72 hours following extubation.

Introduction: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is the commonest benign paediatric neoplasm. There is no curative treatment, but the condition is self-limiting. Current primary treatment is aimed at symptomatic relief, comprising of serial surgical debulking of obstructive papillomas along the respiratory tract, with voice preservation. Adjuvant therapy is indicated in severe cases. Objective: A review of children with JoRRP presenting to the ENT Department at Red Cross War Memorial Children’s Hospital (RCWMCH) over 2 years. Evaluation of the pattern of disease and factors that may contribute to disease severity were reviewed. Method: Retrospective folder review of children with histologically confirmed laryngeal papillomatosis over above the time period. Results: Twenty children were included. Nine were male, 11 were female. The median age at diagnosis was 2.4 years (11 - 109 months). Presentation at < 3 years was noted in 5/7 of the most severe cases. Nine of 20 were HPV serotyped; 5 were type 11, and 4 were type 6. Eighty percent (16/20) were HIV negative; 10% (2/20) HIV positive; and 10% (2/20) were unknown. A total of 90 surgical procedures were performed; the highest number of surgeries per child was 13. Inter-surgical time was 1 to 164 weeks (median 9 weeks). Four received Gardasil vaccination as adjuvant therapy, 3 of who showed a reduction in disease severity. Conclusion: JoRRP commonly presents around the first 3 years of life. Severe cases can be life-threatening, often with multiple hospital admissions for clearance of surgical papillomata. Severe cases presented before 3 years. Gardasil vaccination as adjuvant therapy has promise. No identifiable risk factors in our review were noted. HIV co-infection and HPV type were not risk factors for severity.

Congenital myasthenic syndromes (CMS) are a group of heterogeneous disorders caused by mutations in genes encoding for proteins that are essential for neuromuscular transmission. All CMS share the clinical feature of fatigable muscle weakness. The differential diagnosis of CMS is wide, with a range of diseases going from autoimmune myasthenia gravis to muscle disorders. In this thesis, it was shown that measuring antibodies to clustered acetylcholine receptors (AChRs) by cell-based assay is helpful in the differential diagnosis of CMS. The findings of the current investigations showed that mutations in COL13A1, encoding the Collagen Type XIII α1 chain, were responsible for the symptoms of several patients with previously undefined myasthenias. In addition, this work described the clinical and complementary features of a novel CMS subtype due to mutations in the glycosylation pathway gene GMPPB. Investigations on a novel MUSK missense mutation (p.Ala617Val) uncovered previously unrecognised mechanisms of how levels of MuSK phosphorylation are critical to maintain synaptic structure, and guided suitable treatment for the patient. The study on the clinical and molecular basis of stridor, a novel clinical feature recently identified in patients with DOK7-CMS, prompted the identification of a novel DOK7 isoform, which warrants further investigation to elucidate its role in AChR clustering. Finally, the therapy of patients with severe AChR-deficiency was optimised thanks to a case series study that showed a robust improvement following the addition of β2-adrenergic agonists to their long-term treatment regime that included pyridostigmine.