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1.
J Med Genet ; 60(11): 1092-1104, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37316189

RESUMO

BACKGROUND: Helios (encoded by IKZF2), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognised for its role in the development and function of T lymphocytes, particularly the CD4+ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans. METHODS: We performed detailed phenotypic, genomic and functional investigations on two unrelated individuals with a phenotype of immune dysregulation combined with syndromic features including craniofacial differences, sensorineural hearing loss and congenital abnormalities. RESULTS: Genome sequencing revealed de novo heterozygous variants that alter the critical DNA-binding zinc fingers (ZFs) of Helios. Proband 1 had a tandem duplication of ZFs 2 and 3 in the DNA-binding domain of Helios (p.Gly136_Ser191dup) and Proband 2 had a missense variant impacting one of the key residues for specific base recognition and DNA interaction in ZF2 of Helios (p.Gly153Arg). Functional studies confirmed that both these variant proteins are expressed and that they interfere with the ability of the wild-type Helios protein to perform its canonical function-repressing IL2 transcription activity-in a dominant negative manner. CONCLUSION: This study is the first to describe dominant negative IKZF2 variants. These variants cause a novel genetic syndrome characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.


Assuntos
Anormalidades Craniofaciais , Deficiências do Desenvolvimento , Perda Auditiva , Fator de Transcrição Ikaros , Humanos , Proteínas de Ligação a DNA/genética , Fator de Transcrição Ikaros/genética , Síndrome , Deficiências do Desenvolvimento/genética , Anormalidades Craniofaciais/genética
2.
Otolaryngol Head Neck Surg ; 163(3): 591-599, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32315254

RESUMO

OBJECTIVES: To investigate the outcomes of pediatric tracheostomy as influenced by demographics and comorbidities. STUDY DESIGN: Retrospective national database review. SETTING: Fifty-two children's hospitals across the United States. SUBJECTS AND METHODS: Hospitalization records from Pediatric Health Information System database dated 2010 to 2018 with patients younger than 18 years and procedure codes for tracheostomy were extracted. The primary outcome was total length of stay. The secondary outcomes were 30-day readmission, mortality, and posttracheostomy length of stay. RESULTS: A total of 14,155 children were included in the analysis. The median total length of stay was 77 days and increased from 59 to 103 days between 2010 and 2018 (P < .001). The median posttracheostomy length of stay was 34 days and also increased from 27 to 49 days (P < .001). On multivariate regression analyses, the total and posttracheostomy lengths of stay were significantly increased in children younger than 1 year, patients of black race, hospitals in the non-West regions, those discharged to home, and those with comorbidities. Socioeconomic indicators such as insurance type and estimated household income were associated with no difference or small effect sizes. Regions and comorbidities were associated with differences in 30-day readmission (overall 26%), while in-hospital mortality was primarily associated with age and comorbidities (overall 8.6%). CONCLUSION: Pediatric tracheostomy requires substantial health care resources with length of stay escalating over recent years. Age, race, region, discharge destination, and comorbidities were associated with differences in length of stay.


Assuntos
Hospitalização/estatística & dados numéricos , Traqueostomia/estatística & dados numéricos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Traqueostomia/efeitos adversos , Resultado do Tratamento , Estados Unidos
4.
J Surg Oncol ; 114(8): 907-914, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27774626

RESUMO

Gastric pull-up (GPU) is among the oldest techniques for reconstructing the pharyngoesophageal junction following cancer resection. This review examines morbidity and mortality rates following GPU pharyngoesophageal junction reconstruction from 1959 until present: 77 studies, 2,705 patients. The odds of mortality, anastomotic complications, and other complications decreased by 37.2% (95%CI = 28.0-45.3%; P < 0.0001), 8.0% (95%CI = -2.1 to 17.1%; P = 0.12), 21.0% (95%CI 3.5-35.2%; P = 0.021) per decade respectively. J. Surg. Oncol. 2016;114:907-914. © 2016 Wiley Periodicals, Inc.


Assuntos
Neoplasias Esofágicas/cirurgia , Esôfago/cirurgia , Neoplasias Faríngeas/cirurgia , Faringe/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/epidemiologia , Estômago/cirurgia , Anastomose Cirúrgica , Esofagectomia , Humanos , Laringectomia , Faringectomia , Procedimentos de Cirurgia Plástica/mortalidade , Resultado do Tratamento
5.
Int J Pediatr Otorhinolaryngol ; 79(4): 623-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25683591

RESUMO

Tracheal-bronchus is an aberrant bronchus arising from the lateral tracheal wall, superior to the carina. A "False-carina" can be classified as a sub-type. This clinical entity will be defined and the clinical presentation, diagnosis and management of five patients with variations of the anatomical definition of a False-carina, identified at our institution, will be reviewed. Congenital bronchial abnormalities, including False-carina, have important implications in the overall management of the airway. Management can range from expectant in asymptomatic patients to surgical intervention in cases of recurrent respiratory infections. Awareness and understanding of this clinical entity allows for timely investigation, diagnosis and appropriate intervention.


Assuntos
Brônquios/anormalidades , Estenose Traqueal/diagnóstico , Manuseio das Vias Aéreas , Broncoscopia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Transtornos Respiratórios/diagnóstico , Transtornos Respiratórios/etiologia , Transtornos Respiratórios/terapia , Tomografia Computadorizada por Raios X , Estenose Traqueal/complicações , Estenose Traqueal/terapia
6.
Int J Pediatr Otorhinolaryngol ; 79(2): 254-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25497061

RESUMO

Adenotonsillectomy, a common ambulatory surgical procedure performed in the pediatric population, may at times lead to serious postoperative complications. The case of a 10-year-old with extensive cerebral venous thrombosis (CVT) following routine adenotonsillectomy is presented and the likely risk factors are discussed. Recent literature regarding CVT in children will be reviewed. To our knowledge, there are no previous reports in the Otolaryngology literature of extensive CVT as a complication of adenotonsillectomy. This clinical entity is more common than previously thought. Awareness and a high index of suspicion and initiation of timely management can reduce the risk of potentially fatal outcomes.


Assuntos
Adenoidectomia/efeitos adversos , Trombose Intracraniana/etiologia , Tonsilectomia/efeitos adversos , Trombose Venosa/etiologia , Criança , Humanos , Masculino , Obesidade/complicações , Apneia Obstrutiva do Sono/cirurgia
7.
Case Rep Otolaryngol ; 2014: 286190, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25506453

RESUMO

Calcific tendonitis of the longus colli (CTLC) muscle is an underrecognized cause of spontaneous acute or subacute neck pain, dysphagia, or odynophagia. Imaging may reveal a retropharyngeal fluid collection leading to the presumed diagnosis of retropharyngeal abscess. Recognition of this uncommon presentation is important to prevent unnecessary surgical incision and drainage. A 44-year-old otherwise healthy male presented with a 2-week history of progressive neck pain, stiffness, and odynophagia. A noncontrast CT scan of the cervical spine revealed a retropharyngeal fluid collection with a small area of calcification anterior to C2. There was a presumed diagnosis of retropharyngeal abscess. The patient was afebrile with normal vital signs. Flexible nasolaryngoscopy was unremarkable. C-reactive protein was elevated but all other bloodwork was normal with no evidence of an infective process. A CT scan was repeated with IV contrast showing no enhancement around the fluid collection. A diagnosis of CTLC was made. The patient was successfully managed with a short course of intravenous steroids and oral NSAIDs with complete resolution of symptoms. Clinically CTLC can mimic more serious disease processes. Identifying pathognomonic imaging findings often confirms the diagnosis. Awareness of this condition by the otolaryngologist will ensure proper patient management and avoidance of unnecessary procedures.

8.
JAMA Otolaryngol Head Neck Surg ; 140(10): 934-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25144751

RESUMO

IMPORTANCE: Sinonasal disease and, specifically, nasal polyps, occur frequently in children with cystic fibrosis (CF). As survival rates have improved, it has become imperative that otolaryngologists become involved in the care of patients with CF to provide appropriate medical and surgical interventions for sinonasal disease. Despite significant variability in the subjective reporting of clinical symptoms, previous work has suggested there may be a relationship between clinical indicators and sinonasal disease in this population. OBJECTIVE: To determine whether the 22-item Sino-Nasal Outcome Test (SNOT-22), the University of Pennsylvania Smell Identification Test (UPSIT), and other measures of sinonasal disease could be used to predict the presence of subclinical nasal polyps in children with CF. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study performed from May 2012 through April 2013 at a cystic fibrosis clinic at BC Children's Hospital in Vancouver, British Columbia, Canada. There were 72 eligible children with CF for this study (with a confirmed diagnosis of CF based on genetic testing; their ages ranged from 6 to 18 years, and they were not actively being treated by an otolaryngologist). Thirty-seven of these patients (23 males, 14 females) consented to participate in this study. Twenty-three declined participation, and 12 could not be contacted. MAIN OUTCOMES AND MEASURES: Potential clinical predictors for the presence of subclinical nasal polyps were determined a priori. All 37 recruited participants completed a full study assessment. Nasal endoscopy (the gold standard) was performed to determine the presence of nasal polyps. Potential predictors that were assessed included age, sex, genotype, pancreatic function, SNOT-22 and UPSIT scores, oral culture swab result, and severity of forced expiratory volume in 1 second (FEV(1)). RESULTS: A SNOT-22 score of greater than 11 was the only statistically significant predictor of nasal polyps (P = .04). The positive predictive value was 68.1%, the negative predictive value was 66.7%, and the positive likelihood ratio was 1.82. CONCLUSIONS AND RELEVANCE: Given that the SNOT-22 is easy to administer and inexpensive, this sinus disease-specific questionnaire seems to be an appropriate tool for routine use by respirologists when assessing patients with CF to help predict subclinical nasal polyps.


Assuntos
Fibrose Cística/complicações , Pólipos Nasais/diagnóstico , Pólipos Nasais/cirurgia , Transtornos do Olfato/diagnóstico , Encaminhamento e Consulta , Adolescente , Colúmbia Britânica , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pólipos Nasais/etiologia , Procedimentos Cirúrgicos Otorrinolaringológicos , Resultado do Tratamento
9.
J Clin Microbiol ; 44(10): 3583-8, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17021086

RESUMO

Influenza A viruses cause yearly epidemics, in part, due to their ability to overcome immunity from previous infections through acquisition of mutations. Amino acid sequences encoded by genes 4 (HA), 6 (NA), 7 (M), and 8 (NS) from 77 H3N2 influenza A isolates, collected between November 2003 and March 2005, were analyzed to determine the extent to which the viruses mutated within epidemic periods and between the epidemics. Nucleotide and amino acid sequences were stable throughout the epidemics but experienced substantial changes between epidemics. Major changes occurred in the HA gene in 5 to 7 amino acids and the NA gene in 11 to 13 amino acids and changes of 5 amino acids occurred in the M and NS genes. In the HA gene, changes occurred in sites known to be epitopes that determine the hemagglutination inhibition reactivity, and these were shown to be associated with a change of strain from A/Fujian/411/2002-like to A/California/7/2004-like viruses. Our findings indicate that genotype determination promises to be a rapid approach for detecting new strains of influenza A viruses in a population.


Assuntos
Vírus da Influenza A/genética , Sequência de Aminoácidos , Surtos de Doenças , Variação Genética , Genótipo , Humanos , Influenza Humana/virologia , Filogenia , Proteínas Virais/química , Proteínas Virais/genética
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