DNA rare copy number alterations in Reinke's Edema.

INTRODUCTION: Reinke's Edema (RE) is a laryngeal lesion related to excessive tobacco smoking, voice overuse, and laryngopharyngeal reflux. Although the risk of malignancy has been considered low in literature, RE is classified among precancerous lesions. OBJECTIVES: We investigated DNA Copy Number Alterations (CNAs) in specimens of RE and its potential association with malignant progression. METHODS: We used array-based comparative genomic hybridization (aCGH, Agilent 4 × 180 K platform) to study eight RE cases. All patients were heavy tobacco users for at least 30 years, and none of them progressed to cancer in the follow-up (>8 years). Two RE presented mild dysplasia, one moderate dysplasia, and no histological alterations were found in the remaining five cases. CNAs were compared with the Database of Genomic Variants (DGV) and genes mapped on altered regions had their functions annotated. RESULTS: Six of eight patients showed different rare copy number alterations on chromosomes 2q37.3, 4q13.1, 4q13.3, 7q11.22, 10p14, and 13q34. A gain of the whole chromosome 8 were detected in one case. Of interest, four of eight RE cases showed copy number imbalances involving genes previously described in several tumor types (RASA3, COL6A3, LINC00707, LINP1, SMR3A, and SMR3B). CONCLUSION: The genomic imbalances herein found in RE have the potential to contribute to the phenotype but with limited or no risk of cancer. A long-term follow-up in a large series of patients could clarify the mechanisms involved in the malignant progression of RE.

Manejo del fracaso de la extubación en la unidad de terapia intensiva pediátrica / Management of extubation failure in the pediatric intensive care unit / Gestão de falha de extubação na Unidade de Terapia Intensiva Pediátrica

El fracaso de la extubación es la incapacidad de tolerar el retiro del tubo endotraqueal con necesidad de reintubación. Puede ser causada por la obstrucción de la vía aérea superior y por la aspiración o la incapacidad de manejar las secreciones, factores que se evidencian al retirar el tubo. La reintubación por fracaso respiratorio post-extubación debe ser evitada en lo posible, ya que aumenta el riesgo de neumonía asociada al respirador, la estancia hospitalaria y en terapia intensiva, y la morbimortalidad. Describimos el manejo del fracaso de la extubación de causa laríngea en la Unidad de Terapia Intensiva de un hospital pediátrico.

Extubation failure is the inability to tolerate removal of the endotracheal tube with subsequent reintubation. It can be caused by obstruction of the upper airway and aspiration or inadequate clearance of airway secretion, factors that become evident when removing the tube. Reintubation due to postextubation respiratory failure should be avoided if possible because it increases the risk of ventilator associated pneumonia, hospital and intensive care unit stay, and morbidity and mortality. We describe the management of failed extubation due to laryngeal cause in the Intensive Care Unit of a pediatric hospital.

Falha de extubação é a incapacidade de tolerar a remoção do tubo endotraqueal na necessidade de reintubação. Ela pode ser causada por obstrução das vias aéreas superiores e aspiração ou incapacidade para lidar com secreções, factores que são evidentes para remover o tubo. Reintubação devido a insuficiência respiratória pós-extubação deve ser evitada, se possível, porque aumenta o risco de pneumonia associada à ventilação mecânica, permanência hospitalar e terapia, morbidade e mortalidade. Nós descrevemos a gestão de extubação falhou devido à causa da laringe na Unidade de Terapia Intensiva de um hospital pediátrico.

Angioedema hereditario / Hereditary angioedema

El angioedema hereditario es una enfermedad poco frecuente, con herencia autosómica dominante que se caracteriza por presentar edemas en piel y en la mucosa de diferentes órganos, fundamentalmente el tubo digestivo y el aparato respiratorio. Las manifestaciones clínicas pueden ser ligeras o graves, en dependencia de su intensidad y localización. Las formas más graves son el edema de la glotis y del tubo digestivo, que llegan a ocasionar síntomas como deshidratación intensa y dolor abdominal, el que puede confundirse con un abdomen agudo y llevar a una intervención quirúrgica innecesaria. El edema se caracteriza por no ser pruriginoso, no presentar aumento de la temperatura, no dejar godet al presionarlo y generalmente existen antecedentes familiares. No tiene predilección por sexo, ni por el color de la piel. Para su diagnóstico es necesario hacer un interrogatorio minucioso y exámenes complementarios del sistema complemento. Se han descrito dos formas clásicas denominadas angioedema hereditario tipo I y tipo II, el primero es el más frecuente. Recientemente se ha descrito el tipo III que se presenta solo en mujeres, sin alteración cuantitativa o cualitativa de C1-inhibidor y se asocia con el consumo de medicamentos o anticonceptivos orales que contienen estrógenos. El tratamiento se basa fundamentalmente en el uso de andrógenos atenuados o de los antifibrinolíticos, así como evitar los factores de riesgo en caso de que estos se conozcan. En los casos que presenten cuadros agudos se puede utilizar el plasma fresco congelado y un concentrado purificado de C1- inhibidor (Berinert-500) de uso endovenoso y de respuesta rápida; aunque sin ser muy efectiva se puede usar la epinefrina subcutánea. Los esteroides y los antihistamínicos no tienen ninguna efectividad en el tratamiento de estos pacientes(AU)

Hereditary angioedema is a rare disease with autosomal dominant inheritance that is characterized by edema in skin and mucosa of various organs, mainly gastrointestinal tract and the respiratory system. Clinical manifestations may be mild or severe, depending on their location and intensity. The most severe forms are edema of the glottis, and the edema of gastrointestinal tract which can cause severe dehydration and abdominal pain that can be confused with an acute abdomen and unnecessary surgery. The edema is characterized by not being itchy, no temperature rise, non-marking when pressed and usually have a family history. No predilection for sex, or skin color. Its diagnosis is necessary to make a thorough examination and additional tests of the complement system. They described two classic forms called HAE type I and type II, type I is the most common. Recently it described the type III that occurs only in females, without quantitative or qualitative alteration of C1 inhibitor and is associated with the consumption of drugs or oral contraceptives containing estrogen. The treatment is based primarily on the use of attenuated androgens or antifibrinolytic and avoiding risk factors if they are known. In cases of acute conditions present you can use fresh frozen plasma and purified C1 inhibitor concentrate (Berinert-500) for intravenous use and rapid response; but the use of subcutaneous epinephrine may not be very effective. Steroids and antihistamines have no effectiveness when used in these patients(AU)

Cuff-leak test for the diagnosis of upper airway obstruction in adults: a systematic review and meta-analysis.

PURPOSE: To evaluate, in adults, the diagnostic accuracy of the cuff-leak test for the diagnosis of upper airway obstruction secondary to laryngeal edema and for reintubation secondary to upper airway obstruction. METHODS: Systematic review without language restrictions based on electronic databases and manual review of the literature up to December 2008. When appropriate, a random-effects meta-analysis and meta-regression (Moses' method) were performed. RESULTS: Upper airway obstruction was the outcome in nine studies with an overall incidence of 6.9%. There was significant heterogeneity among studies. The pooled sensitivity was 0.56 (95% confidence interval: 0.48-0.63), the specificity was 0.92 (95% CI: 0.90-0.93), the positive likelihood ratio was 5.90 (95% CI: 4.00-8.69), the negative likelihood ratio was 0.48 (95% CI: 0.33-0.72), and the diagnostic odds ratio was 18.78 (95% CI: 7.36-47.92). The area under the curve of the summary receiver-operator characteristic (SROC) was 0.92 (95% CI: 0.89-0.94). Only three studies have evaluated the accuracy of the cuff-leak test for reintubation secondary to upper airway obstruction. Overall incidence was 7%. The pooled sensitivity was 0.63 (95% CI: 0.38-0.84), the specificity was 0.86 (95% CI: 0.81-0.90), the positive likelihood ratio was 4.04 (95% CI: 2.21-7.40), the negative likelihood ratio was 0.46 (95% CI: 0.26-0.82), and the diagnostic odds ratio was 10.37 (95% CI: 3.70-29.13). CONCLUSIONS: A positive cuff-leak test (absence of leak) should alert the clinician of a high risk of upper airway obstruction.

Disarrangement of collagen fibers in Reinke's edema.

OBJECTIVE/HYPOTHESIS: To describe the arrangement of collagen fibers in the superficial layer of the lamina propria of the vocal folds with Reinke' edema. STUDY DESIGN: Cross sectional analysis of the lamina propria of the vocal folds with Reinke's edema (RE). METHOD: The picrosirius polarization method was used to study the arrangement of collagen fiber. Findings of collagen disarrangement were categorized semiquantitatively and correlated with RE severity, age, cigarette smoking and duration of dysphonia. RESULTS: Analysis of 20 specimens of vocal folds with RE showed that the intertwined network of collagen fibers resembling a wicker-basket normally observed in vocal folds was disarranged in RE. The collagen fibers were loosely arranged, fragmented and intermixed with varying amounts of myxoid stroma. Moderate and large areas of disarrangement (90% of cases) predominated. Collagen fiber arrangement in the region underneath the epithelium was better preserved when compared with fibers in the deeper region of the superficial layer of the lamina propria. There was a statistical difference in collagen disarrangement between grade II and grade III severity (P = .007) that appeared to be due to the large areas of disarrangement observed in 73% of patients with grade III severity and in 44% of grade II severity. Age was the only variable correlated with collagen fiber disarrangement (r = 0.47, P = .037). CONCLUSION: Our findings suggest that the flexible framework which maintains the uniformity of the lamina propria was lost in RE caused by the disarrangement of the collagen fibers.

Insuficiência respiratória aguda e edema de Reinke / Acute respiratory insufficience and Reinke's edema

O odema de Reinke tem sido objeto de pouca atençäo pela literatura médica. Trata-se de um edema acumulado no espaço de Reinke, da lâmina própria das pregas vocais. É descrito como uma alteraçäo benigna, tendo como sintomatologia básica a disfonia e sendo raras as complicaçöes. Os autores apresentam um caso de edema de Reinke associado a laringite, que desenvolveu quadro de insuficiência respiratória aguda como complicaçäo, necessitando de cricotireoidostomia de urgência. Este trabalho relata uma complicaçäo rara do edema de Reinke, bem como uma revisäo literária sobre a patologia

Vía aérea pediátrica y sus complicaciones / The pediatric airway and its complications

El manejo de la vía aérea pediátrica normal, puede resultar sumamente complejo si no se toma en cuenta que se trata de seres en pleno desarrollo. El hecho de que el niño no es un adulto pequeño nunca es más cierto que al estudiar su vía aérea. En el presente trabajo estudiaremos las características anatómicas y fisiológicas de la vía aérea pediátrica en particular, comparándola con la del adulto. Revisaremos las causas y condiciones que puedan generar dificultades en la intubación, y analizaremos los métodos de evaluación utilizados para anticiparse a estas situaciones. Consideraremos en detalle las diferencias que existen en la intubación del paciente pediátrico y el adulto y finalizaremos con una revisión de las complicaciones más frecuentemente asociadas a la intubación endotraqueal.

Vía aérea pediátrica y sus complicaciones / The pediatric airway and its complications

El manejo de la vía aérea pediátrica normal, puede resultar sumamente complejo si no se toma en cuenta que se trata de seres en pleno desarrollo. El hecho de que el niño no es un adulto pequeño nunca es más cierto que al estudiar su vía aérea. En el presente trabajo estudiaremos las características anatómicas y fisiológicas de la vía aérea pediátrica en particular, comparándola con la del adulto. Revisaremos las causas y condiciones que puedan generar dificultades en la intubación, y analizaremos los métodos de evaluación utilizados para anticiparse a estas situaciones. Consideraremos en detalle las diferencias que existen en la intubación del paciente pediátrico y el adulto y finalizaremos con una revisión de las complicaciones más frecuentemente asociadas a la intubación endotraqueal. (AU)