Early Surgical Management of Bronchial Dehiscence After Single-Lung Transplantation: A Case Report.

Anastomotic airway complications after lung transplantation affect up to 20% of patients. Bronchial stenosis is the most frequent complication, while dehiscence of bronchial anastomosis is a rarely seen complication, with report incidences between 1% and 10%. Despite its low incidence, dehiscence of bronchial anastomoses remains a disastrous complication in the posttransplantation period without a well-established management protocol. We present a challenging case of complete bronchial dehiscence after unilateral lung transplantation in a patient with interstitial lung fibrosis (ILF) that occurred on postoperative day 10. The dehiscence was diagnosed early and the patient's status was stable for repeat thoracotomy, therefore, an early surgical approach was preferable to conservative management or bronchoscopy. Aggressive early surgical management in a stable patient allows for complete debridement with removal of the detritus that impedes correct anastomosis healing and permits the removal of microbial vegetations with successful results.

Tracheobronchoplasty after a trial with a silicone Y-stent in a patient with Mounier-Kuhn syndrome.

Tracheobronchomegaly or Mounier-Kuhn syndrome is a rare disorder characterized by the widening of the trachea and the main bronchi. It is a form of tracheomalacia called 'cartilaginous malacic' and is characterized by deformation of the tracheal cartilages and intrusion of the redundant membranous wall into the lumen of the airway. We present a patient with Mounier-Kuhn syndrome managed like patients with tracheomalacia of other aetiologies-a tracheobronchoplasty with a reconstructed D-shaped trachea and stabilization of the posterior membranous wall by attaching a polypropylene mesh to the posterior membranous wall of the trachea and the main bronchi after a trial period with a tracheobronchial Y-shaped silicone stent.

Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome.

OBJECTIVE: To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel. METHODS: Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Platelet reactivity was measured with VerifyNow®. RESULTS: Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01-16.34), age (OR 1.43; 95% CI 1.03-2.00), and body mass index (OR 4.05; 95% CI 1.21-13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%). CONCLUSION: CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables.

Association of polymorphisms in TRAIL1 and TRAILR1 genes with susceptibility to lymphomas.

The TRAILR1/TRAIL system is implicated in the induction of the extrinsic apoptotic pathway and constitutes an emerging target in cancer therapeutics. The objective of this study is to assess lymphoma risk associated with certain polymorphisms in TRAILR1 and TRAIL1 genes. DNA was extracted from 381 subjects (190 lymphoma cases and 191 matched controls) and genotyped for polymorphisms rs20576, rs2230229 and rs20575 in TRAILR1 and rs12488654 in TRAIL gene. In contrast to TRAILR1 polymorphisms, the genotype distribution of rs12488654 in TRAIL gene was different between cases and controls, A allele carriers (CA/AA) being much more common in the cases with different lymphoma types (follicular, 45 %; diffuse large B cell, 45.2 % and Hodgkin lymphomas, 40 %) than in controls (15.7 %) (odds ratio (OR), 3.5; CI, 2.1­5.9; p<0.001; OR, 3.5; CI, 1.6­7.9; p=0.001; OR, 2.9; CI, 1.1­7.5; p=0.027, respectively). This effect was consistently independent of the association with the TRAILR1 polymorphisms studied, as demonstrated by linkage disequilibrium and haplotype analyses. This study is the first one to report an association between a TRAIL polymorphism and lymphoma risk and suggests a possible role of TRAIL in B cell lymphomagenesis.

Polymorphisms in xenobiotic metabolizing genes (EPHX1, NQO1 and PON1) in lymphoma susceptibility: a case control study.

BACKGROUND: The interplay between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. EPHX1, NQO1 and PON1 are three genes encoding proteins directly involved in the detoxification of potential carcinogens. METHODS: We have studied the prevalence of three functional polymorphisms affecting these genes rs1051740 EPHX1, rs1800566 NQO1 and rs662 PON1 in 215 patients with lymphoma and 214 healthy controls. RESULTS: Genotype frequencies for EPHX and NQO1 polymorphisms did not show any correlation with disease. In contrast, the GG genotype in the PON1 polymorphism was found to be strongly associated with the disease (15.3% vs. 4.7%; OR = 3.7 CI (95%): 1.8-7.7; p < 0.001). According to the pathological diagnosis this association was related to follicular (p = 0.004) and diffuse large B-cell (p = 0.016) lymphomas. CONCLUSIONS: Despite the fact that further confirmation is needed, this study shows that the PON1 GG genotype in rs662 polymorphism could be a risk factor for B-cell lymphomas.

Role of GSTT1 and M1 null genotypes as risk factors for B-cell lymphoma: influence of geographical factors and occupational exposure.

The interrelationship between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. Both factors need to be considered to enable assessment of disease risk associated with a given individual under certain environmental conditions. GSTT1 and GSTM1 are two genes whose proteins are involved in the detoxification of potential carcinogens. We have studied the prevalence of GSTT1 and GSTM1 null polymorphisms using a novel PCR multiplex protocol in a group of 158 patients with B-cell lymphoma (BCL, 138 with non-Hodgkin lymphoma and 20 with Hodgkin lymphoma) and 214 healthy controls. A questionnaire regarding occupational exposure and lifestyle factors was also completed by both groups. GSTM1 null genotype showed no significant differences between patients and controls (46.9% and 55.6%, respectively). In contrast, GSTT1 null genotype was observed in 25.3% of patients and 15.4% of controls (P=0.013; OR=1.85; CI (95%):1.11-3.09), suggesting a role for the GSTT1 null genotype in the development of BCL. This effect was even more evident in females (27.5% vs. 14%: P=0.014). No significant association was observed between GST genotypes and disease risk in relation to smoking or occupational exposure.

[Is the incidence of near-fatal asthma decreasing in Spain?]. / Disminuye la incidencia de asma de riesgo vital en España?

OBJECTIVE: A number of studies have shown that both mortality and hospital admissions due to severe asthma have decreased in recent years in many parts of the world. However, the situation is Spain has not yet been analyzed. The aim of this study was to determine the incidence of very severe, near-fatal asthma in recent years in various Spanish hospitals. PATIENTS AND METHODS: A retrospective review of hospital records from 6 hospitals in 5 Spanish autonomous communities was conducted for the period 1997 to 2004 to determine the annual number of patients who required orotracheal intubation and mechanical ventilation due to an asthma attack. RESULTS: Of the 130 patients included in the study, 81 (62%) were women and 61 (47%) were aged between 51 and 75 years. The number of cases observed for the periods 2001-2002 and 2003-2004 (32 and 18, respectively) was significantly lower than that observed for the 1997-1998 and 1999-2000 periods (40 in both cases; P=.019). A significant increase in the incidence was observed in autumn and winter (n=81 [62%]; P=.018). Seventeen patients (13%) died and 8 (6%) developed serious sequelae. CONCLUSIONS: Although our sample of 6 hospitals is not widely representative of the entire population of hospitals in Spain, our findings strongly suggest a decrease in the incidence of near-fatal asthma in Spain in recent years.

¿Disminuye la incidencia de asma de riesgo vital en España? / Is the incidence of near-fatal asthma decreasing in Spain?

Objetivo: Estudios recientes muestran un descenso de la mortalidad y del número de los ingresos hospitalarios por asma grave en los últimos años en diferentes lugares del mundo. Se desconoce la situación en nuestro país. El objetivo del presente estudio ha sido determinar la frecuencia anual de las crisis de asma de riesgo vital muy grave en los últimos años en diversos centros hospitalarios españoles. Pacientes y métodos: Se revisaron retrospectivamente los registros hospitalarios de los pacientes que precisaron intubación orotraqueal y ventilación mecánica por una crisis de asma en 6 hospitales pertenecientes a 5 comunidades autónomas. El estudio recogió el número anual de casos observado durante el período comprendido entre 1997 y 2004. Resultados: De los 130 pacientes incluidos, 81 (62%) eran mujeres y 61 (47%) tenían entre 51 y 75 años de edad. En los 2 últimos bienios (2001-2002 y 2003-2004) el número de pacientes recogidos (32 y 18, respectivamente) fue significativamente inferior al observado en los 2 primeros (1997-1998 y 1999-2000, con 40 cada bienio; p = 0,019). Se constató una incidencia significativamente mayor de casos (n = 81; 62%) durante las estaciones de otoño e invierno (p = 0,018). Fallecieron 17 pacientes (13%) y 8 (6%) presentaron secuelas graves. Conclusiones: Si bien 6 centros hospitalarios no son lo bastante representativos de la totalidad de los centros españoles, los resultados del presente estudio podrían orientar hacia un muy probable descenso en nuestro país de los casos de asma de riesgo vital en los últimos años

Objective: A number of studies have shown that both mortality and hospital admissions due to severe asthma have decreased in recent years in many parts of the world. However, the situation is Spain has not yet been analyzed. The aim of this study was to determine the incidence of very severe, near-fatal asthma in recent years in various Spanish hospitals. Patients and methods: A retrospective review of hospital records from 6 hospitals in 5 Spanish autonomous communities was conducted for the period 1997 to 2004 to determine the annual number of patients who required orotracheal intubation and mechanical ventilation due to an asthma attack. Results: Of the 130 patients included in the study, 81 (62%) were women and 61 (47%) were aged between 51 and 75 years. The number of cases observed for the periods 2001-2002 and 2003-2004 (32 and 18, respectively) was significantly lower than that observed for the 1997-1998 and 1999-2000 periods (40 in both cases; P=.019). A significant increase in the incidence was observed in autumn and winter (n=81 [62%]; P=.018). Seventeen patients (13%) died and 8 (6%) developed serious sequelae. Conclusions: Although our sample of 6 hospitals is not widely representative of the entire population of hospitals in Spain, our findings strongly suggest a decrease in the incidence of near-fatal asthma in Spain in recent years

[Clinical characteristics of the fatal and near-fatal asthma in Alternaria alternata sensitized patients]. / Características clínicas de las crisis de asma de riesgo vital en los pacientes sensibilizados a Alternaria alternata.

BACKGROUND AND OBJECTIVE: Some studies have pointed to Alternaria alternata as a trigger of fatal and near-fatal asthma (NFA) crises. The objective of this study was to determine the clinical characteristics of fatal and NFA crisis in patients sensitized to Alternaria. PATIENTS AND METHOD: One hundred ninety four patients with fatal or NFA attacks were enrolled in a multicenter (33 Spanish hospitals), prospective study. We gathered the characteristics and clinical course of the crises. We performed the following tests: spirometry, prick-test to common allergens, and specific IgE to Alternaria when patients were in stable condition. The sensitization test to Alternaria was performed when the prick-test and/or specific IgE levels were positive. RESULTS: Twenty (10%) patients were sensitized to Alternaria. When compared to non-sensitized patients, Alternaria sensitized patients were significantly younger, 35 (15) vs 50 (21) years old (p<0.001); their hospital admission length was shorter, 6.5 (5.5) against 9 (7) days (p=0.039); they had a higher number of deaths or severe neurological sequelae, 15 vs 3% (p=0.026); they had a higher sensitization frequency to the remaining allergens, 68 against 22% (p=0.003); and they exhibited a fewer bronchodilation response upon inhaled salbutamol, 6 vs 10% (p=0.013). CONCLUSIONS: The clinical characteristics of Alternaria sensitised, fatal-and NFA-patients, seem to identify a particular phenotype. Specific avoidance strategies could be useful to prevent fatal and NFA attacks.

Características clínicas de las crisis de asma de riesgo vital en los pacientes sensibilizados a Alternaria alternata / Clinical characteristics of the fatal and near-fatal asthma in Alternaria alternata sensitized patients

FUNDAMENTO Y OBJETIVO: Algunas observaciones otorgan un papel relevante al hongo Alternaria alternata como desencadenante de crisis de asma de riesgo vital (ARV). El objetivo de este trabajo fue determinar si las crisis de ARV de los pacientes sensibilizados a Alternaria cursan con un perfil clínico diferencial. PACIENTES Y MÉTODO: Estudio descriptivo y multicéntrico (33 hospitales españoles) de 194 pacientes incluidos de forma prospectiva por padecer una crisis de ARV. Se recogieron las características y el curso clínico de la crisis, y cuando alcanzaron la estabilidad clínica se les practicaron una espirometría, pruebas cutáneas de alergia y determinación de IgE a Alternaria. Se estableció la sensibilización a Alternaria cuando la prueba cutánea o bien la IgE específica resultaron positivas. RESULTADOS: En 20 de los pacientes (10 por ciento) se pudo constatar sensibilización a Alternaria. En comparación con el grupo de pacientes no sensibilizados, los sensibilizados a Alternaria resultaron ser significativamente más jóvenes, con una media (DE) de edad de 35 (15) frente a 50 (21) años (p < 0,001); su ingreso hospitalario fue más corto -6,5 (5,5) frente a 9 (7) días (p = 0,039)-; se constató una mayor proporción de muertes o secuelas neurológicas graves -el 15 frente al 3 por ciento (p = 0,026)-; presentaron un mayor porcentaje de casos con sensibilización a otros alérgenos -el 68 frente al 22 por ciento (p = 0,003)- y una menor broncodilatación tras la inhalación de salbutamol -el 6 frente al 10 por ciento (p = 0,013)-. CONCLUSIONES: Las características clínicas constatadas en las crisis de ARV de los pacientes sensibilizados a Alternaria parecen distinguirlos como fenotipo particular. Una conducta de evitación específica podría comportar efectos beneficiosos al prevenir crisis de ARV en los pacientes sensibilizados (AU)