Novel insights into the neurobiology underlying LRRK2-linked Parkinson's disease.

Mutations in LRRK2 (leucine-rich repeat kinase 2) are found associated with both sporadic and familial Parkinson's disease (PD). Pathogenic mutations are localized to the catalytic domains of LRRK2, including kinase and GTPase domains. Altered catalytic activity correlates with neurotoxicity, indicating that targeting those activities may provide clues as to novel therapeutic strategies for LRRK2-linked PD. However, the cellular readout of such altered catalytic activities remains largely unknown. Recent cell biological studies have started to highlight possible early cellular events which are altered in the presence of pathogenic LRRK2 and may ultimately lead to neuronal demise, and these studies link altered LRRK2 function to various abnormal endolysosomal vesicular trafficking events. This review examines our current knowledge of LRRK2 neurobiology and how pathogenic mutations may lead to neurodegeneration in PD.

[Percutaneous tracheostomy in ventilated patients]. / Traqueostomía percutánea en pacientes ventilados.

INTRODUCTION: Percutaneous tracheostomy is an alternative to conventional surgical tracheostomy. It is associated to a more feasible procedure, that is less invasive and linked to a lower degree of complications. Herein, we review our experience since the implementation of this technique in our Department. DESIGN: Retrospective observational. SETTING: Nineteen-bed intensive care department, in a general reference teaching hospital. PATIENTS AND METHOD: A total of 115 of 130 tracheostomies performed from 2001 to 2003 were retrospectively analyzed. Collected data include epidemiological information, reason for performing the procedure, maintenance time of artificial airway before the tracheostomy and type of ventilatory support or oxygen supplementation before and after the procedure. The modified PEEP (PEEP-mod = FiO2 x PEEP) was calculated, sedation level received before and 4-6 hours after the technique and also 24 hours later, were reviewed. Subsequent patient evolution was collected. INTERVENTIONS: Observational study on the results of routine procedures. VARIABLES OF INTEREST: Blood gases indicators of effectiveness in oxygen supply and the need of mechanical ventilation support. RESULTS: Median age of the 115 reviewed patients was 65 years. The most common admission reasons were: brain vascular accident in 25 cases, head and neck injury in 21, cancer in 11 and sepsis in 10 patients. Tracheostomy was indicated because prolonged mechanical ventilation in 52 patients, coma in 28 and emergency or scheduled surgery in 10 cases. Median length of stay in the ICU before tracheostomy was 14 days. Ninety-two patients were discharged from the ICU, and 52 from the Hospital. The remaining patients died during their hospital stay. Serious complications appeared in 5 patients (4%); 3 of them were the development of fistulae and all of them occurred in patients in whom the tracheostomy was performed in the ICU at bedside. Before the procedure, 72 patients were under mechanical ventilation, but only 56 received ventilatory support 24 hours after tracheostomy. When PEEP-mod values were analyzed, first monitoring of median value was 1.6 (range 0 to 2), 4-6 hours time median value was 2 (1.4-2.45), and 24 hours later median value was 1.2 (0-2) (global variation, p < 0.001). CONCLUSIONS: In our experience, percutaneous tracheostomy performed at bedside in the ICU is an adequate solution with a low complication rate and its makes it possible to reduce the level of ventilatory support.

Traqueostomía percutánea en pacientes ventilados / Percutaneous tracheostomy in ventilated patients

Introducción. La traqueostomía percutánea es una alternativa a la traqueostomía quirúrgica convencional, asociada a una realización más ágil, menos invasora y con menor tasa de complicaciones. Revisamos los resultados obtenidos mediante esta técnica desde su implantación en nuestro Servicio. Diseño. Observacional, retrospectivo. Ámbito. Servicio de Medicina Intensiva de un Hospital docente de referencia, dotado de 19 camas. Pacientes y método. Se analizan 115 registros sobre 130 traqueostomías realizadas desde 2001 hasta 2003. Se recogen datos de filiación y epidemiológicos de los pacientes, motivo de realización de la técnica, tiempo de mantenimiento de la vía aérea antes de la traqueostomía y situación de soporte ventilatorio o de oxigenoterapia antes y después del procedimiento. Se calcula la presión positiva al final de la espiración modificada (PEEP-mod) (PEEP-mod = fracción inspirada de oxígeno [FiO2] x PEEP) y se revisa la sedación que recibían los pacientes antes de la traqueostomía, a las 4-6 horas de la misma y transcurridas 24 horas. Igualmente se recoge su evolución posterior. Intervenciones. Estudio observacional de resultados de pauta de actuación rutinaria. Variables de interés. Variables de efectividad de intercambio gaseoso en relación a la FiO2 administrada y la necesidad de soporte ventilatorio mecánico. Resultados. En los 115 pacientes revisados la mediana de edad fue de 65 años. Los diagnósticos de ingreso más comunes fueron: accidente vascular cerebral en 25 pacientes, traumatismos craneoencefálicos y cervicales en 21, neoplasias en 11 y sepsis en 10. Los principales para indicar la traqueostomía fueron: ventilación mecánica prolongada en 52 pacientes, coma en 28 y cirugía en 10. La mediana de estancia en el servicio de Medicina Intensiva antes de realizarse la traqueostomía fue de 14 días. Recibieron el alta del servicio de Medicina Intensiva 92 pacientes y el alta hospitalaria 52 pacientes; el resto falleció. Se produjeron complicaciones graves en 5 pacientes (4%); 3 de ellas consistieron en el desarrollo de fístulas, que ocurren en pacientes a los que se les realiza la traqueostomía en el servicio de Medicina Intensiva. Antes de la traqueostomía 72 pacientes recibían ventilación mecánica, y tras las primeras 24 horas postraqueostomía sólo 56 pacientes recibían soporte ventilatorio. Al analizar los valores de la PEEP-mod, la mediana del primer control es de 1,6 (rango 0 a 2), a las 4-6 horas la mediana es de 2 (1,4-2,45), y a las 24 horas la mediana es de 1,2 (0-2) (variación global, p < 0,001). Conclusiones. En nuestra experiencia la traqueostomía percutánea realizada intra-Unidad de Cuidados Intensivos (UCI) constituye una solución adecuada con una tasa baja de complicaciones y que permite disminuir la intensidad del soporte ventilatorio

Introduction. Percutaneous tracheostomy is an alternative to conventional surgical tracheostomy. It is associated to a more feasible procedure, that is less invasive and linked to a lower degree of complications. Herein, we review our experience since the implementation of this technique in our Department. Design. Retrospective observational. Setting. Nineteen-bed intensive care department, in a general reference teaching hospital. Patients and method. A total of 115 of 130 tracheostomies performed from 2001 to 2003 were retrospectively analyzed. Collected data include epidemiological information, reason for performing the procedure, maintenance time of artificial airway before the tracheostomy and type of ventilatory support or oxygen supplementation before and after the procedure. The modified PEEP (PEEP-mod = FiO2 x PEEP) was calculated, sedation level received before and 4-6 hours after the technique and also 24 hours later, were reviewed. Subsequent patient evolution was collected. Interventions. Observational study on the results of routine procedures. Variables of interest. Blood gases indicators of effectiveness in oxygen supply and the need of mechanical ventilation support. Results. Median age of the 115 reviewed patients was 65 years. The most common admission reasons were: brain vascular accident in 25 cases, head and neck injury in 21, cancer in 11 and sepsis in 10 patients. Tracheostomy was indicated because prolonged mechanical ventilation in 52 patients, coma in 28 and emergency or scheduled surgery in 10 cases. Median length of stay in the ICU before tracheostomy was 14 days. Ninety-two patients were discharged from the ICU, and 52 from the Hospital. The remaining patients died during their hospital stay. Serious complications appeared in 5 patients (4%); 3 of them were the development of fistulae and all of them occurred in patients in whom the tracheostomy was performed in the ICU at bedside. Before the procedure, 72 patients were under mechanical ventilation, but only 56 received ventilatory support 24 hours after tracheostomy. When PEEP-mod values were analyzed, first monitoring of median value was 1.6 (range 0 to 2), 4-6 hours time median value was 2 (1.4-2.45), and 24 hours later median value was 1.2 (0-2) (global variation, p < 0.001). Conclusions. In our experience, percutaneous tracheostomy performed at bedside in the ICU is an adequate solution with a low complication rate and its makes it possible to reduce the level of ventilatory support