RESUMEN
BACKGROUND: Pfeiffer syndrome is characterized by craniosynostosis, mid-face hypoplasia, broad thumbs, and often multilevel airway obstruction. Airway management is often required, including the use of positive airway ventilation, nasopharyngeal airway (NPA), or tracheostomy. OBJECTIVE: The objective of this study was to assess the impact an airway adjunct can have on feeding difficulties in children with Pfeiffer syndrome. METHODS: Retrospective review of patients diagnosed with Pfeiffer syndrome from January 1998 to January 2020 at one of England's 4 supraregional Craniofacial Units, Alder Hey Children's Hospital. Speech & Language Therapy case notes and medical notes were used to gather data, as well as the Oral Feeding Score component of the UK Craniofacial Outcome Score. RESULTS: Eleven patients were included. Six patients had no airway adjunct (55%): 3 had tracheostomy (27%) and 2 patients had NPA (18%). All patients with airway adjuncts were percutaneous endoscopic gastrostomy/percutaneous endoscopic jejunostomy fed. Those who did not require an airway adjunct had an Oral Feeding Score of 4.60 (SD: 0.49). The children who went on to have an airway adjunct had a mean preintervention Oral Feeding Score of 2.4 (SD: 0.8). The mean feeding score (postairway adjunct) in the NPA group was 2.0, compared with the tracheostomy group scoring 3.0. CONCLUSIONS: Children with Pfeiffer syndrome who require airway intervention have more significant feeding problems requiring feeding intervention. Although there were small numbers included in this study, there is a suggestion that airway adjuncts can contribute to feeding difficulties, particularly NPAs.
Asunto(s)
Acrocefalosindactilia , Obstrucción de las Vías Aéreas , Humanos , Niño , Lactante , Acrocefalosindactilia/cirugía , Manejo de la Vía Aérea , Obstrucción de las Vías Aéreas/cirugía , Nasofaringe , Traqueostomía , Estudios RetrospectivosRESUMEN
There is a large demand for online patient information for patients considering rhinoplasty. While there are many resources available, the quality and content of the information provided are unknown. This study aimed to assess the quality of the most popular information available online, using the "Ensuring Quality Information for Patients" (EQIP) tool to evaluate the content, structure, and readability of patient information on websites. Search terms including nose operation, nose job, nose reshaping, nose tip surgery, rhinoplasty, septorhinoplasty, were identified using Google AdWords and Trends. Unique links from the first 10 pages for each term were identified and evaluated with websites written in English and for general non-medical public use were included. 295 websites met the eligibility criteria with a median overall EQIP score of 17. Only 33% contained balanced information on the risks and benefits. Bleeding and infection risk was only mentioned in 29% and 27% of websites, respectively. Two percent described complication rates of the procedures and only 20% of articles explained further surgery may be required to achieve patient cosmetic or functional satisfaction. Information regarding rhinoplasty available online is currently of poor quality. The lack of effective risk counselling, possible outcome management, and complications may likely lead to unrealistic expectations of rhinoplasty. It is crucial the risks of surgery are communicated to the patient to ensure they can make an informed decision. Improved education through online resources would likely help to promote more realistic patient expectations.
Asunto(s)
Información de Salud al Consumidor , Rinoplastia , Humanos , Nariz , Comprensión , InternetRESUMEN
OBJECTIVES: To convey advice from families whose children recently underwent spinal fusion to families whose children are under consideration for initial spinal fusion for neuromuscular scoliosis and to providers who counsel families on this decision. STUDY DESIGN: We interviewed 18 families of children who underwent spinal fusion between August 2017 and January 2019 at a freestanding children's hospital. We conducted phone interviews a median of 65 (IQR 51-77) days after surgery. We audio recorded, transcribed, and coded (line-by-line) interviews using grounded theory by 2 independent reviewers, and discussed among investigators to induce themes associated with surgical decision making and preparation. RESULTS: Six themes emerged about decision making and preparation for spinal fusion: (1) simplify risks and benefits; it is easy to get lost in the details; (2) families prolonging the decision whether or not to pursue spinal fusion surgery may not benefit the child; (3) anticipate anxiety and fear when making a decision about spinal fusion; (4) realize that your child might experience a large amount of pain; (5) anticipate a long recovery and healing process after spinal fusion; and (6) be engaged and advocate for your child throughout the perioperative spinal fusion process. CONCLUSIONS: Parents of children who had recently undergone spinal fusion had strong perceptions about what information to convey to families considering surgery, which may improve communication between future parents and physicians. Further investigation is needed to assess how best to incorporate the wisdom and experiences of parent peers into shared decision making and preparation for spinal fusion in children with neuromuscular scoliosis.
Asunto(s)
Toma de Decisiones , Padres , Grupo Paritario , Escoliosis/cirugía , Fusión Vertebral/psicología , Adolescente , Ansiedad , Niño , Comunicación , Familia , Femenino , Teoría Fundamentada , Humanos , Masculino , Periodo Preoperatorio , Investigación Cualitativa , Riesgo , Apoyo SocialRESUMEN
Epithelial cells are largely immotile under normal circumstances, but become motile during development, repair of tissue damage and during cancer metastasis. Numerous growth factors act to initiate epithelial cell movements. Hepatocyte growth factor (HGF) induces many epithelial cell lines to begin crawling. A number of small GTPases act downstream of HGF to alter cell shape and promote movement. Arf6 is one of these GTPases that can alter the cortical actin cytoskeleton and promote epithelial movement. Activation of Arf6 in MDCK cells by its guanine nucleotide exchange factor cytohesin 2/ARNO produces a scattering response strikingly reminiscent of the action of HGF. We have previously shown that IPCEF1, a scaffold that binds to cytohesin 2, is required for cytohesin-induced scattering. We report here that IPCEF1 is actually the C-terminal half of CNK3. CNKs are scaffolds involved in signal transduction downstream of Ras. We have found that both MDCK and CaCo-2 cells express a fused CNK3/IPCEF1 protein. Knockdown of this protein impairs HGF-induced Arf6 activation and migration in response to HGF treatment.
Asunto(s)
Factores de Ribosilacion-ADP/metabolismo , Proteínas Portadoras/fisiología , Movimiento Celular/genética , Factor de Crecimiento de Hepatocito/farmacología , Proteínas de la Membrana/fisiología , Factor 6 de Ribosilación del ADP , Factores de Ribosilacion-ADP/genética , Animales , Células CACO-2 , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Células Cultivadas , Perros , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Datos de Secuencia Molecular , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/fisiología , Estructura Terciaria de Proteína/genética , Estructura Terciaria de Proteína/fisiología , ARN Interferente Pequeño/farmacología , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/fisiologíaRESUMEN
The Specialised Foundation Programme (SFP), formerly the Academic Foundation Programme, is a highly competitive pathway into academic medicine. There is minimal information available on the demographics of those who apply to the programme, how it scores its applicants and who is successful, making it difficult to assess whether the application process is accessible to all students and promotes a diverse workforce. There are varying levels of support available with coaching, either geographically ring-fenced by universities or available through paid courses. As a result, there is a risk of differential attainment between students who have financial constraints or attend universities where the SFP is less promoted. The aim of the study was to assess student opinion on barriers to the SFP and academic medicine and the demand for the creation of a national, free-to-access SFP mentorship programme to reduce differential attainment amongst student cohorts. Students in the programme received mentorship, peer learning and scheduled teaching events over a six-month period. Surveys were distributed pre- and post-course, and qualitative and quantitative analysis was conducted. Of the respondents, 76% felt that medical schools provided insufficient information on SFP, 31% did not feel financially stable at university and 53% stated that they would not enrol if a cost was present. Applicants were tested on pre- and post-course confidence, all of which showed an increase in mean Likert (1-5) scoring post-mentorship. Financial, institutional and geographical barriers to students applying to the programme were identified. Whilst further research is required to better understand the barriers to academic medicine, national, free-to-access mentorship may effectively reduce differential attainment and improve accessibility amongst students.
RESUMEN
Background: Traditional approaches for surgical site infection (SSI) surveillance have deficiencies that delay detection of SSI outbreaks and other clinically important increases in SSI rates. We investigated whether use of optimised statistical process control (SPC) methods and feedback for SSI surveillance would decrease rates of SSI in a network of US community hospitals. Methods: We conducted a stepped wedge cluster randomised trial of patients who underwent any of 13 types of common surgical procedures across 29 community hospitals in the Southeastern United States. We divided the 13 procedures into six clusters; a cluster of procedures at a single hospital was the unit of randomisation and analysis. In total, 105 clusters were randomised to 12 groups of 8-10 clusters. All participating clusters began the trial in a 12-month baseline period of control or "traditional" SSI surveillance, including prospective analysis of SSI rates and consultative support for SSI outbreaks and investigations. Thereafter, a group of clusters transitioned from control to intervention surveillance every three months until all clusters received the intervention. Electronic randomisation by the study statistician determined the sequence by which clusters crossed over from control to intervention surveillance. The intervention was the addition of weekly application of optimised SPC methods and feedback to existing traditional SSI surveillance methods. Epidemiologists were blinded to hospital identity and randomisation status while adjudicating SPC signals of increased SSI rates, but blinding was not possible during SSI investigations. The primary outcome was the overall SSI prevalence rate (PR=SSIs/100 procedures), evaluated via generalised estimating equations with a Poisson regression model. Secondary outcomes compared traditional and optimised SPC signals that identified SSI rate increases, including the number of formal SSI investigations generated and deficiencies identified in best practices for SSI prevention. This trial was registered at ClinicalTrials.gov, NCT03075813. Findings: Between Mar 1, 2016, and Feb 29, 2020, 204,233 unique patients underwent 237,704 surgical procedures. 148,365 procedures received traditional SSI surveillance and feedback alone, and 89,339 procedures additionally received the intervention of optimised SPC surveillance. The primary outcome of SSI was assessed for all procedures performed within participating clusters. SSIs occurred after 1171 procedures assigned control surveillance (prevalence rate [PR] 0.79 per 100 procedures), compared to 781 procedures that received the intervention (PR 0·87 per 100 procedures; model-based PR ratio 1.10, 95% CI 0.94-1.30, p=0.25). Traditional surveillance generated 24 formal SSI investigations that identified 120 SSIs with deficiencies in two or more perioperative best practices for SSI prevention. In comparison, optimised SPC surveillance generated 74 formal investigations that identified 458 SSIs with multiple best practice deficiencies. Interpretation: The addition of optimised SPC methods and feedback to traditional methods for SSI surveillance led to greater detection of important SSI rate increases and best practice deficiencies but did not decrease SSI rates. Additional research is needed to determine how to best utilise SPC methods and feedback to improve adherence to SSI quality measures and prevent SSIs. Funding: Agency for Healthcare Research and Quality.
RESUMEN
Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid in a 46-year-old woman.
Asunto(s)
Carcinoma Mucoepidermoide , Eosinofilia , Neoplasias de la Tiroides , Carcinoma Mucoepidermoide/complicaciones , Carcinoma Mucoepidermoide/diagnóstico por imagen , Carcinoma Mucoepidermoide/cirugía , Eosinofilia/complicaciones , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/cirugíaRESUMEN
Background Opportunities for new otolaryngology trainees to develop their skills as they embark on specialty training can be limited. Our facility hosted a national simulation-based boot camp for new otolaryngology trainees in the UK. This study aimed to assess the effectiveness of the boot camp in improving trainee confidence as they transitioned from core surgical training (CST) to higher specialty training (HST) in otolaryngology. Methodology We conducted a prospective study on the effectiveness of the boot camp on trainee induction. The boot camp included hands-on simulation, small group teaching and didactic lectures addressing technical skills in the fields of otology, laryngology, rhinology, facial plastics, and paediatrics, as well as non-technical skills involving human factors, simulated ward round, and cognitive simulation. The boot camp curriculum reflected the competencies expected by the Joint Committee of Surgical Training (JCST) at this level of training. Participants completed a pre- and post-course questionnaire addressing their self-confidence for the technical and non-technical skills they developed during the boot camp. All participants were invited to participate in an interview 12 months after the boot camp. Results A total of 27 new otolaryngology trainees (approximately half of all new otolaryngology trainees in the UK) participated in the boot camp. A significant increase in median confidence was observed for all technical and non-technical stations (p < 0.0001). The increase in confidence observed was similar for participants regardless of prior experience in otolaryngology. Five candidates were interviewed a year after the boot camp. Analysis of the transcripts generated distinct comments that were grouped into five key themes. Conclusions A simulation-based boot camp mapped to the JCST curriculum can increase the confidence of new otolaryngology Specialty Training 3 trainees during their transition from CST to HST. It can provide valuable and durable technical and non-technical skills to aid trainees in the clinic, theatre environment, and when on-call during their inaugural year of training.
RESUMEN
BACKGROUND: Virtual Patient Journey (VPJ) is a novel online resource that follows a patient through their illness and integrates first-person video content with in-video decision making, allowing the student to take on the responsibility of a health care professional. The aim of our project was to compare this new VPJ format with standard teaching tutorials. METHODS: Third-year medical students selected from two Bristol hospitals were allocated to either the VPJ format or a typical tutorial-style teaching session. Both formats covered an identical level and scope of material and lasted the same length of time. Data were collected on pre- and post-test knowledge and confidence gain using self-reported questionnaires at the time of the teaching. RESULTS: The study recruited 30 students. The average knowledge gain for the VPJ group and for the tutorial group was 39% and 35%, respectively. The confidence increase was 2.4 and 1.8 on a scale of 1-10 for the VPJ and tutorial groups, respectively. Of the students who used the VPJ, 92% believed that it was a useful teaching resource and 96% enjoyed the VPJ experience and would re-watch the material at home. CONCLUSIONS: VPJ can expose students to clinical situations that they may not see on placement and can help to deliver a baseline level of clinical exposure and knowledge. Our VPJ may help overcome the rigidity of current virtual patients in teaching a range of core competencies and also allowing the students to take responsibility for a patient's care in a safe, controlled environment.
Asunto(s)
Aprendizaje , Estudiantes de Medicina , Personal de Salud , HumanosRESUMEN
OBJECTIVE: Surgical site infections (SSIs) are common costly hospital-acquired conditions. While statistical process control (SPC) use in healthcare has increased, limited rigorous empirical research compares and optimises these methods for SSI surveillance. We sought to determine which SPC chart types and design parameters maximise the detection of clinically relevant SSI rate increases while minimising false alarms. DESIGN: Systematic retrospective data analysis and empirical optimisation. METHODS: We analysed 12 years of data on 13 surgical procedures from a network of 58 community hospitals. Statistically significant SSI rate increases (signals) at individual hospitals initially were identified using 50 different SPC chart variations (Shewhart or exponentially weighted moving average, 5 baseline periods, 5 baseline types). Blinded epidemiologists evaluated the clinical significance of 2709 representative signals of potential outbreaks (out of 5536 generated), rating them as requiring 'action' or 'no action'. These ratings were used to identify which SPC approaches maximised sensitivity and specificity within a broader set of 3600 individual chart variations (additional baseline variations and chart types, including moving average (MA), and five control limit widths) and over 32 million dual-chart combinations based on different baseline periods, reference data (network-wide vs local hospital SSI rates), control limit widths and other calculation considerations. Results were validated with an additional year of data from the same hospital cohort. RESULTS: The optimal SPC approach to detect clinically important SSI rate increases used two simultaneous MA charts calculated using lagged rolling baseline windows and 1 SD limits. The first chart used 12-month MAs with 18-month baselines and best identified small sustained increases above network-wide SSI rates. The second chart used 6-month MAs with 3-month baselines and best detected large short-term increases above individual hospital SSI rates. This combination outperformed more commonly used charts, with high sensitivity (0.90; positive predictive value=0.56) and practical specificity (0.67; negative predictive value=0.94). CONCLUSIONS: An optimised combination of two MA charts had the best performance for identifying clinically relevant small but sustained above-network SSI rates and large short-term individual hospital increases.
Asunto(s)
Auditoría Clínica/métodos , Infección de la Herida Quirúrgica/epidemiología , Hospitales Comunitarios , Humanos , Vigilancia en Salud Pública , Análisis de Regresión , Estudios RetrospectivosRESUMEN
The aim of this study is to assess the impact of preoperative comanagement with complex care pediatricians (CCP) on children with neuromuscular scoliosis undergoing spinal fusion. We performed chart review of 79 children aged 5-21 years undergoing spinal fusion 1/2014-6/2016 at a children's hospital, with abstraction of clinical documentation from preoperative health evaluations performed regularly by anesthesiologists and irregularly by a CCP. Preoperative referrals to specialists, labs, tests, and care plans needed last minute for surgical clearance were measured. The mean age at surgery was 14 (SD 3) years; cerebral palsy (64%) was the most common neuromuscular condition. Thirty-nine children (49%) had a preoperative CCP evaluation a median 63 days (interquartile range (IQR) 33-156) before the preanesthesia visit. Children with CCP evaluation had more organ systems affected by coexisting conditions than children without an evaluation (median 11 (IQR 9-12) vs. 8 (IQR 5-11); p < .001). The rate of last-minute care coordination activities required for surgical clearance was lower for children with versus without CCP evaluation (1.8 vs. 3.6). A lower percentage of children with CCP evaluation required last-minute development of new preoperative plans (26% vs. 50%, p = .002). Children with CCP involvement were better prepared for surgery, requiring fewer last-minute care coordination activities for surgical clearance.
Asunto(s)
Comorbilidad , Cuidados Preoperatorios , Escoliosis , Fusión Vertebral/enfermería , Adolescente , Parálisis Cerebral/complicaciones , Femenino , Hospitales Pediátricos , Humanos , Tiempo de Internación , Masculino , Estudios Retrospectivos , Escoliosis/complicaciones , Escoliosis/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Projecting postoperative recovery in pediatric surgical patients is challenging. We assessed how the patients' number of complex chronic conditions (CCCs) and chronic medications interacted with active health issues to influence the likelihood of postoperative physiologic decline (PoPD). METHODS: A prospective study of 3295 patients undergoing elective surgery at a freestanding children's hospital. During preoperative clinical evaluation, active health problems, CCCs, and medications were documented. PoPD (compromise of cardiovascular, respiratory, and/or neurologic systems) was measured prospectively every 4 hours by inpatient nurses. PoPD odds were estimated with multivariable logistic regression. Classification and regression tree analysis distinguished children with the highest and lowest likelihood of PoPD. RESULTS: Median age at surgery was 8 years (interquartile range: 2-15); 2336 (70.9%) patients had a CCC; and 241 (7.3%) used ≥11 home medications. During preoperative evaluation, 1556 (47.2%) patients had ≥1 active health problem. After surgery, 882 (26.8%) experienced PoPD. The adjusted odds of PoPD were 1.2 (95% confidence interval [CI]: 1.0-1.4) for presence versus absence of an active health problem; 1.4 (95% CI: 1.0-1.9) for ≥11 vs 0 home medications; and 2.2 (95% CI: 1.7-2.9) for ≥3 vs 0 CCCs. In classification and regression tree analysis, the lowest rate of PoPD (8.6%) occurred in children without an active health problem at the preoperative evaluation; the highest rate (57.2%) occurred in children with a CCC who used ≥11 home medications. CONCLUSIONS: Greater than 1 in 4 pediatric patients undergoing elective surgery experienced PoPD. Combinations of active health problems at preoperative evaluation, polypharmacy, and multimorbidity distinguished patients with a low versus high risk of PoPD.
Asunto(s)
Salud Infantil , Procedimientos Quirúrgicos Electivos/efectos adversos , Cuidados Posoperatorios/métodos , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Hospitales Pediátricos , Humanos , Modelos Logísticos , Masculino , Monitoreo Fisiológico/métodos , Análisis Multivariante , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores SexualesRESUMEN
BACKGROUND: Traditional strategies for surveillance of surgical site infections (SSI) have multiple limitations, including delayed and incomplete outbreak detection. Statistical process control (SPC) methods address these deficiencies by combining longitudinal analysis with graphical presentation of data. METHODS: We performed a pilot study within a large network of community hospitals to evaluate performance of SPC methods for detecting SSI outbreaks. We applied conventional Shewhart and exponentially weighted moving average (EWMA) SPC charts to 10 previously investigated SSI outbreaks that occurred from 2003 to 2013. We compared the results of SPC surveillance to the results of traditional SSI surveillance methods. Then, we analysed the performance of modified SPC charts constructed with different outbreak detection rules, EWMA smoothing factors and baseline SSI rate calculations. RESULTS: Conventional Shewhart and EWMA SPC charts both detected 8 of the 10 SSI outbreaks analysed, in each case prior to the date of traditional detection. Among detected outbreaks, conventional Shewhart chart detection occurred a median of 12 months prior to outbreak onset and 22 months prior to traditional detection. Conventional EWMA chart detection occurred a median of 7months prior to outbreak onset and 14 months prior to traditional detection. Modified Shewhart and EWMA charts additionally detected several outbreaks earlier than conventional SPC charts. Shewhart and SPC charts had low false-positive rates when used to analyse separate control hospital SSI data. CONCLUSIONS: Our findings illustrate the potential usefulness and feasibility of real-time SPC surveillance of SSI to rapidly identify outbreaks and improve patient safety. Further study is needed to optimise SPC chart selection and calculation, statistical outbreak detection rules and the process for reacting to signals of potential outbreaks.
Asunto(s)
Infección Hospitalaria/epidemiología , Vigilancia en Salud Pública/métodos , Infección de la Herida Quirúrgica/epidemiología , Bases de Datos Factuales , Brotes de Enfermedades/estadística & datos numéricos , Monitoreo Epidemiológico , Hospitales Comunitarios , Humanos , Control de Infecciones , Proyectos Piloto , Estudios Retrospectivos , Sudeste de Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To systematically identify and summarise the literature on perceived life expectancy among individuals with non-cancer chronic disease. SETTING: Published and grey literature up to and including September 2016 where adults with non-cancer chronic disease were asked to estimate their own life expectancy. PARTICIPANTS: From 6837 screened titles, 9 articles were identified that met prespecified criteria for inclusion. Studies came from the UK, Netherlands and USA. A total of 729 participants were included (heart failure (HF) 573; chronic obstructive pulmonary disease (COPD) 89; end-stage renal failure 62; chronic kidney disease (CKD) 5). No papers reporting on other lung diseases, neurodegenerative disease or cirrhosis were found. PRIMARY AND SECONDARY OUTCOME MEASURES: All measures of self-estimated life expectancy were accepted. Self-estimated life expectancy was compared, where available, with observed survival, physician-estimated life expectancy and model-estimated life expectancy. Meta-analysis was not conducted due to the heterogeneity of the patient groups and study methodologies. RESULTS: Among patients with HF, median self-estimated life expectancy was 40% longer than predicted by a validated model. Outpatients receiving haemodialysis were more optimistic about prognosis than their nephrologists and overestimated their chances of surviving 5â years. Patients with HF and COPD were approximately three times more likely to die in the next year than they predicted. Data available for patients with CKD were of insufficient quality to draw conclusions. CONCLUSIONS: Individuals with chronic disease may have unrealistically optimistic expectations of their prognosis. More research is needed to understand how perceived life expectancy affects behaviour. Meanwhile, clinicians should attempt to identify each patient's prognostic preferences and provide information in a way that they can understand and use to inform their decisions. TRIAL REGISTRATION NUMBER: CRD42015020732.
Asunto(s)
Enfermedad Crónica , Conocimientos, Actitudes y Práctica en Salud , Insuficiencia Cardíaca , Fallo Renal Crónico , Esperanza de Vida , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Crónica/mortalidad , Insuficiencia Cardíaca/mortalidad , Humanos , Fallo Renal Crónico/mortalidad , Países Bajos , Optimismo , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Diálisis Renal , Reino Unido , Estados UnidosRESUMEN
When expressed in epithelial cells, cytohesin-2/ARNO, a guanine nucleotide exchange factor (GEF) for ARF small GTPases, causes a robust migration response. Recent evidence suggests that cytohesin-2/ARNO acts downstream of small the GTPase R-Ras to promote spreading and migration. We hypothesized that cytohesin-2/ARNO could transmit R-Ras signals by regulating the recycling of R-Ras through ARF activation. We found that Eps15-homology domain 1 (EHD1), a protein that associates with the endocytic recycling compartment (ERC), colocalizes with active R-Ras in transiently expressed HeLa cells. In addition, we show that EHD1-positive recycling endosomes are a novel compartment for cytohesin-2/ARNO. Knockdown or expression of GEF-inactive (E156K) cytohesin-2/ARNO causes R-Ras to accumulate on recycling endosomes containing EHD1 and inhibits cell spreading. E156K-ARNO also causes a reduction in focal adhesion size and number. Finally, we demonstrate that R-Ras/ARNO signaling is required for recycling of α5-integrin and R-Ras to the plasma membrane. These data establish a role for cytohesin-2/ARNO as a regulator of R-Ras and integrin recycling and suggest that ARF-regulated trafficking of R-Ras is required for R-Ras-dependent effects on spreading and adhesion formation.