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INTRODUCTION: Enhanced recovery after surgery (ERAS) programmes which advocate early mobility after surgery have improved immediate clinical outcomes for patients undergoing abdominal cancer resections with curative intent. However, the impact of continued physical activity on patient-related outcomes and functional recovery is not well defined. The aim of this review was to assess the impact of postoperative aerobic exercise training, either alone or in conjunction with another exercise modality, on patients who have had surgery for intra-abdominal cancer. METHODS: A literature search was performed of electronic journal databases. Eligible papers needed to report an outcome of aerobic capacity in patients older than 18 years of age, who underwent cancer surgery with curative intent and participated in an exercise programme (not solely ERAS) that included an aerobic exercise component starting at any point in the postoperative pathway up to 12 weeks. RESULTS: Eleven studies were deemed eligible for inclusion consisting of two inpatient, one mixed inpatient/outpatient and eight outpatient studies. Meta-analysis of four outpatient studies, each reporting change in 6-min walk test (6MWT), showed a significant improvement in 6MWT with exercise (MD 74.92 m, 95% CI 48.52-101.31 m). The impact on health-related quality of life was variable across studies. CONCLUSION: Postoperative exercise confers benefits in improving aerobic function post surgery and can be safely delivered in various formats (home-based or group/supervised).
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Neoplasias , Calidad de Vida , Humanos , Lactante , Ejercicio Físico , Tolerancia al Ejercicio , Pacientes InternosRESUMEN
The distribution of impact craters on the ejecta of Giordano Bruno, a recent (<10 Ma) 22-km diameter crater within the lunar highlands, exhibits substantial variations. We surveyed craters D ≥ 10 m across a 1,323 km2 area of Giordano Bruno's ejecta and compared the distribution of craters with variations in thermophysical properties derived from the Lunar Reconnaissance Orbiter Diviner instrument. We used Diviner-derived rock abundance and nighttime regolith temperatures along with thermal model-predicted surface temperatures for a diversity of terrains to identify and isolate areas of the ejecta based on thermophysical properties such as bulk density and thermal conductivity. We found that thermophysical properties of the ejecta vary considerably both laterally and vertically, and consistently differ from typical regolith, indicating the presence of higher thermal inertia materials. Crater-size frequencies are significantly lower in areas with terrain properties exhibiting higher: rock abundance, nighttime temperatures, and/or modeled thermal inertia. This discrepancy in crater distribution increases for craters smaller than â¼25 m. These thermophysical variations indicate changes in the mechanical properties of the target materials. We suggest that these variations-specifically, terrain-dependent crater scaling variations and impactor-scale heterogeneities in material properties such as the presence or absence of large boulders-may influence crater diameters or inhibit crater production altogether in Giordano Bruno's ejecta; furthermore, these factors are size-dependent.
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Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a great demand for new therapies to improve survival and mitigate bleeding in H-ARS. Thrombopoiesis requires interactions between megakaryocytes (MKs) and endothelial cells. 16, 16-dimethyl prostaglandin E2 (dmPGE2), a longer-acting analogue of PGE2, promotes hematopoietic recovery after total-body irradiation (TBI), and various angiotensin-converting enzyme (ACE) inhibitors mitigate endothelial injury after radiation exposure. Here, we tested a combination therapy of dmPGE2 and lisinopril to mitigate thrombocytopenia in murine models of H-ARS following TBI. After 7.75 Gy TBI, dmPGE2 and lisinopril each increased survival relative to vehicle controls. Importantly, combined dmPGE2 and lisinopril therapy enhanced survival greater than either individual agent. Studies performed after 4 Gy TBI revealed reduced numbers of marrow MKs and circulating platelets. In addition, sublethal TBI induced abnormalities both in MK maturation and in in vitro and in vivo platelet function. dmPGE2, alone and in combination with lisinopril, improved recovery of marrow MKs and peripheral platelets. Finally, sublethal TBI transiently reduced the number of marrow Lin-CD45-CD31+Sca-1- sinusoidal endothelial cells, while combined dmPGE2 and lisinopril treatment, but not single-agent treatment, accelerated their recovery. Taken together, these data support the concept that combined dmPGE2 and lisinopril therapy improves thrombocytopenia and survival by promoting recovery of the MK lineage, as well as the MK niche, in the setting of H-ARS.
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16,16-Dimetilprostaglandina E2/uso terapéutico , Síndrome de Radiación Aguda/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Plaquetas/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Trastornos Hemorrágicos/tratamiento farmacológico , Lisinopril/uso terapéutico , Megacariocitos/efectos de los fármacos , Trombocitopenia/tratamiento farmacológico , Trombopoyesis/efectos de los fármacos , Síndrome de Radiación Aguda/complicaciones , Animales , Plaquetas/efectos de la radiación , Médula Ósea/efectos de los fármacos , Médula Ósea/efectos de la radiación , Proteína C-Reactiva/análisis , Radioisótopos de Cesio , Evaluación Preclínica de Medicamentos , Células Endoteliales/efectos de la radiación , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/efectos de la radiación , Femenino , Rayos gamma/efectos adversos , Trastornos Hemorrágicos/etiología , Megacariocitos/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Selectina-P/análisis , Agregación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de la radiación , Factor Plaquetario 4/análisis , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Traumatismos Experimentales por Radiación/etiología , Trombocitopenia/etiología , Trombopoyesis/efectos de la radiación , Irradiación Corporal Total , Factor de von Willebrand/análisisRESUMEN
BACKGROUND: To achieve completion of training in general surgery, trainees are required to demonstrate competency in common procedures performed at emergency laparotomy. The aim of this study was to describe the patterns of trainee-led emergency laparotomy operating and the association between postoperative outcomes. METHODS: Data on all patients who had an emergency laparotomy between December 2013 and November 2017 were extracted from the National Emergency Laparotomy Audit database. Patients were grouped by grade of operating surgeon: trainee (specialty registrar) or consultant (including post-Certificate of Completion of Training fellows). Trends in trainee operating by deanery, hospital size and time of day of surgery were investigated. Univariable and adjusted regression analyses were performed for the outcomes 90-day mortality and return to theatre, with analysis of patients in operative subgroups segmental colectomy, Hartmann's procedure, adhesiolysis and repair of perforated peptic ulcer disease. RESULTS: The study cohort included 87 367 patients. The 90-day mortality rate was 15·1 per cent in the consultant group compared with 11·0 per cent in the trainee group. There were no increased odds of death by 90 days or of return to theatre across any of the operative groups when the operation was performed with a trainee listed as the most senior surgeon in theatre. Trainees were more likely to operate independently in high-volume centres (highest- versus lowest-volume centres: odds ratio (OR) 2·11, 95 per cent c.i. 1·91 to 2·33) and at night (00.00 to 07.59 versus 08.00 to 11.59 hours; OR 3·20, 2·95 to 3·48). CONCLUSION: There is significant variation in trainee-led operating in emergency laparotomy by geographical area, hospital size and by time of day. However, this does not appear to influence mortality or return to theatre.
ANTECEDENTES: Para completar la formación en cirugía general, se requiere que los aspirantes demuestren solvencia en la práctica de los procedimientos comunes efectuados por laparotomía de urgencia. El objetivo de este estudio fue describir los esquemas de formación de los aspirantes en laparotomía de urgencia y su asociación con los resultados postoperatorios. MÉTODOS: Todos los pacientes a los que se realizó una laparotomía de urgencia entre diciembre del 2013 y noviembre del 2017 se obtuvieron a partir de la base de datos de la Auditoría Nacional de Laparotomía de Urgencia (National Emergency Laparotomy Audit, NELA). Los pacientes se agruparon según la experiencia del cirujano; cirujanos en periodo de formación (residentes, speciality registrar) o consultores (incluyendo los que habían completado la especialidad). Se investigaron las tendencias entre los residentes por universidad, tamaño del hospital y hora del día de la cirugía. Se realizaron análisis de regresión univariable y ajustados para la mortalidad a los 90 días y la reoperación, así como análisis de subgrupos para los procedimientos quirúrgicos de colectomía segmentaria, intervención de Hartmann, liberación de bridas y la sutura de una úlcera péptica perforada. RESULTADOS: La cohorte de estudio incluyó 87.367 pacientes. La mortalidad a los 90 días en el grupo de consultores fue del 15% en comparación con el 11% en el grupo de residentes. No hubo aumento del riesgo de mortalidad a los 90 días o de reoperación en ninguno de los subgrupos de las diferentes operaciones cuando la cirugía era efectuada por el residente considerado como el más senior en las listas de quirófano. Los residentes tenían más probabilidades de operar solos en centros de alto volumen (en comparación con centros de bajo volumen; razón de oportunidades, odds ratio (OR) 2,11, i.c. del 95% 1,91-2,33) o durante la noche (00:00-07:59 horas en comparación con 08:00-11:59; OR 3,20; i.c. del 95% 2,95-3,48). CONCLUSIÓN: Existen diferencias significativas en la formación que reciben los residentes en laparotomía de urgencia según el área geográfica, el tamaño del hospital y la hora del día. Sin embargo, estas diferencias no parecen afectar a la mortalidad ni a la tasa de reoperaciones.
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Urgencias Médicas , Internado y Residencia , Laparotomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Inglaterra , Femenino , Cirugía General/educación , Hospitales de Alto Volumen/estadística & datos numéricos , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Cuidados Nocturnos/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Gales , Adulto JovenRESUMEN
OBJECTIVES: To assess the efficacy of high-intensity interval training (HIIT) for improving cardiorespiratory fitness (CRF) in patients awaiting resection for urological malignancy within four weeks. SUBJECTS/PATIENTS AND METHODS: A randomised control trial of consecutive patients aged (>65 years) scheduled for major urological surgery in a large secondary referral centre in a UK hospital. The primary outcome is change in anaerobic threshold (VO2AT) following HIIT vs. standard care. RESULTS: Forty patients were recruited (mean age 72 years, male (39): female (1)) with 34 completing the protocol. Intention to treat analysis showed significant improvements in anaerobic threshold (VO2AT; mean difference (MD) 2.26 ml/kg/min (95% CI 1.25-3.26)) following HIIT. Blood pressure (BP) also significantly reduced in following: HIIT (SBP: -8.2 mmHg (95% CI -16.09 to -0.29) and DBP: -6.47 mmHg (95% CI -12.56 to -0.38)). No reportable adverse safety events occurred during HIIT and all participants achieved >85% predicted maximum heart rate during sessions, with protocol adherence of 84%. CONCLUSIONS: HIIT can improve CRF and cardiovascular health, representing clinically meaningful and achievable pre-operative improvements. Larger randomised trials are required to investigate the efficacy of prehabilitation HIIT upon different cancer types, post-operative complications, socio-economic impact and long-term survival.
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Capacidad Cardiovascular/fisiología , Entrenamiento de Intervalos de Alta Intensidad/métodos , Neoplasias Renales/cirugía , Ejercicio Preoperatorio/fisiología , Neoplasias de la Próstata/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Ejercicio Físico , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Aceptación de la Atención de Salud/estadística & datos numéricos , Seguridad del Paciente , Neoplasias de la Próstata/patología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Delay to theatre for patients with intra-abdominal sepsis is cited as a particular risk factor for death. Our aim was to evaluate the potential relationship between hourly delay from admission to surgery and post-operative mortality in patients with perforated peptic ulcer (PPU). METHODS: All patients entered in the National Emergency Laparotomy Audit who had an emergency laparotomy for PPU within 24 h of admission from December 2013 to November 2017 were included. Time to theatre from admission was modelled as a continuous variable in hours. Outcome was 90-day mortality. Logistic regression adjusting for confounding factors was performed. RESULTS: 3809 patients were included, and 90-day mortality rate was 10.61%. Median time to theatre was 7.5 h (IQR 5-11.6 h). The odds of death increased with time to operation once adjustment for confounding variables was performed (per hour after admission adjusted OR 1.04 95% CI 1.02-1.07). In patients who were physiologically shocked (N = 334), there was an increase of 6% in risk-adjusted odds of mortality for every hour Em Lap was delayed after admission (OR 1.06 95% CI 1.01-1.11). CONCLUSION: Hourly delay to theatre in patients with PPU is independently associated with risk of death by 90 days. Therefore, we suggest that surgical source control should occur as soon as possible after admission regardless of time of day.
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Laparotomía , Úlcera Péptica Perforada/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Urgencias Médicas , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Úlcera Péptica Perforada/mortalidad , Factores de Riesgo , Tiempo de TratamientoRESUMEN
BACKGROUND: Current evidence suggests that pelvic floor reconstruction following extralevator abdominoperineal excision of rectum (ELAPER) may reduce the risk of perineal herniation of intra-abdominal contents. Options for reconstruction include mesh and myocutaneous flaps, for which long-term follow-up data is lacking. The aim of this study was to evaluate the long-term outcomes of biological mesh (Surgisis®, Biodesign™) reconstruction following ELAPER. METHODS: A retrospective review of all patients having ELAPER in a single institution between 2008 and 2018 was perfomed. Clinic letters were scrutinised for wound complications and all available cross sectional imaging was reviewed to identify evidence of perineal herniation (defined as presence of intra-abdominal content below a line between the coccyx and the lower margin of the pubic symphysis on sagittal view). RESULTS: One hundred patients were identified (median age 66, IQR 59-72 years, 70% male). Median length of follow-up was 4.9 years (IQR 2.3-6.7 years). One, 2- and 5-year mortality rates were 3, 8 and 12%, respectively. Thirty three perineal wounds had not healed by 1 month, but no mesh was infected and no mesh needed to be removed. Only one patient developed a symptomatic perineal hernia requiring repair. On review of imaging a further 7 asymptomatic perineal hernias were detected. At 4 years the cumulative radiologically detected perineal hernia rate was 8%. CONCLUSIONS: This study demonstrates that pelvic floor reconstruction using biological mesh following ELAPER is both safe and effective as a long-term solution, with low major complication rates. Symptomatic perineal herniation is rare following mesh reconstruction, but may develop sub clinically and be detectable on cross-sectional imaging.
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Hernia Abdominal/prevención & control , Hernia Incisional/prevención & control , Diafragma Pélvico/cirugía , Procedimientos de Cirugía Plástica/métodos , Proctectomía/efectos adversos , Mallas Quirúrgicas , Anciano , Femenino , Hernia Abdominal/etiología , Humanos , Hernia Incisional/etiología , Masculino , Persona de Mediana Edad , Perineo/cirugía , Recto/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Approximately 30 000 emergency laparotomies are performed each year in England and Wales. Patients with pathology of the gastrointestinal tract requiring emergency laparotomy are managed by general surgeons with an elective special interest focused on either the upper or lower gastrointestinal tract. This study investigated the impact of special interest on mortality after emergency laparotomy. METHODS: Adult patients having emergency laparotomy with either colorectal or gastroduodenal pathology were identified from the National Emergency Laparotomy Audit database and grouped according to operative procedure. Outcomes included all-cause 30-day mortality, length of hospital stay and return to theatre. Logistic and Poisson regression were used to analyse the association between consultant special interest and the three outcomes. RESULTS: A total of 33 819 patients (28 546 colorectal, 5273 upper gastrointestinal (UGI)) were included. Patients who had colorectal procedures performed by a consultant without a special interest in colorectal surgery had an increased adjusted 30-day mortality risk (odds ratio (OR) 1·23, 95 per cent c.i. 1·13 to 1·33). Return to theatre also increased in this group (OR 1·13, 1·05 to 1·20). UGI procedures performed by non-UGI special interest surgeons carried an increased adjusted risk of 30-day mortality (OR 1·24, 1·02 to 1·53). The risk of return to theatre was not increased (OR 0·89, 0·70 to 1·12). CONCLUSION: Emergency laparotomy performed by a surgeon whose special interest is not in the area of the pathology carries an increased risk of death at 30 days. This finding potentially has significant implications for emergency service configuration, training and workforce provision, and should stimulate discussion among all stakeholders.
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Competencia Clínica/estadística & datos numéricos , Gastroenterología , Cirugía General , Laparotomía/mortalidad , Especialización , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Urgencias Médicas , Inglaterra/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Auditoría Médica , Persona de Mediana Edad , Oportunidad Relativa , Distribución de Poisson , Estudios Prospectivos , Factores de Riesgo , Gales/epidemiología , Adulto JovenRESUMEN
Demand for critical care among older patients is increasing in many countries. Assessment of frailty may inform discussions and decision making, but acute illness and reliance on proxies for history-taking pose particular challenges in patients who are critically ill. Our aim was to investigate the inter-rater reliability of the Clinical Frailty Scale for assessing frailty in patients admitted to critical care. We conducted a prospective, multi-centre study comparing assessments of frailty by staff from medical, nursing and physiotherapy backgrounds. Each assessment was made independently by two assessors after review of clinical notes and interview with an individual who maintained close contact with the patient. Frailty was defined as a Clinical Frailty Scale rating > 4. We made 202 assessments in 101 patients (median (IQR [range]) age 69 (65-75 [60-80]) years, median (IQR [range]) Acute Physiology and Chronic Health Evaluation II score 19 (15-23 [7-33])). Fifty-two (51%) of the included patients were able to participate in the interview; 35 patients (35%) were considered frail. Linear weighted kappa was 0.74 (95%CI 0.67-0.80) indicating a good level of agreement between assessors. However, frailty rating differed by at least one category in 47 (47%) cases. Factors independently associated with higher frailty ratings were: female sex; higher Acute Physiology and Chronic Health Evaluation II score; higher category of pre-hospital dependence; and the assessor having a medical background. We identified a good level of agreement in frailty assessment using the Clinical Frailty Scale, supporting its use in clinical care, but identified factors independently associated with higher ratings which could indicate personal bias.
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Cuidados Críticos/métodos , Fragilidad/diagnóstico , Evaluación Geriátrica/métodos , Anciano , Anciano de 80 o más Años , Enfermedad Crítica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Escocia , Índice de Severidad de la Enfermedad , GalesRESUMEN
BACKGROUND: Radiologically defined sarcopenia has been shown to predict negative outcomes after cancer surgery, however radiological assessment of sarcopenia often requires additional software and standardisation against anthropomorphic data. Measuring psoas density using hospital Picture Archiving and Communication Systems (PACS), universally available in the UK, may have advantages over methods requiring the use of additional specialist and often costly software. The aim of this study was to assess the association between radiologically defined sarcopenia measured by psoas density and postoperative outcome in patients having a colorectal cancer resection. METHODS: All patients having a resection for colorectal cancer, discussed by the colorectal multi-disciplinary team in one institution between 1/1/15 and 31/12/15, were retrospectively identified. Mean psoas density at the level of the L3 vertebra was analysed from preoperative computed tomography (CT) scans to define sarcopenia using the Picture Archiving and Communication Systems (PACS). Postoperative complications and mortality were recorded. RESULTS: One hundred and sixty-nine patients had a colorectal resection for cancer and 140 of these had a primary anastomosis. Ninety-day mortality and 1-year mortality were 1.1% and 7.1%, respectively. Eighteen (10.7%) patients suffered a Clavien-Dindo grade 3 or 4 complication of which 6 (33%) were anastomotic leaks. In the whole cohort, sarcopenia was associated with an increased risk of Clavien-Dindo grade 3 or 4 complications [adjusted OR 6.33 (1.65-24.23) p = 0.007]. In those who had an anastomosis, sarcopenia was associated with an increased risk of anastomotic leak [adjusted OR 14.37 (1.37-150.04) p = 0.026]. CONCLUSIONS: A quick and easy radiological assessment of sarcopenia by measuring psoas density on preoperative CT scan using software universally available in the UK is highly predictive of postoperative morbidity in colorectal cancer patients.
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Fuga Anastomótica/mortalidad , Colectomía/efectos adversos , Neoplasias Colorrectales/diagnóstico por imagen , Complicaciones Posoperatorias/mortalidad , Proctectomía/efectos adversos , Músculos Psoas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/etiología , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Músculos Psoas/patología , Estudios Retrospectivos , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiología , Sarcopenia/cirugíaRESUMEN
PURPOSE: Cardiovascular disease (CVD) is the leading cause of death worldwide. Many risk factors for CVD can be modified pharmacologically; however, uptake of medications is low, especially in asymptomatic people. Exercise is also effective at reducing CVD risk, but adoption is poor with time-commitment and cost cited as key reasons for this. Repeated remote ischaemic preconditioning (RIPC) and isometric handgrip (IHG) training are both inexpensive, time-efficient interventions which have shown some promise in reducing blood pressure (BP) and improving markers of cardiovascular health and fitness. However, few studies have investigated the effectiveness of these interventions in premenopausal women. METHOD: Thirty healthy females were recruited to twelve supervised sessions of either RIPC or IHG over 4 weeks, or acted as non-intervention controls (CON). BP measurements, flow-mediated dilatation (FMD) and cardiopulmonary exercise tests (CPET) were performed at baseline and after the intervention period. RESULTS: IHG and RIPC were both well-tolerated with 100% adherence to all sessions. A statistically significant reduction in both systolic (- 7.2 mmHg) and diastolic (- 6 mmHg) BP was demonstrated following IHG, with no change following RIPC. No statistically significant improvements were observed in FMD or CPET parameters in any group. CONCLUSIONS: IHG is an inexpensive and well-tolerated intervention which may improve BP; a key risk factor for CVD. Conversely, our single arm RIPC protocol, despite being similarly well-tolerated, did not elicit improvements in any cardiorespiratory parameters in our chosen population.
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Capacidad Cardiovascular/fisiología , Enfermedades Cardiovasculares/terapia , Ejercicio Físico/fisiología , Contracción Isométrica/fisiología , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/fisiopatología , Endotelio Vascular/fisiología , Femenino , Fuerza de la Mano/fisiología , Humanos , Hipertensión/fisiopatología , Persona de Mediana Edad , Vasodilatación/fisiologíaAsunto(s)
Morfina , Pregabalina , Dolor Agudo , Analgésicos Opioides , Humanos , Dolor PostoperatorioRESUMEN
BACKGROUND & AIMS: ß-hydroxy-ß-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) - differences in plasma bioavailability have been reported. We previously reported that â¼3 g oral FA-HMB increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB). The objective of the present study was to quantify muscle protein metabolism responses to oral Ca-HMB. METHODS: Eight healthy young males received a primed constant infusion of 1,2 13C2 leucine and 2H5 phenylalanine to assess MPS (by tracer incorporation in myofibrils) and MPB (via arterio-venous (A-V) dilution) at baseline and following provision of â¼3 g of Ca-HMB; muscle anabolic (MPS) and catabolic (MPB) signalling was assessed via immunoblotting. RESULTS: Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 µM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < 0001) and suppressions in MPB (PA: 7.6 ± 1.2 µmol Phe per leg min-1, Ca-HMB: 5.2 ± 0.8 µmol Phe per leg min-1, p < 0.01). Increases in the phosphorylation of mTORc1 substrates i.e. p70S6K1 and RPS6 were also observed, with no changes detected in the MPB targets measured. CONCLUSIONS: These findings support the pro-anabolic properties of HMB via mTORc1, and show that despite proposed differences in bioavailability, Ca-HMB provides a comparable stimulation to MPS and suppression of MPB, to FA-HMB, further supporting its use as a pharmaconutrient in the modulation of muscle mass.
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Calcio/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Valeratos/metabolismo , Adulto , Disponibilidad Biológica , Calcio/farmacocinética , Señalización del Calcio , Suplementos Dietéticos , Humanos , Masculino , Proteínas Musculares/química , Músculo Esquelético/química , Valeratos/farmacocinética , Adulto JovenRESUMEN
INTRODUCTION: Simulation-based training (SBT) has become an increasingly important method by which doctors learn. Stress has an impact upon learning, performance, technical, and non-technical skills. However, there are currently no studies that compare stress in the clinical and simulated environment. We aimed to compare objective (heart rate variability, HRV) and subjective (state trait anxiety inventory, STAI) measures of stress theatre with a simulated environment. METHODS: HRV recordings were obtained from eight anesthetic trainees performing an uncomplicated rapid sequence induction at pre-determined procedural steps using a wireless Polar RS800CX monitor © in an emergency theatre setting. This was repeated in the simulated environment. Participants completed an STAI before and after the procedure. RESULTS: Eight trainees completed the study. The theatre environment caused an increase in objective stress vs baseline (p = .004). There was no significant difference between average objective stress levels across all time points (p = .20) between environments. However, there was a significant interaction between the variables of objective stress and environment (p = .045). There was no significant difference in subjective stress (p = .27) between environments. DISCUSSION: Simulation was unable to accurately replicate the stress of the technical procedure. This is the first study that compares the stress during SBT with the theatre environment and has implications for the assessment of simulated environments for use in examinations, rating of technical and non-technical skills, and stress management training.
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Simulación por Computador , Educación de Postgrado en Medicina/métodos , Estrés Psicológico/epidemiología , Estudiantes de Medicina/psicología , Anestesia/métodos , Competencia Clínica , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Estrés Psicológico/fisiopatologíaRESUMEN
Neurofibromatosis type 1 (NF1) is an inherited disease in which affected patients are predisposed to develop benign Schwann cell (SC) tumours called neurofibromas. In the mouse, loss of Nf1 in the SC lineage causes neurofibroma formation. The tyrosine kinase receptor EGFR is expressed in Schwann cell precursors (SCP), which have been implicated in plexiform neurofibroma initiation. To test if EGFR activity affects neurofibroma initiation, size, and/or number, we studied mice expressing human EGFR in SCs and SCP in the context of mice that form neurofibromas. Neurofibroma number increased in homozygous CNP-hEGFR mice versus heterozygous littermates, and neurofibroma number and size increased when CNP-hEGFR was crossed to Nf1fl/fl;DhhCre mice. Conversely, diminished EGFR signalling in Nf1fl/fl;DhhCre;Wa2/+ mice decreased neurofibroma number. In vivo transplantation verified the correlation between EGFR activity and neurofibroma formation. Mechanistically, expression of CNP-hEGFR increased SCP/neurofibroma-initiating cell self-renewal, a surrogate for tumour initiation, and activated P-Stat3. Further, Il-6 reinforced Jak2/Stat3 activation in SCPs and SCs. These gain- and loss-of function assays show that levels of tyrosine kinase expression in SCPs modify neurofibroma initiation.
Asunto(s)
Transformación Celular Neoplásica/metabolismo , Receptores ErbB/metabolismo , Neurofibroma/metabolismo , Neuroglía/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Receptores ErbB/genética , Femenino , Homocigoto , Humanos , Interleucina-6/metabolismo , Janus Quinasa 2/metabolismo , Masculino , Ratones , Ratones Transgénicos , Mutación , Neurofibroma/mortalidad , Neurofibroma/patología , Neurofibromina 1/genética , Neuroglía/patología , Carga TumoralRESUMEN
BACKGROUND: The aims of this study were to determine if patient ASA grade was associated with increased stress in anaesthetists with a subsequent effect on non-technical skills. METHODS: Stress was measured using a validated objective (heart rate variability or heart rate) and subjective tool. We studied eight consultant anaesthetists at baseline (rest) and during 16 episodes of intubation with an ASA 1 or 2 patient vs. an ASA 3 or 4 patient. The primary outcome for the study was objective and subjective stress between both patient groups. Secondary outcomes were non-technical skill ratings and the association between stress measurements. RESULTS: ASA 3 or 4 patients were associated with increases in objective stress when compared to baseline (mean 4.6 vs. 6.7; P = 0.004). However, ASA 1 or 2 patients were not associated with increases in stress when compared to baseline (mean 4.6 vs. 4.7; P = 1). There was no significant difference in subjective stress between the groups (P = 0.18). Objective stress negatively affected situational awareness (P = 0.03) and decision-making (P = 0.03); however, these did not decline to a clinically significant threshold. Heart rate variability (r = 0.60; P = 0.002) better correlated with subjective stress when compared to heart rate (r = 0.30; P = 0.15). Agreement between raters for Anaesthetic Non-Technical Skills (ANTS) scores was acceptable (ICC = 0.51; P = 0.003). CONCLUSION: This study suggests that higher patient ASA grade can increase stress in anaesthetists, which may impair non-technical skills.