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1.
Nat Commun ; 13(1): 5998, 2022 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-36220817

RESUMEN

Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.


Asunto(s)
Células Endoteliales , Nanopartículas , Aminas , Anticuerpos , Sistemas de Liberación de Medicamentos , Humanos , Nanomedicina , Oligonucleótidos
2.
Br J Surg ; 108(9): 1072-1081, 2021 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-33963377

RESUMEN

BACKGROUND: Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation. Oxidative damage to mitochondria is an early event in IR injury. Therefore, the uptake, safety, and efficacy of the mitochondria-targeted antioxidant MitoQ were investigated in models of transplant IR injury. METHODS: MitoQ uptake by warm and cooled pairs of pig and declined human kidneys was measured when preserved in cold static storage or by hypothermic machine perfusion. Pairs of pigs' kidneys were exposed to defined periods of warm and cold ischaemia, flushed and stored at 4°C with or without MitoQ (50 nmol/l to 250 µmol/l), followed by reperfusion with oxygenated autologous blood in an ex vivo normothermic perfusion (EVNP). Pairs of declined human kidneys were flushed and stored with or without MitoQ (5-100 µmol/l) at 4°C for 6 h and underwent EVNP with ABO group-matched blood. RESULTS: Stable and concentration-dependent uptake of MitoQ was demonstrated for up to 24 h in pig and human kidneys. Total blood flow and urine output were significantly greater in pig kidneys treated with 50 µmol/l MitoQ compared with controls (P = 0.006 and P = 0.007 respectively). In proof-of-concept experiments, blood flow after 1 h of EVNP was significantly greater in human kidneys treated with 50 µmol/l MitoQ than in controls (P ≤ 0.001). Total urine output was numerically higher in the 50-µmol/l MitoQ group compared with the control, but the difference did not reach statistical significance (P = 0.054). CONCLUSION: Mitochondria-targeted antioxidant MitoQ can be administered to ischaemic kidneys simply and effectively during cold storage, and may improve outcomes after transplantation.


Asunto(s)
Trasplante de Riñón/efectos adversos , Riñón/irrigación sanguínea , Preservación de Órganos/métodos , Compuestos Organofosforados/farmacología , Daño por Reperfusión/terapia , Ubiquinona/análogos & derivados , Animales , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Humanos , Porcinos , Ubiquinona/farmacología
3.
BJS Open ; 5(2)2021 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-33839750

RESUMEN

BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5-3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer's solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5-3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions.


Asunto(s)
Intestino Delgado/irrigación sanguínea , Intestino Delgado/trasplante , Preservación de Órganos/métodos , Perfusión/métodos , Animales , Intestino Delgado/patología , Poscondicionamiento Isquémico , Precondicionamiento Isquémico , Masculino , Porcinos
5.
Public Health ; 185: 212-217, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32653631

RESUMEN

OBJECTIVES: To explore sports organisation members' attitudes to sponsorship of sport by energy-dense, nutrient-poor food and drink ('junk food') brands. STUDY DESIGN: The study design is a cross-sectional study. METHODS: An online survey of adult members of three sports organisations that did not accept junk food sponsorship in Victoria, Australia in 2018: one was responsible for an elite team in a national competition (5000-10,000 members); one managed a team sport competition across Victoria (50,000-100,000 registered junior and adult participants, referees and coaches); and one administered a junior team sport competition for boys and girls in a major city (10,000-15,000 participants). RESULTS: Most (71%) of the 2224 respondents reported it was important/very important that their organisation did not accept junk food sponsorship. A higher proportion was concerned/very concerned about junk food companies sponsoring children's sport (60%) compared with such companies sponsoring elite (49%, P < 0.001) or community adult (39%, P < 0.001) sport. A higher proportion of respondents were likely/very likely to support a policy that restricted junk food sponsorship of children's sport (84%), compared with a policy restricting sponsorship of elite (76%, P > 0.001) and adult community (74%, P > 0.001) sport. Two-thirds of respondents supported restricting junk food companies from sponsoring sport, even if fees for children's (66%) and community adult (65%) sport increased, or if membership and attendance costs for elite sport supporters increased (63%). CONCLUSIONS: In the Australian context of this study, junk food sponsorship of sport, particularly children's sport, is a concern to members of sports organisations. Although still high, support for restricting such sponsorship declines if members perceive it will lead to increases in participation costs and decreases in participation opportunities. Initiatives restricting junk food sponsorship of sport are likely to receive strong support from the sports community, particularly when the focus is on children's sport, and participation costs and opportunities are not negatively impacted.


Asunto(s)
Actitud Frente a la Salud , Industria de Alimentos , Organizaciones , Deportes/economía , Adulto , Niño , Estudios Transversales , Comida Rápida , Femenino , Apoyo Financiero , Alimentos , Humanos , Masculino , Afiliación Organizacional , Políticas , Encuestas y Cuestionarios , Victoria
6.
Public Health ; 166: 1-9, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30414533

RESUMEN

OBJECTIVES: Energy-dense, nutrient-poor food and drink ('junk food') brands sponsoring sport is a growing public health concern. This study explored sports administrators' perceptions of the barriers to rejecting junk food sponsorship. STUDY DESIGN: This study used concept mapping. METHODS: The Concept Systems Global MAX™ web platform was used to collect and analyse data from 29 sports administrators across all levels of sport in Victoria, Australia. RESULTS: Brainstorming generated 33 barriers to rejecting junk food sponsorship. After the barriers were synthesised and edited, participants sorted and rated 32 barriers. Multidimensional scaling and hierarchical cluster analysis identified a four-cluster solution: community attitudes and values (seven barriers); junk food is the easy sell (retail; five barriers); financial viability (16 barriers); and organisational capability (policy and governance; four barriers). The financial viability barriers were rated the most important (mean = 3.65 of 5) and the hardest to overcome (1.42). The organisational capability (policy and governance) barriers were rated the least important (2.14) and the easiest to overcome (3.20). CONCLUSIONS: Sports administrators clearly perceive that rejecting junk food sponsorship could place significant financial strain on their organisations. There appears to be considerable scope to build the capacity of sporting organisations to rejecting junk food sponsorship. Despite the literature indicating that most parents think junk food companies are not suitable sponsors, sports administrators perceive that there is a broad public acceptance of junk food sponsorship in sport. The fact that sports administrators perceive a link between junk food sponsorship and the lack of healthy options at club canteens and venue food outlets adds an additional, not previously identified, level of complexity to the junk food sponsorship in sport debate.


Asunto(s)
Personal Administrativo/psicología , Comida Rápida , Apoyo Financiero , Mercadotecnía/economía , Deportes/economía , Formación de Concepto , Humanos , Percepción , Victoria
7.
Br J Surg ; 106(3): 199-205, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30346041

RESUMEN

BACKGROUND: Renal transplant surgeons are making increasing use of live donor kidneys with multiple renal arteries. This study aimed to identify independent risk factors for the development of transplant renal artery stenosis (TRAS) in the modern era of complex arterial reconstruction for multiple vessels. METHODS: Multivariable logistic regression analysis with a stepwise variable deletion model was used to identify risk factors for the development of TRAS in a consecutive series of live donor kidney transplants. RESULTS: Of 506 kidney transplants, 19 (3·8 per cent) had evidence of significant TRAS on CT angiography. Functional TRAS, defined by improvement in BP control or renal function after correction of a stenosis by angioplasty, occurred in 13 of 506 patients (2·6 per cent). Independent risk factors for TRAS were: use of an explanted internal iliac artery graft from the recipient (odds ratio (OR) 4·95; P = 0·020) and total ischaemia time (OR 1·82; P = 0·010). TRAS was associated with a lower 5-year allograft survival rate (79 versus 88·7 per cent; P = 0·020) but only one graft loss was attributed directly to TRAS. The 5-year allograft survival rate after internal iliac artery grafting was 86 per cent. CONCLUSION: Although use of an internal iliac artery graft is an independent risk factor for TRAS after live donor kidney transplantation, this technique is still a useful option for complex arterial reconstruction.


Asunto(s)
Trasplante de Riñón/efectos adversos , Donadores Vivos , Obstrucción de la Arteria Renal/etiología , Aloinjertos/fisiología , Femenino , Supervivencia de Injerto/fisiología , Humanos , Arteria Ilíaca/trasplante , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Factores de Riesgo , Trasplante Homólogo
8.
Br J Surg ; 105(4): 388-394, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29210064

RESUMEN

BACKGROUND: A significant proportion of donation after circulatory death (DCD) kidneys are declined for transplantation because of concerns over their quality. Ex vivo normothermic machine perfusion (NMP) provides a unique opportunity to assess the quality of a kidney and determine its suitability for transplantation. METHODS: In phase 1 of this study, declined human DCD kidneys underwent NMP assessment for 60 min. Kidneys were graded 1-5 using a quality assessment score (QAS) based on macroscopic perfusion, renal blood flow and urine output during NMP. In phase 2 of the study, declined DCD kidneys were assessed by NMP with an intention to transplant them. RESULTS: In phase 1, 18 of 42 DCD kidneys were declined owing to poor in situ perfusion. After NMP, 28 kidneys had a QAS of 1-3, and were considered suitable for transplantation. In phase 2, ten of 55 declined DCD kidneys underwent assessment by NMP. Eight kidneys had been declined because of poor in situ flushing in the donor and five of these were transplanted successfully. Four of the five kidneys had initial graft function. CONCLUSION: NMP technology can be used to increase the number of DCD kidney transplants by assessing their quality before transplantation.


Asunto(s)
Selección de Donante , Trasplante de Riñón , Riñón/irrigación sanguínea , Preservación de Órganos/métodos , Perfusión/métodos , Adulto , Anciano , Muerte , Femenino , Humanos , Riñón/fisiología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Temperatura
10.
Health Educ Res ; 32(1): 48-57, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28087587

RESUMEN

Approximately one in four Australian children aged 5-17 years are overweight or obese. Most of the health effects of overweight and obesity in childhood do not eventuate until into adulthood; therefore, motivation for children to have a healthy diet may be low. This scoping review examined the literature for associations between diet quality in 5-18 year olds and 'school-valued' outcomes including student attendance, academic performance, behaviour at school and mental health. A literature search for studies that assessed dietary intake and at least one 'school-valued' outcome in schoolchildren, in highly developed countries was conducted. After applying selection criteria, 35 studies were included examining academic performance (46%), behaviour (11%), mental health (31%) and 11% examining two of these outcomes each. No relevant studies addressed attendance. In general, dietary factors including consumption of fruit and vegetables, discretionary foods and/or beverages, or overall diet quality, were suggested to be correlates of the 'school-valued' outcomes. However, the evidence is not comprehensive. This review elucidates the extent and nature of available literature, and provides a basis for future research where the potential benefits of diet on 'school-valued' outcomes can be thoroughly explored.


Asunto(s)
Dieta Saludable , Obesidad/prevención & control , Instituciones Académicas , Éxito Académico , Australia , Bebidas , Niño , Frutas , Humanos , Salud Mental , Verduras
11.
Int J Clin Pract ; 70(10): 806-824, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27582503

RESUMEN

BACKGROUND: Vital signs monitoring is an old hospital practice for patient safety but evaluation of its effectiveness is not widespread. We aimed to identify strategies to improve intermittent or continuous vital signs monitoring in general wards; and their effectiveness in preventing adverse events on general hospital wards. METHODS: Publications searched between 1980 and June 2014 in five databases. Main outcome measures were in-hospital death, cardiac arrest, intensive care unit (ICU) transfers, length of stay, identification of physiological deterioration and activation of rapid response systems. RESULTS: Twenty-two studies assessing the effect of continuous (9) or intermittent monitoring (13) and reporting outcomes on 203,407 patients in-hospital wards across 13 countries were included in this review. Both monitoring practices led to early identification of patient deterioration, increased rapid response activations and improvements in timeliness or completeness of vital signs documentation. Innovative intermittent monitoring approaches are associated with modest reduction in in-hospital mortality over intermittent vital signs monitoring in 'usual care'. However, there was no evidence of significant reduction in ICU transfers or other adverse events with either intermittent or continuous monitoring. CONCLUSIONS: This review of heterogeneous monitoring approaches found no conclusive confirmation of improvements in prevention of cardiac arrest, reduction in length of hospital stay, or prevention of other neurological or cardiovascular adverse events. The evidence found to date is insufficient to recommend continuous vital signs monitoring in general wards as routine practice. Future evaluations of effectiveness need to be undertaken with more rigorous methods and homogeneous outcome measurements.


Asunto(s)
Hospitalización , Monitoreo Fisiológico/métodos , Seguridad del Paciente , Signos Vitales/fisiología , Cuidados Críticos , Paro Cardíaco/prevención & control , Equipo Hospitalario de Respuesta Rápida , Humanos , Tiempo de Internación , Transferencia de Pacientes/estadística & datos numéricos , Habitaciones de Pacientes
12.
Am J Transplant ; 16(11): 3282-3285, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27273794

RESUMEN

We report the successful transplantation of a pair of human kidneys that were declined for transplantation due to inadequate in situ perfusion but subsequently transplanted after perfusion and assessment using ex vivo normothermic perfusion (EVNP). The kidneys were from a 35-year-old man, a donation after circulatory death donor. Both kidneys were declined by all UK transplant centers. On arrival, the kidneys had significant areas of incomplete clearance of blood from the microcirculation that did not clear after a further attempt to flush them. Kidneys underwent 60 min of EVNP with an oxygenated packed red blood cell-based solution warmed to 35.2°C. During EVNP, the patchy areas cleared in both kidneys. The mean renal blood flow and total urine output were 68.0 mL/min/100 g and 560 mL in the left kidney and 59.9 mL/min/100 g, 430 mL in the right, respectively. Based on the EVNP perfusion parameters, both kidneys were deemed suitable for transplantation. They were transplanted without any complications, and both recipients had initial graft function. The serum creatinine levels at 3 months were 1.2 mg/dl in the recipient of the left kidney and 1.62 mg/dl in the recipient of the right kidney. EVNP technology can be used to assess and rescue kidneys previously deemed unsuitable for transplantation.


Asunto(s)
Trasplante de Riñón , Hígado/metabolismo , Preservación de Órganos , Perfusión/métodos , Donantes de Tejidos/provisión & distribución , Supervivencia Tisular , Obtención de Tejidos y Órganos/métodos , Adulto , Anciano , Femenino , Rechazo de Injerto/prevención & control , Humanos , Pruebas de Función Renal , Hígado/irrigación sanguínea , Masculino , Evaluación de Resultado en la Atención de Salud
14.
Int J Nurs Stud ; 56: 9-16, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26775214

RESUMEN

BACKGROUND: High profile safety failures have demonstrated that recognising early warning signs of clinical and physiological deterioration can prevent or reduce harm resulting from serious adverse events. Early warning scoring systems are now routinely used in many places to detect and escalate deteriorating patients. Timely and accurate vital signs monitoring are critical for ensuring patient safety through providing data for early warning scoring systems, but little is known about current monitoring practices. OBJECTIVE: To establish a profile of nurses' vital signs monitoring practices, related dialogue, and adherence to health service protocol in New South Wales, Australia. METHODS: Direct observations of nurses' working practices were conducted in two wards. The observations focused on times of the day when vital signs were generally measured. Patient interactions were recorded if occurring any time during the observation periods. Participants (n=42) included nursing staff on one chronic disease medical and one acute surgical ward in a large urban teaching hospital in New South Wales. RESULTS: We observed 441 patient interactions. Measurement of vital signs occurred in 52% of interactions. The minimum five vital signs measures required by New South Wales Health policy were taken in only 6-21% of instances of vital signs monitoring. Vital signs were documented immediately on 93% of vitals-taking occasions and documented according to the policy in the patient's chart on 89% of these occasions. Nurse-patient interactions were initiated for the purpose of taking vital signs in 49% of interactions, with nurse-patient discourse observed during 88% of all interactions. Nurse-patient dialogue led to additional care being provided to patients in 12% of interactions. CONCLUSION: The selection of appropriate vital signs measured and responses to these appears to rely on nurses' clinical judgement or time availability rather than on policy-mandated frequency. The prevalence of incomplete sets of vital signs may limit identification of deteriorating patients. The findings from this study present an important baseline profile against which to evaluate the impact of introducing continuous monitoring approaches on current hospital practice.


Asunto(s)
Monitoreo Fisiológico , Relaciones Enfermero-Paciente , Personal de Enfermería en Hospital , Signos Vitales , Humanos , Nueva Gales del Sur , Investigación Cualitativa
15.
J Transl Med ; 13: 329, 2015 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-26474973

RESUMEN

BACKGROUND: Many kidneys are rejected for transplantation due to inadequate in situ perfusion during organ retrieval because of the risk of additional ischaemic injury and microvasculature thrombosis. This study describes the use of ex vivo normothermic perfusion (EVNP) for the resuscitation and assessment of human kidneys that were discarded after inadequate in situ perfusion. METHODS: Twenty-two human kidneys were retrieved but then deemed unsuitable for transplantation, primarily due to inadequate in situ perfusion. After a period of static cold storage, kidneys were perfused for 60 min with an oxygenated red cell based solution at 36 °C. RESULTS: Nineteen out of 22 kidneys (86 %) were from DCD donors. During EVNP, kidneys were assessed and scored based on their macroscopic appearance, measures of renal blood flow and urine production. Kidneys were scored from 1 indicating the least injury to 5, indicating the worst. Twelve kidneys had an EVNP score of 1-2, 7 scored 3-4 and 3 kidneys scored 5. The EVNP score 5 kidneys had a low level of tubular function compared to the score 1-4 kidneys. Their perfusion parameters did not improve during EVNP and they were considered non-transplantable. There was no association between the histological evaluation and EVNP parameters. CONCLUSION: EVNP restores function ex vivo and enables an assessment of kidneys that have been declined for transplantation due to inadequate in situ perfusion.


Asunto(s)
Riñón/irrigación sanguínea , Adulto , Anciano , Femenino , Humanos , Técnicas In Vitro , Riñón/fisiología , Masculino , Persona de Mediana Edad , Perfusión , Donantes de Tejidos
16.
Br J Surg ; 102(12): 1517-25, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26263908

RESUMEN

BACKGROUND: Ischaemic conditioning, using short repeated sequences of intermittent ischaemia, is a strategy that may ameliorate ischaemia-reperfusion injury. The aim of the study was to assess the effects of direct and remote ischaemic conditioning in a porcine model of renal warm ischaemia-reperfusion injury. METHODS: Pigs (50 kg) underwent laparotomy and 60-min occlusion of the left renal pedicle followed by right nephrectomy. Animals were divided into three groups: untreated controls (n = 8); direct postconditioning involving six 15-s cycles of clamping then releasing of the left renal artery (n = 7); or remote periconditioning involving four 5-min cycles of clamping then releasing of the left common iliac artery (n = 8). After 7 days kidney tissue was harvested, and blood and urine samples were collected on postoperative days 1, 3 and 7. RESULTS: The direct postconditioning group had a lower area under the serum creatinine curve (mean(s.d.) 1378(157) versus 2001(1022) µmol/l · day respectively; P = 0.036) and peak creatinine level (316(46) versus 501(253) µmol/l respectively; P = 0.033) compared with values in control animals. There was a significant increase in serum levels of tumour necrosis factor α on day 1 in control animals but not in the conditioning groups (P = 0.013). Urinary levels of neutrophil gelatinase-associated lipocalin increased over the study period in both the control and remote groups (P = 0.001 for both), but not in the direct group (P = 0.176). There was no mortality and no complications related to either conditioning technique. CONCLUSION: In this in vivo large-animal model, direct renal artery ischaemic postconditioning protected kidneys against warm ischaemia injury. This straightforward technique could readily be translated into clinical practice. Surgical relevance Ischaemic conditioning has been shown to improve outcomes in both experimental studies and clinical trials in cardiac surgery. Evidence from small-animal and human studies assessing ischaemic conditioning techniques in renal transplantation have not yet established the optimal technique and timing of conditioning. In this study, a large-animal model of renal warm ischaemia was used to compare different conditioning techniques. Postconditioning applied directly to the renal artery was shown to reduce renal injury. Furthermore, new evidence is provided that shorter cycles of ischaemic postconditioning than previously described can protect against renal injury. Evidence from a large-animal model is provided for different conditioning techniques. The beneficial postconditioning technique described is straightforward to perform and provides an alternative method of conditioning following renal transplantation, with potential for application in clinical practice.


Asunto(s)
Lesión Renal Aguda/prevención & control , Poscondicionamiento Isquémico/métodos , Riñón/irrigación sanguínea , Isquemia Tibia/métodos , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Biopsia con Aguja Gruesa , Creatinina/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Riñón/patología , Porcinos
17.
Br J Surg ; 102(11): 1433-40, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26313559

RESUMEN

BACKGROUND: A significant proportion of kidneys procured for transplantation are discarded because of concerns about their suitability. In this study ex vivo normothermic perfusion (EVNP) was used as a quality assessment device before renal transplantation. METHODS: Seventy-four human kidneys deemed unsuitable for transplantation following retrieval underwent 60 min of EVNP with an oxygenated red cell-based solution at 36°C. Receiver operating characteristic (ROC) curves were used to identify thresholds of renal blood flow and urine output. These thresholds and a grading of macroscopic appearance were incorporated into an EVNP assessment score (highest quality, 1; lowest, 5). This was applied to a series of 36 kidneys transplanted after EVNP. RESULTS: In the discarded kidney series, 60 (81 per cent) scored 1-4 and 14 (19 per cent) scored 5. Although none of these kidneys was transplanted, those with a score from 1 to 4 were considered suitable for transplantation. In the 36 transplanted kidneys, the score ranged between 1 and 3 (score 1, 17; score 2, 11; score 3, 8). All of these kidneys were transplanted without any complications or primary non-function. The delayed graft function rate was 6 per cent (1 of 17) in kidneys scoring 1, 0 per cent (0 of 11) in those scoring 2 and 38 per cent (3 of 8) in those scoring 3 (P = 0·024). The mean(s.d.) estimated glomerular filtration rate at 12 months was 51(16), 63(15) and 38(21) ml in kidneys scoring 1, 2 and 3 respectively (P = 0·015). CONCLUSION: EVNP combined with a simple scoring system is an innovative technology for pretransplant assessment of kidney quality and acceptability for transplantation. This study suggests that a high percentage of retrieved kidneys are being discarded unnecessarily.


Asunto(s)
Selección de Donante/métodos , Trasplante de Riñón , Perfusión/métodos , Adulto , Anciano , Toma de Decisiones Clínicas , Funcionamiento Retardado del Injerto/diagnóstico , Funcionamiento Retardado del Injerto/etiología , Funcionamiento Retardado del Injerto/prevención & control , Selección de Donante/normas , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Curva ROC , Temperatura
18.
J Transl Med ; 13: 207, 2015 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-26123198

RESUMEN

BACKGROUND: Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model. METHODS: Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology. RESULTS: Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia. CONCLUSIONS: Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.


Asunto(s)
Pruebas de Función Renal , Riñón/fisiopatología , Isquemia Tibia , Animales , Biomarcadores/orina , Creatinina/sangre , Femenino , Hemodinámica , Riñón/irrigación sanguínea , Riñón/patología , Consumo de Oxígeno , Reperfusión , Sodio/metabolismo , Sus scrofa
19.
Vet Comp Orthop Traumatol ; 28(4): 250-5, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26167862

RESUMEN

OBJECTIVES: To prospectively compare the accuracy of three preoperative measurement techniques in tibial plateau levelling osteotomy (TPLO) planning. METHODS: Fifty-nine dogs were randomly assigned to one of three measurement techniques; A, B or C. Surgeons measured the intended osteotomy location on preoperative radiographs according to the assigned technique. Measurements were used intra-operatively during osteotomy placement. Postoperative measurements were made by a single blinded observer and compared to preoperative measurements. RESULTS: Fifty-one dogs were included for final statistical analysis. The mean absolute differences between pre- and postoperative measurements was 1.72 mm ± 0.958, 1.79 mm ± 1.010, and 3.56 mm ± 1.839, for techniques A, B and C, respectively. No significant differences were identified for patient age, gender, limb or surgeon. Techniques A and B were not significantly different (p = 0.8799). Techniques A and B were significantly more accurate than C (p = 0.0001 and p = 0.0003, respectively). Weight was significantly different among the groups (p = 0.047) but the statistical results did not change when an adjustment was made for bodyweight (p = 0.4971, p <0.001 and p = 0.0007, respectively). CLINICAL SIGNIFICANCE: Preoperative measuring for planning a TPLO osteotomy is recommended. Techniques A and B in the current study were clinically practical and significantly more accurate compared to technique C.


Asunto(s)
Osteotomía/veterinaria , Tibia/cirugía , Animales , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/cirugía , Enfermedades de los Perros/cirugía , Perros/cirugía , Femenino , Periodo Intraoperatorio , Masculino , Osteotomía/métodos , Cuidados Posoperatorios , Periodo Preoperatorio , Radiografía , Rodilla de Cuadrúpedos/diagnóstico por imagen , Rodilla de Cuadrúpedos/cirugía , Tibia/diagnóstico por imagen
20.
Am J Transplant ; 15(9): 2475-82, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25989187

RESUMEN

A significant number of pancreases procured for transplantation are deemed unsuitable due to concerns about graft quality and the associated risk of complications. However, this decision is subjective and some declined grafts may be suitable for transplantation. Ex vivo normothermic perfusion (EVNP) prior to transplantation may allow a more objective assessment of graft quality and reduce discard rates. We report ex vivo normothermic perfusion of human pancreases procured but declined for transplantation, with ABO-compatible warm oxygenated packed red blood cells for 1-2 h. Five declined human pancreases were assessed using this technique after a median cold ischemia time of 13 h 19 min. One pancreas, with cold ischemia over 30 h, did not appear viable and was excluded. In the remaining pancreases, blood flow and pH were maintained throughout perfusion. Insulin secretion was observed in all four pancreases, but was lowest in an older donation after cardiac death pancreas. Amylase levels were highest in a gland with significant fat infiltration. This is the first study to assess the perfusion, injury, as measured by amylase, and exocrine function of human pancreases using EVNP and demonstrates the feasibility of the approach, although further refinements are required.


Asunto(s)
Toma de Decisiones Clínicas , Funcionamiento Retardado del Injerto/prevención & control , Selección de Donante , Preservación de Órganos , Trasplante de Páncreas , Perfusión/métodos , Recolección de Tejidos y Órganos , Adolescente , Adulto , Amilasas/metabolismo , Funcionamiento Retardado del Injerto/diagnóstico , Funcionamiento Retardado del Injerto/metabolismo , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Temperatura
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