Long-term ex situ normothermic perfusion of human split livers for more than 1 week.

Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed to develop a long-term model of ex situ perfusion including a surgical split and simultaneous perfusion of both partial organs. Human livers declined for transplantation were perfused using a red blood cell-based perfusate under normothermic conditions (36 °C) and then split and simultaneously perfused on separate machines. Ten human livers were split, resulting in 20 partial livers. The median ex situ viability was 125 h, and the median ex situ survival was 165 h. Long-term survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. Here, we report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol.

Combined Liver-Kidney Transplant for Juvenile Polycystic Kidney Disease and Concomitant Hereditary Factor V Deficiency.

Factor V deficiency is a congenital bleeding diathesis that, in selected cases, may be managed with liver transplant. In this case, we describe the treatment of an adult patient with kidney failure secondary to juvenile onset polycystic kidney disease who received a combined liver-kidney transplant as a method to manage the risks associated with the need for a kidney transplantin the setting of factorV deficiency and high sensitization.

Addressing the challenges of split liver transplantation through technical advances. A systematic review.

BACKGROUND: Split liver transplantation addresses donor shortages by facilitating the transplant of two recipients using one donor liver. Some still consider these grafts inferior due to prolonged cold ischaemia time and at times difficult vascular reconstruction. Techniques such as in-situ splitting, machine perfusion and interposition grafts may address these challenges and thereby address these concerns. The aim of this review is to assess these technical advances in split liver transplantation, their utility and outcomes. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Keywords included 'split liver transplantation', 'arterial reconstruction', and 'machine perfusion'. Data found was synthesised into sections including: methods of splitting, full-left full-right splitting, donor cholangiography, machine perfusion and arterial reconstruction. RESULTS: A total of 78 articles met inclusion criteria after screening of 151 eligible articles. These were subdivided into the following categories: in-situ (25), ex-vivo (25), full-left full-right splitting (15), donor cholangiography (2), machine perfusion (6), and arterial reconstruction (5). The in-situ splitting technique reduces the cold ischaemia time compared to the ex-vivo technique which may improve graft quality and liver splitting during normothermic machine perfusion is a novel technique with the potential to incorporate the best aspects of both techniques. Interposition grafts are often required during split liver transplantation but have an increased risk of hepatic artery thrombosis. CONCLUSION: Advancements in technique have allowed many of the unique challenges of split liver transplantation to be overcome. Overall, this supports the use of split liver transplantation in broader and riskier settings and we advocate for liver transplant surgeons to not hesitate in using these grafts liberally and expanding their recipient selection criteria.

Too many pills to swallow: A case of a mixed overdose.

Propranolol is a highly lipid-soluble beta-receptor antagonist. We describe a case of mixed overdose, including propranolol, amlodipine and olanzapine, resulting in severe resistant hypotension which was successfully treated. A 21-year-old student ingested 6.4 g of propranolol, 280 mg of amlodipine and 560 mg of olanzapine. The patient was brought to the emergency department and exhibited signs of severe systemic toxicity - profound hypotension and circulatory collapse, respiratory depression and coma. The patient had conventional therapy but failed to respond to this and was therefore commenced on IntraLipid infusion, high-dose insulin infusion and inotrope infusion. An endoscopy was performed in intensive care which revealed a large drug beozar - this was removed. We believe that this combination of infusions with early endoscopy could be beneficial in treating similar patients in the future and present the first case of a propranolol drug bezoar.

The use of reflection in emergency medicine education.

Reflection is a cognitive process in which new information and experiences are integrated into existing knowledge structures and mental models, resulting in meaningful learning. Reflection often occurs after an experience is over, promoting professional development and lifelong learning. However, a reflective emergency physician (EP) is also able to apply reflection in real time: self-monitoring, coping with the unexpected, and quickly thinking on his or her feet to solve complicated, unique, and challenging clinical problems. Reflection is a skill that can be taught and developed in medical education. Evidence demonstrating the value of teaching reflection is emerging that substantiates longstanding educational theories. While a few educators have started to explore the use of reflection for emergency medicine (EM) learners, the potential for broader application exists. This review summarizes the literature regarding reflection in medical education and provides a basic primer for teaching reflection.

Heat shock proteins induction reduces stress kinases activation, potentially improving insulin signalling in monocytes from obese subjects.

Induction of heat shock proteins (Hsp) 72 and 27 can improve insulin signalling in obesity and type 2 diabetes via inhibition of key stress kinases. In metabolic disease, altered insulin signalling, as illustrated by increased serine phosphorylation of insulin receptor substrate (IRS)-1 (Ser312), is not confined to muscle or liver and can also affect other tissues and cell types, potentially impairing their primary biological function. This study specifically investigated insulin-stimulated glucose metabolism in monocytes and examined the impact of HSP induction on insulin signalling. Control (CG, BMI < 25 kg/m(2)) or obese (OG, BMI > 30 kg/m(2)) participants were included in the study. Glucose transporter (GLUT)4 expression on monocytes, phosphorylated JNK, IKK-ß and IRS-1, as well as Hsp27 and Hsp72, were measured in monocytes under fasting conditions. GLUT4 expression was also measured during an oral glucose tolerance test (OGTT). HSP induction as well as JNK, IKK-ß activation and IRS-1 serine phosphorylation was investigated following heat stress. Obese patients showed lower GLUT4 levels on monocytes during the OGTT. pJNK, pIKK-ß and pIRS-1 levels were increased in OG with pJNK and pIKK-ß levels positively correlated with serine pIRS-1 and negatively with GLUT4 supporting their role in insulin resistance. Heat exposure induced Hsp72 and Hps27, but only in CG for the latter, and decreased pJNK, pIKK-ß and pIRS-1. Our results show that induction of Hsp72 and 27 via heat stress is associated with inactivation of stress kinases and reduced serine pIRS-1 in monocytes from obese participants. This indicates that metabolic diseases can also affect monocyte metabolism via cellular stress that can be modulated via HSP induction.

Educating the delivery of bad news in medicine: Preceptorship versus simulation.

Simulation experiences have begun to replace traditional education models of teaching the skill of bad news delivery in medical education. The tiered apprenticeship model of medical education emphasizes experiential learning. Studies have described a lack of support in bad news delivery and inadequacy of training in this important clinical skill as well as poor familial comprehension and dissatisfaction on the part of physicians in training regarding the resident delivery of bad news. Many residency training programs lacked a formalized training curriculum in the delivery of bad news. Simulation teaching experiences may address these noted clinical deficits in the delivery of bad news to patients and their families. Unique experiences can be role-played with this educational technique to simulate perceived learner deficits. A variety of scenarios can be constructed within the framework of the simulation training method to address specific cultural and religious responses to bad news in the medical setting. Even potentially explosive and violent scenarios can be role-played in order to prepare physicians for these rare and difficult situations. While simulation experiences cannot supplant the model of positive, real-life clinical teaching in the delivery of bad news, simulation of clinical scenarios with scripting, self-reflection, and peer-to-peer feedback can be powerful educational tools. Simulation training can help to develop the skills needed to effectively and empathetically deliver bad news to patients and families in medical practice.

Factors associated with incomplete small bowel capsule endoscopy studies.

AIM: To identify patient risk factors associated with incomplete small bowel capsule endoscopy (CE) studies. METHODS: Data from all CE procedures performed at St. Paul's Hospital in Vancouver, British Columbia, Canada, between December 2001 and June 2008 were collected and analyzed on a retrospective basis. Data collection for complete and incomplete CE study groups included patient demographics as well as a number of potential risk factors for incomplete CE including indication for the procedure, hospitalization, diabetes mellitus with or without end organ damage, limitations in mobility, renal insufficiency, past history of bowel obstruction, abdominal surgery, abdominal radiation therapy and opiate use. Risk factors were analyzed using a univariable and multivariable logistic regression model. RESULTS: From a total of 535 CE procedures performed, 158 were incomplete (29.5%). The univariable analysis showed that CE procedures performed for overt gastrointestinal bleeding (P = 0.002), and for patients with a prior history of abdominal surgery (P = 0.023) or bowel obstruction (P = 0.023) were significantly associated with incomplete CE studies. Patients on opiate medications (P = 0.094) as well as hospitalized patients (P = 0.054) were not statistically significant, but did show a trend towards incomplete CE. The multivariable analysis showed that independent risk factors for an incomplete CE procedure include prior history of bowel obstruction [odds ratios (OR) 2.77, P = 0.02, 95% confidence intervals (CI): 1.17-6.56] and procedures performed for gastrointestinal bleeding (Occult OR 2.04, P = 0.037, 95% CI: 1.04-4.02 and Overt OR 2.69, P = 0.002, 95% CI: 1.44-5.05). Patients with a prior history of abdominal surgery (OR 1.46, P = 0.068, 95% CI: 0.97-2.19), those taking opiate medications (OR 1.54, P = 0.15, 95% CI: 0.86-2.76) and hospitalized patients (OR 1.82, P = 0.124, 95% CI: 0.85-3.93) showed a trend towards statistical significance. CONCLUSION: We have identified a number of risk factors for incomplete CE procedures that can be used to risk-stratify patients and guide interventions to improve completion rates.

Diagnostic yield of repeat capsule endoscopy and the effect on subsequent patient management.

BACKGROUND: Capsule endoscopy (CE) has been shown to produce a high diagnostic yield in patients with obscure gastrointestinal bleeding (OGIB); however, in those with negative studies, management is controversial. Very few studies have reported on repeat CE in the same patient; data regarding this diagnostic strategy are limited. OBJECTIVE: To determine the diagnostic yield of repeated CE studies and how this yield affects subsequent patient management. METHODS: A retrospective chart review of all patients who underwent CE at St Paul's Hospital (Vancouver, British Columbia) between December 2001 and June 2009 was conducted. Patients who underwent subsequent repeat CE were identified and divided into one of four subgroups. Findings were classified as positive or negative. RESULTS: Eighty-two of 676 patients underwent more than one CE study. Group 1 (incomplete study) included 22 patients (27%) and yielded 10 positive findings (45%). Group 2 (screening) comprised four patients (5%) and yielded two positive findings (50%). Group 3 (ongoing symptoms despite previous negative study) totalled 26 patients (32%) and yielded 10 positive findings (38%). Group 4 (previous positive study with treatment/investigation) included 30 patients (37%) and yielded 23 positive findings (77%). Overall, the present study found positive findings in 55% (45 of 82) of repeated CE cases, which resulted in a change in management in 39% (n=32) of the patients. CONCLUSION: Due to the high diagnostic yield and noninvasive nature of CE, repeat CE appears to be of benefit and should be considered for specific patients before other types of small bowel studies.