Bimbi Fernando

8-Isoprostaglandin F2 alpha, a product of lipid peroxidation, increases portal pressure in normal and cirrhotic rats

BACKGROUND & AIMS The F2-isoprostanes are a recently described class of prostaglandins formed by free radical-mediated lipid peroxidation. 8-Isoprostaglandin F2 alpha (8-iso-PGF2 alpha), an F2-isoprostane, has previously been shown to be a potent renal vasoconstrictor acting via a thromboxane-like receptor. The aim of this study was to investigate whether 8-iso-PGF2 alpha increases portal pressure. METHODS Livers from normal and bile duct-ligated cirrhotic rats were perfused, and portal pressure response to infused agonist was monitored continuously. RESULTS Infusion of 8-iso-PGF2 alpha increased portal pressure in both groups, with a significantly greater response in cirrhotic rats. At a dose of 2.5 nmol/min, the mean portal pressure increased from a baseline of 8.2 +/- 0.6 to 9.8 +/- 1.3 mm Hg, whereas in cirrhotic animals, the increase was from 12.0 +/- 0.9 to 18.6 +/- 1.8 mm Hg. This response was completely blocked by SQ29548, a thromboxane receptor antagonist. A similar response pattern was observed with the thromboxane receptor agonist U46619. CONCLUSIONS 8-iso-PGF2 alpha can increase portal pressure in cirrhotic rats. If extrapolated to patients with cirrhosis, lipid peroxidation secondary to alcoholic liver injury, sepsis, or other liver pathology may cause an acute increase in portal pressure such as that observed in acute liver injury.

Risk factors for recurrent primary sclerosing cholangitis after liver transplantation

BACKGROUND & AIMS The association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is well recognised. However, the relationship between IBD and recurrent PSC (rPSC) is less well understood. We assessed the prevalence of rPSC and analysed the factors associated with rPSC post-liver transplantation and its influence on graft and patient survival. METHODS This is a UK multicentre observational cohort study across six of the seven national liver transplant units. All patients undergoing a first liver transplant for PSC between January 1 1990 and December 31 2010 were included. Prospectively collected liver transplant data was obtained from NHSBT and colitis data was retrospectively collected from individual units. RESULTS There were 679 (8.8%) first transplants for PSC. 347 patients (61.4%) had IBD, of which 306 (88.2%) had ulcerative colitis (UC). 81 (14.3%) patients developed rPSC and 37 (48.7%) of them developed graft failure from rPSC. Presence of UC post-liver transplant (HR=2.40, 95% CI 1.44-4.02) and younger age (HR=0.78, 95% CI 0.66-0.93) were the only factors significantly associated with rPSC. rPSC was associated with over a 4-fold increase in the risk of death (HR=4.71, 95% CI 3.39, 6.56) with 1, 5, and 10-year graft survival rates of 98%, 84%, and 56% respectively compared to 95%, 88%, and 72% in patients who did not develop rPSC. CONCLUSION The presence of UC post-liver transplant is associated with a significantly increased risk of rPSC. Furthermore, the presence of rPSC increases the rate of graft failure and death, with higher re-transplantation rates.

Resource implications of expanding the use of donation after circulatory determination of death in liver transplantation

In the United Kingdom, liver transplantation using donation after circulatory determination of death (DCDD) organs has increased steadily over the last few years and now accounts for 20% of UK transplant activity. The procurement of DCDD livers is actively promoted as a means of increasing the donor pool and bridging the evolving disparity between the wait‐list length and the number of transplants performed. The objective of this retrospective study of a cohort of patients who were matched for age, liver disease etiology, and Model for End‐Stage Liver Disease score was to determine whether differences in perioperative costs and resource utilization are associated with the use of such organs. Our results showed an increased prevalence of reperfusion syndrome in the DCDD cohort (P < 0.001), a prolonged heparin effect (P = 0.01), a greater incidence of hyperfibrinolysis (P = 0.002), longer periods of postoperative ventilator use (P = 0.03) and vasopressor support (P = 0.002), and a prolonged length of stay in the intensive therapy unit (ITU; P = 0.02). The peak posttransplant aspartate aminotransferase level was higher in the DCDD group (P = 0.007), and there was significantly more graft failure at 12 months (P = 0.03). In conclusion, we have demonstrated different perioperative and early postoperative courses for DCDD and donation after brain death (DBD) liver transplants. The overall quality of DCDD grafts is poorer; as a result, the length of the ITU stay and the need for multiorgan support are increased, and this has significant financial and resource implications. We believe that these implications require a careful real‐life consideration of benefits. It is essential for DCDD not to be seen as a like‐for‐like alternative to DBD and for every effort to be continued to be made to increase the number of donations from brain‐dead patients as a first resort. Liver Transpl, 2012.

Establishing a curriculum for the acquisition of laparoscopic psychomotor skills in the virtual reality environment

BACKGROUND The unique psychomotor skills required in laparoscopy result in reduced patient safety during the early part of the learning curve. Evidence suggests that these may be safely acquired in the virtual reality (VR) environment. Several VR simulators are available, each preloaded with several psychomotor skills tasks that provide users with computer-generated performance metrics. This review aimed to evaluate the usefulness of specific psychomotor skills tasks and metrics, and how trainers might build an effective training curriculum. METHODS We performed a comprehensive literature search. RESULTS The vast majority of VR psychomotor skills tasks show construct validity for one or more metrics. These are commonly for time and motion parameters. Regarding training schedules, distributed practice is preferred over massed practice. However, a degree of supervision may be needed to counter the limitations of VR training. CONCLUSIONS In the future, standardized proficiency scores should facilitate local institutions in establishing VR laparoscopic psychomotor skills curricula.

Early changes in scores of chronic damage on transplant kidney protocol biopsies reflect donor characteristics, but not future graft function

The amount of irreversible injury on renal allograft biopsy predicts function, but little is known about the early evolution of this damage. In a single‐center cohort, we examined the relationship between donor‐, recipient‐, and transplantation‐associated factors and change in a morphometric index of chronic damage (ICD) between protocol biopsies performed at implantation and at 2–3 months. We then investigated whether early delta ICD predicted subsequent biochemical outcomes. We found little evidence to support differences between the study group, who had undergone serial biopsies, and a contemporaneous control group, who had not. In allografts with serial biopsies (n = 162), there was an increase in ICD between implantation (median: 2%, IQR:0–8) and 2–3 months post‐transplant (median 8% IQR:4–15; p < 0.0001). Donation from younger or live donors was independently associated with smaller early post‐transplant increases in ICD. There was no evidence for a difference in delta ICD between donation after cardiac death vs. donation after brain death, nor association with length of cold ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD after three months did not predict allograft function at one yr. These findings suggest that graft damage develops shortly after transplantation and reflects donor factors, but does not predict future biochemical outcomes.

The emerging role of screen based simulators in the training and assessment of colonoscopists

Incorporation of screen based simulators into medical training has recently gained momentum, as advances in technology have coincided with a government led drive to increase the use of medical simulation training to improve patient safety with progressive reductions in working hours available for junior doctors to train. High fidelity screen based simulators hold great appeal for endoscopy training. Potentially, their incorporation into endoscopy training curricula could enhance speed of acquisition of skills and improve patient comfort and safety during the initial phase of learning. They could also be used to demonstrate competence as part of the future relicensing and revalidation of trained endoscopists. Two screen based simulators are widely available for lower gastrointestinal endoscopy training, with a third recently produced in prototype. The utility of these simulators in lower gastrointestinal endoscopy training has been investigated, and construct and expert validity has been shown. Novices demonstrate a learning curve with simulator training that appears to represent real learning of colonoscopy skills. This learning transfers well to the real patient environment, with improvements in performance and patient discomfort scores in subsequent initial live colonoscopy. The significant limitations of currently available screen based simulators include cost implications, and restrictions on a role in certification and revalidation. Many questions remain to be answered by future research, including how best to incorporate screen based simulators into a colonoscopy training programme, their role in training in therapeutic endoscopy and the impact of simulator training on patient safety.

Renal Transplant and Vascular Procedures

Ureteroneocystostomy (UNC) is the implantation of the ureter onto the bladder. The indications for this are: Implantation of a donor ureter during renal allotransplantation Re-implantation of the native ureter during renal autotransplantation (a treatment for complex renal artery aneurysm) Re-implantation of the native or transplant ureter due to disease of the distal ureter (such as vesicoureteral reflux in native kidneys, or ureteric stenosis in transplant kidneys)

Incidence and outcome of colorectal cancer in liver transplant recipients: A national, multicentre analysis on 8115 patients

De novo malignancies after liver transplantation represent one of the leading causes of death in the long‐term. It remains unclear whether liver transplant recipients have an increased risk of colorectal cancer and whether this negatively impacts on survival, particularly in those patients affected by primary sclerosing cholangitis and ulcerative colitis.

Post-operative arterio-venous fistula blood flow influences primary and secondary patency following access surgery

PURPOSE Primary arteriovenous fistula arterio venous fistula (AVF) formation has proven to be the best and optimal vascular access for the majority of haemodialysis patients. At present there are limited data to suggest which haemodynamic parameters most correlate with the likelihood of early failure. The aim of this study is to identify the haemodynamic predictors of early failure, hence identify which fistulae may benefit from timely pre-emptive intervention. MATERIAL AND METHODS Retrospective analysis of data was performed of 201 patients undergoing native AVF creation over a one year period. Demographic details, co-morbidity, preoperative vessel calibre were collected. Flow was measured by duplex ultrasound post operatively. RESULTS Preoperative vein calibre (p = 0.01) and fistula flow (p < 0.001) positively affected primary patency. Age, gender, ethnicity, type of fistula, hypertension and preoperative arterial calibre did not influence outcome. Regression analysis showed that the strength of correlation between early postoperative fistula flow and patency decreased progressively with time. Six week flow predicts early, but not late, failure. ROC analysis identified 300 ml/min flow as the best predictor of patency. Fistulae with flow above 300 ml/min were more likely to remain patent over the next 12 months (p < 0.001, HR = 7.4). CONCLUSION Postoperative fistula flow of less than 300 ml/min identifies AVFs at high risk of early failure. These may be candidates for early intervention with balloon assisted maturation. The findings of this retrospective cohort study strongly support the need for a more robust prospectively designed trial identifying haemodynamic factors that can predict mid and long-term AVF patency.

Cardiac arrest following arteriovenous fistula manipulation: a cautionary note

Arteriovenous fistulas can lead to a number of different chronic complications. We describe a case where a patient developed a thrombosis within her brachiobasilic arteriovenous fistula, which was manually manipulated in order to restore fistula flow. This resulted in a pulseless electrical activity cardiac arrest within a few minutes. After ten minutes of chest compressions and intubation, there was return of spontaneous circulation. No epinephrine was given nor shocks administered. Patient was extubated within minutes and was alert, orientated and haemodynamically stable. CT pulmonary angiogram showed extensive bilateral pulmonary emboli. Manual manipulation of the arteriovenous fistula lead to significant amounts of thrombus embolising to the pulmonary arteries, and resultant cardiac arrest due to circulatory compromise. Chest compressions likely dislodged these emboli, allowing circulation to recommence. We publish this as a cautionary note of a rare but potentially fatal complication.