Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

Multicentre Analysis of Cost, Uptake and Safety of Canadian Multidisciplinary Pancreatic Cyst Guidelines.

Background: Pancreatic cystic lesions (PCLs) are common, with several guidelines providing surveillance recommendations. The Canadian Association of Radiologists published surveillance guidelines (CARGs) intended to provide simplified, cost-effective and safe recommendations. This study aimed to evaluate cost savings of CARGs compared to other North American guidelines including American Gastroenterology Association guidelines (AGAG) and American College of Radiology guidelines (ACRG), and to evaluate CARG safety and uptake. Methods: This is a multicentre retrospective study evaluating adults with PCL from a single health zone. MRIs completed from September 2018-2019, one year after local CARG guideline implementation, were reviewed to identify PCLs. All imaging following 3-4 years of CARG implementation was reviewed to evaluate true costs, missed malignancy and guideline uptake. Modelling, including MRI and consultation, predicted and compared costs associated with surveillance based on CARGs, AGAGs and ACRGs. Results: 6698 abdominal MRIs were reviewed with 1001 (14.9%) identifying PCL. Application of CARGs over 3.1 years demonstrated a >70% cost reduction compared to other guidelines. Similarly, the modelled cost of surveillance for 10-years for each guideline was $516,183, $1,908,425 and $1,924,607 for CARGs, AGAGs and ACRGs respectively. Of patients suggested to not require further surveillance per CARGs, approximately 1% develop malignancy with fewer being candidates for surgical resection. Overall, 44.8% of initial PCL reports provided CARG recommendations while 54.3% of PCLs were followed as per CARGs. Conclusions: CARGs are safe and offer substantial cost and opportunity savings for PCL surveillance. These findings support Canada-wide implementation with close monitoring of consultation requirements and missed diagnoses.

Association between academic degrees and research productivity: an assessment of Canadian academic general surgeons.

BACKGROUND: For academic hiring committees and surgical trainees, the benefits of a graduate degree are unclear. We sought to identify if graduate degrees or professorship status were associated with increased research productivity among Canadian academic surgeons. METHODS: We included general surgeons from the largest hospitals associated with accredited residency programs. We classified staff surgeons active between 2013 and 2018 by degree (MD only, master's degree, PhD) and professorship (assistant, associate, professor) status. We identified their publications from January 2013 to December 2018. Variables of interest included publications per year, citations per article, journal of publication, CiteScore, author's Hirsch (h) index and the revised h-index (r-index). We used Kruskal-Wallis tests and the Dunn multiple comparison test to assess statistical significance. RESULTS: We identified 3262 publications from 187 surgeons, including 78 (41.7%) with no graduate degree, 84 (44.9%) with master's degrees and 25 (13.4%) with PhDs. Surgeons with graduate degrees had more publications per year, higher CiteScores, more citations per article, and higher h- and r-indices than those without graduate degrees. Surgeons with doctorates had the highest median values in all domains, but differences were not significant compared with surgeons with master's degrees. Seventy-seven (41.8%) surgeons were assistant professors, 63 (34.2%) were associate professors and 44 (23.9%) were full professors. Statistically, full professors had a greater number of publications per year and higher h- and r-indices than their counterparts. CONCLUSION: Surgeons with graduate degrees or more advanced professorships had the greatest research productivity. Surgeons with doctorates trended toward greater research productivity than those holding master's degrees.

Cost-utility analysis of normothermic machine perfusion compared to static cold storage in liver transplantation in the Canadian setting.

To estimate the incremental cost-effectiveness of a liver transplant program that utilizes normothermic machine perfusion (NMP) alongside static cold storage (SCS) compared to SCS alone (control). A Markov model compared strategies (NMP vs. control) using 1-year cycle lengths over a 5-year time horizon from the public healthcare payer perspective. Primary micro-costing data from a single center retrospective trial were applied along with utility values from literature sources. Transition probabilities were deduced using the retrospective trial cohort, local transplant data, and supplemented with literature values. Scenario and probabilistic sensitivity analysis (PSA) were conducted. The NMP strategy was cost-effective in comparison to the control strategy, which was dominated. The mean cost for NMP was $456 455 (2021 US$) and the control was $519 222. The NMP strategy had greater incremental quality-adjusted life years (QALYs) gains over 5 years compared to the control, with 3.48 versus 3.17, respectively. The overarching results remained unchanged in scenario analysis. In PSA, NMP was cost-effective in 63% of iterations at a willingness-to-pay threshold of $40 941. The addition of NMP to a liver transplant program results in greater QALY gains and is cost-effective from the public healthcare payer perspective.

The Actual Operative Costs of Liver Transplantation and Normothermic Machine Perfusion in a Canadian Setting.

BACKGROUND: Liver transplantation is an effective treatment for end-stage liver disease. However, waiting lists continue to lengthen as demand exceeds supply. Use of extended criteria donors has helped but is associated with increased rates of complications. The application of normothermic machine perfusion (NMP) has been shown to be protective, especially in more marginal grafts. Despite this benefit, no cost-effectiveness studies have been published. OBJECTIVE: This study serves as a prelude to a cost-effectiveness analysis of the costs of liver procurement, transplantation, and machine perfusion in a Canadian setting. METHODS: The total costs were calculated for 106 in-province procurements, the set cost for 237 out-of-province procurements, and 343 liver transplantations. These costs include overheads, supplies, anaesthesia technologist and nursing salaries, and physician billings. Base and modified costs for all procedures were calculated, with consideration of physician billing modifiers. The total cost per run of NMP was calculated, with a range based on variations in the exchange rates for Great British pounds (£) to Canadian dollars ($Can), year 2019 values. RESULTS: Costs were $Can30,770.22 for in-province and $Can44,636.73 for out-of-province liver procurement and transplantation. These increased to $Can35,659.22 and 48,076.18 when considering modifiers. The minimum cost per NMP run was $Can18,593.02. CONCLUSIONS: Although the cost per run is substantial, NMP could potentially lead to cost savings by decreasing night-time salary premiums, complications, and patient length of stay. A formal cost-effectiveness study of NMP in liver transplantation is underway to help clarify the financial benefit or burden of this new technology.

Downstaging prior to liver transplantation for hepatocellular carcinoma: advisable but at the price of an increased risk of cancer recurrence - a retrospective study.

The use of downstaging prior to liver transplantation for hepatocellular carcinoma (HCC) still needs refinement. This study included patients with HCC listed for transplantation according to the Total Tumour Volume (TTV) ≤115 cm3 and alpha fetoprotein (AFP) ≤400 ng/ml criteria, with and without previous downstaging. Overall, 455 patients were listed, and 286 transplanted. Post-transplant follow-up was 38.5 ± 1.7 months. Patients downstaged to TTV115/AFP400 (n = 29) demonstrated similar disease-free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 (n = 257). Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Among patients downstaged to Milan, those originally beyond TTV115/AFP400 (n = 27) had similar outcomes as those originally beyond Milan, but within TTV115/AFP400 (n = 53). However, the likelihood of being within Milan at transplant was lower for patients with more advanced original HCCs (P < 0.0001). Overall, despite an expected increase in post-transplant HCC recurrence, similar survivals can be achieved with and without downstaging, using the TTV115/AFP400 transplantation criteria, and including patients with advanced original HCCs. Downstaging should continue to be performed.

Organ donation and transplantation: a survey of critical care health professionals in nontransplant hospitals.

CONTEXT: Exploration of the role of critical care professionals in improving organ donation within Canada has been limited to tertiary care centers while donor potential in smaller nontransplant hospitals remains unknown. OBJECTIVE: To gain an understanding of the knowledge, attitudes, and perceived barriers that healthcare professionals in 5 nontransplant hospitals in Alberta have toward organ donation and transplantation, and to identify factors that influenced participation in the donation process. DESIGN: A descriptive survey of critical care professionals. Setting-Five nontransplant hospitals in Alberta, Canada. RESULTS: Of the 135 respondents, 98 were critical care nurses, 32 were physicians, and 5 were hospital administrators. Respondents were least knowledgeable about transplant statistics and religious beliefs regarding donation, although overall, attitudes reflected positive support for organ donation. Respondents exhibited reluctance in approaching a potential donor family, and believed inadequate resources were allocated for organ donation. CONCLUSIONS: Educational programs are needed to increase knowledge of organ donation and transplantation as well as the development of an in-house coordinator program in nontransplant hospitals for critical care personnel.

Beta-score: an assessment of beta-cell function after islet transplantation.

OBJECTIVE: Success after islet transplantation can be defined in terms of insulin independence, C-peptide secretion, or glycemic control. These measures are interdependent and all need to be considered in evaluating beta-cell function after islet transplantation. For the current study, a composite beta-score was developed that provides an integrated measure of beta-cell function success after islet transplantation. RESEARCH DESIGN AND METHODS: The proposed scoring system gave 2 points each for normal fasting glucose, HbA(1c), stimulated C-peptide, and absence of insulin or oral hypoglycemic agent use. No points were awarded if the fasting glucose was in the diabetic range, the HbA(1c) was >6.9%, C-peptide secretion was absent on stimulation, or daily insulin use was in excess of 0.24 units/kg. One point was given for intermediate values. The score ranged from 0 to 8 and was correlated with the glucose value 90 min after a standard mixed meal challenge (n = 218) in 57 subjects before and after islet transplantation. The score was also used to follow subjects for up to 5 years after islet transplantation. RESULTS: The beta-score correlated well with the plasma glucose level 90 min after a mixed meal challenge (r = -0.849, P < 0.001). On follow-up, the beta-score rose after the first transplant and was maintained up to 5 years, demonstrating continuing function of the transplanted beta-cells. CONCLUSIONS: The beta-score provides a simple clinical scoring system that encompasses glycemic control, diabetes therapy, and endogenous insulin secretion that correlates well with physiological measures of beta-cell function. On this basis, it is suitable as an overall measure of beta-cell transplant function. The beta-score gives an integrated measure of beta-cell function as a continuum that may be more useful than simply assessing the presence or absence of insulin independence.

Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation.

Currently, the major indications for solitary islet transplantation are recurrent severe hypoglycemia and labile glucose control. Quantifying these problems remains subjective. We have developed a scoring system for both hypoglycemia and glycemic lability, established normative data, and used them in patients who have undergone islet transplantation. A composite hypoglycemic score (HYPO score) was devised based on the frequency, severity, and degree of unawareness of the hypoglycemia. In addition, using 4 weeks of glucose records, a lability index (LI) was calculated based on the change in glucose levels over time and compared with a clinical assessment of glycemic lability. A mean amplitude of glycemic excursions (MAGE) was also calculated based on 2 consecutive days of seven readings each day. These scores were determined in 100 randomly selected subjects with type 1 diabetes from our general clinic to serve as a control group and in patients before and after islet transplantation. The mean age of the control diabetic subjects was 38.4 +/- 1.3 years (+/-SE), with a duration of diabetes of 21.5 +/- 1.1 years. The median HYPO score in the control subjects was 143 (25th to 75th interquartile range: 46-423). The LI in the diabetic control subjects was 223 (25th to 75th interquartile range: 130-329 mmol/l(2)/h.week(-1)). The LI correlated much more closely than the MAGE with the clinical assessment of lability. A HYPO score of > or = 1,047 (90th percentile) or an LI > or = 433 mmol/l(2)/h.week(-1) (90th percentile) indicated serious problems with hypoglycemia or glycemic lability, respectively. The islet transplant patients (n = 51) were 42.1 +/- 1.4 years old, with a duration of diabetes of 25.7 +/- 1.4 years. Islet transplant patients had a mean HYPO score of 1,234 +/- 184 pretransplant, which was significantly higher than that of the control subjects (P < 0.001), which became negligible posttransplantation with the elimination of hypoglycemia. The median LI pretransplant was 497 mmol/l(2)/h.week(-1) (25th to 75th interquartile range: 330-692), significantly higher than that of control subjects (P < 0.001), and fell to 40 (25th to 75th interquartile range: 14-83) within a month after the final transplant. In those who had lost graft function, the LI rose again. The HYPO score and LI provide measures of the extent of problems with hypoglycemia and glycemic lability, respectively, complement the clinical assessment of the problems with glucose control before islet transplantation, and will allow comparison of selection of subjects for transplants between centers.