Impact of hypoalbuminemia on outcomes following pancreaticoduodenectomy: a NSQIP retrospective cohort analysis of 25,848 patients.

BACKGROUND: Efforts to preoperatively risk stratify and optimize patients before pancreaticoduodenectomy continue to improve outcomes. This study aims to determine the impact of hypoalbuminemia on outcomes following pancreaticoduodenectomy and outline optimal hypoalbuminemia cut-off values in this population. METHODS: The ACS-NSQIP (2016-2021) database was used to extract patients who underwent pancreaticoduodenectomy, comparing those with hypoalbuminemia (< 3.0 g/L) to those with normal albumin. Demographics and 30-day outcomes were compared. Multivariable modeling evaluated factors including hypoalbuminemia to characterize their independent effect on serious complications, and mortality. Optimal albumin cut-offs for serious complications and mortality were evaluated using receiver-operating characteristic curves. RESULTS: We evaluated 25,848 pancreaticoduodenectomy patients with 2712 (10.5%) having preoperative hypoalbuminemia. Patients with hypoalbuminemia were older (68.2 vs. 65.1; p < 0.0001), and were significantly more likely to be ASA class 4 or higher (13.9% vs. 6.7%; p < 0.0001). Patients with hypoalbuminemia had significantly more 30-day complications and after controlling for comorbidities hypoalbuminemia remained a significant independent factor associated with 30-day serious complications (OR 1.80, p < 0.0001) but not mortality (OR 1.37, p = 0.152). CONCLUSIONS: Hypoalbuminemia plays a significant role in 30-day morbidity following pancreaticoduodenectomy. Preoperative albumin may serve as a useful marker for risk stratification and optimization.

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.

Persistent hyperbilirubinemia following preoperative biliary stenting in patients undergoing anatomic hepatectomy predicts serious complications.

BACKGROUND: Biliary obstruction before liver resection is a known risk factor for post-operative complications. The aim of this study was to determine the impact of persistent hyperbilirubinemia following preoperative biliary drainage before liver resection. METHODS: The ACS-NSQIP (2016-2021) database was used to extract patients with cholangiocarcinoma who underwent anatomic liver resection with preoperative biliary drainage comparing those with persistent hyperbilirubinemia (> 1.2 mg/dL) to those with resolution. Patient characteristics and outcomes were compared with bivariate analysis. Multivariable modeling evaluated factors including persistent hyperbilirubinemia to evaluate their independent effect on serious complications, liver failure, and mortality. RESULTS: We evaluated 463 patients with 217 (46.9%) having hyperbilirubinemia (HB) despite biliary stenting. Bivariate analysis demonstrated that patients with HB had a higher rate of serious complications than those with non-HB (80.7% vs 70.3%; P = 0.010) including bile leak (40.9% vs 31.8%; P = 0.045), liver failure (26.7% vs 17.9%; P = 0.022), and bleeding (48.4% vs 36.6%; P = 0.010). Multivariable analysis demonstrated that persistent HB was independently associated with serious complications (OR 1.88, P = 0.020) and mortality (OR 2.39, P = 0.049) but not post-operative liver failure (OR 1.65, P = 0.082). CONCLUSIONS: Failed preoperative biliary decompression is a predictive factor for post-operative complications and mortality in patients undergoing hepatectomy and may be useful for preoperative risk stratification.

Evaluating Islet Cell Isolation and Transplantation From Donors Following Medical Assistance in Dying.

Background: Limited information is available regarding outcomes of islet cell isolation (ICI) and transplantation (ITx) using medical assistance in dying (MAiD) donors. We aimed to assess the feasibility and outcomes of ICI and ITx in MAiD donors. Methods: ICI and ITx from MAiD were compared with donation after circulatory death (DCD) type III between 2016 and 2023. Differences of isolated islet equivalents (IEQs), numeric viability and other quantitative in vitro metabolic measures were assessed. Results: Overall, 81 ICIs were available of whom 34 (42%) and 47 (58%) from MAiD and DCD-III, respectively. There were no differences of pancreas and digested tissue weight and islets viability among the 2 groups; however, cold ischemic time was longer in MAiD (11.5 versus 9.1 h; P = 0.021). The IEQ (P < 0.001) and percent trapped (P < 0.001) were higher in the DCD-III; however, MAiD islets demonstrated a higher purity (P = 0.020). Overall, 15 ITx were performed of whom 3 (8.8%) and 12 (25.5%) from MAiD and DCD-III, respectively (P = 0.056). Patients had a median fasting C-peptide of 0.51 ng/mL (interquartile range, 0.30-0.76 nmol/L), with no differences between groups (MAiD = 0.52 versus DCD-III = 0.51; P = 0.718). The median HbA1c was 6.2% (interquartile range, 5.7%-7%) (MAiD = 6.3% versus DCD-III = 6.1%; P = 0.815) and BETA2 scores (MAiD = 7.4 versus DCD-III = 12.8; P = 0.229) did not differ. Conclusions: ICI from MAiD donor pancreas may be successfully transplanted with comparable outcomes to DCD-III and may be used for research. These results justify additional efforts to consider MAiD as another valuable source of grafts for ITx. Further multicenter studies and larger clinical experience are needed to validate our findings.

Exploring the Impact of In Basket Metrics on the Adoption of a New Electronic Health Record System Among Specialists in a Tertiary Hospital in Alberta: Descriptive Study.

BACKGROUND: Health care organizations implement electronic health record (EHR) systems with the expectation of improved patient care and enhanced provider performance. However, while these technologies hold the potential to create improved care and system efficiencies, they can also lead to unintended negative consequences, such as patient safety issues, communication problems, and provider burnout. OBJECTIVE: This study aims to document metrics related to the In Basket communication hub (time in In Basket per day, time in In Basket per appointment, In Basket messages received per day, and turnaround time) of the EHR system implemented by Alberta Health Services, the province-wide health delivery system called Connect Care (Epic Systems). The objective was to identify how a newly implemented EHR system was used, the timing of its use, and the duration of use specifically related to In Basket activities. METHODS: A descriptive study was conducted. Due to the diversity of specialties, the providers were grouped into medical and surgical based on previous similar studies. The participants were further subgrouped based on their self-reported clinical full-time equivalent (FTE ) measure. This resulted in 3 subgroups for analysis: medical FTE <0.5, medical FTE >0.5, and surgical (all of whom reported FTE >0.5). The analysis was limited to outpatient clinical interactions and explicitly excluded inpatient activities. RESULTS: A total of 72 participants from 19 different specialties enrolled in this study. The providers had, on average, 8.31 appointments per day during the reporting periods. The providers received, on average, 21.93 messages per day, and they spent 7.61 minutes on average in the time in In Basket per day metric and 1.84 minutes on average in the time in In Basket per appointment metric. The time for the providers to mark messages as done (turnaround time) was on average 11.45 days during the reporting period. Although the surgical group had, on average, approximately twice as many appointments per scheduled day, they spent considerably less connected time (based on almost all time metrics) than the medical group. However, the surgical group took much longer than the medical group to mark messages as done (turnaround time). CONCLUSIONS: We observed a range of patterns with no consistent direction. There does not seem to be evidence of a "learning curve," which would have shown a consistent reduction in time spent on the system over time due to familiarity and experience. While this study does not show how the included metrics could be used as predictors of providers' satisfaction or feelings of burnout, the use trends could be used to start discussions about future Canadian studies needed in this area.

Cyclosporine A Does Not Mitigate Liver Ischemia/Reperfusion Injury in an Ex Vivo Porcine Model of Donation After Circulatory Death.

BACKGROUND Ischemia/reperfusion injury (IRI) is an inherent problem in organ transplantation, owing to the obligate period of ischemia that organs must endure. Cyclosporine A (CsA), though better know as an immunosuppressant, has been shown to mitigate warm IRI in a variety of organ types, including the liver. However, there is little evidence for CsA in preventing hepatic IRI in the transplant setting. MATERIAL AND METHODS In the present study, we tested the effect of CsA on hepatic IRI in a large-animal ex vivo model of donation after circulatory death (DCD). Porcine donors were pre-treated with either normal saline control or 20 mg/kg of CsA. Animals were subject to either 45 or 60 minutes of warm ischemia before hepatectomy, followed by 2 or 4 hours of cold storage prior to reperfusion on an ex vivo circuit. Over the course of a 12-hour perfusion, perfusion parameters were recorded and perfusate samples and biopsies were taken at regular intervals. RESULTS Peak perfusate lactate dehydrogenase was significantly decreased in the lower-ischemia group treated with CsA compared to the untreated group (4220 U/L [3515-5815] vs 11 305 [10 100-11 674]; P=0.023). However, no difference was seen between controls and CsA-treated groups on other parameters in perfusate alanine or asparagine aminotransferase (P=0.912, 0.455, respectively). Correspondingly, we found no difference on midpoint histological injury score (P=0.271). CONCLUSIONS We found minimal evidence that CsA is protective against hepatic IRI in our DCD model.

Islet transplantation outcomes in type 1 diabetes and transplantation of HLA-DQ8/DR4: results of a single-centre retrospective cohort in Canada.

Background: In solid organ transplantation, HLA matching between donor and recipient is associated with superior outcomes. In islet transplantation, an intervention for Type 1 diabetes, HLA matching between donor and recipient is not performed as part of allocation. Susceptibility to Type 1 diabetes is associated with the presence of certain HLA types. This study was conducted to determine the impact of these susceptibility antigens on islet allograft survival. Methods: This is a single-centre retrospective cohort study. This cohort of transplant recipients (n = 268) received islets from 661 donor pancreases between March 11th, 1999 and August 29th, 2018 at the University of Alberta Hospital (Edmonton, AB, Canada). The frequency of the Type 1 diabetes susceptibility HLA antigens (HLA-A24, -B39, -DQ8, -DQ2 and-DQ2-DQA1∗05) in recipients and donors were determined. Recipient and donor HLA antigens were examined in relation to time to first C-peptide negative status/graft failure or last observation point. Taking into account multiple transplants per patient, we fitted a Gaussian frailty survival analysis model with baseline hazard function stratified by transplant number, adjusted for cumulative islet dose and other confounders. Findings: Across all transplants recipients of donors positive for HLA-DQ8 had significantly better graft survival (adjusted HRs 0.33 95% CI 0.17-0.66; p = 0.002). At first transplant only, donors positive for HLA-DQ2-DQA1∗05 had inferior graft survival (adjusted HR 1.96 95% CI 1.10-3.46); p = 0.02), although this was not significant in the frailty analysis taking multiple transplants into account (adjusted HR 1.46 95% CI 0.77-2.78; p = 0.25). Other HLA antigens were not associated with graft survival after adjustment for confounders. Interpretation: Our findings suggest islet transplantation from HLA-DQ8 donors is associated with superior graft outcomes. A donor positive for HLA-DQ2-DQA1∗05 at first transplant was associated with inferior graft survival but not when taking into account multiple transplants per recipient. The relevance of HLA-antigens on organ allocation needs further evaluation and inclusion in islet transplant registries and additional observational and interventional studies to evaluate the role of HLA-DQ8 in islet graft survival are required. Funding: None.

Myocardial Injury After Noncardiac Surgery in Major General Surgical Patients a Prospective Observational Cohort Study.

OBJECTIVE: The objective of this study was to determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in major general surgery patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in major general surgical patients have not been described. METHODS: This was an international prospective cohort study of a representative sample of 22,552 noncardiac surgery patients 45 years or older, of whom 4490 underwent major general surgery in 24 centers in 13 countries. All patients had fifth-generation plasma high-sensitivity troponin T (hsTnT) concentrations measured during the first 3 postoperative days. MINS was defined as a hsTnT of 20-65 ng/L and absolute change >5 ng/L or hsTnT ≥65 ng/L secondary to ischemia. The objectives of the present study were to determine (1) whether MINS is prognostically important in major general surgical patients, (2) the clinical characteristics of major general surgical patients with and without MINS, (3) the 30-day outcomes for major general surgical patients with and without MINS, and (4) the proportion of MINS that would have gone undetected without routine postoperative monitoring. RESULTS: The incidence of MINS in the major general surgical patients was 16.3% (95% CI, 15.3-17.4%). Thirty-day all-cause mortality in the major general surgical cohort was 6.8% (95% CI, 5.1%-8.9%) in patients with MINS compared with 1.2% (95% CI, 0.9%-1.6%) in patients without MINS ( P <0.01). MINS was independently associated with 30-day mortality in major general surgical patients (adjusted odds ratio 4.7, 95% CI, 3.0-7.4). The 30-day mortality was higher both among MINS patients with no ischemic features (ie, no ischemic symptoms or electrocardiogram findings) (5.4%, 95% CI, 3.7%-7.7%) and among patients with 1 or more clinical ischemic features (10.6%, 95% CI, 6.7%-15.8%). The proportion of major general surgical patients who had MINS without ischemic symptoms was 89.9% (95% CI, 87.5-92.0). CONCLUSIONS: Approximately 1 in 6 patients experienced MINS after major general surgery. MINS was independently associated with a nearly 5-fold increase in 30-day mortality. The vast majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Long-term outcomes after normothermic machine perfusion in liver transplantation-Experience at a single North American center.

Normothermic machine perfusion (NMP) has emerged as a valuable tool in the preservation of liver allografts before transplantation. Randomized trials have shown that replacing static cold storage (SCS) with NMP reduces allograft injury and improves graft utilization. The University of Alberta's liver transplant program was one of the early adopters of NMP in North America. Herein, we describe our 7-year experience applying NMP to extend preservation time in liver transplantation using a "back-to-base" approach. From 2015 to 2021, 79 livers were transplanted following NMP, compared with 386 after SCS only. NMP livers were preserved for a median time of minutes compared with minutes in the SCS cohort (P < .0001). Despite this, we observed significantly improved 30-day graft survival (P = .030), although there were no differences in long-term patient survival, major complications, or biliary or vascular complications. We also found that although SCS time was strongly associated with increased graft failure at 1 year in the SCS cohort (P = .006), there was no such association among NMP livers (P = .171). Our experience suggests that NMP can safely extend the total preservation time of liver allografts without increasing complications.

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.

Trends in types of graduate degrees and research output for academic general surgeons in Canada.

SummaryThe proportion of general surgeons with graduate degrees in Canada is increasing. We sought to evaluate the types of graduate degree held by surgeons in Canada, and whether differences in publication capacity exist. We evaluated all general surgeons working at English-speaking Canadian academic hospitals to determine the types of degrees achieved, changes over time and research output associated with each degree. We identified 357 surgeons, of whom 163 (45.7 %) had master's degrees and 49 (13.7 %) had PhDs. Achievement of graduate degrees increased over time, with more surgeons earning master's degrees in public health (MPH), clinical epidemiology and education (MEd), and fewer master's degrees in science (MSc) or PhDs. Most publication metrics were similar by degree type, but surgeons with PhDs published more basic science research than those with clinical epidemiology, MEd or MPH degrees (2.0 v. 0.0, p < 0.05); surgeons with clinical epidemiology degrees published more first-author articles than surgeons with MSc degrees (2.0 v. 0.0, p = 0.007). An increasing number of general surgeons hold graduate degrees, with fewer pursuing MSc and PhD degrees, and more holding MPH or clinical epidemiology degrees. Research productivity is similar for all groups. Support to pursue diverse graduate degrees could enable a greater breadth of research.

COVID-19 Infection and Acute Pancreas Transplant Graft Thrombosis.

The coronavirus disease 2019 (COVID-19) pandemic created an unprecedented challenge for healthcare, and the world continues to struggle in recovering from its aftermath. COVID-19 has been clearly linked to hypercoagulable states and can lead to end-organ ischemia, morbidity, and mortality. Immunosuppressed solid organ transplant recipients represent a highly vulnerable population for the increased risk of complications and mortality. Early venous or arterial thrombosis with acute graft loss after whole pancreas transplantation is well-described, but late thrombosis is rare. We herein report a case of acute, late pancreas graft thrombosis at 13 years post pancreas-after-kidney (PAK) transplantation coinciding with an acute COVID-19 infection in a previously double-vaccinated recipient.

Examining need and capacity for the development of a pediatric liver transplantation program in Kenya.

BACKGROUND: In Africa, pediatric liver transplantation (PLT) is currently only performed in Egypt and South Africa, leaving those who require treatment in Kenya to travel abroad. The aim of this study was to determine whether sufficient capacity and need exists in Kenya to establish a safe and sustainable PLT program. METHODS: A descriptive analysis of the intensive care unit (ICU) beds, surgical workforce, current hepatobiliary volume, and estimated prevalence of pediatric liver disease (PLD) was conducted across 17 hospitals in Kenya between July and September 2020. Data were collected from medical superintendents, directors of surgical departments, or nominated proxies at Kenyan Level 5 and 6 hospitals via a web-based survey. RESULTS: A total of 165 ICU beds were reported at 17 facilities, with 15 facilities reporting five or more beds. About 39% of general surgeons at responding hospitals performed hepatobiliary procedures, and 30% performed pediatric surgeries. Only 10% of surgeons had pediatric training. Over half (57%) of hospitals performed hepatobiliary procedures; at the maximum, 1-5 cases were performed per week including cholecystectomy to Kasai portoenterostomy and hepatectomy. Across 13 hospitals, there were an estimated 192-570 cases of PLD seen per month. The most common PLDs were hepatitis B, neonatal hepatitis, cirrhosis, and acute hepatic failure. Overall, two hospitals possessed the minimum workforce and resources to attempt PLT. CONCLUSIONS: In Kenya, ICU bed availability, pediatric surgical training, and hepatobiliary volume are limited. However, the high prevalence of PLD demonstrated a significant need for PLT across all Kenyan hospitals.

C-peptide Targets and Patient-centered Outcomes of Relevance to Cellular Transplantation for Diabetes.

BACKGROUND: C-peptide levels are a key measure of beta-cell mass following islet transplantation, but threshold values required to achieve clinically relevant patient-centered outcomes are not yet established. METHODS: We conducted a cross-sectional retrospective cohort study evaluating patients undergoing islet transplantation at a single center from 1999 to 2018. Cohorts included patients achieving insulin independence without hypoglycemia, those with insulin dependence without hypoglycemia, and those with recurrent symptomatic hypoglycemia. Primary outcome was fasting C-peptide levels at 6 to 12 mo postfirst transplant; secondary outcomes included stimulated C-peptide levels and BETA-2 scores. Fasting and stimulated C-peptide and BETA-2 cutoff values for determination of hypoglycemic freedom and insulin independence were evaluated using receiver operating characteristic curves. RESULTS: We analyzed 192 patients, with 122 (63.5%) being insulin independent without hypoglycemia, 61 (31.8%) being insulin dependent without hypoglycemia, and 9 (4.7%) experiencing recurrent symptomatic hypoglycemia. Patients with insulin independence had a median (interquartile range) fasting C-peptide level of 0.66 nmol/L (0.34 nmol/L), compared with 0.49 nmol/L (0.25 nmol/L) for those being insulin dependent without hypoglycemia and 0.07 nmol/L (0.05 nmol/L) for patients experiencing hypoglycemia ( P < 0.001). Optimal fasting C-peptide cutoffs for insulin independence and hypoglycemia were ≥0.50 nmol/L and ≥0.12 nmol/L, respectively. Cutoffs for insulin independence and freedom of hypoglycemia using stimulated C-peptide were ≥1.2 nmol/L and ≥0.68 nmol/L, respectively, whereas optimal cutoff BETA-2 scores were ≥16.4 and ≥5.2. CONCLUSIONS: We define C-peptide levels and BETA-2 scores associated with patient-centered outcomes. Characterizing these values will enable evaluation of ongoing clinical trials with islet or stem cell therapies.

Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years.

OBJECTIVE: To provide the largest single-center analysis of islet (ITx) and pancreas (PTx) transplantation. SUMMARY BACKGROUND DATA: Studies describing long-term outcomes with ITx and PTx are scarce. METHODS: We included adults undergoing ITx (n=266) and PTx (n=146) at the University of Alberta from January 1999 to October 2019. Outcomes include patient and graft survival, insulin independence, glycemic control, procedure-related complications, and hospital readmissions. Data are presented as medians (interquartile ranges, IQR) and absolute numbers (percentages, %) and compared using Mann-Whitney and χ2 tests. Kaplan-Meier estimates, Cox proportional hazard models and mixed main effects models were implemented. RESULTS: Crude mortality was 9.4% and 14.4% after ITx and PTx, respectively ( P= 0.141). Sex-adjusted and age-adjusted hazard-ratio for mortality was 2.08 (95% CI, 1.04-4.17, P= 0.038) for PTx versus ITx. Insulin independence occurred in 78.6% and 92.5% in ITx and PTx recipients, respectively ( P= 0.0003), while the total duration of insulin independence was 2.1 (IQR 0.8-4.6) and 6.7 (IQR 2.9-12.4) year for ITx and PTx, respectively ( P= 2.2×10 -22 ). Graft failure ensued in 34.2% and 19.9% after ITx and PTx, respectively ( P =0.002). Glycemic control improved for up to 20-years post-transplant, particularly for PTx recipients (group, P= 7.4×10 -7 , time, P =4.8×10 -6 , group*time, P= 1.2×10 -7 ). Procedure-related complications and hospital readmissions were higher after PTx ( P =2.5×10 -32 and P= 6.4×10 -112 , respectively). CONCLUSIONS: PTx shows higher sex-adjusted and age-adjusted mortality, procedure-related complications and readmissions compared with ITx. Conversely, insulin independence, graft survival and glycemic control are better with PTx. This study provides data to balance risks and benefits with ITx and PTx, which could improve shared decision-making.

Rate of prophylactic anti-Xa achievement and impact on venous thromboembolism following oncologic hepato-pancreatico-biliary surgery: A prospective cohort study.

BACKGROUND: Hepato-pancreatico-biliary (HPB) patients experience competing risk of venous thromboembolism (VTE) and bleeding. We sought to evaluate the effect of anti-Xa levels on VTE and bleeding, and to characterize factors associated with subprophylaxis. METHODS: This prospective cohort study evaluated adult HPB surgical patients; cohorts were described by anti-Xa levels as subprophylactic (<0.2 IU/mL), prophylactic (0.2-0.5 IU/mL), and supraprophylactic (>0.5 IU/mL). Primary outcome evaluated bleeding and VTE complications. Secondary outcomes evaluated factors associated with subprophylaxis. RESULTS: We included 157 patients: 68 (43.6%) attained prophylactic anti-Xa and 89 (56.7%) were subprophylactic. Subprophylactic patients experienced more VTE compared to prophylactic patients (6.9% vs 0%; p = 0.028) without differences in bleeding complications (14.6% vs 5.9%; p = 0.081). Factors associated with subprophylactic anti-Xa included female sex (OR 2.90, p = 0.008), and Caprini score (OR 1.30, p = 0.035). Enoxaparin was protective against subprophylaxis compared to tinzaparin (OR 0.43, p = 0.029). CONCLUSIONS: Many HPB patients have subprophylactic anti-Xa levels, placing them at risk of VTE. Enoxaparin may be preferential, however, studies evaluating optimized prophylaxis are needed.

Model of Acute Liver Failure in an Isolated Perfused Porcine Liver-Challenges and Lessons Learned.

Acute liver failure (ALF) is a rare but devastating disease associated with substantial morbidity and a mortality rate of almost 45%. Medical treatments, apart from supportive care, are limited and liver transplantation may be the only rescue option. Large animal models, which most closely represent human disease, can be logistically and technically cumbersome, expensive and pose ethical challenges. The development of isolated organ perfusion technologies, originally intended for preservation before transplantation, offers a new platform for experimental models of liver disease, such as ALF. In this study, female domestic swine underwent hepatectomy, followed by perfusion of the isolated liver on a normothermic machine perfusion device. Five control livers were perfused for 24 h at 37 °C, while receiving supplemental oxygen and nutrition. Six livers received toxic doses of acetaminophen given over 12 h, titrated to methemoglobin levels. Perfusate was sampled every 4 h for measurement of biochemical markers of injury (e.g., aspartate aminotransferase [AST], alanine aminotransferase [ALT]). Liver biopsies were taken at the beginning, middle, and end of perfusion for histological assessment. Acetaminophen-treated livers received a median dose of 8.93 g (8.21-9.75 g) of acetaminophen, achieving a peak acetaminophen level of 3780 µmol/L (3189-3913 µmol/L). Peak values of ALT (76 vs. 105 U/L; p = 0.429) and AST (3576 vs. 4712 U/L; p = 0.429) were not significantly different between groups. However, by the end of perfusion, histology scores were significantly worse in the acetaminophen treated group (p = 0.016). All acetaminophen treated livers developed significant methemoglobinemia, with a peak methemoglobin level of 19.3%, compared to 2.0% for control livers (p = 0.004). The development of a model of ALF in the ex vivo setting was confounded by the development of toxic methemoglobinemia. Further attempts using alternative agents or dosing strategies may be warranted to explore this setting as a model of liver disease.

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study.

BACKGROUND: Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited. METHODS: This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018. Primary outcome was stimulated C-peptide level. Secondary outcomes were fasting plasma glucose, BETA-2 scores, and fasting C-peptide level. Multivariable logistic modeling evaluated factors independently associated with a composite variable of early graft failure and primary nonfunction within 60 d of ITx. RESULTS: Of 264 patients, 9 (3.5%) received extrahepatic ITx (gastric submucosal = 2, subcutaneous = 3, omental = 4). Group demographics were similar at baseline (age, body mass index, diabetes duration, and glycemic control). At 1-3 mo post-first infusion, patients receiving extrahepatic ITx had significantly lower stimulated C-peptide (0.05 nmol/L versus 1.2 nmol/L, P < 0.001), higher fasting plasma glucose (9.3 mmol/L versus 7.3 mmol/L, P < 0.001), and lower BETA-2 scores (0 versus 11.6, P < 0.001) and SUITO indices (1.5 versus 39.6, P < 0.001) compared with those receiving intraportal ITx. Subjects receiving extrahepatic grafts failed to produce median C-peptide ≥0.2 nmol/L within the first 60 d after transplant. Subsequent intraportal infusion following extrahepatic transplants achieved equivalent outcomes compared with patients receiving intraportal transplant alone. Extrahepatic ITx was independently associated with early graft failure/primary non-function (odds ratio 1.709, confidence interval 73.8-39 616.0, P < 0.001), whereas no other factors were independently predictive. CONCLUSIONS: Using current techniques, intraportal islet infusion remains the gold standard for clinical ITx, with superior engraftment, graft function, and glycemic outcomes compared with extrahepatic transplantation of human islets.