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2.
J Med Internet Res ; 26: e53122, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684079

ABSTRACT

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.


Subject(s)
Electronic Health Records , Tertiary Care Centers , Alberta , Humans , Specialization
4.
EClinicalMedicine ; 67: 102333, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38169703

ABSTRACT

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.

5.
Ann Transplant ; 29: e941054, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38287661

ABSTRACT

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.


Subject(s)
Cyclosporine , Reperfusion Injury , Swine , Animals , Cyclosporine/pharmacology , Cyclosporine/therapeutic use , Liver/pathology , Reperfusion Injury/pathology , Perfusion , Reperfusion , Organ Preservation/methods
6.
Ann Surg ; 278(6): e1192-e1197, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37459169

ABSTRACT

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.


Subject(s)
Postoperative Complications , Troponin T , Humans , Prospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prognosis , Incidence , Risk Factors
7.
J Can Assoc Gastroenterol ; 6(2): 86-93, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37025512

ABSTRACT

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.

8.
Am J Transplant ; 23(7): 976-986, 2023 07.
Article in English | MEDLINE | ID: mdl-37086951

ABSTRACT

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.


Subject(s)
Liver Transplantation , Humans , Organ Preservation , Liver/blood supply , Perfusion , Graft Survival
9.
Cureus ; 15(1): e34087, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36843771

ABSTRACT

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.

10.
Can J Surg ; 66(1): E88-E92, 2023.
Article in English | MEDLINE | ID: mdl-36813299

ABSTRACT

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.


Subject(s)
Biomedical Research , Surgeons , Humans , Canada , Public Health/education , Hospitals
11.
Pediatr Transplant ; 27(2): e14462, 2023 03.
Article in English | MEDLINE | ID: mdl-36604852

ABSTRACT

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.


Subject(s)
Liver Transplantation , Child , Infant, Newborn , Humans , Kenya , Hospital Bed Capacity , Surveys and Questionnaires , Egypt
12.
Am J Surg ; 225(6): 1022-1028, 2023 06.
Article in English | MEDLINE | ID: mdl-36526454

ABSTRACT

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.


Subject(s)
Enoxaparin , Heparin, Low-Molecular-Weight , Venous Thromboembolism , Adult , Female , Humans , Anticoagulants/therapeutic use , Enoxaparin/therapeutic use , Hemorrhage/complications , Heparin, Low-Molecular-Weight/therapeutic use , Prospective Studies , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
13.
Ann Surg ; 277(4): 672-680, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36538619

ABSTRACT

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.


Subject(s)
Islets of Langerhans Transplantation , Pancreas Transplantation , Adult , Humans , Pancreas , Insulin
14.
Transplantation ; 107(3): 774-781, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36253897

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Islets of Langerhans Transplantation , Humans , C-Peptide , Diabetes Mellitus, Type 1/therapy , Retrospective Studies , Cross-Sectional Studies , Blood Glucose , Follow-Up Studies , Insulin/therapeutic use , Patient-Centered Care
15.
Biomedicines ; 10(10)2022 Oct 06.
Article in English | MEDLINE | ID: mdl-36289758

ABSTRACT

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.

16.
Transplantation ; 106(11): 2224-2231, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35676866

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 1 , Islets of Langerhans Transplantation , Humans , Islets of Langerhans Transplantation/adverse effects , Islets of Langerhans Transplantation/methods , Blood Glucose , C-Peptide , Cohort Studies , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/surgery
17.
JHEP Rep ; 4(7): 100495, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35600667

ABSTRACT

Background & Aims: Association between sarcopenia and mortality in cirrhosis is well recognised; however, little is known about the clinical implications of adipose tissue radiodensity, indicative of biological features. This study aimed to determine an association between high subcutaneous adipose tissue (SAT) radiodensity and survival, compare the prevalence of high SAT radiodensity between healthy population and patients with cirrhosis, and identify an association between computed tomography (CT)-measured SAT radiodensity and histological characteristics. Methods: Adult patients with cirrhosis (n = 786) and healthy donors (n = 129) with CT images taken as part of the liver transplant (LT) assessment were included. Abdominal SAT biopsies (1-2 g) were harvested from the incision site at the time of LT from 12 patients with cirrhosis. Results: The majority of patients were male (67%) with a mean model for end-stage liver disease (MELD) score of 15 ± 8. SAT radiodensity above -83 HU in females (sub-distribution hazard ratio [sHR] 1.84, 95% CI 1.20-2.85, p = 0.006) and higher than -74 HU in males (sHR 1.51, 95% CI 1.05-1.18, p = 0.02) was associated with the highest mortality risk after adjusting for confounders in competing risk analysis. The frequency of high SAT radiodensity was 26% for those with cirrhosis, compared with 2% in healthy donors (p <0.001). An inverse correlation was found between SAT radiodensity and the mean cross-sectional area of SAT adipocytes (r = -0.67, p = 0.02). Shrunken, smaller adipocytes with expanded interstitial space were predominant in patients with high SAT radiodensity, whereas larger adipocytes with a thin rim of cytoplasm were observed in patients with low SAT radiodensity (744 ± 400 vs. 1,521 ± 1,035 µm2, p <0.001). Conclusion: High SAT radiodensity frequently presents and is associated with a higher mortality in cirrhosis. SAT morphological rearrangement in patients with high SAT radiodensity might indicate diminished lipid stores and alterations in tissue characteristics. Lay summary: Poor quality of subcutaneous adipose tissue (fat under the skin) is associated with higher mortality in patients with end-stage liver disease. Fat cells are smaller in patients with poor adipose tissue quality.

18.
Can J Surg ; 65(3): E372-E380, 2022.
Article in English | MEDLINE | ID: mdl-35613720

ABSTRACT

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.


Subject(s)
Internship and Residency , Surgeons , Canada , Efficiency , Humans , United States
19.
Lancet Diabetes Endocrinol ; 10(7): 519-532, 2022 07.
Article in English | MEDLINE | ID: mdl-35588757

ABSTRACT

BACKGROUND: Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation. METHODS: This cohort study included patients older than 18 years with type 1 diabetes undergoing allogeneic islet transplantation between March 11, 1999, and Oct 1, 2019, at the University of Alberta Hospital (Edmonton, AB, Canada). Patients who underwent islet-after-kidney transplantation and islet transplantation alone or islet transplantation before whole-pancreas transplantation (follow-up was censored at the time of whole-pancreas transplantation) were included. Patient survival, graft survival (fasting plasma C-peptide >0·1 nmol/L), insulin independence, glycaemic control, and adverse events are reported. To identify factors associated with prolonged graft survival, recipients with sustained graft survival (≥90% of patient follow-up duration) were compared with those who had non-sustained graft survival (<90% of follow-up duration). Multivariate binary logistic regression analyses were done to determine predictors of sustained graft survival. FINDINGS: Between March 11, 1999, and Oct 1, 2019, 255 patients underwent islet transplantation and were included in the analyses (149 [58%] were female and 218 [85%] were White). Over a median follow-up of 7·4 years (IQR 4·4-12·2), 230 (90%) patients survived. Median graft survival was 5·9 years (IQR 3·0-9·5), and graft failure occurred in 91 (36%) patients. 178 (70%) recipients had sustained graft survival, and 77 (30%) had non-sustained graft survival. At baseline, compared with patients with non-sustained graft survival, those with sustained graft survival had longer median type 1 diabetes duration (33·5 years [IQR 24·3-41·7] vs 26·2 years [17·0-35·5]; p=0·0003), median older age (49·4 years [43·5-56·1] vs 44·2 years [35·4-54·2]; p=0·0011), and lower median insulin requirements (0·53 units/kg per day [0·45-0·67] vs 0·59 units/kg per day [0·48-0·70]; p=0·032), but median HbA1c concentrations were similar (8·2% [7·5-9·0] vs 8·5% [7·8-9·2]; p=0·23). 201 (79%) recipients had insulin independence, with a Kaplan-Meier estimate of 61% (95% CI 54-67) at 1 year, 32% (25-39) at 5 years, 20% (14-27) at 10 years, 11% (6-18) at 15 years, and 8% (2-17) at 20 years. Patients with sustained graft survival had significantly higher rates of insulin independence (160 [90%] of 178 vs 41 [53%] of 77; p<0·0001) and sustained improvements in glycaemic control mixed-main-effects model group effect, p<0·0001) compared with those with non-sustained graft survival. Multivariate analyses identified the combined use of anakinra plus etanercept (adjusted odds ratio 7·5 [95% CI 2·7-21·0], p<0·0001) and the BETA-2 score of 15 or higher (4·1 [1·5-11·4], p=0·0066) as factors associated with sustained graft survival. In recipients with sustained graft survival, the incidence of procedural complications was lower (23 [5%] of 443 infusions vs 17 [10%] of 167 infusions; p=0·027), whereas the incidence of cancer was higher (29 of [16%] of 178 vs four [5%] of 77; p=0·015) than in those with non-sustained graft survival; most were skin cancers (22 [67%] of 33). End-stage renal disease and severe infections were similar between groups. INTERPRETATION: We present the largest single-centre cohort study of long-term outcomes following islet transplantation. Although some limitations with our study remain, such as the retrospective component, a relatively small sample size, and the absence of non-transplant controls, we found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes, and therefore these factors could inform clinical practice. FUNDING: None.


Subject(s)
Diabetes Mellitus, Type 1 , Islets of Langerhans Transplantation , Cohort Studies , Diabetes Mellitus, Type 1/surgery , Etanercept/therapeutic use , Female , Graft Survival , Humans , Insulin/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Male , Retrospective Studies , Treatment Outcome
20.
Hepatobiliary Pancreat Dis Int ; 21(3): 207-217, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35232658

ABSTRACT

BACKGROUND: Hepato-pancreatico-biliary (HPB) patients experience significant risk of preoperative frailty. Studies assessing preventative prehabilitation in HPB populations are limited. This systematic review and meta-analysis evaluates outcomes for HPB patients treated with exercise prehabilitation. DATA SOURCES: A comprehensive search of MEDLINE (via Ovid), Embase (Ovid), Scopus, Web of Science Core Collection, Cochrane Library (Wiley), ProQuest Dissertations, Theses Global, and Google Scholar was conducted with review and extraction following PRISMA guidelines. Included studies evaluated more than 5 adult HPB patients undergoing ≥ 7-day exercise prehabilitation. The primary outcome was postoperative length of stay (LOS); secondary outcomes included complications, mortality, physical performance, and quality of life. RESULTS: We evaluated 1778 titles and abstracts and selected 6 (randomized controlled trial, n = 3; prospective cohort, n = 1; retrospective cohort, n = 2) that included 957 patients. Of those, 536 patients (56.0%) underwent exercise prehabilitation and 421 (44.0%) received standard care. Patients in both groups were similar with regards to important demographic factors. Prehabilitation was associated with a 5.20-day LOS reduction (P = 0.03); when outliers were removed, LOS reduction decreased to 1.85 days and was non-statistically significant (P = 0.34). Postoperative complications (OR = 0.70; 95% CI: 0.39 to 1.26; P = 0.23), major complications (OR = 0.83; 95% CI: 0.60 to 1.14; P = 0.24), and mortality (OR = 0.67; 95% CI: 0.17 to 2.70; P = 0.57) were similar. Prehabilitation was associated with improved strength, cardiopulmonary function, quality of life, and alleviated sarcopenia. CONCLUSIONS: Exercise prehabilitation may reduce LOS and morbidity following HPB surgery. Studies with well-defined exercise regimens are needed to optimize exercise prehabilitation outcomes.


Subject(s)
Preoperative Exercise , Quality of Life , Humans , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Preoperative Care/adverse effects , Prospective Studies , Retrospective Studies , Treatment Outcome
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