Microdialysis and CO2 sensors detect pancreatic ischemia in a porcine model

Background: Pancreatic transplantation is associated with a high rate of early postoperative graft thrombosis. If a thrombosis is detected in time, a potentially graft-saving intervention can be initiated. Current postoperative monitoring lacks tools for early detection of ischemia. The aim of this study was to investigate if microdialysis and tissue pCO2 sensors detect pancreatic ischemia and whether intraparenchymal and organ surface measurements are comparable. Methods: In 8 anaesthetized pigs, pairs of lactate monitoring microdialysis catheters and tissue pCO2 sensors were simultaneously inserted into the parenchyma and attached to the surface of the pancreas. Ischemia was induced by sequential arterial and venous occlusions of 45-minute duration, with two-hour reperfusion after each occlusion. Microdialysate was analyzed every 15 minutes. Tissue pCO2 was measured continuously. We investigated how surface and parenchymal measurements correlated and the capability of lactate and pCO2 to discriminate ischemic from non-ischemic periods. Results: Ischemia was successfully induced by arterial occlusion in 8 animals and by venous occlusion in 5. During all ischemic episodes, lactate increased with a fold change of 3.2–9.5 (range) in the parenchyma and 1.7–7.6 on the surface. Tissue pCO2 increased with a fold change of 1.6–3.5 in the parenchyma and 1.3–3.0 on the surface. Systemic lactate and pCO2 remained unchanged. The area under curve (AUC) for lactate was 0.97 (95% confidence interval (CI) 0.93–1.00) for parenchymal and 0.90 (0.83–0.97) for surface (p<0.001 for both). For pCO2 the AUC was 0.93 (0.89–0.96) for parenchymal and 0.85 (0.81–0.90) for surface (p<0.001 for both). The median correlation coefficients between parenchyma and surface were 0.90 (interquartile range (IQR) 0.77–0.95) for lactate and 0.93 (0.89–0.97) for pCO2. Conclusions: Local organ monitoring with microdialysis and tissue pCO2 sensors detect pancreatic ischemia with adequate correlation between surface and parenchymal measurements. Both techniques and locations seem feasible for further development of clinical pancreas monitoring.publishedVersio

Calcium : A Crucial Potentiator for Efficient Enzyme Digestion of the Human Pancreas

Background: Effective digestive enzymes are crucial for successful islet isolation. Supplemental proteases are essential because they synergize with collagenase for effective pancreatic digestion. The activity of these enzymes is critically dependent on the presence of Ca2+ ions at a concentration of 5-10 mM. The present study aimed to determine the Ca2+ concentration during human islet isolation and to ascertain whether the addition of supplementary Ca2+ is required to maintain an optimal Ca2+ concentration during the various phases of the islet isolation process. Methods: Human islets were isolated according to standard methods and isolation parameters. Islet quality control and the number of isolations fulfilling standard transplantation criteria were evaluated. Ca2+ was determined by using standard clinical chemistry routines. Islet isolation was performed with or without addition of supplementary Ca2+ to reach a Ca2+ of 5 mM. Results: Ca2+ concentration was markedly reduced in bicarbonate-based buffers, especially if additional bicarbonate was used to adjust the pH as recommended by the Clinical Islet Transplantation Consortium. A major reduction in Ca2+ concentration was also observed during pancreatic enzyme perfusion, digestion, and harvest. Additional Ca2+ supplementation of media used for dissolving the enzymes and during digestion, perfusion, and harvest was necessary in order to obtain the concentration recommended for optimal enzyme activity and efficient liberation of a large number of islets from the human pancreas. Conclusions: Ca2+ is to a large extent consumed during clinical islet isolation, and in the absence of supplementation, the concentration fell below that recommended for optimal enzyme activity. Ca2+ supplementation of the media used during human pancreas digestion is necessary to maintain the concentration recommended for optimal enzyme activity. Addition of Ca2+ to the enzyme blend has been implemented in the standard isolation protocols in the Nordic Network for Clinical Islet Transplantation.Peer reviewe

First Experience With Rectus Sheath Block for Postoperative Analgesia After Pancreas Transplant: A Retrospective Observational Study

Background Standard of care for postoperative analgesia after pancreas transplant has been thoracic epidural analgesia (TEA). A high incidence of venous graft thrombosis necessitated a change to a more aggressive anticoagulation protocol. To minimize the risk of epidural hemorrhages, we changed from TEA to rectus sheath block (RSB) in 2017. Methods From June 2016 to December 2017, a total of 29 consecutive pancreas transplant recipients were included. Sixteen were treated with TEA and 13 were treated with RSB. In the TEA group, the catheter was inserted before induction of general anesthesia, and an epidural infusion was started intraoperatively. An ultrasound-guided RSB was performed bilaterally, and a bolus of local anesthetic was administered before an 18G catheter was inserted. The patients received intermittent local anesthetic boluses every 4 hours in addition to an intravenous patient-controlled analgesia with oxycodone. Both groups received oral acetaminophen and additional rescue opioids. Results The administered amount of intravenous morphine equivalents (MEQ) was not significantly different between the RSB and TEA groups. The median MEQ consumption per day during the stay at the surgical ward was 23 mg MEQ/d (interquartile range [IQR], 14–33 mg MEQ/d) in the TEA group compared with 19 mg MEQ/d (IQR, 14–32 mg MEQ/d) in the RSB group (P = .4). The duration of the pain catheters was significantly longer in the RSB group. We had no complications related to insertion, use, or removal of the RSB or the TEA catheters, and overall patient satisfaction and comfort was good. Conclusion Compared with TEA, RSB was equally effective and safe for postoperative analgesia in heavily anticoagulated pancreas transplant patients.publishedVersio

Transcriptional and functional profiling defines human small intestinal macrophage subsets

Contains fulltext : 189872.pdf (publisher's version ) (Open Access

Microbubble contrast-enhanced ultrasound in the vascular evaluation after pancreas transplantation: a single-center experience

Background: Arterial and venous thrombosis are feared complications of pancreas transplantation (PTx). Microbubble contrast-enhanced ultrasound (CEUS) is a non-invasive imaging technique that can augment diagnostic capabilities of transplant organ perfusion. Purpose: To document the state to which CEUS can improve the vascular evaluation of PTx compared to conventional Doppler ultrasound (US) directly after surgery. Material and Methods: A total of 129 consecutive PTx in 128 adult patients were eligible for inclusion. The duodenal segment of the graft was anastomosed to the native duodenum. Within 12 h postoperatively, graft- circulation was monitored by Doppler US in 116 PTx performed in 116 patients (69 men, 47 women; mean age 41 years). CEUS was performed with a sulfur hexafluoride-containing contrast agent (SonoVue) intravenously if the examiner was not able to confirm normal graft circulation. Image quality was documented by two independent observers on a 4-point scale: 1 excellent; 2 minor diagnostic limitations; 3 major diagnostic limitations; and 4 non-diagnostic. Results: In the early postoperative phase, 79 (68%) of 116 PTx were examined with Doppler US only. Of these, 52 were of excellent quality (grade 1), 22 of good quality (grade 2), and five were of grade 3 or 4 quality. Thirty-seven (32%) examinations were supplemented by CEUS. CEUS significantly improved examination quality compared to Doppler US alone (median visualization score 1.5 vs. 2.5, respectively; P < 0.0001). Conclusion: CEUS can significantly improve vascular evaluation of PTx compared to Doppler US alone in the early postoperative phase

First Experience With Rectus Sheath Block for Postoperative Analgesia After Pancreas Transplant: A Retrospective Observational Study

Background Standard of care for postoperative analgesia after pancreas transplant has been thoracic epidural analgesia (TEA). A high incidence of venous graft thrombosis necessitated a change to a more aggressive anticoagulation protocol. To minimize the risk of epidural hemorrhages, we changed from TEA to rectus sheath block (RSB) in 2017. Methods From June 2016 to December 2017, a total of 29 consecutive pancreas transplant recipients were included. Sixteen were treated with TEA and 13 were treated with RSB. In the TEA group, the catheter was inserted before induction of general anesthesia, and an epidural infusion was started intraoperatively. An ultrasound-guided RSB was performed bilaterally, and a bolus of local anesthetic was administered before an 18G catheter was inserted. The patients received intermittent local anesthetic boluses every 4 hours in addition to an intravenous patient-controlled analgesia with oxycodone. Both groups received oral acetaminophen and additional rescue opioids. Results The administered amount of intravenous morphine equivalents (MEQ) was not significantly different between the RSB and TEA groups. The median MEQ consumption per day during the stay at the surgical ward was 23 mg MEQ/d (interquartile range [IQR], 14–33 mg MEQ/d) in the TEA group compared with 19 mg MEQ/d (IQR, 14–32 mg MEQ/d) in the RSB group (P = .4). The duration of the pain catheters was significantly longer in the RSB group. We had no complications related to insertion, use, or removal of the RSB or the TEA catheters, and overall patient satisfaction and comfort was good. Conclusion Compared with TEA, RSB was equally effective and safe for postoperative analgesia in heavily anticoagulated pancreas transplant patients

Endothelial function after pancreas transplantation - A single-center observational study

Background - Patients with diabetes mellitus treated with successful pancreas transplantation (PTX) normalize hyperglycemia, but are exposed to immunosuppressive drugs that may impair endothelial function. This study aimed to evaluate endothelial function in single PTX recipients. Methods - Flow‐mediated dilatation (FMD) in the brachial artery was measured by ultrasound 8 weeks after transplantation in single PTX (n = 27) and compared with healthy controls (n = 58), simultaneous pancreas and kidney recipients (n = 9), and kidney transplant recipients with (n = 41) and without (n = 95) diabetes mellitus. Adjustments for age, gender, blood pressure, and body mass index were included in a linear regression model. Changes in FMD from before to 1 year after transplantation were assessed in a subgroup of PTX recipients (n = 9). Results - Flow‐mediated dilatation% in PTX recipients was not inferior to healthy controls (8.7 ± 3.6 vs 7.7 ± 3.3, P = .06) and simultaneous pancreas and kidney recipients (6.7 ± 4.5, P = .24) in an adjusted model, and superior to kidney recipients with and without diabetes (3.0 ± 3.0 and 4.8 ± 3.3, respectively, both P P = .03). Conclusion - Flow‐mediated dilatation is well preserved in patients undergoing pancreas transplantation and is not impaired when immunosuppressive drugs are introduced

Patient selection for islet or solid organ pancreas transplantation: experiences from a multidisciplinary outpatient-clinic approach

Objective β-cell replacement therapy (βCRT), including pancreas transplantation alone (PTA) and islet transplantation (ITX), is a treatment option for selected type 1 diabetes patients. All potential candidates for βCRT in Norway are referred to one national transplant centre for evaluation before any pre-transplant workup is started. This evaluation was performed by a transplant nephrologist alone prior to 2015 and by a multidisciplinary team (MDT) from 2015. We have reviewed the allocation of patients to treatment modality and the 1-year clinical outcome for the patients after transplantation. Research design and methods Medical charts of all patients evaluated for βCRT between 2010 and 2020 in Norway were retrospectively analysed and the outcome of patients receiving βCRT were studied. Results One hundred and forty-four patients were assessed for βCRT eligibility between 2010 and 2020. After MDT evaluation was introduced for βCRT eligibility in 2015, the percentage of referred patients accepted for the transplant waiting list fell from 84% to 40% ( P &lt; 0.005). One year after transplantation, 73% of the PTA and none of the ITX patients were independent of exogenous insulin, 8% of the PTA and 90% of the ITX patients had partial graft function while 19% of the PTA and 10% of the ITX patients suffered from graft loss. Conclusion The acceptance rate for βCRT was significantly reduced during a 10-year observation period and 81% of the PTA and 90% of the ITX patients had partial or normal graft function 1 year post-transplant

Validating the US pancreas donor risk index in a Norwegian population, a retrospective observational study

OBJECTIVES Despite advances in immunosuppression and surgical technique, pancreas transplantation is still associated with a significant graft loss rate. The Pancreas Donor Risk Index (PDRI) is a pre-transplant scoring tool derived from a US population. We sought to validate the PDRI in a Norwegian population. METHODS We retrospectively retrieved donor data for 344 pancreas transplants undertaken in Norway between 2000 and 2019, utilising the Scandiatransplant database, and matched these to the respective recipients. The PDRI score was calculated for each transplanted pancreas, these were then stratified into quintiles. The association between the PDRI quintiles and 1-year graft survival was calculated, and this was repeated for the different types of pancreas transplantation. The association between PDRI as a continuous variable, and graft survival was determined. Donor and recipient data were compared to the original US population. RESULTS The overall 1-year graft survival was 82.7%. There were no significant differences in survival between the different PDRI quintiles. When viewed as a continuous variable, increased PDRI score was not associated with decreased graft survival. Significant differences between the Norwegian and US populations were found. CONCLUSIONS When applied to a Norwegian population, the PDRI score was unable to predict 1-year graft survival