International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Patient safety and sense of security when telemonitoring chronic conditions at home: the views of patients and healthcare professionals - a qualitative study.

BACKGROUND: Chronic diseases are increasing worldwide, and the complexity of disease management is putting new demands on safe healthcare. Telemonitoring technology has the potential to improve self-care management with the support of healthcare professionals for people with chronic diseases living at home. Patient safety threats related to telemonitoring and how they may affect patients' and healthcare professionals' sense of security need attention. This study aimed to explore patients' and healthcare professionals' experiences of safety and sense of security when using telemonitoring of chronic conditions at home. METHODS: Semi-structured interviews were conducted with twenty patients and nine healthcare professionals (nurses and physicians), recruited from four primary healthcare centers and one medical department in a region in southern Sweden using telemonitoring service for chronic conditions in home healthcare. RESULTS: The main theme was that experiences of safety and a sense of security were intertwined and relied on patients´ and healthcare professionals´ mutual engagement in telemonitoring and managing symptoms together. Telemonitoring was perceived to increase symptom awareness and promote early detection of deterioration promoting patient safety. A sense of security emerged through having someone keeping track of symptoms and comprised aspects of availability, shared responsibility, technical confidence, and empowering patients in self-management. The meeting with technology changed healthcare professionals' work processes, and patients' daily routines, creating patient safety risks if combined with low health- and digital literacy and a naïve reliance on technology. Empowering patients' self-management ability and improving shared understanding of the patient's health status and symptom management were prerequisites for safe care and the patient´s sense of security. CONCLUSIONS: Telemonitoring chronic conditions in the homecare context can promote a sense of security when care is co-created in a mutual understanding and responsibility. Attentiveness to the patient's health literacy, symptom management, and health-related safety behavior when using eHealth technology may enlighten and mitigate latent patient safety risks. A systems approach indicates that patient safety risks related to telemonitoring are not only associated with the patient's and healthcare professionals functioning and behavior or the human-technology interaction. Mitigating patient safety risks are likely also dependent on the complex management of home health and social care service.

Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial.

Posttransplant diabetes mellitus (PTDM) and prediabetes (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) are associated with cardiovascular events. We assessed the diagnostic performance of fasting plasma glucose (FPG) and HbA1c as alternatives to oral glucose tolerance test (OGTT)-derived 2-hour plasma glucose (2hPG) using sensitivity and specificity in 263 kidney transplant recipients (KTRs) from a clinical trial. Between visits at 6, 12, and 24 months after transplantation, 28%-31% of patients switched glycemic category (normal glucose tolerance [NGT], IGT/IFG, PTDM). Correlations of FPG and HbA1c against 2hPG were lower at 6 months (r = 0.59 [FPG against 2hPG]; r = 0.45 [HbA1c against 2hPG]) vs. 24 months (r = 0.73 [FPG against 2hPG]; r = 0.74 [HbA1c against 2hPG]). Up to 69% of 2hPG-defined PTDM cases were missed by conventional HbA1c and FPG thresholds. For prediabetes, concordance of FPG and HbA1c with 2hPG ranged from 6%-9%. In conclusion, in our well-defined randomized trial cohort, one-third of KTRs switched glycemic category over 2 years and although the correlations of FPG and HbA1c with 2hPG improved with time, their diagnostic concordance was poor for PTDM and, especially, prediabetes. Considering posttransplant metabolic instability, FPG's and HbA1c 's diagnostic performance, the OGTT remains indispensable to diagnose PTDM and prediabetes after kidney transplantation.

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.

Insulin secretion and action after pancreas transplantation. A retrospective single-center study.

We explored glucometabolic and renal function after engraftment in all 159 consecutive patients with type 1 diabetes who received pancreas transplantation alone (PTA, n = 80) or simultaneous pancreas and kidney transplantation (SPK, n = 79) in Norway from 2012 until 2017. We report fasting levels of plasma glucose (FPG), C-peptide, eGFR and the homeostasis model assessment of insulin sensitivity (HOMA2(%S)) and beta-cell function (HOMA2(%B)) measured one to three times weekly during the first 8 and at 52 weeks after transplantation. One year after engraftment, in the PTA and SPK groups 52 and 64 were normoglycaemic without exogenous insulin, and two and zero patients were dead. Data at the 52-week visit were missing for 5 and 6 patients in the respective groups. During the first 8 weeks, FPG was lower, C-peptide and HOMA2(%S) were higher and eGFR was lower in the SPK group as compared with the PTA group (all p < .05). 30 out of 157 living patients needed insulin treatment 52 weeks after transplantation, 9/79 in the SPK group and 21/78 in the PTA group (p = .02). In conclusion, patients who underwent SPK showed lower insulin sensitivity, but higher insulin secretory capacity and lower mean blood glucose levels the first 8 weeks after transplantation. Also, a higher proportion of patients in the SPK group were insulin-free after 1 year, compared with the PTA group.

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 < .005). FMD% improved significantly from eight weeks to one year after PTX, mean 7.9 ± 4.2% vs 11.8 ± 4.8% (N = 9; P = .03). CONCLUSION: Flow-mediated dilatation is well preserved in patients undergoing pancreas transplantation and is not impaired when immunosuppressive drugs are introduced.

Donor-derived strongyloidiasis after organ transplantation in Norway.

Strongyloides stercoralis is an intestinal helminth which in humans can cause asymptomatic chronic infection maintained for decades through its auto-infective cycle. During solid organ transplantation, recipients may unintentionally receive an organ infected with strongyloides. This is a very rare complication but may have deadly outcome if not detected. We hereby report two transplant recipients whom developed Strongyloides hyperinfection syndrome after organ transplantation from the same deceased donor. Recipient 1 was kidney transplanted and presented at day 65 post engraftment with diarrhea and subsequent septicemia and gastric retention. Larvae were detected in gastric aspirate. Recipient 2 was simultaneously kidney and pancreas transplanted and presented at day 90 post engraftment also with gastric retention and septicemia. Larvae were demonstrated on duodenal biopsy and stool sample. The clinical course was complicated with severe duodenal bleedings, gastric retention, meningitis, and prolonged hospitalization. Retrospective testing of pre-transplant donor serum was positive for Strongyloides stercoralis antibodies. As a result of disease severity and gastric retention albenazole was administered via a jejunal tube and ivermectin subcutaneously in both recipients. S stercoralis was successfully eradicated and the transplants ended up with unaffected graft function. Following these two cases, we started systematic screening of all deceased donors for serum Strongyloides IgG in October 2016. After having screened 150 utilized donors one tested positive for Strongyloides, which initiated prophylactic ivermectin treatment to organ recipients. No symptoms or disease developed. Our center will continue to screen all donors as prophylactic treatment may avert this potentially lethal complication in cases of donor-derived Strongyloides infection.

Validation of diagnostic utility of fasting plasma glucose and HbA1c in stable renal transplant recipients one year after transplantation.

BACKGROUND: The use of HbA1c ≥6.5% for diagnosis of diabetes has been challenged for post-transplantation diabetes mellitus (PTDM) also known as new onset diabetes after transplantation (NODAT) due to a low sensitivity early after renal transplantation. PTDM diagnosed with an oral glucose tolerance test (OGTT) is highly predictable for long-term patient mortality. HbA1c was introduced for diagnosis based on the risk of developing diabetic retinopathy. The utility of HbA1c measures versus glucose criteria has not been widely assessed in stable transplant patients but still HbA1c is widely used in this population. The aim of the present analyses was to validate the utility of fasting plasma glucose (FPG) together with HbA1c in diagnosing PTDM in stable renal transplant recipients (RTRs). METHODS: OGTT's were performed one year after transplantation in 494 consecutive RTRs without diabetes. FPG and HbA1c were obtained the same day, before starting the OGTT. Validation was performed using C-statistics and logistic regression analyses. RESULTS: PTDM was diagnosed in 51 patients (10.3%) by glucose criteria, 38 (74%) patients were diagnosed by FPG ≥7.0 mmol/L [126.1 mg/dl], and 13 (26%) only by 2-h plasma glucose. Six of the latter had HbA1c ≥6.5%. Only seven patients out of the 51 (13.7%) PTDM patients remained undiagnosed when HbA1c ≥6.5% was used together with FPG, and five of these regressed to normal after a median follow-up of 14 months. ROC curves including FPG and HbA1c versus OGTT derived criteria revealed an AUC of 0.858. CONCLUSIONS: Combining standard diagnostic FPG and HbA1c criteria captured almost all patients with persistent PTDM in stable RTRs. The combined use of the criteria appears to be an applicable diagnostic strategy for PTDM without the need of an OGTT one year post-transplant. TRIAL REGISTRATION: Retrospectively registered.

A systematic review and proposed framework for sustainable learning healthcare systems.

BACKGROUND: The healthcare sector is a complex domain that faces challenges in effectively learning from practices and outcome data. The Learning Health System (LHS) has emerged as a potential framework to improve healthcare by promoting continuous learning. However, its adoption remains limited, often involving only a single clinical department or a part of the LHS cycle. There is a need to gain a better understanding of implementing LHS on a larger scale. AIM: To identify complete implementations of the LHS for providing recommendations into their implementation strategies, success factors, barriers, and outcomes. METHODS: A systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using PubMed and Scopus databases. Data from the included papers were thematically categorized into four primary areas: (1) Scale of LHS Implementation; (2) Implementation strategies and the factors that facilitated the implementation of LHS; (3) LHS outcomes; and (4) Barriers /challenges related to the LHS implementation. RESULTS: We identified 1,279 papers, of which 37 were included in the final analysis. Barriers to implementing LHS included interoperability, data integration, electronic health records (EHRs) challenges, organizational culture, leadership, and regulatory hurdles. Most LHS initiatives lacked discussion on long-term economic sustainability models, and only 16 papers provided objective measurements of performance changes. Drawing from the findings of the included studies, this paper offers recommendations for the effective implementation of the LHS. CONCLUSION: The establishment of sustainable LHS necessitates several key components. First, there is a need to develop long-term economic sustainability models. Secondly, governance at the national level should promote common Application Programming Interfaces (APIs) across LHS implementations, communication channels to share tacit knowledge, efficient Institutional Review Board, ethical approval processes, and connect various initiatives currently operating independently. Lastly, the success of LHS relies not only on technological infrastructure but also on the active participation of multidisciplinary teams in decision-making and sharing of tacit knowledge.

The Knowledge of Implementation Strategies: Impact of the Installed Base.

This study uses three case studies to investigate how the installed base affects Electronic Health Records (EHR) implementation in European hospitals: i) transition from paper-based records to EHRs; ii) replacement of an existing EHR with a similar system; and iii) replacing existing EHR system with a radically different one. Using a meta-analysis approach, the study employs the theoretical framework of Information Infrastructure (II) to analyze user satisfaction and resistance. Results show that the existing infrastructure and time factor significantly impact EHR outcomes. Implementation strategies that build upon the current infrastructure and offer immediate user benefits yield higher satisfaction rates. The study highlights the importance of considering the installed base and adapting implementation strategies to maximize EHR system benefits.

Case Report: Let Us Not Forget the Treatment That Some Patients Have Received-The Brief 50-Year History of a Kidney Transplant Survivor.

Background: There has been a considerable improvement in post-transplant care since the early 1960s. Some patients we meet in the clinic have personally experienced this progress and have histories to tell that one must not forget. This is the brief history of a long-time "transplant survivor." Case Presentation: In 1970, a young woman developed acute oedema, proteinuria, hypertension and oliguria during pregnancy. Labor was induced, but neither the child nor the kidney function could be saved. Our patient started dialysis, and 4 years later received a kidney transplant donated by her father (then 55 years of age). Maintenance immunosuppression consisted of prednisolone and azathioprine until 2011, when azathioprine was switched to everolimus due to skin cancer. Before this, our patient was highly satisfied with prednisolone/azathioprine, despite discussions regarding newer immunosuppressive drugs, and always reminded the treating physician that one should "never change a winning team." Retrospectively, the avoidance of calcineurin inhibitors might have been beneficial for this patient who still has preserved an excellent renal function with s-creatinine levels around 100 µmol/L and just had sparse fibrosis detected in a recently performed transplant biopsy. The transplanted kidney is now 101 years old and is still working 24/7. Conclusions: Our patient received a kidney transplant for 46 years ago and still has a remarkably stable transplant function with s-creatinine levels around 100 µmol/L. This case report illustrates the potential endurance of the kidneys and is a reminder to keep taking individualized treatment decisions even though new treatment alternatives promise superiority.

Chronic kidney disease in patients with diabetes mellitus.

Chronic kidney disease is a common complication and concomitant condition of diabetes mellitus. The treatment of patients with diabetes and chronic kidney disease, including intensive control of blood sugar and blood pressure, has been very similar for type 1 and type 2 diabetes patients. New therapeutic targets have shown promising results and may lead to more specific treatment options for patients with type 1 and type 2 diabetes.

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

OBJECTIVE: ß-cell replacement therapy (ßCRT), including pancreas transplantation alone (PTA) and islet transplantation (ITX), is a treatment option for selected type 1 diabetes patients. All potential candidates for ßCRT 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 ßCRT between 2010 and 2020 in Norway were retrospectively analysed and the outcome of patients receiving ßCRT were studied. RESULTS: One hundred and forty-four patients were assessed for ßCRT eligibility between 2010 and 2020. After MDT evaluation was introduced for ßCRT eligibility in 2015, the percentage of referred patients accepted for the transplant waiting list fell from 84% to 40% (P < 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 ßCRT 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.

Early detection of complications in pancreas transplants by microdialysis catheters, an observational feasibility study.

BACKGROUND: Despite advances in immunosuppression and surgical technique, pancreas transplantation is encumbered with a high rate of complication and graft losses. Particularly, venous graft thrombi occur relatively frequently and are rarely detected before the transplant is irreversibly damaged. METHODS: To detect complications early, when the grafts are potentially salvageable, we placed microdialysis catheters anteriorly and posteriorly to the graft in a cohort of 34 consecutive patients. Glucose, lactate, pyruvate, and glycerol were measured at the bedside every 1-2 hours. RESULTS: Nine patients with graft venous thrombosis had significant lactate and lactate-to-pyruvate-ratio increases without concomitant rise in blood glucose or clinical symptoms. The median lactate in these patients was significantly higher in both catheters compared to non-events (n = 15). Out of the nine thrombi, four grafts underwent successful angiographic extraction, one did not require intervention and four grafts were irreversibly damaged and explanted. Four patients with enteric anastomosis leakages had significantly higher glycerol measurements compared to non-events. As with the venous thrombi, lactate and lactate-to-pyruvate ratio were also increased in six patients with graft surrounding hematomas. CONCLUSIONS: Bedside monitoring with microdialysis catheters is a promising surveillance modality of pancreatic grafts, but differentiating between the various pathologies proves challenging.

Preserved insulin secretion and kidney function in recipients with functional pancreas grafts 1 year after transplantation: a single-center prospective observational study

Objective: Successful simultaneous pancreas and kidney transplantation (SPK) or pancreas transplantation alone (PTA) restores glycemic control. Diabetes and impaired kidney function are common side effects of immunosuppressive therapy. This study addresses glucometabolic parameters and kidney function during the first year. Methods: We examined 67 patients with functioning grafts (SPK n = 30, PTA n = 37) transplanted between September 2011 and November 2016 who underwent repeated oral glucose tolerance tests (OGTTs) 8 and 52 weeks after transplantation. Another 19 patients lost their graft the first year post-transplant and 28 patients did not undergo repeated OGTTs and could not be studied. All patients received ATG induction therapy plus tacrolimus, mycophenolate and prednisolone. Glomerular filtration rate was measured before and 8 and 52 weeks after transplantation by serum clearance methods. Results: From week 8 to 52 after transplantation, mean fasting glucose decreased (SPK: 5.4 ± 0.7 to 5.1 ± 0.8 mmol/L, PTA: 5.4 ± 0.6 to 5.2 ± 0.7 mmol/L; both P < 0.05), and also 120-min post-OGTT glucose (SPK: 6.9 ± 2.9 to 5.7 ± 2.2 mmol/L; P = 0.07, PTA: 6.5 ± 1.7 to 5.7 ± 1.2 mmol/L; P < 0.05). Fasting C-peptide levels also decreased (SPK: 1500 ± 573 to 1078 ± 357 pmol/L, PTA: 1210 ± 487 to 1021 ± 434 pmol/L, both P < 0.005). Measured GFR decreased from enlistment to 8 weeks post transplant in PTA patients (94 ± 22 to 78 ± 19 mL/min/1.73 m2; P < 0.005), but did not deteriorate from week 8 to week 52 (SPK: 55.0 ± 15.1 vs 59.7 ± 11.3 ml/min/1.73 m²; P = 0.19, PTA: 76 ± 19 vs 77 ± 19 mL/min/1.73 m²; P = 0.74). Conclusion: Glycemic control and kidney function remain preserved in recipients with functioning SPK and PTA grafts 1 year after transplantation.

First Scandinavian Protocol for Controlled Donation After Circulatory Death Using Normothermic Regional Perfusion.

BACKGROUND: Donation after circulatory death (DCD) can increase the pool of available organs for transplantation. This pilot study evaluates the implementation of a controlled DCD (cDCD) protocol using normothermic regional perfusion in Norway. METHODS: Patients aged 16 to 60 years that are in coma with documented devastating brain injury in need of mechanical ventilation, who would most likely attain cardiac arrest within 60 minutes after extubation, were eligible. With the acceptance from the next of kin and their wish for organ donation, life support was withdrawn and cardiac arrest observed. After a 5-minute no-touch period, extracorporeal membrane oxygenation for post mortem regional normothermic regional perfusion was established. Cerebral and cardiac reperfusion was prevented by an aortic occlusion catheter. Measured glomerular filtration rates 1 year postengraftment were compared between cDCD grafts and age-matched grafts donated after brain death (DBD). RESULTS: Eight cDCD were performed from 2014 to 2015. Circulation ceased median 12 (range, 6-24) minutes after withdrawal of life-sustaining treatment. Fourteen kidneys and 2 livers were retrieved and subsequently transplanted. Functional warm ischemic time was 26 (20-51) minutes. Regional perfusion was applied for 97 minutes (54-106 minutes). Measured glomerular filtration rate 1 year postengraftment was not significantly different between cDCD and donation after brain death organs, 75 (65-76) vs 60 (37-112) mL/min per 1.73 m2 (P = 0.23). No complications have been observed in the 2 cDCD livers. CONCLUSION: A protocol for cDCD is successfully established in Norway. Excellent transplant outcomes have encouraged us to continue this work addressing the shortage of organs for transplantation.

Resolution of Calciphylaxis After Urgent Kidney Transplantation in 3 Patients With End-Stage Kidney Failure.

BACKGROUND: Calcific uremic arteriolopathy (CUA), also referred to as calciphylaxis, is a rare and serious complication of kidney failure with limited treatment options. Kidney transplantation (KTX) restores kidney function and is hence a potential treatment option for CUA. We present 3 patients who had their CUA lesions successfully healed after urgent KTX. METHODS: Data were retrospectively retrieved from hospital records at our national transplant center. RESULTS: All 3 patients had previously been kidney transplanted and had experienced graft loss and were in stage 5 kidney failure when CUA developed. One patient was on warfarin treatment for pulmonary embolism. Skin lesions developed in the lower limbs in all 3 patients. Multidisciplinary care including intensified hemodialysis did not induce any clinically relevant improvement of the lesions. The recipients were enlisted on a clinically urgent waitlist for KTX and received a deceased donor kidney after 2 to 4 weeks. All recipients experienced good graft function. The lesions healed completely within 6 weeks in 2 patients. In the third patient, partial healing occurred after 2 months and complete healing was achieved 4 months after transplantation. CONCLUSIONS: These cases indicate that urgent KTX may contribute to an efficient treatment for end-stage renal disease patients with CUA.