Environmental Benefits of Electronic Table of Contents of Journals Over Print.

Recent discussion has driven debate on the best format for journals to deliver content to their readers. Traditional dogma necessitated a physical print copy, which was sent to subscribers automatically and came with the benefits of ease of use and familiarity. With the passage of time, electronic tables of contents, with or without the option for a print copy, have been used in lieu to save cost and environmental concerns and to allow content to be consumed in a more convenient, tidier way.

Graft repair of arteriovenous fistula aneurysms is associated with decreased long-term patency.

INTRODUCTION: Arteriovenous fistula (AVF) aneurysms are a chronic complication which can be disfiguring, painful, and can rupture. Here, we compare the outcomes between three different methods of AVF aneurysm repair. METHODS: One-way ANOVA, Chi-square, and Fisher Exact analyses were used to compare demographics. Multivariate logistic regression compared outcomes. Kaplan-Meier estimate illustrated long-term fistula patency. RESULTS: There were no differences between demographics in the aneurysmorrhaphy, end-to-end anastomosis, and synthetic graft groups. The odds of patients who received graft repair losing primary patency within one year compared to the aneurysmorrhaphy group was 3.5 (p = 0.025). Graft repair patients were 6.7 times more likely to develop an infection compared to aneurysmorrhaphy (p = 0.014). Synthetic grafts also exhibited accelerated rates of complete access loss compared to autogenous methods (p = 0.034). CONCLUSIONS: Graft repair of AVF aneurysms results in higher rates of infection and decreased primary and ultimate patency compared to autogenous repair techniques. Therefore, synthetic grafts should be avoided whenever possible.

Can Donor-Derived Cell-Free DNA Detect Graft-Versus-Host Disease in Solid Organ Transplantation: A Case Report.

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic symptoms of maculopapular rash, diarrhea, and pancytopenia. However, this patient had unexplained elevations in donor-derived cell-free DNA (dd-cfDNA) for months before the onset of GVHD symptoms. We hypothesize that GVHD may be associated with elevated dd-cfDNA as a result of massive donor lymphocyte proliferation and turnover. Further investigation is warranted because earlier diagnosis and treatment could improve outcomes in an otherwise lethal disease.

Arguments against the Requirement of a Biological License Application for Human Pancreatic Islets: The Position Statement of the Islets for US Collaborative Presented during the FDA Advisory Committee Meeting.

The Food and Drug Administration (FDA) has been regulating human islets for allotransplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA's position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021. We provided evidence that BLA requirement and drug related regulations are inadequate in reassuring islet product quality and potency as well as patient safety and clinical outcomes. As leaders in the field of transplantation and endocrinology under the "Islets for US Collaborative" designation, we examined the current regulatory status of islet transplantation in the US and identified several anticipated negative consequences of the BLA approval. In our commentary we also offer an alternative pathway for islet transplantation under the regulatory framework for organ transplantation, which would address deficiencies of in current system.

Comparative incidence and outcomes of COVID-19 in kidney or kidney-pancreas transplant recipients versus kidney or kidney-pancreas waitlisted patients: A single-center study.

BACKGROUND: COVID-19 epidemiologic studies comparing immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressants on outcomes. METHODS: In this retrospective cohort study, we assembled kidney or kidney-pancreas transplant recipients who underwent transplant from January 1, 2010, to June 30, 2020, and kidney or kidney-pancreas waitlisted patients who were ever on the waitlist from January 1, 2019, to June 30, 2020. We identified laboratory-confirmed COVID-19 until January 31, 2021, and tracked its outcomes by leveraging informatics infrastructure developed for an outcomes research network. RESULTS: COVID-19 was identified in 62 of 887 kidney or kidney-pancreas transplant recipients and 20 of 434 kidney or kidney-pancreas waitlisted patients (7.0% vs. 4.6%, p = .092). Of these patients with COVID-19, hospitalization occurred in 48 of 62 transplant recipients and 8 of 20 waitlisted patients (77% vs. 40%, p = .002); intensive care unit admission occurred in 18 of 62 transplant recipients and 2 of 20 waitlisted patients (29% vs. 10%, p = .085); and 7 transplant recipients were mechanically ventilated and died, whereas no waitlisted patients were mechanically ventilated or died (11% vs. 0%, p = .116). CONCLUSIONS: Our study provides single-center data and an informatics approach that can be used to inform the design of multicenter studies.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

Should Pre-Transplant Hemoglobin A1c Be Used to Predict Post-Transplant Compliance in End-Stage Renal Disease Patients Undergoing Kidney Transplantation?

BACKGROUND Patient compliance with immunosuppressive therapy after transplant has impacts on both graft and patient outcomes. For diabetic end-stage renal disease (ESRD) patients who are undergoing evaluation for kidney transplantation in our program, hemoglobin A1c (HbA1c) level of >10% is used as a flag that the patient may be at risk for noncompliance and that more comprehensive psychosocial screening is needed prior to transplant. We evaluated the association between pre-transplant HbA1c level and post-transplant compliance, as no study to date has looked at this in the transplant population. MATERIAL AND METHODS The charts of 392 patients who received a kidney transplant at a single institution between July 2008 and June 2012 were retrospectively reviewed. One hundred and sixty-five diabetic patients who received a kidney transplant alone were included in the final analysis. Our predictive variable was HbA1c level greater than 7.7% based on previous reports in the diabetic population. Outcome measures were graft survival, rejection episodes, unexplained low immunosuppressant levels, and documented noncompliance. RESULTS There were no statistically significant differences between the HbA1c groups of ≤7.7% and >7.7% in outcomes of failed grafts (22.0% and 17.8%, p=0.2), rejection episodes (15.0% and 6.7%, p=0.3), unexplained low immunosuppressant level (46.6% and 37.9%, p=0.3), and documented noncompliance (25.0% and 16.7%, p=0.4). CONCLUSIONS In diabetic ESRD patients selected for renal transplantation, elevated pre-transplant HbA1c levels, defined as HbA1c >7.7%, are not predictive of post-transplant medication compliance. We advocate that this group of patients should not be denied transplant solely on their elevated pre-transplant HbA1c.

C-peptide levels do not correlate with pancreas allograft failure: Multicenter retrospective analysis and discussion of the new OPT definition of pancreas allograft failure.

The OPTN Pancreas Transplantation Committee performed a multicenter retrospective study to determine if undetectable serum C-peptide levels correspond to center-reported pancreas graft failures. C-peptide data from seven participating centers (n = 415 graft failures for transplants performed from 2002 to 2012) were analyzed pretransplant, at graft failure, and at return to insulin. One hundred forty-nine C-peptide values were submitted at pretransplant, 94 at return to insulin, and 233 at graft failure. There were 77 transplants with two available values (at pretransplant and at graft failure). For recipients in the study with pretransplant C-peptide <0.75 ng/mL who had a posttransplant C-peptide value available (n = 61), graft failure was declared at varying levels of C-peptide. High C-peptide values at graft failure were not explained by nonfasting testing or by individual center bias. Transplant centers declare pancreas graft failure at varying levels of C-peptide and do not consistently report C-peptide data. Until February 28, 2018, OPTN did not require reporting of posttransplant C-peptide levels and it appears that C-peptide levels are not consistently used for evaluating graft function. C-peptide levels should not be used as the sole criterion for the definition of pancreas graft failure.

Expanding the envelope: the posterior rectus sheath-liver vascular composite allotransplant.

BACKGROUND: Primary abdominal wall reconstruction after liver transplantation presents a challenge in patients with size mismatch, multivisceral transplants, and prior recipient abdominal surgery. The authors report their experience with a novel technique for abdominal wall reconstruction with a new vascular composite allotransplant. METHODS: Five posterior rectus sheath-liver composite vascular allotransplants were procured by a multidisciplinary team and transplanted into four patients over the course of 2 years. Liver transplantation was performed in the standard manner, and the posterior rectus sheath was inset as an inlay flap. RESULTS: Abdominal wall integrity was reestablished with vascularized fascia in all five cases. In two cases, the fascia was closed immediately at the time of initial transplantation. In three cases, the abdomen was left open for a planned second look and closed definitively when the liver appeared satisfactory. In one patient, hepatic artery thrombosis was detected 11 days after transplantation, requiring a second posterior rectus sheath-liver transplant. Skin closure was performed for all transplants in either an immediate or a delayed fashion. Reoperation requiring elevation of the posterior rectus sheath flap for a suprahepatic vena cava stenosis was performed in one patient. CONCLUSIONS: Closure of the abdominal cavity is critical to the success of liver transplantation for organ survival and overall patient morbidity and mortality. The authors describe their institutional experience with a novel method of concurrent abdominal wall reconstruction and liver transplantation using the posterior rectus sheath-liver vascular composite allotransplant in situations of size mismatch, multivisceral transplants, and compromised abdominal wall of the recipient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.

To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.