Outcome after Desensitization in HLA or ABO-Incompatible Kidney Transplant Recipients: A Single Center Experience

Background The shortage of deceased donors led to an increase of living donor kidney (LDK) transplantations performed in the presence of donor-specific antibodies (DSA) or ABO incompatibility (ABOi) using various desensitization protocols. Methods We herein analyzed 26 ABOi and 8 Luminex positive DSA patients who were successfully desensitized by anti-CD20, antigen-specific immunoadsorption and/or plasmapheresis to receive an LDK transplant. Twenty LDK recipients with non-donor-specific HLA-antibodies (low risk) and 32 without anti-HLA antibodies (no risk) served as control groups. Results 1-year graft survival rate and renal function was similar in all 4 groups (creatinine: 1.63 +/- 0.5 vs 1.78 +/- 0.6 vs 1.64 +/- 0.5 vs 1.6 +/- 0.3 mg/dl in ABOi, DSA, low risk and no risk group). The incidence of acute T-cell mediated rejections did not differ between the 4 groups (15% vs 12, 5% vs 15% vs 22% in ABOi, DSA, low risk and no risk), while antibody-mediated rejections were only found in the DSA (25%) and ABOi (7.5%) groups. Incidence of BK nephropathy (BKVN) was significantly more frequent after desensitization as compared to controls (5/34 vs 0/52, p = 0.03). Conclusion We demonstrate favorable short-term allograft outcome in LDK transplant recipients after desensitization. However, the desensitization was associated with an increased risk of BKVN

Nanoparticles modified with multiple organic acids

Surface-modified nanoparticles of boehmite, and methods for preparing the same. Aluminum oxyhydroxide nanoparticles are surface modified by reaction with selected amounts of organic acids. In particular, the nanoparticle surface is modified by reactions with two or more different carboxylic acids, at least one of which is an organic carboxylic acid. The product is a surface modified boehmite nanoparticle that has an inorganic aluminum oxyhydroxide core, or part aluminum oxyhydroxide core and a surface-bonded organic shell. Organic carboxylic acids of this invention contain at least one carboxylic acid group and one carbon-hydrogen bond. One embodiment of this invention provides boehmite nanoparticles that have been surface modified with two or more acids one of which additional carries at least one reactive functional group. Another embodiment of this invention provides boehmite nanoparticles that have been surface modified with multiple acids one of which has molecular weight or average molecular weight greater than or equal to 500 Daltons. Yet, another embodiment of this invention provides boehmite nanoparticles that are surface modified with two or more acids one of which is hydrophobic in nature and has solubility in water of less than 15 by weight. The products of the methods of this invention have specific useful properties when used in mixture with liquids, as filler in solids, or as stand-alone entities

Benefit in liver transplantation: a survey among medical staff, patients, medical students and non-medical university staff and students

Background: The allocation of any scarce health care resource, especially a lifesaving resource, can create profound ethical and legal challenges. Liver transplant allocation currently is based upon urgency, a sickest-first approach, and does not utilize capacity to benefit. While urgency can be described reasonably well with the MELD system, benefit encompasses multiple dimensions of patients' well-being. Currently, the balance between both principles is ill-defined. Methods: This survey with 502 participants examines how urgency and benefit are weighted by different stakeholders (medical staff, patients on the liver transplant list or already transplanted, medical students and non-medical university staff and students). Results: Liver transplant patients favored the sickest-first allocation, although all other groups tended to favor benefit. Criteria of a successful transplantation were a minimum survival of at least 1 year and recovery of functional status to being ambulatory and capable of all self-care (ECOG 2). An individual delisting decision was accepted when the 1-year survival probability would fall below 50%. Benefit was found to be a critical variable that may also trigger the willingness to donate organs. Conclusions: The strong interest of stakeholder for successful liver transplants is inadequately translated into current allocation rules

Disqualification of Donor and Recipient Candidates From the Living Kidney Donation Program: Experience of a Single-Center in Germany

Background: Kidney transplantation is the best treatment option for patients with end-stage kidney disease (ESKD) with a superiority of graft survival after living kidney donation (LKD) compared to deceased donation. However, a large part of potential donors and recipients are ineligible for LKD. Here, we analyze the leading causes for disqualification of potential living donor-recipient pairs from the LKD program and the health-related consequences for ESKD patients excluded from the LKD program in a German transplant center. Methods: In this single-center retrospective cohort study we evaluated all candidates (potential donors and recipients) presenting for assessment of LKD from 2012 to 2020 at our transplant center. Thereby we focused on candidates excluded from the LKD program. Main reasons for disqualification were categorized as medical (donor-related), psychosocial, immunological, recipient-related, and unknown. Results: Overall, 601 donor-recipient pairs were referred to our transplant center for LKD assessment during the observation time. Out of those, 326 (54.2%) discontinued the program with 52 (8.7%) dropouts and 274 (45.6%) donor-recipient pairs being ineligible for LKD. Donor-related medical contraindications were the main reason for disqualification [139 out of 274 (50.7%) potential donors] followed by recipient-related contraindications [60 out of 274 (21.9%) of potential donor-recipient pairs]. Only 77 out of 257 (29.9%) potential recipients excluded from the LKD program received a kidney transplant afterward with a median waiting time of 2 (IQR: 1.0–4.0) years. Overall, 18 (7.0%) ESKD patients initially declined for LKD died in this period. Conclusion: A large percentage of donor-recipient pairs are disqualified from the German LKD program, mostly due to medical reasons related to the donor and with partly severe consequences for the potential recipients. For these, alternative solutions that promptly enable kidney transplantation are essential for improving patient quality of life and survival

Incidence of rejection.

<p>The number of patient experiencing 1 or more biopsy proven rejections (including borderline cases with impaired renal graft function) according to the Banff 97 classification: 2 = antibody mediated rejection (AMR), 3 = borderline lesion, 4 I and 4 II = acute cellular rejection.</p

Loss of renal function within the first year.

<p>The GFR slope within the first year was assessed according to the following formula: GFR _{at 1 month}−GFR _{at 12 month}.</p

Machine learning identifies ICU outcome predictors in a multicenter COVID-19 cohort

Background: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. Methods: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. Results: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict “survival”. Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients’ age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. Conclusions: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration “ClinicalTrials” (clinicaltrials.gov) under NCT04455451