Clinical and histopathological characteristics of acute kidney injury in a cohort of brain death donors with procurement biopsies.

BACKGROUND: Kidney biopsies are routinely used for diagnostic and prognostic purposes but their utility in the intensive care unit (ICU) setting is limited. We investigated the associations of clinical and histopathological risk factors with ICU-acute kidney injury (AKI) in donors with brain death (DBD) with kidneys of lower quality and procurement biopsies. METHODS: Overall, 221 donors with brain death, 239 biopsies and 197 recipients were included. The biopsies were reread and scored according to the Banff recommendations. Clinical and histopathological data were compared between donors with and without AKI defined by serum creatinine and by urine output. Logistic regression analysis was applied to identify independent clinical and histopathological risk factors for both phenotypes. Lastly, the impact of each AKI phenotype on outcome was explored. AKI was diagnosed based on the RIFLE (Risk, Injury, Failure, Loss of function, End-stage kidney disease) AKIN (Acute Kidney Injury Network) or KDIGO (Kidney Disease Improving Global Outcomes) criteria. RESULTS: Acute kidney injury occurred in 65% of donors based both upon serum creatinine and by urine output. Serum creatinine was able to better discriminate AKI. Multiorgan failure and severe AKI were captured by serum creatinine, and hemodynamic instability by urine output. Donors with serum creatinine-AKI showed lower chronic macrovascular scores, while donors with urine output-AKI had higher chronic microvascular and tubulointerstitial scores. Tubular injury was similar between the subgroups. Except for delayed graft function and one-year death-censored graft survival, the other short-term recipient outcomes were similar for both AKI phenotypes. CONCLUSION: Serum creatinine is more suitable than urine output for defining AKI in donors with brain death. There are distinct clinical risk factors for each AKI-ICU phenotype. Donor AKI phenotype does not predict the recipient´s prognosis. Kidney biopsies do not seem to confer any tangible benefit in defining AKI in donors with brain death.

2-Step-Scores with optional nephropathology for the prediction of adverse outcomes for brain-dead donor kidneys in Eurotransplant.

BACKGROUND AND HYPOTHESIS: The decision for acceptance or discard of the increasingly rare and marginal brain-dead donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores called 2-Step Scores for the prognosis of delayed graft function (DGF) and one-year death-censored transplant loss (1y-tl) reflecting the current practice of six ET countries including Croatia and Belgium. METHODS: The training set was n=620 for DGF and n=711 for 1y-tl, with validation sets n=158 and n=162. In step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology. RESULTS: Step 1 revealed an increased risk of DGF with increased cold ischaemia time, donor and recipient BMI, dialysis vintage, number of HLA-DR mismatches or recipient CMV IgG positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c statistics of 0.696 and 0.701, respectively).Risk of 1y-tl increased in recipients with cold ischaemia time, sum of HLA-A. -B, -DR mismatches and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set. CONCLUSION: Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pump use.

Acceptance and utilization of web-based self-help for caregivers of children with externalizing disorders.

BACKGROUND: Web-based self-help interventions for parents of children with ADHD and other externalizing disorders have been proven to be effective. In order to recommend individualized and optimized interventions, a better understanding of the acceptance and utilization of this innovative treatment approach is needed. Previous research has frequently employed subjective reports of utilization, but the validity of these studies may be limited. METHODS: Data from the German WASH study were used. Participants (n = 276) were randomly assigned to the intervention condition (a) web-based self-help or (b) web-based self-help with optional telephone-based support calls. Data collection took place at baseline (T1) and 12 weeks later (T2). Utilization data were tracked using a log file generated for each participant at T2. Prediction models were calculated using CART (Classification and Regression Trees), a method known mostly from the field of machine learning. RESULTS: Acceptance, of the intervention as defined in this paper was very high on objective (89.4% have taken up the intervention) and subjective measures (91.4% reported having used the intervention and 95.3% reported they would recommend the intervention to a friend). The average number of logins corresponded to recommendations. Predictors of acceptance and predictors of utilization were similar and included, e.g., child's externalizing symptoms, parental psychopathology, and above all additional telephone-based support by counselors. CONCLUSIONS: Through a detailed identification of acceptance and utilization, and the predictors thereof, we were able to gain a better understanding of the acceptance and utilization of web-assisted self-help for a parent management intervention in the treatment of children with ADHD and ODD. These findings can be used to recommend web-based interventions to particularly suitable families. It should be noted that some form of support is required for an intensive engagement with the content of the program. TRIAL REGISTRATION: The protocol of the study (German Clinical Trials Register DRKS00013456 conducted on January 3rd, 2018) was approved by the Ethics Committee of the University Hospital, Cologne.

Results of the Cologne Corona Surveillance (CoCoS) project- a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection, and moderate-to-severe course in primarily immunized adults.

BACKGROUND: Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. METHODS: The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants' demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. RESULTS: A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415-0.823) and older age (HR = 0.974, 95%CI 0.966-0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949-0.977). Female sex (HR = 2.570, 95%CI1.435-4.603), smoking (HR = 1.965, 95%CI1.147-3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465-5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. CONCLUSION: The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Asymmetric Adrenals: Sexual Dimorphism of Adrenal Tumors.

CONTEXT: Sexual dimorphism has direct consequences on the incidence and survival of cancer. Early and accurate diagnosis is crucial to improve prognosis. OBJECTIVE: This work aimed to characterized the influence of sex and adrenal asymmetry on the emergence of adrenal tumors. METHODS: We conducted a multicenter, observational study involving 8037 patients with adrenal tumors, including adrenocortical carcinoma (ACC), aldosterone-producing adenoma (APA), cortisol-secreting adrenocortical adenomas (CSAs), non-aldosterone-producing adrenal cortical adenoma (NAPACA), pheochromocytoma (PCC), and neuroblastoma (NB), and investigated tumor lateralization according to sex. Human adrenal tissues (n = 20) were analyzed with a multiomics approach that allows determination of gene expression, catecholamine, and steroid contents in a single sample. In addition, we performed a literature review of computed tomography and magnetic resonance imaging-based studies examining adrenal gland size. RESULTS: ACC (n = 1858); CSA (n = 68), NAPACA (n = 2174), and PCC (n = 1824) were more common in females than in males (female-to-male ratio: 1.1:1-3.8:1), whereas NBs (n = 2320) and APAs (n = 228) were less prevalent in females (0.8:1). ACC, APA, CSA, NAPACA, and NB occurred more frequently in the left than in the right adrenal (left-to-right ratio: 1.1:1-1.8:1), whereas PCC arose more often in the right than in the left adrenal (0.8:1). In both sexes, the left adrenal was larger than the right adrenal; females have smaller adrenals than males. CONCLUSION: Adrenal asymmetry in both sexes may be related to the pathogenesis of adrenal tumors and should be considered during the diagnosis of these tumors.

Pre-Implantation Kidney Biopsies in Extended Criteria Donors: From On Call to Expert Pathologist, from Conventional Microscope to Digital Pathology.

The number of patients awaiting a kidney transplant is constantly rising but lack of organs leads kidneys from extended criteria donors (ECD) to be used to increase the donor pool. Pre-transplant biopsies are routinely evaluated through the Karpinski-Remuzzi score but consensus on its correlation with graft survival is controversial. This study aims to test a new diagnostic model relying on digital pathology to evaluate pre-transplant biopsies and to correlate it with graft outcomes. Pre-transplant biopsies from 78 ECD utilized as single kidney transplantation were scanned, converted to whole-slide images (WSIs), and reassessed by two expert nephropathologists using the Remuzzi-Karpinski score. The correlation between graft survival at 36 months median follow-up and parameters assigned by either WSI or glass slide score (GSL) by on-call pathologists was evaluated, as well as the agreement between the GSL and the WSIs score. No relation was found between the GSL assessed by on-call pathologists and graft survival (P = 0.413). Conversely, the WSI score assigned by the two nephropathologists strongly correlated with graft loss probability, as confirmed by the ROC curves analysis (DeLong test P = 0.046). Digital pathology allows to share expertise in the transplant urgent setting, ensuring higher accuracy and favoring standardization of the process. Its employment may significantly increase the predictive capability of the pre-transplant biopsy evaluation for ECD, improving the quality of allocation and patient safety.

Performance of Scores Predicting Adverse Outcomes in Procurement Kidney Biopsies From Deceased Donors With Organs of Lower-Than-Average Quality.

Several scores have been devised for providing a prognosis of outcomes after kidney transplantation. This study is a comprehensive test of these scores in a cohort of deceased donors with kidneys of lower-than-average quality and procurement biopsies. In total, 15 scores were tested on a retrospective cohort consisting of 221 donors, 223 procurement biopsies, and 223 recipient records for performance on delayed graft function, graft function, or death-censored graft loss. The best-performing score for DGF was the purely clinical Chapal score (AUC 0.709), followed by the Irish score (AUC 0.684); for graft function, the Nyberg score; and for transplant loss, the Snoeijs score (AUC 0.630) and the Leuven scores (AUCs 0.637 and 0.620). The only score with an acceptable performance was the Chapal score. Its disadvantage is that knowledge of the cold ischemia time is required, which is not known at allocation. None of the other scores performed acceptably. The scores fared better in discarded kidneys than in transplanted kidneys. Our study shows an unmet need for practical prognostic scores useful at the time of a decision about discarding or accepting deceased donor kidneys of lower-than-average quality in the Eurotransplant consortium.

Histological and clinical evaluation of discarded kidneys in a European cohort of deceased brain death donor kidneys of marginal quality.

BACKGROUND: Despite organ shortages, the discard rate of deceased donor kidneys is high. Risk factors for this trend warrant further study. METHODS: We investigated reasons for discard in a cohort of brain death donors with marginal kidneys and procurement biopsies. Paraffin embedded procurement biopsies were systematically reevaluated and graded for the purpose of the study. Assessment included percentage of global glomerulosclerosis, Banff Lesion scores and tubular epithelial damage. Donor-, transplant process-, perfusion quality-, histopathology-, and recipient-related parameters were compared between discarded and transplanted organs. RESULTS: Although most clinical characteristics were similar between donors whose kidneys were transplanted and those whose kidneys were procured but discarded, discarded kidneys were more likely to be from donors with hepatitis C, to have undergone wedge biopsies, to show changes of acute and chronic injury and to be deemed poor quality. Except for obvious anatomic abnormalities, kidneys were often discarded due to the findings of procurement biopsies. Donors of kidneys discarded for histologic reasons more often had hypertension, coronary artery disease, stroke, and increased serum creatinine. The reason for discard was unknown in 20% of cases. Discarded kidneys came from donors who appeared to be clinically similar to donors whose kidneys were utilized for transplant. CONCLUSION: A considerable proportion of discarded kidneys were of acceptable quality. The analysis of the outcome of every recovered organ could help to overcome this problem. Procurement biopsies more often lead to discard than to transplantation of recovered organs. Proper handling during allocation has to be determined.

Performance and limitations of a supervised deep learning approach for the histopathological Oxford Classification of glomeruli with IgA nephropathy.

BACKGROUND AND OBJECTIVE: The Oxford Classification for IgA nephropathy is the most successful example of an evidence-based nephropathology classification system. The aim of our study was to replicate the glomerular components of Oxford scoring with an end-to-end deep learning pipeline that involves automatic glomerular segmentation followed by classification for mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S) and active crescents (C). METHODS: A total number of 1056 periodic acid-Schiff (PAS) whole slide images (WSIs), coming from 386 kidney biopsies, were annotated. Several detection models for glomeruli, based on the Mask R-CNN architecture, were trained on 587 WSIs, validated on 161 WSIs, and tested on 127 WSIs. For the development of segmentation models, 20,529 glomeruli were annotated, of which 16,571 as training and 3958 as validation set. The test set of the segmentation module comprised of 2948 glomeruli. For the Oxford classification, 6206 expert-annotated glomeruli from 308 PAS WSIs were labelled for M, E, S, C and split into a training set of 4298 glomeruli from 207 WSIs, and a test set of 1908 glomeruli. We chose the best-performing models to construct an end-to-end pipeline, which we named MESCnn (MESC classification by neural network), for the glomerular Oxford classification of WSIs. RESULTS: Instance segmentation yielded excellent results with an AP50 ranging between 78.2-80.1 % (79.4 ± 0.7 %) on the validation and 75.1-77.7 % (76.5 ± 0.9 %) on the test set. The aggregated Jaccard Index was between 73.4-75.9 % (75.0 ± 0.8 %) on the validation and 69.1-73.4 % (72.2 ± 1.4 %) on the test set. At granular glomerular level, Oxford Classification was best replicated for M with EfficientNetV2-L with a mean ROC-AUC of 90.2 % and a mean precision/recall area under the curve (PR-AUC) of 81.8 %, best for E with MobileNetV2 (ROC-AUC 94.7 %) and ResNet50 (PR-AUC 75.8 %), best for S with EfficientNetV2-M (mean ROC-AUC 92.7 %, mean PR-AUC 87.7 %), best for C with EfficientNetV2-L (ROC-AUC 92.3 %) and EfficientNetV2-S (PR-AUC 54.7 %). At biopsy-level, correlation between expert and deep learning labels fulfilled the demands of the Oxford Classification. CONCLUSION: We designed an end-to-end pipeline for glomerular Oxford Classification on both a granular glomerular and an entire biopsy level. Both the glomerular segmentation and the classification modules are freely available for further development to the renal medicine community.

Cusp overlap versus standard three-cusp technique for self-expanding Evolut transcatheter aortic valves.

BACKGROUND: Reducing rates of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is important for achieving the best procedural outcomes. The cusp overlap technique (COT) implements procedural steps including an overlap angulation of the right and left coronary cusp to mitigate this complication. AIMS: We investigated the incidence of PPI and complication rates following the COT compared to the standard three-cusp implantation technique (3CT) in an all-comers cohort. METHODS: A total of 2,209 patients underwent TAVI with the self-expanding Evolut platform from January 2016 to April 2022 at five sites. Baseline, procedural and in-hospital outcome characteristics were compared for both techniques before and after one-to-one propensity score matching. RESULTS: A total of 1,151 patients were implanted using the 3CT and 1,058 using the COT. At discharge, the rates of PPI (17.0 vs 12.3%; p=0.002) and moderate/severe paravalvular regurgitation (4.6% vs 2.4%; p=0.006) were significantly reduced with the COT compared with 3CT within the unmatched cohort. Overall procedural success and complication rates were similar; major bleeding was less common in the COT group (7.0% vs 4.6%; p=0.020). These results remained consistent after propensity score matching. In multivariable logistic regression analysis, right bundle branch block (odds ratio [OR] 7.19, 95% confidence interval [CI]: 5.18-10.0; p<0.001) and diabetes mellitus (OR 1.38, 95% CI: 1.05-1.80; p=0.021) emerged as predictors of PPI, whereas the COT (OR 0.63, 95% CI: 0.49-0.82; p<0.001) was protective. CONCLUSIONS: The introduction of the COT was associated with a significant and relevant reduction of PPI and paravalvular regurgitation rates without an increase in complication rates.

Genomic ALK alterations in primary and relapsed neuroblastoma.

BACKGROUND: Genomic alterations of the anaplastic lymphoma kinase gene (ALK) occur recurrently in neuroblastoma, a pediatric malignancy of the sympathetic nervous system. However, information on their development over time has remained sparse. METHODS: ALK alterations were assessed in neuroblastomas at diagnosis and/or relapse from a total of 943 patients, covering all stages of disease. Longitudinal information on diagnostic and relapsed samples from individual patients was available in 101 and 102 cases for mutation and amplification status, respectively. RESULTS: At diagnosis, ALK point mutations occurred in 10.5% of all cases, with highest frequencies in stage 4 patients <18 months. At relapse, ALK alteration frequency increased by 70%, both in high-risk and non-high-risk cases. The increase was most likely due to de novo mutations, frequently leading to R1275Q substitutions, which are sensitive to pharmacological ALK inhibition. By contrast, the frequency of ALK amplifications did not change over the course of the disease. ALK amplifications, but not mutations, were associated with poor patient outcome. CONCLUSIONS: The considerably increased frequency of ALK mutations at relapse and their high prevalence in young stage 4 patients suggest surveying the genomic ALK status regularly in these patient cohorts, and to evaluate ALK-targeted treatment also in intermediate-risk patients.

Prognostic impact of resting full-cycle ratio and diastolic non-hyperemic pressure ratios in patients with deferred revascularization.

BACKGROUND: Non-hyperemic pressure ratios (NHPRs) like resting full-cycle ratio (RFR), diastolic pressure ratio during entire diastole (dPR[entire]) and diastolic pressure ratio during wave-free period (dPR[WFP]) are increasingly used to guide revascularization. The effect of NHPRs on mid-term prognosis has not been well established. OBJECTIVE: We investigated the prognostic implications of NHRPs in patients whose revascularization was deferred based on fractional flow reserve (FFR) in a single-centre population. METHODS: NHPRs and FFR were calculated offline from pressure tracings by an independent core laboratory. Follow-up data were acquired through records of hospital visits or telephone interviews. The primary outcome was a vessel-oriented composite outcome (VOCO) (a composite of cardiac death, vessel-related myocardial infarction, and ischemia-driven revascularization) in deferred vessels at 2 years. RESULTS: 316 patients with 377 deferred lesions were analysed. Discordance of NHPRs and FFR was found in 13.0-18.3% of lesions. The correlation coefficient between NHPRs was 0.99 (95% confidence interval 0.99-1.00). At 2 years, VOCO occurred in 19 lesions (5.0%). Estimated glomerular filtration rate < 30 mL/min/1.73 m2 [hazard ratio (HR) 5.7, p = 0.002], previous myocardial infarction (HR 3.3, p = 0.018), diabetes (HR 2.7, p = 0.042), RFR ≤ 0.89 (HR 2.7, p = 0.041) and dPR[WFP] ≤ 0.89 (HR 2.7, p = 0.049) were associated with higher incidence of VOCO at 2 years in the univariable analysis. A non-significant trend was found for dPR[entire] (HR 1.9, p = 0.26). CONCLUSION: A positive RFR or dPR[WFP] were associated with a worse prognosis in deferred lesions, suggesting that the use of NHPRs in addition to FFR may improve risk estimation.

Incidence of premature battery depletion in subcutaneous cardioverter-defibrillator patients: insights from a multicenter registry.

BACKGROUND: The subcutaneous ICD established its role in the prevention of sudden cardiac death in recent years. The occurrence of premature battery depletion in a large subset of potentially affected devices has been a cause of concern. The incidence of premature battery depletion has not been studied systematically beyond manufacturer-reported data. METHODS: Retrospective data and the most recent follow-up data on S-ICD devices from fourteen centers in Europe, the US, and Canada was studied. The incidence of generator removal or failure was reported to investigate the incidence of premature S-ICD battery depletion, defined as battery failure within 60 months or less. RESULTS: Data from 1054 devices was analyzed. Premature battery depletion occurred in 3.5% of potentially affected devices over an observation period of 49 months. CONCLUSIONS: The incidence of premature battery depletion of S-ICD potentially affected by a battery advisory was around 3.5% after 4 years in this study. Premature depletion occurred exclusively in devices under advisory. This is in line with the most recently published reports from the manufacturer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04767516 .

Short-term outcomes after transplantation of deceased donor kidneys with acute kidney injury: a retrospective analysis of a multicenter cohort of marginal donor kidneys with post-explantation biopsies.

BACKGROUND: Deceased donor kidneys with acute kidney injury (AKI) are often discarded because of concerns about inferior transplant outcomes. A means of grading the quality of such kidneys is the performance of procurement biopsies. METHODS: This is a retrospective study of 221 brain death donors with marginal kidneys transplanted in 223 recipients in Germany. Marginal kidneys were defined as kidneys with procurement biopsies done exceptionally to assess suitability for transplantation in otherwise potentially discarded organs. The impact of deceased donor AKI on patient survival and death-censored graft survival at 1, 3 and 5 years and graft function at 1 and 3 years after transplantation was investigated. RESULTS: Recipients of kidneys with stage 3 AKI had a greater incidence of delayed graft function [DGF; ORStage 1: 1.435 (95% CI 0.438-0.702), ORStage 2: 2.463 (95% CI 0.656-9.245), ORStage 3: 4.784 (95% CI 1.421-16.101)] but a similar graft and patient survival compared to recipients of donors without AKI and with AKI stage 1 and 2 as well. The coexistence of recipient DGF and donor AKI was associated with the lowest graft survival and function rates. CONCLUSION: The transplantation of deceased donor marginal kidneys with AKI confers a higher risk for DGF but is associated with acceptable graft and patient outcomes, which do not differ in comparison with marginal donor kidneys without AKI. Graft prognosis is especially poor if donor AKI and recipient DGF concur. Donor AKI was a risk factor independent of the histological lesions of procurement biopsies.

Feasibility and Potential of Transcriptomic Analysis Using the NanoString nCounter Technology to Aid the Classification of Rejection in Kidney Transplant Biopsies.

BACKGROUND: Transcriptome analysis could be an additional diagnostic parameter in diagnosing kidney transplant (KTx) rejection. Here, we assessed feasibility and potential of NanoString nCounter analysis of KTx biopsies to aid the classification of rejection in clinical practice using both the Banff-Human Organ Transplant (B-HOT) panel and a customized antibody-mediated rejection (AMR)-specific NanoString nCounter Elements (Elements) panel. Additionally, we explored the potential for the classification of KTx rejection building and testing a classifier within our dataset. METHODS: Ninety-six formalin-fixed paraffin-embedded KTx biopsies were retrieved from the archives of the ErasmusMC Rotterdam and the University Hospital Cologne. Biopsies with AMR, borderline or T cell-mediated rejections (BLorTCMR), and no rejection were compared using the B-HOT and Elements panels. RESULTS: High correlation between gene expression levels was found when comparing the 2 chemistries pairwise (r = 0.76-0.88). Differential gene expression (false discovery rate; P < 0.05) was identified in biopsies diagnosed with AMR (B-HOT: 294; Elements: 76) and BLorTCMR (B-HOT: 353; Elements: 57) compared with no rejection. Using the most predictive genes from the B-HOT analysis and the Element analysis, 2 least absolute shrinkage and selection operators-based regression models to classify biopsies as AMR versus no AMR (BLorTCMR or no rejection) were developed achieving an receiver-operating-characteristic curve of 0.994 and 0.894, sensitivity of 0.821 and 0.480, and specificity of 1.00 and 0.979, respectively, during cross-validation. CONCLUSIONS: Transcriptomic analysis is feasible on KTx biopsies previously used for diagnostic purposes. The B-HOT panel has the potential to differentiate AMR from BLorTCMR or no rejection and could prove valuable in aiding kidney transplant rejection classification.

Effect of creatinine metrics on outcome after transplantation of marginal donor kidneys.

INTRODUCTION: Predicting outcome after transplantation of marginal kidneys is a challenging task. Donor creatinine or estimated glomerular filtration rate (eGFR) are integral components of the respective risk scores. However, there is uncertainty on which of their values obtained successively during procurement is the most suitable. MATERIAL AND METHODS: This is a retrospective study of 221 adult brain death donors with marginal kidneys, transplanted in 223 recipients. We applied logistic regression analysis to investigate the association between initial (at hospital admission), nadir (lowest), zenith (highest) and terminal (at recovery) donor eGFR with primary non-function (PNF), delayed graft function (DGF), 3- and 12-month graft function and 1- and 3-year patient- and death-censored graft survival. RESULTS: In the multivariate analysis, admission, terminal, and the lowest donor eGFR could most accurately predict DGF. The respective ORs [95% CI] were: 0.875 [0.771-0.993], 0.818 [95% CI: 0.726-0.922] and 0.793 [0.689-0.900]. Although not being significant for DGF (OR 0.931 [95% CI: 0.817-1.106]), the highest eGFR was the best predictor of 3-month graft function (adjusted b coefficient 1.161 [95% CI: 0.355-1.968]). Analysis of primary nonfunction showed that determination of initial and the highest eGFR proved to be the best predictors. The respective ORs [95% CI] were: 0.804 [0.667-0.968] and 0.750 [0.611-0.919]. There were no differences in the risk associations of each of the four eGFR recordings with patient- and graft survival. CONCLUSION: The various eGFR recordings determined during the procurement process of marginal donors can predict PNF, DGF and 3- and 12-month graft function. Regarding short-term patient- and graft survival, there appears to be impacted by recipient factors rather than donor kidney function.

Influence of patient sex on outcomes after pancreatic surgery: multicentre study.

BACKGROUND: Recent findings support the hypothesis of sex-related differences in inflammatory and immunological responses to trauma. The aim of this study was to address sex-specific aspects in patients who underwent pancreatic surgery. METHODS: This retrospective study used data from the German StuDoQ registry. Patients who underwent pancreatic surgery between 2010 and 2020 were stratified according to procedure (pancreatic head resection, distal pancreatectomy (DP), total pancreatectomy (TP)). Each cohort underwent propensity score matching (PSM) with the co-variables BMI, ASA, age, coronary heart disease (CHD), diabetes, hypertension with medication, and histology to level the distribution of co-morbidities between men and women. The main outcomes were morbidity and mortality. RESULTS: The total cohort consisted of 10 224 patients (45.3 per cent women). Men had higher ASA grades, and more often had CHD, diabetes, and hypertension with medication. Women had fewer overall complications (57.3 versus 60.1 per cent; P = 0.005) and a lower mortality rate (3.4 versus 4.9 per cent; P < 0.001). Rates of pancreatic surgery-specific complications, such as clinically relevant postoperative pancreatic fistula (POPF) (grade B/C: 14 versus 17 per cent; P < 0.001), delayed gastric emptying (grade B/C: 7.8 versus 9.2 per cent; P = 0.014), and postpancreatectomy haemorrhage (grade B/C: 7.1 versus 9.0 per cent; P < 0.001), were also lower in women. After PSM, 8358 patients were analysed. In the pancreatic head resection cohort (5318 patients), women had fewer complications (58.6 versus 61.4 per cent; P = 0.044), a lower in-hospital mortality rate (3.6 versus 6.1 per cent; P < 0.001), and less often had clinically relevant POPF (11.6 versus 16.2 per cent; P < 0.001). After DP, the clinically relevant POPF rate was lower in women (22.5 versus 27.3 per cent; P = 0.012). In the TP cohort, men more often developed intra-abdominal abscess requiring drainage (5.0 versus 2.3 per cent; P = 0.050). CONCLUSION: Women had favourable outcomes after pancreatic surgery.

Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients-a CERTAIN registry analysis.

BACKGROUND: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients. METHODS: This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26. RESULTS: One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented. CONCLUSION: This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated.

Short-term outcome of Ivor Lewis esophagectomy following neoadjuvant chemoradiation versus perioperative chemotherapy in patients with locally advanced adenocarcinoma of the esophagus and gastroesophageal junction: a propensity score-matched analysis.

BACKGROUND: Patients with locally advanced esophageal or gastroesophageal adenocarcinoma benefit from multimodal therapy concepts including neoadjuvant chemoradiation (nCRT), respectively, perioperative chemotherapy (pCT). However, it remains unclear which treatment is superior concerning postoperative morbidity. METHODS: In this study, we compared the postsurgical survival (30-day/90-day/1-year mortality) (primary endpoint), treatment response, and surgical complications (secondary endpoints) of patients who either received nCRT (CROSS protocol) or pCT (FLOT protocol) due to esophageal/gastroesophageal adenocarcinoma. Between January 2013 and December 2017, 873 patients underwent Ivor Lewis esophagectomy in our high-volume center. 339 patients received nCRT and 97 underwent pCT. After 1:1 propensity score matching (matching criteria: sex, age, BMI, ASA score, and Charlson score), 97 patients per subgroup were included for analysis. RESULTS: After matching, tumor response (ypT/ypN) did not differ significantly between nCRT and pCT (p = 0.118, respectively, p = 0.174). Residual nodal metastasis occurred more often after pCT (p = 0.001). Postsurgical mortality was comparable within both groups. No patient died within 30 or 90 days after surgery while the 1-year survival rate was 72.2% for nCRT and 68.0% for pCT (p = 0.47). Only grade 3a complications according to Clavien-Dindo were increased after pCT (p = 0.04). There was a trend towards a higher rate of pylorospasm within the pCT group (nCRT: 23.7% versus pCT: 37.1%) (p = 0.061). Multivariate analysis identified pCT, younger age, and Charlson score as independent variables for pylorospasm. CONCLUSION: Both nCRT and pCT are safe and efficient within the multimodal treatment of esophageal/gastroesophageal adenocarcinoma. We did not observe differences in postoperative morbidity. However, functional aspects such as gastric emptying might be more frequent after pCT.

Genetic Alterations and Resectability Predict Outcome in Patients with Neuroblastoma Assigned to High-Risk Solely by MYCN Amplification.

BACKGROUND: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). METHODS: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). RESULTS: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39-54%) and 56% (95%-CI 49-63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18-31%, p < 0.001; OS 32% 95%-CI 25-39%, p < 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both p < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p < 0.001 and p = 0.011, respectively). CONCLUSIONS: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.