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Pascal Delsart1, Marco Midulla2, Jonathan Sobocinski3, Charles Achere4, Stephan Haulon3, Gonzague Claisse1, Claire Mounier-Vehier11Vascular Medicine and Hypertension Department, Cardiology Hospital, CHRU Lille, 2Radiology and Cardiovascular Imaging Department, Cardiology Hospital, CHRU Lille, 3Vascular Surgery Department, Cardiology Hospital, CHRU Lille, 4Cardiology Department, Cardiology Hospital, CHRU Lille, FranceAbstract: The chronic management of post-acute aortic dissection (AD) of the descending aorta (Type B) is based on optimal control of blood pressure (BP), with a target BP < 135/80 mmHg. The aim of our study was to determine and verify effective blood pressure control with an objective measurement method and to identify predicting factors.Methods: We collected data from 26 patients hospitalized in the acute phase of a Type B AD between 2006 and 2009. Two groups were defined according to 24 hour BP monitoring results at follow-up. Group 1 consisted of patients with a controlled BP (< 130/80 mmHg), and Group 2 consisted of patients with an uncontrolled BP.Results: Thirty four percent of patients showed an uncontrolled BP at checkup. Vascular history before AD (P = 0.06), high baseline BP trend (P = 0.01 for systolic and P = 0.08 for diastolic), and greater diameter of the descending aorta (P = 0.02) were associated with poor BP control.Conclusion: Prognosis after AD is associated with BP control. Therefore, 24 hour BP monitoring can be made.Keywords: acute aortic syndrome, blood pressure monitoring, hypertension

Abstract Background The Wuschel related homeobox (WOX) family proteins are key regulators implicated in the determination of cell fate in plants by preventing cell differentiation. A recent WOX phylogeny, based on WOX homeodomains, showed that all of the Physcomitrella patens and Selaginella moellendorffii WOX proteins clustered into a single orthologous group. We hypothesized that members of this group might preferentially share a significant part of their function in phylogenetically distant organisms. Hence, we first validated the limits of the WOX13 orthologous group (WOX13 OG) using the occurrence of other clade specific signatures and conserved intron insertion sites. Secondly, a functional analysis using expression data and mutants was undertaken. Results The WOX13 OG contained the most conserved plant WOX proteins including the only WOX detected in the highly proliferating basal unicellular and photosynthetic organism Ostreococcus tauri. A large expansion of the WOX family was observed after the separation of mosses from other land plants and before monocots and dicots have arisen. In Arabidopsis thaliana, AtWOX13 was dynamically expressed during primary and lateral root initiation and development, in gynoecium and during embryo development. AtWOX13 appeared to affect the floral transition. An intriguing clade, represented by the functional AtWOX14 gene inside the WOX13 OG, was only found in the Brassicaceae. Compared to AtWOX13, the gene expression profile of AtWOX14 was restricted to the early stages of lateral root formation and specific to developing anthers. A mutational insertion upstream of the AtWOX14 homeodomain sequence led to abnormal root development, a delay in the floral transition and premature anther differentiation. Conclusion Our data provide evidence in favor of the WOX13 OG as the clade containing the most conserved WOX genes and established a functional link to organ initiation and development in Arabidopsis, most likely by preventing premature differentiation. The future use of Ostreococcus tauri and Physcomitrella patens as biological models should allow us to obtain a better insight into the functional importance of WOX13 OG genes.

Introduction: The International IgA Nephropathy Network developed a tool (IINN-PT) for predicting the risk of end-stage renal disease (ESRD) or a 50% decline in the estimated glomerular filtration rate (eGFR). We aimed to validate this tool in a French cohort with longer follow-up than previously published validation studies., Methods: The predicted survival of patients with biopsy-proven immunoglobulin A nephropathy (IgAN) from the Saint Etienne University Hospital cohort was computed with IINN-PT models with or without ethnicity. The primary outcome was the occurrence of either ESRD or a 50% decline in eGFR. The models' performances were evaluated through c-statistics, discrimination and calibration analysis., Results: There were 473 patients with biopsy-proven IgAN, with a median follow-up of 12.4 years. Models with and without ethnicity showed areas under the curve (95% confidence interval) of 0.817 (0.765; 0.869) and 0.833 (0.791; 0.875) and R2D of 0.28 and 0.29, respectively, and an excellent discrimination of groups of increasing predicted risk (P < .001). The calibration analysis was good for both models up to 15 years after diagnosis. The model without ethnicity exhibited a mathematical issue of survival function after 15 years., Discussion: The IINN-PT provided good performances even after 10 years post-biopsy as showed by our study based on a cohort with a longer follow-up than previous cohorts (12.4 versus <6 years). The model without ethnicity exhibited better performances up to 15 years but became aberrant beyond this point due to a mathematical issue affecting the survival function. Our study sheds light on the usefulness of integrating ethnicity as a covariable for prediction of IgAN course., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: HLAs contain combinations of multiple eplets, sometimes shared between numerous HLA alleles. Some authors suggested that single antigen bead (SAB) assays may underestimate the signal of anti-HLA antibodies (Ab) when several beads share the targeted eplet. However, this assumption has not yet been validated experimentally., Methods: We selected 5 eplets shared by 1-24 beads of the routine SAB kits: the eplet 163LS/G; the 3 eplets 127K, 62GE, and 62GRN thereafter called cross-reactive group 2C; the 82LR eplet, well-known as Bw4; the locally called QB2A5 eplet associated with the DQA1*05:01/DQB1*02:01 combination; and the 40GR DQ eplet. We selected a dozen of sera for each eplet with Ab mean fluorescence intensity (MFI) between 1000 and 15 000 for the beads carrying the targeted eplet. We tested them with the classical SAB panel (SABp), with an isolated bead carrying the eplet (isolated SAB [SABi]) and with a mixture of both (SABp+i)., Results: No significant difference in MFI was detected among SABi, SABp, and SABp+i conditions for all the eplets., Conclusions: We noticed only a nonsignificant difference in the Ab MFI signal due to eplet sharing on the SAB assay. We, therefore, conclude that this phenomenon should no longer be considered as a significant risk factor during patient follow-up pre- or posttransplantation., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Metformin is the first-line treatment used for type 2 diabetes mellitus for more than 60 years. Metformin-associated lactic acidosis is the most serious adverse effect of metformin and is most widely defined as metabolic acidosis with elevated lactate levels in the presence of metformin. However, there is no consensus regarding the role of metformin in metformin-associated lactic acidosis onset. This study aimed to determine the metformin toxicity threshold (the metformin plasma concentration that predicts the occurrence of lactic acidosis) and the metformin dialysis threshold (the metformin plasma concentration strongly correlated with dialysis introduction)., Methods: This was a retrospective multicenter cohort study conducted from January 1, 2013, to December 31, 2020. All consecutive adult patients with at least one metformin-detectable blood concentration measurement were included., Results: In total, 169 patients (92 men; mean age, 70 ± 11 years) were included in this study. A receiver operating characteristic analysis using Youden index showed that a metformin plasma concentration threshold of 17.9 mg/L was associated with lactic acidosis (sensitivity: 43.8%; specificity: 90.5%). Another receiver operating characteristic analysis using Youden index showed that a metformin plasma concentration threshold of 17.5 mg/L was associated with dialysis (sensitivity, 53.0%; specificity: 94.2%)., Conclusions: The retrospective study design, lack of clinical data, and selection bias (patients in whom metformin was prescribed owing to pathological conditions) were major limitations, resulting in only preliminary findings. However, this study could serve as a basis for future prospective clinical studies to evaluate the use of these clinical threshold values as therapeutic guides., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: The purpose of this study was to assess urinary (TIMP-2)*(IGFBP7) for prevention of acute kidney injury (AKI) in patients undergoing elective cardiac surgery. Materials & methods: Two retrospective cohorts were analyzed before and after the implementation of urinary (TIMP-2)*(IGFBP7). The control cohort had a standard supportive care. For the (TIMP-2)*(IGFBP7) cohort, patients with the (TIMP-2)*(IGFBP7) >0.3 received renal supportive measures. Results: A total of 382 patients were included, 197 in the control cohort and 185 in intervention cohort. The incidence of AKI was significantly reduced in the (TIMP-2)*(IGFBP7) cohort (20.5 vs 29.9%, p < 0.05). In multivariate analysis, patients of the (TIMP-2)*(IGFBP7) cohort had a lower risk of developing AKI (p = 0.029). Conclusion: In conclusion, renal supporting care based on AKI risk stratification using urinary (TIMP-2)*(IGFBP7) may reduce AKI incidence.

Long-term safety of living kidney donation (LKD), especially for young donors, has become a real matter of concern in the transplant community and may contribute to creating resistance to LKD. In this context, the criteria that govern living donor donations must live up to very demanding standards as well as adjust to this novel reality. In the first part, we review the existing guidelines published after 2010 and critically examine their recommendations to see how they do not necessarily lead to consistent and universal practices in the choice of specific thresholds for a parameter used to accept or reject a living donor candidate. In the second part, we present the emergence of a new paradigm for LKD developed in the 2017 Kidney Disease: Improving Global Outcomes guidelines with the introduction of an integrative risk-based approach. Finally, we focus on predonation renal function evaluation, a criteria that remain central in the selection process, and discuss several issues surrounding the donor candidate's glomerular filtration rate assessment.

Background: The prognosis of IgA nephropathy (IgAN) is very heterogeneous. Predicting the nature and the rate of the disease progression is crucial for refining patient treatment. The aim of this study was to evaluate the prognostic impact of an Oxford classification-based repeat kidney tissue evaluation to predict end-stage renal disease (ESRD)., Methods: Patients with biopsy-proven primary IgAN who underwent two renal biopsies at our centre were analyzed retrospectively. Renal biopsies were scored by two pathologists blinded to the clinical data and according to the updated Oxford classification. Cox models were generated to evaluate the prognostic impact considering the Oxford classification elementary lesions from the first (Model 1) or the second (Model 2) biopsy, adjusted on clinical data at time of reevaluation. The prognostic impacts of the dynamic evolution of each elementary lesion between biopsies were also assessed through univariate and multivariate evaluation., Results: A total of 168 adult patients were included, with a median follow-up duration of 18 (range 11-24) years. The second biopsy was performed either systematically (n = 112) of for-cause (n = 56), after a median time of 5.4 years. The prognostic performances of Model 2 (second biopsy) were significantly better than Model 1 (first biopsy, analysis of deviance P < 0.0001). The dynamic changes of C and T lesions were significantly associated with the progression toward ESRD after adjustment on variables from Model 2., Conclusion: Both static and dynamic Oxford-based histological evaluation offered by a repeat biopsy improves the prediction of ESRD in patients with IgAN., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)