Centre Hospitalier Régional de Namur

Abstract Background and Aims In recent years, an innovative strategy using laser microdissection and mass spectrometry (LCM/MS) markedly expanded the landscape of antigens associated with membranous nephropathy (MN). Specific associations with phenotypes, diseases and sometimes reversible triggers led to a novel antigen-based classification of MN, paving the way for precision medicine and stressing the need for more routine use of proteomics in MN. Method In this work, we expanded the original technique of LCM/MS by integrating the more comprehensive data-independent acquisition (DIA) approach. Compared to conventional data-dependent acquisition (DDA), DIA MS enables the identification and quantification of every detectable peptide in a sample. It is also more reproducible, especially for low-abundance species. Computational analysis tools, including principal component analysis and differential abundance analyses, were then used to analyze and compare protein abundances. Results First, as a validation of our pipeline, we confirmed the significant enrichment in PLA2R, IgG4 and complement proteins and provided molecular evidence for complement activation in glomeruli from patients with PLA2R-MN. Next, we showed that, compared to conventional DDA, DIA increased the number of glomerular proteins (∼3800 vs ∼1200) identified in healthy glomeruli; allowed the detection of all known antigens except NELL1 in normal glomeruli; and increased the detection rate of antigens from 46% to 83% in PLA2R-negative MN. Out of 23 PLA2R-negative MN cases, with a non-significant staining for PLA2R on immunohistochemistry, our proteomic workflow identified NELL1 in seven (30%); THSD7A in three (13%); PLA2R in three (13%); NCAM1 in two (9%); PCSK6 in two (9%); CNTN1 in one (4%) and NDNF in one (4%). Confocal microscopy confirmed the suspected target antigens in immune deposits along glomerular basement membranes. Reverse phenotyping showed that three out of the seven cases of NELL1-MN were associated with malignancies; the two patients with NCAM1-MN had mixed connective tissue disease; one of the three patients with THSD7A-MN had neuroendocrine malignancy; the patient with NDNF-MN had syphilis; and one patient with PCSK6-MN had systemic sclerosis. Conclusion An integrative approach combining LCM and DIA MS is a powerful tool to identify target antigens and unravel disease mechanisms in MN.

Two OFFO (Objective-Function Free Optimization) noise tolerant algorithms are presented that handle bound constraints, inexact gradients and use second-order information when available.The first is a multi-level method exploiting a hierarchical description of the problem and the second is a domain-decomposition method covering the standard addditive Schwarz decompositions. Both are generalizations of the first-order AdaGrad algorithm for unconstrained optimization. Because these algorithms share a common theoretical framework, a single convergence/complexity theory is provided which covers them both. Its main result is that, with high probability, both methods need at most $O(\epsilon^{-2})$ iterations and noisy gradient evaluations to compute an $\epsilon$-approximate first-order critical point of the bound-constrained problem. Extensive numerical experiments are discussed on applications ranging from PDE-based problems to deep neural network training, illustrating their remarkable computational efficiency.

The prevention and management of allergic reactions at school is now recognized as a public health concern in many countries, with around 10% of pediatric anaphylaxis cases occurring at school [1]. In France, prevention measures in allergic children at school have been updated in 2021 and national policies mandated secondary schools to stock undesignated adrenaline auto-injectors (AAI) since 2019 [2]. There are only few published data on anaphylaxis at school, many from the United States [3]. The aim of our study was to analyze data on food-induced anaphylaxis (FIA) at school and describe their main characteristics and time trends. We conducted a retrospective analysis of an FIA cohort based on the Allergy-Vigilance Network (AVN) database (2002–2023) (see Supporting Information for Methods). Of the 3119 FIA reactions recorded by the AVN, 1762 (56.5%) involved school-age children (3–18 years) and 157 (8.9%) occurred at school. The main characteristics and treatment of these 157 cases are detailed in Table 1 (see Supporting Information for additional results). Three groups of children have been identified according to a history of food allergy (group 1: no prior food allergy; group 2: known food allergy to the culprit food; group 3: food allergy for another culprit food) with no difference between the three groups, except a history of asthma which was more frequently observed in group 3 compared to both other groups (p = 0.03) (Table 1). Of the 112 food allergic children, 52 (46.4%) had received an individual healthcare plan (IHP) with an AAI available in 43 (82.7%). 5 (3.2) 4 deaths 4 (5.6) 4 deaths The main foods involved in the FIA at school were peanut (n = 33; 21.0%) and cow, goat, and sheep milk (n = 18; 11.5%) (Figure S1). According to severity (Ring classification modified by Behrendt), 41 (26.1%) cases were classified as grade 3 and 5 (3.2%) as grade 4, including four deaths (all induced by milk) [4]. Intramuscular adrenaline was administered in 41 (26.1%) children but only in 22 (14.0%) at school (with an AAI in 17 [10.8%]). Comparing the three time periods, there was an increase in the absolute number of FIA cases at school and in adrenaline use (p < 10−3) but no significant variation in the rate of FIA cases among the number of FIA cases in school-aged children (p = 0.71), in the distribution of cases according to severity (p = 0.99) or food triggers (peanut or other foods) (p = 0.48 and p = 0.28, respectively) (Figure 1 and Figure S2). Our data illustrate how difficult it is to prevent the occurrence of anaphylaxis at school, with 29% of FIA occurring in children with no food allergy and a large variety of food allergens. Conversely, 45% of FIA occurred in children with a known food allergy and should be therefore avoidable. Most cases were related to accidental exposure and resulted in a complex series of avoidable errors or shortcomings from all parties. Peanut remains the most frequent food involved in FIA as reported throughout the world [1, 5]. To address issues regarding food avoidance, some schools have opted for allergen restrictions in school settings, but there is a lack of evidence that they are effective strategies [6]. A number of countries now require schools to have specific policies and procedures to keep food-allergic children safe. Our data also highlight shortcomings regarding recognition and management of FIA cases with an alarming underuse (26%) of adrenaline. However, we found an increasing rate of adrenaline use over time, rising at 41% of cases from 2016 to 2023. In conclusion, our study highlights that anaphylaxis occurring at school may lead to severe reactions, including death, with frequent unknown allergy to the culprit food and insufficient adrenaline use. There is a huge room for improvement in the prevention and management of anaphylaxis at school to focus on IHP use for food allergic children, promotion of training programs to school-canteen staff. G.P. analyzed, interpreted the data, and wrote the draft. Y.K.-A. performed the statistical analysis, interpreted the data, and reviewed the draft. G.P., A.D.-C., Y.K.-A., C.B., and D.S.-L. were major contributors in reviewing the draft and improving the paper with critical analysis. S.T. collected data from the Allergy-Vigilance Network. We acknowledge all the Allergy-Vigilance Network members who participated in this study and collected data. G.P. has provided consultation and speaker services for AI Therapeutics, Bausch+Lomb, Stallergenes, Novartis, DVB technology, ALK-Abello; serves as a medical consultant/advisor for Bioprojet, Theravia. The authors have nothing to report. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

IntroductionAbdominal surgical emergencies have a high mortality rate. Effective management primarily relies on the early identification of patients at high risk of postoperative complications. The objective of our study was to determine the prognostic factors associated with poor outcomes from abdominal surgical emergencies in Senegal and to establish a predictive score for mortality for preoperative risk evaluation (NDAR (New Death Assessment Risk) score).MethodologyThis was a retrospective national cross-sectional study conducted over one year in 14 regions of Senegal. Adult patients (aged > 15 years) who presented with a traumatic or non-traumatic abdominal surgical emergency were included. The studied variables included clinical and paraclinical data. The variable of interest was death within 30 days of the surgery. Logistic regression was used to identify the factors independently associated with mortality. Risk factors identified after logistic regression analysis were weighted using odds ratio (OR) values rounded to the nearest whole number. The predictive capacity of the score was evaluated by analyzing the ROC (Receiver Operating Characteristic) curve based on the area under the curve (AUC).ResultsA total of 1114 patient records were included, with a mortality rate of 4.4%. Diagnoses were observed in patients included appendicitis in 39.8% of cases (n = 444), followed by peritonitis in 22.3% (n = 249), intestinal obstruction in 18.5% (n = 205), strangulated hernias in 10.5% (n = 117), and abdominal trauma in 6.1%. Logistic regression, established the following scores: age > 40 years (score 2), ASA status grade 2 or higher (score 1), presence of a positive QSIRS score (score 2), diagnosis of peritonitis (score 2), diagnosis of intestinal obstruction (score 1), and the presence of intestinal necrosis (score 3). The score is positive if the total is strictly greater than 5, indicating a 17.7% risk of mortality. This score had a high predictive capacity with an AUC of 0.7397.ConclusionThis study enabled the establishment of a score that allows for the early identification of at-risk patients, even in constrained resource settings, facilitating appropriate perioperative management and timely surgical intervention to reduce the risk of complications. This approach, focused on early recognition of high-risk patients, is crucial for improving clinical outcomes in abdominal surgical emergencies.

ABSTRACTBackgroundThe use of interstitial glucose monitoring devices such as flash glucose monitoring has been shown to be beneficial in patients with type 1 diabetes mellitus (T1DM). However, these devices have been little studied in patients with diabetes treated by chronic haemodialysis (HD).MethodsThe goal of this prospective, observational, multicentric study was to evaluate the analytical performance of the FreeStyle Libre 2 (FSL2) sensor in T1DM patients during HD sessions. During three HD sessions, interstitial fluid glucose (ISFG) concentrations given by the FSL2 were compared every 15 minutes with blood glucose (BG) concentrations obtained simultaneously. BG concentrations were measured by two different glucometers: the Accu-Chek Guide and StatStrip meters.ResultsTwelve HD patients were included, with a mean age of 54 ± 11 years and a mean diabetes duration of 36.5 ± 11.6 years. Dialysis vintage was 35 ± 22 months. A total of 565 pairs of ISFG/BG values were available for analysis. The mean absolute relative difference, defined as the mean of the absolute relative differences between the ISFG and BG measurements, was 17.4% and 20.9% when the ISFG was compared with the StatStrip meter or Accu-Chek Guide, respectively. Interstitial results tend to underestimate blood results, but all values were classified as having clinically acceptable error. The differences observed remained stable during the dialysis session and were not associated with the ultrafiltration rate.ConclusionUse of the FSL2 interstitial glucose monitoring device in HD patients with T1DM is clinically acceptable, even though the accuracy of the device is generally poorer than in studies including non-dialysis patients.

Background We aimed to share our methods and experience of persistent AF ablation without a circular mapping catheter (CMC), thereby avoiding femoral venous and transseptal punctures, decreasing the cost of the procedure, and possibly reducing the duration of the procedure and fluoroscopy time. Methods We report our experience with 261 persistent AF ablations performed without a CMC over the past 3 years. Results The procedures were performed with no apparent loss of efficacy or safety. Freedom from recurrence was defined as a 1-year absence of AF/atrial flutter (AFL) episodes >30 s, beyond the 3-month blanking period. At 1 year, 72% of the patients were free from arrythmias. Conclusions Persistent AF ablation is feasible without a CMC, reducing the need for venous and transseptal punctures and the cost of the procedure. We suggest that prospective studies should aim to characterise the reduction in procedure and fluoroscopy times as a result of this technique.