[Magnesium: the missing link between kidneys and vessels?]. / Magnésium: le lien manquant entre reins et vaisseaux?

Chronic kidney disease is highly prevalent worldwide and is associated with important cardiovascular morbidity and mortality. The search for new prognostic factors and therapeutic targets is therefore essential. There has been recently an increased interest about magnesium, poorly studied yet in that context. In this article, we review the most recent studies looking at the associations between magnesium, cardiovascular and chronic kidney disease. According to the available data, hypomagnesemia seems to alter negatively cardiovascular and renal prognosis. Maintaining normal magnesium levels could then be protective. However, studied populations are heterogeneous, most of the data is only observational and residual confounding factors still need to be considered. All those issues limit currently any definitive therapeutic recommendations.

Deep Learning Enables Spatial Mapping of the Mosaic Microenvironment of Myeloma Bone Marrow Trephine Biopsies.

Bone marrow trephine biopsy is crucial for the diagnosis of multiple myeloma. However, the complexity of bone marrow cellular, morphologic, and spatial architecture preserved in trephine samples hinders comprehensive evaluation. To dissect the diverse cellular communities and mosaic tissue habitats, we developed a superpixel-inspired deep learning method (MoSaicNet) that adapts to complex tissue architectures and a cell imbalance aware deep learning pipeline (AwareNet) to enable accurate detection and classification of rare cell types in multiplex immunohistochemistry images. MoSaicNet and AwareNet achieved an AUC of >0.98 for tissue and cellular classification on separate test datasets. Application of MoSaicNet and AwareNet enabled investigation of bone heterogeneity and thickness as well as spatial histology analysis of bone marrow trephine samples from monoclonal gammopathies of undetermined significance (MGUS) and from paired newly diagnosed and posttreatment multiple myeloma. The most significant difference between MGUS and newly diagnosed multiple myeloma (NDMM) samples was not related to cell density but to spatial heterogeneity, with reduced spatial proximity of BLIMP1+ tumor cells to CD8+ cells in MGUS compared with NDMM samples. Following treatment of patients with multiple myeloma, there was a reduction in the density of BLIMP1+ tumor cells, effector CD8+ T cells, and regulatory T cells, indicative of an altered immune microenvironment. Finally, bone heterogeneity decreased following treatment of patients with multiple myeloma. In summary, deep learning-based spatial mapping of bone marrow trephine biopsies can provide insights into the cellular topography of the myeloma marrow microenvironment and complement aspirate-based techniques. SIGNIFICANCE: Spatial analysis of bone marrow trephine biopsies using histology, deep learning, and tailored algorithms reveals the bone marrow architectural heterogeneity and evolution during myeloma progression and treatment.

Adaptation of a multiple myeloma minimal residual disease multicolor flow cytometry assay for real-world practice.

BACKGROUND: Achieving minimal residual disease (MRD) negativity following treatment for multiple myeloma (MM) is associated with improved progression free and overall survival. In the UK, MRD assessments in MM are not incorporated into routine clinical use outside trials. Widely used in other haematological malignancies, there is a role for widening the availability of myeloma MRD assays to laboratories outside larger treating centers. METHODS: We set up and assessed concordance of a multicolor flow cytometry (MCF) assay for MM MRD in collaboration with a reference center including validity following delayed processing of samples using an optimized fixation step. We then conducted a real-world snapshot of MRD results in a cohort of newly diagnosed transplant-eligible patients treated with UK standard induction therapies at the time of analysis. RESULTS: 43 MCF MRD samples run in parallel with a reference center showed high correlation and minimal bias. 24 samples were split and processed in duplicate both fixed and fresh, with strong correlation, minimal bias, and no change in plasma cell phenotype by flow markers confirming a 6-day delay in processing did not affect assay performance. A real-world snapshot found 17% (10/58) of patients were MRD-negative post-bortezomib-based triplet induction therapy. CONCLUSIONS: We successfully adopted a reference MCF MM MRD method which was stable for up to 6 days following sample collection potentially allowing broader access of this assay to smaller laboratories which would facilitate further investigation of the prognostic value and clinical utility of MRD assessments outside the trial setting in real-world practice.

Evaluation of Disease Risk Comorbidity Index after Allogeneic Stem Cell Transplantation in a Cohort with Patients Undergoing Transplantation with In Vitro Partially T Cell Depleted Grafts.

Outcomes of hematopoietic stem cell transplantation (HSCT) are influenced by comorbidities, disease type, and status at transplantation. Several prognostic scores can be used, such as the disease risk index (DRI) or the hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Recently, a new prognostic tool, the disease risk comorbidity index (DRCI), combining the DRI and the HCT-CI, was published. The DRCI determines 6 patient groups (very low risk [VLR], low risk [LR], intermediate risk 1 [IR-1], intermediate risk 2 [IR-2], high risk [HiR], and very high risk [VHR]) with a significant predictive value for overall survival (OS), disease-free survival (DFS), relapse incidence (RI), and graft-versus-host disease-free/relapse-free survival (GRFS). However, the DRCI has not been evaluated for patients allografted with partially in vitro T cell depleted (pTDEP) grafts. In our center, we offer pTDEP to reduce graft-versus-host disease for patients in complete remission at transplant time. In this retrospective study, we investigated the DRCI in 404 adult patients (including 37.6% pTDEP) undergoing a first HSCT for hematological malignancies from 2008 to 2018. Because of the small number of patients in LR, VLR and LR were combined for analysis. In the entire cohort, 2-year OS was 84.4% (95% CI, 71.6% to 97.2%) for LR, 61.6% (54.8% to 68.4%) for IR-1, 45.7% (33.3% to 58.1%) for IR-2, 31% (19.4% to 42.6%) for HiR, and 30.9% (14.5% to 47.3%) for VHR (P < .001). In addition, the DRCI was predictive of DFS, RI, and GRFS but not of nonrelapsed mortality and graft-versus-host disease. Our study confirms similar results with the original publication but gives less accurate prognosis information than the DRI and HCT-CI when used separately. In conclusion, the DRCI does not seem to offer more relevant information than the DRI and HCT-CI to help physicians and patients for the HSCT decision.

Process Evaluation of a Medical Student-Delivered Smoking Prevention Program for Secondary Schools: Protocol for the Education Against Tobacco Cluster Randomized Trial.

BACKGROUND: Most smokers start smoking during their early adolescence under the impression that smoking entails positive attributes. Given the addictive nature of cigarettes, however, many of them might end up as long-term smokers and suffering from tobacco-related diseases. To prevent tobacco use among adolescents, the large international medical students' network Education Against Tobacco (EAT) educates more than 40,000 secondary school students per year in the classroom setting, using evidence-based self-developed apps and strategies. OBJECTIVE: This study aimed to evaluate the long-term effectiveness of the school-based EAT intervention in reducing smoking prevalence among seventh-grade students in Germany. Additionally, we aimed to improve the intervention by drawing conclusions from our process evaluation. METHODS: We conduct a cluster-randomized controlled trial with measurements at baseline and 9, 16, and 24 months postintervention via paper-and-pencil questionnaires administered by teachers. The study groups consist of randomized schools receiving the 2016 EAT curriculum and control schools with comparable baseline data (no intervention). The primary outcome is the difference of change in smoking prevalence between the intervention and control groups at the 24-month follow-up. Secondary outcomes are between-group differences of changes in smoking-related attitudes and the number of new smokers, quitters, and never-smokers. RESULTS: A total of 11,268 students of both sexes, with an average age of 12.32 years, in seventh grade of 144 secondary schools in Germany were included at baseline. The prevalence of cigarette smoking in our sample was 2.6%. The process evaluation surveys were filled out by 324 medical student volunteers, 63 medical student supervisors, 4896 students, and 141 teachers. CONCLUSIONS: The EAT cluster randomized trial is the largest school-based tobacco-prevention study in Germany conducted to date. Its results will provide important insights with regards to the effectiveness of medical student-delivered smoking prevention programs at school. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13508.

A Medical Student-Delivered Smoking Prevention Program, Education Against Tobacco, for Secondary Schools in Brazil: Study Protocol for a Randomized Trial.

BACKGROUND: Smoking is the largest preventable cause of morbidity and mortality in Brazil. Education Against Tobacco (EAT) is a large network of medical students in 13 countries who volunteer for school-based prevention in the classroom setting. A recent quasi-experimental EAT study conducted in Germany showed significant short-term smoking cessation effects on 11- to 15-year-old adolescents. OBJECTIVE: The aim of this study is both to describe and to provide the first randomized long-term evaluation of the EAT intervention involving a photoaging app for its effectiveness to reduce the smoking prevalence among 12- to 17-year-old pupils in Brazilian public schools. METHODS: A randomized controlled trial will be conducted among approximately 1500 adolescents aged 12 to 17 years in grades 7-11 of public secondary schools in Brazil. The prospective experimental study design includes measurements at baseline and at 6 and 12 months postintervention. The study groups will consist of randomized classes receiving the standardized EAT intervention (90 minutes of mentoring in a classroom setting) and control classes within the same schools (no intervention). The questionnaire measures smoking status, gender, social, and cultural aspects as well as predictors of smoking. Biochemical validation of smoking status is conducted via random carbon monoxide measurements. The primary end point is the difference of the change in smoking prevalence in the intervention group versus the difference in the control group at 12 months of follow-up. The differences in smoking behavior (smoking onset, quitting) between the 2 groups as well as effects on the different genders will be studied as secondary outcomes. RESULTS: The recruitment of schools, participating adolescents, and medical students was conducted from August 2016 until January 2017. The planned period of data collection is February 2017 until June 2018. Data analysis will follow in July 2018 and data presentation/publication will follow shortly thereafter. CONCLUSIONS: This is the first evaluative study of a medical student-delivered tobacco prevention program in Brazil and the first randomized trial on the long-term effectiveness of a school-based medical student-delivered tobacco prevention program in general. CLINICALTRIAL: ClinicalTrials.gov NCT02725021; https://clinicaltrials.gov/ct2/show/NCT02725021 (archived by WebCite at http://www.webcitation.org/6njy3nNml).