Reduced parathyroid functional mass after successful kidney transplantation

Reduced parathyroid functional mass after successful kidney transplantation.BackgroundChronic uremia is responsible for secondary hyperparathyroidism (HPT II). Parathyroid secretion usually tends to normalize after kidney transplantation (KT), but the parameters of the reversibility of HPT II remain poorly defined, particularly the intrinsic mechanisms underlying the improvement of parathyroid function.MethodsThe kinetic functional parameters of the ionized calcium (iCa)/parathormone (PTH) relationship curve were studied in 11 patients with mild to moderate HPT II one and six months after successful KT. Hypercalcemia and hypocalcemia were induced, respectively, by CaCl2 and Na2-ethylenediaminetetraacetic acid (Na2-EDTA) infusions.ResultsThe mean glomerular filtration rate remained stable during follow-up. Basal PTH decreased from 195 ± 54 pg/ml before KT to 70 ± 12 pg/ml six months later (P < 0.005). During the tests, mean PTH levels decreased significantly between the two measured times for all iCa levels, indicating an improved parathyroid function. An analysis of the kinetic parameters of the curves showed significant decreases of the mean maximal and minimal PTH levels, respectively, from 340 ± 91 to 220 ± 30 pg/ml (P = 0.03) and from 25 ± 6 to 15 ± 5 pg/ml (P = 0.005). On the other hand, no change was noted in the parathyroid-cell calcium-sensitivity parameters (slope, set point) assessed using two different approaches, either the entire curve or the limited calcium-mediated suppression curve.ConclusionImprovement of the parathyroid function between the first and sixth months post-KT seems mainly attributable to a reduction of the parathyroid functional mass

L’Asie du Sud-Est 2023 : bilan, enjeux et perspectives

Chaque année, l’Institut de recherche sur l’Asie du Sud-Est contemporaine (IRASEC), basé à Bangkok, mobilise une vingtaine de chercheurs et d’experts pour mieux comprendre l’actualité régionale de ce carrefour économique, culturel et religieux, au cœur de l’Indo-Pacifique. Cette collection permet de suivre au fil des ans l’évolution des grands enjeux contemporains de cette région continentale et archipélagique de plus de 680 millions d’habitants, et d’en comprendre les dynamiques d’intégration régionale et de connectivités avec le reste du monde. L’Asie du Sud-Est 2023 propose une analyse synthétique et détaillée des principaux événements politiques et diplomatiques, ainsi que des évolutions économiques, sociales et environnementales de l’année 2022 dans chacun des onze pays de la région. Ce décryptage est complété pour chaque pays par un focus sur deux personnalités de l’année et une actualité marquante en image. L’ouvrage propose également cinq dossiers thématiques qui abordent des sujets traités à l’échelle régionale sud-est asiatique : les ressorts institutionnels de l’approche de santé intégrée One Health, le vieillissement de la population et sa prise en compte par les politiques publiques, les câbles sous-marins au cœur de la connectivité sud-est asiatique, l’aménagement du bassin du Mékong et ses multiples acteurs, et les enjeux politiques et linguistiques des langues transnationales. Des outils pratiques sont également disponibles : une fiche et une chronologie par pays et un cahier des principaux indicateurs démographiques, sociaux, économiques et environnementaux

Weak Spatial and Temporal Population Genetic Structure in the Rosy Apple Aphid, Dysaphis plantaginea, in French Apple Orchards

We used eight microsatellite loci and a set of 20 aphid samples to investigate the spatial and temporal genetic structure of rosy apple aphid populations from 13 apple orchards situated in four different regions in France. Genetic variability was very similar between orchard populations and between winged populations collected before sexual reproduction in the fall and populations collected from colonies in the spring. A very small proportion of individuals (∼2%) had identical multilocus genotypes. Genetic differentiation between orchards was low (FST<0.026), with significant differentiation observed only between orchards from different regions, but no isolation by distance was detected. These results are consistent with high levels of genetic mixing in holocyclic Dysaphis plantaginae populations (host alternation through migration and sexual reproduction). These findings concerning the adaptation of the rosy apple aphid have potential consequences for pest management

PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratificatio

BMJ Med

OBJECTIVE: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial). DESIGN: Open label, randomised clinical trial. SETTING: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021. PARTICIPANTS: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms 40. MAIN OUTCOME MEASURES: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids. RESULTS: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10). CONCLUSIONS: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further. TRIAL REGISTRATION: ClinicalTrials.gov NCT04345991

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology