Diagnostic prénatal non-invasif des maladies génétiques par l'étude des cellules fœtales circulant dans le sang maternel (revue de la bibliographie)

PARIS-BIUP (751062107) / SudocSudocFranceF

A new approach to assessing calcium status via a machine learning algorithm.

peer reviewed("[en] BACKGROUND AND AIMS: Calcium plays a fundamental role in biological processes. Ionized calcium (Ca2+), is the biologically active fraction, but in practice total or corrected calcium assays are routinely used to determine calcium status. MATERIALS AND METHODS: We retrospectively compared total and corrected calcium to assess the calcium status, with ionized calcium which is considered for now like the best indicator. To compensate for their lack of performance we created a machine learning algorithm to predict calcium status. RESULTS: Corrected calcium performed less well than total calcium with 58% and 74% agreement, respectively, in our population. Total calcium was especially good for hypocalcemic samples: 93% agreement versus 45% for normocalcemic and 54% for hypercalcemic samples. Corrected calcium was especially good for hypercalcemic and normocalcemic samples: 90% and 84% agreement respectively versus 40% for hypocalcemic samples. Corrected calcium is mainly faulty in hypoalbuminemia, acid-base disorders, renal insufficiency, hyperphosphatemia, or inflammatory syndrome. With our ML algorithm, we obtained 81% correct classifications. Its main advantage is that its performance are not influenced by the variables studied or the calcium status. CONCLUSION: In many situations, corrected calcium should not be used. Our ML algorithm may make a better assessment of calcium status than total calcium. Finally, if doubt, an ionized calcium assay should be performed.","[en] ",""

Heterogeneity of Cause, Care, and Prognosis in Severe Acute Kidney Injury in Hospitalized Patients: A Prospective Observational Study

International audienceKDIGO (Kidney Disease: Improving Global Outcomes) defines acute kidney injury (AKI) solely by serum creatinine (SCr) and urine output variation. Severe AKI is a syndrome covering various clinical situations.Objective:To describe severe AKI heterogeneity by department of hospitalization.Design:This is a prospective observational single-center study.Setting:Adult patients hospitalized in a French tertiary hospital from August 2016 to December 2017.Patients:All adults with severe AKI, defined by dialysis for AKI or an increase in SCr above 354 μmol/L.Measurements:Patient characteristics, clinical and laboratory presentation, AKI cause, medical indication for renal replacement therapy (RRT), planned palliative care, and vital status 30 days after severe AKI.Methods:A global description of patient characteristics, care, and prognosis and comparison by department of hospitalization: intensive care unit (ICU), nephrology, and others.Results:The study included 480 patients (73% men, median age: 72 years, range: 64-83), with medical histories including cardiovascular disease, diabetes, cancer, and chronic kidney disease. Principal causes were sepsis (104; 22%), hypovolemia (98; 20%), obstructive AKI (84; 18%), acute tubular necrosis (ATN; 74; 15%), and cardiorenal syndrome (51; 11%). Severe AKI was diagnosed in the ICU for 188 (39%) patients, the nephrology department for 130 (27%), and in other wards for 162 (34%). Patient characteristics differed by department for age, comorbidity, cause, and RRT use and indications. Palliative care was planned for 72 (15%) patients, most frequently in other wards.Limitations:We studied a subgroup of stage 3 KDIGO AKI patients in a single center without cardiac surgery.Conclusion:Patients hospitalized for severe AKI have frequent and various comorbidities, different clinical presentations, care, hospitalization in various departments, and different prognosis. The heterogeneity of this severe AKI implies the need for personalized care, which requires prognostic tools that include information besides SCr and diuresis.Le KDIGO définit l’insuffisance rénale aigüe (IRA) uniquement par une variation de la créatinine sérique (SCr) et de la diurèse. L’IRA grave est un syndrome couvrant diverses situations cliniques.Objectif:Décrire l’hétérogénéité de l’IRA grave selon l’unité d’hospitalisation.Type d’étude:Étude observationnelle prospective menée dans un seul centre.Sujets:Des adultes hospitalisés entre août 2016 et décembre 2017 dans un centre de soins tertiaires en France.Participants:Tous les adultes atteints d’IRA grave, définie par un traitement de dialyse ou un taux de SCr au-delà de 354 µmol/l.Mesures:Les caractéristiques du patient, le tableau clinique et de laboratoire, l’étiologie de l’IRA, l’indication médicale pour une thérapie de remplacement rénal (TRR), le plan de soins palliatifs et le statut vital 30 jours après l’épisode d’IRA grave.Méthodologie:Une description globale des caractéristiques des patients, des soins et du pronostic, ainsi qu’une comparaison selon l’unité d’hospitalisation: unité de soins intensifs (USI), néphrologie et autres.Résultats:L’étude portait sur 480 patients (73 % d’hommes) âgés de 64 à 83 ans (âge médian: 72 ans) avec des antécédents incluant maladies cardiovasculaires, diabète, cancer ou insuffisance rénale chronique. Les principales causes de l’IRA grave étaient une septicémie (104, 22 %), une hypovolémie (98, 20 %), une IRA obstructive (84, 18 %), une nécrose tubulaire aigüe (74, 15 %) ou un syndrome cardio-rénal (51, 11 %). Le diagnostic avait été posé à l’USI pour 188 patients (39 %), en néphrologie pour 130 patients (27 %) et dans d’autres unités pour 162 patients (34 %). Les caractéristiques des patients différaient entre les unités de soins en ce qui concerne l’âge, les comorbidités, l’étiologie et les indications de TRR. Un plan de soins palliatifs existait pour 72 patients (15 %), le plus souvent dans les autres unités.Limites:Nous avons étudié un sous-groupe de patients atteints d’IRA de stade 3 (classification KDIGO) dans un seul centre sans chirurgie cardiaque.Conclusion:Les patients hospitalisés pour une IRA grave présentent des comorbidités, des tableaux cliniques, des soins et des pronostics variés et sont admis dans différentes unités d’hospitalisation. Cette hétérogénéité de l’IRA grave met en relief le besoin de soins personnalisés qui nécessitent des outils pronostics basés sur des informations autres que la SCr et la diurèse

Parathyroid Hormone Assays following Total Thyroidectomy: Is There a Predictive Value?

International audienceObjectives:Parathyroid hormone (PTH) is a risk marker for hypoparathyroidism (hypoPTH). This study aimed to determine the predictive values of early PTH assays carried out at the moment of skin closure (PTH SC), to establish a treatment algorithm, identifying two threshold values. We assessed the reproducibility of this approach with two different immunoassay kits (hypoPTH) after total thyroidectomy, but its practical application is not consensual.Study Design:We conducted a prospective descriptive study, including all patients who underwent a total thyroidectomy between March 2012 and November 2013. Postoperative PTH SC levels, corrected calcium on postoperative days, and occurrence of hypoPTH symptoms were collected.Results:Of 257 patients, the rate of hypoPTH was 20%. Threshold values to obtain a 100% positive predictive value to identify patients for whom hypoPTH was absolutely certain were: PTH SC <7 ng/L for the Roche kit and PTH SC <4 ng/L for the Beckman-Coulter kit. Threshold values to obtain a 100% negative predictive value to identify patients for whom the absence of hypoPTH was absolutely certain were: PTH SC ≥19 ng/L for the Roche kit and PTH SC ≥9 ng/L the Beckman-Coulter kit.Conclusions:A single serum PTH sampled at skin closure is a reliable test to predict hypoPTH after a total thyroidectomy. The use of a threshold based on a 100% negative predictive value enables patients with no risk of hypoPTH to be safely discharged within the first 24 h postoperatively without unnecessary calcium and vitamin treatment. This medication can be given promptly to patients at risk of hypoPTH to limit the occurrence of hypocalcaemia

La concentration d'hormone anti-müllérienne régule les niveaux d'expression de l'activin receptor-like kinase-2/3 avec des effets opposés sur la survie des cellules cancéreuses ovariennes

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A Novel Heterozygous Deletion Variant in <i>KLOTHO</i> Gene Leading to Haploinsufficiency and Impairment of Fibroblast Growth Factor 23 Signaling Pathway

Hyperphosphatemia is commonly present in end-stage renal disease. Klotho (KL) is implicated in phosphate homeostasis since it acts as obligate co-receptor for the fibroblast growth factor 23 (FGF23), a major phosphaturic hormone. We hypothesized that genetic variation in the KL gene might be associated with alterations in phosphate homeostasis resulting in hyperphosphatemia. We performed sequencing for determining KL gene variants in a group of resistant hyperphosphatemic dialysis patients. In a 67-year-old female, blood DNA sequencing revealed a heterozygous deletion of a T at position 1041 (c.1041delT) in exon 2. This variation caused a frameshift with substitution of isoleucine for phenylalanine and introduction of a premature termination codon (p.Ile348Phefs*28). cDNA sequencing showed absence of deletion-carrier transcripts in peripheral blood mononuclear cells suggesting degradation of these through a nonsense-mediated RNA decay pathway. Experiments in vitro showed that p.Ile348Phefs*28 variant impaired FGF23 signaling pathway, indicating a functional inactivation of the gene. In the patient, serum levels of KL were 2.9-fold lower than the mean level of a group of matched dialysis subjects, suggesting a compromise in the circulating protein concentration due to haploinsufficiency. These findings provide a new loss-of-function variant in the human KL gene, suggesting that genetic determinants might be associated to clinical resistant hyperphosphatemia