Is severe hypocalcemia immediately life threatening?

Objective: Severe hypocalcemia (Ca <1.9 mmol/L) is often considered an emergency because of a potential risk of cardiac arrest or seizures. However, there is little evidence to support this. The aim of our study was to assess whether severe hypocalcemia was associated with immediately life-threatening cardiac arrhythmias or neurological complications. Methods: A retrospective observational study was carried out over a 2-year period in the Adult Emergency Department (ED) of Nantes University Hospital. All patients who had a protein-corrected calcium concentration measure were eligible for inclusion. Patients with multiple myeloma were excluded. The primary outcome was the number of life-threatening cardiac arrhythmias and/or neurological complications during the stay in the ED. Results: A total of 41,823 patients had protein-corrected calcium (pcCa) concentrations measured, 155 had severe hypocalcemia, 22 were excluded because of myeloma leaving 133 for analysis. Median pcCa concentration was 1.73 mmol/L (1.57–1.84). Seventeen (12.8%) patients presented a life-threatening condition, 14 (10.5%) neurological and 3 (2.2%) cardiac during ED stay. However, these complications could be explained by the presence of underlying co-morbidities and or electrolyte disturbances other than hypocalcemia. Overall, 24 (18%) patients died in hospital. Vitamin D deficiency, chronic kidney disease and hypoparathyroidism were the most frequently found causes of hypocalcemia. Conclusion: Thirteen percent of patients with severe hypocalcemia presented a life-threatening cardiac or neurological complication on the ED. However, a perfectly valid alternative cause could account for these complications. Further research is warranted to define the precise role of hypocalcemia

Diagnostic biologique des hyperplasies congénitales des surrénales au CHU de Nantes (analyse rétrospective sur 8 années)

L'hyperplasie congénitale des surrénales (HCS) fait l'objet d'un dépistage néonatal systématique et le dosage sérique de 17a-hydroxyprogestérone (170HP) par méthode radio-immunologique permet de confirmer le diagnostic rapidement. L'existence de concentrations augmentées de ce paramètre, malgré une extraction préalable au dosage (élimination de la réactivité croisée liée à la 17a-hydroxyprégnènolone), pose le problème de l'exclusion diagnostique. Au cours d'un travail rétrospectif sur 8 ans, nous avons étudié les dossiers des enfants ayant eu une 170HP > 2 ng/mL : 16 présentaient une HCS, alors que 42 en étaient exempts. Parmi ces derniers, nous avons donc recherché les étiologies possibles de ces concentrations augmentées. Ni une corticothérapie anténatale, ni la présence d'une HTA maternelle, ni la présence d'un sepsis, d'une détresse respiratoire ou d'une hyperbilirubinémie ne sont liées à une 170HP élevée. En revanche le terme de naissance est corrélé de façon négative et significative aux concentrations de 170HP. Cette corrélation peut être expliquée soit par une élimination insuffisante de 1 a 17a-hydroxyprégnènolone lors de l'extraction, soit par une 170HP réellement augmentée liée à la prématurité. Pour optimiser la performance diagnostique de ce dosage, il serait intéressant de définir des valeurs normales obtenues après extraction de la 170HP chez l'enfant en fonction du terme.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Dépistage néonatal des maladies métaboliques (projet d'extension et bilan de la prise en charge de la phénylcétonurie au CHU de Nantes)

La phénylcétonurie, est une maladie métabolique grave, engendrant des retards mentaux sévères et irréversibles si elle n'est pas prise en charge précocement. Elle fait partie des cinq maladies qui sont dépistées en France à ce jour. Depuis la fin des années 1990, l'application de la spectrométrie de masse au dépistage néonatal permet de dépister plus d une trentaine d erreurs innées du métabolisme. En France, cette technique n'est pas utilisée. Des groupes de travail se sont néanmoins constitués et ont permis d'aboutir à l élaboration d un PNDS. Deux maladies ont ainsi été retenues pour la mise en place du projet : le déficit en acyl-CoA déshydrogénase des acides gras à chaîne moyenne et la phénylcétonurie. Ce travail décrit la situation actuelle du dépistage néonatal en Europe, aux Etats-Unis et en Australie et les perspectives à venir en termes d'extension dans notre pays ainsi que les caractéristiques de la phénylcétonurie. Un travail rétrospectif sur 10 années a été mené. Durant cette période 322 226 nouveau-nés ont été dépistés au CHU de Nantes, parmi eux 36 étaient atteints de phénylcétonurie. L étude des dossiers de ces patients a permis de confirmer les données de la littérature et de mettre en évidence l intérêt d un régime strict jusqu à l âge de 10 ans et d un suivi médical à vie, Sur le même modèle que celui de la phénylcétonurie, il apparaît donc primordial d'étendre (comme le préconise le PNDS) le dépistage néonatal à d'autres maladies tel le déficit en acyl-CoA déshydrogénase des acides gras à chaîne moyenne, pour lequel une prise en charge précoce apporte un réel bénéfice au patient.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Rôle de l'apolipoprotéine E dans le métabolisme des lipoprotéines riches en triglycérides, relations avec l'inflammation

L'apolipoprotéine E est présente à jeun au sein des VLDL et des KDL et joue un rôle majeur dans la clairance hépatique des lipoprotéines riches en triglycérides.... Les obèses et les diabétiques présentent souvent une hypertriglycéridémie modérée et un léger état inflammatoire chronique. C'est pourquoi, nous avons étudié chez ces sujets, (1) le rôle de l'apo E dans le métabolisme des lipoprotéines riches en triglycérides et, (2) ses relations in vivo avec l'inflammation. Nos résultats montrent que la concentration plasmatique et la production de l'apo E des VLDL sont augmentées chez les diabétiques et suggèrent que, chez ces derniers, l'apo E pourrait lutter contre la surproduction hépatique de ces lipoprotéines en accélérant leur clairance hépatique directe par l'intermédiaire de ses récepteurs spécifiques....L'apo E pourrait ainsi moduler les conséquences délétères de l'inflammation sur le développement des lésions athéroscléreuses.Apolipoprotein E is present in VLDL and HDL and plays a crucial role in hepatic clearance of triglyceride rich lipoproteins. It has also been found in some Lp(a) subspecies, VLDL-like, mostly described during fed state. Neither the role of apo E in lipoprotein metabolism during moderate hypertriglyceridemia, nor its role in Lp(a) are known. Although some effects of apo E against inflammation have been described in vitro, they have not been shown in vivo. Obese and diabetics currently present systemic inflammation and moderate hypertriglyceridemia. That is the reason why we have chosen to study in these subjects: (1) the role of apo E in triglyceride rich lipoprotein metabolism and (2) its relations in vivo with inflammation....Thus, apo E could modulate deleterious effects of inflammation on atheroscierotic injuries.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Diagnostic performance of serum blood urea nitrogen to creatinine ratio for distinguishing prerenal from intrinsic acute kidney injury in the emergency department

Abstract Background The blood urea nitrogen to creatinine ratio (BCR) has been used since the early 1940s to help clinicians differentiate between prerenal acute kidney injury (PR AKI) and intrinsic AKI (I AKI). This ratio is simple to use and often put forward as a reliable diagnostic tool even though little scientific evidence supports this. The aim of this study was to determine whether BCR is a reliable tool for distinguishing PR AKI from I AKI. Methods We conducted a retrospective observational study over a 13 months period, in the Emergency Department (ED) of Nantes University Hospital. Eligible for inclusion were all adult patients consecutively admitted to the ED with a creatinine >133 μmol/L (1.5 mg/dL). Results Sixty thousand one hundred sixty patients were consecutively admitted to the ED. 2756 patients had plasma creatinine levels in excess of 133 μmol/L, 1653 were excluded, leaving 1103 patients for definitive inclusion. Mean age was 75.7 ± 14.8 years old, 498 (45%) patients had PR AKI and 605 (55%) I AKI. BCR was 90.55 ± 39.32 and 91.29 ± 39.79 in PR AKI and I AKI groups respectively. There was no statistical difference between mean BCR of the PR AKI and I AKI groups, p = 0.758. The area under the ROC curve was 0.5 indicating that BCR had no capacity to discriminate between PR AKI and I AKI. Conclusions Our study is the largest to investigate the diagnostic performance of BCR. BCR is not a reliable parameter for distinguishing prerenal AKI from intrinsic AKI

Crosstalk between omega-6 oxylipins and the enteric nervous system: Implications for gut disorders?

The enteric nervous system (ENS) continues to dazzle scientists with its ability to integrate signals, from the outside as well as from the host, to accurately regulate digestive functions. Composed of neurons and enteric glial cells, the ENS interplays with numerous neighboring cells through the reception and/or the production of several types of mediators. In particular, ENS can produce and release n-6 oxylipins. These lipid mediators, derived from arachidonic acid, play a major role in inflammatory and allergic processes, but can also regulate immune and nervous system functions. As such, the study of these n-6 oxylipins on the digestive functions, their cross talk with the ENS and their implication in pathophysiological processes is in full expansion and will be discussed in this review

Prostaglandine D2 et homéostasie de la barrière épithéliale intestinale

La prostaglandine D2 (PGD2) et ses dérivés sont des médiateurs lipidiques participant à l’homéostasie de la barrière épithéliale intestinale. Leur implication dans la physiopathologie des maladies inflammatoires chroniques de l’intestin reste encore débattue. Plusieurs résultats soulignent la dualité de la PGD2 quant à son rôle anti- ou pro-inflammatoire. Cette dualité semble liée à une expression différentielle de ses récepteurs par les cellules épithéliales intestinales et par les cellules immunocompétentes environnantes. Les cellules gliales du système nerveux entérique sont capables de sécréter ces médiateurs. Le rôle protecteur du système nerveux entérique dans le contrôle de l’homéostasie de la barrière épithéliale intestinale a été démontré. Ainsi, la PGD2 et ses dérivés se révèlent être de nouveaux acteurs de l’unité neuro-glio-épithéliale impliqués dans la régulation des fonctions des cellules épithéliales intestinales

Neutrophil gelatinase-associated lipocalin, a marker of tubular dysfunction, is not increased in long-term virologically controlled patients receiving a tenofovir/emtricitabine + nevirapine regimen

International audienceOBJECTIVES: Tenofovir may be associated with nephrotoxicity. Several studies have shown that an early increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) may predict the occurrence of acute kidney injury. We investigated urine and plasma NGAL in patients on long-term treatment with nevirapine associated with either tenofovir/emtricitabine or abacavir/lamivudine.PATIENTS AND METHODS: We studied 40 virologically controlled Caucasian patients on stable treatment (median >4 years) with tenofovir/emtricitabine + nevirapine (n = 20) or abacavir/lamivudine + nevirapine (n = 20), and no history of kidney disease, high blood pressure or diabetes. Plasma immunovirological parameters (NGAL and C-reactive protein) and urinary NGAL, β2-microglobulin and α1-microglobulin were measured during a routine clinical visit.RESULTS: Median concentrations of NGAL were in the normal range, but were significantly higher in the abacavir/lamivudine group compared with the tenofovir/emtricitabine group both in the plasma, at 74.9 and 66.0 ng/mL (P = 0.032), respectively, and in the urine, at 36.1 and 12.8 ng/mL (P = 0.017), respectively.CONCLUSIONS: Plasma and urinary NGAL concentrations remained in the normal range in this long-term virologically controlld population without any overt renal disease. The usefulness of NGAL in detecting sub-clinical renal dysfunction appears to be very limited

Cortisol total/CRP ratio for the prediction of hospital-acquired pneumonia and initiation of corticosteroid therapy in traumatic brain- injured patients

International audienceBACKGROUND:To propose a combination of blood biomarkers for the prediction of hospital-acquired pneumonia (HAP) and for the selection of traumatic brain-injured (TBI) patients eligible for corticosteroid therapy for the prevention of HAP.METHODS:This was a sub-study of the CORTI-TC trial, a multicenter, randomized, double-blind, controlled trial evaluating the risk of HAP at day 28 in 336 TBI patients treated or not with corticosteroid therapy. Patients were between 15 and 65 years with severe traumatic brain injury (Glasgow coma scale score ≤ 8 and trauma-associated lesion on brain CT scan) and were enrolled within 24 h of trauma. The blood levels of CRP and cortisoltotal&free, as a surrogate marker of the pro/anti-inflammatory response balance, were measured in samples collected before the treatment initiation. Endpoint was HAP on day 28.RESULTS:Of the 179 patients with available samples, 89 (49.7%) developed an HAP. Cortisoltotal&free and CRP blood levels upon ICU admission were not significantly different between patients with or without HAP. The cortisoltotal/CRP ratio upon admission was 2.30 [1.25-3.91] in patients without HAP and 3.36 [1.74-5.09] in patients with HAP (p = 0.021). In multivariate analysis, a cortisoltotal/CRP ratio > 3, selected upon the best Youden index on the ROC curve, was independently associated with HAP (OR 2.50, CI95% [1.34-4.64] p = 0.004). The HR for HAP with corticosteroid treatment was 0.59 (CI95% [0.34-1.00], p = 0.005) in patients with a cortisoltotal/CRP ratio > 3, and 0.89 (CI95% [0.49-1.64], p = 0.85) in patients with a ratio  3 upon admission may predict the development of HAP in severe TBI. Among these patients, corticosteroids reduce the occurrence HAP. We suggest that this ratio may select the patients who may benefit from corticosteroid therapy for the prevention of HAP

Activation of the prostaglandin D2 metabolic pathway in Crohn’s disease: involvement of the enteric nervous system

Background: Recent works provide evidence of the importance of the prostaglandin D2 (PGD2) metabolic pathway in inflammatory bowel diseases. We investigated the expression of PGD2 metabolic pathway actors in Crohn's disease (CD) and the ability of the enteric nervous system (ENS) to produce PGD2 in inflammatory conditions.Methods: Expression of key actors involved in the PGD2 metabolic pathway and its receptors was analyzed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in colonic mucosal biopsies of patients from three groups: controls, quiescent and active CD patients. To determine the ability of the ENS to secrete PGD2 in proinflammatory conditions, Lipocalin-type prostaglandin D synthase (L-PGDS) expression by neurons and glial cells was analyzed by immunostaining. PGD2 levels were determined in a medium of primary culture of ENS and neuro-glial coculture model treated by lipopolysaccharide (LPS).Results: In patients with active CD, inflamed colonic mucosa showed significantly higher COX2 and L-PGDS mRNA expression, and significantly higher PGD2 levels than healthy colonic mucosa. On the contrary, peroxysome proliferator-activated receptor Gamma (PPARG) expression was reduced in inflamed colonic mucosa of CD patients with active disease. Immunostaining showed that L-PGDS was expressed in the neurons of human myenteric and submucosal plexi. A rat ENS primary culture model confirmed this expression. PGD2 levels were significantly increased on primary culture of ENS treated with LPS. This production was abolished by AT-56, a specific competitive L-PGDS inhibitor. The neuro-glial coculture model revealed that each component of the ENS, ECG and neurons, could contribute to PGD2 production.Conclusions: Our results highlight the activation of the PGD2 metabolic pathway in Crohn's disease. This study supports the hypothesis that in Crohn's disease, enteric neurons and glial cells form a functional unit reacting to inflammation by producing PGD2