Publications by authors named "Steven Grange"

32 Publications

[ESUR recommendations on the use of contrast media: Practice survey, review and commentary by CJN, FIRN and SFNDT].

Nephrol Ther 2021 Feb 4. Epub 2021 Feb 4.

Commission Néphrologie Clinique de la SFNDT, 24, Montée des Roches, Saint-Sorlin, 69440 Chabanière, France; Service de néphrologie, hémodialyse, transplantation rénale, lithiase rénale, hypertension artérielle, unité de surveillance continue, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France.

Contrast media administration is classically considered to cause or worsen kidney failure. Recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. The present work evaluates the practice of French nephrologists, and provides a commentary on these recommendations based on an updated review of the literature. We conducted survey among French nephrologists, using an electronic questionnaire distributed by the Société Francophone de Néphrologie, Dialyse et Transplantation, the French Intensive care Renal Network and the Club des Jeunes Néphrologues. 266 responses were collected. The European Society of Urogenital Radiology guidelines are poorly known among the panel of nephrologists. Their practices differ from the guidelines by the more frequent and earlier implementation of measures to prevent renal failure post contrast media. In accordance with the guidelines, hydration is prescribed as a first-line preventive measure, mainly with saline and bicarbonate. Inhibitors of the renin-angiotensin-aldosterone system are frequently discontinued before an injection of contrast media, contrary to what is recommended. In conclusion, the European Society of Urogenital Radiology guidelines, which the working group endorses, but which are still too little known and applied in clinical nephrology in France, prompt nephrologists to lift some of the restrictions on the use of PCI as well as on the continuation of ARS inhibitors before injecting PCI.
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http://dx.doi.org/10.1016/j.nephro.2020.10.011DOI Listing
February 2021

Kidney and contrast media: Common viewpoint of the French Nephrology societies (SFNDT, FIRN, CJN) and the French Radiological Society (SFR) following ESUR guidelines.

Diagn Interv Imaging 2021 Mar 30;102(3):131-139. Epub 2021 Jan 30.

Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000 Rouen, France.

Contrast medium administration is classically considered to cause or worsen kidney failure, but recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. Kidney injury does not constitute a contra-indication to the administration of iodinated contrast medium, as long as the benefit-risk ratio justifies it. Intravenous hydration with 0.9% NaCl or 1.4% sodium bicarbonate is the only validated measure for the prevention of post-iodine contrast nephropathy. This is necessary for intravenous or intra-arterial administration of iodinated contrast agent without first renal pass when the glomerular filtration rate is less than 30mL/min/1.73m, for intra-arterial administration of iodinated contrast agent with first renal passage when the glomerular filtration rate is less than 45mL/min/1.73m, or in patients with acute renal failure. The use of iodinated contrast medium should allow the carrying out of relevant examinations based on an analysis of the benefit-risk ratio and the implementation of measures to prevent toxicity when necessary.
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http://dx.doi.org/10.1016/j.diii.2021.01.007DOI Listing
March 2021

The prognostic value of the neutrophil-to-lymphocyte ratio in critically ill cirrhotic patients.

Eur J Gastroenterol Hepatol 2021 Jan 18. Epub 2021 Jan 18.

Department of Anesthesiology and Critical Care, APHP, Beaujon Hospital, Clichy Medical Intensive Care Unit, Rouen University Hospital, Rouen UMR_S 1149 Centre for research on Inflammation - Inserm/Université de Paris, Paris Anesthesiology and Intensive Care, Anesthesia and Critical Care Department B, Saint Eloi Teaching Hospital, PhyMedExp, University of Montpellier, INSERM U1046, CNRS, UMR 9214, Montpellier Département Hospitalo-Universitaire UNITY, Service d'Hépatologie, APHP, Hôpital Beaujon, Clichy Medical Intensive Care Unit, University Hospital of Besancon, Besançon Normandie University, UNIROUEN, INSERM U1096 EnVI, Rouen, France.

Background: Hospital death rates following ICU admission of cirrhotic patients remain high. Identifying patients at high risk of mortality after few days of aggressive management is imperative for providing adequate interventions. Herein, we aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) combined with usual organ failure scores in the outcome prediction of cirrhotic patients hospitalized more than 3 days in ICU.

Methods: We conducted a retrospective bicentric study in two cohorts of cirrhotic patients hospitalized more than 3 days in French university hospital ICUs. At admission and day 3, we calculated several clinico-biological scores grading liver disease and organ failure severity and calculated the NLR. The primary outcome was 28-day mortality.

Results: The test cohort included 116 patients. At day 28, 43 (37.1%) patients had died. Variations of MELD score (ΔMELD), SOFA score (ΔSOFA), CLIF-SOFA score (ΔCLIF-SOFA) and NLR (ΔNRL) between admission and day 3 were significantly associated with 28-day mortality in univariate analysis. When included in bivariate analysis ΔNLR remained a significant predictor of 28-day mortality independently of these severity scores. Kaplan-Meier curves and statistics using reclassification methods showed a better 28-day mortality risk prediction using ΔNRL in association with ΔSOFA in comparison to ΔSOFA alone. These results were confirmed in an external validation cohort, including 101 critically ill cirrhotic patients.

Conclusions: ΔNLR is an independent predictor of mortality in the critically ill cirrhotic patients' population who requires intensive care supportive treatment and should be used in association with ΔSOFA as a prognostic biomarker.
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http://dx.doi.org/10.1097/MEG.0000000000002063DOI Listing
January 2021

SARS-CoV-2 Versus Influenza-associated Acute Respiratory Distress Syndrome Requiring Veno-venous Extracorporeal Membrane Oxygenation Support.

ASAIO J 2021 02;67(2):125-131

From the Medical Intensive Care Unit, CHU Lille, Lille, France.

No study has compared patients with COVID-19-related refractory ARDS requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO) to a relevant and homogenous control population. We aimed to compare the outcomes, the clinical characteristics, and the adverse effects of COVID-19 patients to a retrospective cohort of influenza patients. This retrospective case-control study was conducted in the ICUs of Lille and Rouen University Hospitals between January 2014 and May 2020. Two independent cohorts of patients with ARDS requiring V-V ECMO infected with either COVID-19 (n = 30) or influenza (n = 22) were compared. A 3-month follow-up was completed for all patients. Median age of COVID-19 and influenza patients was similar (57 vs. 55 years; p = 0.62). The 28-day mortality rate did not significantly differ between COVID-19 (43.3%) and influenza patients (50%, p = 0.63). There was no significant difference considering the cumulative incidence of ECMO weaning, hospital discharge, and 3-month survival. COVID-19 patients had a lower SAPS II score (58 [37-64] vs. 68 [52-83]; p = 0.039), a higher body mass index (33 [29-38] vs. 30 [26-34] kg/m2; p = 0.05), and were cannulated later (median delay between mechanical support and V-V ECMO 6 vs. 3 days, p = 0.004) compared with influenza patients. No difference in overall adverse events was observed between COVID-19 and influenza patients (70% vs. 95.5% respectively; p = 0.23). Despite differences in clinical presentation before V-V ECMO implantation, 28-day and 3-month mortality rate did not differ between COVID-19 and influenza patients. Considering the lack of specific treatment for COVID-19, V-V ECMO should be considered as a relevant rescue organ support.
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http://dx.doi.org/10.1097/MAT.0000000000001325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846248PMC
February 2021

Correction to: Adrenocortical carcinoma complicated by renal thrombotic microangiopathy, a case-series.

BMC Nephrol 2020 Feb 10;21(1):44. Epub 2020 Feb 10.

Department of Medical Critical Care, Rouen University Hospital, Rouen, France.

Following publication of the original article [1], we have been notified that the name of one author was spelled incorrectly as Julien Haddoux, when the correct spelling is Julien Hadoux.
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http://dx.doi.org/10.1186/s12882-020-1712-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008570PMC
February 2020

Adrenocortical carcinoma complicated by renal thrombotic microangiopathy, a case-series.

BMC Nephrol 2020 01 30;21(1):35. Epub 2020 Jan 30.

Department of Medical Critical Care, Rouen University Hospital, Rouen, France.

Background: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare entity associated with a dismal prognosis. Usually, CR-TMA is associated with mucin-producing carcinomas among which stomach, breast, prostate, lung and pancreas tumours are the most frequent.

Cases Presentation: We describe for the first time three cases of CR-TMA due to adrenocortical carcinoma (ACC). All of them had mechanical hemolytic anemia and thrombocytopenia without any other identifiable cause. Bicytopenia was diagnosed either simultaneously with ACC or at the time of metastatic evolution. Two patients had acute kidney injury (AKI) with severe pathological findings on kidney biopsy. Despite total adrenalectomy, chemotherapy, and specific treatment of TMA with plasma-exchanges, renal failure and hemolytic anemia remained. The only manifestation of CR-TMA in the third patient was hemolytic anemia, which resolved after surgical removal of ACC. The evolutions in these patients suggests ACC-related TMA may be related to a circulating factor.

Conclusions: CR-TMAs are rare. Here we describe the first case series of ACC-related TMA, among which two had renal involvement. This entity is associated with dismal renal prognosis despite specific treatment of TMA. According to patients' evolution, the persistence of TMA may reflect an uncontrolled malignancy.
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http://dx.doi.org/10.1186/s12882-020-1703-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993319PMC
January 2020

The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial.

Trials 2019 Dec 16;20(1):726. Epub 2019 Dec 16.

French National Institute of Health and Medical Research (INSERM), UMR_S1155, Remodeling and Repair of Renal Tissue, Hôpital Tenon, Sorbonne Université, F-75020, Paris, France.

Background: The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed "standard") with another in which RRT is further delayed for a longer period (termed "delayed strategy").

Methods/design: This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects.

Discussion: The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019.

Trial Registration: ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.
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http://dx.doi.org/10.1186/s13063-019-3774-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915917PMC
December 2019

In-Hospital Mortality-Associated Factors in Patients With Thrombotic Antiphospholipid Syndrome Requiring ICU Admission.

Chest 2020 May 26;157(5):1158-1166. Epub 2019 Nov 26.

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital La Pitié-Salpêtrière, Institut E3M, Service de Médecine Interne 2, Centre de Référence National Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Autres Maladies Auto-Immunes Systémiques Rares, Paris, France.

Background: The antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic events that can require ICU admission because of organ dysfunction related to macrovascular and/or microvascular thrombosis. Critically ill patients with thrombosis and APS were studied to gain insight into their prognoses and in-hospital mortality-associated factors.

Methods: This French national, multicenter, retrospective study included all patients with APS and any new thrombotic manifestations admitted to 24 ICUs (January 2000-September 2018).

Results: During the study period, 134 patients (male/female ratio, 0.4) with 152 APS episodes were admitted to the ICU (mean age at admission, 46.0 ± 15.1 years). In-hospital mortality of their 134 last episodes was 35 of 134 (26.1%). The Cox multivariable model retained certain factors (hazard ratio [95% CI]: age ≥ 40 years, 11.4 [3.1-41.5], P < .0001; mechanical ventilation, 11.0 [3.3-37], P < .0001; renal replacement therapy, 2.9 [1.3-6.3], P = .007; and in-ICU anticoagulation, 0.1 [0.03-0.3], P < .0001) as independently associated with in-hospital mortality. For the subgroup of definite/probable catastrophic APS, the Cox bivariable model (including the Simplified Acute Physiology Score II score) retained double therapy (corticosteroids + anticoagulant, 0.2 [0.07-0.6]; P = .005) but not triple therapy (corticosteroids + anticoagulant + IV immunoglobulins or plasmapheresis: hazard ratio, 0.3 [0.1-1.1]; P = .07) as independently associated with in-hospital mortality.

Conclusions: In-ICU anticoagulation was the only APS-specific treatment independently associated with survival for all patients. Double therapy was independently associated with better survival of patients with definite/probable catastrophic APS. In these patients, further studies are needed to determine the role of triple therapy.
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http://dx.doi.org/10.1016/j.chest.2019.11.010DOI Listing
May 2020

Gene Expression of Protein Tyrosine Phosphatase 1B and Endoplasmic Reticulum Stress During Septic Shock.

Front Med (Lausanne) 2019 1;6:240. Epub 2019 Nov 1.

Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, Rouen, France.

Protein Tyrosine Phosphatase 1B (PTP1B) and endoplasmic reticulum stress (ERS) are involved in the septic inflammatory response. Their inhibition is associated with improved survival in murine models of sepsis. The objective was to describe PTP1B and ERS expression during septic shock in human. Prospective study including patients admitted to intensive care unit (ICU) for septic shock. Blood samples were collected on days 1 (D1), 3 and 5 (D5). Quantitative PCR (performed from whole blood) evaluated the expression of genes coding for PTP1B () and key elements of ERS (GRP78, ATF6, CHOP) or for endothelial dysfunction-related markers (ICAM1 and ET1). We analyzed gene variation between D5 and D1, collected glycemic parameters, insulin resistance and organ failure was evaluated by Sequential Organ Failure Assessment (SOFA) score. We included 44 patients with a mean SAPS II 50 ± 16 and a mortality rate of 13.6%. Between D1 and D5, there was a significant decrease of ( < 0.001) and ( < 0.001) expressions. Their variations of expression were correlated with SOFA variation ( = 0.35, CI 95% [0.05; 0.54], = 0.03 and = 0.45 CI 95% [0.20; 0.65], < 0.001). We did not find any correlation between expression and insulin resistance or glycemic parameters. Between D1 and D5, and expressions were correlated with that of . Our study has evaluated for the first time the expression of PTP1B and ERS in patients with septic shock, revealing that gene expression variation of and are partly correlated with the evolution of septic organ failure and with endothelial dysfunction markers expression.
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http://dx.doi.org/10.3389/fmed.2019.00240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839276PMC
November 2019

Ipilimumab-induced renal granulomatous arteritis: a case report.

BMC Nephrol 2019 10 11;20(1):366. Epub 2019 Oct 11.

Nephrology department, Rouen University Hospital, 147 avenue du Maréchal Juin 76230 Bois Guillaume, Rouen, France.

Background: Immune Checkpoint Inhibitors (ICPIs) are promising new drugs in treatment of advanced tumours targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD1) or its ligand (PDL-1). Ipilimumab is a monoclonal antibody targeting the CTLA-4 receptor used in treatment of metastatic melanoma. By increasing activity of the immune system, ICPIs lead to immune-related adverse events, such as dermatitis, colitis or hepatitis. ICPIs-related kidney adverse events are rare and acute tubulointerstitial nephritis with or without granuloma have mainly been reported.

Case Presentation: We report a case of acute kidney injury in a patient with melanoma treated by ipilimumab. Kidney biopsy revealed acute interlobular and juxtaglomerular granulomatous arteritis, which has not yet been reported in patients treated by ICPIs. Kidney function partially recovered after ipilimumab discontinuation and oral prednisone. Unfortunately, the patient died a few months later from progression of his melanoma.

Conclusion: This case highlights a new mechanism of acute kidney injury related to ICPIs and supports the interest of kidney biopsy in case of ICPIs related acute renal failure.
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http://dx.doi.org/10.1186/s12882-019-1552-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788031PMC
October 2019

Rescue stem cell allograft in intensive care unit patients during septic shock with multi-organ failure.

J Crit Care 2019 12 2;54:122-124. Epub 2019 Jul 2.

Department of Medical Intensive Care, Rouen University Hospital, 76000 Rouen, France. Electronic address:

Purpose: We describe what we believe to be the first two cases of patients who received an allograft in intensive care unit (ICU) despite severe septic shock with multi-organ failure (MOF).

Results: One patient had aggressive large B-cell lymphoma. After allograft, the patient initially improved after withdrawing norepinephrine and renal replacement therapy but he subsequently died thirty-two days later because of a new relapse of the disease. The second patient had acute myeloid leukemia type 1 with a need for an allograft after a first complete remission. She was discharged from ICU at D23 after allograft and still alive 7 months later with complete remission. For the two patients, allograft conditioning was performed before admission to our ICU. These two cases highlight one major problem in such situations which is to find the best time to perform the allograft, particularly in ventilated patients with septic shock and MOF. We performed the allograft when we thought that the risk-benefit ratio was in favor of restoring immunity.

Conclusion: Allograft should be considered as a rescue therapy in ICU for patients with aplasia, during septic shock with multi-organ failure, however close multidisciplinary discussion is required between intensivists and onco-hematologists.
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http://dx.doi.org/10.1016/j.jcrc.2019.07.002DOI Listing
December 2019

CAPS criteria fail to identify most severely-ill thrombotic antiphospholipid syndrome patients requiring intensive care unit admission.

J Autoimmun 2019 09 26;103:102292. Epub 2019 Jun 26.

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital La Pitié-Salpêtrière, Institut E3M, Service de Médecine Interne 2, Centre de Référence National Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et autres maladies auto-immunes systémiques rares, Paris, France.

Purpose: Catastrophic antiphospholipid syndrome (CAPS), the most severe manifestation of antiphospholipid syndrome (APS), is characterised by simultaneous thromboses in multiple organs. Diagnosing CAPS can be challenging but its early recognition and management is crucial for a favourable outcome. This study was undertaken to evaluate the frequencies, distributions and ability to predict mortality of "definite/probable" or "no-CAPS" categories of thrombotic APS patients requiring admission to the intensive care unit (ICU).

Methods: This French national multicentre retrospective study, conducted from January 2000 to September 2018, included all APS patients with any new thrombotic manifestation(s) admitted to 24 ICUs.

Results: One hundred and thirty-four patients (male/female ratio: 0.4; mean age at admission: 45.4 ± 15.0 years), who experienced 152 CAPS episodes, required ICU admission. The numbers of definite, probable or no-CAPS episodes, respectively, were: 11 (7.2%), 60 (39.5%) and 81 (53.3%). No histopathological proof of microvascular thrombosis was the most frequent reason for not being classified as definite CAPS. Overall, 35/152 (23.0%) episodes were fatal, with comparable rates for definite/probable CAPS and no CAPS (23% vs. 28.8% respectively, p = 0.4). The Kaplan-Meier curve of estimated probability of survival showed no between-group survival difference (log-rank test p = 0.5).

Conclusions: In this study, CAPS criteria were not associated with mortality of thrombotic APS patients requiring ICU admission. Further studies are need evaluate the adequacy of CAPS criteria for critically-ill APS patients.
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http://dx.doi.org/10.1016/j.jaut.2019.06.003DOI Listing
September 2019

Skeletal muscle mass and adipose tissue alteration in critically ill patients.

PLoS One 2019 13;14(6):e0216991. Epub 2019 Jun 13.

Normandie University, UNIROUEN, Inserm U 1096, Rouen University Hospital, Rouen, France.

Background: Increasing numbers of studies in chronic diseases have been published showing the relationship between body composition (BC) parameters (i.e. skeletal muscle mass (SMM) and adipose tissue (AT)) and outcomes. For patients admitted to intensive care unit (ICU), BC parameters have rarely been described as a prognostic marker of outcome. The primary objective was to evaluate the relationship between body composition at ICU admission and major clinical outcomes. Secondary objectives were to assess the relationship between BC parameters and other parameters (systemic inflammatory markers, Sequential Organ Failure Assessment (SOFA) score, albumin level) at ICU admission, and between BC alterations during ICU stay and outcomes.

Patients And Methods: This retrospective study enrolled 25 adult patients who had two abdominal CT scans for clinical indication: first, within 48 hours of ICU admission (initial assessment), and second, 7 to 14 days later (late assessment). Skeletal Muscle radiodensity (SMD), cross-sectional area of SMM, Visceral Adipose Tissue (VAT) and Subcutaneous Adipose Tissue (SAT) were measured at the third lumbar vertebra. Cox regression analysis was used to determine the association between these parameters and mortality.

Results: Patients' mean age was 64.6 years. Their mean BMI was 27.7 kg/m2 (SD = 6.0). ICU mortality was 36%. There was no correlation between BC parameters at initial assessment and ICU outcomes. We observed a negative correlation between SMM index and SOFA score at initial assessment (r = -0.458, p = 0.037). There was a significant loss of VAT between two CT assessments which was associated with mortality (-22.34cm2 / m2 in non-survivors versus -6.22 cm2 / m2 in survivors, p = 0.039). Loss of SMD was greater with the occurrence of an infection than without (Delta SMD = -5.642 vs +1.957, p = 0.04).

Conclusions: Our results show alterations in body composition during ICU stay with a loss of muscle quality (decreased SMD) and adipose tissue. These findings require confirmation in future studies but already show that BC assessments at ICU admission and BC alterations during ICU stay are important factors for outcome in critically ill patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216991PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563951PMC
February 2020

[Kidney disease in cobalamin C deficiency].

Nephrol Ther 2019 Jul 23;15(4):201-214. Epub 2019 May 23.

Service de néphrologie, dialyse et transplantation, CHU de Rouen, 1, rue de Germont, 76031 Rouen, France; Inserm U1096, UFR médecine pharmacie, 22, boulevard Gambetta, 76183 Rouen, France.

Cobalamin C deficiency (cblC) is the most common inborn error of vitamin B metabolism. This autosomal recessive disease is due to mutations in MMACHC gene, encoding a cyanocobalamin decyanase. It leads to hyperhomocysteinemia associated with hypomethioninemia and methylmalonic aciduria. Two distinct phenotypes have been described : early-onset forms occur before the age of one year and are characterized by a severe multisystem disease associating failure to thrive to neurological and ophthalmological manifestations. They are opposed to late-onset forms, less severe and heterogeneous. CblC deficiency-associated kidney lesions remain poorly defined. Thirty-eight cases have been described. Age at initial presentation varied from a few days to 28 years. Most of the patients presented renal thrombotic microangiopathy (TMA) associated with acute renal failure, and 21 patients presented typical lesions of renal thrombotic microangiopathy on kidney biopsy. Prognosis was poor, leading to death in the absence of treatment, and related to the severity of renal lesions in the early-onset forms. Late-onset disease had better prognosis and most of patients were weaned off dialysis after treatment initiation. We suggest that all the patients with renal TMA be screened for cobalamin metabolism disorder, regardless of age and even in the absence of neurological symptoms, to rapidly initiate the appropriate treatment.
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http://dx.doi.org/10.1016/j.nephro.2019.03.011DOI Listing
July 2019

Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors.

Kidney Int 2019 06 15;95(6):1443-1452. Epub 2019 Mar 15.

Centre de Recherche en Transplantation et Immunologie, UMR 1064, INSERM, Université de Nantes, Nantes, France; Institut de Transplantation Urologie Néphrologie, CHU Nantes, Nantes, France; Department of Nephrology and Immunology, Center Hospitalier Universitaire de Nantes, Nantes, France. Electronic address:

Secondary hemolytic uremic syndrome (HUS) is a heterogeneous group of thrombotic microangiopathies associated with various underlying conditions. Whether it belongs to the spectrum of complement-mediated HUS remains controversial. We analysed the presentation, outcome, and frequency of complement gene rare variants in a cohort of 110 patients with secondary HUS attributed to drugs (29%), autoimmune diseases (24%), infections (17%), malignancies (10%), glomerulopathies (9%), extra-renal organ transplantation (8%), and pancreatitis (3%). The frequency of complement gene rare variants was similar in patients with secondary HUS (5%) and in healthy individuals (6% and 8% in French and European controls, respectively). At diagnosis, 40% of patients required dialysis and 18% had neurological manifestations. Fifty percent of patients received plasmatherapy and 35% were treated with eculizumab. Haematological and complete renal remission was achieved in 80% and 24% of patients, respectively. Thirty-nine percent of patients progressed to chronic kidney disease (stages 3-4) and an additional 37% reached end-stage renal disease. Eleven percent of patients died, most often from complications of the underlying cause of HUS. Only one patient experienced an HUS relapse. Patients treated with eculizumab presented with more severe HUS and were more likely to require dialysis at the time of diagnosis as compared to patients not treated with eculizumab. Rates of hematological remission, chronic kidney disease (stages 3-4), and end-stage renal disease were similar in the two groups. Secondary HUS is an acute nonrelapsing form of HUS, not related to complement dysregulation. The efficacy of eculizumab in this setting is not yet established.
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http://dx.doi.org/10.1016/j.kint.2019.01.023DOI Listing
June 2019

Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort.

Br J Clin Pharmacol 2019 02 18;85(2):403-412. Epub 2018 Dec 18.

Department of Nephrology, Aix-Marseille University, AP-HM Hôpital de la Conception, Marseille, France.

Aims: Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine-associated TMA (G-TMA).

Methods: From 1998 to 2015, all cases of G-TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed.

Results: G-TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m . Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new-onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored.

Conclusion: This large cohort confirms the severity of G-TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.
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http://dx.doi.org/10.1111/bcp.13808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339967PMC
February 2019

Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal Arteriolar and Glomerular Thrombotic Microangiopathy.

Kidney Int Rep 2018 Sep 8;3(5):1153-1162. Epub 2018 Jun 8.

Nephrology Department, Rouen University Hospital, Rouen, France.

Introduction: Cobalamin C (cblC) deficiency is the most common inborn error of vitamin B metabolism. Renal failure attributed to thrombotic microangiopathy (TMA) has occasionally been described in the late-onset presentation of cblC deficiency, but kidney lesions associated with cblC deficiency remain poorly defined. This study aims to describe the characteristics of kidney disease in cblC deficiency, and to provide a comparative histological analysis with cblC-independent renal TMA.

Methods: We performed a multicenter retrospective study including 7 patients with cblC deficiency and 16 matched controls with cblC-independent TMA. The patients included were aged 6 to 26 years at the time of the first manifestations. All patients presented with acute renal failure, proteinuria, and hemolysis; 5 patients required dialysis.

Results: The histological study revealed arteriolar and glomerular TMA in all patients. After comparison with the cblC-independent TMA control group, a vacuolated aspect of the glomerular basement membrane and the intensity of glomerular capillary wall IgM deposits were more present in cblC deficiency patients than in controls. Six patients were treated with hydroxycobalamin. All of them improved, with disappearance of hemolysis, and 3 of the 4 patients requiring renal replacement therapy were weaned off dialysis.

Conclusion: This study provides a precise description of kidney pathology in cblC deficiency. Due to major therapeutic implications, we suggest that patients with renal TMA be screened for cblC deficiency regardless of age, particularly when the kidney biopsy provides evidence of long-lasting TMA, including a vacuolated aspect of the glomerular basement membrane and glomerular capillary wall IgM deposition.
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http://dx.doi.org/10.1016/j.ekir.2018.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127440PMC
September 2018

Management of dabigatran after overdosage: two case reports and suggestions for monitoring.

Blood Coagul Fibrinolysis 2018 Nov;29(7):653-655

Normandie Univ, UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit.

: Bleeding is the main complication of anticoagulant treatments as dabigatran etexilate. In patients with atrial fibrillation, dabigatran, at certain doses, has been associated with similar rates of stroke and embolism, and a lower rate of major hemorrhage compared to warfarin. Before the recent possibility of reversing the anticoagulant effect of dabigatran with idarucizumab, prothrombin complex concentrate (PCC) was the main available treatment in cases of severe bleeding or emergency surgery . We describe two different cases with very high overdosage in which PCC or idarucizumab was used to reverse the effect of dabigatran etexilate.
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http://dx.doi.org/10.1097/MBC.0000000000000763DOI Listing
November 2018

Admission of tetanus patients to the ICU: a retrospective multicentre study.

Ann Intensive Care 2017 Nov 7;7(1):112. Epub 2017 Nov 7.

Département de réanimation médicale et médecine hyperbare, CHU Angers et faculté de santé Angers, 49933, Angers, France.

Background: An extended course of tetanus (up to 6 weeks) requiring ICU admission and protracted mechanical ventilation (MV) may have a significant impact on short- and long-term survival. The subject is noteworthy and deserves to be discussed.

Methods: Twenty-two ICUs in France performed tetanus screenings on patients admitted between January 2000 and December 2014. Retrospective data were collected from hospital databases and through the registers of the town hall of the patients.

Results: Seventy patients were included in 15 different ICUs. Sixty-three patients suffered from severe or very severe tetanus according to the Ablett classification. The median age was 80 years [interquartile range 73-84], and 86% of patients were women. Ninety per cent of patients (n = 63) required MV for a median of 36 days [26-46], and 66% required administration of a neuromuscular-blocking agent for 23 days [14-29]. A nosocomial infection occurred in 43 patients (61%). ICU and 1-year mortality rates were 14% (n = 10) and 16% (n = 11), respectively. Forty-five per cent of deaths occurred during the first week. Advanced age, a higher SAPS II, any infection, and the use of vasopressors were significantly associated with a lower number of days alive without ventilator support by day 90. Age was the only factor that significantly differed between deceased and survivors at 1 year (83 [81-85] vs. 79 [73-84] years, respectively; p = 0.03). Sixty-one per cent of survivors suffered no impairment to their functional status.

Conclusion: In a high-income country, tetanus mainly occurs in healthy elderly women. Despite prolonged MV and extended ICU length of stay, we observed a low 1-year mortality rate and good long-term functional status.
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http://dx.doi.org/10.1186/s13613-017-0333-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676569PMC
November 2017

Thrombotic microangiopathies and antineoplastic agents.

Nephrol Ther 2017 Apr;13 Suppl 1:S109-S113

Centre de référence des microangiopathies thrombotiques (CNR-MAT), AP-HP, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France.

Thrombotic microangiopathy is a well-described complication of cancer treatment. Its incidence has increased these last decades, as a result of a better awareness of this complication in cancer patients in one hand, but also of a larger array of therapeutic compounds including anti-vascular endothelium growth factor (VEGF) drugs. It is therefore mandatory to recognize these conditions since they have a significant impact in thrombotic microangiopathies management and prognosis. Practitioners should be aware of the more classical antineoplastic agents associated with thrombotic microangiopathies, the mechanisms by which they induce them, and the resulting management and prognosis. Since malignancy itself can induce thrombotic microangiopathies, it is also mandatory to know how to distinguish rapidly those caused by antineoplastic agents from those associated with cancer, for an adapted management. Thrombotic microangiopathies associated with chemotherapy remain of dismal prognosis. A better understanding of pathophysiology in these forms of thrombotic microangiopathies, in association with a more empirical approach through the use of new therapeutic agents that can also help in the understanding on new mechanisms a posteriori, should improve their prognosis. The preliminary encouraging results reported with complement blockers in this field could represent a convincing example.
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http://dx.doi.org/10.1016/j.nephro.2017.01.016DOI Listing
April 2017

Life-Threatening Pneumopathy and in a STAT3-Deficient Hyper-IgE Syndrome Patient.

Pediatrics 2017 Jun 17;139(6). Epub 2017 May 17.

Departments of Pediatric Respiratory and Allergy Diseases and.

A deficiency in signal transducer and activator of transcription 3 (STAT3) is responsible for autosomal dominant hyperimmunoglobulin E syndrome, an immunodeficiency syndrome causing , , , and, rarely, and infections. Currently, intracellular pathogens are not targeted in the management of severe infections. The pathophysiologic mechanism of hyperimmunoglobulin E syndrome immunodeficiency has recently been linked to a disorder in the T helper 17 pathway and disruption of the interleukin -23/interleukin-17 axis. We report an unusual case of severe pleuropneumopathy by in a teenage girl with STAT3-deficient hyperimmunoglobulin E syndrome (STAT3 HIES). A previous case of severe lung infection by has already been described in a STAT3-deficient patient, but has never been reported in patients with STAT3 HIES. After a review of the literature, it seems that the specific immunodeficiency pathway of STAT3 HIES exposes STAT3 HIES patients to lung infections because the pathophysiology of STAT3 HIES and is based on STAT3 and T helper 17 cells.
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http://dx.doi.org/10.1542/peds.2016-0845DOI Listing
June 2017

Patients with ANCA-associated vasculitis admitted to the intensive care unit with acute vasculitis manifestations: a retrospective and comparative multicentric study.

Ann Intensive Care 2017 Dec 5;7(1):39. Epub 2017 Apr 5.

Néphrologie-Dialyse-Transplantation, CHU Angers, 4 rue Larrey, 49933, Angers Cedex 9, France.

Purpose: Data for ANCA-associated vasculitis (AAV) patients requiring intensive care are scarce.

Methods: We included 97 consecutive patients with acute AAV manifestations (new onset or relapsing disease), admitted to 18 intensive care units (ICUs) over a 10-year period (2002-2012). A group of 95 consecutive AAV patients with new onset or relapsing disease, admitted to two nephrology departments with acute vasculitis manifestations, constituted the control group.

Results: In the ICU group, patients predominantly showed granulomatosis with polyangiitis and proteinase-3 ANCAs. Compared with the non-ICU group, the ICU group showed comparable Birmingham vasculitis activity score and a higher frequency of heart, central nervous system and lungs involvements. Respiratory assistance, renal replacement therapy and vasopressors were required in 68.0, 56.7 and 26.8% of ICU patients, respectively. All but one patient (99%) received glucocorticoids, 85.6% received cyclophosphamide, and 49.5% had plasma exchanges as remission induction regimens. Fifteen (15.5%) patients died during the ICU stay. The following were significantly associated with ICU mortality in the univariate analysis: the need for respiratory assistance, the use of vasopressors, the occurrence of at least one infection event in ICU, cyclophosphamide treatment, sequential organ failure assessment at admission and simplified acute physiology score II. After adjustment on sequential organ failure assessment or infection, cyclophosphamide was no longer a risk factor for mortality. Despite a higher initial mortality rate of ICU patients within the first hospital stay (p < 0.0001), the long-term mortality of hospital survivors did not differ between ICU and non-ICU groups (18.6 and 20.4%, respectively, p = 0.36). Moreover, we observed no renal survival difference between groups after a 1-year follow-up (82.1 and 80.5%, p = 0.94).

Conclusion: This study supports the idea that experiencing an ICU challenge does not impact the long-term prognosis of AAV patients.
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http://dx.doi.org/10.1186/s13613-017-0262-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382116PMC
December 2017

Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre.

Am J Hematol 2017 Apr 21;92(4):381-387. Epub 2017 Feb 21.

Service de Médecine Interne, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France.

Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.
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http://dx.doi.org/10.1002/ajh.24665DOI Listing
April 2017

The Use of Ferritin to Identify Critically Ill Patients With Secondary Hemophagocytic Lymphohistiocytosis.

Crit Care Med 2016 Nov;44(11):e1045-e1053

1Medical Intensive Care Unit, Rouen University Hospital, Rouen, France. 2Department of Hematology, Rouen University Hospital, Rouen, France. 3Department of Nephrology, Rouen University Hospital, Rouen, France.

Objectives: Thrombocytopenia is a common, multifactorial, finding in ICU. Hemophagocytosis is one of the main explanatory mechanisms, possibly integrated into hemophagocytic lymphohistiocytosis syndrome, of infectious origin in the majority of cases in ICU. The hemophagocytic lymphohistiocytosis is probably underdiagnosed in the ICU, although it is associated with dramatic outcomes. The main objectives of this work were to identify the frequency of secondary hemophagocytic lymphohistiocytosis, and the main prognostic factors for mortality.

Design/setting: We conducted a retrospective observational study in all adult patients admitted with suspected or diagnosed hemophagocytic lymphohistiocytosis, between January 1, 2000, and August 22, 2012.

Patients: A total of 106 patients (42%) had significant hemophagocytosis on bone marrow examination, performed for exploration of thrombocytopenia, bicytopenia, or pancytopenia.

Measurements And Main Results: The median age was 56 (45-68) and the median Simplified Acute Physiology Score 2 was 55 (38-68). The main reason for ICU admission was hemodynamic instability (58%), predominantly related to sepsis (45% cases). The main precipitating factor found was a bacterial infection in 81 of 106 patients (76%), including 32 (30%) with Escherichia coli infection. Forty six of 106 patients (43%) died in the ICU. They were significantly older, had higher Simplified Acute Physiology Score 2, plasma lactate deshydrogenase bilirubin, and serum ferritin. The fibrinogen and the percentage of megakaryocytes were significantly lower in nonsurvivors when compared with survivors. In multivariate analysis, only serum ferritin significantly predicted death related to hemophagocytosis. A serum ferritin greater than 2,000 μg/L predicted death with a sensitivity of 71% and a specificity of 76%. A decreased percentage of megakaryocytes also predicted patient death in the ICU.

Conclusions: Hemophagocytosis is common in thrombocytopenic patients with sepsis, frequently included in a postinfectious hemophagocytic lymphohistiocytosis setting. Our study reveals that ferritin could be a reliable prognostic marker in these patients, and hold particular interest in discussing a specific treatment for hemophagocytic lymphohistiocytosis.
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http://dx.doi.org/10.1097/CCM.0000000000001878DOI Listing
November 2016

Epidemiology of Weaning Outcome according to a New Definition. The WIND Study.

Am J Respir Crit Care Med 2017 03;195(6):772-783

26 Keenan Research Centre, Li Ka Shing Knowledge Institute, Saint Michael's Hospital, Toronto, Ontario, Canada; and.

Rationale: The weaning process concerns all patients receiving mechanical ventilation. A previous classification into simple, prolonged, and difficult weaning ignored weaning failure and presupposed the use of spontaneous breathing trials.

Objectives: To describe the weaning process, defined as starting with any attempt at separation from mechanical ventilation and its prognosis, according to a new operational classification working for all patients under ventilation.

Methods: This was a multinational prospective multicenter observational study over 3 months of all patients receiving mechanical ventilation in 36 intensive care units, with daily collection of ventilation and weaning modalities. Pragmatic definitions of separation attempt and weaning success allowed us to allocate patients in four groups.

Measurements And Main Results: A total of 2,729 patients were enrolled. Although half of them could not be classified using the previous definition, 99% entered the groups on the basis of our new definition as follows: 24% never started a weaning process, 57% had a weaning process of less than 24 hours (group 1), 10% had a difficult weaning of more than 1 day and less than 1 week (group 2), and 9% had a prolonged weaning duration of 1 week or more (group 3). Duration of ventilation, intensive care unit stay, and mortality (6, 17, and 29% for the three groups, respectively) all significantly increased from one group to the next. The unadjusted risk of dying was 19% after the first separation attempt and increased to 37% after 10 days.

Conclusions: A new classification allows us to categorize all weaning situations. Every additional day without a weaning success after the first separation attempt increases the risk of dying.
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http://dx.doi.org/10.1164/rccm.201602-0320OCDOI Listing
March 2017

Pre-oxygenation with high-flow nasal cannula oxygen therapy and non-invasive ventilation for intubation in the intensive care unit.

Intensive Care Med 2016 Aug 5;42(8):1291-2. Epub 2016 May 5.

Department of Medical Intensive Care, Rouen University Hospital, 76031, Rouen cedex, France.

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http://dx.doi.org/10.1007/s00134-016-4369-5DOI Listing
August 2016

Outcomes of patients admitted to intensive care units for acute manifestation of small-vessel vasculitis: a multicenter, retrospective study.

Crit Care 2016 Jan 26;20:27. Epub 2016 Jan 26.

Brabois Medical Intensive Care Unit, Nancy University Hospital, Vandoeuvre-les-Nancy, Nancy, 54000, France.

Background: The outcomes of patients admitted to the intensive care unit (ICU) for acute manifestation of small-vessel vasculitis are poorly reported. The aim of the present study was to determine the mortality rate and prognostic factors of patients admitted to the ICU for acute small-vessel vasculitis.

Methods: This retrospective, multicenter study was conducted from January 2001 to December 2014 in 20 ICUs in France. Patients were identified from computerized registers of each hospital using the International Classification of Diseases, Ninth Revision (ICD-9). Inclusion criteria were (1) known or highly suspected granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis (respectively, ICD-9 codes M31.3, M30.1, and M31.7), or anti-glomerular basement membrane antibody disease (ICD-9 codes N08.5X-005 or M31.0+); (2) admission to the ICU for the management of an acute manifestation of vasculitis; and (3) administration of a cyclophosphamide pulse in the ICU or within 48 h before admission to the ICU. The primary endpoint was assessment of mortality rate 90 days after admission to the ICU.

Results: Eighty-two patients at 20 centers were included, 94% of whom had a recent (<6 months) diagnosis of small-vessel vasculitis. Forty-four patients (54%) had granulomatosis with polyangiitis. The main reasons for admission were respiratory failure (34%) and pulmonary-renal syndrome (33%). Mechanical ventilation was required in 51% of patients, catecholamines in 31%, and renal replacement therapy in 71%. Overall mortality at 90 days was 18% and the mortality in ICU was 16 %. The main causes of death in the ICU were disease flare in 69% and infection in 31%. In univariable analysis, relevant factors associated with death in nonsurvivors compared with survivors were Simplified Acute Physiology Score II (median [interquartile range] 51 [38-82] vs. 36 [27-42], p = 0.005), age (67 years [62-74] vs. 58 years [40-68], p < 0.003), Sequential Organ Failure Assessment score on the day of cyclophosphamide administration (11 [6-12] vs. 6 [3-7], p = 0.0004), and delayed administration of cyclophosphamide (5 days [3-14] vs. 2 days [1-5], p = 0.0053).

Conclusions: Patients admitted to the ICU for management of acute small-vessel vasculitis benefit from early, aggressive intensive care treatment, associated with an 18% death rate at 90 days.
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http://dx.doi.org/10.1186/s13054-016-1189-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729170PMC
January 2016

Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency.

Lancet 2015 Sep;386(9997):1011-2

Nephrology Department, Rouen University Hospital, Rouen, France; INSERM U1096, Rouen University Medical School, Rouen, France; IRIB, Institute for Research and Innovation in Biomedicine, Rouen, France.

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http://dx.doi.org/10.1016/S0140-6736(15)00076-8DOI Listing
September 2015

[Successful treatment of extreme hypernatremia by continuous veno-venous hemodiafiltration].

Nephrol Ther 2015 Nov 11;11(6):492-5. Epub 2015 Jul 11.

Pôle réanimation-anesthésie-Samu, réanimation chirurgicale, CHU Charles Nicolle, 1, rue de Germont, 76031 Rouen, France.

Extreme hypernatremia in intensive care unit are frequently associated with a poor prognosis and their treatment, when associated with acute renal failure, is not consensual. We report the case of a 39-year-old man admitted in our intensive care unit for coma who presented extreme hyperosmolar hypernatremia (sodium 180 mmol/L, osmolarity 507 mOsm/L) associated with acute renal failure (urea 139.3 mmol/L, creatinine 748 μmol/L) and many other metabolic abnormalities. He was treated with hypotonic fluid administration and continuous renal replacement therapy (veno-venous hemodiafiltration) using an industrial dialysate fluid. Natremia was controlled by modulating intravenous water and sodium intake according to biological data. After 10 days, continuous renal replacement therapy was stopped and neurological exam was normal. Continuous veno-venous hemodiafiltration may be useful for treatment of extreme hypernatremia by allowing gradual correction of fluid and electrolyte disorders.
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http://dx.doi.org/10.1016/j.nephro.2015.04.004DOI Listing
November 2015