Anti-N-Methyl-d-Aspartate Receptor Encephalitis in Adult Patients Requiring Intensive Care.

Abstract:

RATIONALE:Encephalitis caused by anti-N-methyl-d-aspartate receptor (NMDAR) antibodies is the leading cause of immune-mediated encephalitis. There are limited data on intensive care unit (ICU) management of these patients. OBJECTIVES:To identify prognostic factors of good neurologic outcome in patients admitted to an ICU with anti-NMDAR encephalitis. METHODS:This was an observational multicenter study of all consecutive adult patients diagnosed with anti-NMDAR encephalitis at the French National Reference Centre, admitted to an ICU between 2008 and 2014. The primary outcome was a good neurologic outcome at 6 months after ICU admission, defined by a modified Rankin Scale score of 0-2. MEASUREMENTS AND MAIN RESULTS:Seventy-seven patients were included from 52 ICUs. First-line immunotherapy consisted of steroids (n = 61/74; 82%), intravenous immunoglobulins (n = 71/74; 96%), and plasmapheresis (n = 17/74; 23%). Forty-five (61%) patients received second-line immunotherapy (cyclophosphamide, rituximab, or both). At 6 months, 57% of patients had a good neurologic outcome. Independent factors of good neurologic outcome were early (≤8 d after ICU admission) immunotherapy (odds ratio, 16.16; 95% confidence interval, 3.32-78.64; for combined first-line immunotherapy with steroids and intravenous immunoglobulins vs. late immunotherapy), and a low white blood cell count on the first cerebrospinal examination (odds ratio, 9.83 for <5 vs. >50 cells/mm3; 95% confidence interval, 1.07-90.65). Presence of nonneurologic organ failures at ICU admission and occurrence of status epilepticus during ICU stay were not associated with neurologic outcome. CONCLUSIONS:The prognosis of adult patients with anti-NMDAR encephalitis requiring intensive care is good, especially when immunotherapy is initiated early, advocating for prompt diagnosis and early aggressive treatment.

authors

de Montmollin E,Demeret S,Brulé N,Conrad M,Dailler F,Lerolle N,Navellou JC,Schwebel C,Alves M,Cour M,Engrand N,Tonnelier JM,Maury E,Ruckly S,Picard G,Rogemond V,Magalhaes É,Sharshar T,Timsit JF,Honnorat J,Sonnevil

doi

10.1164/rccm.201603-0507OC

subject

Has Abstract

pub_date

2017-02-15 00:00:00

pages

491-499

issue

4

eissn

1073-449X

issn

1535-4970

journal_volume

195

pub_type

杂志文章,多中心研究
  • Skeletal muscle adaptation to endurance training in patients with chronic obstructive pulmonary disease.

    abstract::The purpose of this study was to evaluate the physiologic responses to endurance training in patients with moderate to severe airflow obstruction by specifically looking at changes in skeletal muscle enzymatic activities. Eleven patients (age = 65 +/- 7 yr, mean +/- SD, FEV1 = 36 +/- 11% of predicted value, range = 24...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.154.2.8756820

    authors: Maltais F,LeBlanc P,Simard C,Jobin J,Bérubé C,Bruneau J,Carrier L,Belleau R

    更新日期:1996-08-01 00:00:00

  • Sleep deprivation per se does not decrease the hypercapnic ventilatory response in humans.

    abstract::Several studies have found that sleep deprivation reduces the hypercapnic ventilatory response (HCVR). Such results may have been affected by uncontrolled activities or environmental influences during the sleep deprivation period. The current study determined the "pure" effect of sleep deprivation on respiratory contr...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.161.4.9906026

    authors: Spengler CM,Shea SA

    更新日期:2000-04-01 00:00:00

  • Airway smooth muscle hypertrophy and hyperplasia in asthma.

    abstract:RATIONALE:Increased thickness of the airway smooth muscle (ASM) layer in asthma may result from hyperplasia or hypertrophy of muscle cells or increased extracellular matrix (ECM). OBJECTIVES:To relate ASM hypertrophy, ASM hyperplasia, and deposition of ECM to the severity and duration of asthma. METHODS:Airways from ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201110-1849OC

    authors: James AL,Elliot JG,Jones RL,Carroll ML,Mauad T,Bai TR,Abramson MJ,McKay KO,Green FH

    更新日期:2012-05-15 00:00:00

  • Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease.

    abstract:RATIONALE:Comorbidities contribute to disease severity and mortality in patients with chronic obstructive pulmonary disease (COPD). Comorbidities have been studied individually and were mostly based on self-reports. The coexistence of objectively identified comorbidities and the role of low-grade systemic inflammation ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201209-1665OC

    authors: Vanfleteren LE,Spruit MA,Groenen M,Gaffron S,van Empel VP,Bruijnzeel PL,Rutten EP,Op 't Roodt J,Wouters EF,Franssen FM

    更新日期:2013-04-01 00:00:00

  • Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report.

    abstract::Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1164/rccm.201604-0801CI

    authors: Collard HR,Ryerson CJ,Corte TJ,Jenkins G,Kondoh Y,Lederer DJ,Lee JS,Maher TM,Wells AU,Antoniou KM,Behr J,Brown KK,Cottin V,Flaherty KR,Fukuoka J,Hansell DM,Johkoh T,Kaminski N,Kim DS,Kolb M,Lynch DA,Myers JL,R

    更新日期:2016-08-01 00:00:00

  • Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis.

    abstract:RATIONALE:The molecular mechanisms underlying acute exacerbations of idiopathic pulmonary fibrosis (IPF) are poorly understood. We studied the global gene expression signature of acute exacerbations of IPF. OBJECTIVES:To understand the gene expression patterns of acute exacerbations of IPF. METHODS:RNA was extracted ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200810-1596OC

    authors: Konishi K,Gibson KF,Lindell KO,Richards TJ,Zhang Y,Dhir R,Bisceglia M,Gilbert S,Yousem SA,Song JW,Kim DS,Kaminski N

    更新日期:2009-07-15 00:00:00

  • Mouse model of airway remodeling: strain differences.

    abstract::We found that continuous eosinophilic inflammation after repeated antigen instillation into the nose was observed only in A/J mice, not in three other strains. Histologic analysis of tissues from A/J mice revealed features typical of airway remodeling, i.e., airway wall thickening and increased collagen depositions we...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200210-1188OC

    authors: Shinagawa K,Kojima M

    更新日期:2003-10-15 00:00:00

  • Glutathione s-transferases M1 and P1 prevent aggravation of allergic responses by secondhand smoke.

    abstract:RATIONALE:Secondhand tobacco smoke (SHS) and traffic-related air pollutants are associated with asthma and allergy. Diesel exhaust particles (DEPs) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species. Glutathione S-transferases (GSTs) metabolize rea...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.1164/rccm.200509-1424OC

    authors: Gilliland FD,Li YF,Gong H Jr,Diaz-Sanchez D

    更新日期:2006-12-15 00:00:00

  • Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs.

    abstract:RATIONALE:In cigarette smoking-induced chronic obstructive pulmonary disease, structural and functional derangements are characterized by parenchymal destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase inhibitors that have been used as lipid-lowering agents. These drugs ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200501-041OC

    authors: Lee JH,Lee DS,Kim EK,Choe KH,Oh YM,Shim TS,Kim SE,Lee YS,Lee SD

    更新日期:2005-10-15 00:00:00

  • Long-term follow-up of hexamethylene diisocyanate-, diphenylmethane diisocyanate-, and toluene diisocyanate-induced asthma.

    abstract::In 1976-1992 245 new cases of asthma induced by diisocyanates were diagnosed, caused by hexamethylene diisocyanate (HDI) in 39%, diphenylmethane diisocyanate (MDI) in 39%, and toluene diisocyanate (TDI) in 17% of the cases. Our aim was to study the clinical outcome of diisocyanate-induced asthma. A questionnaire was s...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.162.2.9909026

    authors: Piirilä PL,Nordman H,Keskinen HM,Luukkonen R,Salo SP,Tuomi TO,Tuppurainen M

    更新日期:2000-08-01 00:00:00

  • Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.

    abstract:RATIONALE:Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. OBJECTIVES:To evaluate the safety and efficacy of tezacaft...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1164/rccm.201704-0717OC

    authors: Donaldson SH,Pilewski JM,Griese M,Cooke J,Viswanathan L,Tullis E,Davies JC,Lekstrom-Himes JA,Wang LT,VX11-661-101 Study Group.

    更新日期:2018-01-15 00:00:00

  • Airway Sensory Nerve Density Is Increased in Chronic Cough.

    abstract::Rationale: Chronic cough is characterized by frequent urges to cough and a heightened sensitivity to inhaled irritants. Airway sensory nerves trigger cough. We hypothesized that sensory nerve density is increased in chronic cough, which may contribute to excessive and persistent coughing.Objectives: To measure airway ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201912-2347OC

    authors: Shapiro CO,Proskocil BJ,Oppegard LJ,Blum ED,Kappel NL,Chang CH,Fryer AD,Jacoby DB,Costello RW,Drake MG

    更新日期:2021-02-01 00:00:00

  • Novel action of indoleamine 2,3-dioxygenase attenuating acute lung allograft injury.

    abstract:RATIONALE:Lung allografts are prone to reperfusion injury and acute rejection, which, in addition to infiltrating lymphocytes, are accompanied by neutrophil infiltration and neutrophil-associated oxidative stress. Indoleamine 2,3-dioxygenase (IDO) is a unique cytosolic enzyme that possesses T-cell-suppressive and antio...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200509-1413OC

    authors: Liu H,Liu L,Fletcher BS,Visner GA

    更新日期:2006-03-01 00:00:00

  • The affective dimension of laboratory dyspnea: air hunger is more unpleasant than work/effort.

    abstract:RATIONALE:It is hypothesized that the affective dimension of dyspnea (unpleasantness, emotional response) is not strictly dependent on the intensity of dyspnea. OBJECTIVES:We tested the hypothesis that the ratio of immediate unpleasantness (A(1)) to sensory intensity (SI) varies depending on the type of dyspnea. METH...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.1164/rccm.200711-1675OC

    authors: Banzett RB,Pedersen SH,Schwartzstein RM,Lansing RW

    更新日期:2008-06-15 00:00:00

  • The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury.

    abstract::Acute lung injury was produced in C57BL/6 mice by the intratracheal (i.t.) administration of bleomycin (BLM). Following injection of 0.1 U BLM, CD3+ lymphocytes and the production of the T-helper-1 (Th1) lymphokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were increased in lung and lymph nodes. The produ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.154.1.8680680

    authors: Sharma SK,MacLean JA,Pinto C,Kradin RL

    更新日期:1996-07-01 00:00:00

  • Gelsolin secretion in interleukin-4-treated bronchial epithelia and in asthmatic airways.

    abstract:RATIONALE:The airway surface liquid, the thin layer of liquid covering the airways, is essential for mucociliary clearance and as a barrier against microbial and other noxious agents. Proteins secreted into the airway surface liquid by epithelial and nonepithelial cells may be important in innate immunity and to improv...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200409-1185OC

    authors: Candiano G,Bruschi M,Pedemonte N,Caci E,Liberatori S,Bini L,Pellegrini C,Viganò M,O'Connor BJ,Lee TH,Galietta LJ,Zegarra-Moran O

    更新日期:2005-11-01 00:00:00

  • Rapid screening for alpha1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood specimens.

    abstract::We describe two reliable methods for high-throughput screening of proteinase inhibitor (PI) S and PI Z alpha(1)-antitrypsin (alpha(1)-AT) deficiency alleles from dried blood spot (DBS) specimens using the LightCycler fluorimetric analyzer. The method was used to study 72 patients with chronic obstructive pulmonary dis...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.2203025

    authors: Rodriguez F,Jardí R,Costa X,Cotrina M,Galimany R,Vidal R,Miravitlles M

    更新日期:2002-09-15 00:00:00

  • Population-based incidence estimates of influenza-associated respiratory failure hospitalizations, 2003 to 2009.

    abstract:RATIONALE:The incidence of influenza-associated acute respiratory failure is unknown. OBJECTIVES:To estimate the population-based incidence of influenza-associated acute respiratory failure hospitalizations. METHODS:This is a cohort study from January 2003 through March 2009 using hospitalization databases for Arizon...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201212-2341OC

    authors: Ortiz JR,Neuzil KM,Rue TC,Zhou H,Shay DK,Cheng PY,Cooke CR,Goss CH

    更新日期:2013-09-15 00:00:00

  • Cell infiltration, ICAM-1 expression, and eosinophil chemotactic activity in asthmatic sputum.

    abstract::We have applied the technique of sputum induction by hypertonic saline in asthmatics and nonatopic control subjects to study an array of indices of airway inflammation believed to be relevant to asthma pathogenesis. Compatible with a central role for eosinophils and mast cells in asthma, sputum of asthmatic subjects c...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章

    doi:10.1164/ajrccm.155.2.9032180

    authors: Louis R,Shute J,Biagi S,Stanciu L,Marrelli F,Tenor H,Hidi R,Djukanović R

    更新日期:1997-02-01 00:00:00

  • Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.

    abstract:RATIONALE:The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. OBJECTIVES:To determine the extent of lung disease in a geographically defined...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200901-0069OC

    authors: Sly PD,Brennan S,Gangell C,de Klerk N,Murray C,Mott L,Stick SM,Robinson PJ,Robertson CF,Ranganathan SC,Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF).

    更新日期:2009-07-15 00:00:00

  • T-bet polymorphisms are associated with asthma and airway hyperresponsiveness.

    abstract:RATIONALE:T-bet (TBX21 or T-box 21) is a critical regulator of T-helper 1 lineage commitment and IFN-gamma production. Knockout mice lacking T-bet develop airway hyperresponsiveness (AHR) to methacholine, peribronchial eosinophilic and lymphocytic inflammation, and increased type III collagen deposition below the bronc...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200503-505OC

    authors: Raby BA,Hwang ES,Van Steen K,Tantisira K,Peng S,Litonjua A,Lazarus R,Giallourakis C,Rioux JD,Sparrow D,Silverman EK,Glimcher LH,Weiss ST

    更新日期:2006-01-01 00:00:00

  • Influence of ambient air pollutant sources on clinical encounters for infant bronchiolitis.

    abstract:RATIONALE:Data regarding the influence of ambient air pollution on infant bronchiolitis are few. OBJECTIVES:We evaluated the impact of several air pollutants and their sources on infant bronchiolitis. METHODS:Infants in the Georgia Air Basin of British Columbia with an inpatient or outpatient clinical encounter for b...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200901-0117OC

    authors: Karr CJ,Demers PA,Koehoorn MW,Lencar CC,Tamburic L,Brauer M

    更新日期:2009-11-15 00:00:00

  • Daytime pulmonary hemodynamics in patients with obstructive sleep apnea without lung disease.

    abstract::It is controversial whether obstructive sleep apnea (OSA) causes pulmonary hypertension (PH) in the absence of hypoxemic lung disease. To investigate this further we measured awake pulmonary hemodynamics, pulmonary gas exchange, and small airways function in 32 patients with OSA (apnea- hypopnea index, mean +/- SE, 46...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.159.5.9805086

    authors: Sajkov D,Wang T,Saunders NA,Bune AJ,Neill AM,Douglas Mcevoy R

    更新日期:1999-05-01 00:00:00

  • Tracheal microvascular responses to beta-adrenergic stimulation in anesthetized rats.

    abstract::Previous study of adrenergic control of the tracheal vasculature in rats (1) demonstrated that beta-adrenergic blockade heightened arteriolar and large venular contractile responses to norepinephrine, a nonselective alpha-adrenergic agonist. The present study was undertaken to confirm the presence of functional beta-a...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.153.3.8630550

    authors: Corboz MR,Ballard ST,Inglis SK,Taylor AE

    更新日期:1996-03-01 00:00:00

  • Influence of the route of allergen administration and genetic background on the murine allergic pulmonary response.

    abstract::We used various ovalbumin sensitization and challenge protocols to determine the importance of the route of allergen administration and the genetic background in modulating the physiologic, inflammatory, and immunologic features characteristic of allergen-induced asthma. In BALB/c mice, induction of maximal airway hyp...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.155.2.9032210

    authors: Zhang Y,Lamm WJ,Albert RK,Chi EY,Henderson WR Jr,Lewis DB

    更新日期:1997-02-01 00:00:00

  • Progression of Lung Disease in Preschool Patients with Cystic Fibrosis.

    abstract:RATIONALE:Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES:To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progress...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,多中心研究

    doi:10.1164/rccm.201610-2158OC

    authors: Stanojevic S,Davis SD,Retsch-Bogart G,Webster H,Davis M,Johnson RC,Jensen R,Pizarro ME,Kane M,Clem CC,Schornick L,Subbarao P,Ratjen FA

    更新日期:2017-05-01 00:00:00

  • Partial inhibition of the early and late asthmatic response by a single dose of salmeterol.

    abstract::The long-acting beta 2-agonist salmeterol has been suggested to have other pharmacologic activities, that is, antiinflammatory capacities, in addition to its bronchodilator properties. We investigated the protective effect of 50 micrograms salmeterol in a placebo-controlled study on house dust mite-induced early- and ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章

    doi:10.1164/ajrccm.150.5.7952550

    authors: Weersink EJ,Aalbers R,Koëter GH,Kauffman HF,De Monchy JG,Postma DS

    更新日期:1994-11-01 00:00:00

  • Persistent airway inflammation but accommodated antioxidant and lung function responses after repeated daily exposure to nitrogen dioxide.

    abstract::Nitrogen dioxide (NO2) is a common indoor and outdoor air pollutant that may induce deterioration of respiratory health. In this study the effects of repeated daily exposure to NO2 on airway antioxidant status, inflammatory cell and mediator responses, and lung function were examined. Healthy nonsmoking subjects were ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章

    doi:10.1164/ajrccm.159.2.9711068

    authors: Blomberg A,Krishna MT,Helleday R,Söderberg M,Ledin MC,Kelly FJ,Frew AJ,Holgate ST,Sandström T

    更新日期:1999-02-01 00:00:00

  • Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary.

    abstract::This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructiv...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,实务指引

    doi:10.1164/rccm.201701-0218PP

    authors: Vogelmeier CF,Criner GJ,Martinez FJ,Anzueto A,Barnes PJ,Bourbeau J,Celli BR,Chen R,Decramer M,Fabbri LM,Frith P,Halpin DM,López Varela MV,Nishimura M,Roche N,Rodriguez-Roisin R,Sin DD,Singh D,Stockley R,Vestbo J,W

    更新日期:2017-03-01 00:00:00

  • Autologous transfusion of stored red blood cells increases pulmonary artery pressure.

    abstract:RATIONALE:Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction. OBJECTIVES:We hypothesized that transfu...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.1164/rccm.201405-0850OC

    authors: Berra L,Pinciroli R,Stowell CP,Wang L,Yu B,Fernandez BO,Feelisch M,Mietto C,Hod EA,Chipman D,Scherrer-Crosbie M,Bloch KD,Zapol WM

    更新日期:2014-10-01 00:00:00