title: Brain During Effort : Effects of Hypoxia With Respiratory Patients

acronym: NEUROX

summary:
Brain oxygenation is determined by the product of CaO2 and the cerebral blood flow (CBF), the modification of one or the other can affect the neuronal O2 availability.

Besides the effect of the PaO2, the CBF is also regulated by the PaCO2. During effort in state of hypoxia, the drop of the PaO2 associated to a potential decrease of the PaCO2 and therefore of the CBF, can create an important dizziness between the demand and the supply of cerebral O2.

It seems that hypoxia can trouble in a significant way the response of central neurons, just as the production of a motor cortex generated motor command.

Studies suggest that exercise in severe hypoxia condition can constitute a necessary threat for brain oxygenation and the motor command, with the consequence a decrease of the exercise performance.

This projects aim to study effects of hypoxia on the brain function for patients suffering from chronic respiratory disease. Neurophysiologic responses of the brain while resting or exercising, including drip and cerebral oxygenation, cortical excitation and motor command resulting for hypoxic subjects before and after a treatment to correct abnormalities of gaz in blood.

The study will use a multidisciplinary and supplementary methodological approach : the near-infrared spectroscopy (NIRS) to appreciate the drip and cerebral oxygenation, CBF, neurostimulation procedures and electromyography (EMG) to appreciate the cortical excitability, measure the level of central activation and motor command.

The goals of this study will be :

Measure the drip and cerebral oxygenation, the cortical excitability, mechanisms of voluntary activation and central fatigue to the effort for the chronic hypoxemic patient compared to healthy control subjects.
Analyse disruptions of locomotion parameters and posturographyc, in simple and double task, involving different levels of cerebral task.
Analyse acute effects of an improvement of arterial oxygenation for patients suffering from chronic obstructive pulmonary disease (COPD) on drip and cerebral oxygenation, cortical excitability, mechanisms of voluntary activation and central fatigue.
Evaluate effects of a treatment by continuous positive airway pressure (CPAP) for patients suffering from obstructive sleep apnea (OSA) with the same parameters.

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title: Organ Procurement : Usefulness of a Guide for Meeting With the Next of Kin

acronym: CANEVAS

summary: A dedicated guide for physicians and organ procurement nurses meeting with the next of kin could be associated with a reduction in organ donation refusal rate, and in anxiety of professionals involved in such meetings

study_start_date_type: Actual

status: Completed

study_completion_date_type: Actual

study_type: Observational

time_perspective: Prospective

enrollment_type: Actual

ipd_sharing: Undecided

lead_sponsor: Assistance Publique - Hôpitaux de Paris

lead_sponsor_type: academique

status_simplified: Completed


title: Improving Genetic Counseling for Patients With Spina Bifida Using Next Generation Sequencing

acronym: EXOSPINA

summary: The main objective is to improve genetic counseling in patients with Spina Bifida, by the characterization of variants in new genes using high throughput sequencing either on a panel of targeted genes or on exome in families.

time_perspective: Retrospective

lead_sponsor: Rennes University Hospital

location_facility: Centre hospitalier universitaire de RENNES

intervention_type: Genetic


title: Epidemiology of ST131 in Besançon University Hospital

summary: The sequence type 131 (ST131) is a predominant lineage among extraintestinal pathogenic Escherichia coli. It plays a major role in the worldwide dissemination of E. coli that produce extended-spectrum beta-lactamase (ESBL). The aim of this study was to describe the epidemiology of ESBL producing ST131clonal group in our university hospital. All patients with an infection due to ESBL E. coli will be prospectively included for a 2-year period. ST131 isolates will be identified and risk factors associated to ST131 will be determined in comparison to non-ST131 ESBL E. coli.

ReferenceType: background

ReferenceCitation: Nicolas-Chanoine MH, Bertrand X, Madec JY. Escherichia coli ST131, an intriguing clonal group. Clin Microbiol Rev. 2014 Jul;27(3):543-74. doi: 10.1128/CMR.00125-13. Review.

ReferenceCitation: Lafolie J, Nicolas-Chanoine MH, Grenouillet F, Hocquet D, Bertrand X. Prevalence of Escherichia coli sequence type 131 and its H30 subclone among E. coli isolates in a French hospital. Int J Antimicrob Agents. 2014 Nov;44(5):466-8. doi: 10.1016/j.ijantimicag.2014.07.016. Epub 2014 Sep 3.

ReferenceCitation: Lafolie J, Sauget M, Cabrolier N, Hocquet D, Bertrand X. Detection of Escherichia coli sequence type 131 by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: implications for infection control policies? J Hosp Infect. 2015 Jul;90(3):208-12. doi: 10.1016/j.jhin.2014.12.022. Epub 2015 Feb 28.

ReferenceCitation: Can F, Azap OK, Seref C, Ispir P, Arslan H, Ergonul O. Emerging Escherichia coli O25b/ST131 clone predicts treatment failure in urinary tract infections. Clin Infect Dis. 2015 Feb 15;60(4):523-7. doi: 10.1093/cid/ciu864. Epub 2014 Nov 6.

ipd_sharing: No

lead_sponsor: Centre Hospitalier Universitaire de Besancon

location_facility: Centre Hospitalier Régional Universitaire


title: Characterization of Endothelial Dysfunction as a Function of Hyperaemia of the Brachial Artery During Cardiac Surgery

acronym: GLYNO

summary: The glycocalyx is a layer of proteins and complex sugars covering the endothelium of vessels. Its role as capillary filtration control is important. In case of alteration of the glycocalyx, experimental models and some clinical studies show an increased capillary leak responsible for interstitial edema. The analysis of glycocalyx in routine care is important to guide volume expansion. Indeed, the literature provides evidence about the poor prognosis of excess water and its impact on organ. This analysis challenge is to justify filling solution of choice according to the characteristic of this capillary leakage.

status: Unknown status

study_completion_date_type: Anticipated

ReferenceCitation: Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. Erratum in: J Am Coll Cardiol 2002 Mar 20;39(6):1082.

ReferenceCitation: Becker BF, Jacob M, Leipert S, Salmon AH, Chappell D. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol. 2015 Sep;80(3):389-402. doi: 10.1111/bcp.12629. Epub 2015 May 22. Review.

ReferenceCitation: Chawla LS, Ince C, Chappell D, Gan TJ, Kellum JA, Mythen M, Shaw AD; ADQI XII Fluids Workgroup. Vascular content, tone, integrity, and haemodynamics for guiding fluid therapy: a conceptual approach. Br J Anaesth. 2014 Nov;113(5):748-55. doi: 10.1093/bja/aeu298. Epub 2014 Sep 17.

lead_sponsor: Centre Hospitalier Universitaire, Amiens

intervention_type: Biological

status_simplified: Unknown


title: Measurement of Antibodies in Adults With a History of Kawasaki Disease

acronym: KAWASAKI Ac

summary:
Kawasaki disease (KD) is an acute systemic vasculitic syndrome with coronary tropism. It has been reported worldwide, but it is ten times more common in Asian population. It is the second vasculitis of the child by its frequency after rheumatoid purpura. It occurs in 80% of cases between 1 and 5 years, with a maximal incidence around the age of 12 months.

KD is not well understood and the cause is yet unknown. It may be an autoimmune disorder. The problem affects the mucous membranes, lymph nodes, walls of the blood vessels, and the heart.The clinical picture of KD associate a persistent fever and an antipyretics resistance with mucocutaneous signs and bulky cervical lymphadenopathy usually unilateral.

There is currently no vaccine available against Kawasaki disease so it is extremely important to be able to recognize symptoms before they set in and become too severe.

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi. Acute CD occurs immediately after infection, may last up to a few weeks or months. Infection may be mild or asymptomatic. There may be fever or swelling around the site of inoculation, and acute infection may result in severe inflammation of the heart muscle. The notion that the pathology of CD has an autoimmune component was initially based on the finding of circulating antibodies binding heart tissue antigens in patients chronically infected with T. cruzi.

A recent study reports a possible antigen (non-cruzi-related antibody NCRA) mimicry characterized by a serological reactivity to a well-defined T. cruzi antigen in blood samples from individuals not exposed to the parasite. The measured seroprevalence of such cross-reactivity is in favor of a highly prevalent immunogen acquired in childhood.

There are similarities in mechanism of CD and KD: it could be interesting to explore the presence of NCRA in blood samples from adults with a history of KD.

The objective of the study is the measurement of the biomarker NCRA in serum in adults with a history of KD compare to a control population. This measurement and the prevalence may permit to associate the NCRA to a possible pathogenic agent.

lead_sponsor: Hospices Civils de Lyon

location_facility: Hôpital Louis Pradel - Service de Pharmacologie Clinique

intervention_type: Other


type: EudraCT Number

title: Transversal Monocentric Study of the Anatomophysiological Effect of Botulinum Toxin on the Spastic Muscle of Children With Cerebral Palsy

summary:
Cerebral palsy (CP) is a group of non-progressive motor dysfunction but often changing, secondary to injury or brain abnormalities that occur in early stages of development. In children with CP, the brain injury lead to a delayed motor development in the first weeks, associated with muscular spasticity. Drug treatments include oral treatments (baclofen and tizanidine) and injectable treatments like Botox (intramuscular injection) and neurolysis with alcohol or phenol (local injection into the nerve).

Regarding botulinum toxin, there is no study questioning its effectiveness. However, no publication on the pathophysiology of human muscle of the CP child after toxin injection was found. The action of the toxin on the neuromuscular junction (NMJ) and muscle structure is unknown in children with CP.

The primary objective of this study is to describe structural abnormalities of the CP child's muscle following multiple toxin injections in terms of NMJ fragmentation and axonal sprouting.

Secondary objectives:

To evaluate the relationship between:

The severity of the motor impairment and muscle structural abnormalities.
The clinical measure of spasticity and muscle structural abnormalities.
To compare the structure spastic muscles with toxin injections and spastic muscle without toxin injections

For muscles with multiple toxin injections, assessing the relationship between :

The number of toxin injections and muscle structural abnormalities.
The date of the first injection and muscle structural abnormalities.
The total dose of injected toxin in the muscle and its structural abnormalities.
The nature of the product injected in the muscle and its structural abnormalities.

This innovative study will improve the knowledge on the effects of long-term botulinum toxin injections on the muscle (and therefore its safety in usual care), on the spastic muscle NMJ of CP children, on the pathophysiology of the CP child's muscle.

All the visits all acts will be performed according to usual patient follow-up. Only a biopsy will be performed in addition, taken from an injected muscle during a planned operation. A biopsy may also be performed on a muscle without toxin injection if the act is made possible by the planned surgery. No biopsy will be made on a muscle that would not require surgery.

study_type: Interventional

primary_purpose: Basic Science

intervention_type: Procedure


title: Efficacy and Safety of Estracyt® in Metastatic Breast Cancer Hormonal Estrogen Receptor (HER 2) Negative, Hormone Receptor (HR) Positive.

acronym: BEST

summary: This study evaluates efficacy, safety and quality of life in patients affected by metastatic breast cancer RH+/ HER2- and treated by estramustine phosphate.

status: Withdrawn

design_allocation: Randomized

primary_purpose: Treatment

ipd_sharing: Yes

ipd_sharing_description: The Committee shall meet twice a year

intervention_type: Drug


title: Study on Fluids Associated to Lung Cancer, of the Ectopic Expression of Cancer Testis Gene and Mutation as Diagnostics and Prognosis Biomarkers

acronym: ECTOPIC/MUTAS

summary:
The diagnosis of lung cancer is the first cause of cancer deaths for man and woman. It requires invasive procedures (at least endoscopy, transthoracic puncture, or surgery).

This study is about the set up of an innovative test for lung cancer prognosis, based on biopsies and surgical material : LungCancerTest, with the creation of a start-up in progress.

The main goal of this study is to approve the diagnostic value of the molecular signature of the 26 genes (LungCancerTest) revealed in blood and respiratory fluids among patients with lung cancer.

design_allocation: Non-Randomized

primary_purpose: Diagnostic

ReferenceCitation: Toffart AC, Timsit JF, Couraud S, Merle P, Moro-Sibilot D, Perol M, Mastroianni B, Souquet PJ, Girard N, Jeannin G, Romand P, Chatellain P, Vesin A, Brambilla C, Brambilla E. Immunohistochemistry evaluation of biomarker expression in non-small cell lung cancer (Pharmacogenoscan study). Lung Cancer. 2014 Feb;83(2):182-8. doi: 10.1016/j.lungcan.2013.12.003. Epub 2013 Dec 21.

ReferenceCitation: Rousseaux S, Debernardi A, Jacquiau B, Vitte AL, Vesin A, Nagy-Mignotte H, Moro-Sibilot D, Brichon PY, Lantuejoul S, Hainaut P, Laffaire J, de Reyniès A, Beer DG, Timsit JF, Brambilla C, Brambilla E, Khochbin S. Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers. Sci Transl Med. 2013 May 22;5(186):186ra66. doi: 10.1126/scitranslmed.3005723.

ReferenceCitation: BRAMBILLA C., ROUSSEAUX S., DE BERNARDI A., JACQUIAU B., VITTE A.L., ARBIB F., LEMAITRE N., LANTUEJOUL S., MIGNOTTE H, MORO-SIBILOT D., TOFFART A.C., BRAMBILLA E., KOCHBIN S. A PCR-based test detecting ectopic expressions of placenta/germline genes can predict aggressive lung tumours. J. Thor. Oncol. • Volume 8, Supplement 2, November 2013 S1048

ReferenceCitation: Vignot S, Frampton GM, Soria JC, Yelensky R, Commo F, Brambilla C, Palmer G, Moro-Sibilot D, Ross JS, Cronin MT, André F, Stephens PJ, Lazar V, Miller VA, Brambilla E. Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer. J Clin Oncol. 2013 Jun 10;31(17):2167-72. doi: 10.1200/JCO.2012.47.7737. Epub 2013 Apr 29.

ReferenceCitation: PEIFER M, FERNÁNDEZ-CUESTA L, SOS ML, GEORGE J, SEIDEL D, KASPER LH, PLENKER D, LEENDERS F, SUN R, ZANDER T, MENON R, KOKER M, DAHMEN I, MÜLLER C, DI CERBO V, SCHILDHAUS HU, ALTMÜLLER J, BAESSMANN I, BECKER C, DE WILDE B, VANDESOMPELE J, BÖHM D, ANSÉN S, GABLER F, WILKENING I, HEYNCK S, HEUCKMANN JM, LU X, CARTER SL, CIBULSKIS K, BANERJI S, GETZ G, PARK KS, RAUH D, GRÜTTER C, FISCHER M, PASQUALUCCI L, WRIGHT G, WAINER Z, RUSSELL P, PETERSEN I, CHEN Y, STOELBEN E, LUDWIG C, SCHNABEL P, HOFFMANN H, MULEY T, BROCKMANN M, ENGEL-RIEDEL W, MUSCARELLA LA, FAZIO VM, GROEN H, TIMENS W, SIETSMA H, THUNNISSEN E, SMIT E, HEIDEMAN DA, SNIJDERS PJ, CAPPUZZO F, LIGORIO C, DAMIANI S, FIELD J, SOLBERG S, BRUSTUGUN OT, LUND-IVERSEN M, SÄNGER J, CLEMENT JH, SOLTERMANN A, MOCH H, WEDER W, SOLOMON B, SORIA JC, VALIDIRE P, BESSE B, BRAMBILLA E, BRAMBILLA C, LANTUEJOUL S, LORIMIER P, SCHNEIDER PM, HALLEK M, PAO W, MEYERSON M, SAGE J, SHENDURE J, SCHNEIDER R, BÜTTNER R, WOLF J, NÜRNBERG P, PERNER S, HEUKAMP LC, BRINDLE PK, HAAS S, THOMAS RK. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer.Nat Genet. 2012;44(10):1104-10

ReferenceCitation: Nagy-Mignotte H, Guillem P, Vignoud L, Coudurier M, Vesin A, Bonneterre V, Toffart AC, Sakhri L, Brambilla C, Brambilla E, Timsit JF, Moro-Sibilot D; Multidisciplinary Thoracic Oncology Group. Outcomes in recurrent small-cell lung cancer after one to four chemotherapy lines: a retrospective study of 300 patients. Lung Cancer. 2012 Oct;78(1):112-20. doi: 10.1016/j.lungcan.2012.06.006. Epub 2012 Jul 12.

ReferenceCitation: Lecourtois B, Jankowski A, Arbib F, Lantuejoul S, Brichon PY, Moro-Sibilot D, Brambilla C, Ferretti G. Endobronchial tumours in a campaign for early detection of bronchial cancer: Computed tomography versus endoscopy. Diagn Interv Imaging. 2012 Jul;93(7-8):604-11. doi: 10.1016/j.diii.2012.05.002. Epub 2012 Jul 6.

ReferenceCitation: Mortamais M, Chevrier C, Philippat C, Petit C, Calafat AM, Ye X, Silva MJ, Brambilla C, Eijkemans MJ, Charles MA, Cordier S, Slama R. Correcting for the influence of sampling conditions on biomarkers of exposure to phenols and phthalates: a 2-step standardization method based on regression residuals. Environ Health. 2012 Apr 26;11:29. doi: 10.1186/1476-069X-11-29.

ReferenceCitation: Brambilla C, Sánchez-Chardi A, Pérez-Trujillo M, Julián E, Luquin M. Cyclopropanation of α-mycolic acids is not required for cording in Mycobacterium brumae and Mycobacterium fallax. Microbiology (Reading). 2012 Jun;158(Pt 6):1615-1621. doi: 10.1099/mic.0.057919-0. Epub 2012 Apr 5.

ReferenceCitation: Han N, Dol Z, Vasieva O, Hyde R, Liloglou T, Raji O, Brambilla E, Brambilla C, Martinet Y, Sozzi G, Risch A, Montuenga LM; EUELC Consortium, Brass A, Field JK. Progressive lung cancer determined by expression profiling and transcriptional regulation. Int J Oncol. 2012 Jul;41(1):242-52. doi: 10.3892/ijo.2012.1421. Epub 2012 Mar 28.

ReferenceCitation: Pajares MJ, Agorreta J, Larrayoz M, Vesin A, Ezponda T, Zudaire I, Torre W, Lozano MD, Brambilla E, Brambilla C, Wistuba II, Behrens C, Timsit JF, Pio R, Field JK, Montuenga LM. Expression of tumor-derived vascular endothelial growth factor and its receptors is associated with outcome in early squamous cell carcinoma of the lung. J Clin Oncol. 2012 Apr 1;30(10):1129-36. doi: 10.1200/JCO.2011.37.4231. Epub 2012 Feb 21.

ReferenceCitation: Hammerman PS, Sos ML, Ramos AH, Xu C, Dutt A, Zhou W, Brace LE, Woods BA, Lin W, Zhang J, Deng X, Lim SM, Heynck S, Peifer M, Simard JR, Lawrence MS, Onofrio RC, Salvesen HB, Seidel D, Zander T, Heuckmann JM, Soltermann A, Moch H, Koker M, Leenders F, Gabler F, Querings S, Ansén S, Brambilla E, Brambilla C, Lorimier P, Brustugun OT, Helland A, Petersen I, Clement JH, Groen H, Timens W, Sietsma H, Stoelben E, Wolf J, Beer DG, Tsao MS, Hanna M, Hatton C, Eck MJ, Janne PA, Johnson BE, Winckler W, Greulich H, Bass AJ, Cho J, Rauh D, Gray NS, Wong KK, Haura EB, Thomas RK, Meyerson M. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2011 Jun;1(1):78-89. doi: 10.1158/2159-8274.CD-11-0005.

ReferenceCitation: Scoccianti C, Vesin A, Martel G, Olivier M, Brambilla E, Timsit JF, Tavecchio L, Brambilla C, Field JK, Hainaut P; European Early Lung Cancer Consortium. Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer: the EUELC cohort. Eur Respir J. 2012 Jul;40(1):177-84. doi: 10.1183/09031936.00097311. Epub 2012 Jan 20.

ReferenceCitation: Philippat C, Mortamais M, Chevrier C, Petit C, Calafat AM, Ye X, Silva MJ, Brambilla C, Pin I, Charles MA, Cordier S, Slama R. Exposure to phthalates and phenols during pregnancy and offspring size at birth. Environ Health Perspect. 2012 Mar;120(3):464-70. doi: 10.1289/ehp.1103634. Epub 2011 Sep 7. Erratum in: Environ Health Perspect. 2012 Mar;120(3):470.

ReferenceCitation: Thunnissen FB, Prinsen C, Hol B, Van der Drift M, Vesin A, Brambilla C, Montuenga L, Field JK; EUELC consortium. Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development. Lung Cancer. 2012 Feb;75(2):156-60. doi: 10.1016/j.lungcan.2011.07.013. Epub 2011 Aug 11.

ReferenceCitation: Nagy-Mignotte H, Guillem P, Vesin A, Toffart AC, Colonna M, Bonneterre V, Brichon PY, Brambilla C, Brambilla E, Lantuejoul S, Timsit JF, Moro-Sibilot D; Multidisciplinary Thoracic Oncology Group at Grenoble University Hospital. Primary lung adenocarcinoma: characteristics by smoking habit and sex. Eur Respir J. 2011 Dec;38(6):1412-9. doi: 10.1183/09031936.00191710. Epub 2011 Aug 4.

ReferenceCitation: Bousquet J, Anto JM, Sterk PJ, Adcock IM, Chung KF, Roca J, Agusti A, Brightling C, Cambon-Thomsen A, Cesario A, Abdelhak S, Antonarakis SE, Avignon A, Ballabio A, Baraldi E, Baranov A, Bieber T, Bockaert J, Brahmachari S, Brambilla C, Bringer J, Dauzat M, Ernberg I, Fabbri L, Froguel P, Galas D, Gojobori T, Hunter P, Jorgensen C, Kauffmann F, Kourilsky P, Kowalski ML, Lancet D, Pen CL, Mallet J, Mayosi B, Mercier J, Metspalu A, Nadeau JH, Ninot G, Noble D, Oztürk M, Palkonen S, Préfaut C, Rabe K, Renard E, Roberts RG, Samolinski B, Schünemann HJ, Simon HU, Soares MB, Superti-Furga G, Tegner J, Verjovski-Almeida S, Wellstead P, Wolkenhauer O, Wouters E, Balling R, Brookes AJ, Charron D, Pison C, Chen Z, Hood L, Auffray C. Systems medicine and integrated care to combat chronic noncommunicable diseases. Genome Med. 2011 Jul 6;3(7):43. doi: 10.1186/gm259.

ReferenceCitation: Edmond V, Brambilla C, Brambilla E, Gazzeri S, Eymin B. SRSF2 is required for sodium butyrate-mediated p21(WAF1) induction and premature senescence in human lung carcinoma cell lines. Cell Cycle. 2011 Jun 15;10(12):1968-77. Epub 2011 Jun 15.

ReferenceCitation: Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011 Feb;6(2):244-85. doi: 10.1097/JTO.0b013e318206a221. Review.

ReferenceCitation: Garelli M, Righini C, Faure C, Jankowski A, Brambilla C, Ferretti GR. Imaging of a case of extramedullary solitary plasmacytoma of the trachea. Case Rep Radiol. 2011;2011:687203. doi: 10.1155/2011/687203. Epub 2011 Sep 22.

ReferenceCitation: Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schöttle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansén S, Rauh D, Baessmann I, Altmüller J, Wainer Z, Conron M, Wright G, Russell P, Solomon B, Brambilla E, Brambilla C, Lorimier P, Sollberg S, Brustugun OT, Engel-Riedel W, Ludwig C, Petersen I, Sänger J, Clement J, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman D, Cappuzzo F, Ligorio C, Damiani S, Hallek M, Beroukhim R, Pao W, Klebl B, Baumann M, Buettner R, Ernestus K, Stoelben E, Wolf J, Nürnberg P, Perner S, Thomas RK. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med. 2010 Dec 15;2(62):62ra93. doi: 10.1126/scitranslmed.3001451. Erratum in: Sci Transl Med. 2011 Jan 19;3(66):66er2. Sci Transl Med. 2012 Apr 18;4(130):130er2.

ReferenceCitation: Edmond V, Moysan E, Khochbin S, Matthias P, Brambilla C, Brambilla E, Gazzeri S, Eymin B. Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin. EMBO J. 2011 Feb 2;30(3):510-23. doi: 10.1038/emboj.2010.333. Epub 2010 Dec 14.

ReferenceCitation: Larrieu D, Ythier D, Brambilla C, Pedeux R. ING2 controls the G1 to S-phase transition by regulating p21 expression. Cell Cycle. 2010 Oct 1;9(19):3984-90. Epub 2010 Oct 1.

ReferenceCitation: Ythier D, Larrieu D, Binet R, Binda O, Brambilla C, Gazzeri S, Pedeux R. Sumoylation of ING2 regulates the transcription mediated by Sin3A. Oncogene. 2010 Nov 4;29(44):5946-56. doi: 10.1038/onc.2010.325. Epub 2010 Aug 2.

ReferenceCitation: Bryant CM, Albertus DL, Kim S, Chen G, Brambilla C, Guedj M, Arima C, Travis WD, Yatabe Y, Takahashi T, Brambilla E, Beer DG. Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study. PLoS One. 2010 Jul 22;5(7):e11712. doi: 10.1371/journal.pone.0011712.

ReferenceCitation: Merdzhanova G, Gout S, Keramidas M, Edmond V, Coll JL, Brambilla C, Brambilla E, Gazzeri S, Eymin B. The transcription factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth factor-A to inhibit neovascularization in vivo. Oncogene. 2010 Sep 30;29(39):5392-403. doi: 10.1038/onc.2010.281. Epub 2010 Jul 19.

ReferenceCitation: Van den Berg RM, Brokx H, Vesin A, Field JK, Brambilla C, Meijer CJ, Sutedja GT, Heideman DA, Postmus PE, Smit EF, Snijders PJ. Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project. Int J Oncol. 2010 Aug;37(2):455-61.

ReferenceCitation: Caron C, Lestrat C, Marsal S, Escoffier E, Curtet S, Virolle V, Barbry P, Debernardi A, Brambilla C, Brambilla E, Rousseaux S, Khochbin S. Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers. Oncogene. 2010 Sep 16;29(37):5171-81. doi: 10.1038/onc.2010.259. Epub 2010 Jun 28.

ReferenceCitation: Lantuejoul S, Raynaud C, Salameire D, Gazzeri S, Moro-Sibilot D, Soria JC, Brambilla C, Brambilla E. Telomere maintenance and DNA damage responses during lung carcinogenesis. Clin Cancer Res. 2010 Jun 1;16(11):2979-88. doi: 10.1158/1078-0432.CCR-10-0142. Epub 2010 Apr 19.

ReferenceCitation: Ythier D, Brambilla E, Binet R, Nissou D, Vesin A, de Fraipont F, Moro-Sibilot D, Lantuejoul S, Brambilla C, Gazzeri S, Pedeux R. Expression of candidate tumor suppressor gene ING2 is lost in non-small cell lung carcinoma. Lung Cancer. 2010 Aug;69(2):180-6. doi: 10.1016/j.lungcan.2009.11.006. Epub 2009 Dec 4.

ReferenceCitation: Wattrelot P, Brion JP, Labarère J, Billette de Villemeur A, Girard-Blanc MF, Stahl JP, Brambilla C. [Vaccination practices following the end of compulsory BCG vaccination. A cross-sectional survey of general practitioners and pediatricians]. Arch Pediatr. 2010 Feb;17(2):118-24. doi: 10.1016/j.arcped.2009.10.025. Epub 2009 Dec 2. French.

ReferenceCitation: Binet R, Ythier D, Robles AI, Collado M, Larrieu D, Fonti C, Brambilla E, Brambilla C, Serrano M, Harris CC, Pedeux R. WNT16B is a new marker of cellular senescence that regulates p53 activity and the phosphoinositide 3-kinase/AKT pathway. Cancer Res. 2009 Dec 15;69(24):9183-91. doi: 10.1158/0008-5472.CAN-09-1016.

ReferenceCitation: Field JK, Liloglou T, Niaz A, Bryan J, Gosney JR, Giles T, Brambilla C, Brambilla E, Vesin A, Timsit JF, Hainaut P, Martinet Y, Vignaud JM, Thunnissen FB, Prinsen C, Snijders PJ, Smit EF, Sozzi G, Roz L, Risch A, Becker HD, Elborn JS, Magee ND, Montuenga LM, Pajares MJ, Lozano MD, O'Byrne KJ, Harrison DJ, Niklinski J, Cassidy A; EUELC Collaborators. EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration. Eur Respir J. 2009 Dec;34(6):1477-86. doi: 10.1183/09031936.00077809.

ReferenceCitation: Felix L, Serra-Tosio G, Lantuejoul S, Timsit JF, Moro-Sibilot D, Brambilla C, Ferretti GR. CT characteristics of resolving ground-glass opacities in a lung cancer screening programme. Eur J Radiol. 2011 Mar;77(3):410-6. doi: 10.1016/j.ejrad.2009.09.008. Epub 2009 Oct 4.

ReferenceCitation: Larrieu D, Ythier D, Binet R, Brambilla C, Brambilla E, Sengupta S, Pedeux R. ING2 controls the progression of DNA replication forks to maintain genome stability. EMBO Rep. 2009 Oct;10(10):1168-74. doi: 10.1038/embor.2009.180. Epub 2009 Sep 4.

ReferenceCitation: Cassidy A, Balsan J, Vesin A, Wu X, Liloglou T, Brambilla C, Timsit JF, Field JK; EUELC Consortium. Cancer diagnosis in first-degree relatives and non-small cell lung cancer risk: results from a multi-centre case-control study in Europe. Eur J Cancer. 2009 Nov;45(17):3047-53. doi: 10.1016/j.ejca.2009.05.006. Epub 2009 May 29.

ReferenceCitation: Delloye-Bourgeois C, Brambilla E, Coissieux MM, Guenebeaud C, Pedeux R, Firlej V, Cabon F, Brambilla C, Mehlen P, Bernet A. Interference with netrin-1 and tumor cell death in non-small cell lung cancer. J Natl Cancer Inst. 2009 Feb 18;101(4):237-47. doi: 10.1093/jnci/djn491. Epub 2009 Feb 10.

ReferenceCitation: Brambilla C. From surgical to molecular scalpel: ERJ lung cancer series for 2009. Eur Respir J. 2009 Jan;33(1):9-10.

ReferenceCitation: Verri C, Roz L, Conte D, Liloglou T, Livio A, Vesin A, Fabbri A, Andriani F, Brambilla C, Tavecchio L, Calarco G, Calabrò E, Mancini A, Tosi D, Bossi P, Field JK, Brambilla E, Sozzi G; EUELC Consortium. Fragile histidine triad gene inactivation in lung cancer: the European Early Lung Cancer project. Am J Respir Crit Care Med. 2009 Mar 1;179(5):396-401. doi: 10.1164/rccm.200807-1153OC. Epub 2008 Dec 18.

ReferenceCitation: Van Den Broeck A, Brambilla E, Moro-Sibilot D, Lantuejoul S, Brambilla C, Eymin B, Gazzeri S. Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin Cancer Res. 2008 Nov 15;14(22):7237-45. doi: 10.1158/1078-0432.CCR-08-0869. Epub 2008 Oct 30. Erratum in: Clin Cancer Res. 2020 Jun 1;26(11):2767. Clin Cancer Res. 2020 Jun 1;26(11):2768.

ReferenceCitation: Merdzhanova G, Edmond V, De Seranno S, Van den Broeck A, Corcos L, Brambilla C, Brambilla E, Gazzeri S, Eymin B. E2F1 controls alternative splicing pattern of genes involved in apoptosis through upregulation of the splicing factor SC35. Cell Death Differ. 2008 Dec;15(12):1815-23. doi: 10.1038/cdd.2008.135. Epub 2008 Sep 19.

ReferenceCitation: Ythier D, Larrieu D, Brambilla C, Brambilla E, Pedeux R. The new tumor suppressor genes ING: genomic structure and status in cancer. Int J Cancer. 2008 Oct 1;123(7):1483-90. doi: 10.1002/ijc.23790. Review.

ReferenceCitation: Bertrand D, Righini C, Ferretti G, Brambilla C, Moro-Sibilot D. [Early diagnosis of bronchial carcinoma after head and neck cancer]. Rev Mal Respir. 2008 May;25(5):559-68. French.

ReferenceCitation: Ferretti GR, Jankowski A, Rodière M, Brichon PY, Brambilla C, Lantuejoul S. CT-guided biopsy of nonresolving focal air space consolidation. J Thorac Imaging. 2008 Feb;23(1):7-12. doi: 10.1097/RTI.0b013e3181453e04.

ReferenceCitation: Brambilla C, Colonna M. Cannabis: the next villain on the lung cancer battlefield? Eur Respir J. 2008 Feb;31(2):227-8. doi: 10.1183/09031936.00157607.

lead_sponsor: University Hospital, Grenoble


title: Retrospective Study to Estimate Screening of the Type 2 Diabetes of Women Who Had Childbirth in the Hospital Center Rene Dubos and Having Gestational Diabetes

summary: Retrospective study to estimate screening of the type 2 diabetes of women who had childbirth in the Hospital center Rene Dubos and having gestational diabetes.

lead_sponsor: Centre Hospitalier René Dubos


title: A Double-Blind, Placebo-Controlled Single Dose Escalating Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP2151 in Healthy Male Subjects, Followed by an Open, Two-Period Crossover Study to Assess the Effect of Fed Conditions on the Safety, Tolerability and Pharmacokinetics of ASP2151

summary:
The objective of this study is to evaluate the safety and tolerability of single rising doses of ASP2151 under fasted condition in healthy male subjects.

The study will also evaluate the pharmacokinetics (PK) of a single dose of ASP2151 under fasted versus fed conditions in healthy male subjects.

ReferenceType: derived

ReferenceCitation: Kusawake T, Keirns JJ, Kowalski D, den Adel M, Groenendaal-van de Meent D, Takada A, Ohtsu Y, Katashima M. Pharmacokinetics and Safety of Amenamevir in Healthy Subjects: Analysis of Four Randomized Phase 1 Studies. Adv Ther. 2017 Dec;34(12):2625-2637. doi: 10.1007/s12325-017-0642-4. Epub 2017 Nov 13.

lead_sponsor: Astellas Pharma Europe Ltd.

lead_sponsor_type: industriel


title: Does Micro-albuminuria is a Predictive Factor for Cognitive Impairment in Persons Living With HIV (PLHIV) Who Achieve cART-sustained Immunovirological Control ?

acronym: ALCOVE

summary: Chronic kidney disease (CKD), frequent in PLHIV, is a risk factor for cognitive impairment. Micro-albuminuria is an early manifestation of CKD and a marker of vascular risk, notably affecting the small vessels. In the older general population microalbuminuria is associated with greater annual cognitive decline and has been proposed as an easily and inexpensive measured marker predicting future cognitive function decline. Ageing of the PLH leads to an increase of cognitive disorders and chronic renal failure incidence and could imply a common underlying mechanism affecting the renal and cerebral microvasculature. In this setting the investigators undertake this prospective, cross-sectional, case-control study to determine whether the presence of a microalbuminuria at least 5 years ago in PLHs with sustained good combination antiretroviral therapy (cART)-controlled immunovirological parameters could be a marker predicting future cognitive impairment. They chose PLHs infected for at least 5 years and with cART-sustained immunovirological control for at least 1 year.

lead_sponsor: Fondation Ophtalmologique Adolphe de Rothschild

intervention_type: Behavioral


title: Risk-stratified Randomized Controlled Trial in Paediatric Crohn Disease:Methotrexate vs Azathioprine or Adalimumab for Maintaining Remission in Patients at Low or High Risk for Aggressive Disease Course, respectively-a Treatment Strategy

acronym: RCT

summary:
The purpose of this study is to compare the effectiveness of weekly subcutaneously administered Methotrexate for maintaining relapse-free sustained steroid/Enteral Nutrition -free 1-year remission compared with:

daily oral Azathioprine / 6 mercaptopurine in low risk paediatric Crohn's disease
subcutaneously administered adalimumab in high risk paediatric Crohn's disease

enrollment_type: Anticipated

ReferenceCitation: Pearson DC, May GR, Fick G, Sutherland LR. Azathioprine for maintaining remission of Crohn's disease. Cochrane Database Syst Rev. 2000;(2):CD000067. Review. Update in: Cochrane Database Syst Rev. 2009;(1):CD000067.

ReferenceCitation: Faubion WA Jr, Bousvaros A. Medical therapy for refractory pediatric Crohn's disease. Clin Gastroenterol Hepatol. 2006 Oct;4(10):1199-213. Epub 2006 Jul 26. Review.

ReferenceCitation: Candy S, Wright J, Gerber M, Adams G, Gerig M, Goodman R. A controlled double blind study of azathioprine in the management of Crohn's disease. Gut. 1995 Nov;37(5):674-8.

ReferenceCitation: Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology. 2000 Oct;119(4):895-902.

ReferenceCitation: D'Haens G, Geboes K, Rutgeerts P. Endoscopic and histologic healing of Crohn's (ileo-) colitis with azathioprine. Gastrointest Endosc. 1999 Nov;50(5):667-71.

ReferenceCitation: Chatu S, Subramanian V, Saxena S, Pollok RC. The role of thiopurines in reducing the need for surgical resection in Crohn's disease: a systematic review and meta-analysis. Am J Gastroenterol. 2014 Jan;109(1):23-34; quiz 35. doi: 10.1038/ajg.2013.402. Epub 2013 Dec 10.

ReferenceCitation: Panés J, López-Sanromán A, Bermejo F, García-Sánchez V, Esteve M, Torres Y, Domènech E, Piqueras M, Gomez-García M, Gutiérrez A, Taxonera C, Sans M; AZTEC Study Group. Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn's disease. Gastroenterology. 2013 Oct;145(4):766-74.e1. doi: 10.1053/j.gastro.2013.06.009. Epub 2013 Jun 13.

ReferenceCitation: Cosnes J, Bourrier A, Laharie D, Nahon S, Bouhnik Y, Carbonnel F, Allez M, Dupas JL, Reimund JM, Savoye G, Jouet P, Moreau J, Mary JY, Colombel JF; Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial. Gastroenterology. 2013 Oct;145(4):758-65.e2; quiz e14-5. doi: 10.1053/j.gastro.2013.04.048. Epub 2013 Apr 30.

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ReferenceCitation: Holtmann MH, Krummenauer F, Claas C, Kremeyer K, Lorenz D, Rainer O, Vogel I, Böcker U, Böhm S, Büning C, Duchmann R, Gerken G, Herfarth H, Lügering N, Kruis W, Reinshagen M, Schmidt J, Stallmach A, Stein J, Sturm A, Galle PR, Hommes DW, D'Haens G, Rutgeerts P, Neurath MF. Long-term effectiveness of azathioprine in IBD beyond 4 years: a European multicenter study in 1176 patients. Dig Dis Sci. 2006 Sep;51(9):1516-24. Epub 2006 Aug 22.

ReferenceCitation: Lémann M, Mary JY, Colombel JF, Duclos B, Soule JC, Lerebours E, Modigliani R, Bouhnik Y; Groupe D'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif. A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine. Gastroenterology. 2005 Jun;128(7):1812-8.

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ReferenceCitation: Oren R, Moshkowitz M, Odes S, Becker S, Keter D, Pomeranz I, Shirin H, Reisfeld I, Broide E, Lavy A, Fich A, Eliakim R, Patz J, Villa Y, Arber N, Gilat T. Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial. Am J Gastroenterol. 1997 Dec;92(12):2203-9. Erratum in: Am J Gastroenterol. 2015 Apr;110(4):608. Shirin, C [corrected to Shirin, H].

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ReferenceCitation: Uhlen S, Belbouab R, Narebski K, Goulet O, Schmitz J, Cézard JP, Turck D, Ruemmele FM. Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study. Inflamm Bowel Dis. 2006 Nov;12(11):1053-7.

ReferenceCitation: Turner D, Grossman AB, Rosh J, Kugathasan S, Gilman AR, Baldassano R, Griffiths AM. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn's disease. Am J Gastroenterol. 2007 Dec;102(12):2804-12; quiz 2803, 2813.

ReferenceCitation: Hyams J, Crandall W, Kugathasan S, Griffiths A, Olson A, Johanns J, Liu G, Travers S, Heuschkel R, Markowitz J, Cohen S, Winter H, Veereman-Wauters G, Ferry G, Baldassano R; REACH Study Group. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology. 2007 Mar;132(3):863-73; quiz 1165-6. Epub 2006 Dec 3.

ReferenceCitation: Hyams JS, Griffiths A, Markowitz J, Baldassano RN, Faubion WA Jr, Colletti RB, Dubinsky M, Kierkus J, Rosh J, Wang Y, Huang B, Bittle B, Marshall M, Lazar A. Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children. Gastroenterology. 2012 Aug;143(2):365-74.e2. doi: 10.1053/j.gastro.2012.04.046. Epub 2012 May 2.

ReferenceCitation: D'Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van De Mierop FJ, Coche JR, van der Woude J, Ochsenkühn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008 Feb 23;371(9613):660-667. doi: 10.1016/S0140-6736(08)60304-9.

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ReferenceCitation: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Colitis Foundation of America, Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, Higuchi LM, Hyams JS, Kirschner BS, Kugathasan S, Baldassano RN, Russo PA. Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America. J Pediatr Gastroenterol Nutr. 2007 May;44(5):653-74.

ReferenceCitation: Winther KV, Føgh P, Thomsen OØ, Brynskov J. Inflammatory bowel disease (ulcerative colitis and Crohn's disease): diagnostic criteria and differential diagnosis. Drugs Today (Barc). 1998 Nov;34(11):935-42.

ReferenceCitation: Rosh JR. Methotrexate. In: Mamula P, Baldassano RN, Markowitz JE, editors. Pediatric inflammatory bowel disease2007. p. In press.

ReferenceCitation: Ruemmele FM, Veres G, Kolho KL, Griffiths A, Levine A, Escher JC, Amil Dias J, Barabino A, Braegger CP, Bronsky J, Buderus S, Martín-de-Carpi J, De Ridder L, Fagerberg UL, Hugot JP, Kierkus J, Kolacek S, Koletzko S, Lionetti P, Miele E, Navas López VM, Paerregaard A, Russell RK, Serban DE, Shaoul R, Van Rheenen P, Veereman G, Weiss B, Wilson D, Dignass A, Eliakim A, Winter H, Turner D; European Crohn's and Colitis Organisation; European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. J Crohns Colitis. 2014 Oct;8(10):1179-207. doi: 10.1016/j.crohns.2014.04.005. Epub 2014 Jun 6.

ReferenceCitation: Frøslie KF, Jahnsen J, Moum BA, Vatn MH; IBSEN Group. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007 Aug;133(2):412-22. Epub 2007 Jun 2.

ReferenceCitation: Vernier-Massouille G, Balde M, Salleron J, Turck D, Dupas JL, Mouterde O, Merle V, Salomez JL, Branche J, Marti R, Lerebours E, Cortot A, Gower-Rousseau C, Colombel JF. Natural history of pediatric Crohn's disease: a population-based cohort study. Gastroenterology. 2008 Oct;135(4):1106-13. doi: 10.1053/j.gastro.2008.06.079. Epub 2008 Jul 3.

ReferenceCitation: Van Limbergen J, Russell RK, Drummond HE, Aldhous MC, Round NK, Nimmo ER, Smith L, Gillett PM, McGrogan P, Weaver LT, Bisset WM, Mahdi G, Arnott ID, Satsangi J, Wilson DC. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008 Oct;135(4):1114-22. doi: 10.1053/j.gastro.2008.06.081. Epub 2008 Jul 3.

ReferenceCitation: Pigneur B, Escher J, Elawad M, Lima R, Buderus S, Kierkus J, Guariso G, Canioni D, Lambot K, Talbotec C, Shah N, Begue B, Rieux-Laucat F, Goulet O, Cerf-Bensussan N, Neven B, Ruemmele FM. Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group. Inflamm Bowel Dis. 2013 Dec;19(13):2820-8. doi: 10.1097/01.MIB.0000435439.22484.d3.

ReferenceCitation: Pigneur B, Seksik P, Viola S, Viala J, Beaugerie L, Girardet JP, Ruemmele FM, Cosnes J. Natural history of Crohn's disease: comparison between childhood- and adult-onset disease. Inflamm Bowel Dis. 2010 Jun;16(6):953-61. doi: 10.1002/ibd.21152.

ReferenceCitation: Ruemmele FM, Lachaux A, Cézard JP, Morali A, Maurage C, Giniès JL, Viola S, Goulet O, Lamireau T, Scaillon M, Breton A, Sarles J; Groupe Francophone d'Hépatologie, Gastroentérologie et Nutrition Pédiatrique. Efficacy of infliximab in pediatric Crohn's disease: a randomized multicenter open-label trial comparing scheduled to on demand maintenance therapy. Inflamm Bowel Dis. 2009 Mar;15(3):388-94. doi: 10.1002/ibd.20788.

ReferenceCitation: Sharma S, Eckert D, Hyams JS, Mensing S, Thakkar RB, Robinson AM, Rosh JR, Ruemmele FM, Awni WM. Pharmacokinetics and exposure-efficacy relationship of adalimumab in pediatric patients with moderate to severe Crohn's disease: results from a randomized, multicenter, phase-3 study. Inflamm Bowel Dis. 2015 Apr;21(4):783-92. doi: 10.1097/MIB.0000000000000327.

ReferenceCitation: Khanna R, Bressler B, Levesque BG, Zou G, Stitt LW, Greenberg GR, Panaccione R, Bitton A, Paré P, Vermeire S, D'Haens G, MacIntosh D, Sandborn WJ, Donner A, Vandervoort MK, Morris JC, Feagan BG; REACT Study Investigators. Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial. Lancet. 2015 Nov 7;386(10006):1825-34. doi: 10.1016/S0140-6736(15)00068-9. Epub 2015 Sep 3.

ReferenceCitation: Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P; SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr 15;362(15):1383-95. doi: 10.1056/NEJMoa0904492.

ReferenceCitation: Torres J, Caprioli F, Katsanos KH, Lobatón T, Micic D, Zerôncio M, Van Assche G, Lee JC, Lindsay JO, Rubin DT, Panaccione R, Colombel JF. Predicting Outcomes to Optimize Disease Management in Inflammatory Bowel Diseases. J Crohns Colitis. 2016 Dec;10(12):1385-1394. Epub 2016 Jun 9. Erratum in: J Crohns Colitis. 2016 Dec;10 (12 ):1457.

ReferenceCitation: Neyt M, Christiaens A, Aloi M, de Ridder L, Croft NM, Koletzko S, Levine A, Turner D, Russell RK, Ruemmele FM, Veereman G. Identifying Health Economic Considerations to Include in the Research Protocol of a Randomized Controlled Trial (the REDUCE-RISK Trial): Systematic Literature Review and Assessment. JMIR Form Res. 2021 Jan 25;5(1):e13888. doi: 10.2196/13888. Review.

ReferenceCitation: Harris RE, Aloi M, de Ridder L, Croft NM, Koletzko S, Levine A, Turner D, Veereman G, Neyt M, Bigot L, Ruemmele FM, Russell RK; PIBD SETQuality consortium and PIBDnet. Protocol for a multinational risk-stratified randomised controlled trial in paediatric Crohn's disease: methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or high risk for aggressive disease course. BMJ Open. 2020 Jul 1;10(7):e034892. doi: 10.1136/bmjopen-2019-034892.

lead_sponsor: PIBD-Net

location_facility: Hôpital Necker -Enfants Malades (Service de gastro-enterologie)


title: Assessment of a Tool for Decision Making in Case of Worsening Condition of Cancer Patients

acronym: CBP-Aggrav

summary: Observational two year study to evaluate the utility of a decision-support sheet on how to proceed in case of aggravation of a patient's condition with advanced disease.

ReferenceCitation: Toffart AC, Sakhri L, Girard N, Couraud S, Merle P, Fournel P, Perol M, Souquet PJ, Timsit JF, Moro-Sibilot D. [Assessment of a tool for decision making in case of worsening condition of cancer patients]. Rev Mal Respir. 2015 Jan;32(1):66-72. doi: 10.1016/j.rmr.2014.02.006. Epub 2014 Mar 20. French.

ReferenceCitation: Toffart AC, Pizarro CA, Schwebel C, Sakhri L, Minet C, Duruisseaux M, Azoulay E, Moro-Sibilot D, Timsit JF. Selection criteria for intensive care unit referral of lung cancer patients: a pilot study. Eur Respir J. 2015 Feb;45(2):491-500. doi: 10.1183/09031936.00118114. Epub 2014 Oct 16.

ReferenceCitation: Detering KM, Hancock AD, Reade MC, Silvester W. The impact of advance care planning on end of life care in elderly patients: randomised controlled trial. BMJ. 2010 Mar 23;340:c1345. doi: 10.1136/bmj.c1345.

ReferenceCitation: Garrouste-Orgeas M, Tabah A, Vesin A, Philippart F, Kpodji A, Bruel C, Grégoire C, Max A, Timsit JF, Misset B. The ETHICA study (part II): simulation study of determinants and variability of ICU physician decisions in patients aged 80 or over. Intensive Care Med. 2013 Sep;39(9):1574-83. doi: 10.1007/s00134-013-2977-x. Epub 2013 Jun 14.

ReferenceCitation: Denis N, Timsit JF, Giaj Levra M, Sakhri L, Duruisseaux M, Schwebel C, Merle P, Pinsolle J, Ferrer L, Moro-Sibilot D, Toffart AC. Impact of systematic advanced care planning in lung cancer patients: A prospective study. Respir Med Res. 2020 Mar;77:11-17. doi: 10.1016/j.resmer.2019.09.003. Epub 2019 Oct 28.


title: Etude de Concordance Entre la Technique OSNA et Les Techniques Classiques Pour la Recherche de métastases Ganglionnaires Des Cancers Des VADS

acronym: OSNA-ORL

summary: The investigators main objective is to show that OSNA technique is as accurate as pathological analysis (frozen section / HE staining and immunochemistry) to detect occult lymph node metastasis (micro and macrometastasis).

ReferenceCitation: Peigné L, Godey F, Le Gallo M, Le Gall F, Fautrel A, Morcet J, Jégoux F. One-step nucleic acid amplification for detecting lymph node metastasis of head and neck squamous cell carcinoma. Oral Oncol. 2020 Mar;102:104553. doi: 10.1016/j.oraloncology.2019.104553. Epub 2020 Jan 28.

location_facility: Centre hospitalier universitaire de Rennes


title: Urinary Markers of Detrusor Overactivity in Spina Bifida Patients

acronym: BUHD-SPINA

summary: The purpose of this study is to assess diagnostic performance of urinary markers of detrusor overactivity (Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), adenosine triphosphate (ATP), Prostaglandine E2) in detected high pressure bladder un spina bifida patients.


title: Assessment of the Prevalence of Lysosomal Acid Lipase Deficiency in Patients Waiting for a Liver Transplant.

summary:
Lysosomal Acid Lipase (LAL) deficiency is a rare, autosomal recessive storage disease linked to decrease enzymatic activity of LAL, responsible for intracellular accumulation of cholesterol esters and triglycerides.

The accumulation of lipid is in hepatocytes, Kupffer cells and macrophages leading to a fatty liver, hepatic fibrosis that can evolve up to cirrhosis.

LAL deficiency is responsible for significant morbidity and early mortality in children, adolescents and adults in connection with a multi visceral disease reaching the liver, gastrointestinal tract and the vascular endothelium. The disease is caused by homozygous or heterozygous mutations in the gene (LIPA chromosome 10q23.2-23.3) which is responsible for the synthesis of the LAL.

The disease can be diagnosed by enzymatic analysis using few drops of blood absorbed onto blotting paper .

Patients with this deficiency LAL, have no or reduced activity of this enzyme. Because of its rarity, the deficit in LAL is under diagnosed or is diagnosed in patients with liver biological disturbances and / or lipid profile disturbances, steatohepatitis-hepatitis (NASH), the steatosis (NAFLD), the cryptogenic cirrhosis or Wilson disease.

Inclusion period of 12 to 18 months (100 patients).

location_facility: Hépato-Gastro-Entérologie, Hôpital de la Croix Rousse, 103 gde rue de la Croix Rousse


title: Screening for Frailty in Elderly Subjects Living at Home : Validation of the Modified Short Emergency Geriatric Assessment (SEGAm) Instrument

acronym: SEGAm

summary:
"Many tools to evaluate frailty have been developed. However, at the time our study was designed, none of these instruments had been validated in terms of psychometric properties. The aim of this study was to validate the modified version of the Short Emergency Geriatric Assessment (SEGAm) frailty instrument in elderly people living at home.

It was an observational, longitudinal, prospective, multicentre study, set up in four departments (Ardennes, Marne, Meurthe-et-Moselle, Meuse) in two French regions (Champagne-Ardenne and Lorraine). Subjects was aged 65 years or more, living at home, and was able to read and understand French, with a degree of autonomy corresponding to groups 5, or 6 in the AGGIR autonomy evaluation scale. Assessment included demographic characteristics, comprehensive geriatric assessment, and the SEGAm instrument. Psychometric validation was used to study feasibility and acceptability, internal structure validity, reliability, and discriminant validity of the SEGAm instrument. "

status: Terminated

time_perspective: Other

ReferenceCitation: Oubaya N, Mahmoudi R, Jolly D, Zulfiqar AA, Quignard E, Cunin C, Nazeyrollas P, Novella JL, Dramé M. Screening for frailty in elderly subjects living at home: validation of the Modified Short Emergency Geriatric Assessment (SEGAm) instrument. J Nutr Health Aging. 2014;18(8):757-64. doi: 10.1007/s12603-014-0466-8.

lead_sponsor: CHU de Reims


title: Validation of an Attachment Picture Set in School-adolescent

summary: this study aims to validate a picture data set that particularly activates the attachment process and that could be used in attachment studies.

ReferenceType: result

ReferenceCitation: Szymanska M, Monnin J, Noiret N, Tio G, Galdon L, Laurent E, Nezelof S, Vulliez-Coady L. The Besançon Affective Picture Set-Adolescents (the BAPS-Ado): Development and validation. Psychiatry Res. 2015 Aug 30;228(3):576-84. doi: 10.1016/j.psychres.2015.04.055. Epub 2015 Jun 20.


title: Oculomotor and Neurophysiological Markers of Emotion Regulation and Attachment Styles in Adolescence

summary: The study aims to identify specific visual scanning patterns of attachment pictures in adolescent with different attachment style.

ReferenceCitation: Szymanska M, Monnin J, Tio G, Vidal C, Girard F, Galdon L, Smith CC, Bifulco A, Nezelof S, Vulliez-Coady L. How do adolescents regulate distress according to attachment style? A combined eye-tracking and neurophysiological approach. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:39-47. doi: 10.1016/j.pnpbp.2018.08.019. Epub 2018 Aug 27.


title: Prospective Study on the Interest of ß 1-3 D Glucan Assays in Screening for the Onset of Invasive Aspergillosis in Neutropenic Patients With Acute Leukaemia.

acronym: BETA GLUCAN

summary: In the context of screening for infectious fungal diseases in patients with malignant haemopathy, and particularly patients with acute leukaemia, the investigator aims to evaluate the performance of an already commercialized but little used serum screening test (Fungitell® test) and to determine its place in the management strategy for invasive aspergillosis.

lead_sponsor: Centre Hospitalier Universitaire Dijon


title: Interest of Eye Movement Measurements in the Comprehension of Dry Eyes Symptoms (BOSO)

acronym: BOSO

summary: Dry eye syndrome is a benign situation however its impact on patient's quality of live and on health system is not trivial. One problem is the lack of correlation between patient's symptoms and physical sign observed on slit lamp examination. Eye blinking is a parameter of increased interest in this pathology particularly its frequency. To date no treatment of dry eye syndrome has a proven impact on eye blinking frequency. However recording of blinks has mostly been performed on short duration (3 to 5 minutes) and the distribution of intervals between 2 blinks is not gaussian but exponential. In this study, it is proposed to use modern eye-movement recorder to measure the blink frequency on longer duration (12 minutes) while reading on a screen computer and during a face-to-face interview before and after treatment of meibomian gland dysfunction responsible of moderate to severe dry eye syndrome.

location_facility: Fondation Ophtalmologique Adolphe de Rothschild (FOR)

intervention_type: Device


acronym: CANALHEMO

summary:
The aim of the study is to evaluate the risk in intra-operative nasal hemorrhage when using a "pushed" probe (Master Ka) in the treatment of naso lacrimal duct obstruction (NLDO).

In the investigator's experience, this risk seemed to minus using a pushed probe rather than the classical pulled-type probes.

A lower risk of hemorrhage could lead to a change in the anesthetic procedure. The gold standard in NLDO is the use of an orotracheal intubation. It could then be replaced by the use of an orolaryngeal mask. A forthcoming study will evaluate the results of this anesthetic change.

location_facility: Fondation Ophtalmologique A. de Rothschild


title: Phospholipid and Sphingolipid Composition of High-density Lipoproteins (HDL) in Obese Non-diabetic Patients With Metabolic Syndrome

acronym: SPHINGO

summary:
HDL in obese non-diabetic patients show major alterations in their function and thus their cardio-protective effects. These alterations could be explained by the quantitative and qualitative anomalies in the phospholipids and sphingolipids in the HDL. These molecules play a major role in HDL function and probably present early modifications in obesity, even before the onset of glycaemia deregulation.

The aim of this study is to show the presence of qualitative and quantitative modifications of phospholipids and sphingolipids in HDL from obese patients compared with HDL from non-obese controls.

primary_purpose: Other


title: Assessement of the Prevalence of Lysosomal Acid Lipase Deficiency in Liver Post-transplant Patients

summary:
Lysosomal Acid Lipase (LAL) deficiency is a rare, autosomal recessive storage disease linked to decrease enzymatic activity of LAL, responsible for intracellular accumulation of cholesterol esters and triglycerides.

The accumulation of lipid is in hepatocytes, Kupffer cells and macrophages leading to a fatty liver, hepatic fibrosis that can evolve up to cirrhosis.

LAL deficiency is responsible for significant morbidity and early mortality in children, adolescents and adults in connection with a multi visceral disease reaching the liver, gastrointestinal tract and the vascular endothelium. The disease is caused by homozygous or heterozygous mutations in the gene (LIPA chromosome 10q23.2-23.3) which is responsible for the synthesis of the LAL.

The disease can be diagnosed by enzymatic analysis using few drops of blood absorbed onto blotting paper.

Patients with this deficiency LAL, have no or reduced activity of this enzyme. Because of its rarity, the deficit in LAL is under diagnosed or is diagnosed in patients with liver biological disturbances and / or lipid profile disturbances, steatohepatitis-hepatitis (NASH), the steatosis (NAFLD), the cryptogenic cirrhosis or Wilson disease.

Inclusion period of 12 to 18 months (100 patients).


title: Proof of Concept Study Concerning Vestibular Stimulation Using a New Method of Dynamic Posturography.

acronym: POSTURODYN

summary:
Falls in the elderly population are a major public health problem because of their frequency and their consequences, notably in terms of dependence their cost to society. In most cases, balance disorders related to an impaired vestibular system are blamed, even though there is no formal evidence that this is the case.

Vestibular tests in routine otoneurological practice are based on the exploration of vestibulo-ocular or even vestibulo-cortical reflexes. They are not particularly suitable to screen for vestibular disorders in falls.

A prototype rocking chair has been developed to test psycho-vestibular pathways, defined as the pathways via which vestibular afferents are transported to the subject's conscience. Thanks to this apparatus, a stimulus of body movement will be generated, but with limited tactile, visual and proprioceptive afferents, in such a way that the vestibular system alone is able to indicate to subjects their position in space. The subject will be required to detect oscillatory movement, and then to distinguish between a vestibular stimulus and a pulsed auditory stimulus.

The study hypothesis is that the movement stimulation generated by our prototype will be sufficient to stimulate the vestibular system, which will manifest itself as a conscious sensation of movement and by a vestibulo-ocular reflex causing oculomotor manifestations.


title: Prevalence and Risk Factors of Dreentilation Syndrome in a Population of Patients Under Ventilation for Whatever Reason

acronym: DEVENTILATION

summary:
Non-invasive nocturnal ventilation is an effective treatment for chronic respiratory failure, whether due to obstructive (COPD), restrictive or neuromuscular causes, notably for patients in the last two categories for whom it significantly prolongs life expectancy. Overall, the treatment is well tolerated, its principal adverse effects being discomfort related to the mask.

In certain patients, morning dyspnoea when the mask is removed has been described. This is disabling as it limits everyday activities for at least 30 minutes, and defines deventilation syndrome. The pathophysiology of this syndrome is uncertain, notably the roles of hyperinflation, patient/ventilator asynchrony, or the sudden increase in diaphragmatic work after a night of rest.

The aim of this study is to investigate the prevalence of and factors associated with reventilation syndrome (DS) in a population of patients with ventilation whatever the reason, in a stable state, and followed by the medical devices department of Dijon CHU, so as to better understand the mechanisms. Patients with DS will subsequently be invited to participate in a therapeutic trial.


title: Evaluate the Protective Effect of Conditioning With Sevoflurane Versus Propofol on the Myocardium in Scheduled Aortic Valve Replacement Surgery

acronym: SUPRA

summary:
Heart surgery is a considerable source of stress for the myocardium that must be minimized.

Troponin Ic is a reliable marker to determine the level of this myocardial stress.

Studies have shown that post-conditioning with AVH has a protective effect on the myocardium, if the treatment is initiated at the start of the ischemia.

The aim of this study is to evaluate the protective effect on the myocardium (by measuring troponin levels) of the association of pre-conditioning and post-conditioning with Sevoflurane (AVH) sedation administered during and after scheduled surgery for valve replacement, via sternotomy or thoracotomy compared with total intravenous anaesthesia with Propofol.


title: Interest of Spectroscopy in the Diagnosis of Cancerous and Precancerous Lesions of the Upper Airways (UA): Pilot Study

summary:
The detection of suspect lesions is based on the clinical examination of the oral cavity and pharyngolaryngeal endoscopy, but the examination to confirm the diagnosis is a pathology examination of the biopsy taken during the endoscopy. Taking the biopsy, however, can be difficult. On the one hand , it is an invasive procedure, and may engender complications, and on the other hand, certain modifications of the mucosa may be discrete, or not particularly specific or, on the contrary, disseminated or extremely widespread.

Non-invasive tools to help the diagnosis could prove to be particularly interesting 1) to restrict the use of biopsies to patients in whom it is really necessary 2) and to identify the area where the biopsy should be done in cases of multiple lesions. In this context, spectroscopy could be a promising alternative.

The investigator puts forward the hypothesis that cancerous and precancerous lesions of the mucosa of the upper airways and digestive tract present a characteristic spectrometric profile. Indeed, as malignant tumours are hypervascularized and as precancerous tumours show signs of angiogenesis, investigators expect that the reflectance of haemoglobin will be diminished in the specific wavelengths of 540 and 575 nm, corresponding to the principal wavelengths absorbed by haemoglobin.

This pilot study will make it possible to construct an algorithm that could be used to classify lesions of the upper airways and digestive tract as either seemingly benign or cancerous.


title: Evaluation Of The Efficacy Of A Bolus Infiltration Of The Anaesthetic Tramadol Associated With Continuous Local Anaesthesia Administered Via A Wound Catheter Following Heart Surgery Via Sternotomy At Dijon Chu Single-Centre, Double-Blind, Randomized, Controlled Clinical Trial

acronym: ATLAS

summary:
Sternotomy, the reference approach for heart surgery, may induce profound and intense post-operative pain. One method of analgesia used is patient-controlled intravenous morphine.

The analgesic efficacy of continuous wound infiltration at the sternum following heart surgery has been demonstrated.

The analgesic catheter placed near the sternotomy wound reduces the consumption of morphine.

The aim of this study is to determine whether a bolus of tramadol associated with the continuous administration of levobupivacaine via the wound catheter could potentiate the local anaesthetic effects, thus leading to a decreased consumption of postoperative intravenous morphine, and a decrease in morphine-related side effects.

ReferenceCitation: Bethenod F, Ellouze O, Berthoud V, Missaoui A, Cransac A, Aho S, Bouchot O, Girard C, Guinot PG, Bouhemad B. A single dose of tramadol in continuous wound analgesia with levobupivacaine does not reduce post-sternotomy pain: a randomized controlled trial. J Pain Res. 2019 Sep 18;12:2733-2741. doi: 10.2147/JPR.S211042. eCollection 2019. Review.


title: Coordinate Regulation of Transfusions by Uploading

acronym: RTT

summary:
Currently in the Toulouse University Hospital, the organization of transfusion care for patients requiring regular transfusions is based on reading the biological results received by fax before confirming or disproving a planned hospitalization or program a new hospital if needed.

Remote transmission of laboratory results, replacing fax communication might facilitate the coordination of care that results from these laboratory results and provide a better respect of the Plan Custom Care Transfusion (PPST).

The investigators offer organization of transfusion supportive care for patients with conditions requiring biological monitoring using the techniques of information and communication telemedicine.

Primary objective

- Assess the feasibility of setting up an upload procedure biological results in the treatment of transfusion supportive care.

Secondary objectives

Assess the evolution of the quality of life of patients during the treatment
Assess changes in patient satisfaction over the support
Assess the evolution of the satisfaction of the medical team at home and at Toulouse University Hospital
Describe the programming time (hospitalization, consultations)
Estimate the loss of biological results
Assessment of the descriptive use of hospitalization, consultation and biological examinations in both groups. This remedy shall be valued in Euros thanks to GHS rates for hospitalizations, general nomenclature for Professional acts (NGAP) and biology nomenclature (NABM) for biological tests.

lead_sponsor: University Hospital, Toulouse


type: Other Identifier

title: Search for New Genetic Mutations Major Effect in Crohn's Disease

acronym: MC-WES

summary: This study highlight genetics mutations with major effect in Crohn's Disease (CD) by WES in individuals affected and healthy individuals from EPIMAD Inserm InVS registry families.

ReferenceCitation: Frade-Proud'Hon-Clerc S, Smol T, Frenois F, Sand O, Vaillant E, Dhennin V, Bonnefond A, Froguel P, Fumery M, Guillon-Dellac N, Gower-Rousseau C, Vasseur F. A Novel Rare Missense Variation of the NOD2 Gene: Evidencesof Implication in Crohn's Disease. Int J Mol Sci. 2019 Feb 15;20(4). pii: E835. doi: 10.3390/ijms20040835.

lead_sponsor: University Hospital, Lille


title: Study of Neurophysiological Correlates of the Link Between Perception and Action Through Varied Protocols of Sensorimotor Studies

summary: The main goal of this study is to better understand the link between motor system (action) and perception in variable sensorial forms by examining the time course and the dynamic of electroencephalography (EEG) activations. To do so, differents sensimotor study protocols in linguistics and in the fiels of emotional and spatial perception will be realised in order to study prcisely differents links parception-action.

status: Recruiting

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status_simplified: Ongoing


title: Protected by Nature: Could Physical Activity Help to Counteract the Blood Haemophilia Disturbance? A Pilot Study.

acronym: END-HEMO

summary:
Physical activity is lower in patients with haemophilia than in their healthy peers. Nevertheless, exercize is recommended for those patients and supported by evidence. Until 2013, scientific and medical evidence to encourage physical activity for patients with haemophilia were listed to increase their locomotor function, their metabolic status, their fitness level and their well-being. In 2013, an original publication by Groen et al. suggested that physical activity could also interact with the specific and biological disturbance of the disease.

We propose to consider that regular endurance exercize prescription should be encouraged in patients with haemophilia not only for a healthier lifestyle but also because it could positively alter the specific biological blood disturbance seen in haemophilia. Nevertheless, before planning a well powered intervention trial we need to determine the acceptability of regular exercize and the expected value of factor Factor VIII, von Willebrand factor and von Willebrand propeptide after an endurance training program.