Pre-Operative Cytokine-Induced Mobilization of Bone Marrow-Derived Cells, Followed by Revascularization Surgery: Early and Long-Term Results of a Prospective Study in Patients with End-Stage Ischemic Cardiac Disease
Notice bibliographique
Résumé
Abstract Abstract 318 Introduction Coronary artery disease (CAD), along with its main complications, acute myocardial infarction (AMI) and congestive heart failure (CHF), remains a serious worldwide problem. Despite advances in medical and surgical treatments, CAD is still associated with a high mortality rate and markedly affects the quality of life of patients. The possibility to replace the scarring by inducing neoangiogenesis and possibly regeneration of injured myocardium is an attractive option to improve the prognosis of CAD patients. For this purpose, cytokine-induced mobilization of bone marrow stem cells (BMCs) into the peripheral blood might represents a potential pathway to activate the regenerative process. Some observations suggest that circulating BMCs may lodge in non-hematopoietic tissues such as muscle, liver and myocardium where the tissue injury or the local inflammation may promote stem cells migration. Thus, the association between cytokine induced BMCs migration and tissue injury, may induce tissue repair since the stem cells are usually attracted from the inflamed tissues. A phase II prospective study was performed combining BMCs migration, obtained by cytokines, and cardiac inflammation, induced by myocardial punctures. Results at early and long-term follow-up are here reported. Patients and methods BMCs mobilization was performed in 15 patients undergoing surgery for coronary artery bypass grafting (CABG) and/or mitral valve surgery and/or ventricular remodeling combined to multiple trans-myocardial punctures (Sen technique) in ungraftable non-viable fibrotic areas. BMC mobilization was induced by granulocyte colony stimulating factor (G-CSF) (Lenogastrim) given at 5 μgr/kg s.c. b.i.d. for 5 to 6 consecutive days, starting on day-3 before surgery along with granulocyte-macrophage colony stimulating factor (GM-CSF) (Molgramostim) at 2.5 μgr/kg s.c./day. Patients entered the study protocol on the basis of the following inclusion criteria: i. severe heart failure with left ventricular ejection fraction (EF) < 35%; ii. ineligibility to cardiac transplantation; iii. widespread myocardial ischemia with at least one area of akinetic and nonviable myocardium, detected by cardiac stress scintigraphy with Thallium; iv. presence of other combined surgical indications, including the requirement of surgery for CABG on areas other than nonviable scars; v. one or more previous myocardial infarction. The study protocol was approved by our local Institutional Review Board and Ethics Committee and all patients signed the informed written consent. Results Cytokine administration induced a variable increase in circulating CD34+ve cells in all patients, with peak values recorded between day +4 and day +6. There were no in hospital (0–30 days) deaths. All 15 patients were discharged from the ICU after a median of 2 days, while the overall in hospital stay was 10.5+4.2 days (range 7–21) and all patients were discharged in good clinical condition. There were two sudden deaths over the mid-term, at postoperative day +32 and +45: both patients had troublesome ECC weaning without other postoperative complications. Presently, at a median follow-up of 48 mos, four patients died, 11 patients are alive, one of them after heart transplantation. Among the 10 non-transplanted long-term survivors, there was a significant improvement of the NYHA class from 2,1±0,8 to 1,3±0,5 (p<0,005) and of the Canadian Class score from 2,6±0,5 to 1,0±0,0 (p<0,005); moreover, a significant increase of the ejection fraction from 31,4±7,3% to 41,7±12,6% (p<0,05) was documented. Conclusions The study suggests that cytokine-induced BMC mobilization combined to CABG along with multiple trans-myocardial punctures: i. is an innovative and safe procedure; ii. offers some clinical benefits in patients with end-stage CAD requiring cardiac surgery. Based on these results, a randomized trial has been launched, with the aim to define the beneficial effect of pre-operative cytokine-induced BMC mobilization in patients undergoing cardiac surgery. Disclosures: Off Label Use: G-CSF + GM-CSF in CAD.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».