Corrigendum to "Increasing Dose of Autologous Bone Marrow Mononuclear Cells Transplantation Is Related to Stroke Outcome: Results from a Pooled Analysis of Two Clinical Trials".

[This corrects the article DOI: 10.1155/2016/8657173.].

Increasing Dose of Autologous Bone Marrow Mononuclear Cells Transplantation Is Related to Stroke Outcome: Results from a Pooled Analysis of Two Clinical Trials.

Background and Purpose. BM-MNC transplantation improves recovery in experimental models of ischemic stroke. Clinical trials are ongoing to test efficacy in stroke patients. However, whether cell dose is related to outcomes is not known. Methods. We performed a pooling data analysis of two pilot clinical trials with autologous BM-MNCs transplantation in ischemic stroke patients. Cell dose and route were analyzed to evaluate their relation to good outcome (m-Rankin scale [mRS] score 0-2) at 6 months. Results. Twenty-two patients were included. A median of 153 × 10(6) (±121 × 10(6)) BM-MNCs was injected. Intra-arterial route was used in 77.3% of cases. A higher number of cells injected were associated with better outcomes at 180 days (390 × 10(6) [320-422] BM-MNCs injected in those patients with mRS of 0-2 at 6 months versus 130 × 10(6) [89-210] in those patients with mRS 3-6, p = 0.015). In the intra-arterially treated patients, a strong correlation between dose of cells and disability was found (r = -0.63, p = 0.006). A cut point of 310 × 10(6) injected cells predicted good outcome with 80% sensitivity and 88.2% specificity. Conclusions. Similar to preclinical studies, a higher dose of autologous BM-MNC was related to better outcome in stroke patients, especially when more than 310 × 10(6) cells are injected. Further interventional studies are warranted to confirm these data.

Predictors of Restenosis Following Carotid Angioplasty and Stenting.

BACKGROUND AND PURPOSE: Restenosis after carotid angioplasty (with or without stent) is associated with increased rate of stroke and death. Our aim was to determine risk and predictive factors related to carotid restenosis post carotid angioplasty and its association to recurrent cerebrovascular events. METHODS: All consecutive patients with carotid stenosis treated with angioplasty (n=1060) in a single University Hospital were included (from 2002 to 2013). Follow-up was done prospectively evaluating restenosis, ipsilateral stroke, or death. Restenosis was defined as a narrowing of ≥70% of a previously treated vessel evaluated by ultrasonography. RESULTS: Of the 1060 patients treated, 9.2% (97) of patients experienced restenosis during follow up (median 12 [9-32] months). Occurrence of restenosis was associated with ipsilateral stroke during follow-up (P=0.049). After Cox regression analysis, hypertension (hazard ratio, 6.2 [1.9-19.9]; P=0.002), impaired vasoreactivity (hazard ratio, 1.7 [1.09-2.8]; P=0.019), and angioplasty without stent (hazard ratio, 2.9 [1.2-6.8]; P=0.012) were independent risk predictors of >70% restenosis. CONCLUSIONS: Carotid restenosis after carotid angioplasty is associated with ipsilateral stroke occurrence. In our sample, hypertension, angioplasty without stent, and impaired vasoreactivity identify patients at high risk of restenosis and could help to select patients for follow-up ultrasonography imaging.

Resistance of subventricular neural stem cells to chronic hypoxemia despite structural disorganization of the germinal center and impairment of neuronal and oligodendrocyte survival.

Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or in patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon is unknown. We have found that adult rodents exposed for several days/weeks to hypoxia, with an arterial oxygen tension similar to that of chronically hypoxemic patients, manifest a partially irreversible structural disarrangement of the subventricular neurogenic niche (subventricular zone) characterized by displacement of neurons and myelinated axons, flattening of the ependymal cell layer, and thinning of capillary walls. Despite these abnormalities, the number of neuronal and oligodendrocyte progenitors, neuroblasts, and neurosphere-forming cells as well as the proliferative activity in subventricular zone was unchanged. These results suggest that neural stem cells and their undifferentiated progeny are resistant to hypoxia. However, in vivo and in vitro experiments indicate that severe chronic hypoxia decreases the survival of newly generated neurons and oligodendrocytes, with damage of myelin sheaths. These findings help explain the effects of hypoxia on adult neurogenesis and provide new perspectives on brain responsiveness to persistent hypoxemia.

Intra-arterial bone marrow mononuclear cell transplantation correlates with GM-CSF, PDGF-BB, and MMP-2 serum levels in stroke patients: results from a clinical trial.

Bone marrow mononuclear cell (BM-MNC) intra-arterial transplantation improves recovery in experimental models of ischemic stroke through secretion of cytokines and growth factors (GFs), enhancing neoangiogenesis, and enhancing neuroplasticity. In this study, we tested whether BM-MNC transplantation in stroke patients induces changes in serum levels of cytokines and GFs. A phase I/II trial was conducted in middle cerebral artery (MCA) stroke patients with autologous intra-arterial BM-MNC transplantation between 5 and 9 days after stroke. Follow-up was done for up to 6 months. Eight cases and nine controls were included, and the serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), ß nerve growth factor (ß-NGF), and matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) were measured before and 4, 8, and 90 days after transplantation. The correlation of these serum levels with dose of cells and clinical outcomes was studied. A total of 1.59 × 10(8) (±1.21 × 10(8)) BM-MNCs were injected in cases; of them 3.38 × 10(6) (±2.33 × 10(6)) were CD34(+) cells. There was a positive correlation between total BM-MNCs injected and levels of GM-CSF and PDGF-BB at 90 days after transplantation (r = 0.929, p = 0.001 and r = 0.714, p = 0.047, respectively), and a negative correlation between total CD34(+) cells injected and MMP-2 levels at 4 days after transplantation (r = -0.786, p = 0.036). Lower plasma levels of MMP-2 at 4 days and higher levels of PDGF-BB at 90 days were associated with better functional outcomes during follow-up (p = 0.019 and p = 0.037, respectively). When administered intra-arterially in subacute MCA stroke patients, BM-MNCs seem to induce changes in serum levels of GM-CSF, PDGF-BB, and MMP-2, even 3 months after transplantation, which could be associated with better functional outcomes. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Development, Implementation, and Evaluation of a Telemedicine Service for the Treatment of Acute Stroke Patients: TeleStroke.

BACKGROUND: Health care service based on telemedicine can reduce both physical and time barriers in stroke treatments. Moreover, this service connects centers specializing in stroke treatment with other centers and practitioners, thereby increasing accessibility to neurological specialist care and fibrinolytic treatment. OBJECTIVE: Development, implementation, and evaluation of a care service for the treatment of acute stroke patients based on telemedicine (TeleStroke) at Virgen del Rocío University Hospital. METHODS: The evaluation phase, conducted from October 2008 to January 2011, involved patients who presented acute stroke symptoms confirmed by the emergency physician; they were examined using TeleStroke in two hospitals, at a distance of 16 and 110 kilometers from Virgen del Rocío University Hospital. We analyzed the number of interconsultation sheets, the percentage of patients treated with fibrinolysis, and the number of times they were treated. To evaluate medical professionals' acceptance of the TeleStroke system, we developed a web-based questionnaire using a Technology Acceptance Model. RESULTS: A total of 28 patients were evaluated through the interconsultation sheet. Out of 28 patients, 19 (68%) received fibrinolytic treatment. The most common reasons for not treating with fibrinolysis included: clinical criteria in six out of nine patients (66%) and beyond the time window in three out of nine patients (33%). The mean "onset-to-hospital" time was 69 minutes, the mean time from admission to CT image was 33 minutes, the mean "door-to-needle" time was 82 minutes, and the mean "onset-to-needle" time was 150 minutes. Out of 61 medical professionals, 34 (56%) completed a questionnaire to evaluate the acceptability of the TeleStroke system. The mean values for each item were over 6.50, indicating that respondents positively evaluated each item. This survey was assessed using the Cronbach alpha test to determine the reliability of the questionnaire and the results obtained, giving a value of 0.97. CONCLUSIONS: The implementation of TeleStroke has made it possible for patients in the acute phase of stroke to receive effective treatment, something that was previously impossible because of the time required to transfer them to referral hospitals.