Václav Procházka

Cell Therapy, a New Standard in Management of Chronic Critical Limb Ischemia and Foot Ulcer

Fifty percent of diabetics (7% of general population) suffer from peripheral arterial occlusive disease, which may lead to amputation due to critical limb ischemia (CLI). The aim of our study was to prevent major limb amputation (MLA) in this group of patients using a local application of autologous bone marrow stem cells (ABMSC) concentrate. A total of 96 patients with CLI and foot ulcer (FU) were randomized into groups I and II. Patients in group I (n = 42, 36 males, 6 females, 66.2 ± 10.6 years) underwent local treatment with ABMSC while those in group II (n = 54, control, 42 males, 12 females, 64.1 ± 8.6 years) received standard medical care. The frequency of major limb amputation in groups I and II was 21% and 44% within the 120 days of follow up, respectively (p < 0.05). Only in salvaged limbs of group I both toe pressure and toe brachial index increased (from 22.66 ± 5.32 to 25.63 ± 4.75 mmHg and from 0.14 ± 0.03 to 0.17 ± 0.03, respectively, mean ± SEM). The CD34+ cell counts in bone marrow concentrate (BMC) decreased (correlation, p = 0.024) with age, even though there was no correlation between age and healing. An unexpected finding was made of relative, bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy (21% of MLA). This difference was statistically significant (p < 0.040). We conclude ABMSC therapy results in 79% limb salvage in patients suffering from CLI and FU. In the remaining 21% lymphopenia and thrombocytopenia were identified as potential causative factors, suggesting that at least a partial correction with platelet supplementation may be beneficial.

Detection of Intracranial Arterial Stenosis Using Transcranial Color-Coded Duplex Sonography, Computed Tomographic Angiography, and Digital Subtraction Angiography

The aim of this retrospective study was to compare intracranial arterial stenosis in patients with stroke using 3 different methods: transcranial color‐coded duplex sonography, computed tomographic (CT) angiography, and digital subtraction angiography in a common clinical practice.

Diagnosis of Recanalization of the Intracranial Artery Has Poor Inter-Rater Reliability

BACKGROUND AND PURPOSE: Recanalization is the important outcome measure for acute stroke therapy. Several methods of recanalization assessment are used in clinical practice, but few studies have addressed their reliability. We, therefore, sought to assess interobserver reliability of the diagnosis of intracranial artery recanalization following intervention by using TIMI criteria. MATERIALS AND METHODS: The digital angiography scans of all patients with acute ischemic stroke during 2009 undergoing DSA and endovascular procedures at Ostrava University Hospital were assessed in the study. Images were retrospectively evaluated for intracranial artery recanalization on the TIMI scale by 2 experienced neuroradiologists who were blinded to clinical findings and to each other. RESULTS: The angiography scans of 43 patients (16 females; age, 70.5 ± 14 years; median baseline NIHSS score, 15 [IQR, 11–18]) were retrospectively evaluated in our study. At 3 months, 27% of patients had mRS scores ≤ 2 and mortality was 18%. Two radiologists diagnosed TIMI grades as follows: TIMI 0, 16%, and 16%; TIMI 1, 21%, and 8%; TIMI 2a, 32% and 29%; TIMI 2b, 13% and 16%; TIMI 3, 18, and 31%. Interobserver agreement for recanalization was weighted κ = 0.4 (95% CI, 0.2–0.6). CONCLUSIONS: The diagnosis of recanalization after interventional procedures was found to have poor interobserver agreement between 2 experienced neuroradiologists. TIMI criteria, therefore, do not permit reliable comparison of the efficacy of recanalization therapy among different studies.

A Controlled Trial of Revascularization in Acute Stroke

PURPOSE To compare safety and utility of intraarterial revascularization with use of stents to no revascularization in patients who either failed to respond to intravenous thrombolysis (IVT) or have contraindications to IVT. MATERIALS AND METHODS The case-control study was approved by local ethics committees; all patients signed informed consent. One hundred thirty-one patients (74 men; mean age, 65.9 years ± 12.3; range, 25-86 years) with acute ischemic stroke (AIS) due to middle cerebral artery (MCA) occlusion were enrolled; 75 underwent IVT. No further recanalization therapy was performed in 26 (35%) IVT-treated patients with MCA recanalization (group 1). Patients with IVT failure after 60 minutes were allocated to endovascular treatment (group 2A) or no further therapy (group 2B). Patients with contraindication to IVT were allocated to endovascular treatment within 8 hours since AIS onset (group 3A) or to no recanalization therapy (group 3B). Neurologic deficit at admission, MCA recanalization, symptomatic intracerebral hemorrhage (SICH), and 3-month clinical outcome were evaluated. Favorable clinical outcome was defined as modified Rankin scale score 0-2 at 3 months after stroke onset. Two-sided Mann-Whitney U test, independent samples t test, Fisher exact test, multivariate logistic regression analysis of baseline variables, and complete MCA recanalization for the prediction of favorable clinical outcome were used for statistical evaluation. RESULTS Median National Institutes of Health Stroke Scale score at admission was 13.5, 16.0, 15.5, 15.0, and 16.0 in groups 1, 2A, 2B, 3A, and 3B, respectively (P > .05); SICH occurred in one of 26 (3.8%), one of 23 (4.3%), one of 26 (3.8%), one of 31 (3.2%), and one of 25 (4.0%) patients, respectively (P > .05). MCA recanalization after endovascular treatment was achieved in 50 of 54 (92.6%) patients. Favorable outcome was significantly different between groups 2A and 2B (10 of 23 [43.5%] and four of 26 [15.4%], respectively; P = .03) and groups 3A and 3B (14 of 31 [45.2%] and two of 25 [8.0%], respectively; P = .004) and was dependent on MCA recanalization (odds ratio, 5.55; P = .006). CONCLUSION In this controlled trial, intraarterial revascularization with stents was an effective and safe-effective treatment option in patients with acute MCA occlusion with contraindication to IVT or after IVT failure.

Prior Use of Antiplatelet Therapy Can Be Associated with a Higher Chance for Early Recanalization of the Occluded Middle Cerebral Artery in Acute Stroke Patients Treated with Intravenous Thrombolysis

Background: The early recanalization (ER) of an occluded cerebral artery is important for clinical improvement in acute ischemic stroke. The aim of the study was to assess the possible association between the prior use of antiplatelets (AP) and ER of occluded middle cerebral artery (MCA) after intravenous thrombolysis (IVT). Methods: In 146 consecutive acute ischemic stroke patients presenting with occluded MCA and treated with IVT, the ER and incidence of symptomatic intracerebral hemorrhage (SICH) were compared according to the presence or absence of prior AP use. ER was assessed by transcranial Doppler or digital subtraction angiography within 2 h after the end of IVT. Results: Fifty-six patients (28 males, mean age: 69.8 ± 9.8 years) used AP and 90 patients were AP naïve (51 males, mean age: 65.8 ± 12.5 years). Prior AP use was associated with a higher rate of early MCA recanalization (53.6 vs. 29.5% in AP naïve, p = 0.007) and was shown as a predictor of ER (OR: 2.30, 95% CI: 1.14–4.65; p = 0.020) in unadjusted analysis. No difference was found in the occurrence of SICH. Conclusion: Prior use of AP was associated with a higher rate of ER of occluded MCA, but with no increase of SICH after IVT.

Transcranial Duplex Sonography and CT Angiography in Acute Stroke Patients

Acute occlusion of cervical or intracranial arteries is the most common cause of ischemic stroke (IS). The aims of the current study were to compare the occurrence of acute pathologic findings in intracranial arteries using transcranial color‐coded sonography (TCCS) and computed tomographic angiography (CTA) performed within 3 hours of IS onset and to assess the correlation between the vascular findings on admission and the patients clinical state on admission and 3 months after the IS. Forty‐five consecutive patients with an acute IS were included in the prospective study during an 18‐month period. All patients underwent CTA and TCCS within the first 3 hours of symptom onset. A high rate of pathologic findings in the intracranial circulation was found (70.9% in CTA and 77.4% in TCCS examinations). The CTA and TCCS findings with respect to the intracranial arteries were consistent in 87.1% of cases (Cohens κ, .797). The sensitivity, specificity, and positive and negative predictive values achieved with TCCS in patients with middle cerebral artery main stem occlusion were 92.3%, 94.4%, and 92.3% and 94.4%, respectively. There was no correlation between the patients clinical status on admission and 3 months after the onset of the IS and the CTA or the TCCS findings (P > .1 in all cases). A substantial agreement was found between TCCS and CTA in the detection of pathologic findings in intracranial vessels in acute stroke patients. Both methods can be used for this purpose.

EkoSonicSV endovascular system for recanalization of the basilar artery occlusion

The interventional management of stroke may consist of the use of angioplasty, stenting or mechanical thrombus removal technique. For this purpose several retrieval devices are being used. Recently the new alternative device - EkoSonicSV has been introduced, which is particularly suitable for recanalization of the occluded basilar artery (BA). Here we are presenting a complete recanalization of BA using this device in two patients with stroke over a short period of time together with the intra-arterial use of recombinant tissue plasminogen activator and application of intravascular ultrasound.

Detection of dural ectasia in diagnosis of Marfan's syndrome

BACKGROUND Marfans syndrome is an inherited connective tissue disorder that affects many organ systems and has widespread phenotype expression. The diagnosis is therefore made by phenotype assessment. Dural ectasia has been classified as a major diagnostic criterium with a prevalence of over 90% in patients with Marfans syndrome. The objective of this study determine the feasibility of performing CT angiographic examination of aorta and large vessels for dural ectasia grading in a single CT exam of patients with Marfans syndrome. PATIENTS AND METHODS 7 examinations in Marfan patients were performed of which 6 were CTA. In all exams the aorta was evaluated and simultaneously the lumbosacral region of the spine was well delineated. We performed calculation of spinal canal (SCI) and dural sac (DSI) indices and also qualitative grading of dural sac involvement. RESULTS In 4 patients both SCI (> 4,50) and DSI (> 3,75) fulfil the diagnostic criteria of Marfans syndrome. In 1 patient complete spondyloptosis was detected. CONCLUSIONS Whole body CT examination is the perfect tool for both aorta and spinal canal evaluation. Despite differences in spinal canal grading methods in all of our patients significant changes of the spinal canal in the lumbosacral region were detected. Dural ectasia is easy to detect and quantify and may therefore be used as a sensitive and specific sign of Marfans syndrome.

Safety and Efficacy of Endovascular Sonolysis Using the EkoSonic Endovascular System in Patients with Acute Stroke

BACKGROUND AND PURPOSE: Sonolysis is a new therapeutic procedure for arterial recanalization. The aim of this study was to confirm the safety and efficacy of endovascular sonolysis by using the EkoSonic Endovascular System in subjects with acute ischemic stroke. MATERIALS AND METHODS: Patients with acute ischemic stroke with occlusion of the middle cerebral artery or basilar artery were enrolled consecutively in this prospective study. The control group (44 MCA and 12 BA occlusions) was selected from historical controls. EkoSonic Endovascular System was started within 8 hours after stroke onset. The NIHSS score at hospital admission, after 24 hours, and at 7 days; arterial recanalization; early neurologic improvement; symptomatic intracerebral hemorrhage; and favorable 3-month clinical outcome defined as a modified Rankin Scale score of 0–2 were evaluated by statistical means. RESULTS: Fourteen patients (10 men; mean age, 65.1 ± 11.2 years; median NIHSS score, 16.5) underwent EkoSonic endovascular sonolysis. Arterial recanalization after endovascular treatment was achieved in 6 of 7 (85.7%) patients with MCA occlusion (4 complete recanalizations) and in all 7 (100%) patients with BA occlusion (6 complete recanalizations). No (0%) symptomatic intracerebral hemorrhage or periprocedural complications occurred. Seven (50%) patients were independent at 3 months (median mRS score, 2). Early neurologic improvement and favorable clinical outcome were significantly more frequent in patients with MCA occlusion undergoing EkoSonic endovascular sonolysis than in controls (100% and 71.4% versus 4.6% and 13.6% of patients; P = .0001 and P = .003, respectively). Three-month mortality was significantly lower in patients with BA occlusion undergoing EkoSonic endovascular sonolysis than in controls (0% versus 66.7% patients, P = .013). CONCLUSIONS: In this small study, EkoSonic endovascular sonolysis allowed safe and potentially effective revascularization in patients experiencing acute ischemic stroke.

Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia.

Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent therapeutic cocktail for patients with CLI, many of whom are at risk for amputation of the affected limb.