Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy.

Intra-arterial transplantation of mesoangioblasts proved safe and partially efficacious in preclinical models of muscular dystrophy. We now report the first-in-human, exploratory, non-randomized open-label phase I-IIa clinical trial of intra-arterial HLA-matched donor cell transplantation in 5 Duchenne patients. We administered escalating doses of donor-derived mesoangioblasts in limb arteries under immunosuppressive therapy (tacrolimus). Four consecutive infusions were performed at 2-month intervals, preceded and followed by clinical, laboratory, and muscular MRI analyses. Two months after the last infusion, a muscle biopsy was performed. Safety was the primary endpoint. The study was relatively safe: One patient developed a thalamic stroke with no clinical consequences and whose correlation with mesoangioblast infusion remained unclear. MRI documented the progression of the disease in 4/5 patients. Functional measures were transiently stabilized in 2/3 ambulant patients, but no functional improvements were observed. Low level of donor DNA was detected in muscle biopsies of 4/5 patients and donor-derived dystrophin in 1. Intra-arterial transplantation of donor mesoangioblasts in human proved to be feasible and relatively safe. Future implementation of the protocol, together with a younger age of patients, will be needed to approach efficacy.

Yttrium-90 Infusion: Incidence and Outcome of Delivery System Occlusions during 885 Deliveries.

PURPOSE: To evaluate the incidence, cause, and management of delivery system occlusions during yttrium-90 (90Y) microsphere infusions and to identify techniques to prevent occlusions. MATERIALS AND METHODS: A retrospective review was conducted of 885 consecutive radioembolization deliveries during 820 procedures (some with multiple deliveries) in 503 patients (mean age, 65 y; 293 male) performed between June 2001 and July 2013 at a single academic tertiary care hospital. Occlusions were reported prospectively, and procedural details were reviewed. Statistical analysis assessed associations between catheter occlusions and patient and procedural characteristics. RESULTS: Of 885 90Y microsphere deliveries, 11 resulted in occlusion (1.2%). Five occlusions were associated with contained leakage of radioactive material, and one was associated with a spill. Treatment was completed in the same day in 10 patients; repeat catheterization was required in five patients. One patient returned 1 week later to complete treatment. Occlusions were more frequent with deliveries of resin (11/492; 2.2%) versus glass (0/393; 0%) microspheres (P = .002). Occlusions were more likely to occur within the proximal portion of the delivery apparatus (P = .002). There was no significant relationship with any patient characteristics, and there was no improvement with operator experience. The most common cause of occlusion was resin microsphere delivery device failure. CONCLUSIONS: (90)Y microsphere delivery device occlusion is uncommon but does occur with resin microspheres. Understanding causes and how to troubleshoot can limit the incidence and detrimental effects.

Intra-arterial tirofiban infusion for thromboembolic complication during coil embolization of ruptured intracranial aneurysms.

INTRODUCTION: Intra-arterial (IA) thrombolytic intervention for acute thrombosis has been challenged due to the risk of bleeding during the endovascular treatment of ruptured aneurysms. We present the results of IA tirofiban infusion for thromboembolic complications during coil embolization in patients with ruptured intracranial aneurysms. METHODS: Thromboembolic events requiring thrombolytic intervention occurred in 39 (10.5%) cases during coil embolization of 372 consecutive ruptured intracranial aneurysms. Maximal aneurysm diameters of 39 patients (mean age, 54.7 ± 13.2 years; 23 female, 16 male) ranged from 2.1 to 13.1mm (mean, 6.6 ± 3.0mm). The anterior communicating artery was the most common site (n=13), followed by the middle cerebral artery (n=9) and the posterior communicating artery (n=7). In this series, we used intracranial stents in 10 patients during the procedure. Superselective IA tirofiban infusion through a microcatheter was performed to resolve thrombi and emboli. We assessed the efficacy and safety of IA tirofiban infusion in patients with ruptured aneurysms. RESULTS: Intraarterially administered tirofiban doses ranged from 0.25 to 1.25mg (mean, 0.71 ± 0.26 mg). Effective thrombolysis or recanalization was achieved in 34 patients (87.2%), and three patients (7.7%) suffered distal migration of clots with partial recanalization. The rest (5.1%) had no recanalization. Nonconsequent intracerebral hemorrhage occurred in two patients (5.1%) after the procedure. Thromboemboli-related cerebral infarction developed in eight patients, and only two patients remained infarction related disabilities. CONCLUSION: IA tirofiban infusion seems to be efficacious and safe for thrombolysis during coil embolization in patients with ruptured intracranial aneurysms.

Biliary sclerosis after hepatic arterial infusion pump chemotherapy for patients with colorectal cancer liver metastasis: incidence, clinical features, and risk factors.

BACKGROUND: Hepatic arterial infusion pump chemotherapy (HAIPC) contributes to the prolonged survival of selected patients with colorectal cancer liver metastases (CRCLM). The most clinically important adverse event after HAIPC with floxuridine (FUDR) is biliary sclerosis (BS). Little is known about the etiology of BS. METHODS: HAIPC was administered to 475 consecutive patients who received HAIPC on prospective protocols from 1991 to 2008. The incidence, clinical features, variables related to demographics, comorbidity, medical history, CRCLM, surgery, chemotherapy, and laboratory data were reviewed. An analysis of factors potentially associated with BS, defined as a biliary stricture related to HAIPC requiring stent placement, was performed. RESULTS: The incidence of BS was 5.5% (16 of 293) in patients receiving HAIPC as an adjuvant therapy after hepatectomy, and 2% (2 of 100) in patients receiving HAIPC with FUDR for unresectable disease. The common hepatic duct was the site most frequently affected (87.5%). In patients receiving adjuvant HAIPC, BS was associated with abnormal postoperative flow scans (18.8% vs. 1.8%, P = 0.006), postoperative infectious complications (50.0% vs. 14.8%, P = 0.002), and larger dose/cycle/weight of FUDR (2.6 vs. 2.0 mg/cycle/kg, P = 0.025) than patients without BS. No patient died directly of BS. Median survival was not compromised by the development of BS (BS vs. non-BS: 61.0 months [range 6.2-171.6 months] vs. 47.2 months [range 2.4-200.8 months], P = 0.316, respectively). CONCLUSIONS: BS is an uncommon complication after HAIPC and does not compromise survival if adequately salvaged by stenting or dilatation. Surgical complications as well as type and dose of intra-arterial chemotherapy may contribute to the development of BS.

Long-term follow up of patients with good outcome after intra-arterial thrombolysis for major arterial occlusion in the carotid territory: clinical and magnetic resonance imaging evaluation.

Long-term clinical symptoms, including extrapyramidal signs, and magnetic resonance (MR) imaging studies were retrospectively analyzed in 21 patients with good outcome (modified Rankin scale scores 0-2) after successful recanalization of occluded major arteries by intra-arterial thrombolysis with mechanical disruption. Changes in high intensity areas (HIAs) and cerebral atrophy in the ischemic hemisphere were evaluated on follow-up fluid-attenuated inversion recovery MR images. Extrapyramidal signs, short-stepped gait and/or masked face, were observed in 12 of 21 patients during the follow-up period (11 to 68 months, mean 42 months). Enlargement of HIA was demonstrated in 10 of 18 patients undergoing follow-up MR imaging. Cerebral atrophy in the ischemic hemisphere was revealed on the follow-up MR images in all 18 patients. In nine patients with small infarctions, 20 ml or less on computed tomography scans, cerebral atrophy progressed more rapidly in four patients with extrapyramidal signs compared to the other five patients without extrapyramidal signs (p < 0.05). More than half of the patients with good outcome showed extrapyramidal signs. Extrapyramidal signs in patients with small infarction may indicate rapid progression of cerebral atrophy. The occurrence of extrapyramidal signs might be related to delayed neuronal death in atrophic areas.

Therapy of acute basilar artery occlusion: intraarterial thrombolysis alone vs bridging therapy.

BACKGROUND AND PURPOSE: While intravenous recombinant tissue plasminogen activator (rt-PA) has been approved for acute stroke therapy within 3 hours, the optimum management of basilar artery occlusion (BAO) is still a matter of debate. We compared intraarterial thrombolysis with the combined bridging approach of intravenous abciximab and intraarterial thrombolysis with rt-PA (bridging therapy) in an observational, longitudinal, monocenter study. METHODS: Between 1998 and 2006, information for 106 patients with acute BAO were prospectively entered into a local database. Patients eligible for treatment received either intraarterial thrombolysis with rt-PA alone (intraarterial thrombolysis) or were treated with intravenous abciximab and intraarterial rt-PA (bridging therapy). Outcome parameters were recanalization of the basilar artery according to Trial in Myocardial Infarction criteria, survival, and reduction of severe disability and death at 3 months. Logistic regression was used to identify independent predictors for recanalization, survival, and clinical outcome. RESULTS: Of a total of 106 patients with confirmed BAO, 87 patients underwent subsequent angiography. Among those, 75 patients were identified who received the full treatment protocol. Patients in the bridging group had a better recanalization rate (83.7% vs 62.5%; P=0.03), a higher survival rate (58.1% vs 25%; P=0.01), and a better chance for an outcome with no or only mild to moderate disability (modified Rankin Scale score, 0-3; 34.9% vs 12.5%; P=0.02). Symptomatic intracerebral hemorrhage rates were comparable in both groups (14% in the bridging group vs 18.8%; P=0.41). Independent predictors for recanalization were age (OR, 0.95; 95% CI, 0.91-0.99), atrial fibrillation (OR, 6.53; 95% CI, 1.14-37.49), and bridging therapy (OR, 3.37; 95% CI, 1.02 to 11.18). Independent prognostic factors for outcome were Glasgow coma scale score at presentation (OR, 1.24; 95% CI, 1.03-1.45) and the combination of bridging therapy with successful recanalization (OR, 3.744; 95% CI, 1.04-13.43). CONCLUSIONS: Bridging therapy for acute BAO with intravenous abciximab and intraarterial rt-PA appears to be safe and yields higher recanalization and improved survival rates, as well as an overall improved chance for a better outcome.

[Intra-arterial regional perfusion in destructive forms of acute pancreatitis]. / Vnutriarterial'naia regionarnaia perfuziia pri destruktivnykh formakh ostrogo pankreatita.

The results of using regional infusion therapy in 17 patients with destructive pancreatitis are analyzed which appeared to be more effective, than the systemic infusion of drugs in stopping the symptoms of endotoxicosis leveling the functional insufficiency of the liver and kidneys, disturbances in hemodynamics and hemostasis. The best results have been obtained when using a modified method of regional therapy (celiac-aortal dislocational regional infusion) in the complex treatment of destructive pancreatitis. This method has a number of advantages as compared with intra-aortic variant of regional therapy. Hospital lethality in the process of using the methods of regional therapy in the complex treatment of destructive pancreatitis was 17.5%. In the control group of patients treated without regional infusion lethality was within the limits of 28%. A modified classification of endotoxicosis according to the degree of the disease is proposed. In order to estimate the severity of the syndrome of intoxication and effectiveness of the given therapy principally new integrative parameters of clinical and laboratory research are used.

[Conventional local intra-arterial fibrinolysis, spray lysis and mechanically accelerated fibrinolysis. An assessment of their position in the spectrum of angioplasty technics]. / Konventionelle lokale intraarterielle Fibrinolyse, Spraylyse und mechanisch akzelerierte Fibrinolyse. Standortbestimmung im Spektrum der Angioplastietechniken.

Intra-arterial local fibrinolysis was performed in 72 patients (51 men, 21 women, mean age 66.8 years) during the course of 78 angioplasties. 11.1% were stage IIa (Fontaine), 38.9% were stage II b, 27.8% were stage III and 22.2% were stage IV. The methods used were conventional fibrinolysis (15.4%), spray lysis (47.4%) and mechanically accelerated fibrinolysis (37.2%). In 66.7% the urokinase dose was < 600,000 I.U., in 17.9% it was > 1,000,000 I.U. Additional balloon dilatation was performed in 72 cases, percutaneous aspiration of thrombo-embolic material in 41 cases and stent implantation in 7 cases. Angiographically the procedure was successful in 90.7%; the Doppler index rose from 0.47 +/- 0.27 to 0.85 +/- 0.3 (p < 0.001). At discharge, staging was: I = 38.9%, IIa = 38.9%, IIb = 5.6%, III = 1.4%, IV = 15.3%. There were no systemic bleeding complications. In 5.1%, complications had to be treated surgically.