Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy.

PURPOSE: The perioperative management of patients on antithrombotic therapy is currently an unresolved problem as these therapies pose a considerable risk for perioperative hemorrhagic complications. The presented studies investigated the efficacy of a new collagen technology to achieve hemostasis. A polyethylene glycol-coated collagen pad (PCC) was compared to a marketed fibrinogen-thrombin coated collagen pad (FTC) for the treatment of an aortotomy incision in heparinized swine on dual antiplatelet therapy. MATERIALS AND METHODS: Twenty-eight 3-mm aortotomy incisions were created in nine heparinized pigs without antiplatelet therapy and treated with PCC. Sixty-eight aortotomy incisions were created in ten heparinized pigs that received clopidogrel (10-11 mg/kg) and acetylsalicylic acid (8-11 mg/kg) orally for 5 days, and treated with either PCC or FTC (N = 34/group). Dual antiplatelet therapy resulted in significantly reduced platelet function. Aortotomy incisions resulted in life-threatening bleeding of 35-292 ml/min. RESULTS: In animals without antiplatelet treatment, PCC provided 96% immediate hemostatic success. In animals with antiplatelet treatment, FTC provided 18% immediate hemostatic success increasing to 74% after 10 min. Strikingly, PCC provided 94% immediate success increasing to 100% after 10 min. Controlling for differences in pretreatment bleeding rates, statistical model-estimated time to hemostasis was 12 times shorter in PCC-treated lesions (p < .02). CONCLUSION: The combination of a procoagulant collagen pad with a synthetic sealing component provides excellent hemostatic properties under a worst-case scenario. PCC rapidly and firmly adheres to tissue, thereby controlling severe arterial bleeding, even when platelet function is significantly reduced. Treatment with PCC provided superior time to hemostasis compared to FTC.

An inactivated Ross River virus vaccine is well tolerated and immunogenic in an adult population in a randomized phase 3 trial.

Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. More than 90,000 cases of RRV disease, which is characterized by debilitating polyarthritis, were reported in Australia in the last 20 years. There is no vaccine available to prevent RRV disease. A phase 3 study was undertaken at 17 sites in Australia to investigate the safety and immunogenicity of an inactivated whole-virus Vero cell culture-derived RRV vaccine in 1,755 healthy younger adults aged 16 to 59 years and 209 healthy older adults aged ≥60 years. Participants received a 2.5-µg dose of Al(OH)(3)-adjuvanted RRV vaccine, with a second and third dose after 3 weeks and 6 months, respectively. Vaccine-induced RRV-specific neutralizing and total IgG antibody titers were measured after each immunization. Vaccine safety was monitored over the entire study period. The vaccine was safe and well-tolerated after each vaccination. No cases of arthritis resembling RRV disease were reported. The most frequently reported systemic reactions were headache, fatigue, and malaise; the most frequently reported injection site reactions were tenderness and pain. After the third immunization, 91.5% of the younger age group and 76.0% of the older age group achieved neutralizing antibody titers of ≥1:10; 89.1% of the younger age group and 70.9% of the older age group achieved enzyme-linked immunosorbent assay (ELISA) titers of ≥11 PanBio units. A whole-virus Vero cell culture-derived RRV vaccine is well tolerated in an adult population and induces antibody titers associated with protection from RRV disease in the majority of individuals. (This study is registered at www.clinicaltrials.gov under registration no. NCT01242670.).

A non-adjuvanted whole-virus H1N1 pandemic vaccine is well tolerated and highly immunogenic in children and adolescents and induces substantial immunological memory.

This phase 1/2 open-label, randomized clinical study investigated the safety and immunogenicity of a non-adjuvanted, whole virus, Vero cell-derived H1N1 pandemic influenza vaccine (A/H1N1/California/07/2009) in children and adolescents (6 months to 17 years). Subjects were stratified by age (6-11 months, 12-35 months, 3-8 years, 9-17 years) to receive two vaccinations 21 days apart of either the 3.75 µg or 7.5 µg dose. A booster with a licensed trivalent seasonal (2010/2011) influenza vaccine was administered one year after the first vaccination to a subgroup that had previously received the 7.5 µg dose. A single vaccination with the 7.5 µg dose induced high seroprotection rates in all subjects, namely: 88.0% (9-17 years); 68.0% (3-8 years); 42.9% (12-35 months); and 50.0% (6-11 months). Following a second vaccination, seroprotection rates ranged from 84.2% to 100%. GMTs after two vaccinations with the 7.5 µg dose (as determined by HI) were also substantial: reaching 210.0 (9-17 years), 196.2 (3-8 years), 118.9 (12-35 months) and 99.6 (6-11 months). Antibody persistence was demonstrated at 6 months (GMTs ranging from 65.6 to 212.8 with the 7.5 µg dose) and at 12 months (GMTs ranging from 33.6 to 124.1 with the 7.5 µg dose) after primary vaccination. The booster vaccination induced a strong response to the A/California/07/2009 strain, reaching 100% seroprotection in all age groups, with GMTs ranging from 640.0 to 886.3. The vaccine was well tolerated, inducing low adverse reaction rates (overall fever rate: 6% after the first vaccination; 7% after the second vaccination), even in young children. These data confirm that the H1N1 whole-virus Vero cell-derived pandemic influenza vaccine is suitable for use in children and adolescents; a 2-dose primary vaccination induces a memory response in a naïve population that can be effectively boosted with the A/H1N1/California/07/2009 component of a seasonal influenza vaccine. ClinicalTrials.gov Identifier: NCT00976469.

Safety and immunogenicity of an inactivated whole virus Vero cell-derived Ross River virus vaccine: a randomized trial.

BACKGROUND: Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. Approximately 5000 cases of RRV disease, which is characterized by debilitating polyarthritis, are recorded each year in Australia. This study describes the first clinical trial of a candidate RRV vaccine. METHODS: An inactivated whole-virus Vero cell-derived RRV vaccine was tested in 382 healthy, RRV-naïve adults in a phase 1/2 dose-escalation study at ten sites in Austria, Belgium and The Netherlands. Subjects were equally randomized to receive 1.25 µg, 2.5 µg, 5 µg, or 10 µg aluminum hydroxide-adjuvanted or non-adjuvanted RRV vaccine, with a second dose after three weeks and a booster at six months. Vaccine immunogenicity was determined by measurements of serum IgG and neutralizing antibody titers. Vaccine tolerability and safety were monitored over the entire study period. RESULTS: The optimal vaccine formulation was the adjuvanted 2.5 µg dose, as calculated using a repeated mixed model analysis of covariance comparing log-transformed RRV-specific IgG titers between different dose groups. Geometric means of RRV-specific serum antibodies measured 21 days after the third vaccination with the 2.5 µg adjuvanted formulation were 520.9 (90% CI 377.2-719.4) as determined by IgG ELISA and 119.9 (82.6-173.9) as determined by virus neutralization assay, resulting in seropositivity rates of 92.9% (82.6-98.0) and 92.7% (82.2-98.0), respectively. All vaccine formulations and doses were well tolerated after the first, second and third vaccination. CONCLUSIONS: The adjuvanted, inactivated whole-virus Vero cell-derived Ross River virus vaccine is highly immunogenic in RRV-naïve adults and well tolerated at all dose levels.

Comparison of immunogenicity and safety between two paediatric TBE vaccines.

TBE vaccination strategies capable of inducing strong paediatric immunogenicity and acceptable reactogenicity are still under evaluation. This single-blind, multi-center, randomized, controlled, phase III clinical study compared the immunogenicity and safety of the two paediatric TBE vaccines available in Europe (FSME-IMMUN Junior and Encepur Children) following administration of two doses of either vaccine in 303 children aged 1-11 years. Regardless of immunological test or viral antigen used, immunological responses were consistently higher in children vaccinated with FSME-IMMUN Junior than those vaccinated with Encepur Children. FSME-IMMUN Junior is also non-inferior to Encepur Children, with respect to NT seropositivity rates (p<0.0001). Systemic reaction rates were low and similar between the vaccines. However, among children aged 7-11 years, local reactions were significantly higher after the first (p<0.01) and second (p<0.001) vaccination with Encepur Children than with FSME-IMMUN Junior, affecting half the children in the former group: 22.4% and 10.2% with FSME-IMMUN Junior vs. 49.0% and 51.0% for Encepur Children.

Breast-conserving surgery for T3/T4 breast cancer: an analysis of 196 patients.

INTRODUCTION: Breast conservation therapy (BCT) increases quality of life and self-esteem of breast cancer patients. In special cancer centers up to 90% of patients are treated with BCT. T3/T4 breast cancer is one of the few contraindications for BCT. However, retrospective data suggest that BCT may be eligible in selected cases of T3/T4 breast cancer. METHOD: We analyzed retrospectively 196 breast cancer patients (operated between 1995 and 2004) suffering from T3/T4 tumors and compared BCT and radiotherapy with mastectomy in these patients in terms of overall survival (OS), local recurrence free-survival (LRFS) and breast cancer-related death (BCRD). RESULT: Demographic data showed no significant differences in prognostic factors between patients treated with mastectomy compared with BCT. Kaplan-Meier curves demonstrated no significant difference for OS, LRFS and BCRD between the two groups. DISCUSSION: Our data strongly suggest that BCT with R0 resection followed by radiotherapy is feasible in patients with T3/T4 breast cancer. Prospective studies have to be performed to further investigate this issue.

Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer.

PURPOSE: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial. METHODS AND MATERIAL: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy +/- boost (n = 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months. RESULTS: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival. CONCLUSION: Breast radiotherapy +/- boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse.

Preoperative core needle biopsy does not increase local recurrence rate in breast cancer patients.

OBJECTIVE: Several case reports and clinical studies in the literature demonstrate needle track seeding after core needle biopsy in patients with breast cancer in up to 50% of cases. The impact of this observation on local recurrence and overall survival rate is, however, not fully investigated. PATIENTS AND DESIGN: We retrospectively analysed 719 patients after breast conserving surgery and postoperative radiotherapy for stage I and II breast cancer. We divided this group into patients with (189) and without (530) preoperative core needle biopsy. Demographic data, local recurrence and overall survival rate were compared between these two groups. RESULT: Preoperative core needle biopsy did not significantly influence the local free recurrence rate (median follow-up time of 78 and 71 months, respectively). The prognostic factors and the postoperative therapy did not differ significantly between the two groups. CONCLUSION: Preoperative core needle biopsy seems to have no detrimental impact on local recurrence and overall survival after breast conserving surgery and postoperative radiotherapy.