Aix Scientifics®   Clinical Research Organisation

Publikationen basierend auf Aix Scientifics®-Studienergebnissen

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  • Coronary artery bypass grafting supported with intracardiac microaxial pumps versus normothermic cardio pulmonary bypass: a prospective randomized trial.
    Meyns B, Autschbach R, Böning A, Konertz W, Matschke K, Schöndube F, Wiebe K, Fischer EG (2002)
    Europ.J.Cardio-thoracic Surgery 22,1:112-117   [Bart Meyns et al.] .
    -Objective-: To analyze the difference in coronary artery bypass grafting (CABG) performed with normothermic cardiopulmonary bypass (CPB) and CABG supported with the intracardiac microaxial pump (ICP, Impella, Aachen, Germany). -Methods-: A prospective randomized study was conducted in seven centers. The study population consists of 199 patients undergoing isolated primary CABG (CPB group 94 patients, ICP group 105 patients). Both groups are equal in demographic variables, number of bypasses performed, and Euroscore predicted mortality. We analyzed clinical outcome, myocardial enzymes and blood parameters of hemolysis, organ function and inflammatory response. -Results-: Seventeen patients (16%), randomized in the ICP group, were switched to the CPB group. This was due to the inability to position the right side catheter adequately (n=8), to a pump failure (n=1) or to the perioperative decision that beating heart surgery is technically not possible (n=8). There was no significant difference between the two study arms regarding the pump assistance time (CPB 67.1±22.9 min; ICP 67.7±30.3 min; P=0.88861), the number of grafts (CPB 2.4±0.7; ICP 2.3±0.8) and the number of grafts to the back wall (CFX; both groups n=37). There is no significant difference in clinical outcome, evolution of myocardial enzymes, indices of organ function and hemolysis. There is a reduced inflammatory response in the ICP group as indicated in the postoperative release of granulocyte elastase (CPB 259±195; ICP 150±126 µg/l; P<0.00001) and complement C3 (CPB 0.73±0.2; ICP 0.65±0.2 g/l; P=0.008). -Conclusion-: The intracardiac pump for the right heart is difficult to introduce. As a consequence the right side pump underwent design modifications. There were no differences in clinical outcome between both groups. The inflammatory response is significantly reduced in the ICP group.
  • Collection of WBC-reduced single-donor PLT concentrates with the new blood cell separator: results of a multicentre study.
    [Coleta de concentrados plaquetários de doador único com reduzido teor de leucócitos com um novo separador de células sanguíneas: resultados de um estudo multicêntrico.]
    Moog R, Zeiler T, Heuft HG, Stephan B, Fischer EG, Kretschmer V, Rödel-Spieker R, Strasser E, Zingsem J (2003)
    Transfusion 43,8:1107-1114 + Corrections: 43,10:1502  
    Moog R et al. [English] .   [Português] .
    -BACKGROUND-: A new cell separator (COM.TEC, Fresenius) was recently developed aimed at efficient collection of WBC-reduced single-donor PLT concentrates (SDPs). -STUDY DESIGN AND METHODS-: Five German centers collected 554 WBC-reduced SDPs with help of the COM.TEC cell separator. Two multicenter cell counting studies were performed at the beginning and at the end of the study to document uniform counting results among the participating centers. -RESULTS-: A total of 441 (79.6%) PLT collections were included in the study according to the protocol. A total of 342 single-dose and 99 double-dose SDPs were collected. For single-dose SDPs, an average blood volume of 2826 ± 409 mL was processed in a donation time of 55 ± 11 minutes. Mean PLT yield of these products was 3.11 x 1011 ± 0.40 x 1011 and the WBC contamination was 0.11 x 106 ± 0.20 x 106. For double-dose SDPs (PLT count, 5.29 ± 0.93 x 1011), 3943 ± 639 mL was processed. The average difference between the target and the collected PLT concentration was -2.8 ± 12.0 percent for single-dose SDPs and -1.8 ± 9.5 for double-dose SDPs, respectively. The collection efficiency was 53.7 ± 5.8 percent for single-dose SDPs and 58.2 ± 6.2 percent for double-dose SDPs. If all results of each sample from the counting study were set to unity (to the mean over all centers), most PLT determinations were very similar to the mean, for example, near or 1 if set to unity. -CONCLUSION-: The COM.TEC machine makes it possible to obtain WBC-reduced SDPs that comply with current standards.
    -ANTECEDENTES-: Um novo separador de células (COM.TEC, Fresenius) foi recentemente desenvolvido com vistas à coleta eficiente de concentrados plaquetários de doador único (CPDUs).com reduzido teor de leucócitos. -DELINEAMENTO E MÉTODOS DO ESTUDO-: Cinco centros alemães coletaram 554 CPDUs com reduzido teor de leucócitos com o auxílio do separador de células COM.TEC. Dois estudos multicêntricos de contagem de células foram realizados no início e no final do estudo para documentar os resultados de contagem uniformes entre os centros participantes. -RESULTADOS-: Um total de 441 (79,6%) coletas de plaquetas foi incluído no estudo de acordo com o protocolo. Um total de 342 CPDUs de dose única e 99 de dose dupla foi coletado. Para os CPDUs de dose única, um volume de sangue médio de 2826 ± 409 ml foi processado em um tempo de doação de 55 ± 11 minutos. O rendimento médio de plaquetas desses produtos foi 3,11 x 1011  0,40 x 1011 e a contaminação por leucócitos foi de 0,11 x 106  0,20 x 106. Para os CPDUs de dose dupla (contagem plaquetária, 5,29  0,93 x 1011), 3943  639 ml foram processados. A diferença media entre a concentração de plaquetas alvo e a coletada foi de –2,8  12,0 % para os CPDUs de dose única e –1,8  9,5 para os CPDUs de dose dupla, respectivamente. A eficiência da coleta foi de 53,7  5,8 % para os CPDUs de dose única e 58,2  6,2% para os CPDUs de dose dupla. Se todos os resultados de cada amostra do estudo de contagem fossem ajustados para a unidade (para a média de todos os centros) a maior parte das determinações de plaquetas seria muito similar à média, por exemplo, próximo de 1, ou 1 se ajustada para a unidade. -CONCLUSÃO-: A máquina COM.TEC torna possível obter CPDUs com reduzido teor de leucócitos que atendem aos padrões correntes.
  • Evaluation of the COM.TEC cell separator in predicting the yield of harvested CD34+ cells.
    Movassaghi K, Jaque G, Schmitt-Thomssen A, Fischer EG, Paulus M, Heuft HG, Schwella N (2007)
    Transfusion 47,5:824-831
    -BACKGROUND-: This multicenter study was performed with the intention to evaluate the exactness of the predicted CD34+ cell yield calculated by two leukapheresis programs of the cell separator COM.TEC upon the number of donor's circulating CD34+ cells and the blood volume processed. -STUDY DESIGN AND METHODS-: Patients and healthy donors (n = 166) received mobilization by chemotherapy and/or granulocyte colony-stimulating factor and underwent CD34+ cell harvest by the leukapheresis programs MNC or RV-PBSC (n = 203). RESULTS: CD34+ cells were collected by 112 harvests on MNC and by 91 collections on RV-PBSC. The median collection efficiency of CD34+ cells was significantly better for the program MNC than for RV-PBSC (p < 0.001): 67% (31-109) vs. 42% (19-100). The collected CD34+ cell yield was in median more exactly by MNC than by RV-PBSC (p < 0.001): 85% (31-176) vs. 59% (22-110) of the predicted value. Concentrates obtained by RV-PBSC showed in median significantly higher percentages of mononuclear cells (p < 0.001) and CD34+ cells (p < 0.001), 86% (43-99) vs. 56% (25-95) and 1.2% (0.2-14.3) vs. 0.4% (0.1-6.0), and had lower contaminations by erythrocytes (p < 0.001) and platelets (p < 0.001), 13 mL (4-48) vs. 25 mL (5-60) and 1.9 x 1011 vs. 3.1 x 1011, than those harvested by MNC. CONCLUSION: The significantly better collection efficiency of CD34+ cells and the more exact prediction of the harvested CD34+ cell yield make the leukapheresis program MNC a safe and efficient procedure. However, concentrates collected by RV-PBSC are of a better cellular quality with a significantly higher percentage of mononuclear and CD34+ cells and a lower contamination by erythrocytes and platelets.
  • Initial results of clinical trial with a new left ventricular assist device (LVAD) providing synchronous pulsatile flow.
    Gazzoli F, Viganò M, Merk HF, Pagani F, Silvaggio G, Panzavolta M, el Banaysy A, Körfer R, Morshuis M, Pavie A, Leprince P, Glauber M, del Sarto P, Haxhiademi D, Vitali E, Russo CF, Scuri S. (2009)
    Int. J. Artif. Organs 32(6):344-353
    OBJECTIVES: A multicentric European Clinical Study is ongoing to evaluate safety and efficacy of a new pulsatile implantable LVAD (BestBeat), smaller and lighter than similar devices, capable of providing synchronous and counterpulsating flow with respect to the LV of end-stage heart failure patients. Preliminary clinical results are reported.
    METHODS: The new BestBeat LVAD was used, consisting of an implantable pulsatile blood pump, electromechanically driven by a ball screw mechanism, and a wearable electronic controller and power sources. The clinical trial was conducted at 5 European centers. Adult patients affected by CHF in NYHA Class IV despite optimized medical treatment were enrolled. The primary study endpoint was survival at 90 days. Further study endpoints were maintenance of adequate LVAD pump flow and a minimum rate of adverse events during support.
    RESULTS: As of June 2008, 6 patients received the implant. Cumulative support time was 3.7 years, median support time 176 days. All patients who completed the study survived except for one, who died after 48 days, due to combined infection and cerebrovascular accident. Another two patients died: one from intracranial bleeding 113 days after implant, and one from septic shock after 123 days. Hemodynamic improvement with Cl > 2.0 l/min/m2 and recovery of end-organ function expressed by consistent improvement of BUN, creatinine and bilirubin were reached in all patients. No device failure was observed. There was no bleeding requiring re-exploration, no hemolysis and only two device-related infections (both in one patient). Neurologic events were reported, the most serious ones occurring in patients with pre-implant respiratory and kidney failure. Three patients were discharged home. Two patients were successfully transplanted, one after 6 months and one after 13 months an device.
    CONCLUSIONS: Good performance and efficacy of the device were observed; the endpoints of the study were achieved, and its safety was consistent with expectations. The ongoing study will allow further conclusions to be drawn.
  • Anti-inflammatory effects of alkaline phosphatase in coronary artery bypass surgery with cardiopulmonary bypass.
    Kats S, Ruud Brands R, Seinen W, de Jager W, Bekker MWA, Soliman Hamad MA, Tan MESH, Schönberger JPAM. (2009)
    Recent Patents on Inflammation & Allergy Drug Discovery 3(3):214-220
    Laboratory and clinical data have implicated endotoxin as an important factor in the inflammatory response to cardiopulmonary bypass. Alkaline phosphatase prevents endotoxin-induced systemic inflammation in animals and humans. We assessed the effects of the administration of bovine intestinal alkaline phosphatase on surgical complications in patients undergoing coronary artery bypass grafting. In a double blind, randomized, placebo-controlled study, a total of 63 patients undergoing coronary artery bypass grafting were enrolled. Bovine intestinal alkaline phosphatase or placebo was administered as an intravenous bolus followed by continuous infusion for 36 hours. The primary endpoint was reduction of post-surgical inflammation. No significant safety concerns were identified.. Five patients in the placebo group displayed a significant TNF-α response followed by an increase in plasma levels of IL-6 and IL-8. Such a TNF-α response was not observed in the bovine intestinal alkaline phosphatase group, suggesting anti-inflammatory activity of bovine intestinal alkaline phosphatase. Other variables related to systemic inflammation showed no statistically significant differences. Bovine intestinal alkaline phosphatase can be administered safely in an attempt to reduce the inflammatory response in coronary artery bypass grafting patients with a low to intermediate EuroSCORE. The anti-inflammatory effects might be more pronounced in patients developing more fulminant postoperative inflammatory responses. This will be investigated in a further trial with inclusion of patients undergoing complicated cardiac surgery, demanding extended cardiopulmonary bypass and aortic cross clamp time. In this review article some recent patents related to the field are also discussed.
  • Prospective randomized study on the efficacy of blue light in the treatment of psoriasis vulgaris.
    Weinstabl A, Hoff-Lesch S, Merk HF, von Felbert V (2011)
    Dermatology 223:251-259 (DOI: 10.1159/000333364)
    BACKGROUND: Blue light has no known toxic effects on human skin, but reduces the proliferative capacity of keratinocytes in vitro. We therefore investigated the efficacy of blue light in the treatment of psoriasis vulgaris (PV).
    METHODS: Forty patients with mild to moderate PV and bilateral plaques were assigned to two groups. Group 1 (n = 20) received irradiation at home with blue light (light-emitting diode, LED, emission maximum: 420 nm) once daily for 4 weeks. In parallel, group 2 (n = 20) performed irradiations with another blue light device (LED emission maximum: 453 nm). The contralateral control plaques remained untreated in both groups.
    RESULTS: Thirty-seven patients completed the trial. The main study parameter, the difference of Local Psoriasis Severity Index (LPSI) scores of the irradiated plaques compared to the control plaques, showed statistically significant improvement after 4 weeks of treatment in both groups [group 1 (420 nm): n = 17, p = 0.04; group 2 (453 nm): n = 20, p = 0.04]. Accordingly, plaque status as assessed by both the physicians and the patients improved continuously during the 4 weeks of treatment and steadily declined thereafter.
    CONCLUSION: Blue light appears to be a promising treatment modality in PV that warrants further evaluation in larger studies.
  • Sclerotherapy using air- or CO2-O2-foam - Post-approval study. (en)
    Die Sklerotherapie mit Luft- oder CO2-O2-Schaum - Anwendungsbeobachtung. (de)
    Hesse G, Breu FX, Kuschmann A, Hartmann K, Salomon N (2012)
    Phlebologie 41(2):77-88 [G Hesse et al.(en)] . [G Hesse et al.(de)] .
    OBJECTIVES and IMPLEMENTATION: This observational study (OS) documented the efficacy and side-effects of ultrasound-guided polidocanol foam sclerotherapy (FS) for air and carbon dioxide/dioxygen foam sclerotherapy (CO2-O2 FS) through the use of an internet-based protocol. The patients were included in the study; two centers have consequently treated all their patients with CO2-O2 FS.
    MATERIALS and METHODS: Eleven centers participated in this OS, nine centers worked with air-based FS, two with CO2-O2 FS. Only approved drugs were used. With 376 patients in 553 treatments, air-based FS was performed using 0.25 % to 4 % polidocanol microfoam (Aethoxysklerol®, Kreussler). 125 patients in 152 sessions were treated with CO2-O2-based foam using 1% to 3 % polidocanol with seven parts CO2 (Laparox®, Linde) to three parts O2 (Conoxia®, Linde). For the sterile dispensing of the CO2-O2 FS a mass flow controller was used. A final clinical examination and ultrasonic testing followed four to six weeks after the last therapy session.
    RESULTS: Varicose veins larger than 3 mm were treated with an average of 5.3ml in the air-FS and 8.2 ml in the CO2-O2 FS, significant p<.0001. Side-effects with - Hyperpigmentation: air: 23.3 %, CO2-O2: 13.6 %. - Hematoma: air 14.4 %, CO2-O2: 2.5 %. - Migrane: air: 0.1%, CO2-O2: none. - Matting: air: 1.4 %, CO2-O2: none. - Burning: air: 11.7 %, CO2-O2: 5.5 %. - Thrombosis: air: 1.1 %, CO2-O2: 1.6 %. - Visual impairment: air: 0,2 % , CO2-O2: 2,0 %. There were no differences between the groups when smaller amounts of foam were used in the air-FS. Topical side-effects were smaller in the group using CO2-O2. Treatment was more efficient in that group, because larger volumes could be applied safely. Neither group showed any side effects to the central nervous system; all instances of impaired vision were spontaneously reversible within 20 minutes without further treatment. The findings published here accord with records from over 1000 treatments with CO2-O2 FS. With CO2-O2 FS there were no incidences of strokes or transient ischemic attacks (TIA). It seems that the treatment with CO2-O2 FS is more efficient for larger varicose veins than air FS. The use of physiological gas in foam sclerotherapy is probably safer, but this is not yet proven, and care has always to be taken concerning iatrogenic gas embolism.
    ZIEL und DURCHFÜHRUNG: Die Wirksamkeit und Nebenwirkungen der ultraschallgeführten Polidocanol-Schaumsklerosierung (FS) wurde in dieser Anwendungsbeobachtung (AWB) für Luft-FS und CO2-O2-FS über ein internetbasiertes Protokoll dokumentiert.
    MATERIAL und METHODEN: An der AWB nahmen 11 Zentren teil, neun Zentren arbeiteten mit Luft-FS, zwei Zentren mit CO2-O2-FS. Verwendet wurden zugelassene Medikamente. In 553 Behandlungen wurde bei 376 Patienten für die Luft-FS Polidocanol (Aethoxysklerol®, Kreussler) mit 0,25 % bis 4 % verwendet. In 152 Behandlungen erfolgte bei 125 Patienten die CO2-O2-FS mit Polidocanol 1-3 %, mit CO2 (Laparox®, Linde) und mit O2 (Conoxia®, Linde) im Verhältnis 70:30. Die Abfüllung bei der CO2-O2-FS erfolgte steril mittels der Massendurchfluss-Messtechnik. Eine klinische Abschlussuntersuchung und Ultraschallkontrolle erfolgte zirka 4-6 Wochen nach der letzten Therapie.
    ERGEBNISSE: Krampfadern größer als 3 mm wurden bei Luft-FS im Durchschnitt mit 5,3 ml, bei der CO2-O2-FS mit 8,2 ml behandelt; der Unterschied war signifikant. Nebenwirkungen: Hyperpigmentierungen: Luft 23,3 %, CO2-O2 13,6 %; Hämatom: Luft 14,4 %, CO2-O2 2,5 %; Migräne: Luft 0,1 %, CO2-O2 keine; Matting: Luft 1,4 %, CO2-O2 kein; Brennen: Luft 11,7 %, CO2-O2 5,5 %; Thrombosen: Luft 1,1 %, CO2-O2 1,6 %; Sehstörungen: Luft 0,2 %, CO2-O2 2 %. In beiden Gruppen ergab sich kein Unterschied in der Sicherheit bei durchschnittlich 5,3 ml Schaum in der Luft-FS und 8,2 ml Schaum in der CO2-O2-FS. Lokale Nebenwirkungen waren in der CO2-O2-Gruppe geringer; in dieser Gruppe war die Behandlung effektiver, da größere Volumen sicher angewandt werden konnten. In beiden Gruppen traten keine zentralneurologischen Nebenwirkungen auf, alle Sehstörungen waren innerhalb von 20 Minuten ohne zusätzliche Therapie spontan reversibel.
    CONCLUSIO: Die hier publizierten Ergebnisse stimmen mit über 1 000 Behandlungen für CO2-O2-FS aus der Literatur überein. Unter CO2-O2-FS trat in diesen Arbeiten keine TIA oder Apoplexe auf. Die CO2-O2-FS erscheint insgesamt für größere Krampfadern wirksamer als die Luft-FS. Die Verwendung der physiologischen Gase CO2-O2 in der FS ist möglicherweise sicherer als die Luft-FS. Klare Beweise stehen hier noch aus und die mögliche Komplikation der iatrogenen Gasembolie muss immer berücksichtigt werden.
  • Donor safety in triple plateletpheresis: results from the German and Austrian Plateletpheresis Study Group multicenter trial.
    Heuft HG, Moog R, Fischer EG, Zingsem J; German and Austrian Plateletpheresis Study Group (2013)
    Transfusion 53,1:211-220   [Hans-Gert Heuft et al.] .
    -BACKGROUND-: The objective was to investigate potential risks for apheresis donors associated with a triple-plateletpheresis (TP) program.
    -STUDY DESIGN AND METHODS-: Eleven hemapheresis centers randomly assigned 411 repeat donors (ratio, 1:1.2) to either double plateletpheresis (DP; 185 donors) or TP (226 donors) with a platelet (PLT) target content of at least 5.0 × 1011 PLTs/DP and at least 7.5 × 1011 PLTs/TP. The primary endpoint was procedure-related postapheresis PLT count of at least 150 × 109 /L (probability, ≥98%). Secondary endpoints were apheresis characteristics and donor adverse reactions.
    -RESULTS-: In 6 of 1133 DPs (0.5%) in 4 of 185 donors (2.2%) and in 20 of 1020 TPs (2.0%) in 14 of 226 donors (6.2%), postapheresis PLT counts were below 150 × 9/L. There were marginal but significant differences in collection efficiency (DP, 69.2 ± 9.1%; TP, 70.9 ± 9.0%; p ≤ 0.0001) and collection rate (DP, 10.4 × 109 ± 2.3 × 109 PLTs/min; TP, 10.8 × 109 ± 2.3 × 109 PLTs/min; p ≤ 0.005). The PLT yields were 5.9 × 1011 ± 0.8 × 1011 PLTs for DP and 8.3 × 1011 ± 0.9 × 1011 PLT for TP (p ≤ 0.0001) at processing times of 59 ± 13 minutes (DP) versus 80 ± 16 minutes (TP; p ≤ 0.0001). Significant PLT recruitment (1.10 ± 0.14 vs. 1.20 ± 0.23; p < 0.0001) was seen for both DP and TP. DP and TP did not differ with regard to venous access problems (VAPs) without discontinuation (3.8% for both), but DP induced fewer VAPs with discontinuation (1.1% vs. 3.0%; p < 0.01). Mild citrate toxicity (1.7% vs. 3.9%; p < 0.01) and circulatory reactions (0.4% vs. 2.2%; p < 0.01) were more often noticed in TP, but caused no increase in discontinuations.
    -CONCLUSIONS-: TP results in an increase in mild donor reactions but does not significantly impair donor safety or product quality.
  • Untersuchung zu Wachstums- und Gewichtsverläufen sowie geometrischen Veränderungen des linken Herzens nach interventionellen Verschluss von Ventrikelseptumdefekten mit der Nit-Occlud-Spirale im Kindes- und Jugendalter.
    Mahler K. (2016)
    Dissertation - Medizinischen Fakultät der Universität Hamburg (2014)   [Katrin Mahler] .
    EINLEITUNG: Ventrikelseptumdefekte (VSD) sind die häufigsten angeborenen Herzfehler. Große Defekte verursachen Herzversagen, Gedeihstörungen und pulmonalen Hochdruck. Der offen chirurgische Verschluss im Kindesalter gilt immer noch als Goldstandard, birgt jedoch viele Risiken mit sich. Der Nutzen und die Vorteile des Verschlusses von kleinen bis mittelgroßen VSDs sind weitestgehend ungeklärt. In der vorliegenden retrospektiven Beobachtungsstudie wollen wir untersuchen, wie sich Wachsen, Gedeihen und die Anatomie des linken Herzens nach einem interventionellen Verschluss von kleinen bis mittelgroßen VSDs im Kindesalter entwickeln.
    METHODEN: Daten der 33 Patienten zu Körpergewicht, Körperlänge und zur Anatomie des linken Ventrikels wurden vor und nach dem interventionellen Verschluss mittels der Nit-Occlud-Spirale ausgewertet und mit einem Normalkollektiv verglichen. ERGEBNISSE: Nach dem erfolgreichen Verschluss von kleinen bis mittelgroßen VSDs bei 33 Patienten mit einem durch schnittlichen Alter von 6,4 ± 3,8 Jahren konnte eine signifikante Verbesserung der Gewichtsentwicklung und eine signifikante Verkleinerung des linksventrikulären enddiastolischen Durchmessers (LVEDD) erreicht werden. Nach einem durchschnittlichen Nachsorge-Zeitraum von 2,22 ± 1,42 Jahren zeigt sich eine Gewichtsnormalisierung mit einem Anstieg des z-score von -0,88 ± 1,42 auf -0,46 ± 1,31; (p < 0,01). Der z-score des enddiastolischen linksventrikulären Diameters verbesserte sich zudem signifikant von 0,93 ± 1,12 auf 0,14 ± 0,89; (p < 0,01) und zeigt die erfolgreiche Volumenentlastung des linken Ventrikels.
    SCHLUSSFOLGERUNG: Der interventionelle Verschluss von kleinen und mittelgroßen VSDs mit der Nit-Occlud Lê VSD-Spirale hat sich in unserer Studie als sichere, komplikationsarme Methode bewiesen. Die Patienten profitieren nach diesem Eingriff nachweislich, er reduziert die linksventrikuläre Dilatation und verbessert die Gewichtsentwicklung nach der Intervention signifikant.
  • Tumor volume as a prognostic factor in resectable malignant melanoma.
    Voss B, Wilop S, Jonas S, El-Komy MHM, Schaller J, von Felbert V, Megahed M. (2014)
    Dermatology 228:66-70
    BACKGROUND: Vertical tumor thickness according to Breslow and histological ulceration are still the most powerful predictors for the clinical outcome of resectable cutaneous malignant melanoma (MM) without lymph node infiltration. It has been proposed that tumor volume in MM may also be of prognostic relevance. METHODS: We retrospectively analyzed the prognostic impact of tumor volume and other established risk factors in 122 MM patients with a median follow-up period of 39.7 months. RESULTS: We found the logarithmic tumor volume to be a better prognostic factor compared to Breslow tumor thickness in multivariate analysis. MM with a tumor volume below a threshold of 140 mm3 had a significantly higher relapse-free survival after 5 years of 98% compared to 47% in larger MMs (p < 0.0001). CONCLUSION: In some melanomas with a low tumor thickness, a higher tumor volume appeared to be linked to a higher risk of disease recurrence. Inclusion of tumor volume into the risk assessment of resectable MM may be of benefit in the future.
  • Improvement of pelvic floor-related quality of life and sexual function after vaginal mesh implantation for cystocele: primary endpoint of a prospective multicentre trial.
    Farthmann J, Mengel M, Henne B, Grebe M, Watermann D, Kaufhold J, Stehle M, Fuenfgeld C. (2016)
    Arch Gynecol Obstet 294(1):115-121.  
    PURPOSE: Pelvic organ prolapse (POP) impairs quality of life (QoL) due to vaginal bulge symptoms and changes in bladder/bowel and sexual function. The effect of alloplastic meshes on QoL is still being discussed. The purpose of this study was to prospectively evaluate the effect of mesh implantation on QoL and sexual function over 1 year. METHODS: 289 women with cystocele > stage I were included in this prospective multicenter study, with nine hospitals participating (ClinicalTrials.gov NCT01084889). Mesh exposures rates and pelvic floor-related QoL using the validated German version of the p-QoL questionnaire were evaluated as the primary endpoints. Based on a single-sided binominal test with α = 0.05 and a power of 0.80, a sample size of 225 for the mesh exposures was calculated. The mesh used was a 6-arm mesh with titanium coating (TILOOP® Total 6, sponsor pfm medical ag, Germany). Preoperative data were compared to 6 and 12 months postoperative data, using Wilcoxon test. RESULTS: The mean age of the patients was 67 years (min 43, max 87). All domains of QoL improved significantly compared after surgery: mean prolapse score dropped from 73.7 to 19.4 after 6 and 16.2 after 12 months (p < 0.001). Sexual function also improved significantly. The rate of dyspareunia was lower at follow-up. CONCLUSIONS; In this prospective trial, a significant positive effect of mesh implantation on pelvic floor-related QoL was observed. These findings remained stable 1 year after surgery with further improvement. This trial adds further data to the ongoing discussion on the role and risk of meshes in POP surgery .
  • Donor safety in haemapheresis: Development of an Internet-based registry for comprehensive assessment of adverse events from healthy donors.
    Heuft HG, Fischer EG, Weingand T, Burkhard T, Leitner L, Baume H, Schmidt J, Buser A, Fauchald G, Reinicke Voigt U, Mansouri-Taleghani B, for the Haemapheresis Vigilance Working Party of the German Society for Transfusion Medicine and Immunohaematology (2017)
    Transfus. Med. Hemother. 44(3):188-200   [Hans-Gert Heuft et al.] .
    BACKGROUND: Currently, there is an extensive but highly inconsistent body of literature regarding donor adverse events (AE) in haemapheresis. As the reports diverge with respect to types and grading of AE, to apheresis procedures and machines. the range of haemapheresis-related AE varies widely from about 0.03% to 6.6%. MATERIAL AND METHODS: The German Society for Transfusion Medicine and Immunohaematology (DGTI) formed a “Haemapheresis Vigilance Working Party” (Arbeitsgemeinschaft Hämapheresevigilanz, AGHV) to create an on-line registry for comprehensive and comparable AE assessment with all available apheresis devices in all types of preparative haemapheresis: plasmapheresis (PLS), plateletpheresis (PLT), red blood cell apheresis, all kind of leukaphereses (autologous/allogeneic blood stem cell apheresis , granulocyte apheresis, lymphocyte/monocyte apheresis) and all possible types of multicomponent apheresis. To ensure the comparability of the data, the AGHV adopted the “Standard for Surveillance of Complications Related to Blood Donation” from the International Society for Blood Transfusion in cooperation with the International Haemovigilance Network and the American Association of Blood Banks for AE acquisition and automated evaluation. The registry is embedded in a prospective observational multi-centre study including 20 study centres with a study period of 5 years. RESULTS: A preliminary evaluation encompassed the time period from January, 2012 to December, 2015. During this time the system proved to be safe ad stable. Out of approximately 345.000 haemaphereses 16.477 AE were reported (4.9%). The majority of AE occurred in PLS at 63%, followed by PLT at 34.5% and SC at 2.2%. Blood access problems (BAP) accounted for about 55% of the supplied AE, whereas citrate toxicity symptoms, vasovagal reactions and technical events (e. g. disposable leakages, software failures) rather equally affected haemaphereses at 8-15%. Out of 12.348 finalized AE, 8.759 (70.1%) were associated with a procedure-related break-off with BAP being the prevailing cause (5.463/8.759; 62.4%). An automated centre- and procedure-specific AE evaluation according to the latest IHN- and AGHV-standard is available within a few minutes. CONCLUSIONS: An on-line electronic platform for comprehensive assessment and centre-specific automated evaluation of AE in haemaphereses has been developed and proved to be stable and safe over a period of four years.

Publikationen, die auf Studien von Aix Scientifics® verweisen :

  • New devices and technology in interventional cardiology - Review.
    Tobis JM, Islam Abudayyeh I. (2015)
    J Cardiology 65:5-16 [Jonathan Marvin Tobis et al.] .
    There have been substantial improvements made in the tools and techniques used since the advent of percutaneous coronary intervention. What was primarily developed as a treatment of coronary artery disease is now used to address a variety of structural heart disease problems. The outcomes have been remarkably successful with relatively low complication rates that rival the results of open-heart surgery.
    This article will review some of the new devices available for management of structural cardiac conditions including congenital defects and acquired valvular abnormalities. Transcatheter treatment offers advantages over surgical intervention in recovery time, improved patient satisfaction, lower procedural risk, and avoidance of cardio-pulmonary bypass especially in high-risk patients. We will discuss different medical conditions and introduce the devices used to treat these conditions. Each device or technique has benefits and risks, and familiarity with the devices along with patient selection will best optimize the outcome.
  • Cardiología intervencionista pediátrica. Técnicas de cierre - Cierre percutáneo de la comunicación interventricular y fístulas.
    Comas JG. (ca. 2010)
    Cardiopatías Congenitas, Lisandro Benmaor, Capítulo 52 [José Girona Comas] .
  • Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation.
    Huizinga R, Kreft KL, Onderwater S, Boonstra JG, Brands R, Hintzen RQ, Laman JD. (2012)
    J Neuroinflammation 9:266-278 [Ruth Huizinga et al.] .
    BACKGROUND: Alkaline phosphatase (AP) is a ubiquitously expressed enzyme which can neutralize endotoxin as well as adenosine triphosphate (ATP), an endogenous danger signal released during brain injury. In this study we assessed a potential therapeutic role for AP in inhibiting neuroinflammation using three complementary approaches.
    METHODS: Mice were immunized to induce experimental autoimmune encephalomyelitis (EAE) and treated with AP for seven days during different phases of disease. In addition, serological assays to determine AP activity, endotoxin levels and endotoxin-reactive antibodies were performed in a cohort of multiple sclerosis (MS) patients and controls. Finally, the expression of AP and related enzymes CD39 and CD73 was investigated in brain tissue from MS patients and control subjects.
    RESULTS: AP administration during the priming phase, but not during later stages, of EAE significantly reduced neurological signs. This was accompanied by reduced proliferation of splenocytes to the immunogen, myelin oligodendrocyte glycoprotein peptide. In MS patients, AP activity and isoenzyme distribution were similar to controls. Although endotoxin-reactive IgM was reduced in primary-progressive MS patients, plasma endotoxin levels were not different between groups. Finally, unlike AP and CD73, CD39 was highly upregulated on microglia in white matter lesions of patients with MS.
    CONCLUSIONS: Our findings demonstrate that: 1) pre-symptomatic AP treatment reduces neurological signs of EAE; 2) MS patients do not have altered circulating levels of AP or endotoxin; and 3) the expression of the AP-like enzyme CD39 is increased on microglia in white matter lesions of MS patients.

Veröffentlichungen mit Referenz auf Aix Scientifics® als CRO :

  • Klinische Prüfung im Internet.
    Sänger S (2000)
    Der Onkologe 6(5):460-462
    Der Weg von der Wirkstofffindung bis hin zur Zulassung eines Medikamentes ist lang und teuer 'http://www.bpi.de/internet/PharmaInnovativ/index.htm' (Bundesverband der Pharmazeutischen Industrie). Das bedeutet, daß die Entwicklung eines neuen Medikamentes sorgfältig geplant und durchgeführt werden muß. Wirkungen und Nebenwirkungen neuer Medikamente müssen im Rahmen einer klinischen Prüfung unter genau definierten und kontrollierten Bedingungen ermittelt werden. Was kann das Internet in Bezug auf die Unterstützung der Durchführung klinischer Studien leisten? Durch die Bekanntgabe klinischer Studien im Internet können parallele Aktivitäten durch Zusammenführung von Studien mit gleicher oder ähnlicher Zielsetzung vermieden werden. Neben dem rationellen Ressourceneinsatz hat dies noch den günstigen Effekt, daß mehr Patienten in diese Studien eingeschleust werden können. Über einen 'online-Verbund' im Internet sind Partner für Klinische Prüfungen leichter zu finden, die darüber hinaus die Datenerhebung Online durchführen und Ergebnisse sofort publizieren können. Früher oft mühsam besorgte Papierversionen von Dokumentationsunterlagen für die klinische Prüfung (wie zum Beispiel die Liste der Common Toxicity Criteria oder standardisierte Erhebungsinstrumente für das Quality of Life Assessment u. a.) stehen jederzeit zur Verfügung. Im folgenden sollen Internetressourcen über die Veröffentlichung klinischer Studien im Netz, die Qualität klinischer Studien, Dokumentationsunterlagen für klinische Studien und Adressen von Contract Research Organisationen angeführt werden.
  • Auftragsforschungsinstitute in Deutschland - Eine systematische Analyse.
    Schaper K (2015)
    Thesis - Beuth Hochschule für Technik Berlin [Katharina Schaper] .
    FRAGESTELLUNG: Ziel der Arbeit war, eine systematische Analyse von Auftragsforschungsinstituten in Deutschland durchzuführen. Der Markt in Deutschland ist aufgrund der Auslagerung bestimmter Bereiche aus den pharmazeutischen Unternehmen sehr groß und unübersichtlich. Deshalb sollte erfasst werden, wie viele CROs es gibt, wo sie in Deutschland angesiedelt sind, in welchen Phasen der Arzneimittelentwicklung klinische Prüfungen durchgeführt und welche Tätigkeitsbereiche angeboten werden. Außerdem war von Interesse, ob es sich bei den Auftragsforschungsinstituten um 'Full Service'-CROs, die einen kompletten Service rund um eine klinische Prüfung anbieten, oder um 'Teilservice'-CROs handelt, die nur bestimmte Bereiche einer klinischen Prüfung durchführen.
    MATERIAL und METHODEN: Die genaue Definition eines Auftragsforschungsinstituts stellte einen wesentlichen Bestandteil der systematischen Analyse dar. Auf Grundlage dieser Beschreibung war es möglich, die Recherche stets nach den gleichen Kriterien durchzuführen. Darum wurde nach Sichtung der gesetzlichen Maßgaben (Deklaration von Helsinki - letzte Fassung vom Oktober 2013, ICH-Guidelines, europäische Regularien, Arzneimittel- und Medizinproduktegesetz) und verschiedener Definitionen rund um eine klinische Prüfung (Auftragsforschungsinstitut, Site Management Organization, KKS-Netzwerk, Tätigkeitsbereiche und Phasen der Arzneimittelentwicklung) eine eigene Darstellung für eine 'Full Service'-CRO entwickelt: Eine 'Full Service'-CRO ist ein kommerzielles Unternehmen mit Sitz in Deutschland, welches die Tätigkeitsbereiche Projektmanagement (inkl. Regulatory Affairs), Monitoring, Datenmanagement, Biometrie/Statistik, Medical Writing und Pharmakovigilanz anbietet und mindestens zwei Phasen der Arzneimittelentwicklung unterstützt. Des Weiteren müssen sich die Indikationsgebiete auf medizinische Fachgebiete beziehen. Die Einhaltung bestimmter Qualitätsstandards wird für jede CRO vorausgesetzt. Auf Grundlage dieser Definition war es möglich, die systematische Recherche zu beginnen. Dabei wurden die Mitglieder des Bundesverbands der Pharmazeutischen Industrie e.V. (BPI) und die Mitglieder des Verbands Forschender Arzneimittelhersteller e.V. (vfa) mit der Bitte kontaktiert, kooperierende Auftragsforschungsinstitute zu nennen. Außerdem wurden die Mitglieder des Bundesverbands Medizinischer Auftragsforschungsinstitute e.V. (BVMA) erfasst. Anschließend wurde mittels Internetrecherche nach weiteren CROs gesucht. Die Rechercheergebnisse wurden mithilfe einer Datenbank bzw. einem Katalog systematisch aufbereitet. Weiterhin wurden die Informationen über die Auftragsforschungsinstitute in einer deskriptiven Analyse zusammengefasst.
    ERGEBNISSE: Insgesamt wurden 136 CROs erfasst, von denen 40 Mitglied beim BVMA sind. 22% (n=30) der CROs sind im Raum München angesiedelt, gefolgt von Berlin mit zehn (7%) CROs. Es schließen sich Frankfurt am Main, Freiburg und Hamburg mit jeweils acht (6%) CROs an. Alle weiteren CROs verteilen sich überwiegend auf den süd-/südwestlichen Raum von Deutschland. Insgesamt gibt es 40 (29%) 'Full Service'-CROs, von denen 18 (45%) Mitglied beim BVMA sind. Die Phasen II und III der Arzneimittelentwicklung werden von 91% (n=96) bzw. 92% (n=97) der CROs angeboten. Schlusslicht bildet die Präklinik: nur 14% (n=15) der Auftragsforschungsinstitute führen diese Phase durch. Die definierten Tätigkeitsbereiche einer 'Full Service'-CRO werden zu jeweils ca. 2/3 von allen CROs angeboten. Ausnahme bildet hier die Pharmakovigilanz, sie wird nur von 53% der CROs als Serviceleistung durchgeführt. Im Median werden zwei zusätzliche/andere Tätigkeitsbereiche von den CROs angeboten. Dies sind vor allem die Felder Pharmakologie, Labor/Analytik, Qualitätsmanagement, Qualitätssicherung und Unterstützung beim Marktzugang. SCHLUSSFOLGERUNG: Zusammenfassend lässt sich sagen, dass der Bedarf an Auftragsforschungs-instituten in den nächsten Jahren mit an Sicherheit grenzender Wahrscheinlichkeit weiter steigen wird. Pharmazeutische Unternehmen lagern zunehmend immer mehr Bereiche der klinischen Forschung aus, um bspw. Kosten einzusparen oder weil es sich für die Unternehmen nicht rentiert, kleine Abteilungen wie zum Beispiel die Biometrie/Statistik dauerhaft aufrecht zu erhalten. Die Etablierung einer CRO-Datenbank bzw. eines CRO-Katalogs bringt für beide Parteien Vorteile. Pharmazeutische Unternehmen erkennen auf einen Blick potentielle Partner und können sich eine eigene Recherche im Internet ersparen. Für die Auftragsforschungsinstitute ist die Datenbank/der Katalog kostenlose Werbung, wenn entsprechende Informationen über die CRO vorhanden sind. Des Weiteren bietet der Katalog auch für die Auftragsforschungsinstitute den Vorteil, dass Partnerschaften mit anderen CROs geschlossen oder die Angebote der eigenen CRO erweitert werden können. Durch die Dynamik in der Wirtschaft und der Arzneimittelentwicklung sowie durch gesetzliche Veränderungen wird es schnell zu veralteten Daten in der CRO-Datenbank/im CRO-Katalog kommen. Daher muss diese Datenbank ständig auf dem neuesten Stand gehalten und die Recherche fortgesetzt werden, da wahrscheinlich nicht alle Auftragsforschungsinstitute in Deutschland im Rahmen dieser Arbeit erfasst wurden.
    [AIM: The aim of this thesis was the systematic analysis of contract research organizations (CRO) located in Germany. It had to be examined how many CROs currently exist and where they are located. In addition, the offered key activities and the supported drug development phases had to be analyzed. Each CRO had to be classified as a 'full service' or 'part service' CRO. MATERIAL and METHODS: The definition of a contract research organization is an essential part of this systematic analysis. After reviewing the legal stipulations and several definitions,a 'full service' CRO was defined as follows : a 'full service' CRO is a commercial company located in Germany, which offers certain activities and which supports at least two drug development phases. For the systematic analysis the members of the German Pharmaceutical Industry Association (BPI) were surveyed as well as the members of the Research-Based Pharmaceutical Companies (vfa). Furthermore the members of the Federal Association of Contract Research Organizations (BVMA) were listed and an internet search was done to find more CROs. The research results were entered into a database or a catalogue. Finally the data were subject of a descriptive analysis. RESULTS: A total of 136 CROs were determined, 40 of them are members of the BVMA. 22% (n = 30) of the CROs are located near Munich, followed by Berlin with ten (7%) CROs. All other CROs are distributed mainly across the southern/south-western area of Germany. In total, there are 40 (29%) 'full service' CROs. Phases II and III of drug development are offered by 91% (n = 96) and 92% (n = 97) of the CROs. Each of the defined key activities of a 'full service' CRO are offered by about 2/3 of all CROs. CONCLUSION: In the next few years the need for contract research organizations will increase. The creation of a CRO database or a CRO catalogue is useful for both parties: Potential partner CROs can be found faster and CROs get a free advertising. Due to high dynamics on the market, parts of the research results may become obsolete and so the database must be updated permanently. ]
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