Validierung von Laborparametern zur Diagnose einer DIC beim Hund

In dieser Studie wurden bei 103 traumatisierten Hunden aus der Intensivstation verschiedene Laborparameter erhoben. Innerhalb von 24 Stunden post Trauma wurden folgende Gerinnungstests aus dem Citratplasma bestimmt: der Quick-Wert, optimierter Quick-Wert, die aktivierte partielle Thromboplastinzeit und die Thrombinzeit. Zusätzlich wurden die AT III-Aktivität, die Fibrinogenspalt-produkte (FSP) und die D-Dimere bestimmt. Die Thrombozytenzahl wurde aus EDTA-Blut ermittelt. Bei einer Veränderung von mindestens der Hälfte der Laborparameter wurde zu der bestehenden Diagnose zusätzlich eine DIC diagnostiziert. Die Traumen wurden in die Gruppen Magendrehung, infektiöses Trauma, Autounfall und THR (total hip replacement) unterteilt. Die THR wurde als standartisierte Trauma-Kontrollgruppe gewählt. Die Ergebnisse wurden mit den Messwerten einer Gruppe aus gesunden Hunden verglichen und die Referenz-bereiche der Literatur entnommen. Die Häufigkeit der zusätzlich an DIC-Erkrankten in den einzelnen Untergruppen wurde ermittelt. Diese Studie zeigte, dass Hunde, die eine Magendrehung hatten oder durch ein Auto verunfallt sind, häufig sekundär eine DIC entwickelten. In beiden Fällen ist eine chirurgische Versorgung häufig angezeigt. Deshalb sollte bei der Operations-vorbereitung, vor allem bei sehr schlechtem Allgemeinzustand des Patienten, an die mögliche Entwicklung einer DIC gedacht werden. 40 % der Autounfallsopfer, 38,5 % der Hunde mit einer Magendrehung und 33 % der infektiösen Trauma-gruppe entwickelten sekundär eine DIC. Die Gruppe der Hunde, die eine THR-Operation bekommen haben, entwickelten seltener sekundär eine DIC (19,4 %). Um zu sehen, ob sich die DIC erst später nach der THR-Operation entwickelt, wurde alle zwei Tage Blut entnommen und der Gerinnungsstatus bestimmt. Zum Vergleich wurde die Gruppe der Autounfallshunde in diese Verlaufskontrolle miteinbezogen. In beiden Gruppen entwickelte sich nicht häufiger innerhalb einer Woche nach der Operation oder dem Unfall zusätzlich eine DIC. Die Laborparameter hatten bei beiden Gruppen eher die Tendenz in den Referenz-bereich. Ein weiteres Ziel dieser Studie war es herauszufinden, welche Tests geeignet sind, eine DIC zu diagnostizieren. Der optimierte Quick-Test und die Untersuchung auf D-Dimere waren den anderen Parametern sowohl in der Spezifität als auch in der Sensitivität weit überlegen. Vor allem der D-Dimer-Test lässt sich durch die einfache Handhabung und den relativ geringen zeitlichen und finanziellen Aufwand schnell unter Praxisbedingungen und im Notdienst durchführen

In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma

CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [(68)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases

Selective CXCR4+ Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin

Altres ajuts: CIBER-BBN (project VENOM4CANCER) granted to A.V. The authors are also indebted to the Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) that is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III, with assistance from the European Regional Development Fund. Protein production was partially performed by the ICTS "NANBIOSIS," more specifically by the Protein Production Platform of CIBER-BBN/ IBB (http://www.nanbiosis.es/unit/u1-protein-production-platform-ppp/) and the nanoparticle size analysis by the Biomaterial Processing and Nanostructuring Unit. The authors are also indebted to SCAC (UAB) for cell culture facilities and assistance. R.D. received an overseas predoctoral fellowship from Conacyt (Gobierno de México, 2016). N.S. was supported by a predoctoral fellowship from the Government of Navarra, V.P. received a postdoctoral fellowship from the Spanish Foundation of Hematology and Hemotherapy (FEHH), and U.U. a Sara Borrell postdoctoral fellowship from ISCIII. A.V. holds an ICREA ACADEMIA award.Under the unmet need of efficient tumor-targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22-mRTA-H6) is engineered to self-assemble as protein-only, CXCR4-targeted nanoparticles. The soluble version of the construct self-organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4 cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor-dependent mechanism of cytotoxicity. The insoluble version of T22-mRTA-H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22-mRTA-H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22-mRTA-H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self-mediated intracellular drug delivery

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial

PURPOSE: This randomized, open -label trial compared the efficacy and safety of adjuvant nabpaclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430). METHODS: We assigned 866 treatment -naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m(2)) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28 -day cycles. The primary end point was independently assessed disease -free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS: Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nabpaclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P =.18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P=.02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P =.045). At a 16 -month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P =.0232). At the 5 -year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P =.0091). Eighty-six percent (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade >= 3 treatment -emergent adverse events. Two patients per study arm died of treatment -emergent adverse events. CONCLUSION: The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine

Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL

Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure

Erythropoietin-alfa during neoadjuvant chemotherapy for locally advanced esophagogastric adenocarcinoma.

BACKGROUND: In a previous study we showed that many patients with esophagogastric adenocarcinoma experience anemia during neoadjuvant chemotherapy. We now investigated the role of erythropoietin in managing anemia during neoadjuvant chemotherapy. METHODS: Patients with esophagogastric adenocarcinoma who experienced anemia (hemoglobin < 12 g/dL) during neoadjuvant treatment received erythropoietin 10,000 IE subcutaneously three times a week. Primary outcomes were the response to erythropoietin, safety, the need for allogeneic red blood cell transfusion, and the rate of postoperative complications. RESULTS: Between April 2003 and December 2004, 24 patients (median age, 62 years) were enrolled. The mean hemoglobin level before chemotherapy was 12.5 g/dL and the mean hemoglobin level before patients received erythropoietin was 11.5 g/dL. One year after involvement in the trial, 4 of 17 analyzable patients were still anemic (hemoglobin level < 12 mg/dL). Twenty-two patients received erythropoietin, and 16 (73%) responded. We could observe a significant increase in hemoglobin concentrations under therapy with erythropoietin to 12.6 g/dL (p < 0.001). Two patients (8%) received allogeneic transfusions; the rate of postoperative complications was 16%. There were no erythropoietin-related adverse events. CONCLUSIONS: Treatment with erythropoietin is effective and well tolerated in patients with esophagogastric adenocarcinoma who experience anemia during neoadjuvant chemotherapy

Aphasie im Kindesalter am Beispiel des Landau-Kleffner-Syndroms

Beim Landau-Kleffner-Syndrom (LKS) handelt es sich um eine Erkrankung, die ausschließlich im Kindesalter auftritt, allerdings kann ein eindeutiger Krankheitsbeginn nicht genau definiert werden. Die klassische Definition geht von einer normalen Sprachentwicklung beim Kind aus, das dann plötzlich oder innerhalb von Monaten die rezeptiven und produktiven Sprachfähigkeiten verliert. Diese sprachlichen Störungen sind mit einem auffälligen epilepsietypischen EEG-Befund und möglichen epileptischen Anfällen verbunden. Die intellektuellen Fähigkeiten bleiben meist erhalten. Neuere Untersuchungen haben dem Krankheitsbild des LKS Verhaltensstörungen und psychomotorische Stör\-ungen hinzugefügt. Der ätiologische Hintergrund der Erkrankung ist bis zum heutigen Wissensstand noch nicht eindeutig geklärt worden. In aktueller Zeit werden aber vermehrt metabolische Veränderungen im Gehirn als mögliche Ursache für das LKS diskutiert. Der Verlauf der aphasischen Störungen und der EEG-Veränderungen ist durch Schwankungen gekennzeichnet. Die Prognose hinsichtlich der aphasischen Störungen beim LKS ist komplexer, während die Anfälle und die EEG-Veränderungen mit der Zeit sistieren. Bis heute sind noch keine einheitlichen Therapiekonzepte für das LKS beschrieben worden. Die Aphasie im Kindesalter anderer Ätiologien weist bezüglich ihres Charakters Unterschiede zu der Aphasie beim LKS auf. Beide Aphasien sind durch ihr heterogenes Symptombild gekennzeichnet. Obwohl in der Literatur immer wieder Zuordnungen zu Aphasiesyndromen bei Erwachsenen erfolgen, ist eine einheitliche Zuordnung der Aphasien im Kindesalter und auch der Aphasie beim LKS zu ungenau. Daraus ergibt sich eine dringende Forderung, die aphasischen Defizite bei Aphasien im Kindesalter und beim LKS genauer zu untersuchen.The Landau-Kleffner-Syndrome (LKS) is a disease that only occurs in childhood. However, the specific diseases onset can not be clearly defined. The classic definition emanates from a child’s normal language development, which suddenly or within months looses his/her receptive and productive language skills. These linguistical deficits are connected to a highly abnormal electroencephalogram (EEG) and possible seizures. In most of the cases the intellectual skills remain. Current analyses regarding this pediatric syndrome have added abnormal behaviour and psychomotor disturbances to the symptoms of the disease. The etiological background of this disease has not been fully investigated yet, currently investigators more and more discuss metabolic brain abnormalities as possible causes. The process of the language disturbances and the EEG-abnormalities are characterized by fluctuations. Regarding the aphasic disorders of the LKS, the prognosis is more complex whereas the seizures and the abnormal EEG- abnormalities suspend by and by. To date no consistent therapy concept for the LKS has been described. Childhood aphasia of different etiologies concerning its characteristics shows differences to the aphasia of the LKS. Both aphasias are labelled by heterogenic clinical features. Although in literature classifications to aphasia syndromes of adults are made a consistent classification of childhood aphasia and aphasia in the LKS is too vague. Consequently it is indispensable that further investigation is made, regarding childhood aphasia and aphasia in the LKS

Chemotherapy-induced nausea and vomiting in the treatment of gastrointestinal tumors and secondary prophylaxis with aprepitant.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) belongs to the most feared side-effects of cancer treatment. Its incidence during chemotherapy of gastrointestinal tumors (GITs) with highly and moderately emetogenic regimens is not well documented. It is also unknown whether aprepitant, a neurokinin-1 receptor antagonist, can be used as secondary antiemetic prophylaxis in case of CINV during cycle 1. PATIENTS AND METHODS: Patients with GITs who were treated with highly and moderately emetogenic chemotherapy received standard antiemetic prophylaxis including a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. In case of CINV > grade 1 (National Cancer Institute classification) during the first chemotherapy course, aprepitant was additionally administered with further cycles. RESULTS: We screened 109 patients. 16 patients (15%) experienced acute and/or delayed CINV. Features associated with CINV were low-dose cisplatin-containing chemotherapy (15/16 patients), female gender (11/16 patients), abstinence to alcohol (11/16 patients) and former emesis gravidarum (11/16 patients). 11 patients who got further courses of the same chemotherapy received aprepitant. 7 are fully assessable for response. 5 of 7 patients had a complete protection from CINV (71%) and 1 patient had improved symptoms. CONCLUSIONS: In the majority of cases, primary standard antiemetic prophylaxis provided adequate protection against CINV. In case of failure to primary prophylaxis, secondary prophylaxis with aprepitant showed a high efficacy against CINV

Grundz\ufcge der Besiedlung von Rankweil (Vorarlberg)

vorgelegt von Heinrich Ferd. AbbrederisInnsbruck, Univ., Diss., 194