Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: 10-Year Follow-up of a Randomized Phase III Trial (SAKK 10/94)

To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer.

Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura

It has been shown that β(2) -glycoprotein I (β(2) GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that β(2) GPI might play a role in TTP. We found that β(2) GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that β(2) GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of β(2) GPI to VWF by surface plasmon resonance, and determined that domain I of β(2) GPI is the binding site of VWF A1 domain. Adhesion of β(2) GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that β(2) GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that β(2) GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.

Predictors of severe late radiotherapy-related toxicity after hyperfractionated radiotherapy with or without concomitant cisplatin in locally advanced head and neck cancer. Secondary retrospective analysis of a randomized phase III trial (SAKK 10/94)

This secondary analysis was performed to identify predictive factors for severe late radiotherapy (RT)-related toxicity after treatment with hyperfractionated RT +/- concomitant cisplatin in locally advanced head and neck cancer.

Treatment outcomes and mortality of 94 patients with acromegaly

Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003.

Reprint of "Stereology meets electron tomography: towards quantitative 3D electron microscopy" [J. Struct. Biol. 159 (2007) 443-450]

Stereological tools are the gold standard for accurate (i.e., unbiased) and precise quantification of any microscopic sample. The past decades have provided a broad spectrum of tools to estimate a variety of parameters such as volumes, surfaces, lengths, and numbers. Some of them require pairs of parallel sections that can be produced by either physical or optical sectioning, with optical sectioning being much more efficient when applicable. Unfortunately, transmission electron microscopy could not fully profit from these riches, mainly because of the large depth of field. Hence, optical sectioning was a long-time desire for electron microscopists. This desire was fulfilled with the development of electron tomography that yield stacks of slices from electron microscopic sections. Now, parallel optical slices of a previously unimagined small thickness (2-5nm axial resolution) can be produced. These optical slices minimize problems related to overprojection effects, and allow for direct stereological analysis, e.g., volume estimation with the Cavalieri principle and number estimation with the optical disector method. Here, we demonstrate that the symbiosis of stereology and electron tomography is an easy and efficient way for quantitative analysis at the electron microscopic level. We call this approach quantitative 3D electron microscopy.

Physical examination during chemoradiation predicts outcome of locally advanced head and neck cancer. Secondary results of a randomized phase III trial (SAKK 10/94)

OBJECTIVES To analyze the prognostic value of clinical tumor response during chemoradiation for locally advanced head and neck cancer. PATIENTS AND METHODS The locoregional response at 50.4Gy was assessed by physical examination (PE) in patients treated within the randomized trial SAKK 10/94 using hyperfractionated radiotherapy (RT), median total dose 74.4Gy with or without cisplatin 20mg/m(2) chemotherapy on 5 consecutive days during weeks 1 and 5 or 6 of RT. Response was classified as a complete response (CR), complete response with uncertainty (Cru), partial response (PR), stable disease (SD), or progressive disease (PD). The primary endpoint was time to treatment failure (TTF) due to any cause. Secondary endpoints included locoregional-recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards (PH) models were applied to analyze the associations between survival endpoints and clinical tumor response. RESULTS A total of 136, 131 and 97 patients were evaluable for response at the primary tumor, lymph nodes and both sites combined, respectively. At 50.4Gy 57/136 (42%), 46/131 (35%) and 21/97 (22%) patients had a good response (CR/Cru vs. PR/SD) at the primary tumor, the lymph nodes, and both sites combined, respectively. The median follow-up times were 11.4, 9.6 and 11.4years for the three groups. Good responses were all significantly associated with improved TTF, LRRFS, DMFS and OS in univariate analysis whereas good response at the primary tumor and lymph nodes remained significantly associated with TTF and OS after multivariate Cox PH models. CONCLUSIONS Locoregional response at 50.4Gy was identified as predictor of oncologic outcome. PE during treatment should not be underestimated in clinical practice.

The role of postoperative prophylactic antibiotics in the treatment of facial fractures: a randomised, double-blind, placebo-controlled pilot clinical study. Part 3: Le Fort and zygomatic fractures in 94 patients

The aim of this study was to evaluate the difference between the effect of a 5-day and a 1-day postoperative course of antibiotics on the incidence of infection after midfacial fractures. A total of 98 patients with displaced Le Fort or zygomatic fractures that required operation were randomly assigned into 2 groups, both of which were given amoxicillin/clavulanic acid 1.2g intravenously every 8h from the time of admission until 24h postoperatively. The 5-day group was then given amoxicillin/clavulanic acid 625mg orally 8-hourly for another 4 days. The 1-day group was given placebo orally at the same time points. Patients were followed up 1, 2, 4, 6, and 12 weeks, and 6 months, postoperatively. The development of an infection of the wound was the primary end point. Ninety-four of the 98 patients completed the study. Two of the 45 patients in the 5-day group (4%) and 2/49 in the 1-day group (4%) developed postoperative wound infections. One in each group had a purulent infection, while the others had only wound breakdown. Two patients of the 5-day group and one in the 1-day group developed rashes on the trunk. There were no significant differences in the incidence of infection or side effects between the groups. In midfacial fractures a 1-day course of antibiotics postoperatively is as effective in preventing infective complications as a 5-day regimen.

Atlas-based Segmentation of Tumor-bearing Brain Images

In diagnostic neuroradiology as well as in radiation oncology and neurosurgery, there is an increasing demand for accurate segmentation of tumor-bearing brain images. Atlas-based segmentation is an appealing automatic technique thanks to its robustness and versatility. However, atlas-based segmentation of tumor-bearing brain images is challenging due to the confounding effects of the tumor in the patient image. In this article, we provide a brief background on brain tumor imaging and introduce the clinical perspective, before we categorize and review the state of the art in the current literature on atlas-based segmentation for tumor-bearing brain images. We also present selected methods and results from our own research in more detail. Finally, we conclude with a short summary and look at new developments in the field, including requirements for future routine clinical use.

Zur Stabilität von Motiv- und Zielprofilen im Freizeit- und Gesundheitssport

Einleitung: Massnahmen der Sportförderung werden selten systematisch auf sportbezogene Motive und Ziele ausgerichtet, obwohl sie für das Wohlbefinden und die Aufrechterhaltung des Gesundheitsverhaltens bedeutsam sind. Sudeck, Lehnert und Conzelmann (2011) haben typische Motiv- und Zielprofile im Freizeit- und Gesundheitssport identifiziert. Diese „motivbasierten Sporttypen“ bieten eine Möglich-keit, Menschen im mittleren Erwachsenenalter anhand ihrer Beweggründe zum Sporttreiben zu seg-mentieren und Fördermassnahmen darauf abzustimmen. Motive werden als zeitlich relativ überdau-ernde Dispositionen angesehen (Lehnert, Sudeck & Conzelmann, 2011). Empirische Nachweise für die längerfristige Stabilität von Motiv- und Zielprofilen im Freizeit- und Gesundheitssport fehlen aller-dings bislang. Daher wird im vorliegenden Beitrag die zeitliche Stabilität von Motiv- und Zielprofilen über 15 Monate analysiert. Methoden: Die Basisstichprobe besteht aus 228 Hochschulangestellten (MAlter = 48.1 Jahre, SDAlter = 8.1 Jahre, 61% Frauen), welche im Rahmen des Projekts „Welcher Sport für wen?“ im Mai 2008 (T1) an einem Sport-Check teilnahmen (Sudeck et al., 2011). Am Sport-Check wurden die sportbezogenen Motive und Ziele mit dem Berner Motiv- und Zielinventar (Lehnert, Sudeck & Conzelmann, 2011) schriftlich er-fragt. Bei 100 Personen (MAlter = 46.8 Jahre, SDAlter = 7.6 Jahre, 62% Frauen) konnte das Merkmal im September 2009 (T2) erneut mittels Onlinefragebogen erhoben werden. Die Daten dieser Teilstich-probe wurden mit der LICUR-Methode (Bergman, Magnusson & El-Khouri, 2003) ausgewertet. Zu-nächst wurden zu beiden Messzeitpunkten typische Motiv- und Zielprofile clusteranalytisch be-stimmt. Darauf aufbauend wurde analysiert, inwieweit sich die Cluster von T1 und T2 ähneln (struktu-relle Stabilität) und welche Entwicklungswege zwischen den gefundenen Clustern überzufällig häufig begangenen werden (individuelle Stabilität). Resultate und Diskussion: Zu T1 konnten neun typische Motiv- und Zielprofile identifiziert werden. Diese entsprechen mehrheit-lich den motivbasierten Sporttypen von Sudeck et al. (2011). Zu T2 wurden wiederum neun charakte-ristische Motiv- und Zielprofile ermittelt. Die Clusterlösungen der beiden Messzeitpunkte weisen eine grosse Ähnlichkeit auf. Die signifikanten Entwicklungswege zwischen T1 und T2 verdeutlichen, dass die Mitglieder eines Clusters überzufällig häufig zu einem Clusterpartner – d. h. einem Typen mit sehr ähnlichen Clusterzentroiden – übertreten. Die Ergebnisse sprechen insgesamt für eine hohe struktu-relle und individuelle Stabilität von Motiv- und Zielprofilen im mittleren Erwachsenenalter. Eine Ab-stimmung von mehrwöchigen Sportangeboten und -beratungen auf die individuellen Motive und Ziele scheint aufgrund ihres zeitlich überdauernden Charakters folglich lohnenswert. Literatur: Bergman, L. R., Magnusson, D. & El-Khouri, B. M. (2003). Studying individual development in an inter-individual context. A person-oriented approach. Mahwah, N. J.: Erlbaum. Lehnert, K., Sudeck, G. & Conzelmann, A. (2011). BMZI – Berner Motiv- und Zielinventar im Freizeit- und Gesundheitssport. Diagnostica, 57(3), 146-159. Sudeck, G., Lehnert, K. & Conzelmann, A. (2011). Motivbasierte Sporttypen. Auf dem Weg zur Perso-norientierung im zielgruppenspezifischen Freizeit- und Gesundheitssport. Zeitschrift für Sport-psychologie, 18(1), 1-17.

Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure.

Blood loss and bleeding complications may often be observed in critically ill patients on renal replacement therapies (RRT). Here we investigate procedural (i.e. RRT-related) and non-procedural blood loss as well as transfusion requirements in regard to the chosen mode of dialysis (i.e. intermittent haemodialysis [IHD] versus continuous veno-venous haemofiltration [CVVH]). Two hundred and fifty-two patients (122 CVVH, 159 male; aged 61.5±13.9 years) with dialysis-dependent acute renal failure were analysed in a sub-analysis of the prospective randomised controlled clinical trial-CONVINT-comparing IHD and CVVH. Bleeding complications including severity of bleeding and RRT-related blood loss were assessed. We observed that 3.6% of patients died related to severe bleeding episodes (between group P=0.94). Major all-cause bleeding complications were observed in 23% IHD versus 26% of CVVH group patients (P=0.95). Under CVVH, the rate of RRT-related blood loss events (57.4% versus 30.4%, P=0.01) and mean total blood volume lost was increased (222.3±291.9 versus 112.5±222.7 ml per patient, P <0.001). Overall, transfusion rates did not differ between the study groups. In patients with sepsis, transfusion rates of all blood products were significantly higher when compared to cardiogenic shock (all P <0.01) or other conditions. In conclusion, procedural and non-procedural blood loss may often be observed in critically ill patients on RRT. In CVVH-treated patients, procedural blood loss was increased but overall transfusion rates remained unchanged. Our data show that IHD and CVVH may be regarded as equivalent approaches in critically ill patients with dialysis-dependent acute renal failure in this regard.