Prediction of Distant Metastasis in Head Neck Cancer Patients: Implications for Induction Chemotherapy and Pre-treatment Staging?

Background and Purpose: : Intensity modulated radiation therapy (IMRT) combined treatment approaches, surgical and radiodiagnostic advances, respectively, lead to improved local-regional control in head neck cancer (HNC). With increasing local-regional control, distant metastases (DM) become more meaningful. In some trials without concomitant chemotherapy, induction chemotherapy (IC) resulted in an absolute reduction of DM by ~10-15%. In order to define a more efficient selection of patients at risk for DM with respect to IC and M-staging, we analysed our patients treated by contemporary standards. Patients and Methods: : Between 1/2002 to 12/2007, 409 HNC patients were treated with IMRT; 303/409 (74%) underwent definitive, 106 (26%) postoperative IMRT. The mean/median follow-up was 23/20 months (3-72). 70% tolerated 4-7, 9% 1-3 cycles of simultaneous cisplatin. Treatment followed a prospectively designed protocol. In a previous study with 172 HNC IMRT patients, gross tumor volume (GTV) was found the strongest predictor for local-regional control. In the current study, this criterion has been prospectively tested for DM. Numbers needed to treat were calculated for IC. Results: : DM developed in 28/399 (7%) patients; 10 presented initially with DM (total 38/409). In 13/28 (46%), DM remained the only manifestation of disease. GTV was the strongest predictor for DM (p 70 cc; only 6 of them (6/73, 8%) developed isolated DM. Conclusion: : GTV was the most significant predictor for DM, that could guide selective pre-treatment M-staging. The subgroup with isolated DM in the high risk group, that could benefit from IC, is smal

Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis

Introduction Chemokines and their receptors control immune cell migration during infections as well as in autoimmune responses. A 32 bp deletion in the gene of the chemokine receptor CCR5 confers protection against HIV infection, but has also been reported to decrease susceptibility to rheumatoid arthritis (RA). The influence of this deletion variant on the clinical course of this autoimmune disease was investigated. Methods Genotyping for CCR5d32 was performed by PCR and subsequent electrophoretic fragment length determination. For the clinical analysis, the following extra-articular manifestations of RA were documented by the rheumatologist following the patient: presence of rheumatoid nodules, major organ vasculitis, pulmonary fibrosis, serositis or a Raynaud's syndrome. All documented CRP levels were analyzed retrospectively, and the last available hand and feet radiographs were analyzed with regards to the presence or absence of erosive disease. Results Analysis of the CCR5 polymorphism in 503 RA patients and in 459 age-matched healthy controls revealed a significantly decreased disease susceptibility for carriers of the CCR5d32 deletion (Odds ratio 0.67, P = 0.0437). Within the RA patient cohort, CCR5d32 was significantly less frequent in patients with extra-articular manifestations compared with those with limited, articular disease (13.2% versus 22.8%, P = 0.0374). In addition, the deletion was associated with significantly lower average CRP levels over time (median 8.85 vs. median 14.1, P = 0.0041) and had a protective effect against the development of erosive disease (OR = 0.40, P = 0.0047). Intriguingly, homozygosity for the RA associated DNASE2 -1066 G allele had an additive effect on the disease susceptibility conferred by the wt allele of CCR5 (OR = 2.24, P = 0.0051 for carrier of both RA associated alleles) Conclusions The presence of CCR5d32 significantly influenced disease susceptibility to and clinical course of RA in a German study population. The protective effect of this deletion, which has been described to lead to a decreased receptor expression in heterozygous patients, underlines the importance of chemokines in the pathogenesis of RA

Solidarität wird an Gegenleistung geknüpft: zur Inklusionsbereitschaft der Deutschen gegenüber Zuwanderern

'Angesichts der wachsenden Bedrohung der Sozialsysteme durch die Überalterung der Gesellschaft wurde in den vergangenen Jahren verstärkt auf die Notwendigkeit von Zuwanderung hingewiesen. Allerdings kann die Integration der Migranten in die Sozialsysteme selbst Probleme aufwerfen, so zum Beispiel Finanzierungs- und Legitimationsprobleme. Dies gilt vor allem, wenn Zuwanderung bedeutet, dass Migranten überdurchschnittlich häufig von sozialstaatlicher Unterstützung abhängig sind oder wenn sie in großen Teilen der Bevölkerung vor allem als Nutznießer der Sozialsysteme angesehen werden. Daher steht die Politik vor der Aufgabe, angemessene Inklusionsstrategien für zuwandernde Gruppen zu entwickeln, um einerseits die wachsende Zahl an Zuwanderern in geeigneter Weise sozial abzusichern, zum anderen aber auch die wohlfahrtsstaatliche Leistungsfähigkeit aufrecht zu erhalten und die Solidaritätsbereitschaft der Bevölkerung nicht zu überfordern. Vor diesem Hintergrund stellt sich die Frage, wie die deutsche Bevölkerung auf die Inklusion der Zuwanderer in den Wohlfahrtsstaat reagiert und ob es Vorbehalte gegen eine vollständige Einbeziehung und einen gleichberechtigten Status von Ausländern gibt. Es ist durchaus denkbar, dass die Bürger im Hinblick auf die wohlfahrtsstaatliche Leistungszumessung eine Unterscheidung entsprechend des Aufenthaltsstatus oder der im Erwerbsleben geleisteten Steuern und Sozialbeiträge unterstützen. Ein gleichberechtigter Zugang zu staatlichen Leistungen könnte von der autochthonen Bevölkerung als ungerecht empfunden werden und zu wachsenden Ressentiments gegenüber Ausländern und zu einem Legitimationsverlust des Wohlfahrtsstaats führen. Daher soll in diesem Beitrag der Frage nachgegangen werden, inwiefern die deutsche Bevölkerung die Inklusion von Ausländern begrüßt und welches die Bedingungen sind, von denen die Inklusionsbereitschaft abhängt.' (Autorenreferat

Local tumor control and toxicity in HIV-associated anal carcinoma treated with radiotherapy in the era of antiretroviral therapy

PURPOSE: To investigate the outcome of HIV-seropositive patients under highly active antiretroviral treatment (HAART) with anal cancer treated with radiotherapy (RT) alone or in combination with standard chemotherapy (CT). PATIENTS AND METHODS: Clinical outcome of 81 HIV-seronegative patients (1988 – 2003) and 10 consecutive HIV-seropositive patients under HAART (1997 – 2003) that were treated with 3-D conformal RT of 59.4 Gy and standard 5-fluorouracil and mitomycin-C were retrospectively analysed. 10 TNM-stage and age matched HIV-seronegative patients (1992 – 2003) were compared with the 10 HIV-seropositive patients. Pattern of care, local disease control (LC), overall survival (OS), cancer-specific survival (CSS), and toxicity were assessed. RESULTS: RT with or without CT resulted in complete response in 100 % of HIV-seropositive patients. LC was impaired compared to matched HIV-seronegative patients after a median follow-up of 44 months (p = 0.03). OS at 5 years was 70 % in HIV-seropositive patients receiving HAART and 69 % in the matched controls. Colostomy-free survival was 70 % (HIV+) and 100 % (matched HIV-) and 78 % (all HIV-). No HIV-seropositive patient received an interstitial brachytherapy boost compared to 42 % of all HIV-seronegative patients and adherence to chemotherapy seemed to be difficult in HIV-seropositive patients. Acute hematological toxicity reaching 50 % was high in HIV-seropositive patients receiving MMC compared with 0 % in matched HIV-seronegative patients (p = 0.05) or 12 % in all HIV-seronegative patients. The rate of long-term side effects was low in HIV-seropositive patients. CONCLUSION: Despite high response rates to organ preserving treatment with RT with or without CT, local tumor failure seems to be high in HIV-positive patients receiving HAART. HIV-seropositive patients are subject to treatment bias, being less likely treated with interstitial brachytherapy boost probably due to HIV-infection, and they are at risk to receive less chemotherapy

Measurement of compartment pressure of the rectus sheath during intra-abdominal hypertension in rats

Objective: To investigate whether the compartment pressure of the rectus sheath (CPRS) reflects the intra-abdominal pressure (IAP) under various conditions of intra-abdominal hypertension (IAH). Design and setting: Prospective experimental study with in vivo pressure measurements at the Institute for Clinical and Experimental Surgery, University of Saarland. Animals: Sprague-Dawley rats. Interventions: Stepwise increase and decrease in IAP with continuous measurement of the correspondent CPRS. Measurements and results: Physiological IAP (2 mmHg) and CPRS (6 mmHg) showed astatistically significant difference. Stepwise elevation in IAP was associated with asimultaneous increase in CPRS. Accordingly, stepwise decompression of IAP resulted in astepwise decrease in CPRS. Under both conditions Bland-Altman analysis comparing IAP to correspondent CPRS showed avery good agreement for IAP at or above 12 mmHg. In addition, closure of the overlaying subcutaneous tissue and skin did not affect CPRS or its correlation with IAP. Conclusions: CPRS accurately reflects IAP for IAP of 12 mmHg or higher. Thus CPRS measurements may represent anovel approach for diagnosis and monitoring of IA

Intraoperative low-field MR-guided frameless stereotactic biopsy for intracerebral lesions

Background: To present our intraoperative low-field magnetic resonance imaging (ioMRI) technique for stereotactic brain biopsy in various intracerebral lesions. Method: Seventy-eight consecutive patients underwent stereotactic biopsies with the PoleStar N-20/N-30 ioMRI system and data were evaluated retrospectively. Biopsy technique included ioMRI before surgery, followed by insertion of the biopsy cannula in the lesion, and ioMRI before and after biopsy. Statistical analysis was performed to compare subgroups using Excel and SPSS statistic software. Results: In all patients, stereotactic biopsy was possible, with a mean intraoperative surgery time of 86.2 ± 28.6min and a mean hospital stay of 11.6 ± 4.6days. In 97.4% (n = 76), histology was conclusive, representing 58 brain tumors and 18 other pathologies. Five patients were biopsied previously without conclusive diagnosis, and all biopsies were conclusive this time. Mean cross-sectional lesion size in MRI T1 with contrast (n = 64) was 6.9 ± 5.7cm2, and in lesions without T1 contrast enhancement (n = 14), T2 mean cross-sectional lesion size was 5.5 ± 3.9cm2. Mean distance from the cortex surface to the lesion was 3.4 ± 1.2cm. One patient suffered from a postoperative wound dehiscence; neither clinically or radiologically significant hemorrhage after surgery, nor intraoperative complications occurred. Conclusions: Low-field ioMR-guided frameless stereotactic biopsy accurately diagnosed different intracerebral lesions without major complications for the patients, and within an acceptable surgery time and hospital stay. In repeated non-conclusive biopsies in particular, low-field ioMRI offers a technique for arriving at a diagnosi

First Demonstration of a Post-Quantum Key-Exchange with a Nanosatellite

We demonstrate a post-quantum key-exchange with the nanosatellite SpooQy-1 in low Earth orbit using Kyber-512, a lattice-based key-encapsulation mechanism and a round three finalist in the NIST PQC standardization process. Our firmware solution runs on an on-board computer that is based on the Atmel AVR32 RISC microcontroller, a widely used platform for nanosatellites. We uploaded the new firmware with a 436.2 MHz UHF link using the CubeSat Space Protocol (CSP) and performed the steps of the key exchange in several passes over Switzerland. The shared secret key generated in this experiment could potentially be used to encrypt RF links with AES-256. This implementation demonstrates the feasibility of a quantum-safe authenticated key-exchange and encryption system on SWaP constrained nanosatellites

Intra-operative high frequency ultrasound improves surgery of intramedullary cavernous malformations

Intra-operative ultrasound (ioUS) is a very useful tool in surgery of spinal lesions. Here we focus on modern ioUS to analyze its use for localisation, visualisation and resection control in intramedullary cavernous malformations (IMCM). A series of 35 consecutive intradural lesions were operated in our hospital in a time period of 24months using modern ioUS with a high frequency 7-15MHz transducer and a true real time 3D transducer (both Phillips iU 22 ultrasound system). Six of those cases were treated with the admitting diagnosis of a deep IMCM (two cervical, four thoracic lesions). IoUS images were performed before and after the IMCM resection. Pre-operative and early postoperative MRI images were performed in all patients. In all six IMCM cases a complete removal of the lesion was achieved microsurgically resulting in an improved neurological status of all patients. High frequency ioUS emerged to be a very useful tool during surgery for localization and visualization. Excellent resection control by ultrasound was possible in three cases. Minor resolution of true real time 3D ioUS decreases the actual advantage of simultaneous reconstruction in two planes. High frequency ioUS is the best choice for intra-operative imaging in deep IMCM to localize and to visualize the lesion and to plan the perfect surgical approach. Additionally, high frequency ioUS is suitable for intra-operative resection control of the lesion in selected IMCM case