Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis

Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.” Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly influenced. Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model. Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals (34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis. Conclusion The vagal nerve is therefore an important modulator of the immune system. W. Kessler and T. Traeger contributed equally to this work Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany     

Doing it right the first time: quality improvement and the contaminant blood culture.

The aim of the project was to determine whether the rate of contaminant blood cultures could be reduced by using a team of dedicated phlebotomists. Comparisons were made between adult patients requiring blood cultures for suspected bacteremia on medical and surgical units before and after the introduction and withdrawal of a dedicated blood culture team. The results showed that a significant reduction in the contaminant blood culture rate was achieved by the blood culture team (P < 0.001; chi(2) test). Therefore, in our experience, the rate of contaminant blood cultures can be reduced in a teaching hospital by using a team of dedicated phlebotomists. Calculations made with our data and those published by others suggest that cost savings from reducing false-positive blood cultures are greater than the cost of the blood culture team.     

Clinical indications and perspectives for intraoperative cone-beam computed tomography in oral and maxillofacial surgery.

OBJECTIVES: Intraoperative cone-beam computerized tomography (CBCT) imaging has been introduced in oral and maxillofacial surgery. Using midfacial fractures as the pioneer model, this study describes the spectrum of further promising clinical indications for intraoperative CBCT and a clinical combination with intraoperative navigation. STUDY DESIGN: One hundred seventy-nine patients admitted for surgical treatment of the facial skeleton were included in the study. Intraoperatively, 3-dimensional images were generated with the mobile CBCT scanner Arcadis Orbic 3D, obtained from Siemens Medical Solutions, in a variety of indications. RESULTS: The acquisition of the data sets was uncomplicated, and image quality was sufficient to assess the postoperative result in all cases. In the example of a facial gunshot injury, a navigation system for intraoperative localization of the metal foreign bodies was used.     

Clopidogrel versus Acetylsalicylsäure in der Sekundärprophylaxe vaskulärer Erkrankungen

Ohne Zusammenfassung     

13C-ethanol and 13C-acetate breath tests in normal and aldehyde dehydrogenase deficient individuals

Four normal and five aldehyde dehydrogenase (ALDH) isozyme I deficient individuals were subsequently loaded with (1-13C)ethanol and (1-13C)sodium acetate and the conversion of the label to 13CO2 was determined in expired air by isotope ratio mass spectrometry. In the 13C-acetate breath test, both groups showed virtually identical recovery of the label in expired air, namely 48.5 +/- 2.3% (mean +/- S.D.) for normal and 46.8 +/- 5.7% for deficient individuals. However, in the 13C-ethanol breath test, both the groups performed differently. On average, although a certain overlap of the single data was observed, the recovery of the label after four hours was 43.4 +/- 3.8% for the normal and 35.6 +/- 6.8% for the ALDH deficient subjects. These findings suggest a slower conversion of ethanol to carbon dioxide in aldehyde dehydrogenase deficient individuals, which may be another consequence of this deficiency besides the higher plasma acetaldehyde levels observed after ethanol loading in comparison to individuals with normal aldehyde dehydrogenase activity.     

A novel technique of ab interno glaucoma surgery: follow-up results after 24 months

Purpose It was the aim of this study to investigate the efficacy, longevity, and safety of a new ab interno intervention for the treatment of primary open-angle glaucoma (POAG). Methods The previously described method of radiofrequency-mediated “sclerothalamotomy ab interno” was applied in 53 eyes of consecutive patients with POAG between April 2002 and July 2002. Average preoperative intraocular pressure (IOP) was 25.6±2.3 mmHg (range 18–48 mmHg). Sclerothalamotomies were carried out with a custom-made high-frequency dissection 19 G probe (tip 0.3×1 mm) applying bipolar current with a frequency of 500 kHz (tip temperature 130°C). Results After a follow-up period of 24 months, the average IOP was 15.0±1.6 mmHg (range 11–20 mmHg) (p<0.005). The average number of topical agents was 2.6±1.0 (range 1–5) preoperatively. Twenty-four months after surgery such agents were used in only five (9.6%) eyes and the average was 0.21±0.53 (range 0–2). Transient IOP elevation was observed in 12 of 53 eyes (22.6%) postoperatively. In all cases elevated IOP could efficiently be controlled with topical medication. In general, IOP dropped continuously over the course of the 6 months following surgery and then remained constant. Conclusions This study indicates that sclerothalamotomy ab interno is a safe and efficient surgical method for the treatment of POAG. Long-term results clearly demonstrate the longevity of IOP reduction.