[Quality report 2011 of the German Society of Interventional Radiology (DeGIR)--part 2. Endovascular treatment of aortic aneurysms (EVAR)]. / Qualitätsreport 2011: Bericht über die Behandlungsqualität minimalinvasiver Methoden--Teil 2. Interventionelle Therapie (EVAR) von Aortenaneurysmen.

PURPOSE: To analyze the quality of treatment for endovascular aortic aneurysm repair using the data of the DeGIR quality management system. MATERIALS AND METHODS: A retrospective analysis of all data registered in the DeGIR quality management system of the year 2011 was performed regarding the treatment quality for endovascular aortic aneurysm repair. Registry of data within this system was voluntary. Quality aims of correct indication, treatment strategy and results were examined. Special interest was directed towards treatment success, complication rates and radiation exposure. RESULTS: Out of 82,881 data sets from the year 2011 overall 1167 cases of EVAR were registered. 12.4% of these cases encompassed emergency treatments. The most frequent indication was an abdominal aneurysm with 85% of cases. The median aortic diameter was 56.5 mm. 253 cases showed an aortic diameter between 50 and 55 mm. Technical success was achieved in 94.6% of all cases including emergency indications for aortic rupture. The overall complication rate of all cases was 4% with 2.5% major complications. Examining only the elective cases a mortality rate of 0.34% was found. EVAR of ruptured aneurysms yielded a mortality rate of 12%. Median dose area product and fluoroscopy time were 10,676.5 cGy × cm2 und 17.32 min respectively. CONCLUSION: Data analysis of the DeGIR quality management system proved a very high technical success rate for the registered cases of endovascular aortic aneurysm repair accompanied by a low complication rate. Improvement of data quality will need further mandatory fields within the software to be implemented. KEY POINTS: The voluntary DeGIR quality management system has reached a high acceptance among radiologists. Endovascular aortic aneurysm repair by radiologists has shown a very high technical success rate and a very low complication rate.

Heterozygous mis-sense mutations in Prkcb as a critical determinant of anti-polysaccharide antibody formation.

To identify rate-limiting steps in T cell-independent type 2 antibody production against polysaccharide antigens, we performed a genome-wide screen by immunizing several hundred pedigrees of C57BL/6 mice segregating N-ethyl-N-nitrosurea-induced mis-sense mutations. Two independent mutations, Tilcara and Untied, were isolated that semi-dominantly diminished antibody against polysaccharide but not protein antigens. Both mutations resulted from single-amino-acid substitutions within the kinase domain of protein kinase C-ß (PKCß). In Tilcara, a Ser552>Pro mutation occurred in helix G, in close proximity to a docking site for the inhibitory N-terminal pseudosubstrate domain of the enzyme, resulting in almost complete loss of active, autophosphorylated PKCßI, whereas the amount of alternatively spliced PKCßII protein was not markedly reduced. Circulating B cell subsets were normal and acute responses to B-cell receptor stimulation such as CD25 induction and initiation of DNA synthesis were only measurably diminished in Tilcara homozygotes, whereas the fraction of cells that had divided multiple times was decreased to an intermediate degree in heterozygotes. These results, coupled with evidence of numerous mis-sense PRKCB mutations in the human genome, identify Prkcb as a genetically sensitive step likely to contribute substantially to population variability in anti-polysaccharide antibody levels.

[Quality report 2011 of the Germyn Society of Interventional Radiology (DeGIR) - report about treatment quality of minimal invasive procedures]. / DeGIR-Qualitätsreport 2011 - Bericht über die Behandlungsqualität minimalinvasiver Methoden.

In 1994 the German Society of Interventional Radiology (DeGIR) introduced a voluntary quality mangement program. Out of a total of 82 881 of the year 2011, 36 467 patients, who received interventional recanalisation of pelvic or lower extremity arteries were chosen for an in depth analysis. In 33 104 (90.8 %) cases indication for interventional treatment was determined by at least one further discipline or even a multidisciplinary conference. Most treated patients were classified as Fontaine II or higher. Technical success rate over all procedures and regions was 96.2 % showing a very low failure rate of only 3.8 %. The overall complication rate was 3.2 %, periinterventional morbidity (complication C, D or E according to SIR classification) was 1.37 % and periinterventional mortality was 0.07 % (24 cases). X-ray exposure was recorded as well showing an average fluoroscopy time of 12 minutes and a dose-area product of 5034 cG × cm2. The voluntary quality management system was well accepted by the interventional radiologists. The software allows to compare the individual data of a single institution with the pooled data of all 192 participating radiology departments.

Germline characterization of early-aged onset of hereditary non-polyposis colorectal cancer.

OBJECTIVES: Hereditary non-polyposis colorectal cancer (HNPCC) is characterized by the early onset of colorectal cancer (approximately 40 years). Adolescent colorectal cancer is unusual in HNPCC families. We speculated that some DNA mismatch repair germline mutations might be associated with early onset of disease. STUDY DESIGN: Genomic DNA was extracted from members of a kindred with virulent HNPCC fitting the Amsterdam Criteria for HNPCC and sequenced for 2 DNA mismatch repair genes, hMSH2 and hMLH1. A sigmoid adenocarcinoma from the 14-year-old proband was analyzed for highfrequency microsatellite instability and immunostained for DNA mismatch repair gene expression. RESULTS: A germline mutation was identified at nucleotide 676 (codon 226) of the hMLH1 gene. The C to T transition created a nonsense mutation, truncating the hMLH1 protein. This mutation also alters the splice donor sequence, because nucleotide 676 is 2 base pairs from the 3' end of the exon 8. The proband's tumor demonstrated high-frequency microsatellite instability and displayed loss of hMLH1 expression, indicating bi-allelic inactivation of hMLH1. CONCLUSIONS: A complex mutation of hMLH1 at codon 226 is associated with adolescent onset of colorectal cancer in an HNPCC family. Genetic screening of other suspected HNPCC families with unusually young members with cancer might reveal certain genotypes with particularly virulent forms of this disease.

Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses.

Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H. pylori whole genome microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several strain-specific differences in gene composition including a large deletion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection.

Global analysis of Escherichia coli gene expression during the acetate-induced acid tolerance response.

The ability of Escherichia coli to survive at low pH is strongly affected by environmental factors, such as composition of the growth medium and growth phase. Exposure to short-chain fatty acids, such as acetate, proprionate, and butyrate, at neutral or nearly neutral pH has also been shown to increase acid survival of E. coli and Salmonella enterica serovar Typhimurium. To investigate the basis for acetate-induced acid tolerance in E. coli O157:H7, genes whose expression was altered by exposure to acetate were identified using gene arrays. The expression of 60 genes was reduced by at least twofold; of these, 48 encode components of the transcription-translation machinery. Expression of 26 genes increased twofold or greater following treatment with acetate. This included six genes whose products are known to be important for survival at low pH. Five of these genes, as well as six other acetate-induced genes, are members of the E. coli RpoS regulon. RpoS, the stress sigma factor, is known to be required for acid tolerance induced by growth at nonlethal low pH or by entry into stationary phase. Disruption of the rpoS gene by a transposon insertion mutation also prevented acetate-induced acid tolerance. However, induction of RpoS expression did not appear to be sufficient to activate the acid tolerance response. Treatment with either NaCl or sodium acetate (pH 7.0) increased expression of an rpoS::lacZ fusion protein, but only treatment with acetate increased acid survival.