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Zusammenfassung. Das schulbezogene Wohlbefinden (SBWB) ist eine wichtige Voraussetzung für schulischen Erfolg. Trotzdem existieren – insbesondere mit Blick auf die Erfassung des SBWB von Erstklässlern – im deutschsprachigen Raum nur vereinzelt Studien. Dies lässt sich möglicherweise durch das Fehlen geeigneter Instrumente begründen. Dies gilt auch und insbesondere dann, wenn der Gesundheitszustand der Kinder berücksichtigt werden soll. Das Ziel der vorliegenden Arbeit besteht in der Validierung des adaptierten Fragebogens zur Erfassung von emotionalen und sozialen Schulerfahrungen (FEESS 1 – 2; Rauer & Schuck, 2004 ) mit Fokus auf die Eignung des Instruments für chronisch kranke und gesunde Kinder. Dafür wird zunächst das Konstrukt Wohlbefinden (WB) resp. SBWB definiert und in einschlägige Theorien – die Selbstbestimmungstheorie nach Deci und Ryan (1985) und das Erwartung-mal-Wert-Modell nach Wigfield und Eccles (2000) – eingebettet. Die Bedeutung der verwendeten FEESS-Skalen und ihr Zusammenhang zum schulischen Erfolg werden aufgezeigt. 1491 Kinder wurden zu ihrer Lernfreude (LF), sozialen Integration (SI) und zu ihrem schulbezogenen Fähigkeitsselbstkonzept (SK) befragt. Die Erfassung des Gesundheitszustands wurde über Elternfragebögen und Schuleingangsuntersuchungen eruiert. Zudem wurden die Eltern zur gesundheitsbezogenen Lebensqualität (LQ) ihrer Kinder mit Hilfe eines Fragebogens zur Erfassung der Lebensqualität von Kindern (KINDL; Bullinger, Mackensen & Kirchberger, 1994 ) befragt. Die psychometrische Qualität der adaptierten FEESS-Skalen wurde für beide Gruppen (erkrankt / gesund) auf Skalen- und Itemebene untersucht. Hierzu kamen sowohl klassische Verfahren als auch Verfahren der Item-Response-Theorie zum Einsatz. Die Ergebnisse untermauern die Validität des Konstruktes SBWB und stützen die Annahme der Dreidimensionalität (LF, SI, SK). Alle drei Skalen zeigen eine zufriedenstellende bis sehr gute Reliabilität. Die Items zeigen sehr gute MNSQ-Werte (weighted mean-square; gewichtete Abweichungsquadrate) und geeignete Trennschärfen. Die externe Validität, für deren Berechnung der Zusammenhang zwischen den Angaben der Kinder und den Angaben der Eltern zur gesundheitsbezogenen LQ untersucht wurde, konnte noch nicht ausreichend nachgewiesen werden. Bis auf diese Einschränkung kann mit Hilfe der adaptierten FEESS-Skalen im nächsten Schritt das SBWB von gesunden und erkrankten Kindern verglichen werden, um mögliche Chancenungleichheiten auszugleichen.

BACKGROUND & AIMS: Colorectal cancer is an epigenetically heterogeneous disease, however, the extent and spectrum of the CpG island methylator phenotype (CIMP) is not clear. METHODS: Genome-scale methylation and transcript expression were measured by DNA Methylation and RNA expression microarray in 216 unselected colorectal cancers, and findings were validated using The Cancer Genome Atlas 450K and RNA sequencing data. Mutations in epigenetic regulators were assessed using CIMP-subtyped Cancer Genome Atlas exomes. RESULTS: CIMP-high cancers dichotomized into CIMP-H1 and CIMP-H2 based on methylation profile. KRAS mutation was associated significantly with CIMP-H2 cancers, but not CIMP-H1 cancers. Congruent with increasing methylation, there was a stepwise increase in patient age from 62 years in the CIMP-negative subgroup to 75 years in the CIMP-H1 subgroup (P < .0001). CIMP-H1 predominantly comprised consensus molecular subtype 1 cancers (70%) whereas consensus molecular subtype 3 was over-represented in the CIMP-H2 subgroup (55%). Polycomb Repressive Complex-2 (PRC2)-marked loci were subjected to significant gene body methylation in CIMP cancers (P < 1.6 × 10-78). We identified oncogenes susceptible to gene body methylation and Wnt pathway antagonists resistant to gene body methylation. CIMP cluster-specific mutations were observed in chromatin remodeling genes, such as in the SWItch/Sucrose Non-Fermentable and Chromodomain Helicase DNA-Binding gene families. CONCLUSIONS: There are 5 clinically and molecularly distinct subgroups of colorectal cancer. We show a striking association between CIMP and age, sex, and tumor location, and identify a role for gene body methylation in the progression of serrated neoplasia. These data support our recent findings that CIMP is uncommon in young patients and that BRAF mutant polyps in young patients may have limited potential for malignant progression. ispartof: CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY vol:8 issue:2 pages:269-290 ispartof: location:United States status: published

With improvements in breast imaging and minimally invasive interventions, detection of early breast cancer has increased. However, with the improved diagnostic capabilities, the risk of false-positive benign lesions as well as lesions classified as B3 by histopathology has also increased. Varying rates of malignancies are associated with B3 lesions, raising the question of whether such lesions should always be surgically removed. The results of our retrospective analysis should assist in this decision-making process.307 core needle or vacuum-assisted needle biopsies in which B3 lesions were found were examined. The most common lesions were intraductal papillomas (44 %), atypical ductal hyperplasia (22.8 %), flat epithelial atypia (9.4 %), phyllodes tumours (6.5 %), radial scars (5.9 %), LIN 1 (4.9 %), complex fibroadenomas (3.3 %) and LIN 2 (1.6 %). The frequencies depended considerably on whether the tissue was obtained by core biopsy or vacuum biopsy. Stereotactic vacuum biopsy was generally performed in the case of microcalcification not apparent on sonography. Lesions visible on ultrasound had core needle biopsy.Surgery was performed in 254 cases and a malignancy was found in 27.2 % on the final histopathology. Malignancy was found in 24.6 % of 114 cases initially diagnosed as intraductal papilloma. Similarly, cancer was discovered in 48.4 % of the 62 cases of atypical ductal hyperplasia, in 2.4 % of the 41 cases of flat epithelial atypia, complex fibroadenoma and phyllodes tumour, in 20.7 % of the 29 cases of LIN 1 and radial scar as well as in 50 % of the 8 cases of LIN 2, adenomyoepithelioma and atypical apocrine metaplasia.These data indicate the necessity for complete surgical removal of a B3 lesion when it is discovered using the core needle or vacuum-assisted biopsy technique. The decision not to perform surgery can be made when the risk of associated malignancy is deemed low in the clinical pathology conference, but careful follow-up is essential.

Objective Emotional distress in cancer patients often goes unnoticed in daily routine; therefore, distress screening is now recommended in many national guidelines. However, screening alone does not necessarily translate into better well-being. We examined whether stepped psychooncological care improves referral to consultation-liaison (CL) services and improves well-being. Methods In a cluster-randomized trial, wards were randomly allocated to stepped versus standard care. Stepped care comprised screening for distress, consultation between doctor and patient about the patient's need for CL services, and provision of CL service. Primary outcomes were referral to psychosocial services and emotional well-being half a year after baseline, measured with the Hospital Anxiety and Depression Scale. A secondary endpoint was uptake of outpatient health care. Analysis employed mixed-effects multivariate regression modeling. Results Thirteen wards were randomized; 1012 patients participated. With stepped care (N = 570; 7 wards), 22% of the patients were referred to CL services and 3% with standard care (N = 442; 6 wards; odds ratio [OR] 10.0; P

Background Growth rate of malaria parasites in the blood of infected subjects is an important measure of efficacy of drugs and vaccines. Methods We used log-linear and sine-wave models to estimate the parasite growth rate of the 3D7 strain of Plasmodium falciparum using data from 177 subjects from 14 induced blood stage malaria (IBSM) studies conducted at QIMR Berghofer. We estimated parasite multiplication rate per 48 hour (PMR48), PMR per life-cycle (PMRLC), and parasite life-cycle duration. We compared these parameters to those from studies conducted elsewhere with infections induced by IBSM (n=66), sporozoites via mosquito bite (n=336) or injection (n=51). Results The parasite growth rate of 3D7 in QIMR Berghofer studies was 0.75/day (95% CI: 0.73–0.77/day), PMR48 was 31.9 (95% CI: 28.7–35.4), PMRLC was 16.4 (95% CI: 15.1–17.8) and parasite life-cycle was 38.8 hour (95% CI: 38.3–39.2 hour). These parameters were similar to estimates from IBSM studies elsewhere (0.71/day, 95% CI: 0.67–0.75/day; PMR48 26.6, 95% CI: 22.2–31.8), but significantly higher (P < 0.001) than in sporozoite studies (0.47/day, 95% CI: 0.43–0.50/day; PMR48 8.6, 95% CI: 7.3–10.1). Conclusion Parasite growth rates were similar across different IBSM studies and higher than infections induced by sporozoite.

Dysfunction of homologous recombination is a common denominator of changes associated with breast cancer-predisposing mutations. In our previous work, we identified a functional signature in peripheral blood lymphocytes from women who were predisposed that indicated a shift from homologous recombination to alternative, error-prone DNA double-strand break (DSB) repair pathways. To capture both hereditary and nonhereditary factors, we newly established a protocol for isolation and ex vivo analysis of epithelial cells, epithelial-mesenchymal transition cells (EMTs), and fibroblasts from breast cancer specimens (147 patients). By applying a fluorescence-based test system, we analyzed the error-prone DSB repair pathway microhomology-mediated end joining in these tumor-derived cell types and peripheral blood lymphocytes. In parallel, we investigated DNA lesion processing by quantitative immunofluorescence microscopy of histone H2AX phosphorylated on Ser139 focus after radiomimetic treatment. Our study reveals elevated histone H2AX phosphorylated on Ser139 damage removal in epithelial cells, not EMTs, and poly(ADP-ribose)polymerase inhibitor sensitivities, which suggested a DSB repair pathway shift with increasing patient age. Of interest, we found elevated microhomology-mediated end joining in EMTs, not epithelial cells, from patients who received a treatment recommendation of adjuvant chemotherapy, that is, those with high-risk tumors. Our discoveries of altered DSB repair activities in cells may serve as a method to further classify breast cancer to predict responsiveness to adjuvant chemotherapy and/or therapeutics that target DSB repair-dysfunctional tumors.-Deniz, M., Kaufmann, J., Stahl, A., Gundelach, T., Janni, W., Hoffmann, I., Keimling, M., Hampp, S., Ihle, M., Wiesmüller, L. In vitro model for DNA double-strand break repair analysis in breast cancer reveals cell type-specific associations with age and prognosis.

Aberrant immune responses play a key role in the pathogenesis of inflammatory bowel disease (IBD). Most studies conducted to delineate the underlying molecular mechanisms focus on adults; an understanding of these mechanisms in children remains to be determined. Here, cytokines and transcription factors produced by immune cells within the intestinal mucosa of pediatric patients stricken with ulcerative colitis (UC) and Crohn’s disease (CD) are characterized; potential diagnostic and therapeutic targets are identified. Fifty-two pediatric IBD and non-IBD patients were enrolled in the study. Specimens were taken during ileocolonoscopy. Expression of 16 genes that encode cytokines or transcription molecules was determined by quantitative polymerase chain reaction. Clinical data were collected via retrospective chart review. Overexpression of interleukin-17A (IL-17A) was evident in children with UC compared to both non-IBD and CD patients. IL-22 was strongly increased in UC patients only. Typical proinflammatory and immunoregulatory cytokines were pronounced in IBD patients, although to a lower extent in the latter case. Clustered gene expression enabled differentiation between UC and non-IBD patients. Our findings highlight the crucial involvement of IL-17A immunity in the early course of IBD, particularly UC, and the potential value of gene panels in diagnosing pediatric IBD.

BACKGROUND:Colorectal cancer is an epigenetically heterogeneous disease, however the extent and spectrum of the CpG Island Methylator Phenotype (CIMP) is not clear.RESULTSAn unselected cohort of 216 colorectal cancers clustered into five clinically and molecularly distinct subgroups using Illumina 450K DNA methylation arrays. CIMP-High cancers were most frequent in the proximal colons of female patients. These dichotomised into CIMP-Hl and CIMP-H2 based on methylation profile which was supported by over representation of BRAF (74%, PKRAS (55%, P78). We identified oncogenes susceptible to gene body methylation and Wnt pathway antagonists resistant to gene body methylation. CIMP cluster specific mutations were observed for genes involved in chromatin remodelling, such as in the SWI/SNF and NuRD complexes, suggesting synthetic lethality.CONCLUSIONThere are five clinically and molecularly distinct subgroups of colorectal cancer based on genome wide epigenetic profiling. These analyses highlighted an unidentified role for gene body methylation in progression of serrated neoplasia. Subgroup-specific mutation of distinct epigenetic regulator genes revealed potentially druggable vulnerabilities for these cancers, which may provide novel precision medicine approaches.

We aimed to estimate unbiased effects of mental health problems (MHPs) on school performance in first graders, with an emphasis on rigorous adjustment for potential confounders. A population-based prospective cohort study was performed in the area of Mainz-Bingen (Germany). In 2015, all preschoolers were approached, and the presence and type of MHP (externalising/internalising) and other physical chronic health conditions were identified by the preschool health examination and study-specific questionnaires. At the end of the first grade, school performance (reading, writing, numeracy, and science) was assessed by the class teacher and rated on a four-item scale ranging from − 8 to + 8. Of 3683 children approached, 2003 (54%) were enrolled. School performance was available for 1462 children (51% boys, mean age 7.3 years). Of these, 41% had signs of at least one MHP. Compared to children without indications of mental and physical chronic health conditions, children with MHPs had lower school performance scores [adjusted mean difference − 0.98, 95% CI (− 1.35; − 0.61); P

Acute aortic dissection type A (AADA) is an emergency with excessive mortality if surgery is delayed. Knowledge about independent predictors of mortality on surgically treated AADA patients is scarce. Therefore, this study was conducted to identify pre- and intraoperative risk factors for death.Between July 2006 and June 2010, 2137 surgically treated patients with AADA were enrolled in a multicentre, prospective German Registry for Acute Aortic Dissection type A (GERAADA), presenting perioperative status, operative strategies, postoperative outcomes and AADA-related risk factors for death. Multiple logistic regression analysis was performed to identify the influence of different parameters on 30-day mortality.Overall 30-day mortality (16.9%) increased with age [adjusted odds ratio (OR) = 1.121] and among patients who were comatose (adjusted OR = 3.501) or those who underwent cardiopulmonary resuscitation (adjusted OR = 3.751; all P0.0001). The higher the number of organs that were malperfused, the risk for death was (adjusted OR for one organ = 1.651, two organs = 2.440, three organs or more = 3.393, P0.0001). Mortality increased with longer operating times (total, cardiopulmonary bypass, cardiac ischaemia and circulatory arrest; all P0.02). Arterial cannulation site for extracorporeal circulation, operative techniques and arch interventions had no significant impact on 30-day mortality (all P0.1). No significant risk factors, but relevant increases in mortality, were determined in patients suffering from hemiparesis pre- and postoperatively (each P0.01), and in patients experiencing paraparesis after surgery (P0.02).GERAADA could detect significant disease- and surgery-related risk factors for death in AADA, influencing the outcome of surgically treated AADA patients. Comatose and resuscitated patients have the poorest outcome. Cannulation sites and operative techniques did not seem to affect mortality. Short operative times are associated with better outcomes.

Background Malperfusion adversely affects outcomes in patients with acute type A aortic dissection, but reliable quantitative data are lacking. Objectives The aim of this study was to analyze the impact of various forms of malperfusion on early outcome. Methods A total of 2,137 consecutive patients enrolled in GERAADA (German Registry for Acute Aortic Dissection Type A) who underwent surgery between 2006 and 2010, of whom 717 (33.6%) had any kind of pre-operative malperfusion, were retrospectively analyzed. Results All-cause 30-day mortality was 16.9% and varied substantially according to the number of organ systems affected by malperfusion (none, 12.6%; 1 system, 21.3%; 2 systems, 30.9%; 3 systems, 43.4%; p Conclusions Malperfusion remains a severe clinical condition with strong potential for adverse outcomes in patients undergoing surgery for acute type A aortic dissection. The GERAADA registry suggests that the impact of the number of organs involved and the type of malperfusion on outcome differs substantially. Introducing an appropriate classification system, such as “complicated” and uncomplicated” acute type A aortic dissection, might help predict individual risk as well as select a surgical strategy that may quickly resolve malperfusion.

Objective Children with chronic health conditions may perform poorer at school. Associations may be confounded by numerous social factors. We aimed to estimate the effects of a chronic health condition on overall school performance in first graders with an emphasis on rigorous adjustment for potential confounders. Methods A population-based cohort study was performed in the area of Mainz-Bingen (Germany). In 2015 all preschoolers were approached and the presence of a chronic health condition was assessed by parental questionnaires and preschool health examination data. The identification of a chronic health condition was based on special health care needs and presence of a doctor’s diagnosis out of 24 school-relevant diseases. At the end of the first school year, overall school performance was assessed by teachers and rated on a 5-item scale ranging from -10 to +10. Results Of 3683 children approached, 2003 were enrolled. Overall school performance was available for 1462 children (51% boys). Of these, 52% suffered from a chronic health condition. Compared to children without a chronic health condition, children with special health care needs (15%) performed worse at school (adjusted mean difference: -0.95, 95% CI: [-1.55; -0.35], P = 0.002). Children with a doctor’s diagnosis but without special health care needs (37%) did not perform worse at school. The effect was further analysed considering the extent of special health care needed. Conclusions Chronic health conditions affect overall school performance early in primary school. To identify academically at-risk children, a chronic health condition identification based on special health care needs may be used.

ZusammenfassungDie Akademisierung der Pflege schreitet stetig voran. In den Fokus rücken dabei auch Weiterqualifizierungsmöglichkeiten der Mitarbeiter in der direkten Patientenversorgung.

ObjectiveOur objective was to determine long-term outcome predictors for patients with acute aortic dissection type A (AADA) and aortic root involvement.MethodsFrom 2001 through 2009, 119 of 152 patients operated on for AADA at a tertiary medical center underwent supracoronary ascending aortic replacement (52 women; mean age, 61 ± 15 years). Those with at least 1-year follow-up (n = 97) were retrospectively assessed for preoperative aortic root disease. Follow-up data were assessed for evidence of new-onset aortic root disease by computed tomography and echocardiography, and for reoperation for aortic root disease.ResultsMedian follow-up was 33.8 months (range, 0-112 months). Twenty-six (27%) patients had new-onset aortic root disease at 4.4 ± 2.6 years after the initial procedure (range, 1.0-8.2 years) and 10 required aortic root reoperation. Severe aortic dissection with extension to pelvic arteries was an independent predictor for new-onset aortic root disease (P

OBJECTIVES: Previous investigators have reported a grave prognosis for iatrogenic acute aortic dissection (iAADA), but such studies are limited by their small sample sizes. The purpose of the current study was to analyse the clinical characteristics, current management and surgical outcomes in a large number of iAADA patients identified through a multicentre registry. METHODS: Between July 2006 and June 2010, 50 centres participated in the German Registry for Acute Aortic Dissection Type A (GERAADA). Of the 2137 patients included, 100 (5%) had iAADA. We compared the clinical features and 30-day outcomes of patients with iatrogenic and spontaneous acute aortic dissection type A (sAADA). RESULTS: Patients with iAADA were older than those with sAADA (67.7 ± 9.4 vs 60.1 ± 13.7 years, P< 0.0001). Preoperative cardiac tamponade and hemiplegia or hemiparesis were less frequently observed in patients with iAADA (10 vs 21%, P= 0.003; 1 vs 7%, P= 0.04). Aortic dissection extended to the supra-aortic vessels (19 vs 38%, P= 0.0005) and to iliac arteries (7 vs 25%, P= 0.0002) less frequently in iAADA patients. Those with iAADA were less likely to undergo complex aortic surgery with composite graft implantation (8 vs 20%, P= 0.02), hemiarch (38 vs 47%, P= 0.04) or total arch replacement (9 vs 17%, P= 0.07). The rate of new onset of hemiplegia or hemiparesis after surgery was also lower in iAADA patients (4 vs 10%, P= 0.05). Thirty-day mortality did not differ between the two groups (16 vs 17% for iAADA vs sAADA, P= 0.53). CONCLUSIONS: Early-term surgical outcomes in current iAADA patients are better than those reported previously. Immediate surgical therapy results in acceptable outcomes similar to those in naturally occurring aortic dissection.

Background: Most cardiovascular events have their peak during the cold winter months. Especially for myocardial infarctions the accumulation is already well described. Several studies have investigated the incidence of acute aortic dissections (AAD) but a seasonal increase of AADs could not be shown yet due to the limited power of these studies. Therefore, we investigated the German Registry for Acute Aortic Dissection Type A (GERAADA) data for seasonal accumulations. Methods: All 2137 patients who have been registered in GERAADA from 7/2006 to 6/2010, which is a prospective, multi-centre registry of the German Society of Thoracic and Cardiovascular Surgery, have been analysed. The incidences per year, quarter, season and month were investigated considering covariates such as age, gender and etiology using poisson regression. Results: The distribution of the incidences differed significantly between the quarters. More patients were treated in quarters IV and I (p=0.002). In the months October-February there were more cases than in the rest of the year (p=0.017). Although age, gender, the underlying disease (p 0.5). Conclusions: Our data show that there is a peak of surgically treated AADs within German speaking Europe during winter months independent from patient related factors and the aetiology of the AAD.

Background and Aims Non-invasive markers of liver fibrosis are urgently required, especially for use in non-specialist settings. The aim of this study was to identify novel serum biomarkers of advanced fibrosis. Methods We performed an unbiased screen of 120 serum analytes including cytokines, chemokines and proteases in 70 patients (35 without fibrosis, 35 with cirrhosis on biopsy), and selected a panel of 44 candidate biomarkers, which were subsequently measured in a mixed-etiology cohort of 432 patients with known serum HA, PIIINP and TIMP1 (which comprise the validated Enhanced Liver Fibrosis (ELF) test). Multivariate logistic regression modelling was used to generate models for the prediction of advanced or significant fibrosis (METAVIR ≥F3 and ≥F2, respectively); in addition to identifying biomarkers of disease activity and steatohepatitis. Results Seventeen analytes were significantly differentially expressed between patients with no advanced fibrosis and patients with advanced fibrosis, the most significant being hyaluronic acid (HA) and matrix metalloproteinase (MMP) 7 (p = 2.9E-41 and p = 1.0E-26, respectively). The optimal model for the prediction of advanced fibrosis comprised HA, MMP7, MMP1, alphafetoprotein (AFP) and the AST to platelet ratio index (APRI). We demonstrate enhanced diagnostic accuracy (AUROC = 0.938) compared to a model comprising HA, PIIINP and TIMP1 alone (ELF) (AUROC = 0.898, p

Background Patients with rheumatoid arthritis (RA) are at a higher cardiovascular (CV) risk in comparison to the general population. CV risk associates closely with aortic stiffness. Aim of this exploration was therefore to evaluate aortic stiffness in patients with RA and to examine its association with various RA associated parameters as well as with traditional CV risk factors. Methods Measurements of carotid-femoral pulse wave velocity (cfPWV) were analyzed retrospectively in 38 RA patients and 25 controls. We investigated the statistical difference between cfPWV values in the two groups. Furthermore, we analyzed the associations of cfPWV with laboratory and clinical RA parameters including Disease Activity Score 28 and its components, rheumatoid factor, cyclic citrullinated peptide antibodies, antinuclear antibodies and RA duration. Finally, we explored the relationship of cfPWV with traditional CV risk factors in the RA group. Results cfPWV was not significantly higher in RA patients in comparison to controls in an adjusted statistical model for confounding factors [−0.587 95 % CI (−1.38 to 0.201), p = 0.144]. Among RA patients there was a statistically significant correlation of cfPWV with age (rho = 0.544, p = 0.001) and the count of tender joints [0.051 95 % CI (0.008–0.207), p = 0.034]. Finally, C-reactive protein associated only marginally with cfPWV [0.105 95 % CI (−0.410 to 0.003), p = 0.053]. Conclusions In RA patients the number of tender, rather than swollen joints correlates with stiffness of the aorta, as measured through cfPWV. Therefore, RA associated joint pain might play a role in the development of aortic stiffness and thus increase CV risk.

OBJECTIVES: Acute aortic dissection type A (AADA) is associated with major adverse events, such as transient or persistent neurological dysfunction (ND), which may be patient-, disease- or surgery-related. There is a lack of consensus regarding risk factors for ND in AADA patients. The aim of this study was to analyse and identify risk factors for new postoperative ND after aortic repair for AADA. METHODS: Between July 2006 and June 2010, 2137 AADA patients were enrolled in the multi-centre, prospective German Registry of AADA (GERAADA). Perioperative data were prospectively gathered from 50 institutes in Austria, Switzerland and Germany, and multivariate logistic regression analysis was performed to determine the independent predictors of new onset ND. RESULTS: ND occurred in 20.3% of all patients prior to surgery, 12.6% of which resolved postoperatively and 7.7% persisted. New ND after AADA surgery occurred in 9.5% of patients. Risk factors for an increased rate of postoperative new ND were malperfusion syndrome of three or more territories prior to surgery [odds ratio (OR) = 2.206, P=0.0065], dissection of the supraaortic vessels (OR = 1.468, P=0.0103) and longer operating time (OR = 1.002 per min, P=0.0001). New postoperative ND was associated with an increased rate of mortality (22.5 vs. 16.1%, P=0.0087). Arterial cannulation site had no statistically significant impact on neurological outcomes. CONCLUSIONS: Neurological complications are associated with increased mortality post-AADA repair. New onset ND is associated with extensive malperfusion syndrome, supraaortic vessel dissection and operative time and does not seem to be affected by choice of arterial cannulation site.

Background Representative, population-based epidemiologic data for gastroenteritis caused by rotavirus (RV) are rare. RV vaccines were first licensed in Europe in 2006 and recommended in 5 western federal states in 2008 or thereafter. This study establishes a baseline for assessing the impact of vaccination and delineates the RV disease burden in Germany today. Methods Nationwide data obtained from hospitals for children 0 to 10 years of age and transferred to the Federal Statistical Office were analyzed retrospectively. Acute gastroenteritis cases because of RV were identified by the International Classification of Diseases code (ICD-10) combined with the referring diagnosis-related group code. Coding quality was validated by random sampling the patient records (n=1003). Crude and age-standardized rates per 100,000 person-years were calculated. The rate ratios of seasonal effects and recommended immunization adjusted for year, federal state and age were estimated using Poisson regression. Results Between 2005 and 2010, 5,843,730 children were hospitalized; 520,606 cases were hospitalized because of acute gastroenteritis. RV caused 152,636 of these cases or an age-standardized rate of 302 hospitalizations per 100,000 person-years. Rates were slightly higher in boys than girls, decreased with age, and differed by federal state, year and season. Rate ratios decreased in those western federal states that recommended immunization and were inversely associated with vaccine doses sold. Conclusions With an average of 25,440 children hospitalized yearly, RV infection has a great impact on the German healthcare system. Our findings indicate that RV immunization will lead to a decline in in-patient treatment and associated costs.

Reference limits are estimators for 'extreme' percentiles of the distribution of a quantitative diagnostic marker in the healthy population. In most cases, interest will be in the 90% or 95% reference intervals. The standard parametric method of determining reference limits consists of computing quantities of the form X̅±c·S. The proportion of covered values in the underlying population coincides with the specificity obtained when a measurement value falling outside the corresponding reference region is classified as diagnostically suspect. Nonparametrically, reference limits are estimated by means of so-called order statistics. In both approaches, the precision of the estimate depends on the sample size. We present computational procedures for calculating minimally required numbers of subjects to be enrolled in a reference study. The much more sophisticated concept of reference bands replacing statistical reference intervals in case of age-dependent diagnostic markers is also discussed.

We thank Dr. Li and colleagues for their interest in our paper [(1)][1]. The genuine rationale for classifications is to simplify complexity and, as the investigators state, the Penn classification is an excellent risk stratification tool to predict mortality on the ischemic pattern at clinical

SummaryDiabetes mellitus as a major contributor to cardiovascular disease burden induces dysfunctional platelets. Platelets contain abundant miRNAs, which are linked to inflammatory responses and, thus, may play a role in atherogenesis. While diabetes mellitus affects plasma miRNAs, no data exist on platelet miRNA profiles in this disease. Therefore, this study sought to explore the miRNA profile of platelets in patients with diabetes mellitus that is unrelated to the presence or absence of coronary artery disease (CAD). Platelet miRNA profiles were assessed in stable diabetic and non-diabetic patients (each n=30); 15 patients in each group had CAD. Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma, and miRNA profiling was performed using LNA micro-array technology (miRBase18.0, containing 1,917 human miRNAs). Effects of diabetes mellitus were explored by univariate statistical tests for each miRNA, adjusted for potential confounders, and by developing a multivariable signature; evaluated by resampling techniques. Platelets in non-diabetic patients demonstrated miRNA expression profiles comparable to previous data. The miRNA profiles of platelets in diabetics were similar. Statistical analysis unveiled three miRNAs (miR-377–5p, miR-628–3p, miR-3137) with high reselection probabilities in resampling techniques, corresponding to signatures with modest discriminatory performance. Functional annotation of predicted targets for these miRNAs pointed towards an influence of diabetes mellitus on mRNA processing. We did not find major differences in platelet miRNA profiles between diabetics and non-diabetics. Minor differences pertained to miRNAs associated with mRNA processing. Thus, described differences in plasma miRNAs between diabetic and non-diabetic patients cannot be explained by plain changes in platelet miRNA profile.

OBJECTIVES: Cerebral protection during acute aortic dissection Type A (AADA) surgery may be affected by perfusion strategies and ischaemic protective drugs. METHODS: We analysed the impact of intraoperative barbiturate, steroid and mannitol use and adjunctive cerebral perfusion (CP), on 30-day mortality and new postoperative mortality-corrected permanent neurological dysfunction (PNDmc) in the German Registry for Acute Aortic Dissection Type A. RESULTS: Two thousand one hundred and thirty-seven AADA patients were registered over a 4-year period. The overall 30-day mortality was 16.9%, and the overall rate of PNDmc was 10.0%. A total of 48% of patients received no neuroprotective drugs (control group), steroid monotherapy was used in 11.2% of patients, barbiturates in 8.4%, mannitol in 7.3% and the remainder (25.1%) received a combination of these drugs. The PNDmc rate was 10.6% in the control group and lower (7.1%) in the steroid group (adjusted odds ratio [OR] 0.50; 95% confidence interval [95% CI] 0.24–0.96; P= 0.049). No PNDmc reduction was observed for mannitol or barbiturates. Thirty-day mortality was 18.7% in the control group and with 8.9% lower (P= 0.003) in the mannitol group (adjusted OR 0.58; 95% CI 0.19–1.49; P= 0.295). Hypothermic circulatory arrest that exceeded 30 min was associated with an increased 30-day mortality rate (31.4%) compared with patients who received adjunctive CP >30 min during aortic arch intervention (21.4%) (P= 0.04). We were unable to demonstrate a significant protective effect of any neuroprotective drug on 30-day mortality, or PNDmc rates during prolonged (≥30 min) cerebral ischaemia. CONCLUSION: Mannitol may be associated with decreased mortality in patients undergoing AADA surgery. Steroid administration may be associated with improved neurological outcomes, but more investigation is required.

Most presently known breast cancer susceptibility genes have been linked to DSB repair. To identify novel markers that may serve as indicators for breast cancer risk, we performed DSB repair analyses using a case-control design. Thus, we examined 35 women with defined familial history of breast and/or ovarian cancer (first case group), 175 patients with breast cancer (second case group), and 245 healthy women without previous cancer or family history of breast cancer (control group). We analyzed DSB repair in peripheral blood lymphocytes (PBLs) by a GFP-based test system using 3 pathway-specific substrates. We found increases of microhomology-mediated nonhomologous end joining (mmNHEJ) and nonconservative single-strand annealing (SSA) in women with familial risk vs. controls (P=0.0001-0.0022) and patients with breast cancer vs. controls (P=0.0004-0.0042). Young age (

Background— Cerebral protection during surgery for acute aortic dissection type A relies on hypothermic circulatory arrest, either alone or in conjunction with cerebral perfusion. Methods and Results— The perioperative and intraoperative conditions of 1558 patients submitted from 44 cardiac surgery centers in German-speaking countries were analyzed. Among patients with acute aortic dissection type A, 355 (22.8%) underwent surgery with hypothermic circulatory arrest alone. In 1115 patients (71.6%), cerebral perfusion was used: Unilateral antegrade cerebral perfusion (ACP) in 628 (40.3%), bilateral ACP in 453 (29.1%), and retrograde perfusion in 34 patients (2.2%). For 88 patients with acute aortic dissection type A (5.6%), no circulatory arrest and arch intervention were reported (cardiopulmonary bypass–only group). End points of the study were 30-day mortality (15.9% overall) and mortality-corrected permanent neurological dysfunction (10.5% overall). The respective values for the cardiopulmonary bypass–only group were 11.4% and 9.1%. Hypothermic circulatory arrest alone resulted in a 30-day mortality rate of 19.4% and a mortality-corrected permanent neurological dysfunction rate of 11.5%, whereas the rates were 13.9% and 10.0%, respectively, for unilateral ACP and 15.9% and 11.0%, respectively, for bilateral ACP. In contrast with the ACP groups, there was a profound increase in mortality when systemic circulatory arrest times exceeded 30 minutes in the hypothermic circulatory arrest group ( P Conclusions— This study reflects current surgical practice for acute aortic dissection type A in Central Europe. For arrest times less than 30 minutes, hypothermic circulatory arrest and ACP lead to similar results. For longer arrest periods, ACP with sufficient pressure is advisable. Outcomes with unilateral and bilateral ACP were equivalent.

Objective: The number of elderly patients undergoing emergency surgery for acute aortic dissection type A (AADA) is rising. Published results report a higher risk for thesepatients comparedwith younger patients. The aim of our study wasto analyse the surgicaloutcomeof these patients and to identify those at risk. Methods: Between July 2006 and June 2009, 44 centres participating in the German Registry for Acute Aortic Dissection Type A (GERAADA) reported a total of 1558 patients. As many as 381 patients were between 70 and 80 years of age (septuagenarians), while 83 patients were 80 years and older (octogenarians). We compared the clinical features and events occurring 30 days after surgery.Results: Onadmission,23%(n = 89)ofseptuagenarianshadcardiactamponade,comparedwith31%(n = 26)ofthoseage80years(p = 0.13).Alittlemore than 13% (n = 48) of septuagenarians were intubated at admission compared with 21% (n = 17) of octogenarians (p = 0.06). The septuagenarians’ 30-daypostoperativemortalitywas16%(n = 60),whereasthatofpatientsagedover80 yearswas35%(n = 29)(p < 0.001).Themeanhospitalstay in the younger group was 18 days, of which 12 days were in the intensive care unit, compared with 18 and 13 days for octogenarians, respectively. Conclusions: Emergency surgery for septuagenarians with acute aortic dissection type A (AADA) resulted in acceptable mortality. Octogenarians revealed significantly higher 30-day mortality (odds ratio (OR) = 3.23, confidence interval (CI) = (1.81—5.72)), although it was lower than the mortality among patients without surgical treatment. A surgical approach should be considered in all patients on an individual basis. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

1074 Background: Adjuvant chemotherapy has changed dramatically in the last decades. Anthracycline-/taxane-based and dose-dense chemotherapy regimens improved survival in node positive breast cancer. This study tries to answer the following questions: (1) Are there differences in survival dependent on chemotherapy regimens in 0/0-3/4-10/10 positive LN. Conclusions: Our data confirms that Taxane-based chemotherapy does not improve DFS in LN negative breast cancer, but rather demonstrated an inferior OAS. But in LN positive breast cancer we can demonstrate a benefit by the use of Taxane-based chemotherapy regimens. Furthermore, dose-dense ETC demonstrated a significant benefit in survival in >10 positive LN.

1082 Background: Clinical trials (CT) usually compare a standard treatment regime versus innovative new substances or regimens. However participation in CT is available for only few patients and exclusion criteria is usually very strict. Therefore this study tries to answer the following questions: (1) Does participation in adjuvant CT improve survival in breast cancer (BC)? (2) Is there a difference in survival compared to guideline adherence and what is the role of the other treatments surrounding adjuvant breast cancer treatment? Methods: This German multi-center [17 participating hospitals all are certified as breast cancer centers] retrospective cohort study called BRENDA (BRENDA = quality of breast cancer care under evidence-based guidelines) included 5326 patients obtained from 1992 until 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). Results: 554 (10,4%) patients participated adjuvant clinical trials and 4772 (89,6%) not. There was a trend towards a significantly impaired RFS [p=0.17; HR=0.87 (95% CI: 0.71-1.06)] and OAS [p=0.65; HR=0.84 (95% CI: 0.65-1.09)] when comparing participants (PA) versus non-participants (NPA). When stratifying for guideline adherence (compared to PA-guideline conform in all adjuvant therapies) the outcome was not different in NPA-guideline adherent [RFS: p=0.13; HR=1.25 (95% CI: 0.94-1.67)] [OAS: p=0.83; HR=1.41 (95% CI: 0.96-2.06)]. However survival parameters were significantly impaired in non-guideline conform PA [RFS: p=0.005; HR=1.66 (95% CI: 1.16-2.38)] [OAS: p=0.01; HR=1.83 (95% CI: 1.15-2.92)] and non-guideline conform NPA [RFS: p>0,001; HR=1.70 (95% CI: 1.27-2.26)] [OAS: p=0.002; HR=1.82 (95% CI: 1.24-2.67)]. Conclusions: There is a strong association between guideline adherence in adjuvant treatment in BC and survival. PA in clinical trials trended to an improved survival, but only if guideline adherent treatment was applied. Patients who don`t have access to clinical seem to profit substantially of guideline adherent adjuvant treatment.