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Summary Background The incidence of pilonidal disease is increasing. The choice of surgical approach differs between surgeons and countries. With better understanding of the etiology of the disease, there is a shift toward more successful concepts of treatment. In many cases, management can be challenging owing to the number of previous failed operations. Objective The aim of this retrospective single-center cohort study was to compare recurrence rates and postoperative wound complications between five treatment arms. Methods A total of 299 patients who underwent surgery for pilonidal disease between November 1994 and May 2019 were included. Primary endpoint was time to recurrence, secondary endpoint was wound care complication rate. Results Median follow-up was 85.8 months in 286 patients. An overall recurrence rate of 16.1% was observed at 24 months, 21.4% at 60 months, and 47.4% at 303 months; 24 months postoperatively, there was a range from 10.5% for excision with primary midline closure to 30.0% for the Bascom I procedure. Recurrence in excision with primary midline closure was 71.8% 268 months postoperatively. No statistically significant differences were observed between the five groups (p = 0.54). The highest prevalence of wound complications (46.3%) was in excision with midline closure. Cox regression showed that previous pilonidal operations are an independent prognostic factor for developing recurrence (p = 0.006). Multivariate logistic regression revealed that previous pilonidal operations have a significant predictive value for developing postoperative wound complications (odds ratio = 4.04, 95% confidence interval [1.61–10.18]; p = 0.003). Conclusion In order to improve surgical outcomes, emphasis should be given to adoption of techniques with high success rates.

Supplementary Figures S1-S2; Supplementary Table S1.

Purpose: Heat shock protein-90 (HSP-90), a molecular chaperone required by numerous oncogenic kinases [e.g., HER-2, epidermal growth factor receptor (EGFR), Raf-1, v-Src, and AKT] for conformational stability, has attracted wide interest as a novel target for cancer therapy. HSP-90 inhibition induces degradation of HSP-90 client proteins, leading to a combinatorial inhibition of multiple oncogenic signaling pathways with consecutive growth arrest and apoptosis. MET, a tyrosine kinase that is constitutively active in tumor cells with MET oncogene amplification, has recently been identified as another HSP-90 client.Experimental Design: The aim of our study was to assess the efficacy of SNX-2112, a synthetic HSP-90 inhibitor, in 3 different MET-amplified tumor cell lines (GTL-16, MKN-45, and EBC-1) as well as PR-GTL-16 cells, a GTL-16 subline selected for resistance to the highly selective MET kinase inhibitor PHA-665752.Results: In all cell lines, SNX-2112 led to degradation of MET, HER-2, EGFR, and AKT, as well as abrogation of Ras/Raf/MEK/MAPK and PI3K/AKT signaling, followed by complete cell cycle arrest. SNX-5542, an orally bioavailable prodrug of SNX-2112, displayed significant antitumor efficacy in vivo in nude mice bearing MET-amplified tumor xenografts. Importantly, HSP-90 inhibition maintained its antitumor efficacy in PR-GTL-16 cells both in vitro and in vivo, suggesting that HSP-90 inhibition could be a particularly valuable strategy in MET-amplified tumors that have acquired resistance to MET kinase inhibition.Conclusions: Our study provides evidence for the efficacy of HSP-90 inhibition in MET-amplified cancer cells, particularly when MET kinase inhibitor resistance has emerged. Clin Cancer Res; 17(1); 122–33. ©2011 AACR.

Summary Background Sacral neuromodulation (SNM) is a widely accepted treatment for pelvic floor disorders, including constipation and fecal incontinence (FI). In 2017, a standardized electrode placement method, the H technique, was introduced to minimize failure rates and improve clinical outcomes. We aimed to investigate the technical feasibility and functional outcome of the procedure. Methods In this prospective study, we evaluated the first 50 patients who underwent SNM according to the H technique between 2017 and 2020 at a tertiary care hospital. Patient demographic and clinical data were collected, and the impact of various factors on patients’ postoperative quality of life (QoL) was assessed after a follow-up of 40 months. Functional outcome was monitored prospectively using a standardized questionnaire. Results Of 50 patients, 36 (72%) reported greater than 50% symptom relief and received a permanent implant (95% CI: 58.3–82.5). We observed 75% success in relieving FI (95% CI: 58.9–86.3) and 64% in constipation (95% CI: 38.8–83.7). Complication occurred in five (10%) patients. Preoperative vs. postoperative physical and psychological QoL, Vaizey score, and obstructed defecation syndrome (ODS) scores revealed significant improvements (all p p = 0.035). Conclusion We provide evidence for the technical feasibility and efficacy of the SNM implantation using the H technique. The medium-term results are promising for patients with FI and constipation. Male patients and those with a BMI > 25 are more prone to perioperative complications.

Simple Summary Today, the presence of well-organized functional structures of immune cells at tumor sites, known as ectopic lymphoid structures, and their strong association with patient survival have been reported in more than ten different cancer types. We aimed to investigate whether there is a link between the patient-specific characteristics of pre-formed isolated lymphoid structures in non-tumorous colon tissue and the disease pathobiology for patients with metastatic colorectal cancer. The study employed a powerful approach of quantitative tissue image cytometry to compare lymphoid structures of different anatomical locations within the same patients. We showed that the properties of isolated lymphoid structures in non-tumorous colon tissue predefine the immune phenotype of ectopic lymphoid structures at primary and metastatic sites. We discovered that B-cell-enriched and highly proliferative lymphoid structures are prognostic towards an improved clinical outcome. The knowledge gained from this study expands our understanding of tumor-immune interactions and draws particular attention to the anti-tumor immune response guided by isolated lymphoid structures outside of tumor tissue. Abstract The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC.

Background Taxane-based checkpoint inhibitor combination therapy might improve the outcome in recurrent/metastatic (R/M) head and neck cancer (HNSCC) patients. Thus, we investigated the efficacy and safety of docetaxel (DTX) plus pembrolizumab (P) in a prospective phase I/II trial. Methods Platinum-resistant R/M HNSCC patients received DTX 75 mg/m^2 plus P 200 mg for up to six cycles followed by P maintenance therapy. The primary endpoint was overall response rate (ORR) and safety. Secondary endpoints comprised disease control rate (DCR), overall survival (OS) and progression free survival (PFS). Results Twenty-two patients were enrolled. Nine patients (40.9%) had a primary tumor in the oropharynx, 8 (36.4%) in the oral cavity, 3 (13.6%) in the hypopharynx and 2 (9.1%) in the larynx. The ORR was 22.7% (95% CI 10.1%-43.4%) and one (4.5%) complete response was achieved. The DCR was 54.6% (95% 34.7%-73.1%). The median PFS was 5.8 months (95% CI 2.7–11.6) and the median OS 21.3 months (95% CI 6.3–31.1). The 1-year PFS and OS rates were 27.3% and 68.2%, respectively. While the most frequent adverse event (AE) was myelosuppression, which was reported in all 22 patients, 3 (13.6%) patients experienced grade 3 febrile neutropenia. The most common immune-related AEs were grade skin rash (40.9%) and hypothyroidism (40.9%). One patient (4.5%) experienced grade 5 immune thrombocytopenia. Conclusion DXT in combination with P shows promising activity accompanied with a manageable side effect profile in pre-treated R/M HNSCC patients.

Summary Background After publishing promising results for the treatment of patients with human papilloma virus (HPV) positive oropharyngeal cancer with radiochemotherapy regarding 2‑year survival, we present an update of the disease-specific and disease-free survival after 5 years. Patients and methods A total of 29 patients of which 18 were HPV negative and 11 HPV positive with squamous cell carcinoma of the oropharynx received radiation therapy with or without chemotherapy (cisplatin) or immunotherapy (cetuximab) between 2007 and 2009. At time of the present analysis, six patients are still alive including four with HPV positive and two with HPV negative oropharyngeal carcinoma, while 15 out of 16 patients with HPV negative tumors died and 1 died of another cause with evidence of disease. Results Since the 2‑year disease-specific survival of patients with HPV positive cancer of the oropharynx was published with 100% versus 30.4% in HPV negative tumors, we now present the 5‑year disease-specific survival after treatment, which was 85.7% in HPV positive versus 11.1% in HPV negative patients. Conclusion We present the results of patients receiving radiochemo(immuno)therapy for oropharyngeal cancer regarding the HPV status, which is still promising.

An empirical distribution function estimator for the difference of order statistics from two independent populations can be used for inference between quantiles from these populations. The inferential properties of the approach are evaluated in a simulation study where different sample sizes, theoretical distributions, and quantiles are studied. Small to moderate sample sizes, tail quantiles, and quantiles which do not coincide with the expectation of an order statistic are identified as problematic for appropriate Type I error control.

Objective/Background Matrix metalloproteinases (MMPs) play a pivotal role in the development and progression of abdominal aortic aneurysms (AAAs). The action of MMPs depends on a balance between tissue inhibitors of MMPs (TIMPs) and compounds that may prolong protease activity, such as neutrophil gelatinase-associated lipocalin (NGAL). Methods The study was designed to analyse gene expression and protein concentration of MMPs, TIMPs, and NGAL in AAA walls and intraluminal thrombi (ILTs) of patients on simvastatin (n = 10) and not on statins (n = 10). The patients were matched by age, sex, and AAA diameter. Expression of MMP2, MMP9, TIMP1, TIMP2, and NGAL was investigated by real time polymerase chain reaction, and MMP2, MMP9, MMP9/TIMP1, MMP9/TIMP2, and MMP9/NGAL protein levels by enzyme-linked immunosorbent assay. Results MMP2 and MMP9 protein and mRNA levels were comparable in the simvastatin and non-statin groups (p > .05); however, there was a significant decrease in TIMP1 mRNA in AAA tissue (p = .04). Moreover, a significant increase in MMP9/TIMP2 complex concentration in ILTs of patients on simvastatin was noted (median 94.71 ng/mL in the simvastatin group vs. 36.80 ng/mL in the non-statin group; p = .01). No significant difference was observed for NGAL mRNA or protein content in AAA and ILT. Conclusion Simvastatin treatment in patients with AAAs may influence the concentration of proteases and their inhibitors (TIMPs) in aneurysmal wall tissue and ILTs. Thus, further studies should be undertaken to understand the different influence of statin therapy on the components of the MMP/TIMP system in AAAs and ILTs.

The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens.A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray.A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p0.0001) and need for fasciotomy (p0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p0.0001).A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.

Objectives Statins have been reported to suppress the progression of abdominal aortic aneurysm (AAA). However, the effects of statins on inflammatory processes and free radicals generation are poorly understood. Methods Wall samples from 51 patients (simvastatin patients, n = 34; non-statin patients, n = 17; matched by sex, age and aneurysm size) subjected to elective open AAA repair were analysed. We examined the effects of simvastatin on lipid peroxidation (4-hydroxy-trans-2-nonenal (4-HNE)), hydrogen peroxide (H2O2), tumour necrosis factor alpha (TNF-α) concentration, superoxide dismutase (SOD) and catalase (CAT) activity as well as nuclear factor kappa B (NF-κB) pathway activation in human AAA wall samples. Results Treatment with simvastatin resulted in a decrease in 4-HNE and TNF-α concentration (median 4.18 μg/mg protein vs. 4.75, p = 0.012; median 10.33 pg/ml vs. 11.81, p = 0.026, respectively). CAT activity was higher in the simvastatin group (median 3.98 U ml vs. 3.19, p = 0.023). NF-κB expression was lower (p = 0.018) in the simvastatin group. However, simvastatin had little effect on H2O2 concentration (p = 0.832) and SOD activity (p = 0.401). Conclusion Simvastatin inhibits free radicals and TNF-α generation and improves antioxidant capacity of human AAA wall tissue, possibly through the suppression of NF-κB activity. This may be one possible explanation how statins can inhibit AAA oxidative stress.

Our study aims to determine whether patients with lobular-type breast cancer have significantly improved rates of breast conservation (BCT) after neoadjuvant chemotherapy (nCT). Patients who received nCT and surgery within three prospective trials between 1995 and 2007 at the Medical University of Vienna were retrospectively analyzed. 325 patients had median follow-up of 53 months; 21% had lobular cancer, and 70% of these women were initially scheduled for mastectomy (MX). Twenty-one finally received BCT, yielding a MX–BCT turnover rate of 45%. Of patients primarily scheduled for BCT, 20% had to finally undergo MX in lobular cancer. The 256 patients with ductal-type breast cancer finally had a MX–BCT turnover rate of 52% (p = 0.561 versus lobular) and a BCT–MX turnover rate of 15% (p = 0.933 versus lobular). Secondary MX after initial BCT was necessary in 2% (ductal) and 10% (lobular, p = 0.110). There was no difference in local recurrence in lobular- as compared with ductal-type breast cancer patients after BCT (2.7% versus 10%, p = 0.135), nor was a difference seen in lobular breast cancer patients when comparing BCT with MX (2.7% versus 3.4%, p = 0.795). Tumor type was not an independent predictor for either BCT or local recurrence. We do not suggest excluding patients with lobular-type breast cancer who are primarily scheduled for MX from nCT, since BCT rates may still increase by 45% without influencing the oncologic outcome.

BACKGROUND: The purpose of this study was to evaluate the incidence and clinical significance of HPV (Human papilloma virus) infection in patients with head and neck cancer who had received radiotherapy in Eastern Austria. PATIENTS AND METHODS: 88 patients with head and neck cancer including 26 patients with oral cavity cancer, 45 patients with oropharyngeal cancer, seven patients with laryngeal carcinoma and ten patients with carcinoma of the hypopharynx were screened for high risk HPV by immunohistochemistry, PCR (Polymerase Chain Reaction) and in-situ hybridization. 29 out of 45 patients with a squamous cell carcinoma of the oropharynx received radiotherapy alone, radiotherapy in combination with cisplatin or cetuximab. RESULTS: Of the investigated 29 patients with oropharyngeal cancer receiving conservative treatment, 11 had a HPV-positive and 18 a HPV-negative tumor. Patients received radiation ± cisplatin or cetuximab, where the HPV-positive patients had a significant better response to treatment and overall survival (p = 0.015) as well as disease-free survival (p = 0.001) after therapy. CONCLUSION: Patients with oropharyngeal carcinoma and a positive HPV status respond considerably better to radiochemotherapy than patients with HPV-negative tumors. HPV screening is a simple procedure and can easily be implemented in routine pathology investigations and should be included in standard operational procedures for the diagnosis and therapy of head and neck cancer patients.

Chest compressions and early defibrillation are crucial in cardiopulmonary resuscitation (CPR). The Guidelines 2005 brought major changes to the basic life support and automated external defibrillator (BLS-AED) algorithm. We compared the European Resuscitation Council's Guidelines 2000 (group '00) and 2005 (group '05) on hands-off-time (HOT) and time to first shock (TTFS) in an experimental model.In a randomised, cross-over design, volunteers were assessed in performing BLS-AED over a period of 5min on a manikin in a simulated ventricular fibrillation cardiac arrest situation. Ten minutes of standardised teaching and 10min of training including corrective feedback were allocated for each of the guidelines before evaluation. HOT was chosen as the primary and TTFS as the secondary outcome parameter.Forty participants were enrolled; one participant dropped out after group allocation. During the 5-min evaluation period of adult BLS-AED, HOT was significantly (p0.001) longer in group '00 [273+/-3s (mean+/-standard error)] than in group '05 (188+/-3s). The TTFS was significantly (p0.001) longer in group '00 (91+/-3s) than in group '05 (71+/-3s).In this manikin setting, HOT and TTFS improved with BLS-AED performed according to Guidelines 2005.

Summary Aim of the study To analyse 2 years of experience after introducing automated external defibrillators (AED) all over Austria. Materials and methods This observational study evaluated the number of privately purchased devices and the rate of local bystander-triggered AED deployments from November 2002 to December 2004. As outcome measurements, the hospital discharge rate and neurological condition were recorded. Arrival times of the emergency medical service (EMS) on scene and the time intervals until shock decisions were made were calculated. Shock decisions were verified according to ECG downloads. Results were compared with historical data if applicable. Results During the study period, 1865 devices were installed. Seventy-three AED deployments were recorded. Eleven cases were excluded from the study because bystanders were part of the local EMS. Seventeen out of the remaining 62 (27%) compared to a historical 27 out of 623 (4.3%) individuals were discharged alive from hospital. Fourteen out of 26 (54%) patients who were found with a shockable rhythm survived to hospital discharge. Fifteen of our patients survived in good neurological condition (CPC I and II), two suffered from severe neurological deficit (CPC III and IV) and 45 people died. The median "call-to-AED advice interval" was 3.5min (IQR 2–6min; N =24). In two cases, the AED made inappropriate decisions because of artefacts. Conclusions Compared to historical data, short ‘intervals to shock' delivery and the frequent start of basic life support resulted in an increased hospital discharge rate in good neurological condition. Despite the relatively high number of installed devices, the number of patients reached remained small.

To analyze whether breast-conserving therapy (BCT) may be an oncologically safe approach and result in a good cosmesis in patients with centrally located breast cancer (CLBC).Only underpowered, retrospective, single-arm studies have suggested that oncoplastic BCT for CLBC may be oncologically safe and may result in a good cosmesis.The authors retrospectively analyzed the overall and recurrence-free survival in 1485 patients with breast cancer undergoing BCT comparing CLBC with non-CLBC. Moreover, the authors described 4 different oncoplastic techniques for BCT in patients with CLBC and compared the cosmetic results with simple lumpectomy according to a recently elaborated objective cosmetic evaluation system, the Breast Symmetry Index.Kaplan-Meier curves show no significant difference in a 5-year overall, local, or distant recurrence-free survival between patients with CLBC and non-CLBC after BCT (94% vs. 96%; 100% vs. 98%; 92% vs. 90%; median follow-up, 35.3 months). The cosmetic outcome after oncoplastic BCT compared with simple lumpectomy differed significantly (Breast Symmetry Index: 22 +/- 6%d vs. 44 +/- 12%d; P0.05).The results demonstrate that BCT for CLBC is oncologically safe and that oncoplastic techniques improve cosmesis.

Purpose To describe a way to eliminate the problem caused by missing data due to neodymium:YAG (Nd:YAG) laser capsulotomies before statistical analysis, which leads to incomplete data in long-term studies of posterior capsule opacification (PCO). Setting Medical University of Vienna, Vienna, Austria. Methods To demonstrate the problem, an existing long-term study comparing PCO development in eyes with round-edged and sharp-edged intraocular lenses (IOLs) was analyzed. In the study, several Nd:YAG capsulotomies led to dropouts in the round-edged IOL group. To solve the resulting missing value problem, the missing values were replaced by estimated PCO values in various scenarios; that is, different assumptions were made of how PCO would have developed without a capsulotomy. Standard statistical analyses that included the estimated PCO values rather than excluding the incomplete cases were then performed. Results The analysis of all cases (including the estimated PCO scores) showed a highly significant difference between the round-edged group and the sharp-edged group. Sensitivity analyses confirmed that the difference between the 2 groups remained significant up to highly implausible values chosen for the missing PCO scores, thus proving the correctness of the analysis. Conclusions This study showed it is possible to perform statistical analyses without excluding incomplete cases. This approach is recommended for all studies with Nd:YAG dropouts as it increases the statistical power. Excluding incomplete cases may lead to biased or wrong study conclusions.

Introduction: The purposes of this laboratory investigation were to (1) measure the sagittal and vertical deflection of loaded transpalatal arches (TPAs) connected to a palatal implant, (2) measure the extent of permanent deformation of the connecting TPA in the sagittal and vertical directions, (3) test various wire dimensions in terms of deflection behavior, and (4) evaluate soldering vs laser welding vs adhesive bonding of TPAs in terms of load deflection behavior. Methods: Stainless steel wires of 6 dimensions were tested: 0.8 × 0.8, 0.9, 1, 1.1, 1.2, and 1.2 × 1.2 mm. For each dimension, 10 specimens were soldered to the palatal implant abutment, 10 were laser welded, and 10 were adhesively bonded to the implant abutment (total, 180 specimens). The measuring device applied increments of force of 50 cN, from 0 to 500 cN. Then the specimens were unloaded. The values were statistically described and analyzed with ANOVA and Wilcoxon rank sum tests. Results and Conclusions: Absolute orthodontic anchorage without deformation of TPAs was not observed with the wire dimensions tested. To prevent loss of anchorage greater than 370 μm (sagittal deflection of 1.2 × 1.2 mm adhesively bonded TPA at 500 cN force level), wires thicker than 1.2 × 1.2 mm or cast anchorage elements must be considered for clinical practice. However, larger cross sections might cause more patient discomfort, and laboratory procedures increase costs.

Purpose Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients. Patients and Methods This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin ± zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months. Results Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, −14.4% after 36 months; mean T score reduction, −1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, −17.3%; mean T score reduction, −2.6) compared with patients receiving tamoxifen/goserelin (BMD, −11.6%; mean T score reduction, −1.1). In contrast, BMD remained stable in zoledronic acid–treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted. Conclusion Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

Public access defibrillation (PAD) is a promising strategy to fight sudden cardiac death. The Austrian Red Cross provided automated external defibrillators (AEDs) and basic life support (BLS) training as an "all inclusive package" combined with on site consultation and maintenance with annual retraining as a part of a nationwide PAD programme. A multi media campaign was started to promote the package and to increase awareness about sudden cardiac death. Data about the campaign, its recognition by the public in Austria and the number of packages were recorded. Sixty-eight percent of the Austrian public above the age of 15 years were able to recall the multi media campaign. Comparing the periods before and after the campaign, the number of website hits climbed significantly from 2,931 hits/month (1,866-6,168) to 4,812 hits/month (3,432-13,434) (p=0.0276). The number of AED services implemented before the campaign increased significantly (p=0.0026) in the time after the campaign. Therefore, we conclude that a multi media campaign is useful to stimulate public discussion and it encourages companies to buy "all inclusive packages" containing AEDs, BLS training, on site consultation and maintenance. These measures represent a possible first step in introducing PAD but it seems that they have to be continued on a constant basis.

Objectives: In this study, the authors tested whether electromagnetic interference (EMI) is able to impair correct electrocardiogram analysis and produce false-positive shock advice from automated external defibrillators (AEDs) when the true rhythm is sinus. Methods: Nineteen healthy subjects were used to test five AEDs available on the Austrian market in a prospective, open, and sequence-randomized study. The primary outcome variable was the absolute number of shocks advised in the presence of EMI. The secondary outcome was the number of impaired analyses caused by incorrectly detected patient movements or electrode failure. Results: Of 760 tests run, 18 (2.37%) cases of false-positive results occurred, and two of five AEDs recommended shocks in the presence of sinus rhythm. Of 760 tests run, no electrode failures occurred. There were 27 occurrences (3.55%) of motion detected by an AED in the presence of strong electromagnetic fields. Conclusions: AED models differ in their response to EMI; it may be useful to consider specific safety requirements for areas with such fields present. Working personnel and emergency medical services staff should be informed about potential risks and the possible need for patient evacuation before AEDs are attached and shock recommendations are followed.

Autologous cells migrate only slightly into acellular matrix grafts. This study was carried out in small-diameter, allogeneic matrix grafts to investigate the effects on cell repopulation and remodeling caused by increased wall porosity induced by laser perforation. Allogeneic ovine carotid arteries were decellularized by dye-mediated photooxidation (Photofix). Matrix grafts (10 cm x 4 mm i.d.) were perforated with holes of 50 microm diameter at a density of 50 holes/cm(2) using a Ti-sapphire laser. The grafts were implanted in the carotid arteries of 10 sheep and were compared to nonperforated grafts implanted contralaterally. The prostheses were retrieved after 6 weeks or 3 or 6 months following implantation and were evaluated by histologic examination, immunohistochemical staining, and scanning electron microscopy. All grafts, except one of the perforated specimens, remained patent. Perforated implants, examined at 6 weeks, showed faster recellularization with endothelial cells than did the corresponding contralateral controls. Perforated grafts, examined at 6 months, showed a significantly thicker neointima and clear signs of neovascularization: endothelial cells, basal lamina, elastic fibers, circular and longitudinally orientated smooth muscle cells in comparison to nonperforated specimens. Repopulation of the decellularized matrix with host cells was higher in the perforated than in the nonperforated prostheses. These results suggest that the increased matrix porosity induced by laser perforation promotes graft remodeling and reconstitution with host cells.

Summary objectives Hashimoto's encephalitis is a term which describes encephalopathy associated with autoimmune thyroiditis, but it is not based on evidence, whether Hashimoto's encephalitis is a distinct clinical entity by itself. In previously reported cases of Hashimoto's encephalitis, abnormal brain perfusion studies have been reported. The aim of this study was to evaluate the prevalence of brain perfusion abnormalities in euthyroid patients with autoimmune thyroiditis. methods 99mTc Ethyl cystein dimer (ECD) single photon emission computed tomography (SPECT) studies were performed in a study group of 41 euthyroid patients with autoimmune thyroiditis and a matched control group of 35 healthy individuals. All study participants had a normal neurological investigation and a detailed neurological history taking. Individuals with known or suspected morphological brain abnormalities were excluded from the study. Zung's Self-Rating Anxiety Scale (SAS) and Zung's Self-Rating Depression Scale (SDS) were used to detect depression and mood disorders. Automatic quantification of perfusion was performed with both a voxel-based analysis as well as a volume-of-interest (VOI) based analysis of 46 predefined cortical and subcortical regions. The findings from both groups were compared to a reference template. results In the voxel-based analysis, there was a significant difference between patients and controls in the mean volume of perfusion defects deviating 2SD below the normal values (21·8 ml vs. 10·4 ml; P = 0·02). Hyperperfused areas, however, did not differ significantly between study patients and controls. A significant correlation of the perfusion defects with time since diagnosis of autoimmune thyroiditis was seen (r = 0·42). In the VOI-based analysis, abnormal regions were more frequent in the study group when compared to controls (P

Objective We performed a randomised controlled trial of percutaneous tibial nerve stimulation (PTNS) versus tolterodine for treating treatment naive women with overactive bladder (OAB). Study design 36 patients with symptoms of OAB were randomised to 3 months of treatment with weekly PTNS or tolterodine (2 mg bid p.o.). The primary outcome measure was the difference of micturitions per 24 h. The secondary outcome measure was the impact on quality of life (QoL) measured with a visual analogue scale (VAS) between baseline and after 3 months of therapy. Results Micturition frequencies did not decline significantly ( p = 0.13) over time and there were no significant treatment differences ( p = 0.96). QoL was significantly dependent from its level at baseline ( p = 0.002) and showed improvement over time compared to baseline measurements but no significant differences between both treatment groups ( p = 0.07). Incontinence episodes per 24 h depended significantly on the level at baseline ( p = 0.0001) and declined significantly ( p = 0.03) during 3 months of therapy in both therapy groups. However no significant treatment differences on the reduction of incontinence episodes in 24 h could be shown between both therapy groups ( p = 0.89). PTNS had fewer side effects than tolterodine ( p = 0.04). Conclusion PTNS and tolterodine were both effective in reducing incontinence episodes and improving QoL in patients with OAB but not micturition frequencies. PTNS had fewer side effects.

Preeclampsia is still a leading cause of maternal and fetal morbidity and mortality. There is evidence for the involvement of platelets. Therefore, we investigated the suitability of corrected whole blood impedance aggregometry as an early predictor of preeclampsia in 71 consecutive, high-risk pregnancies. According to the occurrence of preeclampsia, defined postpartum by an independent investigator, and the stage of pregnancy (early and late, cutoff: 25 weeks of gestation), four study groups were defined. Platelet aggregation data were corrected for the influence of hematocrit and platelet count by a special purpose software package. Women developing preeclampsia showed significantly higher platelet aggregation response compared to controls in early and late pregnancy. In early pregnancy, all women developing preeclampsia had aggregation responses to collagen higher than the highest responses among the controls. Hence, this test had a 100% positive predictive value of subsequent preeclampsia. Despite being significantly increased, platelet aggregability was of minor predictive value in late pregnancy. We conclude that preeclampsia is accompanied by exaggerated platelet aggregability, particularly perceptible early in the course of pregnancy. We propose collagen-induced whole blood platelet aggregation with correction for the influence of hematocrit and platelet count for early detection of preeclampsia.

This clinical study evaluated factors affecting the decision for meniscal surgery in a patient population seen routinely at a trauma clinic. The study hypothesis was that patients who sustain a traumatic injury to the knee or have a long history of clinical symptoms are likelier to be operated on. We investigated 149 patients clinically and by magnetic resonance imaging (MRI). Group A (n = 62) underwent arthroscopic surgery and group B (n = 87) were treated conservatively. Multiple logistic regression analysis was used to examine correlations with regard to age, gender, injury pattern, period between the injury and first clinical examination, and MRI results. We found no significant difference between the two groups with regard to gender (P = 0.1), injury pattern (P = 0.44), or period between injury and first clinical examination (P = 0.5). Patients in group A were significantly older than those in group B (P = 0.044), and, as expected, MRI signal alterations were significantly higher in group A than in group B (P = 0.001). In acutely injured patients MRI helps to establish an accurate diagnosis, and in cases of positive MRI findings in a symptomatic patient, the surgeon should not wait 4–6 weeks but should immediately recommend surgery.

Cytokines play a pivotal role in the pathogenesis of septic shock. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) stimulate the progression of septic shock whereas the anti-inflammatory cytokine IL-10 has counterregulative potency. The amino acid glycine (GLY) has been shown to protect against endotoxin shock in the rat by inhibiting TNF-alpha production. In the current study we investigated the role of GLY on lipopolysaccharide (LPS) -induced cell surface marker expression, phagocytosis, and cytokine production on purified monocytes from healthy donors. GLY did not modulate the expression of HLA-DR and CD64 on monocytes, whereas CD11b/CD18 expression (P

Although there are many articles dealing with anterior cruciate ligament (ACL) reconstruction, there are none dealing with the possibility of changes of the patellofemoral alignment after these procedures. Forty-six patients were evaluated preoperatively and 1 year postoperatively, after undergoing intra-articular ACL reconstruction, for changes of the patellofemoral alignment. Patella-tilt and congruence angles were measured on tangential view radiographs that were taken in the supine position. Analysis of covariance was performed and revealed a significant change of the congruence angle 1 year postoperatively. The patella-tilt did not change. One year postoperatively, the patella shifted on average 5 degrees medially after ACL grafting. It can be deduced that anterior knee pain after ACL reconstruction could be caused by distinct changes in the patellofemoral alignment.

In this prospective study, patellar height changes were investigated after anterior cruciate ligament (ACL) reconstruction with a mean follow-up of 22.4 months. A total of 114 patients were included. Fifty-two patients (group A) were treated by multiple suture repair, 27 patients (group B) underwent acute ACL reconstruction, and 35 patients (group C) underwent ACL reconstruction > or =6 weeks after injury with a patellar tendon graft. The patellar vertical height ratios (VHR) were evaluated preoperatively (VHR 1), 6 months postoperatively (VHR 2), and at follow-up (VHR 3). For the studied questions, the following answers were obtained: (1) The change of the patella height was the same in all three groups (i.e., disregarding the different surgical procedures). (2) The time elapsed between injury and ACL reconstruction did not influence the shortening of the patellar tendon. (3) Women showed a more pronounced shortening of the patellar tendon than did men. (4) A significant shortening of the patellar tendon occurred in 30% of our patients, and the process of shortening was finished 6 months postoperatively. (5) Anterior knee pain was present in 27.2% of our patients and occurred significantly more often after patellar tendon graftings. (6) Age had no influence on the changes of the patellar height.

SummaryBackground With respect to the cellular players, mast cells and basophils have been well studied in experimental murine systemic anaphylaxis models, but the role of neutrophils and platelets is not fully understood today. Objective We tested the hypothesis that neutrophils and platelets might participate in an antigen-induced anaphylaxis model. Methods BALB/c mice were sensitized intraperitoneally with alum-adsorbed casein. A period of 2 weeks later, mice were challenged with 100 μg casein intravenously and immediate hypersensitivity reactions were assessed by rectal temperature measurements and monitoring the physical activity. Subsequently, leucocytes were counted in the peripheral blood as well as quantified in situ in typical shock organs like lung, liver and spleen, heart and kidney. Results Mice sensitized with casein showed casein-specific IgG1, IgE, and IgG2a. When sensitized mice were specifically challenged with casein they developed immediate hypersensitivity reactions including drop of temperature and reduced activity. Furthermore, pronounced peripheral neutropenia and reduced platelet counts correlated with the severity of the hypersensitivity reactions. In the histological analyses of collected tissues we observed lung interstitial neutrophilia using Gr-1 staining. These events occurred specifically in mice sensitized and challenged with casein, in contrast to control groups. Conclusions On the basis of our data we suggest that in addition to mast cells and basophils, neutrophils and platelets participate in the anaphylactic response in this BALB/c mouse model. Platelet and neutrophils expressing relevant immunoglobulin receptors may therefore have a synergistic effect with allergen specific IgE as well as IgG antibodies in food-induced anaphylaxis. We suggest that management of these cells could be of clinical importance to handle anaphylaxis.

Pruritus ani is a hidden but frequently occurring clinical condition, with a large impact on patients' quality of life. Currently, therapeutic options are scarce, offering mainly limited success. The authors performed a prospective, open-label, two-centre pilot study to analyse the efficacy and safety of a liquid-film forming acrylate cream for the treatment of pruritus ani and peri-anal skin irritation. A total of 28 patients were included and applied the cream to the cleansed anal and peri-anal skin once daily for a study period of 3–4 weeks. The primary outcome measure was the reduction of pruritis ani, comparing day 0 to day 28 results. For this purpose, a visual analog scale (VAS) was used. Secondary parameters included the physician global assessment score (PGA) of peri-anal skin condition, assessment of patients' quality of life using a specifically designed quality of life scoring tool, and patient satisfaction with the treatment regimen. The application of the acrylate skin protection cream resulted in a fast and substantial improvement of all study parameters, with a high score for patient satisfaction. The cream was well tolerated without any adverse events noted during the study period. The authors' pilot study has generated initial evidence that the acrylate skin protection cream may be effective for the treatment of pruritus ani. However, further randomized controlled studies are needed to confirm the authors' findings.

Purpose: Heat shock protein-90 (HSP-90), a molecular chaperone required by numerous oncogenic kinases [e.g., HER-2, epidermal growth factor receptor (EGFR), Raf-1, v-Src, and AKT] for conformational stability, has attracted wide interest as a novel target for cancer therapy. HSP-90 inhibition induces degradation of HSP-90 client proteins, leading to a combinatorial inhibition of multiple oncogenic signaling pathways with consecutive growth arrest and apoptosis. MET, a tyrosine kinase that is constitutively active in tumor cells with MET oncogene amplification, has recently been identified as another HSP-90 client. Experimental Design: The aim of our study was to assess the efficacy of SNX-2112, a synthetic HSP-90 inhibitor, in 3 different MET-amplified tumor cell lines (GTL-16, MKN-45, and EBC-1) as well as PR-GTL-16 cells, a GTL-16 subline selected for resistance to the highly selective MET kinase inhibitor PHA-665752. Results: In all cell lines, SNX-2112 led to degradation of MET, HER-2, EGFR, and AKT, as well as abrogation of Ras/Raf/MEK/MAPK and PI3K/AKT signaling, followed by complete cell cycle arrest. SNX-5542, an orally bioavailable prodrug of SNX-2112, displayed significant antitumor efficacy in vivo in nude mice bearing MET-amplified tumor xenografts. Importantly, HSP-90 inhibition maintained its antitumor efficacy in PR-GTL-16 cells both in vitro and in vivo, suggesting that HSP-90 inhibition could be a particularly valuable strategy in MET-amplified tumors that have acquired resistance to MET kinase inhibition. Conclusions: Our study provides evidence for the efficacy of HSP-90 inhibition in MET-amplified cancer cells, particularly when MET kinase inhibitor resistance has emerged. Clin Cancer Res; 17(1); 122–33. ©2011 AACR.

Mesh graft infection after prosthetic hernia repair is a challenging complication usually treated by mesh removal. The aim of this study was to identify risk factors associated with mesh infection and to assess the efficacy of conservative wound therapy in preserving an infected mesh.We performed a retrospective analysis of 476 consecutive patients with incisional hernia who received mesh graft repair between February 1, 2000 and February 28, 2005 at our institution using chart review and clinical investigation.Thirty-one of 476 (6.5%) patients developed a deep surgical site infection involving the implanted mesh graft. Upon multivariate analysis, operation time was the only significant risk factor associated with mesh infection (p = 0.0038). Seventeen (55%) of 31 infected mesh grafts were preserved by conservative means. There was a significant association between the type of mesh graft used and the probability of mesh preservation in case of infection: While conservative therapy led to preservation of 100% of infected polyglactin/polypropylene meshes, only 20% of infected polypropylene and 23% of infected PTFE/polypropylene meshes could be salvaged using conservative means (p0.0001). In none of the patients with preserved mesh graft was hernia recurrence at the former site of infection observed.Operation time is the only significant risk factor associated with mesh graft infection following incisional hernia repair. Conservative treatment should be applied in case of infection of absorbable mesh grafts such as polypropylene/polyglactin, while nonabsorbable meshes such as PTFE/polypropylene or pure polypropylene are much less amenable to conservative treatment, usually requiring early surgical removal.

It has been proposed that the timing of breast-cancer surgery in relation to menstrual phase has a prognostic impact on outcome. We carefully evaluated a combined 2-center series of 385 pre-menopausal women operated on for stage-I and stage-II breast cancer with a median follow-up of 5 years for a possible impact on outcome of the date of their last menstrual period (LMP) before surgery. The distribution of risk factors of the study cohort as well as prognostic indicators corresponded to previously published results. Nodal status, grading, and (in part) hormone-receptor status differentiate well between patient subgroups with high and low risk of relapse and death after breast-cancer surgery. In neither univariate nor multivariate analysis was any impact of the so-called “unopposed” estrogen secretion detected. We did not observe any effect of LMP on long-term survival in any of several prognostic subgroups, in particular in hormone-receptor-positive patients. From our results and from the literature, we conclude that LMP does not provide any prognostic information for outcome after breast- cancer surgery and therefore the proposed modification of scheduling of breast-cancer operations is not justified. © 1992 Wiley-Liss, Inc.

BACKGROUND AND AIM: Chest compressions are crucial in cardiopulmonary resuscitation (CPR), although the optimal number, rate and sequence are unknown. The 2005 CPR guidelines of the European Resuscitation Council (ERC) brought major changes to the basic life support algorithm. One of the major aims of the ERC was to decrease hands-off time in order to improve perfusion of the coronary vessels and the brain. Using a manikin model of basic life support in simulated cardiac arrest, we compared hands-off time and total number of chest compressions according to the guidelines of 2000 and those of 2005. METHODS: A total of 50 volunteers performed CPR according to the guidelines of 2000 (Group 2000) and 2005 (Group 2005) in a randomized unblinded cross-over study. Volunteers received 10 min of standardized teaching and 10 min of training, including corrective feedback, for each set of guidelines before performing 5 min of basic life support on a manikin. We compared hands-off time as the primary outcome parameter and the total number of chest compressions as the secondary outcome parameter. RESULTS: Fifty volunteers were enrolled in the study, one individual dropped out after randomization. In Group 2005, hands-off time was significantly lower (mean 107 ± 19 [SD] s vs. 139 ± 15 s in Group 2000 (P < 0.0001) and the total number of chest compressions was significantly higher (347 ± 64 compressions vs. 233 ± 51 compressions; P < 0.0001). CONCLUSION: In this manikin setting, both hands-off time and the total number of chest compressions improved with basic life support performed according to the ERC guidelines of 2005.

Objective We evaluate the number of surgical two-stage procedures after FSA during breast-conserving therapy (clinical false negative result of FSA) and investigate the influence of microcalcifications, small tumour diameter, neoadjuvant therapy and preoperative biopsy on the clinical false negative rate of FSA. Subjects We retrospectively examined 1016 patients after intraoperative FSA during breast-conserving therapy for breast cancer operated between 1995 and 2001 at the Medical University Vienna. Results Only 9% of all patients had to undergo a two-stage operation due to a false negative intraoperative FSA result. The annual local recurrence rate was 1.2% in all patients with no difference between one- and two-stage operated patients. In situ and pT1 lesions were similarly distributed between one-stage and two-stage operated patients. The use of neoadjuvant therapy and stereotactic biopsy (reflecting non-palpable lesions and microcalcifications) were significantly predictive for a false negative FSA result. The use of a preoperative core biopsy, however, reduced the necessity of performing a two-stage operation. Conclusion Our study demonstrates that FSA leads to a low rate of two-stage operations. Small lesions and microcalcifications as well as the occurrence of intraductal cancer cells and neoadjuvant therapy increased while preoperative core biopsy reduced the false negative rate of FSA. Overall local recurrence rates after FSA were acceptable.

Aims: We investigated possible relationships between body constitution, age and sex of school children and their intellectual and physical abilities to provide effective life supporting first aid. Methods: Our observational study was carried out at the end of a school year, after first aid training had been provided by local teachers. As primary outcomes we measured CPR effectiveness parameters (depth of chest-compressions, number of chest-compressions, ventilation volume). As secondary outcomes we rated emergency calls, guideline adherence when checking signs of life and recovery position according to predefined checklists. Possible inter-dependencies between age, sex, body mass index (BMI) and physical or intellectual performance were calculated. Correlations between continuous data were assessed by Spearman rank correlation coefficient and differences between groups were tested by Wilcoxon’s rank-sum test. A p-value < 0.05 was considered significant. Results: We included 147 pupils at the age from 9 to 18 years. The median depth of chest-compressions was calculated at 35 mm (IQR 31– 41 mm), median number of compressions per minute was 129 bpm (IQR 108 ndash;143 bpm). Median volume applicated during mouth-to-mouth ventilation was 540 ml (IQR 0 –750 ml). Secondary outcomes are displayed in table 1 . BMI (r=0.35; p Conclusions: Children above the age of 9 years showed high quality overall performance after beeing trained in life supporting techniques. Effectivness parameters obtained from adults previously seem to be comparable. Even if physical strength could limit CPR effectiveness, children should not be withheld from first aid education. Sec. Outcomes: Check f. vital signs, recovery position, emergency call, chestcompr/ventilation ratio

Reliable determination of Ki67 labeling index (Ki67 LI) on core needle biopsy specimens (CNB) is essential for determining breast cancer intrinsic subtype (IST), preoperative treatment decisions and short-term treatment response during neoadjuvant therapy. However, analyses investigating robustness of Ki67 LI assessment upon repeated tumor biopsies are scarce and results of studies investigating agreement of KI67 LI between CNB and surgical resection (SR) specimens are conflicting. In the present study, we analysed the role of clinical and pathological factors in influencing concordance of Ki67 LI between CNB and SR specimens. 502 matched pairs of CNB and SR specimens of patients with invasive ER-positive, HER2-negative breast cancer were included in our study. Ki67 LI was determined according to recent recommendations. Luminal B disease was defined by Ki67 LI > 20% according to SR. Ki67 LI values were considered concordant by a divergence of 10% points. Agreement was calculated by Cohen's kappa. Associations with clinicopathological factors were analyzed by Chi square test and logistic regression. Factors investigated included age, menopausal status, CNB method, BIRADS assessment category of imaging abnormality, time between CNB and SR, extent of surgery, histological grade (including individual grading score components according to Elston and Ellis), tumor size, lymph node stage, estrogen- (ER), progesterone- (PR) and HER2-receptor status. A cutoff value of 20% for KI67 LI in SR demonstrated a sensitivity of 90% and a specificity of 60% for identifying luminal B breast cancer in CNB. Upon investigating measurement agreement, we found substantial agreement of Ki67 LI between CNB and SR specimens with a weighted kappa value of 0.837. IST assesment in CNB and SR showed only moderate concordance with a kappa value of 0.587. Concordant diagnosis of IST in CNB and SR was significantly associated with PR expression and histological grade (p>0.05). Agreement of Ki67 LI was higher in tumors expressing low and high levels of PR compared to tumors with intermediate PR score. 27% and 22% of low and intermediate grade breast cancers showed discordant IST in CNB and SR, respectively. In contrast, only 3% of high grade breast cancers differed regarding IST upon repeated measurements. Interestingly, concordance of IST was significantly associated with all separate grading score components in CNB samples such as extent of glandular differentiation (p=0.015), nuclear polymorphism (p=0.005) and number of mitotic figures (p>0.001). We conclude that agreement of breast cancer IST according to Ki67 LI between CNB and SR specimens is significantly influenced by histological tumor grade and PR status. These factors, including all three grading score components are likely to mirror tumor heterogeneity that might compromise obtaining a CNB sample representative of the entire tumor. Our results cast a doubt upon robustness of single CNB-driven measurements of prognostic indicators and outcome predictors in estrogen-receptor positive breast cancer of low or intermediate histological grade. Whether molecular testing of CNB specimens improves classification of luminal breast cancer and helps resolve diagnostic disparities remains to be determined. Citation Format: Zsuzsanna Bago-Horvath, Fabian Roessler, Philipp Wimmer, Martina Mittlboeck, Nicolas Kozakowski, Katja Pinker-Domenig, Rupert Bartsch, Peter Dubsky, Martin Filipits, Margaretha Rudas. Factors influencing agreement of Ki67 labeling index between core needle biopsy and surgical resection specimens [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-02-10.

Electromagnetic fields (EMF) reduce the signal quality of electrocardiograms and may lead to the misinterpretation by automated external defibrillators (AED). We designed this investigation as a prospective study, with a randomized sequence of AED applications on healthy volunteers. We chose busy public places where public access defibrillation was possible as test locations. Strong EMF were sought and found at train stations next to accelerating and decelerating trains. The primary outcome variable was the absolute number of shocks advised in the presence of sinus rhythm by five commonly used AED in Austria. For data analysis, the statistician was blinded in regard to the AED models tested. Data analysis was based on a per protocol evaluation. Of 390 tests run, 0 cases of false positive results occurred (95% CI: 0-0.77). AED can be regarded as safe, even with the interference of EMF present at train stations.

Summary Background The European Resuscitation Council (ERC) guidelines 2005 have brought major changes in the BLS algorithm. The aim of our investigation was to look for the practical impact of these modifications. Methods In a randomized cross-over design we evaluated how adults would adhere to the BLS algorithm of the ERC guidelines 2000 (group A) compared to the guidelines 2005 (group B). The secondary endpoint was to determine the amount of time that elapsed before the start of the chest compressions in the two different groups. Participants were recruited from the streets and an office building of the Austrian Red Cross and were randomized to commence either with A or B. The volunteers were taught the allocated BLS sequence according to their group placement, and before evaluation each of the two groups was given the opportunity to train until they felt confident in using the algorithm. Performance during evaluation was documented automatically with a recording resuscitation manikin (Resusci-Anne™, Skill Reporter). Results Sixty people were included in the study, one individual dropped out after randomisation. In group A 9/59 (15.25%) participants followed the algorithm correctly versus 24/59 (40.68%) in group B ( p =0.006). The time to start of chest compressions was significantly shorter in group B (21.31±7.11s), compared to group A (36.68±11.75s, p Conclusion Compared to the 2000 BLS algorithm, the 2005 BLS sequence seems to be easier to learn and to retain, though nearly 60% of participants did not follow the new algorithm correctly. As expected, there was a significantly shorter time elapsing before the start of chest compressions when applying the 2005 algorithm. These findings should translate to better survival after cardiac arrest.

Summary Background Tamoxifen has been the standard adjuvant treatment for postmenopausal women with hormone-responsive early breast cancer for more than 20 years. However, the third-generation aromatase inhibitor anastrozole has proven efficacy and tolerability benefits compared with tamoxifen when used as initial adjuvant therapy. We investigate whether women who have received a period of adjuvant tamoxifen would benefit from being switched to anastrozole. Methods We present a combined analysis of data from two prospective, multicentre, randomised, open-label trials with nearly identical inclusion criteria. Postmenopausal women with hormone-sensitive early breast cancer who had completed 2 years' adjuvant oral tamoxifen (20 or 30 mg daily) were randomised to receive 1 mg oral anastrozole (n=1618) or 20 or 30 mg tamoxifen (n=1606) daily for the remainder of their adjuvant therapy. The primary endpoint was event-free survival, with an event defined as local or distant metastasis, or contralateral breast cancer. Analysis was by intention to treat. Findings 3224 patients were included in analyses. At a median follow-up of 28 months, we noted a 40% decrease in the risk for an event in the anastrozole group as compared with the tamoxifen group (67 events with anastrozole vs 110 with tamoxifen, hazard ratio 0·60, 95% CI 0·44–0·81, p=0·0009). Both study treatments were well tolerated. There were significantly more fractures (p=0·015) and significantly fewer thromboses (p=0·034) in patients treated with anastrozole than in those on tamoxifen. Interpretation These data lend support to a switch from tamoxifen to anastrozole in patients who have completed 2 years' adjuvant tamoxifen.

Summary Background Death due to cardiovascular disease occurs more frequently in prisons than the national average. Due to close surveillance 24 h/day, the ability to reach the patient within 3 min and time consuming access for the EMS crews, it was hypothesised that the deployment of automated external defibrillators (AEDs) might make improvements regarding Call-to-the-First-AED-Prompt (CTP) interval and formed the aim of this study. Methods Our investigation was analysed on an intention to treat basis and conducted in a prospective, open and observational design. As the primary outcome, the CTP-intervals were compared to the arrival intervals of the EMS. As a secondary outcome, an analysis of all deceased inmates was described. Results The average daily population of inmates in Austrian correctional facilities is 7714. During a period of 13 months, 10 instances in which an AED was activated and electrodes attached to a collapsed inmate, were reported. The CTP-interval (median ± S.D.) was 2.3 ± 1.6 S.D. min. It took the EMS 10.0 ± 4.3 S.D. min. to arrive at the patient's side. Four out of 10 cases of cardiac arrest occurred due to myocardial infarction. Of 39 deceased inmates, a post mortem examination was completed in 34 cases. In 13 cases, cardiovascular disease was the cause of death. Discussion The main finding was a four-fold reduction of the CTP-interval. This fact indicates the potential improvements which could be achieved with the deployment of AEDs. Our secondary objective revealed that death due to cardiovascular disease was found in a high proportion and could be considered to be a strong incentive to initiate programmes to counter cardiovascular death in prison.

Hypothesis Individual, group, and organizational factors influence the professional satisfaction of women surgeons in Austria. Design Survey on professional and private issues sent out by mail in 2000 and 2001. Setting Women surgeons working in hospitals and/or in private practices and those who were retired or on maternity leave. Participants All 351 Austrian women surgeons of all core surgical specialties (general, trauma, pediatric, plastic, thoracic, and cardiovascular), certified or in training, were addressed. Main Outcome Measures Proportional odds regression models were used to correlate professional satisfaction with objectively measurable prognostic factors such as age, surgical subspecialty, status of training, type of hospital, location of work (federal states vs the capital), status of activity (active vs on maternity leave). profession of private partner, number of children, and subjectively assessed prognostic factors such as operative volume and departmental organization. Results The response rate was 58.7% (206/351).One hundred eighty-seven surgeons—active or on maternity leave—were included in the analysis. Higher satisfaction was reported by active surgeons in subspecialties, certified surgeons, comparatively younger and older surgeons, surgeons working in hospitals outside the capital, and surgeons with a physician as a partner. When entering subjectively assessed variables into the model, the quality of departmental organization and operative volume ( P P Conclusions Women surgeons’ professional satisfaction highly depends on departmental organization and status of activity. Inadequate leadership, low operative volume, and being on maternity leave have a negative effect on job satisfaction. Private factors seem to be of little influence. Optimal departmental organization would help women to reconcile their professional and their private lives.

The general paradigm for risk assessment of exposures to toxic agents in human environment is the identification and characterization of hazard, assessment of exposure and characterization of risk. Performed in practice risk assessment is addressing particularly the outcome of integrating the data available from epidemiology, long-term mortality and morbidity studies and mechanistic research with information on the type and extent of exposure, as well as statistical analysis properly used. Various technical and non-technical aspects of the design process of the Monte Carlo simulation study will be reported and discussed. Finally, a Monte Carlo computer simulation study was designed in order to examine in detail the influences of various sources of uncertainty and their potential implications on the risk estimates from the Boehringer cohort data is presented.

Hashimoto's encephalitis is a term which describes encephalopathy associated with autoimmune thyroiditis, but it is not based on evidence, whether Hashimoto's encephalitis is a distinct clinical entity by itself. In previously reported cases of Hashimoto's encephalitis, abnormal brain perfusion studies have been reported. The aim of this study was to evaluate the prevalence of brain perfusion abnormalities in euthyroid patients with autoimmune thyroiditis.99mTc Ethyl cystein dimer (ECD) single photon emission computed tomography (SPECT) studies were performed in a study group of 41 euthyroid patients with autoimmune thyroiditis and a matched control group of 35 healthy individuals. All study participants had a normal neurological investigation and a detailed neurological history taking. Individuals with known or suspected morphological brain abnormalities were excluded from the study. Zung's Self-Rating Anxiety Scale (SAS) and Zung's Self-Rating Depression Scale (SDS) were used to detect depression and mood disorders. Automatic quantification of perfusion was performed with both a voxel-based analysis as well as a volume-of-interest (VOI) based analysis of 46 predefined cortical and subcortical regions. The findings from both groups were compared to a reference template.In the voxel-based analysis, there was a significant difference between patients and controls in the mean volume of perfusion defects deviating 2SD below the normal values (21.8 ml vs. 10.4 ml; P = 0.02). Hyperperfused areas, however, did not differ significantly between study patients and controls. A significant correlation of the perfusion defects with time since diagnosis of autoimmune thyroiditis was seen (r = 0.42). In the VOI-based analysis, abnormal regions were more frequent in the study group when compared to controls (P0.01) However, no topographic pattern was apparent. Regarding neurological findings, no significant difference was found between study patients and controls. However, both the SAS and SDS scores differed significantly between the two groups, but there was neither a correlation between the two scores and perfusion abnormalities nor an association with depression in our study group.These findings of impaired brain perfusion in patients with autoimmune thyroiditis further strengthen the hypothesis of a possible cerebral involvement in autoimmune thyroiditis in individual cases. The presence of cerebral hypoperfusion suggests a cerebral vasculitis as the most likely pathogenetic model.