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Focused assessment with sonography for trauma (FAST) is a valuable ultrasound procedure in emergency settings, and there is a need for evidence-based education in FAST to ensure competencies. Immersive virtual reality (IVR) is a progressive training modality gaining traction in the field of ultrasound training. IVR holds several economic and practical advantages to the common instructor-led FAST courses using screen-based simulation (SBS). This prospective, interventional cohort study investigated whether training FAST using IVR unsupervised and out-of-hospital was non-inferior to a historical control group training at a 90 min SBS course in terms of developing FAST competencies in novices. Competencies were assessed in both groups using the same post-training simulation-based FAST test with validity evidence, and a non-inferiority margin of 2 points was chosen. A total of 27 medical students attended the IVR course, and 27 junior doctors attended the SBS course. The IVR group trained for a median time of 117 min and scored a mean 14.2 ± 2.0 points, compared with a mean 13.7 ± 2.5 points in the SBS group. As the lower bound of the 95% confidence interval at 13.6 was within the range of the non-inferiority margin (11.7–13.7 points), training FAST in IVR for a median of 117 min was found non-inferior to training at a 90 min SBS course. No significant correlation was found between time spent in IVR and test scores. Within the limitations of the use of a historical control group, the results suggest that IVR could be an alternative to SBS FAST training and suitable for unsupervised, out-of-hospital courses in basic FAST competencies. [ABSTRACT FROM AUTHOR]

Evidence to support immediate P2Y 12 inhibitor loading in ST-segment elevation myocardial infarction (STEMI) is limited. This study sought to compare outcomes of STEMI patients receiving immediate or delayed P2Y 12 inhibitor treatment. Using data from the prospective Bern-PCI registry between 2016 and 2020, we stratified STEMI patients undergoing percutaneous coronary intervention according to time periods with different institutional recommendations regarding P2Y 12 inhibitor pretreatment. In cohort 1 (October 2016-September 2018), immediate P2Y 12 inhibitor treatment was recommended. In cohort 2 (October 2018-September 2020), P2Y 12 inhibitor treatment was recommended after coronary anatomy was confirmed. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events (MACCEs) defined as all-cause death, recurrent myocardial infarction, stroke, or definite stent thrombosis at 30 days. Sensitivity analysis included only patients in whom these recommendations were followed. Cohort 1 included 1,116 patients; pretreatment was actually given in 708 (63.4%). Cohort 2 included 847 patients; pretreatment was withheld in 798 (94.2%). The mean age was 65 ± 13 years, and 24% were female. Baseline characteristics were well-balanced between groups. The median difference for P2Y 12 loading to angiography was 52 minutes between cohort 1 and 2 and 100 minutes between patients receiving vs not receiving pretreatment. Rates of MACCEs were similar between cohort 1 and cohort 2 (10.1% vs 8.1%; adjusted HR: 0.91; 95% CI: 0.65-1.28; P = 0.59) and between patients receiving vs not receiving pretreatment (7.1% vs 8.4%; adjusted HR: 1.17; 95% CI: 0.78-1.74; P = 0.45). In this cohort study of patients with STEMI undergoing primary percutaneous coronary intervention, P2Y 12 inhibitor pretreatment was not associated with improved MACCEs. [Display omitted] [ABSTRACT FROM AUTHOR]

Whether ultrathin-strut stents are particularly beneficial for lesions requiring implantation of more than 1 stent is unknown. In a post-hoc lesion-level analysis of 2 randomized trials comparing ultrathin-strut biodegradable polymer Sirolimus-eluting stents (BP-SES) vs thin-strut durable polymer Everolimus-eluting stents (DP-EES), lesions were stratified into multistent lesions (MSL) vs single-stent lesions (SSL). The primary endpoint was target lesion failure (TLF), a composite of lesion-related unclear/cardiac death, myocardial infarction (MI), or revascularization, at 24 months. Among 5328 lesions in 3397 patients, 1492 (28%) were MSL (722 with BP-SES, 770 with DP-EES). At 2 years, TLF occurred in 63 lesions (8.9%) treated with BP-SES and 60 lesions (7.9%) treated with DP-EES in the MSL-group (subdistibution hazard ratio [SHR], 1.13; 95% CI, 0.77-1.64; P =.53), and in 121 (6.4%) and 136 (7.4%) lesions treated with BP-SES and DP-EES respectively (SHR, 0.86; 95% CI, 0.62-1.18; P =.35) in the SSL-group (P for interaction =.241). While the rates of lesion-related MI or revascularization were significantly lower in SSL treated with BP-SES as compared to DP-EES (3.5% vs 5.2%; SHR, 0.67; 95% CI 0.46-0.97; P =.036), no significant difference was observed in MSL (7.1% vs 5.4%; SHR, 1.31; 95% CI 0.85-2.03; P =.216) with significant interaction between groups (P for interaction =.014). Rates of TLF are similar between ultrathin-strut BP-SES and thin-strut DP-EES in MSL and SSL. The use of ultrathin-strut BP-SES vs thin-strut DP-EES did not prove to be particularly beneficial for the treatment of multistent lesions. Post-hoc analysis from the BIOSCIENCE (NCT01443104) and BIOSTEMI (NCT02579031) trials. [ABSTRACT FROM AUTHOR]

Focused lung ultrasound (FLUS) has high diagnostic accuracy in many common conditions seen in a variety of emergency settings. Competencies are essential for diagnostic success and patient safety but can be challenging to acquire in clinical environments. Immersive virtual reality (IVR) offers an interactive risk-free learning environment and is progressing as an educational tool. First, this study explored the educational impact of novice FLUS users participating in a gamified or non-gamified IVR training module in FLUS by comparing test scores using a test with proven validity evidence. Second, the learning effect was assessed by comparing scores of each group with known test scores of novices, intermediates and experienced users in FLUS. A total of 48 participants were included: 24 received gamified and 24 received non-gamified IVR training. No significant difference was found between gamified (mean = 15.5 points) and non-gamified (mean = 15.2 points), indicating that chosen gamification elements for our setup did not affect learning outcome (p = 0.66). The mean scores of both groups did not significantly differ from those of known intermediate users in FLUS (gamified p = 0.63, non-gamified p = 0.24), indicating that both IVR modules could be used as unsupervised out-of-hospital training for novice trainees in FLUS. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) is used in various medical specialties as a diagnostic imaging tool and for procedural guidance. Experience in the procedure is currently attained via supervised clinical practice that is challenged by patient availability and risks. Prior simulation-based training and subsequent assessment could improve and ensure competence before performance on patients, but no simulator currently exists. Immersive virtual reality (IVR) is a new promising simulation tool that can replicate complex interactions and environments that are unfeasible to achieve by traditional simulators. This study was aimed at developing an IVR simulation-based test for core CEUS competencies and gathering validity evidence for the test in accordance with Messick's framework. The test was developed by IVR software specialists and clinical experts in CEUS and medical education and imitated a CEUS examination of a patient with a focal liver lesion with emphasis on the pre-contrast preparations. Twenty-five medical doctors with varying CEUS experience were recruited as test participants, and their results were used to analyze test quality and to establish a pass/fail standard. The final test of 23 test items had good internal reliability (Cronbach's α = 0.85) and discriminatory abilities. The risks of false positives and negatives (9.1% and 23.6%, respectively) were acceptable for the test to be used as a certification tool prior to supervised clinical training in CEUS. [ABSTRACT FROM AUTHOR]

Background/purpose: Guidelines recommend intracoronary optical coherence tomography (OCT) to assess stent failure and guide percutaneous coronary intervention (PCI) but OCT may be useful for other indications in routine clinical practice.Methods/materials: We conducted an international registry of OCT cases at two large tertiary care centers to assess clinical indications and the potential impact on decision making of OCT in clinical routine. Clinical indications, OCT findings, and their impact on interventional or medical treatment strategy were retrospectively assessed.Results: OCT was performed in 810 coronary angiography cases (1928 OCT-pullbacks). OCT was used for diagnostic purposes in 67% (N = 542) and OCT-guided percutaneous coronary intervention in 50% (N = 404, 136 cases with prior diagnostic indication). Most frequent indications for diagnostic OCT were culprit lesion identification in suspected ACS (29%) and stent failure assessment (28%). OCT findings in the diagnostic setting influenced patient management in 74%. OCT-guided PCIs concerned ACS patients in 45%. Among the 55% with chronic coronary syndrome, long lesions >28 mm (19%), left main PCI (16%), and bifurcation PCI with side-branch-stenting (5%) were the leading indications for PCI-guidance. Post-procedural OCT findings led to corrective measures in 52% (26% malapposition, 14% underexpansion, 6% edge dissection, 3% intrastent mass, 3% geographic plaque miss).Conclusions: OCT was most frequently performed to identify culprit lesions in suspected ACS, for stent failure assessment, and PCI-guidance. OCT may impact subsequent treatment strategies in two out of three patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact of echocardiographic guidance on the safety and efficacy of left atrial appendage closure (LAAC). Expert consensus documents recommend intraprocedural imaging by means of either transesophageal echocardiography or intracardiac echocardiography to guide LAAC. However, no evidence exists that intraprocedural echocardiographic guidance in addition to fluoroscopy improves the safety and efficacy of LAAC. Consecutive LAAC procedures performed at a high-volume center between January 2009 and October 2020 were stratified on the basis of intraprocedural imaging modalities, including fluoroscopic guidance (FG) only or intraprocedural echocardiographic guidance (EG) in addition to fluoroscopy. The primary safety endpoint was the composite of procedure-related complications occurring within 7 days after the procedure. Technical success at 7 days and at follow-up were secondary endpoints. Among 811 LAAC procedures, 549 (67.7%) and 262 (32.3%) were assigned to the FG and EG groups, respectively. After adjusting for confounders, EG remained associated with a lower rate of the primary safety endpoint (3.4% vs 9.1%; P = 0.004; adjusted odds ratio [OR]: 0.31; 95% CI: 0.11-0.90; P = 0.030). Technical success trended higher at 7 days (92.1% vs 87.2%; P = 0.065; adjusted OR: 1.68; 95% CI: 0.95-3.01; P = 0.079) and was significantly improved with EG compared with FG (87.6% vs 79.9%; P = 0.018; OR: 4.06; 95% CI: 1.60-10.27; P = 0.003) after a median follow-up period of 4.9 months (interquartile range: 3.4 months-6.2 months). In a large cohort of consecutive LAACs, the use of intraprocedural echocardiography to guide intervention in addition to standard fluoroscopy was associated with lower risks for procedural complications and higher mid-term technical success rates. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown.Aims: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI.Methods: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization.Summary: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI.Clinical Trial Registration: NCT03067844. [ABSTRACT FROM AUTHOR]

• Machine learning (ML) models can predict QA results from plan complexity metrics. • Quality Assurance-based Optimization (QAO) uses ML to optimize predicted QA outcomes. • Feasibility of QAO was demonstrated on 13 VMAT plans. • QAO significantly improved initial QA results without degrading plan quality. Previous literature has shown general trade-offs between plan complexity and resulting quality assurance (QA) outcomes. However, existing solutions for controlling this trade-off do not guarantee corresponding improvements in deliverability. Therefore, this work explored the feasibility of an optimization framework for directly maximizing predicted QA outcomes of plans without compromising the dosimetric quality of plans designed with an established knowledge-based planning (KBP) technique. A support vector machine (SVM) was developed – using a database of 500 previous VMAT plans – to predict gamma passing rates (GPRs; 3%/3mm percent dose-difference/distance-to-agreement with local normalization) based on selected complexity features. A heuristic, QA-based optimization (QAO) framework was devised by utilizing the SVM model to iteratively modify mechanical treatment features most commonly associated with suboptimal GPRs. Specifically, leaf gaps (LGs) <50 mm were widened by random amounts, which impacts all aperture-based complexity features. 13 prostate KBP-guided VMAT plans were optimized via QAO using user-specified maximum LG displacements before corresponding changes in predicted GPRs and dose were assessed. Predicted GPRs increased by an average of 1.14 ± 1.25% (p = 0.006) with QAO using a 3 mm maximum random LG displacement. There were small differences in dose, resulting in similarly small changes in tumor control probability (maximum increase = 0.05%) and normal tissue complication probabilities in the bladder, rectum, and femoral heads (maximum decrease = 0.2% in the rectum). This study explored the feasibility of QAO and warrants future investigations of further incorporating QA endpoints into plan optimization. [ABSTRACT FROM AUTHOR]

Abstract Purpose This article investigates dose-volume prediction improvements in a common knowledge-based planning (KBP) method using a Pareto plan database compared with using a conventional, clinical plan database. Methods and materials Two plan databases were created using retrospective, anonymized data of 124 volumetric modulated arc therapy (VMAT) prostate cancer patients. The clinical plan database (CPD) contained planning data from each patient's clinically treated VMAT plan, which were manually optimized by various planners. The multicriteria optimization database (MCOD) contained Pareto-optimal plan data from VMAT plans created using a standardized multicriteria optimization protocol. Overlap volume histograms, incorporating fractional organ at risk volumes only within the treatment fields, were computed for each patient and used to match new patient anatomy to similar database patients. For each database patient, CPD and MCOD KBP predictions were generated for D 10 , D 30 , D 50 , D 65 , and D 80 of the bladder and rectum in a leave-one-out manner. Prediction achievability was evaluated through a replanning study on a subset of 31 randomly selected database patients using the best KBP predictions, regardless of plan database origin, as planning goals. Results MCOD predictions were significantly lower than CPD predictions for all 5 bladder dose-volumes and rectum D 50 (P =.004) and D 65 (P <.001), whereas CPD predictions for rectum D 10 (P =.005) and D 30 (P <.001) were significantly less than MCOD predictions. KBP predictions were statistically achievable in the replans for all predicted dose-volumes, excluding D 10 of bladder (P =.03) and rectum (P =.04). Compared with clinical plans, replans showed significant average reductions in D mean for bladder (7.8 Gy; P <.001) and rectum (9.4 Gy; P <.001), while maintaining statistically similar planning target volume, femoral head, and penile bulb dose. Conclusion KBP dose-volume predictions derived from Pareto plans were more optimal overall than those resulting from manually optimized clinical plans, which significantly improved KBP-assisted plan quality. Summary This work investigates how the plan quality of knowledge databases affects the performance and achievability of dose-volume predictions from a common knowledge-based planning approach for prostate cancer. Bladder and rectum dose-volume predictions derived from a database of standardized Pareto-optimal plans were compared with those derived from clinical plans manually designed by various planners. Dose-volume predictions from the Pareto plan database were significantly lower overall than those from the clinical plan database, without compromising achievability. [ABSTRACT FROM AUTHOR]

Objectives: To examine cross-sectional and longitudinal associations between physical exercise and cognitive function across different age groups in a nationwide population-based sample of adults aged 18-79 years in Germany.Design: Cross-sectional/prospective.Methods: Cognitive function was assessed in the mental health module of the German Health Interview and Examination Survey for Adults (DEGS1-MH, 2009-2012, n=3535), using a comprehensive neuropsychological test battery. Cognitive domain scores for executive function and memory were derived from confirmatory factor analysis. Regular physical exercise in the last three months was assessed by self-report and defined as no exercise, <2 and ≥2h (hours) of exercise per week. A subgroup of DEGS1-MH participants who previously participated in the German National Health Interview and Examination Survey 1998 (GNHIES98, 1997-1999, n=1624) enabled longitudinal analyses with a mean follow-up of 12.4 years.Results: Compared to no exercise, more weekly physical exercise was associated with better executive function in cross-sectional (<2h: β=0.12; ≥2h: β=0.17; all p<0.001) and longitudinal analyses (<2h: β=0.14, p<0.001; ≥2h: β=0.15, p=0.001) using linear regression models adjusted for age, sex, education, smoking, alcohol consumption, fruit and vegetable consumption and obesity. Slightly weaker associations were found for memory in cross-sectional (<2h: β=0.08, p=0.009; ≥2h: β=0.08, p=0.026) and longitudinal analysis (<2h: β=0.09, p=0.036; ≥2h: β=0.08, p=0.114). There was no evidence of interaction between physical exercise and age.Conclusions: Higher levels of physical exercise were associated with better executive function and memory in cross-sectional and longitudinal analyses with no evidence for differential effects by age. [ABSTRACT FROM AUTHOR]

The Ras-Raf-MEK-ERK1/2 signaling pathway regulates fundamental processes in malignant cells. However, the exact contributions of MEK1 and MEK2 to the development of cancer remain to be established. We studied the effects of MEK small-molecule inhibitors (PD98059 and U0126) and MEK1 and MEK2 knock-down on cell proliferation, apoptosis and MAPK activation. We showed a diminution of cell viability that was associated with a downregulation of cyclin D1 expression and an increase of apoptosis marker in MEK2 silenced cells; by contrast, a slight increase of cell survival was observed in the absence of MEK1 that correlated with an augment of cyclin D1 expression. These data indicate that MEK2 but not MEK1 is essential for MDA-MB-231 cell survival. Importantly, the role of MEK2 in cell survival appeared independent on ERK1/2 phosphorylation since its absence did not alter the level of activated ERK1/2. Indeed, we have reported an unrevealed link between MEK2 and MKK3/MKK6-p38 MAPK axis where MEK2 was essential for the phosphorylation of MKK3/MKK6 and p38 MAPK that directly impacted on cyclin D1 expression. Importantly, the MEK1 inhibitor PD98059, like MEK1 silencing, induced an augment of cyclin D1 expression that correlated with an increase of MDA-MB-231 cell proliferation suggesting that MEK1 may play a regulatory role in these cells. In sum, the crucial role of MEK2 in MDA-MB-231 cell viability and the unknown relationship between MEK2 and MKK3/MKK6-p38 axis here revealed may open new therapeutic strategies for aggressive breast cancer. [ABSTRACT FROM AUTHOR]

Background: Several cases of Mycobacterium chimaera infection have recently been reported in cardiosurgical patients. So-called heater-cooler units (HCUs) used in cardiosurgical procedures are suspected to be the reservoir for pathogen growth and dissemination.Aim: To assess the contamination status of HCUs at our facility.Methods: Air sampling for mycobacteria was conducted at different distances from the machines and in the area around the operating table. Air sampling was also conducted for non-fermenters as a surrogate parameter for water-associated pathogens.Findings: Mycobacterium chimaera was detected in the water tanks of the HCUs. When the devices were operating, M. chimaera was also found in their exhaust air, as well as in the area around the operating table. Non-fermenters were identified at different distances from the running HCU and the area around the operating table. Cultures remained negative when the devices were switched off.Conclusions: Exhaust air from HCUs may be a pathway of pathogen transmission to patients undergoing open chest heart surgery. Although, for technical reasons, relocation of HCUs is difficult to achieve, only strict separation of the HCU from the operating room appears to enhance patient safety. Using non-fermenters as a surrogate parameter may be considered a viable option for a timely risk assessment. The design of HCUs should be modified to keep susceptibility to contamination at a minimum. [ABSTRACT FROM AUTHOR]

Abstract: Helical tomotherapy plans using a combination of pitch and jaw width settings were developed for 3 patients previously treated for head and neck cancer. Three jaw widths (5, 2.5, and 1 cm) and 4 pitches (0.86, 0.43, 0.287, and 0.215) were used with a (maximum) modulation factor setting of 4. Twelve plans were generated for each patient using an identical optimization procedure (e.g., number of iterations, objective weights, and penalties, etc.), based on recommendations from TomoTherapy (Madison, WI). The plans were compared using isodose plots, dose volume histograms, dose homogeneity indexes, conformity indexes, radiobiological models, and treatment times. Smaller pitches and jaw widths showed better target dose homogeneity and sparing of normal tissue, as expected. However, the treatment time increased inversely proportional to the jaw width, resulting in delivery times of 24 ± 1.9 min for the 1-cm jaw width. Although treatment plans produced with the 2.5-cm jaw were dosimetrically superior to plans produced with the 5-cm jaw, subsequent calculations of tumor control probabilities and normal tissue complication probabilities suggest that these differences may not be radiobiologically meaningful. Because treatment plans produced with the 5-cm jaw can be delivered in approximately half the time of plans produced with the 2.5-cm jaw (5.1 ± 0.6 min vs. 9.5 ± 1.1 min), use of the 5-cm jaw in routine treatment planning may be a viable approach to decreasing treatment delivery times from helical tomotherapy units. [Copyright &y& Elsevier]

The objective of this case-control study was to investigate the source of contamination and risk factors for colonisation and infection during an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Enterobacter cloacae in the University Medical Center Freiburg. A risk factor analysis was performed on 23 patients with ESBL-producing E. cloacae in the medical and surgical departments by comparing them with 46 non-colonised controls, who were matched for ward and length of hospital stay. For these, a risk factor analysis was conducted. Suspected sources for transmission of ESBL were examined and staff received training in infection control measures. The higher risk in colonised patients was attributed to dialysis with mobile units [odds ratio (OR): 4.00; 95% confidence interval (CI): 1.05-15.234; P=0.04]. Dialysis units were examined, but no contamination was found. Improvement in dialysis procedures, additional staff training and renewed training in standard precautions led to a substantial fall in case numbers. Risk factor analysis showed that colonised patients carried more invasive devices than controls (central venous catheter: OR: 2.50; 95% CI: 0.74-8.45; P=0.14; Foley catheter: 5.08; 0.61-42.23; P=0.13) and were given a greater number of different antibiotics (penicillins: 2.52; 0.71-8.89; P=0.15; fluoroquinolones: 2.37; 0.77-7.28; P=0.13). The differences in mobile dialysis frequency and antibiotic use between cases and controls were relevant, although the latter was not statistically significant. It was possible to contain the high frequency of ESBL colonisation or infection by reinforcing infection control measures and training the staff involved.Copyright © 2010 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Summary: The objective of this case–control study was to investigate the source of contamination and risk factors for colonisation and infection during an outbreak of extended-spectrum β-lactamase (ESBL)-producing Enterobacter cloacae in the University Medical Center Freiburg. A risk factor analysis was performed on 23 patients with ESBL-producing E. cloacae in the medical and surgical departments by comparing them with 46 non-colonised controls, who were matched for ward and length of hospital stay. For these, a risk factor analysis was conducted. Suspected sources for transmission of ESBL were examined and staff received training in infection control measures. The higher risk in colonised patients was attributed to dialysis with mobile units [odds ratio (OR): 4.00; 95% confidence interval (CI): 1.05–15.234; P =0.04]. Dialysis units were examined, but no contamination was found. Improvement in dialysis procedures, additional staff training and renewed training in standard precautions led to a substantial fall in case numbers. Risk factor analysis showed that colonised patients carried more invasive devices than controls (central venous catheter: OR: 2.50; 95% CI: 0.74–8.45; P =0.14; Foley catheter: 5.08; 0.61–42.23; P =0.13) and were given a greater number of different antibiotics (penicillins: 2.52; 0.71–8.89; P =0.15; fluoroquinolones: 2.37; 0.77–7.28; P =0.13). The differences in mobile dialysis frequency and antibiotic use between cases and controls were relevant, although the latter was not statistically significant. It was possible to contain the high frequency of ESBL colonisation or infection by reinforcing infection control measures and training the staff involved. [Copyright &y& Elsevier]

Abstract: Introduction: Colorectal carcinomas exhibit a frequent recurrence after curative surgery, which may partially be due to histopathologically inconspicuous minimal residual disease. Reliable markers for tumor cells in colorectal tissue are still missing. Therefore, in this study we compared the predictive value of the putative tumor markers carcinoembryonic antigen (CEA), cytokeratin-19 (CK19) and cytokeratin-20 (CK20) to that of a novel marker, the human ether-a-go-go-related gene (HERG1) K+ channel, a suggested regulator of tumor cell proliferation. Materials and methods: Using RT-PCR we studied HERG, CEA, CK19 and CK20 expression in colorectal carcinomas and non-carcinoma controls. HERG1 immunhistochemistry was performed in a total of 66 specimens, in colorectal carcinoma (n = 23), in matched histopathologically negative samples (n = 23) taken near the excision site from the same tumor patients and in healthy control biopsies (n = 20). In order to verify the relevance of HERG1 for tumor proliferation we studied the effect of HERG1 inhibition in the Colo-205 colon cancer carcinoma cell line using the MTT-assay. Results: HERG1 was expressed in all tumor samples regardless of their stage and in adenomas larger than 0.4 cm, but absent in small adenomas, sigmadiverticulitis specimen and healthy histopathologically negative samples, except for one which developed a tumor recurrence. In contrast, CEA, CK19 and CK20 were absent in some tumors. The selective HERG1 inhibitor E-4031 dose-dependently impaired tumor growth in the proliferation assays. Discussion: Our data indicate that HERG1, but not CEA, CK19 or CK20, is a highly sensitive and reliable tumor biomarker that may constitute a novel molecular target for tumor treatment. [Copyright &y& Elsevier]

Purpose: To assess the risk of a secondary malignant neoplasm (SMN) from proton therapy relative to intensity-modulated radiation therapy (IMRT) using X-rays, taking into account contributions from both primary and secondary sources of radiation, for prostate cancer. Methods and Materials: A proton therapy plan and a 6-MV IMRT plan were constructed for 3 patients with early-stage adenocarcinoma of the prostate. Doses from the primary fields delivered to organs at risk of developing an SMN were determined from treatment plans. Secondary doses from the proton therapy and IMRT were determined from Monte Carlo simulations and available measured data, respectively. The risk of an SMN was estimated from primary and secondary doses on an organ-by-organ basis by use of risk models from the Committee on the Biological Effects of Ionizing Radiation. Results: Proton therapy reduced the risk of an SMN by 26% to 39% compared with IMRT. The risk of an SMN for both modalities was greatest in the in-field organs. However, the risks from the in-field organs were considerably lower with the proton therapy plan than with the IMRT plan. This reduction was attributed to the substantial sparing of the rectum and bladder from exposure to the therapeutic beam by the proton therapy plan. Conclusions: When considering exposure to primary and secondary radiation, proton therapy can reduce the risk of an SMN in prostate patients compared with contemporary IMRT. [Copyright &y& Elsevier]

Abstract: Very few traditional foods that are consumed have been subjected to systematic toxicological and nutritional assessment, yet because of their long history and customary preparation and use and absence of evidence of harm, they are generally regarded as safe to eat. This ‘history of safe use’ of traditional foods forms the benchmark for the comparative safety assessment of novel foods, and of foods derived from genetically modified organisms. However, the concept is hard to define, since it relates to an existing body of information which describes the safety profile of a food, rather than a precise checklist of criteria. The term should be regarded as a working concept used to assist the safety assessment of a food product. Important factors in establishing a history of safe use include: the period over which the traditional food has been consumed; the way in which it has been prepared and used and at what intake levels; its composition and the results of animal studies and observations from human exposure. This paper is aimed to assist food safety professionals in the safety evaluation and regulation of novel foods and foods derived from genetically modified organisms, by describing the practical application and use of the concept of ‘history of safe use’. [Copyright &y& Elsevier]

Risk factors for the selection of Stenotrophomonas maltophilia were analysed by correlating antimicrobial use and structure parameters (e.g. hospital type) with the incidence density of S. maltophilia and the percentage of S. maltophilia isolated from 39 intensive care units (ICUs). SARI (Surveillance of Antimicrobial Use and Antimicrobial Resistance in German Intensive Care Units) is a prospective unit- and laboratory-based surveillance system that collects data on the 13 most important organisms responsible for nosocomial infections. The percentage of S. maltophilia among these organisms and the number of S. maltophilia per 1000 patient-days were calculated. The data were subsequently correlated with antibiotic use density calculated in defined daily doses (DDDs) per 1000 patient-days and structure parameters. The data covered a total of 28 266 isolates and 431 351 DDDs. The antibiotic use density ranged from 427 to 2218, with the median being 1346. Over the two-year period, the median of S. maltophilia per 1000 patient-days was 1.4 (range 0-7.6). Calculation of antibiotic use and S. maltophilia per 1000 patient-days showed a significant positive correlation with the use of carbapenems, ceftazidime, glycopeptides and fluoroquinolones, as well as with total antibiotic use. In the multiple logistic regression analysis, carbapenem use and >12 ICU beds were independently and positively associated with a high number of S. maltophilia per 1000 patient-days. Benchmarking data provided for incidence densities of S. maltophilia in ICUs revealed the heterogeneous situation of the burden of S. maltophilia in individual ICUs. The multi-centre data showed that carbapenem use and >12 ICU beds were independent risk factors for the isolation of S. maltophilia. Copyright © 2006 The Hospital Infection Society [ABSTRACT FROM AUTHOR]

Conservative testing revealed a stable antibiotic resistance situation for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae in 32 German intensive care units (ICUs) actively participating in the SARI (surveillance of antimicrobial use and antimicrobial resistance in ICUs) project over a three-year period (2001-2003). No significant changes were shown for methicillin-resistant S. aureus (MRSA) (P=0.501; the MRSA rate increased in 18 ICUs and decreased in 14 ICUs). The only exception was an increase in ciprofloxacin-resistant E. coli. Copyright © 2005 The Hospital Infection Society [ABSTRACT FROM AUTHOR]

Abstract: The shortage of donor organs for renal transplantation leads to the necessity of accepting organs with vascular disadvantages, such as venous difficulties (eg, shortness, disrupted vein after explantation) or arterial problems (eg, iatrogenic vascular accidents, arterial plaques, hemodynamically relevant polar arteries) and horseshoe kidneys. Consequently, such organs may not be considered for transplantation. Surgeons still have the ability to use such organs by saphenous vein interposition. This study focused on the frequency of vascular difficulties in 100 randomly selected kidney transplantations and their outcomes after arterial or venous saphenous vein interposition. [Copyright &y& Elsevier]

Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of interferon regulatory factor 3 (IRF-3), nuclear factor κB (NF-κB), and type I interferon (IFN) signaling. Here, we use highly multiplexed proteomics to quantify ∼9,000 cellular proteins and ∼80% of viral proteins at seven time points throughout VACV infection. A total of 265 cellular proteins are downregulated >2-fold by VACV, including putative natural killer cell ligands and IFN-stimulated genes. Two-thirds of these viral targets, including class II histone deacetylase 5 (HDAC5), are degraded proteolytically during infection. In follow-up analysis, we demonstrate that HDAC5 restricts replication of both VACV and herpes simplex virus type 1. By generating a protein-based temporal classification of VACV gene expression, we identify protein C6, a multifunctional IFN antagonist, as being necessary and sufficient for proteasomal degradation of HDAC5. Our approach thus identifies both a host antiviral factor and a viral mechanism of innate immune evasion. • Temporal proteomic analysis quantifies host and viral dynamics during vaccinia infection • Host protein families are proteasomally degraded over the course of vaccinia infection • Vaccinia protein C6 targets HDAC5 for proteasomal degradation • HDAC5 is a host antiviral factor that restricts different families of DNA viruses Soday et al. describe a temporal proteomic analysis of vaccinia virus infection that includes systematic investigation into virally induced host protein degradation. Vaccinia degrades multiple families of immune ligands and interferon-stimulated genes. The viral C6 protein targets histone deacetylase 5 (HDAC5) for proteasomal degradation to evade the antiviral activity of HDAC5. [ABSTRACT FROM AUTHOR]