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Background: Newly diagnosed patients with inflammatory bowel disease (IBD) encounter many physical, mental, and social uncertainties. In other chronic diseases, patients having access to disease-specific information and psychological support adhere better to medical regimens. Currently, there is a paucity of data on how newly diagnosed patients with IBD interact with their medical providers. Methods: Patients diagnosed with IBD within 5 years completed a series of questionnaires related to heath-related quality of life (HRQoL), disease activity, health education resources, medical provider relationship, and psychological support. Results: A total of 89 patients were included in the study. IBD activity correlated with disease-specific quality of life (r=−0.69, p

Can imaging provide sufficient risk stratification to warrant revascularization of a stable plaque with negative fractional flow reserve (FFR)? Prophylactic stenting could at best be applied selectively since the composite group of FFR-negative lesions has a death or myocardial infarction rate of approximately 1%/year or less but modern stents have a rate of 2% to 3.5%/year. Because vulnerable features exist in a minority of lesions, at least 9,000 patients must be screened in order to enroll a cohort with sufficient risk. While several ongoing randomized trials are testing the concept of plaque sealing in FFR-negative lesions, preventive stenting depends on such a small effect that sample sizes to validate or refute its benefit become prohibitive. Since FFR provides a quantitative, straightforward, and reproducible metric of plaque vulnerability and burden without the need for or expense of additional catheter devices, intracoronary imaging cannot meaningfully guide prophylactic stenting when faced with a negative FFR.

Novel phospholipid (PL)-cyclosporine conjugates were prepared and studied as potential prodrugs for inflammatory bowel disease (IBD). Our approach relies on phospholipase A2 (PLA2 ), which is overexpressed in the inflamed intestinal tissues, as the prodrug activator to potentially release cyclosporine at the site of inflammation. PL-cyclosporine prodrug conjugates with methylene linkers of various lengths between the sn-2 position of the PL and cyclosporine were synthesized and evaluated for in vitro activation. Surprisingly, despite previous work indicating that conjugates with six methylene linkers between the lipid and drug would suffer rapid enzymatic hydrolysis, with cyclosporine this was not observed. However, compounds with longer linkers (n=10, 12 methylene units) display complete release of the drug by PLA2 -catalyzed hydrolysis, thus demonstrating the importance and profound impact of structural fine-tuning. This study represents a proof-of-concept for our hypothesis and a first step towards a truly targeted IBD treatment with cyclosporine that could be administered throughout the GI tract.

Introduction: The social impact of inflammatory bowel disease (IBD) on student transition to college is significant, yet poorly understood. Methods: Two 90-min focus groups (FGs) were conducted with eight student-patients with IBD. Reflective journals were used to corroborate, elaborate, or challenge emergent FG findings. Results: Six themes emerged: (1) transitioning to college, (2) interacting with physicians, (3) affecting social life, (4) managing the disease by yourself and through support, (5) coping strategies, and (6) facing disease challenges. These themes remained relevant in the reflective writings. Analysis of serial journal entries showed that students' social life and engagement in coursework was affected 66% and 54% of the time, respectively. Conclusion: Our findings offer guidance for improving students' college success, quality of care, and enhancing physician–patient interactions. Students with IBD have a disability that may not be obvious or visible. They require specific support to help them transition and succeed in college.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking.METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed.RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group.CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

In acute myocardial infarction (AMI), myocardial reperfusion injury may undo part of the recovery after revascularization of the occluded coronary artery. Selective intracoronary hypothermia is a novel method aimed at reducing myocardial reperfusion injury, but its presumed protective effects in AMI still await further elucidation. This proof-of-concept study assesses the potential protective effects of selective intracoronary hypothermia in an ex-vivo, isolated beating heart model of AMI. In four isolated Langendorff perfused beating pig hearts, an anterior wall myocardial infarction was created by inflating a balloon in the mid segment of the left anterior descending (LAD) artery. After one hour, two hearts were treated with selective intracoronary hypothermia followed by normal reperfusion (cooled hearts). In the other two hearts, the balloon was deflated after one hour, allowing normal reperfusion (control hearts). Biopsies for histologic and electron microscopic evaluation were taken from the myocardium at risk at different time points: before occlusion (t = BO); 5 minutes before reperfusion (t = BR); and 10 minutes after reperfusion (t = AR). Electron microscopic analysis was performed to evaluate the condition of the mitochondria. Histological analyses included evaluation of sarcomeric collapse and intramyocardial hematoma. Electron microscopic analysis revealed intact mitochondria in the hypothermia treated hearts compared to the control hearts where mitochondria were more frequently damaged. No differences in the prespecified histological parameters were observed between cooled and control hearts at t = AR. In the isolated beating porcine heart model of AMI, reperfusion was associated with additional myocardial injury beyond ischemic injury. Selective intracoronary hypothermia preserved mitochondrial integrity compared to nontreated controls.

Tracheal tumour is rare but can lead to upper airway obstruction and acute respiratory distress. Its management includes surgical resection, radiotherapy or interventional bronchoscopy. Ventilation or difficulties with tracheal intubation can occur during the peri‐operative course resulting in serious adverse consequences. We report the case of an 83‐year‐old man with an obstructive tracheal chondrosarcoma resected by rigid bronchoscopy undergoing veno‐venous extracorporeal membrane oxygenation. Such support should be considered when the patient's airway patency cannot be ensured by conventional methods.

Objectives: This study aimed to prospectively investigate intra-aortic balloon pump counterpulsation (IABP) support in large myocardial infarction complicated by persistent ischemia after primary percutaneous coronary intervention (PCI). Background: Use of IABP is suggested to be effective by increasing diastolic aortic pressure, thereby improving coronary blood flow. This can only be expected with exhausted coronary autoregulation, typical in acute myocardial infarction complicated by persistent ischemia. In this situation, augmented diastolic pressure is expected to increase myocardial oxygenation. Methods: One hundred patients with large STEMI complicated by persistent ischemia after primary PCI were randomized to treatment with or without IABP therapy on top of standard care. IABP support was initiated following primary PCI, immediately after inclusion. Primary end point was all-cause mortality, need for (additional) mechanical hemodynamic support, or readmission for heart failure within 6 months. Results: Mean age was 63 ± 10 years, 76% were male. Mean systolic and diastolic blood pressure were 120 ± 25 mmHg and 73 ± 17 mmHg. Mean heart rate was 75 ± 18 mmHg. Before PCI, mean summed ST-deviation was 21 ± 8 mm with only minimal ST-resolution after PCI. One patient in the IABP group reached the primary end point versus four patients in the control group (2% vs. 8%; p = 0.16). After primary PCI, resolution of ST-deviation was significantly more pronounced in the IABP group (73 ± 17%) compared to the control group (56 ± 26%; p < 0.01). Conclusions: In this pilot study, in patients with large STEMI and persistent ischemia after primary PCI, use of IABP showed a nonsignificant decrease in mortality, necessity for (additional) mechanical hemodynamic support or readmission for heart failure at 6 months, and resulted in more rapid ST-resolution.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) in adulthood is associated with problems in multiple domains of everyday life, including financial decision-making (FDM). Research on FDM in adults with ADHD is, however, limited and FDM has never been examined in an objective standardized manner in these patients. The aim of the present study is to explore FDM abilities of adults with ADHD, using both subjective and standardized objective measures.METHOD: Adults with ADHD (n = 45) and healthy controls (n = 51) completed a comprehensive test battery, including an evaluation of their personal financial situation, a neuropsychological assessment and standardized tests and questionnaires measuring various aspects of FDM.RESULTS: Adults with ADHD reported to have a significantly poorer financial situation than healthy controls, including having less income, more often debts and less often a savings account. Furthermore, adults with ADHD showed significantly lower scores than healthy controls in standardized tests measuring financial competence and capacity (i.e., understanding bank statements/protocols and evaluating financial problems) as well as in a test measuring decision making with implications for the future. Furthermore, compared with healthy controls, adults with ADHD reported more often to buy on impulse and to use an avoidant or spontaneous decision-making style. A mediating effect of numeracy was found for 2 measures of FDM (i.e., financial competence and capacity); however, group differences on these measures remained statistically significant.CONCLUSIONS: Adults with ADHD have difficulties with several aspects of FDM. These difficulties may at least partly explain the poorer financial situation of adults with ADHD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Purpose A multiphasic cine sequence performed during magnetic resonance enterography (MRE) has been shown to increase diagnostic accuracy of MRE demonstrating limited movement in inflamed intestine in patients with Crohn’s disease (CD). Our aim was to confirm in our study population that intestinal inflammation was associated with decreased motility and determine if factors suggestive of complicated disease such as the presence of a stricture or fistula were associated with decreased motility on the MRE cine sequence. Methods This was a retrospective study of 59 patients (mean age 40.8 ± 16.1) with Crohn’s disease who had a small bowel lesion on MRE. Two gastrointestinal radiologists independently scored MRE findings using a qualitative, subjective scoring system. Univariate and multivariable ordered logistic regression models were used to evaluate the associations between cine sequence score, radiologic image findings, and clinical data. Results On univariate analysis, radiologic findings reflecting active inflammation, the presence of a stricture, and penetrating disease were associated with decreased motility. On multivariable analysis, hyper-enhancement, the presence of a comb sign, and global evidence of active inflammation remained associated with decreased motility. Of the factors suggesting complicated disease, the presence of stricture (Odds Ratio 0.40, 95% Confidence Interval 0.17-0.95, p-value 0.038) was associated with decreased motility. Conclusions As previously shown, well-established radiologic findings of bowel inflammation were associated with decreased small bowel motility. In this study, we have added that the radiologic finding of a fixed stricture is also associated with decreased motility.

Myocardial reperfusion injury—triggered by an inevitable inflammatory response after reperfusion—may undo a considerable part of the myocardial salvage achieved through timely percutaneous coronary intervention in patients with acute myocardial infarction. Because infarct size is strongly correlated to mortality and risk of heart failure, the importance of endeavors for cardioprotective therapies to attenuate myocardial reperfusion injury and decrease infarct size remains undisputed. Myocardial reperfusion injury is the result of several complex nonlinear phenomena, and for a therapy to be effective, it should act on multiple targets involved in this injury. In this regard, hypothermia remains a promising treatment despite a number of negative randomized controlled trials in humans with acute myocardial infarction so far. To turn the tide for hypothermia in patients with acute myocardial infarction, sophisticated solutions for important limitations of systemic hypothermia should continue to be developed. In this review, we provide a comprehensive overview of the pathophysiology and clinical expression of myocardial reperfusion injury and discuss the current status and possible future of hypothermia for cardioprotection in patients with acute myocardial infarction.

Studies on social cognition often use complex visual stimuli to asses neural processes attributed to abilities like "mentalizing" or "Theory of Mind" (ToM). During the processing of these stimuli, eye gaze, however, shapes neural signal patterns. Individual differences in neural operations on social cognition may therefore be obscured if individuals' gaze behavior differs systematically. These obstacles can be overcome by the combined analysis of neural signal and natural viewing behavior. Here, we combined functional magnetic resonance imaging (fMRI) with eye-tracking to examine effects of unconstrained gaze on neural ToM processes in healthy individuals with differing levels of emotional awareness, i.e. alexithymia. First, as previously described for emotional tasks, people with higher alexithymia levels look less at eyes in both ToM and task-free viewing contexts. Further, we find that neural ToM processes are not affected by individual differences in alexithymia per se. Instead, depending on alexithymia levels, gaze on critical stimulus aspects reversely shapes the signal in medial prefrontal cortex (MPFC) and anterior temporoparietal junction (TPJ) as distinct nodes of the ToM system. These results emphasize that natural selective attention affects fMRI patterns well beyond the visual system. Our study implies that, whenever using a task with multiple degrees of freedom in scan paths, ignoring the latter might obscure important conclusions.

Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long‐term clinical outcome of patients with stable coronary artery disease but no ischemia‐inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all‐cause death, myocardial infarction, and any revascularization) after 5 years in 1122 patients without significant stenosis (all FFR >0.80; n=275) or with at least 1 significant stenosis successfully treated by percutaneous coronary intervention (ie, post–percutaneous coronary intervention FFR >0.80; n=847). The patients were stratified into low, mid, or high tertiles of global FFR (≤2.80, 2.80–2.88, and ≥2.88). Patients in the lowest tertile of global FFR showed the highest 5‐year MACE rate compared with those in the mid or high tertile of global FFR (27.5% versus 22.0% and 20.9%, respectively; log‐rank P =0.040). The higher 5‐year MACE rate was mainly driven by a higher rate of revascularization in the low global FFR group (16.4% versus 11.3% and 11.8%, respectively; log‐rank P =0.038). In a multivariable model, an increase in global FFR of 0.1 unit was associated with a significant reduction in the rates of MACE (hazard ratio [HR], 0.988; 95% CI, 0.977–0.998; P =0.023), myocardial infarction (HR, 0.982; 95% CI, 0.966–0.998; P =0.032), and revascularization (HR, 0.985; 95% CI, 0.972–0.999; P =0.040). Conclusions Even in the absence of ischemia‐producing stenoses, patients with a low global FFR, physiologic correlate of global atherosclerotic burden, present a higher risk of MACE at 5‐year follow‐up.

Resume Face a l’emergence de la pandemie a COVID 19, l’activite de chirurgie bariatrique/metabolique a ete arretee. Le confinement et l’arret de cette chirurgie ont eu un impact sous-estime sur la population obese avec prise de poids, et aggravation des comorbidites. Un certain nombre de candidats a cette chirurgie sont exposes a un risque important de mortalite liee a la pandemie. En effet, l’obesite et le diabete sont deux facteurs de risque majeurs de forme grave d’infection a COVID-19. Le seul traitement efficace actuel de l’obesite est la chirurgie metabolique avec un benefice rapide et durable. Il parait donc necessaire de reprendre une activite de chirurgie metabolique. Le but de ce travail est de hierarchiser la reprise chirurgicale afin qu’elle soit progressive et coherente. Les organigrammes proposes aideront les centres a determiner les patients prioritaires selon la balance benefice-risque. Le diabete a une place centrale dans l’arbre decisionnel. Les modalites de reprise seront variables d’un centre a l’autre selon les ressources humaines, materielles et medicamenteuses, et seront a adapter a l’evolution epidemique. Un consentement eclaire specifique sera necessaire. Un depistage chez les patients obeses est a envisager dont les modalites de depistage sont elaborees sur la base des connaissances disponibles. En cas de suspicion de COVID, la chirurgie doit etre differee. Il faut insister sur les mesures et gestes barrieres afin de proteger le patient et le personnel soignant. Un confinement est fortement suggere pour le patient durant le premier mois postoperatoire. Le suivi des patients sera effectue de preference par teleconsultation.

Background: To examine time intervals between needle/core biopsy, breast cancer diagnosis, surgery and radiotherapy (RT) as quality metrics in the management of stage I-III breast cancer in a representative Swiss population sample. Methods: Based on seven regional cancer registries covering 45% of the Swiss population, we identified 2628 women which underwent surgery for stage I-III breast cancer without receiving (neo)-adjuvant chemotherapy between January 1, 2003 and December 31, 2005. Four different time intervals were defined: a) time between needle/core biopsy and diagnosis of breast cancer, b) time between diagnosis of breast cancer and surgery, c) time between needle/core biopsy and surgery, d) time between surgery and adjuvant RT. These four time intervals were analyzed according to age, nationality, health insurance status, public vs. private hospitals and geography. We also investigated whether case discussion at tumor board delayed patient management. A one-way analysis of variance (ANOVA) and multiple comparison tests were used to assess differences between groups. All tests were performed using STATA v.15. Results: 2628 women were identified, median age was 67 years (IQR: 58-77). Breast-conserving surgery was performed in 1899 cases (72.3%), mastectomy in 539 cases (20.5%), unspecified surgery /missing data in 190 cases (7.2%). Adjuvant RT was delivered in 1546/2628 patients (58.8 %). Time interval between biopsy and surgery was age-dependent, ranging from 22 days (95% CI: 19.6 - 25.2) for women < 60 years to 39 days (95% CI: 27.0-50.3) for women 80+ years old (p Time between surgery and RT did not correlate with age (p=0.83); the interval was 33% longer in tertiary teaching hospitals than in private clinics (61 vs. 46 days, p Conclusions: Major differences in treatment waiting times were observed between patients with stage I-III breast cancer. Elderly and foreign patients were at risk for delayed surgery after biopsy. Data from patients with longer timelines need to be analyzed to identify further reasons for delays. Citation Format: Zwahlen DR, Herrmann C, Mousavi M, Bordoni A, Bouchardy C, Konzelmann I, Staehlin K, Rohrmann S, Oehler C, Zimmermann M. Treatment delivery waiting times for stage I-III breast cancer patients in Switzerland : A pooled analysis of 7 cancer registries over the 2003-2008 period [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-32.

Systemic sclerosis (SSc) is a rare chronic disease of unknown pathogenesis characterized by fibrosis of the skin and internal organs, vascular alteration, and dysregulation of the immune system. In order to better understand the immune system and its perturbations leading to diseases, the study of the mechanisms regulating cellular metabolism has gained a widespread interest. Here, we have assessed the metabolic status of plasma and dendritic cells (DCs) in patients with SSc. We identified a dysregulated metabolomic signature in carnitine in circulation (plasma) and intracellularly in DCs of SSc patients. In addition, we confirmed carnitine alteration in the circulation of SSc patients in three independent plasma measurements from two different cohorts and identified dysregulation of fatty acids. We hypothesized that fatty acid and carnitine alterations contribute to potentiation of inflammation in SSc. Incubation of healthy and SSc dendritic cells with etoposide, a carnitine transporter inhibitor, inhibited the production of pro-inflammatory cytokines such as IL-6 through inhibition of fatty acid oxidation. These findings shed light on the altered metabolic status of the immune system in SSc patients and opens up for potential novel avenues to reduce inflammation.

Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein–protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo.

Patients with inflammatory bowel disease (IBD) commonly require surgery despite the availability of an increasingly large repertoire of powerful immunosuppressive medications for the treatment of IBD. Optimizing patients’ care preoperatively is crucial to obtaining good surgical outcomes. This review discusses preoperative assessment and management principles including assessing disease location and activity with cross-sectional or endoscopic imaging, addressing modifiable risk factors (i.e., stopping smoking, weaning steroids, and correcting anemia), and properly managing medications. The major focus of our literature review is the evaluation for malnutrition, a common finding that affects up to 70% of patients with IBD and a well-known, independent risk factor for adverse postoperative outcomes. Our review confirms that whenever feasible, oral or enteral nutrition (EN) is the preferred method of nutritional support; parenteral nutrition (PN) should be reserved for nutritionally deficient IBD patients unable to tolerate EN. In selected patients, recent data demonstrated that the use of preoperative PN resulted in improved nutritional status, fewer postoperative complications, and reduced disease severity. Our review highlights the need for well-designed, prospective trials investigating perioperative nutritional support in patients with IBD. Future studies should perform modern nutritional assessment, standardize for diet, and include patients with UC since this subset of patients is underrepresented in existing studies. In addition, relevant outcome of interest specific to Crohn’s disease (CD) patients such as length of small bowel resected, number of anastomoses, and need for an ostomy should be included as these patients may require repeated small bowel resections.

Although the effects of biologic agents on postoperative outcomes in Crohn's disease patients have been extensively studied, the effects on intraoperative outcomes, including blood loss, operative time, and length of small bowel resection, remain to be determined. This was a retrospective cohort study at a single tertiary referral center. Crohn's disease (CD) patients who underwent major abdominal surgery were identified. Patients receiving preoperative biologic agents were compared with controls. We compare operative outcomes between groups. A total of 144 patients who underwent major abdominal surgery at the University of Florida between March 2007 and March 2017 were included. One hundred and ten patients (76%) who received pre-operative biologic therapy were compared with 34 controls. On univariate analysis, preoperative biologic use was associated with a significantly shorter length of small bowel resection (21.2 cm in biologic group vs 34.5 cm, P = 0.01). There were no significant differences in intraoperative blood loss (100 vs 87.5 mL, P = 0.40) or total operative time (142 vs 154 minutes, P = 0.39) between groups. On multivariate analysis controlling for variables reflecting severity of disease and malnutrition, biologic use remained significantly associated with shorter length of bowel resection (incident rate ratio 0.58, P = 0.04). Preoperative biologic use is associated with a significantly shorter length of bowel resection in CD patients undergoing major abdominal surgery. No negative effects were noted on operative blood loss or total operative time. Our findings allow improved preoperative planning for surgeons and informed decision-making for CD patients undergoing major abdominal surgery.

Computed tomography and magnetic resonance enterography have become routine small bowel imaging tests to evaluate patients with established or suspected Crohn's disease, but the interpretation and use of these imaging modalities can vary widely. A shared understanding of imaging findings, nomenclature, and utilization will improve the utility of these imaging techniques to guide treatment options, as well as assess for treatment response and complications. Representatives from the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society of Pediatric Radiology, the American Gastroenterological Association, and other experts, systematically evaluated evidence for imaging findings associated with small bowel Crohn's disease enteric inflammation and established recommendations for the evaluation, interpretation, and use of computed tomography and magnetic resonance enterography in small bowel Crohn's disease. This work makes recommendations for imaging findings that indicate small bowel Crohn's disease, how inflammatory small bowel Crohn's disease and its complications should be described, elucidates potential extra-enteric findings that may be seen at imaging, and recommends that cross-sectional enterography should be performed at diagnosis of Crohn's disease and considered for small bowel Crohn's disease monitoring paradigms. A useful morphologic construct describing how imaging findings evolve with disease progression and response is described, and standard impressions for radiologic reports that convey meaningful information to gastroenterologists and surgeons are presented.

Background: The aim of this study was to identify factors that influence the delivery of post-mastectomy radiotherapy (PMRT) in Switzerland, and to analyze the adherence to consensus guidelines. Methods: Based on 7 regional cancer registries covering 45% of the Swiss population, we identified 1408 women which underwent mastectomy for stage I-III breast cancer between January 1, 2003 and December 31, 2005. We categorized patients according to ASCO grouping in similar fashion to other comparable studies: low-risk group (T1/T2 N0): PMRT not routinely recommended; intermediate-risk group (T1/T2 N1): PMRT controversial; high risk group (T3-T4 and/or N2-N3): PMRT recommended. We further investigated factors leading to potential overtreatment (PMRT in low-risk group) or undertreatment (absence of PMRT in high-risk group). Data analysis was performed for the entire cohort, and separately for patients Results: A total of 421 patients (29.9%) received adjuvant RT after mastectomy. The rate of PMRT delivery was 67% in the high-risk group, compared to 6% and 18% in the low-risk and intermediate-risk groups, respectively. For patients at high-risk of chest wall recurrence after mastectomy (T3-T4 or N2-N3 disease), the risk of PMRT omission wassignificantly associated to older age (OR 4.25 [95% CI: 2.27-7.95] for patients ≥ 70 years) and to the absence of chemotherapy (OR 4.30 [95% CI: 1.97-9.36]). In patients with T3-T4 disease, PMRT was delivered in 77% of patients < 70 years and in 42% of patients ≥ 70 years (p PMRT was delivered to 28 patients (7%) at low-risk of recurrence after mastectomy (T1-T2 N0, negative margins). It was more frequently offered to patients Positive or close surgical margins (< 1mm) were a strong indicator for PMRT (p=0.001) and chest wall boost (p Conclusions: After mastectomy, one third of patients (33.26%) with high-risk disease did not receive PMRT. Even if we consider only patients < 70 years, a non-trivial proportion of patients with clear indication for treatment delivery did not receive PMRT (T3-T4 disease: 23%; N2-N3 disease: 18%). Further analyses are planned to explain the apparent failure of evidence-based guidelines to impact the adoption of PMRT in women with high-risk breast cancer. Citation Format: Zwahlen DR, Ess S, Zimmermann M, Bordoni A, Bouchardy C, Frick H, Konzelmann I, Mousavi M, Rohrmann S, Oehler C. Disparities in the application of post-mastectomy radiotherapy in Switzerland: A pooled analysis of 7 cancer registries over the 2003-2005 period [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-24.

Patients with rectovaginal fistulas have a significantly reduced quality of life. Therefore, surgical therapy is often needed even in palliative cases. The aim of the present study was to perform an analysis of the results of the different treatment options available today. We performed a retrospective analysis of patients who underwent treatment for rectovaginal fistulas at the Department of Surgery, University of Schleswig–Holstein, Campus Luebeck and the Department of Surgery, WKK Heide, between January 2000 and September 2016. Complication and recurrence rate were retrospectively evaluated. The median follow-up period was 13 months (range 3–36 months). During the observation period, 58 patients underwent surgery (53 curative, 5 palliative) for rectovaginal fistulas. All patients who underwent curative surgery had an omentoplasty, and 39 of 53 (73.6%) patients underwent a resection. Thirty of 39 (77.0%) resections were low anterior resection, while non-continence-preserving resection included subtotal colectomy (n = 5), pelvic exenteration (n = 2), and proctectomy (n = 2). The fistulas were mainly secondary to inflammatory bowel disease (n = 18) or diverticulitis (n = 13), while 19 fistulas were a complication of different cancers or precancerous lesions. The median follow-up time was 13 months (range 6–36). Four patients (6.9%) had fistula recurrence (3 recurrences after low anterior resection, 1 after primary fistula closure). The mortality rate was 6.9% (n = 4). Non-resecting methods should be used only in uncomplicated fistulas. Rectovaginal fistulas secondary to inflammatory or malignant disease mostly require extensive therapy. Omentoplasty is effective for the treatment of both high and low rectovaginal fistulas.

The purpose of the article is to compare information regarding small bowel lesions in Crohn’s disease (CD) patients communicated by a published scoring system and radiology reports from electronic medical record (EMR) of cross-sectional abdominal imaging. Two gastrointestinal radiologists (reference readers) blinded to EMR reports scored cross-sectional imaging exams using a published scoring system. Investigators compared EMR and radiologist scores based on the mentioned findings and severity documentation of each variable. Statistical analysis involved means and difference in proportions and logistic regression modeling. Seventy-three CD patients, with average age 40.6 years (± SD 14.4), having 80 small bowel lesions on imaging were included. EMR reports reliably mentioned within the consensus score included thickness (79%, p = 0.000), enhancement (70%, p = 0.000), active inflammation (86%, p = 0.000), perienteric fluid (82%, p = 0.000), and presence of stricture (62%, p = 0.002). Minimal lumen diameter (19%, p = 0.000), comb sign (19%, p = 0.000), lesion length (57%, p = 0.06), and fistula (50%, p = 1.0) were reported less often. There was a strong association between the EMR and scoring scale in noting severity of active inflammation (88%, p = 0.000), perienteric fluid (76%, p = 0.000), and internal fistula (71%, p = 0.000). The proportion matching severity values of comb sign and minimal lumen were 24% and 21%, respectively (p = 0.000). Severity matches for stricture were less likely among the non-GI radiologists (odds ratio = 0.33, SE = 0.168, p = 0.029). The odds of reporting stricture and fistula severity were 3.6 and 5.7, respectively, on MRE. Findings and severity of inflammation were communicated consistently. Stricture severity including minimal luminal diameter, was less reliably reported, though its prognostic significance impacts management.

Aims Fractional flow reserve (FFR) has proven to its prognostic and therapeutic value. However, the additive prognostic value of coronary flow reserve (CFR) remains unclear. This study sought to investigate the clinical utility of combined FFR and CFR measurements to predict outcomes. Methods and results Using the prospective, multicentre Interventional Cardiology Research Incooperation Society–FFR registry, a total of 2088 lesions from 1837 patients were included in this substudy. Based on baseline and hyperaemic pressure gradients, we computed physiologic limits of CFR [the so called pressure-bounded (pb) CFR] and classified lesions as low (0.80 [adjusted hazard ratio (aHR): 2.15, 95% confidence interval (CI): 1.19–3.89; P = 0.011. In contrast, the incidence of MACE did not differ between patients with pb-CFR 0.99). Conclusions In this large, prospective registry of over 2000 coronary lesions, FFR was strongly associated with clinical outcomes. In contrast, a significant association between pb-CFR and clinical events could not be determined and adding knowledge of pb-CFR did not improve prognostication over FFR alone.

Objective We propose a novel technique called pressure-bounded coronary flow reserve (pb-CFR) and demonstrate its application to the randomized DEFER trial. Background Intracoronary flow reserve assessment remains underutilized relative to pressure measurements partly due to less robust tools. Methods While rest and hyperemic intracoronary pressure measurements cannot quantify CFR exactly, they do provide upper and lower bounds. We validated pb-CFR invasively against traditional CFR, then applied it to high fractional flow reserve (FFR ≥ 0.75) lesions in DEFER randomized to revascularization or medical therapy. Results pb-CFR showed an 84.4% accuracy to predict invasive CFR

BackgroundHeart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer.MethodsRetrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN ResultsA total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN ConclusionsHeart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.

Inflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation comprised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in 2015, and the number keeps increasing over time. IBD has a multifactorial etiology, from genetic to environmental factors. Most of the IBD treatments revolve around disease management, by reducing the inflammatory signals. We previously identified the surface layer protein A (SlpA) of Lactobacillus acidophilus that possesses anti-inflammatory properties to mitigate murine colitis. Herein, we expressed SlpA in a clinically relevant, food-grade Lactococcus lactis to further investigate and characterize the protective mechanisms of the actions of SlpA. Oral administration of SlpA-expressing L. lactis (R110) mitigated the symptoms of murine colitis. Oral delivery of R110 resulted in a higher expression of IL-27 by myeloid cells, with a synchronous increase in IL-10 and cMAF in T cells. Consistent with murine studies, human dendritic cells exposed to R110 showed exquisite differential gene regulation, including IL-27 transcription, suggesting a shared mechanism between the two species, hence positioning R110 as potentially effective at treating colitis in humans.

The reliance on self-reports in detecting noncredible symptom report of attention-deficit/hyperactivity disorder in adulthood (aADHD) has been questioned due to findings showing that symptoms can easily be feigned on self-report scales. In response, Suhr and colleagues developed an infrequency index for the Conners’ Adult ADHD Rating Scale (CII) and provided initial validation for its utility in detecting noncredible symptom report. The aim of this study was to evaluate the utility of the CII in detecting noncredible aADHD symptom report by using a simulation design. Data did not support the validity of the CII for the detection of noncredible aADHD symptoms, as it failed to differentiate instructed malingerers from genuine patients with sufficient accuracy. It is concluded that there is a need for infrequency scales composed of items that were specifically developed to be endorsed infrequently and embedded within valid self-report scales.

In inflammatory bowel disease (IBD) patients, the enzyme phospholipase A2 (PLA2) is overexpressed in the inflamed intestinal tissue, and hence may be exploited as a prodrug-activating enzyme allowing drug targeting to the site(s) of gut inflammation. The purpose of this work was to develop powerful modern computational approaches, to allow optimized a-priori design of phospholipid (PL) based prodrugs for IBD drug targeting. We performed simulations that predict the activation of PL-drug conjugates by PLA2 with both human and bee venom PLA2. The calculated results correlated well with in-vitro experimental data. In conclusion, a-priori drug design using a computational approach complements and extends experimentally derived data, and may improve resource utilization and speed drug development.

A new era of Crohn’s disease management exists where decisions are made by objective data as a necessary adjunct to patient symptoms. Cross-sectional imaging, particularly CT enterography (CTE) and MR enterography (MRE), provides powerful objective insights into the disease process resulting in a firm place for cross-sectional imaging in our current diagnostic and management paradigms. The high sensitivity and specificity of the techniques for the presence of bowel inflammation have helped pinpoint the location and severity of disease enabling diagnosis and facilitating assessment of symptoms. The ability to identify disease complications has helped direct medical therapy and enables more robust presurgical assessment. Emerging data suggest that cross-sectional imaging findings are sensitive to changes in inflammation resulting from our potent biologic therapies and may be used in amazing new ways such as in predicting disease course. Technological advances in CT and MR enterography have provided new insights into the disease processes while enhancing patient safety and tolerability. The goal of this chapter is to provide a gastroenterologist’s view of how cross-sectional imaging fits our current and future management algorithm. These remarkable technologies enable gastroenterologists and radiologists, working together, to serve our patient population in profound ways.

OBJECTIVES: To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). BACKGROUND: The iFR was found to be non-inferior to the gold-standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices. METHODS: Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff \textless/=0.80 and \textless/=0.89, respectively). RESULTS: Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n = 244 (41.6%), or positive, n = 222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR-) in 69 (11.8%) patients and positive discordant (FFR-/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.30[1.68;6.47]), more severe stenosis (OR: 1.77[1.35;2.30]), younger age (OR: 0.93[0.90;0.97]), and slower heart rate (OR: 0.59[0.42;0.75]) were predictors of a negative discordant iFR. Absence of a beta-blocker (OR: 0.41[0.22;0.78]), older age (OR: 1.04[1.00;1.07]), and less severe stenosis (OR: 0.69[0.53;0.89]) were predictors of a positive discordant iFR. CONCLUSIONS: During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR.

Background There is little data regarding postoperative outcomes of patients with obstructive sleep apnea (OSA) undergoing skull base surgery. The purpose of this study is to determine an association between risk factors and proximity of cerebrospinal fluid (CSF) leak to surgery in patients with OSA undergoing endoscopic skull base surgery. Methods A retrospective review of neurosurgical inpatients, with and without OSA, at a tertiary care institution from 2002 to 2015 that experienced a postoperative CSF leak after undergoing endoscopic skull base surgery. Results Forty patients met inclusion criteria, 12 (30%) with OSA. OSA patients had significantly higher body mass index (BMI; median 39.4 vs. 31.7, p Conclusion Patients with OSA trended toward leaking earlier than those without OSA, and no OSA patients repaired with a nasoseptal flap (NSF) had a leak after postoperative day 5. Due to a small sample size this trend did not reach significance. Future studies will help to determine the appropriate timing for restarting PPV in this high risk population. This is important given PPV's significant benefit to the patient's overall health and its ability to lower intracranial pressure.

Aims To assess the effect of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) with contemporary drug-eluting stents on the composite of cardiac death or myocardial infarction (MI) vs. medical therapy in patients with stable coronary lesions. Methods and results We performed a systematic review and meta-Analysis of individual patient data (IPD) of the three available randomized trials of contemporary FFR-guided PCI vs. medical therapy for patients with stable coronary lesions: FAME 2 (NCT01132495), DANAMI-3-PRIMULTI (NCT01960933), and Compare-Acute (NCT01399736). FAME 2 enrolled patients with stable coronary artery disease (CAD), while the other two focused on non-culprit lesions in stabilized patients after acute coronary syndrome. A total of 2400 subjects were recruited from 54 sites world-wide with 1056 randomly assigned to FFR-guided PCI and 1344 to medical therapy. The pre-specified primary outcome was a composite of cardiac death or MI. We included data from extended follow-ups for FAME 2 (up to 5.5 years follow-up) and DANAMI-3-PRIMULTI (up to 4.7 years follow-up). After a median follow-up of 35 months (interquartile range 12-60months), a reduction in the composite of cardiac death or MI was observed with FFR-guided PCI as compared with medical therapy (hazard ratio 0.72, 95% confidence interval 0.54-0.96; P= 0.02). The difference between groups was driven by MI. Conclusion In this IPD meta-Analysis of the three available randomized controlled trials to date, FFR-guided PCI resulted in a reduction of the composite of cardiac death or MI compared with medical therapy, which was driven by a decreased risk of MI.

Aims: Echocardiography and tomographic imaging have documented dynamic changes in aortic stenosis (AS) geometry and severity during both the cardiac cycle and stress-induced increases in cardiac output. However, corresponding pressure gradient vs. flow relationships have not been described. Methods and results: We recruited 16 routine transcatheter aortic valve implantations (TAVI's) for graded dobutamine infusions both before and after implantation; 0.014″ pressure wires in the aorta and left ventricle (LV) continuously measured the transvalvular pressure gradient (ΔP) while a pulmonary artery catheter regularly assessed cardiac output by thermodilution. Before TAVI, ΔP did not display a consistent relationship with transvalvular flow (Q). Neither linear resistor (median R2 0.16) nor quadratic orifice (median R2

Background Despite major advances in the medical management of Crohn’s disease (CD), a significant proportion of patients will require surgery within 5 years of diagnosis. Malnutrition is an independent risk factor for adverse post-operative outcomes following gastrointestinal surgery. Data on the value of pre-operative total parenteral nutrition (TPN) in CD patients are mixed and there is a paucity of data in the biologic era. We aimed to define the role of pre-operative TPN in this population. Methods This was a retrospective cohort study conducted at a tertiary referral center. CD patients who underwent major abdominal surgery were identified. Patients receiving pre-operative TPN were compared to controls. We compared the incidence of 30-day infectious and non-infectious post-operative complications between the two groups. Results A total of 144 CD patients who underwent major abdominal surgery between March 2007 and March 2017 were included. Fifty-five patients who received pre-operative TPN were compared to 89 controls. Twenty-one (14.6%) patients developed infectious complications (18.2% in TPN group vs 12.3% in non-TPN group, P = 0.34) and 23 (15.9%) developed non-infectious complications (14.5% in TPN group vs 16.9% in non-TPN group, P = 0.71). In a multivariate analysis, controlling for differences in baseline disease severity and malnutrition between groups, patients receiving pre-operative TPN for ≥60 days had significantly lower odds of developing non-infectious complications (odds ratio 0.07, 95% confidence interval: 0.01–0.80, P = 0.03). Weight loss of >10% in the past 6 months was a significant predictor of post-operative complications. Conclusions In a subset of malnourished CD patients, TPN is safe and allows comparable operative outcomes to controls. Pre-operative TPN for ≥60 days reduced post-operative non-infectious complications without associated increase in infectious complications.

Background Guidelines recommend coronary artery bypass graft (CABG) surgery over percutaneous coronary intervention (PCI) for the treatment of 3-vessel coronary artery disease (3-VD). The inferior results of PCI demonstrated by previous large randomized trials comparing PCI and CABG might be explained by the use of suboptimal stent technology and by the lack of fractional flow reserve (FFR) guidance of PCI. Trial design The objective of this investigator-initiated, multicenter, randomized clinical trial is to investigate whether FFR-guided PCI with new-generation stents is noninferior to CABG in patients with 3-VD, not including the left main coronary artery. Eligible patients must have ≥50% coronary stenoses in all 3 major epicardial vessels or major side branches. Patients with a nondominant right coronary artery may be included only if the left anterior descending artery and left circumflex have ≥50% stenoses. Consecutive patients who meet all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to either CABG or FFR-guided PCI. Coronary artery bypass graft will be performed based on the angiogram as per clinical routine. Patients assigned to FFR-guided PCI will have FFR measured in each diseased vessel and only undergo stenting if the FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac and cerebrovascular events, including death, myocardial infarction, repeat coronary revascularization, and stroke at 1 year. Key secondary end point will be a composite of death, myocardial infarction, and stroke at 3-year follow-up. Other secondary end points include the individual adverse events, cost-effectiveness, and quality of life at 2-year, 3-year, with up to 5-year follow-up. Conclusion The FAME 3 study will compare in a multicenter, randomized fashion FFR-guided PCI with contemporary drug-eluting stents to CABG in patients with 3-VD.

Hematogenous spreading of tumor cells from primary tumors is a crucial step in the cascade to metastasis, the latter being the most limiting factor for patients' survival prognosis. Therefore, circulating tumor cells (CTCs) have become a field of intensive research. However, the process of isolation and identification of CTCs lacks standardization. This article presents an overview of 71 CTC studies reported in PUBMED since 2000 and focusing on colorectal cancer. These studies are evaluated regarding standardization of CTC isolation and identification, marker proteins used, study population and blood sample quality management, clinical performance, and quality measures. Overall, standardization of CTC assessment seems insufficient. Thus, comparability of CTC studies is hampered and results should be interpreted carefully. We here propose a standardized CTC guideline (CTC Guide) to prospectively design and report studies/trials in a harmonized form. Despite the current interstudy heterogeneity, the data indicate that CTC detection is of clinical relevance and CTCs should be considered as a surrogate prognostic marker. Many studies indicate the high potential for CTCs as prognostic markers, e.g., in colorectal cancer treatment. However, standardized, large-scale multicenter validation studies are still needed to pave the way for clinical implementation of CTC detection that could ameliorate individualized medicine regimes.

BACKGROUND The outcome in children and adolescents with high-risk (HR) acute myeloid leukemia (AML) is still unsatisfactory. Therefore, in study AML-BFM 2004 we aimed to improve outcome of HR-patients by adding moderately dosed 2-Chloro-2-Deoxyadenosine (2-CDA) to the respective consolidation treatment backbone without increasing toxicity. The aim was to improve prognosis especially in FAB M4/M5/MLL patients, who represent the largest subgroup of HR patients. PATIENTS AND METHODS In total, 343 children and adolescents with HR-AML were randomized to receive or not 2-CDA (6 mg/m²/d, days 1, 3) in combination with cytarabine/idarubicine (AI=500 mg/m² cytarabine 5 days continuous infusion plus 7 mg/m²/d idarubicin, days 3 and 5). RESULTS RESULTS for patients of the AI/2-CDA arm (n=168) vs. the AI-arm (n=175) were similar: 5-year overall survival 68±4 vs. 72±4%, plogrank=0.38, event-free survival 53±4 vs. 49±4%, plogrank=0.77; cumulative incidence of relapse at 5 years: 35±4 vs. 37±4%, p(Gray)=0.89. RESULTS in patients with MLL rearrangement or FAB M4/M5 were also similar in the treatment groups. In addition, toxicities did not differ between the two arms. CONCLUSION We conclude that additional, moderate dose 2-CDA does not improve prognosis in HR-patients when given during consolidation treatment. Its effect might be too low in this multidrug regimen, where the strongest effects are achieved during induction, or the chosen dose of 2-CDA might have been too low.

Background— The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results— We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P P =0.001), and improved net clinical benefit (adjusted P P =0.082 for ischemic stroke and adjusted P =0.109 for major hemorrhage). Conclusions— In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00041938.

BACKGROUND AND OBJECTIVES Up until recently no tool for quality assurance (QA) of outpatient pain therapy after outpatient surgery, which currently constitutes one third of all operations, was available with benchmarking capacity. The QUIPS (German abbreviation for quality assurance in postoperative pain therapy) questionnaire, that had primarily been developed and established for inpatient postoperative pain therapy, was to be optimized to not only incorporate the issues with regard to outpatient operations but also a revision for use in the clinical routine. MATERIAL AND METHODS An interdisciplinary task force reviewed and optimized the QUIPS questionnaire. The optimized questionnaire was then used within the scope of outpatient surgery in their clinics. A total of 121 patients and 12 surgeons received a questionnaire on the first postoperative day containing questions on acceptance and understandability of the QUIPS patient outcome questionnaire. RESULTS Of the patients 12 (9.9 %) did not understand the original question on special pain therapy procedures stated during the preoperative counseling. For 15 patients (12.4 %) the original questions on chronic or pre-existing pain were misleading and 4 out of the 12 surgeons (33 %) did not conclusively understand these questions. The optimized questionnaire modified the questions in the preoperative counseling in the segment of postoperative pain as follows: question E1 was changed to a yes/no answer. Question E13 was modified to "how content were you with respect to your post-operative pain therapy?" Question E14 was modified to "did you suffer from other pain prior to the operation, hence pain that continued in addition to the postoperative pain?" These changes improved the understandability of the QUIPS patient outcome questionnaire. Surgeons required on average 9.7 min (SD ±3.2 min) to complete the QUIPS documentation sheets and 83 % of the surgeons rated the optimized QUIPS module as usable in the daily routine. The new module QUIPSambulant will soon be available for download on the QUIPS internet website. DISCUSSION By reducing items on the QUIPS documentation sheets with respect to items relevant for outpatient surgery and redesigning three questions in the patient outcome questionnaire, a new QUIPS module for the QA of postoperative pain in an ambulatory setting is now available for both patients and surgeons. The necessity for quality management (QM) with regard to postoperative pain therapy after outpatient surgery can be considered assured. To what extent the newly adapted QM tool QUIPSambulant will be deemed suitable in a routine hospital setting remains to be seen and requires ongoing investigation.