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• The application of class I medical compression stockings seems to be safe in patients with peripheral arterial disease. • The transcutaneous tissue spectrometry device O2C allows quantitative evaluation of microperfusion of the lower limb. • Medical compression therapy should not be employed in patients with SO2 values below 10%. The use of medical compression stockings (MCS) in patients with peripheral arterial disease (PAD) and diabetes is the subject of an ongoing critical debate. While reducing leg edema of various origins by improving venous back flow, there is a concern about additional arterial flow obstruction when compression therapy is applied in pre-existing PAD. The aim of this study is to obtain further information on the use of class I MCS in patients with advanced PAD and to evaluate the framework conditions for a safe application. The total collective (n = 55) of this prospective, clinical cohort study consisted of 24 patients with PAD Fontaine stage IIb and higher studied before revascularization, of whom 16 patients were examined again after revascularization, and 15 healthy participants included for reference. The microperfusion of the lower extremity of all participants was examined in a supine, elevated, and sitting position using the oxygen to see (O2C) method. The results indicate that leg positioning had the strongest influence on microcirculation (SO2 and flow: p = 0.0001), whereas MCS had no significant effect on the perfusion parameters (SO2: p = 0.9936; flow: p = 0.4967) and did not lead to a deterioration of values into critical ranges. Mild medical compression therapy appears to be feasible even in patients with advanced PAD. Larger studies are warranted to observe any long-term effects, in particular for the treatment of reperfusion edema after revascularization. [ABSTRACT FROM AUTHOR]

Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) remains one of the most common gastrointestinal neonatal malformations. Even though postoperative management is standardized, it differs between hospitals and disease-associated clinical factors that may play a role in outcome have not yet been assessed in detail. In this monocentric retrospective study, data of 43 patients with EA between 2010 and 2018 were analyzed. Analysis includes assessment of the clinical background, surgical technique, postoperative management including application of continuous muscle relaxation (CMR), influence of coagulation parameters such as factor XIII and incidence of complications. 21 patients (49%) were preterm infants with birth weights between 490 and 2840 g (median 1893 g). Only 35% (n = 15) presented without any concomitant malformations. Within the entire study population, representing Vogt II, IIIb and IIIc, we observed an association between the development of a postoperative pneumothorax and anastomotic failure (AF) (p = 0.0013). Furthermore, pneumothorax was associated with anastomotic stenosis (AS) in Vogt IIIb patients (p = 0.0129). CMR (applied since March 2017 in 7 patients in an attempt to prevent anastomotic problems due to high complication rates) and coagulation factor XIII did not significantly correlate with postoperative outcome. Appearance of pneumothorax was correlated with postoperative complications. These children should be monitored carefully in closer scheduled gastroenterological follow-up esophago-gastro-duodenoscopies. CMR and factor XIII substitution did not reduce anastomotic leakage but should be tested within an enlarged study population. [ABSTRACT FROM AUTHOR]

The reason for increased serum creatinine levels in preterm infants often remains unclear. We aimed to determine whether postnatal serum creatinine in preterm infants correlates with intake of amniotic fluid, represented by the amount of amniotic fluid after preterm premature rupture of membranes (PPROM). 74 preterm infants with PPROM > 48 h duration were retrospectively studied. Postnatal creatinine concentration was determined at day 2–5, 10–17 and 26–33 of life and compared between infants with normal intrauterine amniotic volumes, oligohydramnios and anhydramnios. Mean gestational age of included patients was 29.7 weeks (range: 24.0–36.1 weeks) and mean birth weight was 1452 g (range: 560–2940 g). Serum creatinine concentration was similar at day 2–5 and day 10–17 of life between the three groups. We observed a significant decrease in creatinine concentration from day 2–5 to day 26–33 in infants with normal amniotic fluid volume and oligohydramnios (p = 0.0001 and p = 0.0071, respectively), but not in anhydramnios. On day 26–33 of life, infants with anhydramnios showed significantly higher creatinine levels compared to infants with normal amniotic fluid volume and oligohydramnios (p = 0.0211). Postnatal serum creatinine of preterm infants at day 26–33 of life is elevated in infants with PPROM-induced anhydramnios, but not in oligohydramnios. [ABSTRACT FROM AUTHOR]

Objective: The study sought to assess the impact of ischemic (ICMP) compared to non-ischemic cardiomyopathy (NICMP) on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients.Background: Data comparing recurrences of ventricular tachyarrhythmias in ICD recipients with ischemic or non-ischemic cardiomyopathy is limited.Methods: A large retrospective registry was used including all consecutive ICD recipients with first episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. Patients with ICMP were compared to patients with NICMP. The primary prognostic endpoint was first recurrences of ventricular tachyarrhythmias at one year. Secondary endpoints comprised ICD-related therapies, rehospitalization and all-cause mortality at one year. Statistics Kaplan-Meier survival and multivariable Cox regression analyses.Results: A total of 387 consecutive ICD recipients were included retrospectively (ICMP: 82%, NICMP: 18%). At one year of follow-up, freedom from first recurrences of ventricular tachyarrhythmias was lower in NICMP (81% vs. 71%, log-rank p = 0.063; HR = 1.760; 95% CI 0.985-3.002; p = 0.080), mainly attributed to higher rates of sustained VT (20% versus 12%, p = 0.054). Accordingly, freedom from first appropriate device therapies was lower in NICMP (74% vs. 85%, log rank p = 0.004; HR = 1.951; 95% CI 1.121-3.397; p = 0.028), especially in patients with sustained VT or VF at index. Both groups revealed comparable rates of rehospitalization and all-cause mortality at one year.Conclusion: NICMP was associated with higher rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies compared to ICMP at one year of follow-up, whereas rates of rehospitalization and all-cause mortality were comparable.Condensed Abstract: This study retrospectively compared the impact of cardiomyopathy types (ICMP versus NICMP) on recurrences of ventricular tachyarrhythmias in 387 ICD recipients. Freedom from first episodes of ventricular tachyarrhythmias and first appropriate device therapies were lower in patients with NICMP compared to ICMP. [ABSTRACT FROM AUTHOR]

Abstract The Gram-negative bacterium Haemophilus influenzae (H. influenzae) can commensally colonize the upper respiratory tract, but also cause life threatening disease including epiglottitis, sepsis and meningitis. The H. influenzae capsule protects the bacteria against both phagocytosis and opsonization. Encapsulated H. influenzae strains are classified into serotypes ranging from a to f dependent on their distinct polysaccharide capsule. Due to the implementation of vaccination the incidence of invasive H. influenzae type b (Hib) infections has strongly decreased and infections with other capsulated types, including H. influenzae type f (Hif), are emerging. The pathogenesis of H. influenzae meningitis is not clarified. To enter the central nervous system (CNS) the bacteria generally have to cross either the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BSCFB). Using a cell culture model of the BCSFB based on human choroid plexus papilloma (HIBCPP) cells and different H. influenzae strains we investigated whether Hib and Hif invade the cells, and if invasion differs between encapsulated vs. capsular-deficient and fimbriated vs. non-fimbriated variants. We find that Hib can adhere to and invade into HIBCPP cells. Invasion occurs in a strongly polar fashion, since the bacteria enter the cells preferentially from the basolateral "blood "side. Fimbriae and capsule attenuate invasion into choroid plexus (CP) epithelial cells, and capsulation can influence the bacterial distribution pattern. Finally, analysis of clinical Hib and Hif isolates confirms the detected invasive properties of H. influenzae. Our data point to roles of capsule and fimbriae during invasion of CP epithelial cells. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to characterize the pathologic changes of the osteoarthritic humeral head. Methods The study included 55 patients with primary osteoarthritis who underwent anatomic shoulder arthroplasty. Several radiologic parameters (radiography, magnetic resonance imaging) were assessed. Humeral head deformity in the transverse plane and humeral cartilage erosion in the coronal plane were chosen for photographic measurements from the resected humeral heads. Results In the coronal plane, 82% of patients presented with an aspherical humeral head shape with a significantly longer caudal osteophyte. In the transverse plane, 50% of all patients showed a decentered apex. Patients with an aspherical humeral head shape in the transverse plane showed an aspherical humeral head shape in the coronal plane in 94% and a significantly longer osteophyte than patients with spherical humeral head shape, showing a 3-dimensional deformity of the humeral head during progression of primary osteoarthritis. Patients with an osteophyte length between 7 and 12 mm were associated with a glenoid type B2 in 30% and a decentered apex in the transverse plane in 38%. Patients with a humeral osteophyte longer than 13 mm were significantly more frequently associated with a type B2 glenoid (71%; P  < .0001) and a decentered apex in the transverse plane in 52%. Conclusion It seems that the progression of primary osteoarthritis of the glenohumeral joint is characterized by an increasing 3-dimensional deformity of the humeral head related to the glenoid morphology. We therefore propose an extended Samilson-Prieto classification with type A (spherical) and type B (aspherical) and grade I-IV osteophytes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of induction of labour using a double-balloon catheter and, if necessary, sequential oral misoprostol without delay after removal of the catheter, in comparison with oral misoprostol alone.Study Design: This retrospective cohort study included women undergoing induction of labour with oral misoprostol or double-balloon catheter with sequential oral misoprostol in singleton pregnancies at term. The catheter was placed in the evening and removed when there was no onset of labour within 12h. Then oral misoprostol was started within 3h. Primary outcome measure was the caesarean section rate.Results: There were 13,082 deliveries during the study period with 3466 labour inductions out of which 1032 were eligible and analysed. The caesarean section rate was significantly lower in the double-balloon catheter group (26.1% vs. 17.3, p=0.021). Furthermore, in the combination group, the induction-to-delivery interval was shorter (median values 1144 vs. 1365min, p=0.001) and there were more deliveries within 24h (51.9 vs. 64.7%, p=0.003) and 48h (87.4 vs. 95.8%, p=0.002). When stratifying for parity, there were less caesarean sections in the combination group (37.2% vs. 24.2%, p=0.015) in nulliparous women, too. In both, nulliparous and parous women, the induction-to-delivery interval was shorter (1742 vs. 1400min, 0.005; 1020 vs. 912min, p=0.018). Especially in parous women, the rates of delivery within 24h (62.6% vs. 79.0%, p=0.007) and 48h (88.6% vs. 99.0%, p=0.007) were higher in the combination group.Conclusion: Double-balloon catheter and sequential oral misoprostol without long delay in absent onset of labour after removal of the catheter resulted in less caesarean section and shorter induction-to-delivery interval in comparison with oral misoprostol alone. [ABSTRACT FROM AUTHOR]

To systematically review the application of balloon catheters for cervical ripening and labor induction at term after previous cesarean section. All pregnancies at term with previous cesarean section were included when cervical ripening or labor induction was conducted with balloon catheters. MEDLINE, Cochrane database and bibliography of identified articles were searched for English language studies. Reviews and meta-analysis, randomized and non-randomized controlled trials, prospective and retrospective cohort studies as well as case-control studies were considered. A total of 48 potentially relevant studies were identified. The title and abstract were screened for eligibility and 32 articles were excluded. The remaining 16 publications included 1447 women (single-balloon catheter: n=1329, double-balloon catheter: n=118). There were no randomized controlled trials. Most of the trials were retrospective studies (n=10). The rate of uterine rupture after labor induction was low (n=18, 1.2%). Meta-analysis of studies comparing the risk of uterine rupture between labor induction and spontaneous onset of labor found a higher risk after induction (OR 2.45, 95%CI 1.34-4.47, NNH 186). The average rate of oxytocin application was 68.4%, and vaginal birth was achieved in 56.4%. The risk for cesarean delivery was higher when labor was induced (OR 2.63, 95%CI 2.24-3.10). Data on balloon catheters for labor induction after previous cesarean section are limited by small sample size and retrospective analyses. The present data show a moderately increased risk for uterine rupture (OR=2.45) compared to spontaneous onset of labor. However, for evidence based recommendations much more well-conducted trials are needed. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this prospective study was to investigate absolute radiation exposure values and factors that influence radiation exposure of interventionists during CT-guided interventions (CTGIs). To our knowledge, no data exist regarding the radiation dose to which the interventionist is exposed during these procedures. Methods Absolute radiation dose values from a total of 131 CTGIs were analyzed. Radiation dose values were collected by thermoluminescent dosimeters that were positioned above the lead protection being worn, on the forehead, thyroid, chest, gonads, and right and left hand and foot. The radiation doses were analyzed with respect to the experience level of the person performing the procedure, the degree of difficulty measured on a 4-point Likert scale, the lesion size measured on a 3-point Likert scale, and the CT system used. Results Median whole-body dose was 12 μSv. With the exception of the forehead, all whole-body radiation doses were statistically significantly lower in CTGIs performed using the modern dual-source CT system compared with the 16-slice multi-detector CT. For CTGIs rated as more complex, the radiation exposure of the radiologist performing the procedure was statistically significantly higher, with the exception of the left hand. A statistically significantly lower median whole-body dose was measured for inexperienced compared with experienced radiologists. However, a few dose measurements of more than 1 mSv were found at the right hand. Conclusions Radiation exposure measured during CTGIs is low (<50 μSv). Because the radiation dose was higher in more-complex interventions and for 16-slice multi-detector row CT, inexperienced radiologists should focus on less-complex procedures. [ABSTRACT FROM AUTHOR]

Background: Long-term survival after resection for pancreas carcinoma has rarely been reported. Factors influencing long-term survival are still under debate. The aim of this study was to define predictors for long-term survival.Methods: Between 1972 and 2004, a total of 415 patients underwent resection. Data were collected in a prospective data base. Data of 360 patients were available for further analysis in 2011. All specimens of long-term survivors were histologically reviewed.Results: Long-term survivors (n = 69) had a median survival of 91 months. Pathological re-evaluation of all specimens re-confirmed the diagnosis. Predictive factors for long-term survival in univariate analysis were no preoperative biliary stent, low CA 19-9 level, lack of blood transfusion, R0 resection, tumour diameter, and -grading, absence of lymph node or distant metastases, lymphangiosis, and perineural infiltration. Adjuvant chemotherapy showed a significant influence on overall survival but not on long-term survival. In multivariate analysis, lymph node ratio and volume of blood transfusion were predictors of long-term survival.Conclusion: Nearly 20% of patients with pancreas carcinoma who undergo surgical resection have a chance of long-term survival. Survival beyond 5 years is predicted by clinical and tumour-specific factors. Adjuvant chemotherapy might prolong overall survival but is, according to these results, unable to contribute to long-term survival. There is still a risk of recurrence after a 5- or even a 12-year mark. Survival beyond 5 or even 12 years, therefore, does not assure cure. [ABSTRACT FROM AUTHOR]

Background: For years early repolarization (ER) has been considered as a benign electrocardiographic finding. However, recent reports show that ER is associated with a higher incidence of ventricular fibrillation (VF) and sudden cardiac death in patients without structural heart disease. Sporadic case studies have pointed out that ER might be related to an adverse outcome in patients with stable coronary artery disease. Objective: To evaluate the incidence of ER in patients with acute myocardial infarction complicated by VF. Methods: The study population consisted of 60 patients (80% men; mean age 61.8 ± 13.1 years) with acute myocardial infarction. Thirty consecutive patients (80% men; mean age 63.3 ± 12 years) admitted to our hospital had documented VF during myocardial infarction and were successfully resuscitated before hospital admission. A matched control group consisted of 30 patients (80% men; mean age 60.2 ± 14.2 years) with myocardial infarction without ventricular tachyarrhythmias. Twelve-lead electrocardiograms were analyzed for ER defined as J-point elevation ≥ 0.1 mV and “notching” and “slurring” of the terminal part of the QRS complex in at least 2 lateral or inferior leads. Results: The ER pattern was observed in 18 of the 60 patients with acute myocardial infarction. Mean elevation of the J point was 0.151 ± 0.46 mV. Notching of the J wave was observed in 14 of the 18 patients and slurring in 4 of the 18 patients. ER was more common in patients with myocardial infarction complicated by VF than in patients with myocardial infarction without ventricular tachyarrhythmias (47% vs 13%; P = .005). There have been no statistical differences in the distribution of ER in the 12-lead electrocardiogram (inferior 39% vs lateral 33% vs inferolateral 28%; P >.05). Conclusion: Early repolarization pattern seems to be associated with ventricular tachyarrhythmias in the setting of acute myocardial infarction. [Copyright &y& Elsevier]

Purpose: Kyphoplasty immediately improves pain and mobility in patients with painful osteoporotic vertebral fractures, but long-term clinical outcomes are still unclear. This controlled trial evaluates pain, mobility and fracture incidence 3 years after kyphoplasty. Materials and Methods: Kyphoplasty was performed in 40 patients with painful osteoporotic vertebral fractures; 20 patients who were selected for kyphoplasty but chose not to undergo the procedure served as controls. All patients received pharmacologic antiosteoporosis treatment, pain medication, and physiotherapy. Pain (visual analog scale of 0–100), mobility (European Vertebral Osteoporosis Study questionnaire score of 0–100), and incident vertebral fractures were assessed at baseline, postprocedurally, and after 12 and 36 months. Results: Pain score improved after kyphoplasty from 73.8 to 55.9 (immediately after kyphoplasty), 55.6 (12 months), and 54.0 (36 months; P < .001). Pain score in the control group changed from 66.4 to 65.7 at 12 months and 64.0 at 36 months (P = .521). The pain score of the kyphoplasty group was significantly improved versus controls after 36 months (P = .023). Mobility score improved after kyphoplasty from 43.8 to 54.2 (immediately after kyphoplasty), 54.5 (12 months), and 54.8 (36 months; P = .0008) and remained increased (P = .308) compared with controls (39.8 immediately after kyphoplasty, 44.3 at 12 months, and 43.6 at 36 months). The incidence of new vertebral fractures after kyphoplasty was significantly reduced versus controls after 3 years (P = .0341). Conclusions: Kyphoplasty reduces pain and improves mobility as long as 3 years after the procedure. The long-term risk of new vertebral fractures after kyphoplasty of chronically painful vertebral fractures is reduced versus controls. [Copyright &y& Elsevier]

Purpose The texture of the pancreatic tissue is a main risk factor for leakage after pancreaticojejunostomy and can be differentiated using dynamic contrast enhanced magnetic resonance imaging (dMRI). In order to identify risk factors and to assess the role of pancreatic dMRI, a cohort of patients was retrospectively reviewed. Patients and methods One hundred seven consecutive patients were identified in the departmental database and examined by means of a standardized dMRI protocol using a 1.5-T MRI system. Signal intensity (SI) measurements (aorta, body of the pancreas, muscle tissue) were performed in the axial T1-weighted sequences before and after 25 and 60 s after i.v. application of gadolinium-diethylenetriaminepentaacetic acid. For all patients with a standardized contrast medium curve in the aorta (n=72), a muscle-normalized signal intensity curve (SIC) with SIratio was calculated. SIratios were classified in two groups: rapid increase (SIratio≥1.1, early arterial value > portal-venous value, "soft" pancreas) and delayed increase (SIratio <1.1, "firm" or "hard" pancreas). All patients received pancreatic head resection with a duct-to-mucosa pancreaticojejunostomy. The dMRI data was correlated with prospectively acquired clinical data. Results Leakage of the pancreaticojejunostomy occurred more frequently (12/37 vs. two of 35, 32% vs. 6%, p=0.006) in patients with a rapid increase and an SIratio≥1.1 ("soft" pancreas, n=37) compared to those with delayed perfusion (SIratio <1.1, "hard" pancreas, n=35). The more severe type B and C anastomotic leakages occurred only in the group of patients with SIratio≥1.1. Patients with a rapid increase had significantly better preoperative American Society of Anesthesiologists staging, lower carbohydrate antigen 19-9 values, and smaller tumor sizes. Most of them had not only benign tumors but also longer postoperative hospital stay, in comparison to patients with delayed perfusion (SIratio <1.1). Multivariate analysis revealed SIratio of ≥1.1 to be the only preoperative parameter predicting leakage significantly with an odds ratio of 7.9. Conclusion dMRI with SIratio calculation provided reliable information for the prediction of pancreatic texture. Patients with a SIratio≥1.1 had a 7.9-fold increased risk of anastomotic leakage and a prolonged hospital stay. SIC with measurements of SIratio in dMRI could therefore define patients at risk for anastomotic leakage. [ABSTRACT FROM AUTHOR]

PURPOSE: To investigate the role of metallic stents in the treatment of benign biliary strictures and analyze the differences in primary patency associated with the various types of stents deployed. MATERIALS AND METHODS: Between 1990 and 1997, 21 patients with benign obstructive jaundice were treated with transhepatic placement of metallic stents (11 Wallstents in 10 patients, nine Palmaz stents in seven patients, and four tantalum Strecker stents in four patients). Nineteen patients presented with strictures not responding to balloon angioplasty (postsurgical, n = 13; cholangitis, n = 5; unknown, n = 1). Estimates for cumulative patency, patency rate in the different stent groups, and survival were calculated with use of life-table analysis; the log-rank test was used to compare the different stent groups. The prognostic relevance of the selected variables—stent type, stent length, etiology, and location—were modeled with respect to patency according to Weibull distribution. RESULTS: The median follow-up time was 80.5 months (range, 2–116 months). The median survival time was 91 months. One patient was lost to follow-up after 3 months. Repeat intervention for recurrent obstructive jaundice was necessary in 11 patients (55%), and the median patency rate was 26 months (range, 2–96 months). The Palmaz stent was the most effective in achieving long-term patency, with a median patency duration of 36 months (range, 22–96 months), versus 9 months (range, 3–67 months) for the Wallstent and 6 months (range, 2–15 months) for the tantalum Strecker stent. The cumulative patency rate with the Palmaz stent was significantly higher than for the tantalum Strecker stent (log-rank test, P = .017) and nonsignificantly higher compared with the Wallstent (log-rank test, P = .07). Multivariate analysis showed that the type of stent (Wald test, P = .003) and stent length (Wald test, P < .0001) influenced the patency rate. CONCLUSIONS: These results suggest that the type of stent and the stent length have a significant influence on the patency rate. In this series, the Palmaz stent was most effective in achieving long-term patency in benign biliary strictures. [Copyright &y& Elsevier]

Adherence to follow-up (FU) care after bariatric surgery is poor despite strong recommendations. In our pilot Bella trial, we demonstrated that a completely remote follow-up program via smartphone is feasible and safe for patients after bariatric surgery. Building on this, we aim to verify our results in a multicenter, randomized controlled setting. This trial plans to enroll 410 participants undergoing primary bariatric surgery in seven German bariatric centers. Participants are randomized into two groups: a control group receiving in-person FU according to the standard in the bariatric centers, and an interventional group monitored using a smartphone application (app). The app sends standardized questionnaires and reminders regarding regular vitamin intake and exercises. The built-in messaging function enables patients to communicate remotely with medical care professionals. After one year, all participants are evaluated at their primary bariatric centers. The primary outcome is weight loss 12 months after surgery. The secondary outcomes include obesity-related comorbidities, quality of life, serum values of vitamins and minerals, body impedance analysis, visits to the emergency department or readmission, patient compliance, and medical staff workload. The current study is the first prospective, individually randomized-controlled, multicenter trial where a mobile application completely replaces traditional in-person visits for post-bariatric surgery follow-ups in bariatric centers. [ABSTRACT FROM AUTHOR]

Cognitive transfer represents an important issue in surgical education. It is essential for the acquisition of competence, such as decision making and error avoidance. This randomized study aims to compare the effectivity of cognitive transfer by observing the surgery versus using modern virtual reality simulators for learning a laparoscopic cholecystectomy. This was a prospective, randomized, single centre study. 40 medical students from a university hospital, a tertiary care teaching institution, were enrolled. After a short introduction of laparoscopic cholecystectomy, they were randomized into two groups (video group and simulator group). In the video group, participants watched the step-by-step educational video twice. In the simulator group, participants underwent training using the virtual reality simulator, including tutorial procedural tasks of laparoscopic cholecystectomy as well as a complete cholecystectomy on the simulator. After the training, cognitive competence including decision making and error awareness was assessed using a questionnaire. In the most critical step of laparoscopic cholecystectomy, "Dissection in Calot's triangle", as well as in the aspect of planning next step, the video group was superior significantly (P = 0.038 and P = 0.04). No significant differences concerning the recognition of critical anatomical structures, choosing the necessary instruments as well as error awareness were found. Learning by watching a high-quality educational video is more effective in acquiring the cognitive competence to combine learned single tasks. Traditional learning means as watching educational videos and modern, sophisticated VRS should be deployed complementarily to establish cognitive and motor competencies separately. • High-quality educational videos are effective for acquiring cognitive competence. • Virtual reality simulator is not superior to videos in acquiring cognitive skills. • High-quality educational videos and virtual reality simulator should be combined. [ABSTRACT FROM AUTHOR]

Background To comparatively evaluate long-term prognostic values of fibrotic biomarkers galectin-3, gremlin-1 and osteopontin in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF). Methods Patients with acute dyspnea or peripheral edema were enrolled in the ED. Biomarkers were measured and added to prognostic models including 11 conventional risk factors plus NT-proBNP assessing state-of-the-art statistics of discrimination, calibration, reclassification and Cox regression analyses. Prognostic outcomes were long-term all-cause mortality (ACM) and AHF-related rehospitalization (AHF-RH) at 1 and 5 years. Results 401 patients including 122 AHF patients were enrolled (mean age 67 years, males 51%). During 5 years follow-up 129 patients (30%) died and 73 (18%) were re-hospitalized because of AHF. In multivariate analysis, galectin-3 (hazard ratios (HR) range 1.4–1.9; p = 0.03) and osteopontin (HR range 1.2–1.4; p = 0.001) remained associated with ACM overall and in the AHF population at 5 years, whereas gremlin-1 remained associated with AHF-RH at 1 year in AHF patients (HR 1.3; p = 0.002). ACM in whole cohort was best discriminated (AUC = 0.85, p = 0.0001), calibrated and re-classified (NRI + 0.50 to + 0.56, p = 0.0001) by galectin-3, whereas in AHF patients ACM was best discriminated by osteopontin (AUC range: 0.82–0.84, p = 0.0001; NRI + 0.34 to + 0.38, p < 0.1) and AHF-RH at 1 year by gremlin-1 (AUC range: 0.82–0.92, p = 0.0001; NRI + 0.59 to + 0.60, p = 0.006). Conclusions A panel of fibrotic biomarkers, including osteopontin, galectin-3 and gremlin-1, might be useful for long term risk-stratification of symptomatic ED patients being suspected of AHF. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the role of lymph vessel density (LVD) and lymphangiogenesis in nonseminomatous testicular germ cell tumors (NSGCT) using the specific lymphatic endothelial cell (LEC) marker LYVE-1. Materials and methods: NSGCT specimens of 77 patients (32 with and 45 without metastases) were stained immunohistochemically using a LYVE-1 antibody. LVD was measured in different representative areas by the standardized “hot spot” method. Fluorescence double stainings for LYVE-1 and Ki-67 were performed. The median follow-up period was 46 (range 3–170) months. Results: The mean peritumoral (2.16 ± 2.17) and nontumoral LVD (3.17 ± 3.24) were significantly higher than intratumoral LVD (0.16 ± 0.73) (both: P = < 0.001). In 5 patients proliferating LECs were observed. The peritumoral LVD was 2.66 (±2.31) and 1.80 (±2.02) in metastatic and nonmetastatic NSGCT, respectively. A higher peritumoral LVD was associated with the presence of metastases at the time of diagnosis (P = 0.087). The mean peritumoral LVD in tumors with and without lymphovascular invasion (LVI) was 3.33 (±2.20) and 1.62 (±1.95), respectively (P < 0.001). The presence of LVI detected by LYVE-1 (LVI-LYVE-1) was independently associated with metastatic disease (logistic regression; P = 0.045). Conclusions: The presence of a high peritumoral LVD and LVI-LYVE-1 are both associated with metastatic disease in NSGCT. LVI-LYVE-1 was independently associated with the presence of metastases at the time of diagnosis. Proliferating LECs are present, suggesting that lymphangiogenesis may promote metastatic dissemination of tumor cells in NSGCT. [ABSTRACT FROM AUTHOR]

Background: Management of pediatric thermal injuries involves a high standard of care in a multidisciplinary setting. To avoid physical and psychological sequelae, wound dressings should minimize hospitalization time and anesthesia while maximizing patient comfort.Patients and Methods: 190 children with thermal injuries of the torso, arms and legs were treated with polyurethane foam dressings or bacterial nanocellulose sheets. Data were analyzed retrospectively regarding hospitalization, procedures with general anesthesia, scar formation, rate of infection and need for skin grafting.Results: The groups did not differ significantly concerning age, gender distribution or percentage of injured total body surface area. Statistical analysis showed that length of hospitalized care and procedures undergoing anesthesia were significantly reduced in the nanocellulose group (each p < 0.0001). There was no significant difference in rate of complications, wound healing and rate of skin grafting between the two subgroups.Discussion: Acting as a temporary epidermal substitute, bacterial nanocellulose enables undisturbed reepithelialization without further wound dressing changes. In children, no additional topical antimicrobial agents are indicated for unimpaired wound healing.Conclusions: Bacterial nanocellulose is superior to polyurethane foam regarding length of hospitalization and number of interventions under anesthesia. It offers a safe, cost-effective treatment option and provides excellent comfort in pediatric patients. [ABSTRACT FROM AUTHOR]

Pulmonary embolism (PE) occurs frequently in patients with malignant melanoma (MM). The aim of this study is to determine the incidence of PE in patients with MM and to assess the clinical characteristics and mortality of MM patients with PE. Medical records from 381 MM patients who underwent contrast-enhanced computed tomography were evaluated. Imaging parameters including location of PE and measurements of right heart dysfunction and clinical parameters including D-Dimer levels, local and distant tumor stage and time of death were analyzed. PE was found in 23/381 (6%) MM patients, whereby 17/23 (74%) were detected incidentally and only 6/23 (26%) were symptomatic. The presence of PE significantly correlated with elevated D-Dimers (p < 0.001), right ventricular dysfunction (p = 0.04), higher local tumor stage (≥T3) (p = 0.05), presence of visceral (p = 0.02) or cerebral metastases (p = 0.03) and increased mortality (p = 0.05). Further, patients with central PE showed an increased mortality compared to peripheral PE (p = 0.03), but no correlation was found between the localization of PE and the occurrence of clinical symptoms (p = 0.36). PE in patients with MM often occurs without clinical symptoms and is indicative for advanced disease and a poorer prognosis. • PE in patients with MM often occurs without clinical symptoms. • PE in patients with MM is indicative for advanced disease and a poorer prognosis. • Routine anticoagulation therapy should be considered to reduce the risk of PE and improve the tumor-related outcome. [ABSTRACT FROM AUTHOR]

Abstract: This study evaluates potential markers in blood and stools for their ability to distinguish bacterial from viral gastroenteritis. A total of 108 patients were prospectively recruited, of which 27 showed bacterial, 30 viral, and 51 no detectable pathogen, respectively. Cytokines, C-reactive protein (CRP), and white blood cells as well as the 2 fecal markers lactoferrin and calprotectin were determined. Statistics comprised Kruskal-Wallis test and U test in addition to an assessment of receiver operating characteristic. Interferon γ (IFNγ) levels were significantly increased in the viral group compared to the bacterial and nonspecific group. For the bacterial group, both fecal markers lactoferrin and calprotectin as well as CRP were significantly higher in comparison to the other 2 groups. To differentiate between bacterial and viral gastroenteritis, CRP, serum IFNγ, and the fecal proteins lactoferrin and calprotectin may be useful. A corresponding algorithm should be evaluated prospectively. [Copyright &y& Elsevier]

Abstract: Objective: To compare the results of RTE with four different modalities at 3.0T using endorectal and body phased array coil in the detection of PC. Patients and methods: Between May 2009 and July 2010, 50 patients with biopsy proven PC scheduled for radical prostatectomy (RP) were examined. All patients underwent RTE of the prostate and 3.0T endorectal MRI. The investigators were unaware of the clinical data and of each others results. Results: RTE detected PC in 46 (92%) and MRI in 42 (84%) of the patients. Depending on the analysis sensitivity was 44.1–58.9% for RTE and 36.7–43.1% for MRI. Specificity was 83.0–74.8% for RTE and 85.9–79.8% for MRI. Sensitivity was significantly higher for RTE (16-sectors: p =0.0348; 8-sectors: p =0.0002) and showed better results in the dorsal (RTE: 51.9%; MRT: 37.7%) and apical to middle (RTE: 66.7%-80.0%; MRI: 41.7%-60.0%) parts of the prostate. MRI showed better results in the base (MRI: 19.4%; RTE: 14.9%) and transitional zone (TZ) (MRI: 34.7%; RTE: 29.6%). Concerning capsular involvement the results were comparable with sensitivity and specificity of RTE being 79.2% and 80.0% compared to 80.8% and 70.0% of MRI. Conclusions: Concerning sensitivity RTE showed advantages in apical and middle parts whereas MRI may provide advantages in the glands’ base and TZ. Both RTE and MRI have limitations particularly in basal and ventral parts. Most of the undetected tumours were of low tumour volume and Gleason Score. Considering capsular involvement both techniques showed comparable results. [Copyright &y& Elsevier]

Abstract: Introduction: A single nucleotide polymorphism of the factor VII activating protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor for venous thrombosis, but its clinical role has so far been controversial in part due to small cohort sizes. The aim of the present case-control study was to elucidate the impact of the FSAP Marburg I polymorphism (FSAP-MI) on the development of venous thromboembolic disease (VTE) with other known sequence variations, including Factor V Leiden (rs6025) and Factor II G20210A (rs1799963). Materials and Methods: The study included 891 patients (312 male and 579 female) with a history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 1283 healthy blood donors with no history of venous thromboembolic disease. Results: We found that besides to the well-established aforementioned sequence variations of FV and Prothrombin, the FSAP Marburg I (FSAP-MI) polymorphism was significantly associated with the development of DVTs (1.65 (1.16-2.34) OR (95% CI)) and recurrent thromboembolic events (DVT and PE) (2.13 (1.35-3.36) OR (95% CI)). Comparing patients displaying one or more events FSAP-MI was still associated with the development of recurrent thromboembolic events (1.64 (1- 2.69) OR (95% CI)). Conclusions: We conclude that FSAP Marburg-I genotyping may be used to determine the risk for thromboembolic disorders in patients with suspected thrombophilia and known DVT or PE. [Copyright &y& Elsevier]

Objectives: Adjuvant radiochemotherapy improves survival of patients with advanced gastric cancer. We assessed in two sequential cohorts whether improved radiotherapy technique (IMRT) together with intensified chemotherapy improves outcome vs. conventional three-dimensional conformal radiotherapy (3D-CRT) and standard chemotherapy in these patients while maintaining or reducing renal toxicity. Materials and Methods: Sixty consecutive patients treated for gastric cancer either with 3D-CRT (n = 27) and IMRT (n = 33) were evaluated. More than 70% had undergone D2 resection. Although there was a slight imbalance in R0 status between cohorts, N+ status was balanced. Chemotherapy consisted predominantly of 5-fluorouracil/folinic acid (n = 36) in the earlier cohort and mostly of oxaliplatin/capecitabine (XELOX, n = 24) in the later cohort. Primary end points were overall survival (OS), disease-free survival (DFS), and renal toxicity based on creatinine levels. Results: Median follow-up (FU) of all patients in the 3D-CRT group was 18 months and in the IMRT group 22 months (median FU of surviving patients 67 months in the 3D-CRT group and 25 months in the IMRT group). Overall median survival (and DFS) were 18 (13) months in the 3D-CRT group and both not reached in the IMRT group (p = 0.0492 and 0.0216). Actuarial 2-year survival was 37% and 67% in the 3D-CRT and IMRT groups, respectively. No late renal toxicity >Grade 2 (LENT-SOMA scale) was observed in either cohort. Conclusion: When comparing sequentially treated patient cohorts with similar characteristics, OS and DFS improved with the use of IMRT and intensified chemotherapy without signs of increased renal toxicity. [Copyright &y& Elsevier]

Introduction: Direct thrombin inhibitors (DTI) prolong the ecarin clotting time (ECT). Oral anticoagulants (OA) decrease prothrombin levels and thus interact with actions of DTIs on the ECT method during concomitant therapy. Materials and methods: Actions of lepirudin, argatroban and melagatran on ECT were investigated in normal plasma (NP) and in plasma of patients (n=23 each) on stable therapy with phenprocoumon (OACP). Individual line characteristics were tested statistically. Results: Control ECT in OACP was prolonged compared to NP (50.1±0.9 vs. 45.7±0.8 s; p<0.001). Lepirudin prolonged the ECT linearly. Argatroban and melagatran delivered biphasic dose–response curves. OA showed additive effects on the ECT of lepirudin but not of argatroban and melagatran. Both in NP and OACP, the first and second slopes of melagatran were steeper compared to argatroban (primary analysis; p<0.001). When using the same drug, slopes in OACP were steeper than in NP (secondary analysis; p<0.001). At similar molar concentrations, the crossing points of both slopes were significantly higher with melagatran (323.1±11.0 s in NP and 333.2±8.2 s in OACP) than with argatroban (219.6±14.7 and 248.4±15.2 s) corresponding to ratios of 7.1±0.2 and 6.7±0.2 (melagatran) vs. 4.8±0.3 and 4.9±03 with argatroban (p<0.0001). Discussion: The patterns of interactions between vitamin K antagonists and DTI effects are different for bivalent (increase of slope without affecting linearity) and monovalent inhibitors (slight increase or alteration of nonlinear slopes), but there are also differences between the two monovalent inhibitors on thrombin inhibition as determined by ECT. [Copyright &y& Elsevier]

High-risk human papillomavirus (hrHPV) types represent the aetiological agents in a major proportion of anal squamous cell carcinomas (ASCC). Several studies have suggested a prognostic relevance of HPV-related markers, particularly hrHPV DNA and p16INK4a (p16) protein expression, in patients with ASCC. However, broader evaluation of these prognostic marker candidates has been hampered by small cohort sizes and heterogeneous survival data among the individual studies. We conducted an individual patient data (IPD) meta-analysis to determine the prognostic value of hrHPV DNA and p16 in patients with ASCC while controlling for major clinical and tumour covariates. A systematic literature search was conducted to identify all published studies analysing p16 alone or in combination with hrHPV DNA and reporting survival data in patients with ASCC. Clinical and tumour-related IPD were requested from authors of potentially eligible studies. Survival analyses were performed with a proportional hazard Cox model stratified by study and adjusted for relevant covariates. The study-specific hazard ratios (HRs) for the exposures were pooled using a random-effects model. Kaplan-Meier curves from different studies were pooled per exposure group and weighted by the study's total sample size. Seven studies providing IPD from 693 patients with ASCC could be included in the meta-analysis. Seventy-six percent of patients were p16+/hrHPV DNA+, whereas 11% were negative for both markers. A discordant marker status was observed in 13% of cases. Patients with p16+/hrHPV DNA+ ASCC showed significantly superior overall survival (OS) compared with patients with p16-/hrHPV DNA- tumours (pooled adjusted HR = 0.26 [95% confidence interval {CI}, 0.14–0.50]) with pooled three-year OS rates of 86% (95% CI, 82–90%) versus 39% (95% CI, 24–54%). Patients with discordant p16 and hrHPV DNA status showed intermediate three-year OS rates (75% [95% CI, 56–86%] for p16+/hrHPV DNA- and 55% [95% CI, 35–71%] for p16-/hrHPV DNA+ ASCC). This first IPD meta-analysis controlling for confounding variables shows that patients with p16+/hrHPV DNA+ ASCC have a significantly better survival than patients with p16-/hrHPV DNA- tumours. • This is the first IPD meta-analysis on the prognostic value of p16 and/or hrHPV DNA in ASCC. • The majority of ASCC (76%) was p16+/hrHPV DNA+. • A discordant p16/hrHPV DNA marker status was observed in 13% of cases. • A p16+/hrHPV DNA+ tumor status was associated with superior overall survival. [ABSTRACT FROM AUTHOR]

• The JAPAN-FORTA list addresses the appropriateness of drug treatment in older adults in Japan. • The JAPAN-FORTA list contains 210 items aligned to 24 main indications. • The JAPAN-FORTA list should contribute to the improvement of drug therapy in older adults in Japan. Multimorbidity and subsequent polypharmacy are highly prevalent in older people. To improve inappropriate drug treatment, listing approaches such as the Beers or FORTA lists have been developed. Latter is the only clinically validated drug list issuing both positive (FORTA labels A, B) and negative (FORTA labels C, D) recommendations. Several country-specific FORTA lists have been developed to acknowledge national prescription habits, drug availabilities, and expert opinions. Here, this approach was applied to Japan. 13 Japanese experts in geriatric pharmacotherapy participated as raters in a 2-step Delphi consensus validation of the FORTA list. The proposal of FORTA labels was based on the EURO-FORTA List and raters were asked to add, delete or re-evaluate medications, add relevant diagnoses and comments. The final JAPAN-FORTA list contains 210 items aligned to 24 main indication groups. 15 items were added to the proposal and the 71 items either not used/approved in Japan or not evaluated by any rater (oncological drugs) were removed. Excluding latter, the JAPAN-FORTA list differs from the EURO-FORTA list by 23 %. Removals mainly concerned psychotropic drugs. A maximum of one label was changed per indication. The majority (96.9 percent) of the proposed FORTA labels were confirmed, only 6 labels had to be changed. The new JAPAN-FORTA list addresses the appropriateness of drug treatment in older people in Japan. This unique listing approach issuing both positive and negative medication recommendations has been shown to improve of drug therapy in older adults and its country-specific version is now available for Japan. [ABSTRACT FROM AUTHOR]

Polypharmacy and multimorbidity is a threat to older people; hence, listing approaches should support physicians to optimize medication. The FORTA (Fit fOR The Aged) classification of drug appropriateness for older people provides positive or negative labels: A (A-bsolutely), B (B-eneficial), C (C-areful), and D (D-on't). Based on these categories, FORTA-labeled drug lists were developed in 7 European countries or regions; the same approach was used to develop a U.S.-FORTA List reflecting the country-specific availability and usage of drugs. A 2-step Delphi-type approach was employed to add, remove, or relabel drugs from the listing proposal and to add or remove new indications. The proposal utilized the European (EURO)-FORTA list as template. Eight US-based geriatricians/pharmacists served as raters. Measurements: Raters gave recommendations and comments on the list items. The first U.S.-FORTA List contains 273 items aligned to 27 main indication groups; 30 drugs and drug groups were added, and 23 removed as being unavailable in the United States. The highest percentage of changes in FORTA labels as compared to the EURO-FORTA List occurred for sleep disorders associated with dementia (40%). In 8 indications, the labels for 11 items were different from the proposal. Thus, for the majority of the items (n = 232, 95.5%), the proposals were accepted by the US raters. Only 16 (6.6%) of the proposed items (n = 243) had to be re-evaluated in the second round as a result of inconsistent rating in the first round. The U.S.-FORTA List addresses the appropriateness of drugs for older people in the United States reflecting country-specific availability, usage, and expert rating. As shown for the FORTA list in Europe, this listing approach is among the few that are clinically validated and improve well-being and geriatric outcomes. The U.S.-FORTA List now largely enhances the global availability of this approach. [ABSTRACT FROM AUTHOR]