Behavioral Voluntary and Social Bioassays Enabling Identification of Complex and Sex-Dependent Pain-(-Related) Phenotypes in Rats with Bone Cancer.

Cancer-induced bone pain (CIBP) is a common and devastating symptom with limited treatment options in patients, significantly affecting their quality of life. The use of rodent models is the most common approach to uncovering the mechanisms underlying CIBP; however, the translation of results to the clinic may be hindered because the assessment of pain-related behavior is often based exclusively on reflexive-based methods, which are only partially indicative of relevant pain in patients. To improve the accuracy and strength of the preclinical, experimental model of CIBP in rodents, we used a battery of multimodal behavioral tests that were also aimed at identifying rodent-specific behavioral components by using a home-cage monitoring assay (HCM). Rats of all sexes received an injection with either heat-deactivated (sham-group) or potent mammary gland carcinoma Walker 256 cells into the tibia. By integrating multimodal datasets, we assessed pain-related behavioral trajectories of the CIBP-phenotype, including evoked and non-evoked based assays and HCM. Using principal component analysis (PCA), we discovered sex-specific differences in establishing the CIBP-phenotype, which occurred earlier (and differently) in males. Additionally, HCM phenotyping revealed the occurrence of sensory-affective states manifested by mechanical hypersensitivity in sham when housed with a tumor-bearing cagemate (CIBP) of the same sex. This multimodal battery allows for an in-depth characterization of the CIBP-phenotype under social aspects in rats. The detailed, sex-specific, and rat-specific social phenotyping of CIBP enabled by PCA provides the basis for mechanism-driven studies to ensure robustness and generalizability of results and provide information for targeted drug development in the future.

Oxidative DNA damage in reconstituting T cells is associated with relapse and inferior survival after allo-SCT.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only curative treatment option for a number of hematologic malignancies. Its therapeutic potential relies on the potency of donor T cells to eliminate residual malignant cells, the so-called graft-versus-leukemia (GVL) effect. Disease relapse remains the most frequent treatment failure and is associated with poor outcome. Therefore, it is inevitable to decipher mechanisms that weaken GVL. In recent years, studies of tumor biology have revealed that metabolic remodeling of the micromilieu can critically regulate immune responses. Accumulation of reactive oxygen species leads to a metabolic condition known as oxidative stress, which can severely hamper T cells. Currently, only a few studies, mainly using preclinical models, have demonstrated the occurrence of oxidative stress after allo-SCTs. Therefore, we sought to investigate oxidative stress in a well-characterized group of patients who underwent allo-SCT and its impact on reconstituting T cells. We identified high concentrations of serum 8-hydroxydeoxyguanosine (8-OHdG) as an established biomarker for oxidative stress. 8-OHdG is one of the major products of DNA oxidation, which is normally rapidly removed. After allo-SCT, T cells accumulated oxidative DNA damage. High cellular 8-OHdG content (8-OHdGhi) was associated not only with signs of enhanced T-cell activation but also premature exhaustion. The inability of 8-OHdGhi T cells to efficiently target malignant cells or produce cytotoxic granzyme B and interferon gamma was associated with a significantly increased relapse risk and a shorter overall survival. Taken together, our novel findings could give reason to focus on bolstering DNA repair in reconstituting T cells as a means to improve GVL efficacy.

Exploring quantitative cellular bioimaging and assessment of CdSe/ZnS quantum dots cellular uptake in single cells, using ns-LA-ICP-SFMS.

Quantitative bioimaging of Quantum Dots (QDs) uptake in single cells by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a challenging task due to the high sensitivity and high spatial resolution required, and to the lack of matrix-matched reference materials. In this work, high spatially resolved quantitative bioimaging of CdSe/ZnS QDs uptake in single HT22 mouse hippocampal neuronal cells and in single HeLa human cervical carcinoma cells is novelty investigated combining: (a) the use of a ns-LA-ICP-Sector Field (SF)MS unit with mono-elemental fast and sensitive single pulse response for 114Cd+; and (b) the spatially resolved analysis of dried pL-droplets from a solution with a known concentration of these QDs to obtain a response factor that allows quantification of elemental bioimages. Single cells and dried pL-droplets are morphologically characterized by Atomic Force Microscopy (AFM) to determine their volume and thickness distribution. Moreover, operating conditions (e.g. spot size, energy per laser pulse, etc.) are optimized to completely ablate the cells and pL droplets at high spatial resolution. Constant operating conditions for the analysis of the single cells and calibrating samples is employed to reduce potential fractionation effects related to mass load effects in the ICP. A number concentration of CdSe/ZnS QDs between 3.5 104 and 48 104 is estimated to be uptaken by several selected single HT22 and HeLa cells, after being incubated in the presence of a QDs suspension added to a standard cell culture medium. Mono-elemental bioimaging at subcellular resolution seems to show a higher number concentration of the CdSe/ZnS QDs in the cytosol around the cell nucleus.

Dynamics and predisposition of respiratory viral co-infections in children and adults.

OBJECTIVES: The epidemiology of respiratory co-infection pairings is poorly understood. Here we assess the dynamics of respiratory viral co-infections in children and adults and determine predisposition for or against specific viral pairings. METHODS: Over five respiratory seasons from 30 November 2013 through 6 June 2018, the mono-infection and co-infection prevalence of 13 viral pathogens was tabulated at The Cleveland Clinic. Employing a model to proportionally distribute viral pairs using individual virus co-infection rate with prevalence patterns of concurrent co-circulating viruses, we compared predicted occurrence with observed occurrence of 132 viral pairing permutations using binomial analysis. RESULTS: Of 30 535 respiratory samples, 9843 (32.2%) were positive for at least one virus and 1018 (10.8%) of these were co-infected. Co-infected samples predominantly originated from children. Co-infection rate in paediatric population was 35.0% (2068/5906), compared with only 5.8% (270/4591) in adults. Adenovirus C (ADVC) had the highest co-infection rate (426/623, 68.3%) while influenza virus B had the lowest (55/546, 10.0%). ADVC-rhinovirus (HRV), respiratory syncytial virus A (RSVA)-HRV and RSVB-HRV pairings occurred at significantly higher frequencies than predicted by the proportional distribution model (p < 0.05). Additionally, several viral pairings had fewer co-infections than predicted by our model: notably metapneumovirus (hMPV)-parainfluenza virus 3, hMPV-RSVA and RSVA-RSVB. CONCLUSIONS: This is one of the largest studies on respiratory viral co-infections in children and adults. Co-infections are substantially more common in children, especially under 5 years of age, and the most frequent pairings occurred at a higher frequency than would be expected by random. Specific pairings occur at altered rates compared with those predicted by proportional distribution, suggesting either direct or indirect interactions result between specific viral pathogens.

Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 'CREATE'.

BACKGROUND: Clear-cell sarcoma (CCSA) is an orphan malignancy, characterized by a specific t(12;22) translocation, leading to rearrangement of the EWSR1 gene and overexpression of MET. We prospectively investigated the efficacy and safety of the tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic CCSA. PATIENTS AND METHODS: Patients with CCSA received oral crizotinib 250 mg twice daily. Primary end point was objective response rate (ORR), secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate (PFR), overall survival (OS), OS rate and safety. The study design focused on MET+ disease with documented rearrangement of the EWSR1 gene by fluorescence in situ hybridization. RESULTS: Among 43 consenting patients with the local diagnosis of CCSA, 36 had centrally confirmed CCSA, 28 of whom were eligible, treated and assessable. Twenty-six out of the 28 patients had MET+ disease, of whom one achieved a confirmed partial response and 17 had stable disease (SD) (ORR 3.8%, 95% confidence interval: 0.1-19.6). Further efficacy end points in MET+ CCSA were DCR: 69.2% (48.2% to 85.7%), median PFS: 131 days (49-235), median OS: 277 days (232-442). The 3-, 6-, 12- and 24-month PFR was 53.8% (34.6-73.0), 26.9% (9.8-43.9), 7.7% (1.3-21.7) and 7.7% (1.3-21.7), respectively. Among two assessable MET- patients, one had stable disease and one had progression. The most common treatment-related adverse events were nausea [18/34 (52.9%)], fatigue [17/34 (50.0%)], vomiting [12/34 (35.3%)], diarrhoea [11/34 (32.4%)], constipation [9/34 (26.5%)] and blurred vision [7/34 (20.6%)]. CONCLUSIONS: The PFS with crizotinib in MET+ CCSA is similar to results achieved first-line in non-selected metastatic soft tissue sarcomas with single-agent doxorubicin. The PFS is similar to results achieved with pazopanib in previously treated sarcoma patients. CLINICAL TRIAL NUMBER: EORTC 90101, EudraCT number 2011-001988-52, NCT01524926.

Structured pain management reduces patient discomfort after catheter ablation and rhythm device surgery.

BACKGROUND: The goal was to test the effectiveness of a structured pain management programme after invasive electrophysiological interventions in cardiology including ablation of atrial fibrillation (AF) or ventricular tachycardia (VT) and implantation, or explantation, of pacemakers or implantable cardioverter defibrillators. METHODS: This was a prospective study with a pre-/post-design where a post-intervention group (116 consecutive patients) was compared to a pre-intervention group (102 consecutive patients) after implementation of a structured pain-management programme using the numeric rating scale (NRS 0-10) and classified as moderate-to-severe if NRS > 3. Measurements were recorded every two hours during the first 24 h post-operatively. The location of the pain and the amount of analgesic used were also recorded. RESULTS: The proportion of patients who experienced moderate-to-severe pain after the procedure decreased after initiation of the pain-management program: 47% versus 61%; p = 0.048. This difference was driven primarily by reduced pain late (8-24 h) after the procedure; 16% versus 39%; p < 0.001. The risk to develop late (8-24 h) post-procedural pain was reduced approximately three-fold after implementation of the pain-management programme (OR = 0.32, 95% CI 0.16-0.64, p = 0.001). Multivariate analysis indicated chronic pain, early pain (0-6 h), and type of intervention were associated with late post-interventional pain. In contrast, age, diabetes mellitus, BMI, gender and procedure time were not related. CONCLUSION: The findings illustrate the potential value of a structured pain-management programme. The proportion of patients who experienced moderate-to-severe pain after these electrophysiological procedures decreased significantly. SIGNIFICANCE: This is the first exploratory study that evaluates the impact of a multidisciplinary pain-management programme after cardiac electrophysiological interventions. It demonstrates that significant quality improvement is achievable following simple rules together with patient and staff education. The programme reduces the proportion of patients with moderate-to-severe pain after electrophysiological procedures significantly.

Elevated cardiac troponin T indicating myocardial infarction or myocarditis-urgent cardiac catheter examination-or do we have to consider other reasons?

Alveolar rhabdomyosarcoma is an aggressive tumour in adulthood, in which cardiac troponin T seems to be a tumour marker and course parameter. We present the clinical course of a young man suffering from this rare disease and the development of troponin T during therapy. Noninvasive cardiac imaging was used to exclude cardiac involvement, myocardial infarction or inflammation processes.

Genetic variants in DNA repair genes as potential predictive markers for oxaliplatin chemotherapy in colorectal cancer.

Oxaliplatin-based chemotherapy exerts its effects through generating DNA damage. Hence, genetic variants in DNA repair pathways could modulate treatment response. We used a prospective cohort of 623 colorectal cancer patients with stage II-IV disease treated with adjuvant/palliative chemotherapy to comprehensively investigate 1727 genetic variants in the DNA repair pathways as potential predictive markers for oxaliplatin treatment. Single nucleotide polymorphisms (SNP) associations with overall survival and recurrence-free survival were assessed using a Cox regression model. Pathway analysis was performed using the gamma method. Patients carrying variant alleles of rs3783819 (MNAT1) and rs1043953 (XPC) experienced a longer overall survival after treatment with oxaliplatin than patients who did not carry the variant allele, while the opposite association was found in patients who were not treated with oxaliplatin (false discovery rate-adjusted P-values for heterogeneity 0.0047 and 0.0237, respectively). The nucleotide excision repair (NER) pathway was found to be most likely associated with overall survival in patients who received oxaliplatin (P-value=0.002). Our data show that genetic variants in the NER pathway are potentially predictive of treatment response to oxaliplatin.

Genotype-specific differences in the tumor metabolite profile of pheochromocytoma and paraganglioma using untargeted and targeted metabolomics.

CONTEXT AND OBJECTIVE: Pheochromocytomas and paragangliomas (PGLs) are neuroendocrine tumors of sympathetic or parasympathetic paraganglia. Nearly 40% of PGLs are caused by germline mutations. The present study investigated the effect of genetic alterations on metabolic networks in PGLs. DESIGN: Homogenates of 32 sporadic PGLs and 48 PGLs from patients with mutations in SDHB, SDHD, SDHAF-2, VHL, RET, and NF-1 were subjected to proton ((1)H) nuclear magnetic resonance (NMR) spectroscopy at 500 MHz for untargeted and HPLC tandem mass spectrometry for targeted metabolite profiling. RESULTS: (1)H NMR spectroscopy identified 28 metabolites in PGLs of which 12 showed genotype-specific differences. Part of these results published earlier reported low complex II activity (P < .0001) and low ATP/ADP/AMP content (P < .001) in SDH-related PGLs compared with sporadics and PGLs of other genotypes. Extending these results, low levels of N-acetylaspartic acid (NAA; P < .05) in SDH tumors and creatine (P < .05) in VHL tumors were observed compared with sporadics and other genotypes. Positive correlation was observed between NAA and ATP/ADP/AMP content (P < .001) and NAA and complex II activity (P < .0001) of PGLs. Targeted purine analysis in PGLs showed low adenine in cluster 1 compared with cluster 2 tumors (SDH P < .0001; VHL P < .05) whereas lower levels (P < .05) of guanosine and hypoxanthine were observed in RET tumors compared with SDH tumors. Principal component analysis (PCA) of metabolites could distinguish PGLs of different genotypes. CONCLUSIONS: The present study gives a comprehensive picture of alterations in energy metabolism in SDH- and VHL-related PGLs and establishes the interrelationship of energy metabolism and amino acid and purine metabolism in PGLs.

Anal sphincter function after total mesorectal excision is comparable to that of healthy subjects: results of a matched pair analysis.

AIM: The aim of this paper was to compare healthy subjects and patients after total mesorectal excision concerning anal resting/squeeze pressure and surface-electromyography of the sphincter. METHODS: Forty patients (9 female/31 male) after total mesorectal excision due to low or middle rectal cancer were compared to a sex-, age- and BMI-matched group of healthy volunteers by means of anorectal pull-through manometry using a microtip-transducer system and by means of endoanal surface electromyography using a bipolar plug electrode. RESULTS: Resting pressure (59.2 ± 3.1 mmHg vs. 68.3 ± 4.3 mmHg; P=0.056) and squeeze pressure (127.3 ± 3.2 mmHg vs. 128.9 ± 4.6 mmHg; P=0.78) were comparable between patients after total mesorectal excision and healthy volunteers whereas surface electromyography amplitude (9.5 ± 0.4 µV vs. 13.9 ± 0.6 µV; P=0.01) was significant lower in patients after total mesorectal excision compared to healthy subjects. Correlation between squeeze and resting pressure as well as between squeeze pressure and surface electromyography were weaker in patients after total mesorectal excision compared to healthy controls. CONCLUSION: Objective measurable sphincter pressure after total mesorectal excision seems to be comparable to that of healthy subjects whereas surface-electromyography is significant higher in healthy subjects.

The effects of neonatal cryoanaesthesia-induced hypothermia on adult emotional behaviour and stress markers in C57BL/6 mice.

Since the early 1930s, deep hypothermia (cryoanaesthesia) has been a useful anaesthetic in several types of surgery on neonatal rodents. Especially against the background of modern techniques in systems neuroscience, the method enjoys again increasing popularity. However, little is known about its effects on the subsequent adult behavioural and physiological profile. To systematically investigate the effects of neonatal cryoanaesthesia on adult basal and emotional behaviour as well as on physiological development, 59 C57BL/6 mouse pups were randomly assigned to one of three treatment groups: Pups of the first group were exposed to the hypothermia treatment (H) on postnatal day 3, while pups of the other two groups served as controls: These pups either remained in the home cage without any intervention (C), or were separated from the mother for 15 min (MS) to differentiate between effects of neonatal isolation alone versus hypothermia that inevitably goes along with neonatal isolation. Subsequent behavioural analyses were conducted during adulthood (P 84-P 130), including tests for exploratory, anxiety-like and depression-like behaviour. At the age of about 145 days mice were decapitated to record BDNF levels in the hippocampus and serum corticosterone. Altogether, H mice were found to display slightly increased anxiety levels on the O-Maze, but did not differ from the control animals in any other behavioural test. Subtle alterations in anxiety-like behaviour, however, were not accompanied by physiological changes in serum corticosterone and hippocampal BDNF levels, arguing against an overall long-lasting effect of neonatal hypothermia on the emotional profile of adult mice.

Incidental and ablation-induced findings during upper gastrointestinal endoscopy in patients after ablation of atrial fibrillation: a retrospective study of 425 patients.

BACKGROUND: Although rare, atrioesophageal fistula is a serious and often lethal complication of radiofrequency catheter ablation in patients with atrial fibrillation (AF). Consequently, esophagogastroduodenoscopy after AF catheter ablation has been suggested to detect thermal esophageal lesions. OBJECTIVE: To report the incidence of thermal lesions and other incidental gastrointestinal (GI) abnormalities in patients with AF after radiofrequency catheter ablation. METHODS: Four hundred twenty-five (mean age 59 ± 10 years; 64% men) consecutive patients with symptomatic AF who underwent left atrial radiofrequency catheter ablation were scheduled for upper GI endoscopy 1-3 days after the procedure. Patients were asymptomatic for GI diseases, that is, exhibiting no dysphagia, heart burn, or abdominal pain. RESULTS: Pathological GI findings were observed in 328 (77%) patients and included gastral erosions (22%), esophageal erythema (21%), gastroparesis (17%), hiatal hernia (16%), reflux esophagitis (12%), thermal esophageal lesion (11%), and suspected Barrett's esophagus (5%). Biopsies were performed in 70 (17%) patients, showing gastritis (84%), Helicobacter pylori colonization (17%) and mucosa-associated lymphoid tissue (17%), esophagitis (9%), and Barrett's esophagus (4%). Further diagnostic workup or treatment was initiated in 105 (25%) patients. CONCLUSIONS: Upper GI pathologies are observed frequently in asymptomatic patients. Half of all patients have a requirement for treatment. Among the findings, thermal esophageal lesions and gastroparesis can be attributed to AF catheter ablation. The high incidence of gastroparesis is a novel finding that deserves further investigation.

Non-fluoroscopic catheter visualization using MediGuide™ technology: experience from the first 600 procedures.

A novel cardiovascular navigation system known as MediGuide™ (MG) which allows non-fluoroscopic catheter tracking over a background of pre-recorded cine loops was recently introduced. This system allows significant reduction of fluoroscopy exposure which is one of the potentially harmful aspects of today's electrophysiological procedures such as ablations or device implantations. We provide a summary of recently published studies related to this new technological platform and describe our experience from the first 600 MG procedures at our institution.After reviewing the currently available publications in the field of MG-supported EP procedures, we describe the workflows for (1) ablation of supraventricular tachycardia (SVT), atrial fibrillation (AF), and ventricular tachycardia using MG-enabled diagnostic and ablation catheters, as well as (2) implant of cardiac resynchronization therapy (CRT) devices using sensor-equipped delivery tools including sheaths, sub-selectors, and guidewires.As shown in several studies [5-9], MG procedures resulted in similar efficacy as conventional cases but with a significant reduction in fluoroscopy time and dose. In particular, for SVT ablations, the median fluoroscopy time using the MG technology was 0.5 ± 1.4 min compared to 10.2 ± 9.6 min in conventional fluoroscopic settings. Similar reductions were demonstrated for AF ablation procedures from 25 min in conventional settings with electroanatomical mapping systems and live x-ray to 4.6 min with the addition of the MG technology. Recently, it was demonstrated that the application of MG for CRT device implants could successfully result in a median fluoroscopy time of 2.6 min for LV lead deployment.In summary, the first measurable clinical impact of the MG technology on a daily clinical routine is the reduction of fluoroscopy time and radiation exposure for various EP indications. These beneficial effects were achieved without negative consequences on procedural efficacy, complications, or time in more than 600 EP procedures.

Variants of unknown significance in BRCA testing: impact on risk perception, worry, prevention and counseling.

BACKGROUND: Sequence-based BRCA testing can identify variants of unknown significance (VUS). Relatively little is known about how well a test outcome of VUS is understood by patients and referring physicians, and whether genetic counselors have an interest in the development of VUS management guidelines. DESIGN: Self-administered questionnaires were completed by 36 VUS counselees, 75 women with a BRCA mutation and 33 with no mutation found (NMF). We also surveyed 24 genetic counselors and 22 referring family physicians. RESULTS: One-third of VUS failed to recall the clinical significance of their result. Incorrect recall was significantly higher among VUS with high-school-only education (70% versus 19%, P = 0.02). Risk perception, cancer worry and uptake of surveillance and risk-reducing surgeries among VUS counselees were more similar to NMF than to mutation carriers. Genetic counselors accurately predicted the difficulties counselees would have with a VUS result and identified the need for VUS management guidelines. Referring physicians unanimously stated that genetic testing was indicated for unaffected siblings of VUS carriers. CONCLUSIONS: While VUS seems to be correctly perceived by counselees as more similar to NMF than to a pathogenic mutation, miscomprehension of VUS is more common, particularly in counselees with lower education. VUS-related educational interventions for both VUS counselees and their referring physicians are needed. We encourage the development of national VUS-related guidelines for genetic counselors.

Identification of Enterobacteriaceae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the VITEK MS system.

This multicenter study evaluated the accuracy of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry identifications from the VITEK MS system (bioMérieux, Marcy l'Etoile, France) for Enterobacteriaceae typically encountered in the clinical laboratory. Enterobacteriaceae isolates (n = 965) representing 17 genera and 40 species were analyzed on the VITEK MS system (database v2.0), in accordance with the manufacturer's instructions. Colony growth (≤72 h) was applied directly to the target slide. Matrix solution (α-cyano-4-hydroxycinnamic acid) was added and allowed to dry before mass spectrometry analysis. On the basis of the confidence level, the VITEK MS system provided a species, genus only, or no identification for each isolate. The accuracy of the mass spectrometric identification was compared to 16S rRNA gene sequencing performed at MIDI Labs (Newark, DE). Supplemental phenotypic testing was performed at bioMérieux when necessary. The VITEK MS result agreed with the reference method identification for 96.7% of the 965 isolates tested, with 83.8% correct to the species level and 12.8% limited to a genus-level identification. There was no identification for 1.7% of the isolates. The VITEK MS system misidentified 7 isolates (0.7 %) as different genera. Three Pantoea agglomerans isolates were misidentified as Enterobacter spp. and single isolates of Enterobacter cancerogenus, Escherichia hermannii, Hafnia alvei, and Raoultella ornithinolytica were misidentified as Klebsiella oxytoca, Citrobacter koseri, Obesumbacterium proteus, and Enterobacter aerogenes, respectively. Eight isolates (0.8 %) were misidentified as a different species in the correct genus. The VITEK MS system provides reliable mass spectrometric identifications for Enterobacteriaceae.

[Benchmarking surgical resources--a work sampling analysis at a German university hospital]. / Ärztliche Ressourcennutzung in der Chirurgie auf dem Prüfstand--eine Worksampling-Analyse an einer deutschen Universitätsklinik.

INTRODUCTION: Work densification caused by lack of young surgeons with increased clinical documentation keeps surgeons busy. It is proven by many studies that surgeons work significantly longer hours per week and deal with a larger amount of medical and non-medical documentation than staff members in conservative disciplines. The aim of the study was to investigate surgeons work distribution in a surgical university department and to evaluate by means of a work sampling analysis whether it can be standardised and slimmed down by systematic use of IT-supported, process-managed work-flow. In addition the data obtained are compared wuith those from other studies on similar topics. METHODS: Based on the results of an independent pilot observational study, 21 surgeons (14 residents, 7 staff surgeons) had to document over a 10-day period in a self-observation once in an hour their actual activity in a two dimensional matrix concerning medical activity (13 items) and patient contact (5 items). After the study, each physician had to estimate his/her own work distribution. Real percentages of the self-observation study were compared to the physicians' estimates of work distribution. IT-supported clinical pathways have been implemented since 2004 in our department. RESULTS: Over a ten-day evaluation period (1830 observation points), surgeons spent 30.2% of their activity in the operating theatre or on direct patient care. During 13.9% they were in meetings and they spent 10.8% of their time on documentation. Time needed for studying medical records (9.2%) and ward rounds (9.0%) ranged in a similar way. There was a significant accordance of estimated and real work distribution concerning the 5 most frequent daily activities. In only 14% there was no direct patient relationship. CONCLUSION: Application of work sampling analysis in surgery is a valid procedure for the evaluation of work flows in the course of personal observations. Surgeons working time in a hospital is limited. To achieve a maximum of direct patient care, clinical documentation has to be optimised by process automatisation within the context of IT-supported clinical pathways. Surgeons are able to estimate very exactly the distribution of their daily activities so that data of working time estimations is valuable.

[Non-fluoroscopic catheter tracking: the MediGuide™ system]. / Nicht fluoroskopische Katheternavigation: das MediGuide™-System.

Conventional fluoroscopy is the main technology for intracardiac device tracking in interventional cardiovascular procedures. For therapy delivery it carries the advantage of being able to instantaneously localize the device and its spatial relationship with respect to the moving target organ. However, besides the associated X-ray exposure, fluoroscopy only provides 2D orientation. For treatment of complex cardiac anatomies and substrates such as in interventional electrophysiology, 3-D mapping technologies have been introduced to facilitate spatial, anatomic, and electrical orientation. A new technological platform (MediGuide(™)) offers the option to continuously display the catheter tip on a prerecorded cine-loop allowing better anatomic understanding of the underlying substrate. We describe our initial experience using the system with diagnostic catheters only and the first procedures with the MediGuide(™) equipped ablation catheter (available since May 2012). We could show a significant decrease of fluoroscopy time in all types of procedures with comparable procedure times. No increase in complication rates was observed.

[A giant non-parasitic liver cyst as a prominent epigastric mass in an obese patient]. / Riesige nicht-parasitäre Leberzyste als äusserlich sichtbare epigastrische Vorwölbung bei einem adipösen Patienten.

HISTORY AND ADMISSION FINDINGS: A 62-year-old, obese male patient was referred because of an increasing prominent epigastric mass and bloated feeling. An epigastric hernial defect was clinically excluded. INVESTIGATIONS: Abdominal imaging by ultrasound and CT-scan demonstrated a giant liver cyst in the left lobe of 20 cm in diameter with a displacement of the stomach. Endoscopy showed an external compression of the stomach. Cystic echinococcosis was excluded by serology. TREATMENT AND COURSE: Laparoscopic deroofing of the cyst resulted in immediate freedom of symptoms. The further course was uneventful. The patient was discharged one day after the operation. CONCLUSION: Liver cysts may become symptomatic by intestinal compression syndromes or - occasionally - as a prominent abdominal mass. Laparoscopic deroofing is the golden standard of symptomatic non parasitic liver cysts and is associated with a good clinical outcome.