Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients.

BACKGROUND: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. METHODS: The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. RESULTS: Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. CONCLUSIONS: Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.

Combined computational modeling and experimental analysis integrating chemical and mechanical signals suggests possible mechanism of shoot meristem maintenance.

Stem cell maintenance in multilayered shoot apical meristems (SAMs) of plants requires strict regulation of cell growth and division. Exactly how the complex milieu of chemical and mechanical signals interact in the central region of the SAM to regulate cell division plane orientation is not well understood. In this paper, simulations using a newly developed multiscale computational model are combined with experimental studies to suggest and test three hypothesized mechanisms for the regulation of cell division plane orientation and the direction of anisotropic cell expansion in the corpus. Simulations predict that in the Apical corpus, WUSCHEL and cytokinin regulate the direction of anisotropic cell expansion, and cells divide according to tensile stress on the cell wall. In the Basal corpus, model simulations suggest dual roles for WUSCHEL and cytokinin in regulating both the direction of anisotropic cell expansion and cell division plane orientation. Simulation results are followed by a detailed analysis of changes in cell characteristics upon manipulation of WUSCHEL and cytokinin in experiments that support model predictions. Moreover, simulations predict that this layer-specific mechanism maintains both the experimentally observed shape and structure of the SAM as well as the distribution of WUSCHEL in the tissue. This provides an additional link between the roles of WUSCHEL, cytokinin, and mechanical stress in regulating SAM growth and proper stem cell maintenance in the SAM.

Visual field improvement in neglect after virtual reality intervention: a single-case study.

A patient suffering from visuo-spatial neglect was investigated as a special interest case during a study on the effectiveness of "restorative approaches" after visual field loss. This patient trained with our newly developed Virtual Reality (VR) system "Salzburg Visual Field Trainer" for 254 days. Perimetric results show a visual field expansion of 48.8% (left eye) and 36.8% (right eye) translating to an improvement of approximately 5.5° to 10.5° of visual angle. Further, subjective self-report shows improvements of up to 317% in visual field functionality. Our results indicate that patients suffering from visuo-spatial neglect could benefit from a VR-based restorative intervention.

Linear Anterior-Posterior Computed Tomography Parameters Used to Quantify Trochlear Dysplasia Are More Reliable Than Angular Measurements.

PURPOSE: (1) To evaluate the reliability of 9 commonly used quantitative parameters of the trochlear morphology on computed tomography (CT) and (2) to analyze for differences in the reliability regarding patient subgroups (patellofemoral instability [PFI] vs non-PFI). METHODS: A retrospective analysis of lower-limb CT scans performed between August 1996 and February 2013 was performed. The CT scans of all patients with PFI and 30 randomly selected cases without a history of PFI (non-PFI) were included. The following measurements were performed on 1 proximal axial CT slice at the entrance of the trochlear groove and 1 slice 5 mm further distal: relative medial, central, and lateral trochlear height; trochlear depth; relative transverse trochlear shift; trochlear facet asymmetry; sulcus angle; and medial and lateral trochlear slope. Four investigators performed the measurements independently, and intraclass correlation coefficients (ICCs) were calculated for the entire study group, as well as for the PFI and non-PFI groups separately. RESULTS: In total, 66 cases (36 PFI cases) were included in the study. We found almost perfect inter-rater and intrarater agreement for the trochlear height on both axial CT slices (ICC, 0.831-0.977). For the other measurements, we found only fair reliability (ICC < 0.4) on the proximal CT slice, whereas on the distal CT slice, at least moderate reliability (ICC > 0.4) was observed. ICCs were lower for many parameters in the PFI group. Angular values were less reliable than linear values. In particular, measurements involving the medial facet (i.e., sulcus angle, medial trochlear slope, and trochlear facet asymmetry) were less reliable. CONCLUSIONS: When interpreting quantitative parameters defining the trochlear morphology, one must taken into account the considerably lower reliability of angular parameters such as the commonly used sulcus angle compared with linear measurements. Radiologic measurements are less reliable in cases of PFI than in subjects without instability. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Does the type of surgical approach affect the clinical outcome of total knee arthroplasty?

BACKGROUND: The aim of the study was to investigate the issue of medial midvastus (MMV) vs. medial parapatellar (MPP) approaches in total knee arthroplasty (TKA). It was hypothesized that the two surgical approaches would produce significantly different results with respect to patient-reported knee score outcome (hypothesis 1), short-term postoperative range of motion (ROM) (hypothesis 2), long-term postoperative ROM (hypothesis 3) and prosthesis survival (hypothesis 4). METHODS: A retrospective comparative study design was applied. Data sets were obtained from the state arthroplasty registry. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC) data were analyzed from preoperative and 1 year postoperatively. The ROM data were analyzed for the time points preoperative, postoperative days 4 and 10 and 1 year. RESULTS: Available were 627 cases (407 MMV vs. 220 MPP) and 1 year postoperatively there were no significant differences between groups regarding the WOMAC scores (hypothesis 1). Early postoperatively on days 4 and 10 after TKA there were no differences between groups (p = 0.305 and p = 0.383, respectively, hypothesis 2). Likewise, ROM did not significantly differ between the groups 1 year after TKA (p = 0.338, hypothesis 3). The 5­year prosthesis survival did not differ between the groups and showed 94.46% (95% confidence interval, CI 90.69-96.73%) in the MMV group and 94.33% (95% CI 89.96-96.83%) in the MPP group (p = 0.664, hypothesis 4). CONCLUSION: Both surgical approaches produce equivalent clinical results in terms of early postoperative ROM, late postoperative ROM and 1­year WOMAC. The same prosthesis survival rates can be expected.

Emerging Treatment Options in Inflammatory Bowel Disease: Janus Kinases, Stem Cells, and More.

BACKGROUND: Treatment of inflammatory bowel diseases (IBD) has tremendously improved during the last 20 years; however, a substantial fraction of patients does not respond to available therapies or lose response, and new strategies are needed. SUMMARY: Two pharmacological principles have been successfully used for IBD treatment: inhibition of cellular signaling and interference with leukocyte trafficking. Besides tumor necrosis factor, interleukin (IL)-23 is a promising drug target, and antibodies for the combined inhibition of IL-23 and IL-12 (ustekinumab and briakinumab) or selective IL-23 inhibition (brazikumab, risankizumab, and mirikizumab) seem to be effective in Crohn's disease (CD) with emerging evidence also for ulcerative colitis (UC). Janus kinase (JAK) mediates intracellular signaling of a large number of cytokines. Tofacitinib is the first JAK inhibitor approved for UC, and the JAK inhibitors filgotinib and upadacitinib showed potential in CD. Leukocyte trafficking can be inhibited by interference with lymphocyte integrin-α4ß7 or endothelial MadCAM-1. The α4ß7 integrin inhibitor vedolizumab is an established treatment in IBD, and long-term data of pivotal studies are now available. Additional molecules with therapeutic potential are α4ß7-specific abrilumab, ß7-specific etrolizumab, and the α4-specific small molecule AJM300. PF-00547659, an antibody against endothelial MadCAM-1, also showed therapeutic potential in UC. Modulation of sphingosine-1-phosphate receptor (S1PR) activity is necessary for the egress of lymphocytes into the circulation, and S1PR modulation results in lymphocyte trapping in lymphatic organs. Ozanimod, an S1PR1 and S1PR5 inhibitor, has been successfully tested in initial studies in UC. Mesenchymal stem cell therapy has been approved for the treatment of complex, active CD fistula, and mesenchymal stem cell therapy might be a paradigm shift for this condition. Autologous stem cell transplantation (ASCT) has been successfully used in CD case series; however, in a randomized trial, a highly stringent endpoint was not met. However, considering positive effects in secondary endpoints, ASCT might be a future treatment of last resort in severe, refractory CD cases, provided that safer protocols can be provided. Key messages: New IBD treatments are successful for a significant fraction of patients. However, new strategies for patient selection, treatment combinations, and/or additional therapies must be developed to serve the need of all IBD patients.

Treatment Algorithms for Crohn's Disease.

BACKGROUND: Treatment of Crohn's disease (CD) patients is complex as therapy choices depend on a variety of factors, such as location and severity of inflammation, disease behavior (inflammatory, stricturing or penetrating) but also comorbidities, extra-intestinal manifestations, the patient's age, and previous therapies. Subsequently, the choice of treatment should be tailored to the individual patient. SUMMARY: This article gives the reader therapy algorithms as a guide through different CD scenarios to support the physician's decision making. New compounds introduced in CD therapy in recent years justify such an update on standard approaches. Ustekinumab and vedolizumab and their positions within the treatment options are discussed. Fistulizing perianal disease and postoperative medical prophylaxis are depicted in separate chapters with own algorithms. Key Messages: In recent years, a variety of new drugs became available to treat patients with CD - especially those who are antitumor necrosis factor (TNF) experienced with ongoing inflammation. The definitive role of vedolizumab and ustekinumab is not yet fully clarified. However, with the advantage of good safety profiles over TNF-inhibitors, these drugs will be more frequently used in the near future, also as first-line biologicals, compared to TNF-inhibitors. Concerning treatment of fistulizing disease, the knowledge of the exact anatomy of the fistula is of major importance. An interdisciplinary discussion involving gastroenterologists, surgeons, and in some cases gynecologists may help to optimize the treatment plan. Regarding the postsurgical setting in CD patients, according to the very recent Cochrane Network meta-analysis, mesalazine should be at least positioned equivalent to thiopurines and TNF-inhibitors, as shown in our algorithm.

CASP1 variants influence subcellular caspase-1 localization, pyroptosome formation, pro-inflammatory cell death and macrophage deformability.

CASP1 variants result in reduced enzymatic activity of procaspase-1 and impaired IL-1ß release. Despite this, affected individuals can develop systemic autoinflammatory disease. These seemingly contradictory observations have only partially been explained by increased NF-κB activation through prolonged interaction of variant procaspase-1 with RIP2. To identify further disease underlying pathomechanisms, we established an in vitro model using shRNA-directed knock-down of procaspase-1 followed by viral transduction of human monocytes (THP-1) with plasmids encoding for wild-type procaspase-1, disease-associated CASP1 variants (p.L265S, p.R240Q) or a missense mutation in the active center of procaspase-1 (p.C285A). THP1-derived macrophages carrying CASP1 variants exhibited mutation-specific molecular alterations. We here provide in vitro evidence for abnormal pyroptosome formation (p.C285A, p.240Q, p.L265S), impaired nuclear (pro)caspase-1 localization (p.L265S), reduced pro-inflammatory cell death (p.C285A) and changes in macrophage deformability that may contribute to disease pathophysiology of patients with CASP1 variants. This offers previously unknown molecular pathomechanisms in patients with systemic autoinflammatory disease.

Patella Height Correlates With Trochlear Dysplasia: A Computed Tomography Image Analysis.

PURPOSE: The aim of this study was to investigate the position of the patella relative to the trochlea for a possible correlation with radiologic parameters characterizing the form of the trochlea. METHODS: The computed tomography scans of 36 cases with patellofemoral instability and 30 without (mean age, 24.7 ± 6.8 years) were studied. The height of the patella relative to the trochlea was evaluated as the distance between the axial slice where the patella (P) showed its widest diameter, as the patella at this level has the greatest potential to form the trochlea, and the proximal entrance of the femoral trochlea (TE). The correlations between this parameter and several radiologic parameters used to evaluate trochlear dysplasia, including trochlea height, transverse trochlea shift, trochlea depth, sulcus angle, lateral and medial trochlea slope, trochlea facet asymmetry, and the Dejour trochlea type, were calculated. RESULTS: The P-TE distance correlated significantly with all trochlea parameters evaluated, with a more dysplastic trochlea in cases of higher position of the patella: medial, central, and lateral trochlea height (0.287

Segmental torsion assessment is a reliable method for in-depth analysis of femoral alignment in Computer Tomography.

PURPOSE: De-rotational osteotomies are indicated in patients with pathologic femoral torsion. However, there is disagreement whether an osteotomy should be performed proximally or distally. Conventionally only the total torsion is measured, which does not allow differentiation between a torsional deformity located in the proximal or distal metaphysis or the diaphysis. The aim of this study is to validate a new multi-level measurement protocol for evaluation of the magnitude of torsion of the respective femoral segments in CT. PATIENTS AND METHODS: The torsional profile of 30 femora was evaluated in CT scans. For separate measurements of the torsion of the metaphysis and the diaphysis, four axes where determined: one through the femoral neck, a second determined by the midpoint of the femoral shaft and the lesser trochanter, a third determined by a tangent dorsal to the popliteal surface, and a fourth axis posterior to the condyles. The total femoral torsion was measured between the first and the fourth axis, proximal torsion between the first and the second, mid torsion between the second and the third, and distal torsion between the third and the fourth axis. Four investigators performed all measurements independently and intra-class correlation coefficients (ICC) were calculated to evaluate intra- and inter-rater reliability. RESULTS: Average total femoral torsion was 22.6 ± 8.7°, proximal torsion 47.7 ± 10.6°, mid torsion -33.4 ± 9.9°, and distal torsion 8.3 ± 3.2°. Intra-rater ICC ranged between 0.504 and 0.957 and inter-rater ICC between 0.643 and 0.992. The majority of the ICC were graded as "almost perfect" and some as "substantial" agreement. CONCLUSION: Evaluation of the segmental torsion of the femur allows in-depth analysis of femoral alignment. High reliability was shown for this measuring method in computed tomography, which can be deployed when studying interdependencies between joint pathologies and torsional deformities or when planning the site for an osteotomy. LEVEL OF EVIDENCE: Level III.

The use of tibial tuberosity-trochlear groove indices based on joint size in lower limb evaluation.

PURPOSE: The correlation between tibial tuberosity-trochlear groove distance (TT-TG) and joint size, taking into account several different parameters of knee joint size as well as lower limb dimensions, is evaluated in order to assess whether TT-TG indices should be used in instead of absolute TT-TG values. METHODS: This study comprised a retrospective analysis of knee CT scans, including 36 cases with patellofemoral instability (PFI) and 30 controls. Besides TT-TG, five measures of knee joint size were evaluated in axial CT slices: medio-lateral femur width, antero-posterior lateral condylar height, medio-lateral width of the tibia, width of the patella and the proximal-distal joint size (TT-TE). Furthermore, the length of the femur, the tibia and the total leg length were measured in the CT scanogram. Correlation analysis of TT-TG and the other parameters was done by calculating the Spearman correlation coefficient. RESULTS: In the PFI group lateral condylar height (r = 0.370), tibia width (r = 0.406) and patella width (r = 0.366) showed significant moderate correlations (p < 0.03) with TT-TG. Furthermore, we found a significant correlation between TT-TG and tibia length (r = 0.371) and total leg length (r = 381). The control group showed no significant correlation between TT-TG and knee joint size or between TT-TG and measures of lower limb length. CONCLUSIONS: Tibial tuberosity-trochlear groove distance correlates with several parameters of knee joint size and leg length in patients with patellofemoral instability. Application of indices determining TT-TG as a ratio of joint size could be helpful in establishing the indication for medial transfer of the tibial tuberosity in patients with PFI. LEVEL OF EVIDENCE: Level III.

Enzymatically Inactive Procaspase 1 stabilizes the ASC Pyroptosome and Supports Pyroptosome Spreading during Cell Division.

Caspase-1 is a key player during the initiation of pro-inflammatory innate immune responses, activating pro-IL-1ß in so-called inflammasomes. A subset of patients with recurrent febrile episodes and systemic inflammation of unknown origin harbor mutations in CASP1 encoding caspase-1. CASP1 variants result in reduced enzymatic activity of caspase-1 and impaired IL-1ß secretion. The apparent paradox of reduced IL-1ß secretion but systemic inflammation led to the hypothesis that CASP1 mutations may result in variable protein interaction clusters, thus activating alternative signaling pathways. To test this hypothesis, we established and characterized an in vitro system of transduced immortalized murine macrophages expressing either WT or enzymatically inactive (p.C284A) procaspase-1 fusion reporter proteins. Macrophages with variant p.C284A caspase-1 did not secrete IL-1ß and exhibited reduced inflammatory cell death, referred to as pyroptosis. Caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) formed cytosolic macromolecular complexes (so-called pyroptosomes) that were significantly increased in number and size in cells carrying the p.C284A caspase-1 variant compared with WT caspase-1. Furthermore, enzymatically inactive caspase-1 interacted with ASC longer and with increased intensity compared with WT caspase-1. Applying live cell imaging, we documented for the first time that pyroptosomes containing enzymatically inactive variant p.C284A caspase-1 spread during cell division. In conclusion, variant p.C284A caspase-1 stabilizes pyroptosome formation, potentially enhancing inflammation by two IL-1ß-independent mechanisms: pyroptosomes convey an enhanced inflammatory stimulus through the recruitment of additional proteins (such as RIP2, receptor interacting protein kinase 2), which is further amplified through pyroptosome and cell division.

Percutaneous tibial nerve stimulation (pTNS): success rate and the role of rectal capacity.

PURPOSE: Percutaneous tibial nerve stimulation (pTNS) was originally developed to treat urinary incontinence. Recently, some case series have also documented its success in the treatment of fecal incontinence. Nevertheless, the mechanism underlying this effect remains unknown but may be related to changes in rectal capacity. The aim of this study was to investigate the success of pTNS for the treatment of fecal urge incontinence and assess the influence of rectal capacity on treatment efficacy. METHODS: All patients undergoing pTNS for fecal incontinence between July 2009 and March 2014 were enrolled in a prospective, observational study consisting of a therapeutic regimen that lasted 9 months. Therapy success was defined as a reduction in the CCI (Cleveland Clinic incontinence) score of ≥50% and patient-reported success. Furthermore, quality of life (Rockwood's scale) and changes in anorectal physiology were recorded. RESULTS: Fifty-seven patients with fecal urge incontinence were eligible, nine of whom were excluded. The success rate was 72.5%. Incontinence events and urge symptoms were significantly reduced after 3 months and at the end of therapy. The median CCI score decreased from 12 to 4 (P < 0.0001), and the quality of life was significantly improved. However, rectal capacity was not significantly related to treatment success before or after therapy. No adverse events were observed. CONCLUSIONS: These results demonstrate that pTNS can improve the symptoms and quality of life of patients with fecal urge incontinence. However, the study fails to demonstrate a correlation between treatment success and changes in rectal capacity.

Effect of morbid obesity, gastric banding and gastric bypass on esophageal symptoms, mucosa and function.

BACKGROUND: Obesity and gastroesophageal reflux disease (GERD) are commonly associated diseases. Bariatric surgery has been shown to have various impacts on esophageal function and GERD. Our aim was to evaluate changes in symptoms, endoscopic findings, bolus passage and esophageal function in patients after primary gastric bypass surgery as compared to patients converted from gastric banding to gastric bypass. METHODS: Obese patients scheduled for laparoscopic Roux-en-Y gastric bypass (naïve-to-bypass) and patients who previously underwent gastric banding and were considered for conversion from gastric banding to gastric bypass (band-to-bypass) were included. Patients rated esophageal and epigastric symptoms (100 point VAS) and underwent upper endoscopy, impedance-manometry, and modified "timed barium swallow" before/after surgery. RESULTS: Data from 66 naïve-to-bypass patients (51/66, 77 % females, mean age 41.2 ± 11.1 years) and 68 band-to-bypass patients (53/68, 78 % females, mean age 43.8 ± 10.0 years) were available for analysis. Esophageal symptoms, esophagitis, esophageal motility abnormalities and impaired esophageal bolus transit were more common in patients that underwent gastric banding compared to those that underwent gastric bypass. The majority of symptoms, lesions and abnormalities induced by gastric banding were decreased by conversion to gastric bypass. Esophagitis was present in 28/68 (41 %) and 13/47 (28 %) patients in the band-to-bypass group, pre- versus postoperatively, respectively, (p < 0.05). The percentage of swallows with normal bolus transit increased following transformation from gastric band to gastric bypass (57.9 ± 4.1 and 83.6 ± 3.4 %, respectively, p < 0.01). CONCLUSIONS: From an esophageal perspective, gastric bypass surgery induces less motility disorders and esophageal symptoms and should be therefore favored over gastric banding in difficult to treat obese patients at risk of repeated bariatric surgery.

The Clinical Relevance of the IBD-Associated Variation within the Risk Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 2 in Patients of the Swiss IBD Cohort.

BACKGROUND/AIMS: The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) results in a dysfunctional PTPN2 protein is associated with Crohn's disease (CD) and exists in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. We investigated associations of PTPN2 SNP rs1893217 and clinical characteristics of inflammatory bowel disease (IBD) patients. METHODS: One thousand seventy three patients with CD and 734 patients with UC from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 genotypes 'homozygous wild-type' (TT), 'heterozygous' (CT) and 'homozygous variant' (CC). RESULTS: About 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. The CC-genotype was associated with the existence of gallstones in CD and pancolitis in UC patients. The presence of the C-allele (i.e. either CC or CT genotype) was associated with the onset of uveitis, but protected from aphthous oral ulcers in CD patients. UC patients carrying a C-allele were diagnosed at an older age but required intestinal surgery more often. The presence of the C-allele was associated with a successful treatment with anti-TNF antibodies in both CD and UC patients. CONCLUSION: IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course but are more likely to respond to treatment with anti-TNF antibodies. These findings demonstrate a clinical relevance of this PTPN2 risk variant in IBD patients.

The role of single-balloon colonoscopy for patients with previous incomplete standard colonoscopy: Is it worth doing it?

BACKGROUND: The rate of cecal intubation is a well-recognized quality measure of successful colonoscopy. Infrequently, the standard colonoscopy techniques fail to achieve complete examination. The role of single-balloon overtube-assisted colonoscopy (SBC) in these situations has only been sparsely studied. This prospective single-center study aimed to investigate the technical success (rate of cecal intubation) and the diagnostic gain of SBC. METHODS: The study recruited consecutive patients with previous incomplete standard colonoscopy who were admitted for SBC at our tertiary center in Eastern Switzerland between February 2008 and October 2014. The primary outcome was defined as successful cecal intubation. Data on patient characteristics, indication, technical details of procedure, and outcome were collected prospectively. The Olympus enteroscope SIF-Q180 was used. RESULTS: The study included 100 consecutive patients (median age 70 years; range 38-87 years; 54 % female) who were examined using a single-balloon overtube-assisted technique. The cecal intubation rate was 98 % (98/100). The median time of total procedure was 54 min (range 15-119 min); the median time to reach the cecal pole was 27.5 min (range 4-92 min). Passage of the sigmoid colon was not possible in two cases with a fixed, angulated sigmoid colon. The diagnostic gain was 21 % regarding adenomatous polyps in the right colon. The complication rate was 2 % (2/100, minor) without need for surgery. CONCLUSIONS: This prospective patient cohort study shows that single-balloon colonoscopy is a safe and effective procedure to achieve a complete endoscopic examination in patients with a previous failed standard colonoscopy. A significant diagnostic and therapeutic gain in the right colon justifies additional procedure time.

High Femoral Anteversion Is Related to Femoral Trochlea Dysplasia.

PURPOSE: To investigate the possible relation between femoral anteversion (AV) and trochlear morphology. METHODS: Among 560 available lower-limb computed tomography (CT) scans, those with previous fracture, arthroplasty, or osteotomy were excluded and 40 cases were randomly selected. The following 4 lines were determined from the CT scans: 1 through the center of the femoral head and neck; 1 through the lesser trochanter and the center of the femoral shaft; 1 as a tangent to the dorsal part of the distal femur, just above the gastrocnemius insertion; and 1 as a tangent to the posterior condyles. Between the respective lines, the following parameters of femoral AV were determined: (1) total AV, (2) proximal AV, (3) diaphyseal AV, and (4) distal AV. Trochlea parameters were determined from 2 separate axial CT slices (proximal trochlea and 5 mm farther distally): trochlea height (medial, central, lateral), transverse trochlea shift, trochlea depth, sulcus angle, lateral trochlea slope, and Dejour trochlea type. To prove or disprove our study hypothesis, a correlation analysis was performed between the variables of AV and trochlear morphology. RESULTS: The total AV was significantly correlated with the trochlea parameters trochlea depth (P = .032), sulcus angle (P = .05), and lateral trochlea slope (P = .001). The diaphyseal AV was significantly correlated with the sulcus angle (P = .009). The distal AV showed significant correlations with medial, central, and lateral trochlea height (.005

Functional characteristics of control adaptation in intermodal sensory processing.

The present work investigated functional characteristics of control adjustments in intermodal sensory processing. Subjects performed an interference task that involved simultaneously presented visual and auditory stimuli which were either congruent or incongruent with respect to their response mappings. In two experiments, trial-by-trial sequential congruency effects were analysed for specific conditions that allowed ruling out "non-executive" contributions of stimulus or response priming to the respective RT fluctuations. In Experiment 1, conflict adaptation was observed in an oddball condition in which interference emanates from a task-irrelevant and response-neutral low-frequency stimulus. This finding characterizes intermodal control adjustments to be based - at least partly - on increased sensory selectivity, which is able to improve performance in any kind of interference condition which shares the same or overlapping attentional requirements. In order to further specify this attentional mechanism, Experiment 2 defined analogous conflict adaptation effects in non-interference unimodal trials in which just one of the two stimulus modalities was presented. Conflict adaptation effects in unimodal trials exclusively occurred for unimodal task-switch trials but not for otherwise equivalent task repetition trials, which suggests that the observed conflict-triggered control adjustments mainly consist of increased distractor inhibition (i.e., down-regulation of task-irrelevant information), while attributing a negligible role to target amplification (i.e., enhancement of task-relevant information) in this setup. This behavioral study yields a promising operational basis for subsequent neuroimaging investigations to define brain activations and connectivities which underlie the adaptive control of attentional selection.

Patients' perceptions on the impact of coffee consumption in inflammatory bowel disease: friend or foe?--a patient survey.

BACKGROUND: Environmental factors are an integral component in the pathogenesis of inflammatory bowel disease (IBD). There is an increasing interest in nutritive components. While the potential disease-modifying role of coffee has been intensively investigated in a variety of gastrointestinal diseases, the data on the potential impact on IBD is very limited. We aimed to determine the patients' perspective on coffee consumption in IBD. METHODS: We conducted a questionnaire among IBD patients in Switzerland, assessing key questions regarding coffee consumption. Descriptive statistics including chi square testing were used for analysis of questionnaire data. RESULTS: Among a total of 442 patients 73% regularly consume coffee. 96% of patients attributing a positive and 91% of patients attributing no impact of coffee intake on IBD regularly drink coffee and surprisingly even 49% of those patients that assign a negative impact on disease symptoms. Among those patients refraining from regular coffee intake 62% are convinced that coffee adversely influences intestinal symptoms, significantly more in Crohn's disease (CD) than in ulcerative colitis (UC) (76% vs. 44%, p = 0.002). In total, 38% of all study subjects suppose that coffee has an effect on their symptoms of disease, significantly more in CD (54%) compared to UC patients (22%, p < 0.001). Moreover, while 45% of CD patients feel that coffee has a detrimental influence, only 20% of UC patients share this impression (p < 0.001). CONCLUSION: Two thirds of IBD patients regularly consume coffee. More than twice as many CD compared to UC patients attribute a symptom-modifying effect of coffee consumption, the majority a detrimental one. However, this negative perception does not result in abstinence from coffee consumption.

Acute pancreatitis caused by gastric balloon: a case report.

Background: Intragastric balloon (IGB) insertion is a safe and effective method for the treatment of obesity. The most common side effects of the balloon-therapy are nausea/vomiting and abdominal pain, acute pancreatitis has rarely been reported. Case Description: We present the case of a 28-year-old woman who underwent IGB insertion 9 months before onset of intense upper abdominal pain. We confirmed the diagnosis of acute pancreatitis by means of clinical symptoms, serological tests and cross-sectional imaging. Endoscopic removal of the balloon led to a complete resolution of the symptoms. Initial laboratory parameters were normal on admission, only the control of lipase and amylase levels led us to the diagnosis of pancreatitis. On imaging with computed tomography, the filling catheter of the balloon showed to be dislodged in the duodenum. After carrying out a systematic approach, other causes of pancreatitis were ruled out. Conclusions: Laboratory tests including amylase/lipase and adequate imaging should be considered in patients with relevant symptoms after gastric balloon insertion. A possible pathogenesis may be the direct compression and traumatic effect on the pancreas by the balloon or the dislodgement of the catheter into the duodenum and an obstruction/compression of the Papilla. Endoscopic removal of the balloon is not mandatory in every case, it should be decided individually.