Ulrike Grittner

US-based Real-time Elastography for the Detection of Fibrotic Gut Tissue in Patients with Stricturing Crohn Disease

PURPOSEnTo assess whether ultrasonography (US)-based real-time elastography (RTE) can be used to detect gut fibrosis.nnnMATERIALS AND METHODSnIn this institutional review board-approved, prospective, proof-of-concept study, unaffected and affected gut segments in 10 patients with Crohn disease (four women, six men; median age, 49 years) were examined pre-, intra-, and postoperatively with US, including RTE to assess strain. Disease activity was scored by using the Limberg index on the basis of (a) bowel wall thickness and (b) size and extent of Doppler signal. After surgical resection, strain of full gut wall segments was measured with direct tensiometry. Gut wall layers, fibrosis, and collagen content were quantified histologically. Aggregated data per patient, disease status, and available measurements were assessed with mixed-effects models.nnnRESULTSnUnaffected versus affected gut segments yielded higher RTE (mean ± standard deviation, 169.0 ± 27.9 vs 43.0 ± 25.9, respectively) and tensiometry (mean, 77.1 ± 21.4 vs 13.3 ± 11.2, respectively) values used to assess strain (both P < .001). There was good correlation between pre-, intra-, and postoperative RTE values of unaffected (intraclass correlation coefficient, 0.572) and affected (intraclass correlation coefficient, 0.830) segments. RTE was not associated with pre- or intraoperative Limberg scores (median, 1 vs 2; P = .255 and .382, respectively). Affected internal (median, 2011 vs 1363 μm; P = .011) and external (median, 929 vs 632 μm; P = .013) muscularis propria, serosa (median, 245 vs 64 μm; P = .019), and muscularis mucosae (median, 451 vs 80 μm; P = .031) were wider than unaffected segments. Width differences of internal muscularis propria and mucularis mucosae were associated with RTE-assessed strain (P = .044 and .012, respectively) and tensiometry-assessed strain (P = .006 and .014, respectively). Masson trichrome (median, 4 vs 0; P < .001) and elastica-van Gieson (median, 805 346 μm(2) vs 410 649 μm(2); P < .001) stains and western blotting (median, 2.01 vs 0.87; P = .009) demonstrated a higher collagen content in affected versus unaffected segments and were associated with RTE-assessed strain (both P < .001) and tensiometry-assessed strain (P < .001 and 0.025, respectively).nnnCONCLUSIONnRTE can be used to detect fibrosis in human Crohn disease. Online supplemental material is available for this article.

Frequency, phenotype, outcome, and therapeutic impact of skin reactions following initiation of adalimumab therapy: Experience from a consecutive cohort of inflammatory bowel disease patients

Background: The monoclonal anti tumor necrosis factor (TNF) antibody adalimumab has recently been approved for Crohns disease (CD) and evaluated for ulcerative colitis (UC). Cutaneous lesions associated with its administration have not been prospectively studied in inflammatory bowel disease (IBD). Methods: We evaluated the first 50 consecutive patients (female n = 30, median age 32½ years, interquartile range [IQR 27–46]) with CD (n = 46) and UC (n = 4) who received adalimumab (82% induction with 160/80 and 94% maintenance with 40 mg subcutaneously biweekly) at our center and were followed up for a median of 17 months [IQR 12–21]. The Kaplan–Meier method was used to estimate skin reaction free survival (SRFS) and Fishers exact test to examine contingency between demographic variables and outcomes. Results: Sixty‐two percent of all patients developed a dermatological reaction (eczema [n = 9], acne‐like dermatitis [n = 9], psoriasis‐like lesions [n = 6], localized erythema and swelling at injection site [n = 1], dermatitis sicca [n = 1], rosacea [n = 1], prurigo simplex [n = 1], tinea [n = 1], localized herpes simplex [n = 1], and candida [n = 1] infections) that resolved in 12% at follow‐up. SRFS was 12 months [IQR 30–5]. Adalimumab was discontinued in 22% of all patients. Longer disease duration, a lower dose induction schedule, as well as concomitant use of steroids or immunosuppressants were more often associated with an unfavorable skin outcome. Skin outcomes differed significantly between patients who saw a dermatologist (P = 0.022) and/or had a dermatological intervention (P = 0.012). Conclusions: A broad spectrum of adverse cutaneous reactions occurs more frequently and later in adalimumab therapy for IBD compared with other indications. Consultation with a dermatologist is highly recommended.

Tablet computer enhanced training improves internal medicine exam performance

Background Traditional teaching concepts in medical education do not take full advantage of current information technology. We aimed to objectively determine the impact of Tablet PC enhanced training on learning experience and MKSAP® (medical knowledge self-assessment program) exam performance. Methods In this single center, prospective, controlled study final year medical students and medical residents doing an inpatient service rotation were alternatingly assigned to either the active test (Tablet PC with custom multimedia education software package) or traditional education (control) group, respectively. All completed an extensive questionnaire to collect their socio-demographic data, evaluate educational status, computer affinity and skills, problem solving, eLearning knowledge and self-rated medical knowledge. Both groups were MKSAP® tested at the beginning and the end of their rotation. The MKSAP® score at the final exam was the primary endpoint. Results Data of 55 (tablet n = 24, controls n = 31) male 36.4%, median age 28 years, 65.5% students, were evaluable. The mean MKSAP® score improved in the tablet PC (score Δ + 8 SD: 11), but not the control group (score Δ- 7, SD: 11), respectively. After adjustment for baseline score and confounders the Tablet PC group showed on average 11% better MKSAP® test results compared to the control group (p<0.001). The most commonly used resources for medical problem solving were journal articles looked up on PubMed or Google®, and books. Conclusions Our study provides evidence, that tablet computer based integrated training and clinical practice enhances medical education and exam performance. Larger, multicenter trials are required to independently validate our data. Residency and fellowship directors are encouraged to consider adding portable computer devices, multimedia content and introduce blended learning to their respective training programs.

Combining viscoelasticity, diffusivity and volume of the hippocampus for the diagnosis of Alzheimer's disease based on magnetic resonance imaging

Dementia due to Alzheimers Disease (AD) is a neurodegenerative disease for which treatment strategies at an early stage are of great clinical importance. So far, there is still a lack of non-invasive diagnostic tools to sensitively detect AD in early stages and to predict individual disease progression. Magnetic resonance elastography (MRE) of the brain may be a promising novel tool. In this proof-of-concept study, we investigated whether multifrequency-MRE (MMRE) can detect differences in hippocampal stiffness between patients with clinical diagnosis of dementia due to AD and healthy controls (HC). Further, we analyzed if the combination of three MRI-derived parameters, i.e., hippocampal stiffness, hippocampal volume and mean diffusivity (MD), improves diagnostic accuracy. Diagnostic criteria for probable dementia due to AD were in line with the NINCDS-ADRDA criteria and were verified through history-taking (patient and informant), neuropsychological testing, routine blood results and routine MRI to exclude other medical causes of a cognitive decline. 21 AD patients and 21 HC (median age 75 years) underwent MMRE and structural MRI, from which hippocampal volume and MD were calculated. From the MMRE-images maps of the magnitude |G*| and phase angle φ of the complex shear modulus were reconstructed using multifrequency inversion. Median values of |G*| and φ were extracted within three regions of interest (hippocampus, thalamus and whole brain white matter). To test the predictive value of the main outcome parameters, we performed receiver operating characteristic (ROC) curve analyses. Hippocampal stiffness (|G*|) and viscosity (φ) were significantly lower in the patient group (both p < 0.001). ROC curve analyses showed an area under the curve (AUC) for | G*| of 0.81 [95%CI 0.68–0.94]; with sensitivity 86%, specificity 67% for cutoff at |G*| = 980 Pa) and for φ an AUC of 0.79 [95%CI 0.66–0.93]. In comparison, the AUC of MD and hippocampal volume were 0.83 [95%CI 0.71–0.95] and 0.86 [95%CI 0.74–0.97], respectively. A combined ROC curve of |G*|, MD and hippocampal volume yielded a significantly improved AUC of 0.90 [95%CI 0.81–0.99]. In conclusion, we demonstrated reduced hippocampal stiffness and reduced hippocampal viscosity, as determined by MMRE, in patients with clinical diagnosis of dementia of the AD type. Diagnostic sensitivity was further improved by the combination with two other MRI-based hippocampal parameters. These findings motivate further investigation whether MMRE can detect decreased brain stiffness already in pre-dementia stages, and whether these changes predict cognitive decline.

Tablet computer-based multimedia enhanced medical training improves performance in gastroenterology and endoscopy board style exam compared with traditional medical education

We read with interest the paper by Ekkelenkamp et al ,1 who found that the early use of validated simulators during endoscopy training expedites the learning of procedural skills.nnIndeed, traditional teaching concepts do not take full advantage of advanced technology. We therefore prospectively investigated the impact of our self-developed custom wireless-enabled tablet PC-based multimedia training and test system on gastrointestinal endoscopy self-assessment program (GESAP®) exam performance. Control and the tablet groups were tested at the beginning and the end of their rotation by administration of all 200 random generator selected, equally distributed questions from all 11 categories (biliary, colorectal, oesophagus, intestines, nutrition, pancreas, patient preparation, paediatrics, surgery) parsed from the current GESAP® pool.nnMedical students and residents doing an inpatient service rotation were alternatingly assigned to either the active test (tablet PC) or traditional education (control) group, respectively. The multimedia training package included access to the institutional collaborative online course management systems (Moodle and Blackboard), eBooks, eJournals, educational slide kits, podcasts, videos, animations, images from major biomedical and scientific publishers or professional societies, as well as twitter …

Real-life clinical data for dexamethasone and ranibizumab in the treatment of branch or central retinal vein occlusion over a period of six months

PurposeTo evaluate the therapeutic outcome for dexamethasone implant (DEX) or intravitreal ranibizumab (IVR) injections over 6xa0months in patients with macular edema due to branch or central retinal vein occlusion (BRVO, CRVO), in a real-life setting.MethodsA total of 107 patients with BRVO or CRVO were included into this retrospective single-center observational study. Patients were treated with monotherapy consisting of DEX or three monthly IVR injections following a pro re nata regimen (PRN). Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP) were compared between the two therapy groups after 1, 3 and 6xa0months.ResultsBRVO patients treated with DEX achieved a statistically significant gain in BCVA measured in logMAR after 1xa0month (mean gain, 95% CI: 0.21, 0.08–0.34, pu2009=u20090.001), 3xa0months (0.16, 0.03–0.28, pu2009=u20090.012) and 6xa0months (0.19, 0.07–0.32, pu2009=u20090.002), whereas patients treated with IVR showed a statistically significant BCVA gain in month 3 (mean improvement, 95% CI: 0.13, 0.01–0.26, pu2009=u20090.039) and month 6 (0.16, 0.03–0.29, pu2009=u20090.018). BCVA in CRVO patients with DEX worsened slightly at month 6 (mean worsening, 95% CI: −0.08, −0.24 to 0.08, pu2009=u20090.305), while IVR treated-patients achieved a statistically significant BCVA gain at 3xa0months (mean improvement, 95% CI: 0.14, 0.02–0.25, pu2009=u20090.021). Both therapies were accompanied by statistically significant CRT reductions of 150 to 200xa0μm (median). Adverse events reported were predictable and limited.ConclusionsIn a clinical setting, comparable improvement in BCVA and CRT were observed after DEX and IVR injections for treatment of BRVO. CRVO patients showed greater benefit with IVR.

No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults

Object-location memory (OLM) is known to decline with normal aging, a process accelerated in pathological conditions like mild cognitive impairment (MCI). In order to maintain cognitive health and to delay the transition from healthy to pathological conditions, novel strategies are being explored. Tentative evidence suggests that combining cognitive training and anodal transcranial direct current stimulation (atDCS), both reported to induce small and often inconsistent behavioral improvements, could generate larger or more consistent improvements or both, compared to each intervention alone. Here, we explored the combined efficacy of these techniques on OLM. In a subject-blind sham-controlled cross-over design 32 healthy older adults underwent a 3-day visuospatial training paired with either anodal (20 min) or sham (30 s) atDCS (1 mA, temporoparietal). Subjects were asked to learn the correct object-location pairings on a street map, shown over five learning blocks on each training day. Acquisition performance was assessed by accuracy on a given learning block in terms of percentage of correct responses. Training success (performance on last training day) and delayed memory after 1-month were analyzed by mixed model analysis and were controlled for gender, age, education, sequence of stimulation and baseline performance. Exploratory analysis of atDCS effects on within-session (online) and between-session (offline) memory performance were conducted. Moreover, transfer effects on similar trained (visuospatial) and less similar (visuo-constructive, verbal) untrained memory tasks were explored, both immediately after training, and on follow-up. We found that atDCS paired with OLM-training did not enhance success in training or performance in 1-month delayed memory or transfer tasks. In sum, this study did not support the notion that the combined atDCS-training approach improves immediate or delayed OLM in older adults. However, specifics of the experimental design, and a non-optimal timing of atDCS between sessions might have masked beneficial effects and should be more systematically addressed in future studies.

The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial

INTRODUCTIONnNutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine supplementation on memory performance in older adults at risk for the development of Alzheimers disease.nnnMETHODSnCognitively intact participants with subjective cognitive decline (nxa0=xa030, 60-80 years of age) were included in this three-months, randomized, placebo-controlled, double-blind Phase IIa pilot trial with a spermidine-rich plant extract supplement. Effects of intervention were assessed using the behavioral mnemonic similarity task, measured at baseline and post-intervention visits. Data analysis was focused on reporting and interpreting effectiveness based on effect sizes.nnnRESULTSnMemory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention [contrast meanxa0=xa0.17, 95% confidence interval (CI): -.01, .35, Cohens dxa0=xa0.77, 95% CI: 0, 1.53]. Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean differencexa0=xa0-.11, 95% CI: -.19, -.03, Cohens dxa0=xa0.79, 95% CI: .01, 1.55). A similar effect was not found in the placebo-treated group (mean differencexa0=xa0.07, 95% CI: -.13, .27, Cohens dxa0=xa0-.20, 95% CI: -.94, .54).nnnDISCUSSIONnIn this pilot trial, nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. The beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system. A follow-up Phase IIb randomized controlled trial will help validate the therapeutic potential of spermidine supplementation and delineate possible neurophysiological mechanisms of action.nnnTRIAL REGISTRATIONnRegistered in ClinicalTrials.gov with the Identifier NCT02755246.