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[english] Objective: In 1998 an international contest for medical students called “Benjamin Franklin Contest” was initiated by the former university hospital of Freie Universität Berlin on the occasion of the 30th anniversary of its foundation in 1968. Since then, seven teams from Germany, Austria, and Switzerland have been competing against each other every year. Five medical students per team match up in paper cases, diagnosis of medical images, multiple choice tests, and practical skills.Methods: All participants of the 11th Benjamin Franklin Contest (2009) were asked about their motivation, preparation strategy, and experience with the contest. Results: In total 92% (32 of 35) participated in the evaluation study. We show that improvement of medical knowledge is one of the key motivating factors behind participation in the competition. The teams were trained by self-study, tutorials, and learning groups. Remarkably, students invested 54.2 hours (SD 32 hours) of their free time to prepare for the contest. Conclusions: The Benjamin Franklin Contest is an innovative approach to facilitate self-directed learning and develope medical competencies. [german] Zielsetzung: Im Jahr 1998 wurde am damaligen Universitätsklinikum Benjamin Franklin der Freien Universität (FU) in Berlin der internationale Medizinstudierendenwettbewerb „Benjamin Franklin Contest“ (BFC) initiiert. Anlass war damals der 30. Jahrestag der Gründung der Universitätsmedizin an der FU. Seitdem findet jedes Jahr ein Wettbewerb zwischen sieben Teams von medizinischen Fakultäten aus Deutschland, Österreich und der Schweiz statt. Jeweils fünf Studierende messen sich in den Kategorien Papierfälle, Blickdiagnosen, Auswahlfragen und praktische Fähigkeiten.Methodik: Ziel dieser Arbeit ist die Beschreibung des Projektes BFC und eine erste Evaluation der Erfahrung von Teilnehmenden. Dazu wurden alle Teilnehmenden des 11. BFC (2009) mittels eines selbst entwickelten Fragebogens hinsichtlich ihrer Motivation, Art und Aufwand der eigenen Vorbereitung und der Erfahrung mit dem Wettbewerb befragt. Ergebnisse: Insgesamt beteiligten sich 92% (32/35) der Teilnehmenden im Jahr 2009 an der Evaluation des Wettbewerbs. Es zeigte sich, dass die Erweiterung medizinischen Wissens zu den Hauptmotiven für eine Teilnahme am BFC gehört. Zur Vorbereitung auf den Wettbewerb wurden neben dem Selbststudium insbesondere Tutorien und Lerngruppen eingesetzt. Der Aufwand lag bei durchschnittlich 54,2 Stunden (Standardabweichung 32 Stunden). Schlussfolgerungen: Das Konzept des BFC kann als innovativer Ansatz selbstmotivierten Lernens verstanden werden. Die Teilnahme am BFC hat das Potential, neben medizinischen Kompetenzen auch die Fähigkeit zur Teamarbeit zu fördern.

Magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are complementary imaging techniques that detect disease based on viscoelasticity and water mobility, respectively. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering the clinical translation of combined DWI-MRE markers. We used DWI-MRE to study 129 biomaterial samples including native and cross-linked collagen, glycosaminoglycans (GAGs) with different sulfation levels, and decellularized specimens of pancreas and liver, all with different proportions of solid tissue, or solid fractions. We developed a theoretical framework of the relationship between mechanical loss and tissue-water mobility based on two parameters, solid and fluid viscosity. These parameters revealed distinct DWI-MRE property clusters characterizing weak, moderate, and strong water-network interactions. Sparse networks interacting weakly with water, such as collagen or diluted decellularized tissue, resulted in marginal changes in water diffusion over increasing solid viscosity. In contrast, dense networks with larger solid fractions exhibited both free and hindered water diffusion depending on the polarity of the solid components. For example, polar and highly sulfated GAGs as well as native soft tissues hindered water diffusion despite relatively low solid viscosity. Our results suggest that two fundamental properties of tissue networks, solid fraction and network polarity, critically influence solid and fluid viscosity in biological tissues. Since clinical DWI and MRE are sensitive to these viscosity parameters, the framework we present here can be used to detect tissue remodeling and architectural changes in the setting of diagnostic imaging. The viscoelastic properties of biological tissues provide a wealth of information on the vital state of cells and host matrix. Combined measurement of viscoelasticity and water diffusion by medical imaging is sensitive to tissue microarchitecture. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering full exploitation of these properties as a combined clinical biomarker. Therefore, we analyzed the parameter space accessible by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) and developed a theoretical framework for the relationship between water mobility and mechanical parameters in biomaterials. Our theory of solid material properties related to particle motion can be translated to clinical radiology using clinically established MRE and DWI. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Radiographic axial spondyloarthritis (r-axSpA), formerly known as ankylosing spondylitis (AS), is a chronic, inflammatory rheumatic disease associated with symptoms such as inflammatory back pain, morning stiffness, and arthritis. First-line recommendations for patients with AS include treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for reducing pain and stiffness. Objectives: The objective of our study is to evaluate the efficacy and short-term NSAID-sparing effect of secukinumab in patients with AS currently treated with NSAIDs. Design: We assessed the clinical Assessment of SpondyloArthritis International Society (ASAS20) response to secukinumab and evaluated the extent to which the use of concomitant NSAID can be reduced between weeks 4 and 12 in r-axSpA patients treated with secukinumab 150 mg compared with placebo. Methods: ASTRUM was a prospective 24-week randomized controlled trial of adult patients with active r-axSpA [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ⩾4] who had a documented inadequate response to ⩾2 NSAIDs. Patients were randomized (1:1:1) to initiate treatment with subcutaneous secukinumab 150 mg from either week 0 (group 1), week 4 (group 2), or week 16 (group 3). From week 4 onward, tapering of NSAIDs was allowed in all groups. Results: This study included 211 patients (n = 71, 70, and 70 in groups 1, 2, and 3, respectively). ASAS20 response at week 12 for pooled groups 1 and 2 versus group 3 was 51.1% versus 44.3% (p = 0.35). A higher proportion of patients in groups 1 and 2 achieved ASAS40 and BASDAI50 and showed improvements in other secondary clinical outcomes as compared to group 3 at week 16. More patients in groups 1 and 2 versus group 3 stopped their NSAID intake from baseline through week 16. Conclusion: Treatment with secukinumab improved clinical outcomes and showed a short-term NSAID-sparing effect in patients with r-axSpA, even though the primary endpoint was not met. Trial registration: ClinicalTrials.gov; NCT02763046, EudraCT 2015-004575-74. [ABSTRACT FROM AUTHOR]

Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab. Risk of infection in patients with spondyloarthritis and ankylosing spondylitis receiving antitumor necrosis factor therapy: a meta-analysis of randomized controlled trials. Moreover, when ax-SpA patients are in remission for 48 weeks, dose reduction seems to be acceptable with limited adverse events for most patients,[31] but complete discontinuation of TNF inhibitor treatments would increase the risk of flare-up significantly. Clinical response, drug survival and predictors thereof in 432 ankylosing spondylitis patients after switching tumour necrosis factor alpha inhibitor therapy: results from the Danish nationwide DANBIO registry. [Extracted from the article]

Chronic kidney disease (CKD) is characterized by structural changes, such as tubular atrophy, renal fibrosis, and glomerulosclerosis, all of which affect the viscoelastic properties of biological tissues. However, detection of renal viscoelasticity changes because diagnostic markers by in vivo elastography lack histopathological validation through animal models. Therefore, we investigated in vivo multiparametric magnetic resonance imaging (mp‐MRI), including multifrequency magnetic resonance elastography‐based tomoelastography, in the kidneys of 10 rats with adenine‐induced CKD and eight healthy controls. Kidney volume (in mm3), water diffusivity (apparent diffusion coefficient [ADC] in mm2/s), shear wave speed (SWS; in m/s; related to stiffness), and wave penetration rate (PR; in m/s; related to inverse viscosity) were quantified by mp‐MRI and correlated with histopathologically determined renal fibrosis (collagen area fraction [CAF]; in %). Kidney volume (40% ± 29%, p = 0.009), SWS (11% ± 12%, p = 0.016), and PR (20% ± 15%, p = 0.004) were significantly increased in CKD, which was accompanied by ADC (−24% ± 27%, p = 0.02). SWS, PR, and ADC were correlated with CAF with R = 0.63, 0.75, and −0.5 (all p < 0.05), respectively. In the CKD rats, histopathology showed tubule dilation due to adenine crystal deposition. Collectively, our results suggest that collagen accumulation during CKD progression transforms soft‐compliant renal tissue into a more rigid‐solid state with reduced water mobility. We hypothesized that tubule dilation—a specific feature of our model—might lead to higher intraluminal pressure, which could also contribute to elevated renal stiffness. Tomoelastography is a promising tool for noninvasively assessing disease progression, detecting biomechanical properties that are sensitive to different pathologic features of CKD. [ABSTRACT FROM AUTHOR]

The liver is a highly vascularized organ where fluid properties, including vascular pressure, vessel integrity and fluid viscosity, play a critical role in gross mechanical properties. To study the effects of portal pressure, liver confinement, fluid viscosity, and tissue crosslinking on liver stiffness, water diffusion, and vessel size, we applied multiparametric magnetic resonance imaging (mpMRI), including multifrequency magnetic resonance elastography (MRE) and apparent diffusion coefficient (ADC) measurements, to ex vivo livers from healthy male rats (13.6±1.6 weeks) at room temperature. Four scenarios including altered liver confinement, tissue crosslinking, and vascular fluid viscosity were investigated with mpMRI at different portal pressure levels (0-17.5 cmH 2 O). Our experiments demonstrated that, with increasing portal pressure, rat livers showed higher water content, water diffusivity, and increased vessel sizes quantified by the vessel tissue volume fraction (VTVF). These effects were most pronounced in native, unconfined livers (VTVF: 300±120%, p <0.05, ADC: 88±29%, p <0.01), while still significant under confinement (confined: VTVF: 53±32%, p <0.01, ADC: 28±19%, p <0.05; confined-fixed: VTVF: 52±20%, p<0.001, ADC: 11±2%, p <0.01; confined-viscous: VTVF: 210±110%, p <0.01, ADC: 26±9%, p <0.001). Softening with elevated portal pressure (-12±5, p <0.05) occurred regardless of confinement and fixation. However, the liver stiffened when exposed to a more viscous inflow fluid (11±4%, p <0.001). Taken together, our results elucidate the complex relationship between macroscopic-biophysical parameters of liver tissue measured by mpMRI and vascular-fluid properties. Influenced by portal pressure, vascular permeability, and matrix crosslinking, liver stiffness is sensitive to intrinsic poroelastic properties, which, alongside vascular architecture and water diffusivity, may aid in the differential diagnosis of liver disease. Using highly controllable ex vivo rat liver phantoms, hepatic biophysical properties such as tissue-vascular structure, stiffness, and water diffusivity were investigated using multiparametric MRI including multifrequency magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI). Through elaborate tuning of the experimental conditions such as the static portal pressure, flow viscosity, amount and distribution of fluid content in the liver, we identified the contributions of the fluid component to the overall imaging-based biophysical properties of the liver. Our finding demonstrated the sensitivity of liver stiffness to the hepatic poroelastic properties, which may aid in the differential diagnosis of liver diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Cancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increased stiffness has been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissue fluidization, where portions of the tissue can change position across different length scales. Supported by tabletop magnetic resonance elastography (MRE) on stroma mimicking collagen gels and microscopic analysis of live cells inside patient derived tumor explants, an overview is provided of how cancer associated mechanisms, including cellular unjamming, proliferation, microenvironment composition, and remodeling can alter a tissue's fluidity and stiffness. In vivo, state‐of‐the‐art multifrequency MRE can distinguish tumors from their surrounding host tissue by their rheological fingerprints. Most importantly, a meta‐analysis on the currently available clinical studies is conducted and universal trends are identified. The results and conclusions are condensed into a gedankenexperiment about how a tumor can grow and eventually metastasize into its environment from a physics perspective to deduce corresponding mechanical properties. Based on stiffness, fluidity, spatial heterogeneity, and texture of the tumor front a roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented. [ABSTRACT FROM AUTHOR]

Background: Previous experiences with non-medical switching of adalimumab (ADA) in patients with chronic inflammatory rheumatic diseases (CIRD) come mainly from phase III extension of randomised clinical trials and little from routine care. Objectives: To analyse treatment trajectories over 2 years in patients with CIRD conducting a non-medical switch from originator to biosimilar ADA. Design: A retrospective observational cohort study was conducted with data from a third-level rheumatology centre in Germany. CIRD patients on originator ADA who switched to ADA biosimilar from October 2018 onwards were identified and followed until September 2020. Methods: Patients' characteristics were compared between the four a priori defined treatment trajectories 'continued biosimilar ADA therapy', 'back-switch to originator ADA therapy', 'switch to another biological disease-modifying anti-rheumatic drug (bDMARD) therapy' and 'stopped bDMARD therapy/death/drop out'. Factors associated with continuing biosimilar ADA therapy were analysed using Cox proportional hazards regression analyses. Results: A total of 121 CIRD patients were included. Most patients (66.9%) continued therapy with biosimilar ADA over 2 years, with a treatment retention rate of 73.1%. Whereas 21 patients (17.4%) switched back to originator ADA, mainly due to adverse events, and 8 patients (6.6%) switched to a different bDMARD, mainly due to lack of effect. The estimated risk of withdrawal was lower for longer prior duration on originator ADA [hazard ratio (HR): 0.82; 95% CI: 0.69–0.97] and higher for higher C-reactive protein levels at baseline (HR: 1.18; 95% CI: 1.00–1.39). Male patients, older patients and those for whom originator ADA was their first bDMARD tended to have a lower risk of withdrawal. Conclusion: Our results indicated that three of four patients continue biosimilar ADA over 2 years with lower risks of withdrawal for male sex, older age, longer prior duration on originator ADA and originator ADA as first bDMARD. [ABSTRACT FROM AUTHOR]