From amaurotic idiocy to biochemically defined lipid storage diseases: the first identification of GM1-Gangliosidosis

On February 23rd 1936, a boy-child (“Kn”) died in an asylum near Munich after years of severe congenital dis-ease, which had profoundly impaired his development leading to inability to walk, talk and see as well as to severe epilepsy. While a diagnosis of “Little’s disease” was made during life, his postmortem brain investiga-tion at Munich neuropathology (“Deutsche Forschungsanstalt für Psychiatrie”) revealed the diagnosis of “amaurotic idiocy” (AI). AI, as exemplified by Tay-Sachs-Disease (TSD), back then was not yet understood as a specific inborn error of metabolism encompassing several disease entities. Many neuropathological studies were performed on AI, but the underlying processes could only be revealed by new scientific techniques such as biochemical analysis of nervous tissue, deciphering AI as nervous system lipid storage diseases, e.g. GM2-gangliosidosis. In 1963, Sandhoff & Jatzkewitz published an article on a “biochemically special form of AI” reporting striking differences when comparing their biochemical observations of hallmark features of TSD to tissue composition in a single case: the boy Kn. This was the first description of “GM1-Gangliosidosis”, later understood as resulting from genetically determined deficiency in beta-galactosidase. Here we present illus-trative materials from this historic patient, including selected diagnostic slides from the case “Kn” in virtual microscopy, original records and other illustrative material available. Finally, we present results from genetic analysis performed on archived tissue proving beta-galactosidase-gene mutation, verifying the 1963 interpre-tation as correct. This synopsis shall give a first-hand impression of this milestone finding in neuropathology

Characterization and Application of a Disposable Rotating BedBioreactor for Mesenchymal Stem Cell Expansion

Recruitment of mesenchymal stromal cells (MSC) into the field of tissue engineering is a promising development since these cells can be expanded vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into various cell lineages. Safety requirements and the necessity to obtain high cell numbers without frequent subcultivation of cells raised the question of the possibility of expanding MSC in one-way (single-use) disposable bioreactors. In this study, umbilical cord-derived MSC (UC-MSC) were expanded in a disposable Z 2000 H bioreactor under dynamic conditions. Z was characterized regarding residence time and mixing in order to evaluate the optimal bioreactor settings, enabling optimal mass transfer in the absence of shear stress, allowing an reproducible expansion of MSC, while maintaining their stemness properties. Culture of the UC-MSC in disposable Z 2000 H bioreactor resulted in a reproducible 8-fold increase of cell numbers after 5 days. Cells were shown to maintain specific MSC surface marker expression as well as trilineage differentiation potential and lack stress-induced premature senescence

Training in shared decision-making for registered nurses taking a master’s degree and/or a postgraduate programme

Background: Registered nurses play a decisive role in supporting patients to participate in decisions on their own health, also referred to as shared decision-making. Official recommendations and up-to-date knowledge demonstrate that, although shared decision-making is necessary for patients, there are few training programmes within or outside the education system that can meet this need for competence. Objective: To gain insight into how RNs taking a master’s degree and/or a postgraduate programme respond to a three-hour training module in SDM and decision coaching, and how students perceive the effect on learning. We also wanted to identify possible barriers and facilitators in relation to the use of decision coaching. Method: We used a multi-method research design based on Kirkpatrick’s four-step model for evaluating training interventions. We reported on the first two levels – reaction and learning – using a questionnaire to assess how students reacted to and learned from the training. The quantitative data were analysed using descriptive statistics, but we analysed the free-text questions using qualitative content analysis. Results: Eighty-two registered nurses taking a master’s degree and/or a postgraduate programme in cancer nursing or nephrology nursing participated in the course, and 76 of them consented to take part in the study. The registered nurses reported that the teaching was useful for clinical practice and recommended it to others. They also wanted more skills training in order to increase their competence in shared decision-making. They highlighted the ‘Six steps to shared decision-making’ in addition to role play and exercises as among the most useful elements of the training. A broad spectrum of barriers and facilitators across individual, organisational and systemic levels were reported. Conclusion: The study shows that the registered nurses found that the training provided them with relevant knowledge that they could use in their daily work in order to promote the development of knowledge about the shared decision-making process. Further training is both desirable and necessary in order to increase registered nurses’ self-confidence and skills in practising decision coaching

The incidence of eosinophilic oesophagitis in 2007-2017 among children in North Denmark Region is lower than expected

BACKGROUND: In North Denmark Region (NDR), the incidence of Eosinophilic Oesophagitis (EoE) among adults has increased following a new biopsy protocol in 2011, whereas data on the incidence of EoE among children is lacking. AIMS: To describe the incidence of EoE in children aged 0–17 in NDR as well as diagnostic delay, clinical manifestations, treatment and complications. METHODS: This retrospective, register-based DanEoE cohort study included 18 children diagnosed with EoE between 2007–2017 in NDR. Medical files were reviewed with attention to symptoms, reason for referral, disease progress, treatment, symptomatic and histological remission as well as diagnostic delay. RESULTS: The median incidence per year (2007–2017) was 0.86/100,000 children in NDR aged 0–17 years. The median diagnostic delay among children was four years and six months. Sixty percent presented with food impaction at first hospital visit. After initial treatment, only one of 18 children achieved symptomatic and histologic remission and had a long-term treatment plan. CONCLUSIONS: The calculated incidence among children was lower compared to similar studies. Combined with poor remission rates and lack of follow-up, it is likely that EoE is an underdiagnosed and insufficiently treated disease among children in NDR. Our findings suggest that more knowledge concerning EoE in children could lead to a higher incidence, shorter diagnostic delay and more effective treatment

Evaluator-blinded trial evaluating nurse-led immunotherapy DEcision Coaching In persons with relapsing-remitting Multiple Sclerosis (DECIMS) and accompanying process evaluation: Study protocol for a cluster randomised controlled trial

License:Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)Background: Multiple sclerosis is a chronic neurological condition usually starting in early adulthood and regularly leading to severe disability. Immunotherapy options are growing in number and complexity, while costs of treatments are high and adherence rates remain low. Therefore, treatment decision-making has become more complex for patients. Structured decision coaching, based on the principles of evidence-based patient information and shared decision-making, has the potential to facilitate participation of individuals in the decision-making process. This cluster randomised controlled trial follows the assumption that decision coaching by trained nurses, using evidence-based patient information and preference elicitation, will facilitate informed choices and induce higher decision quality, as well as better decisional adherence. Methods/Design: The decision coaching programme will be evaluated through an evaluator-blinded superiority cluster randomised controlled trial, including 300 patients with suspected or definite relapsing-remitting multiple sclerosis, facing an immunotherapy decision. The clusters are 12 multiple sclerosis outpatient clinics in Germany. Further, the trial will be accompanied by a mixed-methods process evaluation and a cost-effectiveness study. Nurses in the intervention group will be trained in shared decision-making, coaching, and evidence-based patient information principles. Patients who meet the inclusion criteria will receive decision coaching (intervention group) with up to three face-to-face coaching sessions with a trained nurse (decision coach) or counselling as usual (control group). Patients in both groups will be given access to an evidence-based online information tool. The primary outcome is ‘informed choice’ after six months, assessed with the multi-dimensional measure of informed choice including the sub-dimensions risk knowledge (questionnaire), attitude concerning immunotherapy (questionnaire), and immunotherapy uptake (telephone survey). Secondary outcomes include decisional conflict, adherence to immunotherapy decisions, autonomy preference, planned behaviour, coping self-efficacy, and perceived involvement in coaching and decisional encounters. Safety outcomes are comprised of anxiety and depression and disease-specific quality of life. Discussion: This trial will assess the effectiveness of a new model of patient decision support concerning MS-immunotherapy options. The delegation of treatment information provision from physicians to trained nurses bears the potential to change current doctor-focused practice in Germany

From amaurotic idiocy to biochemically defined lipid storage diseases: the first identification of GM1-Gangliosidosis

On February 23rd 1936, a boy-child (“Kn”) died in an asylum near Munich after years of severe congenital dis-ease, which had profoundly impaired his development leading to inability to walk, talk and see as well as to severe epilepsy. While a diagnosis of “Little’s disease” was made during life, his postmortem brain investiga-tion at Munich neuropathology (“Deutsche Forschungsanstalt für Psychiatrie”) revealed the diagnosis of “amaurotic idiocy” (AI). AI, as exemplified by Tay-Sachs-Disease (TSD), back then was not yet understood as a specific inborn error of metabolism encompassing several disease entities. Many neuropathological studies were performed on AI, but the underlying processes could only be revealed by new scientific techniques such as biochemical analysis of nervous tissue, deciphering AI as nervous system lipid storage diseases, e.g. GM2-gangliosidosis. In 1963, Sandhoff & Jatzkewitz published an article on a “biochemically special form of AI” reporting striking differences when comparing their biochemical observations of hallmark features of TSD to tissue composition in a single case: the boy Kn. This was the first description of “GM1-Gangliosidosis”, later understood as resulting from genetically determined deficiency in beta-galactosidase. Here we present illus-trative materials from this historic patient, including selected diagnostic slides from the case “Kn” in virtual microscopy, original records and other illustrative material available. Finally, we present results from genetic analysis performed on archived tissue proving beta-galactosidase-gene mutation, verifying the 1963 interpre-tation as correct. This synopsis shall give a first-hand impression of this milestone finding in neuropathology