Purpose The purpose of this study was to revise the clinical use of commercial BMP2 (Infuse) and BMP7 (Osigraft) based bone devices and explore the mechanism of action and efficacy of low BMP6 doses in a novel whole blood biocompatible device OSTEOGROW. Methods Complications from the clinical use of BMP2 and BMP7 have been systemically reviewed in light of their role in bone remodeling. BMP6 function has been assessed in Bmp6-/-mice by μCT and skeletal histology, and has also been examined in mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and osteoclasts. Safety and efficacy of OSTEOGROW have been assessed in rats and rabbits.Results Clinical use issues of BMP2 and BMP7 have been ascribed to the limited understanding of their role in bone remodeling at the time of device development for clinical trials. BMP2 and BMP7 in bone devices significantly promote bone resorption leading to osteolysis at the endosteal surfaces, while in parallel stimulating exuberant bone formation in surrounding tissues. Unbound BMP2 and BMP7 in bone devices precipitate on the bovine collagen and cause inflammation and swelling. OSTEOGROW required small amounts of BMP6, applied in a biocompatible blood coagulum carrier, for stimulating differentiation of MSCs and accelerated healing of critical size bone defects in animals, without bone resorption and inflammation. BMP6 decreased the number of Mladenka Jurin contributed equally to this paper. S. Vukicevic (*) : J. Curak : J. Brkljacic : M. Pauk : I. Erjavec : I. Dumic-Cule : R. Novak : V. Kufner : T. Bordukalo Niksic :

Within the framework of a broader e-health strategy launched a decade ago, in 2015 Switzerland passed a new federal law on patients' electronic health records (EHR). The reform requires hospitals to adopt interoperable EHRs to facilitate data sharing and cooperation among healthcare providers, ultimately contributing to improvements in quality of care and efficiency in the health system. Adoption is voluntary for ambulatories and private practices, that may however be pushed towards EHRs by patients. The latter have complete discretion in the choice of the health information to share. Moreover, careful attention is given to data security issues. Despite good intentions, the high institutional and organisational fragmentation of the Swiss healthcare system, as well as the lack of full agreement with stakeholders on some critical points of the reform, slowed the process of adoption of the law. In particular, pilot projects made clear that the participation of ambulatories is doomed to be low unless appropriate incentives are put in place. Moreover, most stakeholders point at the strategy proposed to finance technical implementation and management of EHRs as a major drawback. After two years of intense preparatory work, the law entered into force in April 2017.

We surveyed European medical schools regarding teaching of prudent antibiotic prescribing in the undergraduate curriculum. We performed a cross-sectional survey in 13 European countries (Belgium, Croatia, Denmark, France, Germany, Italy, Netherlands, Norway, Serbia, Slovenia, Spain, Switzerland, United Kingdom) in 2013. Proportional sampling was used, resulting in the selection of two to four medical schools per country. A standardized questionnaire based on literature review and validated by a panel of experts was sent to lecturers in infectious diseases, medical microbiology and clinical pharmacology. In-depth interviews were conducted with four lecturers. Thirty-five of 37 medical schools were included in the study. Prudent antibiotic use principles were taught in all but one medical school, but only four of 13 countries had a national programme. Interactive teaching formats were used less frequently than passive formats. The teaching was mandatory for 53% of the courses and started before clinical training in 71%. We observed wide variations in exposure of students to important principles of prudent antibiotic use among countries and within the same country. Some major principles were poorly covered (e.g. reassessment and duration of antibiotic therapy, communication skills). Whereas 77% of the respondents fully agreed that the teaching of these principles should be prioritized, lack of time, mainly due to rigid curriculum policies, was the main reported barrier to implementation. Given the study design, these are probably optimistic results. Teaching of prudent antibiotic prescribing principles should be improved. National and European programmes for development of specific learning outcomes or competencies are urgently needed.

The requirement of a bone morphogenetic protein for the maintenance and stimulation of an osteoblast phenotype was examined using mouse MC3T3-E1 cell cultures. Cells expressed BMP-4 mRNA, which correlated with the stimulation of the osteoblast phenotype. The addition of a BMP-4 specific antibody reduced bone nodules, suggesting that BMP-4 is required for the osteogenic activity of osteoblasts in an autocrine manner. Exogenously added BMP-7 gradually decreased the expression of BMP-4 with a concurrent stimulation of the osteoblast phenotype. Exogenous BMP-7 can therefore substitute for endogenously produced BMP-4 acting as a paracrine factor on osteoblasts. The addition of 17beta estradiol decreased BMP-4 expression but initiated synthesis of BMP-6 mRNA, an endocrine signal for osteoblasts, which also substituted for the lack of endogenous BMP-4, as evidenced by normal bone nodule formation. The addition of dexamethasone and parathyroid hormone did not affect the BMP-4 expression but induced transcripts for BMP-2 and BMP-3, respectively, suggesting that their effects on bone can be in part achieved via the BMP signaling. These experiments support the requirement of a BMP for osteoblast differentiation and function, demonstrating for the first time that a BMP can functionally substitute for another BMP in an autocrine/paracrine manner or mediate a response to an endocrine action on osteoblasts.

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Introduction: The development of a fistula and/or an abscess are major complications in patients with Crohn’s disease. An abscess can involve any of the major viscera, including the liver and spleen. Case Report: A 27-year-old male patient with a 6-month history of NOD2/CARD15-positive Crohn’s disease with stenosis of the terminal ileum, previously treated with corticosteroids, was admitted with fever, chills, diarrhea, fatigue and cachexia. Diagnostic work-up revealed sepsis, an abscess in the right hepatic lobe, multiple abdominal collections and right-sided pleural effusion. It was felt that his poor general condition prevented surgical intervention and complex conservative treatment was initiated. It consisted of total parenteral nutrition, antibiotics, percutaneous drainage of the liver abscess, and thoracocentesis. Pus and blood cultures showed Lactobacillus acidophilus. There was a gradual improvement in the patient’s condition and the liver abscess decreased in diameter from 14 to 2 cm. Aminosalicylates and enteral nutrition were gradually introduced. The patient was discharged after 9 weeks in good general condition. Conclusion: Although extremely rarely, L. acidophilus can cause hepatic abscess and sepsis. This can be explained by immunologic incompetence due to corticosteroid treatment of Crohn’s disease.

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INTRODUCTIONPoor prescribing is probably the most common cause of preventable medication errors and many of these events involve junior doctors. In 2009, an electronic problem-based therapeutics course developed at the University of Michigan Medical School (UMMS) was translated and adapted for use at the University of Zagreb Medical School (UZMS). METHODSAfter students from both schools took the course in 2010, we compared their responses with an online questionnaire addressing the course quality and its effectiveness. RESULTSThere were no statistically significant differences in the overall average grades awarded for the course (UZMS 4.11 Ϯ 0.86 vs. UMMS 3.96 Ϯ 0.93; 95% CI mean difference (MD) -0.36, 0.07; P = 0.175) with both student groups expressing high satisfaction rates with its quality, accessibility and overall design. UZMS students reported spending less time working through the course than their American colleagues (2.14 Ϯ 1.01 vs. 2.89 Ϯ 1.02 on a five point Likert scale; 95% CI MD 0.51, 0.99; P < 0.05). Furthermore, Croatian students indicated greater difficulty with course materials (3.54 Ϯ 0.59 vs. 3.25 Ϯ 0.59; 95% CI MD -0.42, -0.15; P < 0,05) and weekly multiple choice questions (3.83 Ϯ 0.62 vs. 3.4 Ϯ 0.61; 95% CI MD -0.58, -0.29; P < 0,05) compared with the UMMS students.