Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network.

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.

[Long-Term Implementation of Structures and Activities Needed for Health Promotion]. / Was fördert die Verstetigung von Strukturen und Angeboten der Gesundheitsförderung?

To achieve sustainable effects of health promotion interventions, first of all, long-term implementation is needed. However, there are just a few studies that explore how to maintain health-promoting structures and activities after external funding comes to an end. Using a mixed-methods approach, the evaluation study of the Bielefeld University analysed long-term implementation of government-funded projects. Our results show that maintenance of project structures and activities is a multiplex and contextual process. Apart from conceptual factors that can be influenced by project activities, interviewees reported on contextual factors (e. g., political support) that particularly affect successful long-term implementation. Thus, strategies need to be planned and initiated in the early stages of a project.

[There is no Need to Reinvent the Wheel - Requirements for a Successful Project Transfer]. / "Man muss das Rad nicht neu erfinden, sondern damit fahren." ­ Voraussetzungen für einen erfolgreichen Projekttransfer.

Although the transfer of an existing project can be a resource-efficient form of implementation of successful interventions, project transfers are rarely carried out in practice. The aim of this article is to pool the experience of 3 projects about the transfer of their prevention approaches to other municipalities and regions, as well as to make recommendations for future trans-regional transfer processes in the field of disease prevention and health promotion. To achieve this, documentation sheets were used and interviews were conducted with team members of the transfer projects. The results show that the ability to adapt intervention to context is an essential condition of successful implementation. In addition, there has to be a need for the intervention in the transfer region and a benefit to the participant organizations as well as to the team members. Furthermore, constructive and personal communication and cooperation between the participants of the original and the transferred project are required for successful transfer.

[Gastrointestinal stromal tumours (GIST)--development in pathology, surgery and medical therapy. Developed during the 10th German GIST-meeting, Göttingen]. / Gastrointestinale Stromatumoren (GIST)--Neues zu Pathologie, Chirurgie und medikamentöser Therapie. Erarbeitet im Rahmen des 10. Deutschen GIST-Treffens, Göttingen.

The first description of ligand-independent activating mutations in the KIT gene, which encodes the tyrosine-kinase KIT, greatly improved our understanding of gastrointestinal stromal tumour (GIST) biology. The therapeutic success in GIST has made tyrosine kinase inhibitors a "paradigm of targeted therapy". Deciphering resistance mechanisms in GIST has had implications for many other kinase-driven cancers. To exchange current knowledge within the field of GIST, the German GIST Meeting has taken place for now 10 years, traditionally in Göttingen. Subjects discussed include clinical diagnostics, pathology, surgery, and medical therapy. The following presentation gives an overview of the last meeting held in December 2013, including distinctive features in GIST and current data on the different topics.

Prevalence and risk factors of actinic keratoses in Germany--analysis of multisource data.

BACKGROUND: In Europe, only few and inconsistent data on the prevalence and treatment of actinic keratoses (AK) are available. OBJECTIVES: To determine the prevalence of AK in Germany, to identify potential predictors and to estimate the number of AK cases treated in dermatological practices. METHODS: In a multiple-source approach, prevalence was assessed from whole-body examinations in a cohort of 90 800 employees and from nationwide statutory health insurance (SHI) data of 2008. The number of cases documented in dermatological offices was estimated from statistics of a SHI Physicians Association. RESULTS: Standardized prevalence of AK from dermatological examinations was 2.7%; the rate increased with age (11.5% in the group 60-70 years) and was higher for men (3.9%) than for women (1.5%). Significant associations were also identified for skin phototype I, sunburns in childhood and solar lentigines. Vitiligo and a history of melanoma were also, but not significantly, associated with AK. In the SHI data analysis, standardized AK prevalence was 1.8%. Age-specific rates were below 1.5% up to 60 years and rose to 8.2% (13.2% in men) in the group 80-89 years. The prevalence from these large data sets--which is at the lower limit of studies from other countries--suggests about 1.7 million estimated AK cases in Germany. In 2011, AK accounted for 8.3% of the hundred most frequently treated dermatological outpatient diagnoses. The proportion of AK cases has risen almost continuously over the last 10 years, compared to other dermatological conditions. Estimated annual number of AK cases documented by dermatologists in Germany is about 1.7 million. CONCLUSIONS: Actinic keratosis is a frequent condition in higher age groups and more prevalent in men; a relevant need for health care is evident. Predictors and risk factors for AK are easy to identify in the population, which could also help to detect groups with special need for preventive measures.

Always expect the unexpected: lung abscess due to pseudomonas aeruginosa mimicking pulmonary aspergilloma in acute B-cell leukemia.

We report on a case of Pseudomonas aeruginosa sepsis and consecutive lung abscess in a 13-year-old patient with acute B-cell leukemia. At first, radiographic findings strongly suggested presence of pulmonary aspergilloma and only microbiological testing of the surgically enucleated mass revealed the correct underlying pathogen and confirmed final diagnosis.

Prevalence and disease burden of hyperhidrosis in the adult population.

BACKGROUND: Although hyperhidrosis is a common and burdensome condition, little is known about the population-based prevalence. OBJECTIVE: To evaluate the epidemiology, disease burden and medical care of hyperhidrosis in German adults. METHODS: Employees of fifty-two companies underwent skin screenings and interviews including hyperhidrosis questions. RESULTS: 14,336 individuals were investigated (36% women, mean age 42 years) of whom 2,340 (16.3%) reported hyperhidrosis, including 869 (6.1%) with frequent or continuous disturbing sweating. 28% showed focal hyperhidrosis, whilst 68% had a generalized condition. Predictors of hyperhidrosis were male gender and concomitant drug medication. Moreover, persons with psoriasis and with metabolic comorbidity were at increased risk. Only 27% of those with focal hyperhidrosis had consulted a physician, and only 28% used prescribed medication or self-medication. CONCLUSION: Hyperhidrosis is a frequent skin condition predicted by medical and personal factors. In spite of the disease burden, few individuals utilize medical care. Affected individuals should be encouraged to refer to a dermatologist.

Maxillary reaction patterns identified by three-dimensional analysis of casts from infants with unilateral cleft lip and palate.

OBJECTIVES: In order to visualize and quantify the direction and extent of morphological upper-jaw changes in infants with unilateral cleft lip and palate (UCLP) during early orthodontic treatment, a three-dimensional method of cast analysis for routine application was developed. In the present investigation, this method was used to identify reaction patterns associated with specific cleft forms. MATERIALS AND METHODS: The study included a cast series reflecting the upper-jaw situations of 46 infants with complete (n=27) or incomplete (n=19) UCLP during week 1 and months 3, 6, and 12 of life. Three-dimensional datasets were acquired and visualized with scanning software (DigiModel®; OrthoProof, The Netherlands). Following interactive identification of landmarks on the digitized surface relief, a defined set of representative linear parameters were three-dimensionally measured. At the same time, the three-dimensional surfaces of one patient series were superimposed based on a defined reference plane. Morphometric differences were statistically analyzed. RESULTS: Thanks to the user-friendly software, all landmarks could be identified quickly and reproducibly, thus, allowing for simultaneous three-dimensional measurement of all defined parameters. The measured values revealed that significant morphometric differences were present in all three planes of space between the two patient groups. Patients with complete UCLP underwent significantly larger reductions in cleft width (p<0.001), and sagittal growth in the complete UCLP group exceeded sagittal growth in the incomplete UCLP group by almost 50% within the first year of life. CONCLUSION: Based on patients with incomplete versus complete UCLP, different reaction patterns were identified that depended not on apparent severities of malformation but on cleft forms.

[Oncological patients' decision making processes concerning their pain medication at home: a qualitative secondary analysis]. / Entscheidungswege von onkologischen Patienten im Umgang mit Schmerzmedikamenten im häuslichen Umfeld: eine qualitative Sekundäranalyse.

Unrelieved pain affects up to 75 % of cancer patients. Possible reasons for the undertreatment of pain are, amongst others, patient-related barriers towards cancer pain management. However the way patients decide on the use of analgesics remains unclear. The purpose of this qualitative study was to explore decision-making processes of four women and four men with diverse cancers concerning their pain medications. Audiotaped protocols of the 10-week-intervention and interviews of the PEINCA-pilot study provided data for a secondary analysis. This pilot study was conducted at a comprehensive cancer centre in Germany to test the German version of a cancer pain self-management intervention to enhance oncology patients' pain self-management for the first time. The data of purposively selected patients were analysed using content analysis. The results showed that these patients were very ambivalent about their analgesic use. The need to relieve severe pain conflicted with the desire to avoid opioids at any price. Decisions were reconsidered and overturned even after good experiences with analgesics. This study seems to provide a first look into decision-making processes over 10 weeks during a self-management education. Individually tailored counselling by a professional within the education programme helped the patients adopt new attitudes towards analgesics and gradually reduce their pain levels. Previous experiences of the patients and their possible ambivalence towards analgesics should be considered in a pain therapy, and patients should be coached by professionals.

[Evaluation of the sponsoring initiative of the "action plan healthy life-style and life worlds" - instruments and first results on planning quality]. / Evaluation der Förderinitiative "Aktionsbündnisse Gesunde Lebensstile und Lebenswelten" - Instrumentarium und erste Ergebnisse zur Planungsqualität.

In line with the National Action Plan "IN FORM" the German Federal Ministry of Health funds the establishment of 11 regional community health promotion networks (alliances). To meet quality development standards, an external evaluation project has been established in addition to the alliances' internal evaluation. Scientific monitoring focuses on alliance-spanning investigation of quality of planning, structures and processes and uses different methods and instruments (e.g., guided interviews, analytical framework, Goal Attainment Scaling). Regional networks also receive support for their efforts to quality development. Up to now concluding analysis can be done on aspects of planning quality based on findings of the analytical framework developed within the project. 5 selected results presented in the article reveal a heterogeneous picture: on one hand the standard on which the alliances' rationales on demands justifying the project's strategy are written at is very encouraging. The situation is similar with the descriptions of the work planning and statements concerning the sustainability at which the implemented activities are aimed. On the other hand, in explaination criteria like consideration of target group's needs or definition of goals the possibilities are not exhausted yet considering the state of the debate. Hence in similar future projects there is a clear necessity of assistance in approaching these aspects, provided preferably in an early stage of the planning phase.

Infliximab as therapeutic option in steroid-refractory ulcerative colitis after kidney transplantation: case report.

In inflammatory bowel disease refractory to established therapies, treatment with biological agents such as monoclonal tumor necrosis factor-α antibodies is an established therapeutic option. However, application in renal allograft recipients is either not licensed or has not yet been systematically examined. Herein, we present 2 case reports of renal allograft recipients who had steroid-refractory ulcerative colitis who demonstrated improvement of symptoms after treatment with infliximab, without signs of effect on transplant function. In both patients, stool frequency decreased significantly. Colonoscopy controls and histologic examination after initiation of treatment revealed a state of remission. Renal function parameters and drug concentrations remained constant.

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion.

The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model. Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4 degrees C, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included "worst case" without Perfadex and surfactant (5), "no injury" without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood-air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (P(pa)) were determined during reperfusion in groups 1 to 4. Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood-air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4. P(pa) did not differ between the groups. In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood-air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.

Prevalence of skin diseases in a cohort of 48,665 employees in Germany.

BACKGROUND: Epidemiological data are important for planning medical care. Thus far, only few prevalence data for skin diseases have been published in Germany, most of them not population based. OBJECTIVES: Estimation of prevalences of common skin diseases in a sample of employees of German companies. METHODS: Whole-body examinations were performed by trained dermatologists in 150 companies as part of skin cancer screenings. Using a standardized and computerized data entry, all clinical dermatological findings were documented. Explicitly skin lesions requiring current treatment were noted. The retrospective evaluation of the data was descriptive, using the diagnoses defined a priori in the data entry mask. RESULTS: 48,665 persons (52.8% male) with a mean age of 43.2 years were examined. The following frequencies of chronic and acute inflammatory skin diseases were observed: contact eczema 8.9%, acne 4.2%, seborrhoeic eczema 3.4%, rosacea 2.2%, psoriasis vulgaris 2.1%, atopic eczema 1.4% and lichen ruber 0.07%. In total, dermatological findings needing treatment were observed in 19% of the study cohort; 1.3% of the participants presented a suspicious finding requiring diagnostics for skin malignoma. CONCLUSIONS: There is a high frequency of chronic inflammatory skin diseases in the general working population and a high need for dermatological treatment.

Benefit evaluation in vitiligo treatment: development and validation of a patient-defined outcome questionnaire.

BACKGROUND: In addition to clinical efficacy, patient-defined benefit assessment has become an important outcome parameter. Thus far, no such instrument has been developed for vitiligo. OBJECTIVES: Development and validation of a patient-defined benefit questionnaire in the therapy of vitiligo. METHODS: Open questioning of 50 vitiligo patients generated 110 benefit items, which were converted into a 26-item questionnaire by a panel of dermatologists, psychologists and patients. This was used to record patient-defined needs prior to therapy and to evaluate patient benefit attained after therapy. A 'patient benefit index' (PBI) was formed on the basis of both. Validation was based on data of n = 1,023 vitiligo patients. RESULTS: The questionnaires were feasible in clinical practice, Cronbach's alpha (patient need questionnaire) was 0.94. The PBI showed convergent and discriminant validity with respect to quality of life and patient satisfaction. CONCLUSION: The PBI for vitiligo is a valid instrument, which is highly accepted in practice for recording patient-reported benefit.

No evidence for the 'Meselson effect' in parthenogenetic oribatid mites (Oribatida, Acari).

It has been hypothesized that in ancient apomictic, nonrecombining lineages the two alleles of a single copy gene will become highly divergent as a result of the independent accumulation of mutations (Meselson effect). We used a partial sequence of the elongation factor-1alpha (ef-1alpha) and the heat shock protein 82 (hsp82) genes to test this hypothesis for putative ancient parthenogenetic oribatid mite lineages. In addition, we tested if the hsp82 gene is fully transcribed by sequencing the cDNA and we also tested if there is evidence for recombination and gene conversion in sexual and parthenogenetic oribatid mite species. The average maximum intra-specific divergence in the ef-1alpha was 2.7% in three parthenogenetic species and 8.6% in three sexual species; the average maximum intra-individual genetic divergence was 0.9% in the parthenogenetic and 6.0% in the sexual species. In the hsp82 gene the average maximum intra-individual genetic divergence in the sexual species Steganacarus magnus and in the parthenogenetic species Platynothrus peltifer was 1.1% and 1.2%, respectively. None of the differences were statistically significant. The cDNA data indicated that the hsp82 sequence is transcribed and intron-free. Likelihood permutation tests indicate that ef-1alpha has undergone recombination in all three studied sexual species and gene conversion in two of the sexual species, but neither process has occurred in any of the parthenogenetic species. No evidence for recombination or gene conversion was found for sexual or parthenogenetic oribatid mite species in the hsp 82 gene. There appears to be no Meselson effect in parthenogenetic oribatid mite species. Presumably, their low genetic divergence is due to automixis, other homogenizing mechanisms or strong selection to keep both the ef-1alpha and the hsp82 gene functioning.

[Renal artery stenosis: screening, diagnostic and therapeutic options]. / Nierenarterienstenose: Screening, Diagnostik und Therapiemöglichkeiten.

Hypertension is a frequent disease and renal artery stenosis, as a potential cause of hypertension, can be cured. Therefore, we frequently need to exclude a renal artery stenosis in patients with hypertension in our daily routine. This calls for a screening procedure which is non-invasive, highly effective and not too expensive. This paper describes the advantages and limitations of colour Doppler ultrasound in diagnosing renal artery stenosis. Colour Doppler ultrasound with intrarenal Doppler analysis is an ideal tool in the screening for relevant renal artery stenosis in patients with hypertension. This technique, however, requires a careful approach and extrarenal abnormalities need to be considered.

Colonic perforation by ventriculoperitoneal shunt tubing: a case of suspected silicone allergy.

BACKGROUND: A case of colonic perforation by a ventriculoperitoneal shunt is presented in a patient with several previous complications associated with shunt tubing. CASE DESCRIPTION: Initially managed by intravenous antibiotics, shunt externalization, and colonoscopy, the entire ventriculoperitoneal shunt system was subsequently replaced after cerebrospinal fluid cultures had grown Propionibacterium acnes and Streptococcus sanguis organisms. The patient has had three episodes of skin breakdown over his shunt tubing (two prior and one subsequent to colonic perforation) without evidence of shunt infection or malfunction. CONCLUSIONS: The etiology of these complications is consistent with silicone tubing allergy. Replacement with a polyurethane system produced no similar complications thus far, which further supports a possible silicone allergy to the ventriculoperitoneal shunt and possible etiology of this patient's colonic perforation.

[Communication in environmental health protection and in environmental medicine counseling]. / Kommunikation im gesundheitlichen Umweltschutz und in der umweltmedizinischen Beratung.

Practically all municipal health authorities, including the Bremen health authorities, now offer advice with regard to healthy environmental protection, i. e. environmental-medical consulting activities. The majority of the consultantcy services deal with individual inquiries made by citizens. This is supplemented by counselling and discussions with groups in various contexts. It is frequent for extremely difficult counselling contents, situations and deficits in the conducting of the discussions by the consultants who are specialised in natural science subjects to coincide. Within the framework of a further training course designed for these specific needs, the staff of the Bremen health authorities, with specialist instruction, were successful in acquitting skill in the communication of risks, which is a qualification that should become self-evident also in this sphere.

An approach to the treatment of recurring polyarthralgia after jejunoileal bypass.

Polyarthralgia after jejunoileal bypass (JI) is a well-documented complication. In the past, this was treated by antibiotic therapy, but definitive therapy uncommonly necessitated surgical reversal of the JI bypass. This case report discusses the etiology of arthralgias and presents a technique for its treatment without bypass reversal.

Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice.

The cytosolic phosphoenolpyruvate carboxykinase (PEPCK) gene is expressed in multiple tissues and is regulated in a complex tissue-specific manner. To map the cis-acting DNA elements that direct this tissue-specific expression, we made transgenic mice containing truncated PEPCK-human growth hormone (hGH) fusion genes. The transgenes contained PEPCK promoter fragments with 5' endpoints at -2088, -888, -600, -402, and -207 bp, while the 3' endpoint was at +69 bp. Immunohistochemical analysis showed that the -2088 transgene was expressed in the correct cell types (hepatocytes, proximal tubular epithelium of the kidney, villar epithelium of the small intestine, epithelium of the colon, smooth muscle of the vagina and lungs, ductal epithelium of the sublingual gland, and white and brown adipocytes). Solution hybridization of hGH mRNA expressed from the transgenes indicated that white and brown fat-specific elements are located distally (-2088 to -888 bp) and that liver-, gut-, and kidney-specific elements are located proximally (-600 to +69 bp). However, elements outside of the region tested are necessary for the correct developmental pattern and level of PEPCK expression in kidney. Both the -2088 and -402 transgenes responded in a tissue-specific manner to dietary stimuli, and the -2088 transgene responded to glucocorticoid stimuli. Thus, different tissues utilize distinct cell-specific cis-acting elements to direct and regulate the PEPCK gene.