Medizin - Open Access LMU - Teil 21/22 Ludwig-Maximilians-Universität München

Background: Recurrent respiratory papillomatosis (RRP) is a rare disease, which is characterised by the growth of papillomavirus-induced papillomas within the respiratory tract. Malignant transformation occurs in less than 1\% of the cases. Case presentation: We report a case of human papillomavirus (HPV) type 11-associated juvenile-onset RRP (JORRP) initially diagnosed at the age of two years. Remarkably high copy numbers of HPV11 DNA and antibody titres targeting the capsid protein L1 were detected in the patient's serum. The patient developed squamous cell carcinomas in both lungs and extraordinarily an HPV11 DNA-positive papillary endocardial lesion in the left atrium of the heart, which caused thromboembolic events leading to the patient's death at 19 years old. Conclusion: We here report a severe case of JORRP hallmarked by HPV11 DNAemia and very high antibody titres directed against the major viral capsid protein L1. Furthermore, the extent of malignant transformation and the discovery of a very rare fatal endocardial lesion highlight the unpredictability of JORRP and the complexity of its clinical management.

Numerous high-throughput sequencing studies have focused on detecting conventionally spliced mRNAs in RNA-seq data. However, non-standard RNAs arising through gene fusion, circularization or trans-splicing are often neglected. We introduce a novel, unbiased algorithm to detect splice junctions from single-end cDNA sequences. In contrast to other methods, our approach accommodates multi-junction structures. Our method compares favorably with competing tools for conventionally spliced mRNAs and, with a gain of up to 40% of recall, systematically outperforms them on reads with multiple splits, trans-splicing and circular products.

Background: We report on the design and implementation of a study protocol entitled Acupuncture randomised trial for post anaesthetic recovery and postoperative pain - a pilot study (ACUARP) designed to investigate the effectiveness of acupuncture therapy performed in the perioperative period on post anaesthetic recovery and postoperative pain. Methods/Design: The study is designed as a randomised controlled pilot trial with three arms and partial double blinding. We will compare (a) press needle acupuncture, (b) no treatment and (c) press plaster acupressure in a standardised anaesthetic setting. Seventy-five patients scheduled for laparoscopic surgery to the uterus or ovaries will be allocated randomly to one of the three trial arms. The total observation period will begin one day before surgery and end on the second postoperative day. Twelve press needles and press plasters are to be administered preoperatively at seven acupuncture points. The primary outcome measure will be time from extubation to `ready for discharge' from the post anaesthesia care unit (in minutes). The `ready for discharge' end point will be assessed using three different scores: the Aldrete score, the Post Anaesthetic Discharge Scoring System and an In-House score. Secondary outcome measures will comprise pre-, intra- and postoperative variables (which are anxiety, pain, nausea and vomiting, concomitant medication). Discussion: The results of this study will provide information on whether acupuncture may improve patient post anaesthetic recovery. Comparing acupuncture with acupressure will provide insight into potential therapeutic differences between invasive and non-invasive acupuncture techniques.

Background: MYH9-related disease (MYH9-RD) is a rare syndromic disorder deriving from mutations in MYH9, the gene for the heavy chain of non-muscle myosin IIA. Patients present with congenital thrombocytopenia and giant platelets and have a variable risk of developing sensorineural deafness, kidney damage, presenile cataract, and liver abnormalities. Almost all MYH9-RD patients develop the hearing defect, which, in many individuals, progresses to severe to profound deafness with high impact on quality of life. These patients are potential candidates for cochlear implantation (CI), however, no consistent data are available about the risk to benefit ratio of CI in MYH9-RD. The only reported patient who received CI experienced perisurgery complications that have been attributed to concurrent platelet defects and/or MYH9 protein dysfunction. Methods: By international co-operative study, we report the clinical outcome of 10 patients with MYH9-RD and severe to profound deafness who received a CI at 8 institutions. Results: Nine patients benefited from CI: in particular, eight of them obtained excellent performances with restoration of a practically normal hearing function and verbal communication abilities. One patient had a slightly worse performance that could be explained by the very long duration of severe deafness before CI. Finally, one patient did not significantly benefit from CI. No adverse events attributable to MYH9-RD syndrome were observed, in particular no perisurgery bleeding complications due to the platelet defects were seen. Patients' perioperative management is described and discussed. Conclusions: CI is safe and effective in most patients with MYH9-RD and severe to profound deafness and should be offered to these subjects, possibly as soon as they develop the criteria for candidacy.

Background: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data. Methods: Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications. Results: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (400 mu M) and NTBC-levels in the therapeutic range (20-40 mu M). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood). Conclusion: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

Background: This article examines spiritual care training provided to healthcare professionals in Germany, Austria and Switzerland. The paper reveals the current extent of available training while defining the target group(s) and teaching aims. In addition to those, we will provide an analysis of delivered competencies, applied teaching and performance assessment methods. Methods: In 2013, an anonymous online survey was conducted among the members of the International Society for Health and Spiritual Care. The survey consisted of 10 questions and an open field for best practice advice. SPSS21 was used for statistical data analysis and the MAXQDA2007 for thematic content analysis. Results: 33 participants participated in the survey. The main providers of spiritual care training are hospitals (36%, n = 18). 57% (n = 17) of spiritual care training forms part of palliative care education. 43% (n = 13) of spiritual care education is primarily bound to the Christian tradition. 36% (n = 11) of provided trainings have no direct association with any religious conviction. 64% (n = 19) of respondents admitted that they do not use any specific definition for spiritual care. 22% (n = 14) of available spiritual care education leads to some academic degree. 30% (n = 19) of training form part of an education programme leading to a formal qualification. Content analysis revealed that spiritual training for medical students, physicians in paediatrics, and chaplains take place only in the context of palliative care education. Courses provided for multidisciplinary team education may be part of palliative care training. Other themes, such as deep listening, compassionate presence, bedside spirituality or biographical work on the basis of logo-therapy, are discussed within the framework of spiritual care. Conclusions: Spiritual care is often approached as an integral part of grief management, communication/interaction training, palliative care, (medical) ethics, psychological or religious counselling or cultural competencies. Respondents point out the importance of competency based spiritual care education, practical training and maintaining the link between spiritual care education and clinical practice. Further elaboration on the specifics of spiritual care core competencies, teaching and performance assessment methods is needed.