Effect of 12-months testosterone replacement therapy on bone mineral density and markers of bone turnover in testicular cancer survivors - results from a randomized double-blind trial.

BACKGROUND: Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. METHODOLOGY: In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). RESULTS: After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): -0.01 - 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: -0.01-0.03), BMD of the left femoral neck: 0.00, (95% CI: -0.01-0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. CONCLUSION: 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort.

Absence of clinical benefit of FDG PET-CT in staging T1 part-solid lung adenocarcinoma.

AIM: To assess the rates of nodal and metastatic disease and change in management when staging part-solid T1 lung adenocarcinomas using integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) in a UK population. MATERIALS AND METHODS: This was a retrospective review of PET-CT examinations performed to stage radiologically suspected T1 part-solid lung adenocarcinoma (n=58) from two different centres. Rates of detection of nodal and metastatic disease, change in management, and final patient outcome were recorded. RESULTS: PET-CT changed the stage in one patient from N0 to N1. It did not change final management in any patient. CONCLUSIONS: In this UK population, PET-CT had minimal additional diagnostic benefit in staging patients with T1 part-solid lung adenocarcinoma. Especially given its cost, the inclusion of PET-CT for this indication in guidelines should be reviewed.

Unilateral axillary adenopathy following COVID-19 vaccination: a multimodality pictorial illustration and review of current guidelines.

We present a multimodality pictorial review of axillary lymphadenopathy in patients recently vaccinated against COVID-19. As the mass vaccination programme continues to be rolled out worldwide in an effort to combat the pandemic, it is important that radiologists consider recent COVID-19 vaccination in the differential diagnosis of unilateral axillary lymphadenopathy and are aware of typical appearances across all imaging methods. We review current guidelines on the management of unilateral axillary lymphadenopathy in the context of recent COVID-19 vaccination.

Improved algorithm with adaptive regularization for tomographic reconstruction of gas distributions using DOAS measurements.

Differential optical absorption spectroscopy (DOAS) is notably well suited for the retrieval of UV-absorbing trace gases present in the atmosphere. We combine multi-axis DOAS observations to perform a tomographic reconstruction of the distribution of gases emitted from different sources. We use a new algorithm based on a regularized minimization approach embedding key physical aspects of the solution to constrain the inversion. In this work, we take into account that the spatial sampling of the plume being scanned by the instruments is not homogeneous. Therefore, we introduce an adaptive approach with a locally tuned regularization weight according to the uncertainty levels introduced by the sampling scheme. We tested our approach on reconstructions of simulated gas distributions and different configurations applicable to multi-axis DOAS. Finally, our approach is applied to experimental data for the retrieval of the distribution of ${\rm NO}_2$NO2 within a plume cross section emitted from a group of stacks.

Outcomes of extended radical resections for locally advanced and recurrent pelvic malignancy involving the aortoiliac axis.

AIM: Currently, there is no clear consensus on the role of extended pelvic resections for locally advanced or recurrent disease involving major vascular structures. The aims of this study were to report the outcomes of consecutive patients undergoing extended resections for pelvic malignancy involving the aortoiliac axis. METHODS: Prospective data were collected on patients having extended radical resections for locally advanced or recurrent pelvic malignancies, with aortoiliac axis involvement, requiring en bloc vascular resection and reconstruction, at a single institution between 2014 and 2018. RESULTS: Eleven patients were included (median age 60 years; range 31-69 years; seven women). The majority required resection of both arterial and venous systems (n = 8), and the technique for vascular reconstruction was either interposition grafts or femoral-femoral crossover grafts. The median operative time was 510 min (range 330-960 min). Clear resection margins (R0) were achieved in nine patients. The median length of stay was 25 days (range 7-83 days). Seven patients did not suffer an early complication. There was one serious complication (Clavien-Dindo ≥ 3), an arterial graft occlusion secondary to thrombus in the immediate postoperative period, requiring a return to theatre and thrombectomy. The median length of follow-up in this study was 22 months (range 4-58 months). CONCLUSION: This series demonstrates that en bloc major vascular resection and reconstruction can be performed safely and can achieve clear resection margins in selected patients with locally advanced or recurrent pelvic malignancy at specialist surgery centres.

Improving diagnostic performance of 18F-FDG-PET/CT for assessment of regional nodal involvement in non-small cell lung cancer.

AIM: To assess the diagnostic performance of combined 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) mediastinal blood pool (MBP) activity cut-off for staging nodal involvement, and to examine other variables that may improve the diagnostic performance of PET/CT in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: All patients diagnosed with NSCLC who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and 18F-FDG-PET/CT between June 2016 and August 2018 were included. Nodal station and nodal staging-based analyses were performed, comparing the MBP cut-off and five other PET/CT parameters (node maximum standardised uptake value [SUVmax], node/MBP SUVmax ratio, node/tumour SUVmax ratio, node short axis diameter, and node SUVmax/node short axis diameter ratio) with histopathology results. The optimal cut-off value for each PET/CT parameter was determined using receiver operating characteristic curve analysis. RESULTS: One hundred and thirteen patients with a total of 321 nodes with pathological sampling were included. Nodal activity above MBP on PET/CT demonstrated 97.4% sensitivity, 35.8% specificity, 32.8% positive predictive value, and 97.8% negative predictive value. Of the five other PET/CT parameters examined, the two most promising were node SUVmax and node/MBP SUVmax. The node SUVmax cut-off of 3.9 demonstrated 90.9% sensitivity and 61.9% specificity, and the node/MBP SUVmax cut-off of 1.7 demonstrated 90.9% sensitivity and 60.7% specificity. CONCLUSION: Compared to the MBP cut-off, use of a higher node/MBP SUVmax ratio cut-off and use of other PET/CT variables can improve the diagnostic performance of PET/CT for NSCLC nodal staging. In particular, specificity for detecting malignant nodal involvement is improved while maintaining high sensitivity.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) as a therapeutic target in psoriasis: randomized, controlled investigation using namilumab, a specific human anti-GM-CSF monoclonal antibody.

BACKGROUND: The relevance of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of psoriasis has not been studied previously. GM-CSF is important in the initiation and maintenance of chronic inflammatory processes. OBJECTIVES: To investigate the clinical use of GM-CSF neutralization by evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody GM-CSF inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS: A phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group, dose-finding, proof-of-concept study (NEPTUNE) was conducted. Four doses of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared with placebo. Assessment of the primary end point - the proportion of patients achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75 treatment response) - was performed at week 12. Exploratory investigation at the tissue level was conducted in a subset of the overall study population. The trial was registered with the number NCT02129777. RESULTS: In total, 122 patients were enrolled and 106 (86·9%) completed the double-blind treatment; 16 (13·1%) prematurely discontinued study medication. Serum concentration-time profiles were as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and exposure increased proportionally with dose elevation. The number of patients showing PASI 75 treatment response at week 12 was low in all groups; no significant difference was recorded in this end point between placebo and any namilumab group. Similar outcomes were recorded for other clinical study end points. Moreover, no significant treatment-related changes from baseline were observed in laboratory investigations of cell types or subpopulations, or cytokines relevant to inflammatory pathways in psoriasis. CONCLUSIONS: GM-CSF blockade is not critical for suppression of key inflammatory pathways underlying psoriasis.

Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds.

PURPOSE: 18F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis underwent 18F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123I-serum amyloid P component (SAP). 18F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUVmean) were produced. RESULTS: All 17 patients showed 18F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. CONCLUSION: 18F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool for AL.

Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis.

BACKGROUND: Namilumab (AMG203) is an immunoglobulin G1 monoclonal antibody that binds with high affinity to the GM-CSF ligand. This was a phase 1b, randomized, double-blind study (PRIORA) to assess namilumab in active, mild-to-moderate rheumatoid arthritis (RA). The primary outcome was the safety and tolerability of repeated subcutaneous injections of namilumab in patients with mild-to-moderate RA. METHODS: Adults with mild-to-moderate RA on stable methotrexate doses for ≥12 weeks were eligible. Patients received three subcutaneous injections of namilumab 150 or 300 mg, or placebo on days 1, 15, and 29, with 12 weeks' follow-up. Primary objective was safety/tolerability. RESULTS: Patients in cohort 1 were randomized to namilumab 150 mg (n = 8) or placebo (n = 5). In cohort 2, patients were randomized to namilumab 300 mg (n = 7) or placebo (n = 4). Incidence of treatment-emergent adverse events (TEAEs) was similar across the three groups (namilumab 150 mg: 63%; namilumab 300 mg: 57%; placebo: 56%). TEAEs in ≥10% of patients were nasopharyngitis (17%) and exacerbation/worsening of RA (13%). No anti-namilumab antibodies were detected. The pharmacokinetics of namilumab were linear and typical of a monoclonal antibody with subcutaneous administration. In a post hoc efficacy, per protocol analysis (n = 21), patients randomized to namilumab showed greater improvement in Disease Activity Score 28 (erythrocyte sedimentation rate and C-reactive protein [CRP]), swelling joint counts and tender joint counts compared with placebo. Difference in mean DAS28-CRP changes from baseline between namilumab and placebo favored namilumab at both doses and at all time points. In addition area under the curve for DAS28-CRP was analyzed as time-adjusted mean change from baseline. A significant improvement in DAS28-CRP was shown with namilumab (150 and 300 mg groups combined) compared with placebo at day 43 (p = 0.0117) and also 8 weeks after last dosing at day 99 (p = 0.0154). CONCLUSIONS: Subcutaneous namilumab was generally well tolerated. Although namilumab demonstrated preliminary evidence of efficacy, patient numbers were small; phase 2 studies are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01317797 . Registered 18 February 2011.

[Possible Significance of Bronchoalveolar Lavage Cytology at Initial Diagnosis and Follow-up of Lung Cancer]. / Evaluation zum möglichen Stellenwert der Bronchiallavagezytologie bei Erstdiagnose und Nachsorge des Lungenkarzinoms.

Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer. Results We observed an elevated level of CD25 lymphocytes as well as an increased expression of DR antigen, both signaling lymphocyte activation. We could not find a typical cytologic pattern of inflammatory cells in lung carcinoma patients. Sensitivity of BAL to malignant cells was rare, thus confirming earlier analysis. Conclusion We could not demonstrate typical cellular patterns in BAL of lung cancer patients. Evaluation of specific microRNA patterns might play a supporting role in the initial diagnosis as well as follow-up of lung cancer patients.

O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies.

The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. The lack of O-GlcNAcylation diminished phospho-ERK and phospho-AKT levels. Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. O-GlcNAcylation of STAT5 could be required for nutrient sensing and metabolism of cancer cells.

Phytochemical, Antioxidant and Anticancer Activities of Extracts of Seven Fruits Found in the Southern Brazilian Flora.

Methanol extracts of seven edible fruits found in southern Brazil: Garcinia achachairu, Rubus imperialis, Rubus rosaefolius, Solanum quitoense, Solanum sessiliflorun, Diospyros inconstans and Plinia glomerata, were evaluated for their total phenol content and antioxidant activity in different in vitro free radical scavenging models. In addition, studies were performed on cell viability of extracts of the seeds of G. achachairu against murine melanoma cells. The fruits peel and seeds of G. achachairu were very promising in terms of total phenol content (data in gallic acid equivalent per gram), as assessed by the Folin-Ciocalteu method, with values of 9.70±3.2 and 8.40±1.1, respectively. On the other hand, antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl scavenging assay showed that the fruit pulp and peel of P. glomerata presented the best profile, with values of the 16.3±1.8 and 15.9±2.4 µg/ml, respectively. Regarding the cytotoxic effect of methanol extract and guttiferone A from G. achachairu, we have observed that both inhibit the growth of B16F10 tumor cells, with calculated IC50 values of 49.6±2.1 mg/ml and 48.6±5.4 mM, respectively.

In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells.

Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS(61K) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.

[Epitheloid cell granulomas in bronchial invasive mucinous adenocarcinoma]. / Epitheloidzellige Granulome bei bronchialem Adenokarzinom vom überwiegend muzinösen Typ.

Granulomatous lung diseases are frequently occurring pulmonary diseases.Important granulomatous lung diseases are sarcoidosis and pulmonary tuberculosis. Furthermore, granulomas can be caused by foreign body reactions like berylliosis or silicosis as well as by other infections (e. g. by nocardia spp.).Granulomatous systemic inflammatory diseases such as the Churg Strauss syndrome or the Wegener's granulomatosis can harm the lung as well.In this case report, we describe a patient who visited our emergency room because of apparent refractory pneumonia. First histologic specimens showed sarcoid-like lesions. Subsequent investigation showed invasive mucinous adenocarcinoma of the lung.

Erratum to "Practical guidelines: lung transplantation in patients with cystic fibrosis".

[This corrects the article DOI: 10.1155/2014/621342.].

Surgical management of haemorrhaging renal angiomyolipoma in pregnancy.

INTRODUCTION: Renal angiomyolipoma (AML) is a benign mesenchymal tumour of the kidney with a tendency of aneurysm formation at risk of rupturing. Due to increased maternal circulation and hormonal influences, rupture risk is greater in pregnancy, often leading to a vascular emergency and premature delivery or termination. PRESENTATION OF CASE: A 24-weeks pregnant woman (45 years old, G6P1) presented with haematuria and flank pain. CT showed AML with acute haemorrhage. The patient became haemodynamically unstable and underwent urgent embolisation and follow-on total radical nephrectomy with the foetus being left in-utero. This involved a multidisciplinary team (urologist, vascular surgeon, interventional radiologist and obstetrician). The procedure was uncomplicated and the pregnancy went to term with a healthy girl delivered at 38 weeks. DISCUSSION: The incidence of AML is 0.13% in the general population. 21 reports of haemorrhaging AML in pregnancy have been published in the last 35 years. Mean gestational age was 29.6 weeks. Eight were treated conservatively to term, one underwent exploratory laparotomy with evacuation of haematoma only, five were embolised, and seven were managed with nephrectomy. Of the nephrectomy subgroup, one was preceded by vaginal delivery and five underwent concurrent caesarean section (one with pre-op embolisation). There were two associated foetal deaths. CONCLUSION: This case demonstrates that with a multidisciplinary approach, it is possible to successfully leave a foetus undelivered whilst performing a radical nephrectomy for a large bleeding AML in a woman carrying a late second trimester pregnancy.

Per-operative hemodynamic instability in normotensive patients with incidentally discovered pheochromocytomas.

CONTEXT: The per-operative hemodynamic behavior of normotensive incidentally discovered pheochromocytomas is poorly documented. OBJECTIVE: To compare the per-operative hemodynamic instability and early postoperative outcome of normotensive pheochromocytomas, hypertensive pheochromocytomas, and benign non-pheochromocytoma adrenal incidentalomas (AIs). DESIGN: Retrospective cohort treated in a single center. PATIENTS AND METHODS: Fifty patients (10 normotensive pheochromocytomas, 24 hypertensive pheochromocytomas, and 16 AIs) were anesthetized and operated on by the same team, using laparoscopy in 78% of cases. Before surgery, 60% of normotensive and 95.8% of hypertensive pheochromocytomas received pretreatment with α-receptor or calcium channel blockers. All of the patients received the same intraoperative hemodynamic monitoring, including continuous direct intra-arterial pressure recording. RESULTS: All the features of hemodynamic instability, with the exception of the diastolic pressure nadir and fluid volume requirements, differed between hypertensive pheochromocytomas and AIs. Conversely, all features of hemodynamic instability were similar in hypertensive and normotensive pheochromocytomas. More specifically, by comparison with AIs, normotensive pheochromocytomas displayed higher maximal systolic pressure; more hypertensive, severe hypertensive, and hypotensive episodes; and a higher minimal heart rate, and also required more interventions to treat undesirable blood pressure elevations. Postoperative complications, all of which were mild, were more frequent in hypertensive pheochromocytomas than in normotensive pheochromocytomas (P < .03). CONCLUSIONS: Normotensive pheochromocytomas have roughly comparable per-operative hemodynamic instability to hypertensive pheochromocytomas and differ markedly from non-pheochromocytoma AIs. It is therefore crucial to identify normotensive pheochromocytomas among AIs when surgery is scheduled and to apply the standard of care for pheochromocytoma anesthesia.

Novel dendritic cell-based vaccination in late stage melanoma.

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play an important role in stimulating an immune response of both CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes (CTLs). As such, DCs have been studied extensively in cancer immunotherapy for their capability to induce a specific anti-tumor response when loaded with tumor antigens. However, when the most relevant antigens of a tumor remain to be identified, alternative approaches are required. Formation of a dentritoma, a fused DC and tumor cells hybrid, is one strategy. Although initial studies of these hybrid cells are promising, several limitations interfere with its clinical and commercial application. Here we present early experience in clinical trials and an alternative approach to manufacturing this DC/tumor cell hybrid for use in the treatment of late stage and metastatic melanoma.

[Measures to improve the health situation of patients with rare diseases in Germany. A comparison with the National Action Plan]. / Maßnahmen zur Verbesserung der gesundheitlichen Situation von Menschen mit seltenen Erkrankungen in Deutschland. Ein Vergleich mit dem Nationalen Aktionsplan.

BACKGROUND: Approximately 4 million patients with a rare disease live in Germany. The medical care of these patients is problematic because of the rarity and heterogeneity of different clinical pictures. The Federal Ministry of Health has therefore published a research report on "Measures to improve the health situation of people with rare diseases in Germany" in 2009. OBJECTIVE: The aim of this paper is to present the main recommendations of this research report and relate it to current developments in the field of medical care for people with rare diseases. METHODOLOGY: The care situation of patients with rare diseases was determined using questionnaires, expert interviews and focus group discussions with representatives of patients, service providers and stakeholders from the health institutions. RESULTS: The main range of actions that have been identified in the research report were centre and network formation, specialized forms of medical care, diagnosis and treatment, information and experience exchange, performance fees and reimbursement of the costs, guidelines and patient pathways, the research, the implementation of a National Action Alliance and the development of a National Action Plan. DISCUSSION: In March 2010 a National Action League for People with Rare Diseases (NAMSE) was founded. The NAMSE created a national plan of action for people with rare diseases for improving medical care in the field of rare diseases which was approved by the Federal Government in August 2013. Thus, two important areas of the research report have already been implemented. In a comparison of the areas of activity of the research report with those of the National Action Plan it becomes clear that priorities will be in the context of health services research in rare diseases, for example the introduction of centres of reference for rare diseases, measures to accelerate the diagnostic process and the promotion of research and information management in the future.

Practical guidelines: lung transplantation in patients with cystic fibrosis.

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.