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Liepe K.,GH Kassel | Kotzerke J.,University Hospital Dresden
Methods | Year: 2011

Internal radiotherapy is effective in the treatment of metastatic bone pain and can improve quality of life. A number of controlled studies using various agents have shown a mean response rate in pain relief of 70-80% of treated patients. Some investigators prefer radionuclides which emit low beta particles for the treatment of bone pain, because the assumption of lower bone marrow toxicity of this agents. However, neither dosimetric data for radiation absorbed dose to the bone marrow nor clinical blood count depression have shown any significant differences between these agents. Other researchers suggest enhanced antitumoral effects using high-energy beta emitters and propose aggressive first-line treatment in the early disease stage instead of using these radiopharmaceuticals only in end-stage patients suffering intractable bone pain. Another approach consists of including other treatment modalities such as autologous stem cell rescue or in combination with chemo or bisphosphonate therapy to a radionuclide treatment scheme. Future research should focus more on the curative effects of combination with radiosensitizer, for example, chemotherapy, or repeated treatments with bone seeking agents. © 2011 Elsevier Inc.


Kuester D.,University Hospital Dresden | Kuester D.,TU Dresden | Schmitt J.,University Hospital Dresden | Schmitt J.,TU Dresden
Journal of Allergy and Clinical Immunology | Year: 2014

Background Many patients with moderate-to-severe atopic dermatitis (AD) require systemic immunomodulating treatment to achieve adequate disease control. Objective We sought to systematically evaluate the efficacy and safety of systemic treatments for moderate-to-severe AD. Methods A systematic literature search was performed in MEDLINE, EMBASE, and CENTRAL (until June 2012). Randomized controlled trials (RCTs) evaluating systemic immunomodulating treatments for moderate-to-severe AD were included. Selection, data extraction, quality assessment, and generation of treatment recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were performed independently by 2 reviewers. Efficacy outcomes were clinical signs, symptoms, quality of life, and the course of AD. Safety data were compared by calculating the weekly incidence rates (as percentages) for adverse events. Results Thirty-four RCTs with 12 different systemic treatments and totaling 1653 patients were included. Fourteen trials consistently indicate that cyclosporin A efficaciously improves clinical signs of AD. Cyclosporin A is recommended as first-line treatment for short-term use. A second-line treatment option is azathioprine, but efficacy is lower, and evidence is weaker. Methotrexate can be considered a third-line treatment option. Recommendations are impossible for mycophenolate, montelukast, intravenous immunoglobulins, and systemic glucocorticosteroids because of limited evidence. A meta-analysis was not performed because of a lack of standardization in outcome measures. Conclusion Although 12 different interventions for moderate-to-severe AD have been studied in 34 RCTs, strong recommendations are only possible for the short-term use of cyclosporin A. Methodological limitations in the majority of trials prevent evidence-based conclusions. Large head-to-head trials evaluating long-term treatments are required. © 2013 American Academy of Allergy, Asthma & Immunology.


Lenders J.W.M.,Radboud University Nijmegen | Duh Q.-Y.,University of California at San Francisco | Eisenhofer G.,University Hospital Dresden | Gimenez-Roqueplo A.-P.,Assistance Publique Hopitaux de Paris | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Objective: The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. Conclusions: The Task Force recommends that initial biochemical testing for PPGLs should include measurements of plasma free or urinary fractionated metanephrines. Consideration should be given to preanalytical factors leading to false-positive or false-negative results. All positive results require follow-up. Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. 123I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic PPGLs. We recommend consideration of genetic testing in all patients, with testing by accredited laboratories. Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations. All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications. Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension. We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas. Partial adrenalectomy is an option for selected patients. Lifelong follow-up is suggested to detect recurrent or metastatic disease. Wesuggest personalized management with evaluation and treatment by multidisciplin aryteams with appropriate expertise to ensure favorable outcomes. © 2014 by the Endocrine Society.


News Article | November 30, 2016
Site: www.eurekalert.org

Brain scientists are using tropical fish to investigate how the spinal cord can be coaxed to repair itself after injury. The European research team has received £1.1 million (€1.3m) to investigate how zebrafish are able to repair and replace damaged nerve cells. Researchers will explore how these mechanisms can be triggered in other animals and human cells. They hope their findings will reveal new therapies that could be tested in patients with neurodegenerative conditions, such as motor neuron disease and multiple sclerosis. Such treatments could also help people with certain types of paralysis. The spinal cord carries vital connections between the brain and muscles called motor neurons, which are crucial for controlling movement of the body. Damage to these fragile nerve cells - either by injury or disease - is permanent and results in irreversible paralysis. Zebrafish have the remarkable ability to repair injured connections and replace damaged motor neurons, enabling them to regain full movement within four weeks after injury. They are also able to repair the specialised sheath that surrounds nerve cells - called myelin - which helps speed up the transmission of nerve impulses that control movement. The team - coordinated by the University of Edinburgh - includes brain experts from the French National Institute of Health and Medical Research (Inserm), University Hospital Dresden, DFG Centre for Regenerative Therapies Dresden, the Free University of Brussels (VUB) and the Nencki Institute of Experimental Biology of the Polish Academy of Sciences. Researchers are developing specialised microscope techniques to monitor the mechanisms of nerve cell repair in action. They hope to identify the molecular signals that instruct stem cells in the zebrafish's spinal cord to produce new motor neurons and stimulate repair of the myelin sheath. These factors will then be examined in further animal studies and laboratory tests on human cells. At the end of the three-year study, the researchers hope to identify potential therapies that can be taken forward into clinical trials involving patients with neurodegenerative diseases. The study is funded by the European Commission through the European Research Area Network for Neuroscience Research (ERA-NET NEURON) and co-funded through national funding agencies. Lead researcher Professor Catherina Becker, Director of the University of Edinburgh's Centre for Neuroregeneration, said: "This exciting project brings together leading experts from across Europe to explore the intrinsic capacity of the spinal cord to repair itself. We hope this will eventually lead to urgently needed therapies for people who have damage to their spinal cord, either from disease or injury."


Metzler K.D.,Max Planck Institute for Infection Biology | Fuchs T.A.,Max Planck Institute for Infection Biology | Fuchs T.A.,Harvard University | Nauseef W.M.,University of Iowa | And 6 more authors.
Blood | Year: 2011

The granule enzyme myeloperoxidase (MPO) plays an important role in neutrophil antimicrobial responses. However, the severity of immunodeficiency in patients carrying mutations in MPO is variable. Serious microbial infections, especially with Candida species, have been observed in a subset of completely MPOdeficient patients. Here we show that neutrophils from donors who are completely deficient in MPO fail to form neutrophil extracellular traps (NETs), indicating that MPO is required for NET formation. In contrast, neutrophils from partially MPOdeficient donors make NETs, and pharmacological inhibition of MPO only delays and reduces NET formation. Extracellular products of MPO do not rescue NET formation, suggesting that MPO acts cellautonomously. Finally, NET-dependent inhibition of Candida albicans growth is compromised in MPO-deficient neutrophils. The inability to form NETs may contribute in part to the host defense defects observed in completely MPO-deficient individuals. © 2011 by The American Society of Hematology.


Schmitt J.,University Hospital Dresden | Schmitt J.,TU Dresden | Langan S.,London School of Hygiene and Tropical Medicine | Deckert S.,University Hospital Dresden | And 4 more authors.
Journal of Allergy and Clinical Immunology | Year: 2013

Background: Clinical signs are a core outcome domain for atopic dermatitis (AD) trials. The current lack of standardization of outcome measures in AD trials hampers evidence-based communication. Objective: We sought to provide evidence-based recommendations for the measurement of clinical signs in AD trials and to inform the Harmonising Outcome Measures for Atopic Dermatitis Initiative. Methods: We conducted a systematic review on measurement properties of outcome measurements for clinical signs of AD. We systematically searched MEDLINE and Embase (until October 1, 2012) for validation studies on instruments measuring the clinical signs of AD. Grading of the truth, discrimination, and feasibility of scales; methodological study quality; and recommendations were based on predefined criteria. Results: Sixteen eligible instruments were identified, of which 2 were best validated. The Eczema Area and Severity Index has adequate validity, responsiveness, internal consistency, intraobserver reliability, and intermediate interobserver reliability but unclear interpretability and feasibility. The Severity Scoring of Atopic Dermatitis Index (SCORAD) has adequate validity, responsiveness, interobserver reliability, and interpretability and unclear intraobserver reliability. Only the objective SCORAD (ie, the clinical signs domain of the SCORAD) is internally consistent. The Six Area, Six Sign Atopic Dermatitis Index severity score and Three Item Severity Score fulfill some quality criteria, but the performance in other required measurement properties is unclear. The Patient-oriented Eczema Measure is reliable and responsive but has inadequate content validity to assess clinical signs of AD. The remaining 11 scales have either (almost) not been validated or performed inadequately. Conclusions: The Eczema Area and Severity Index and SCORAD are the best instruments to assess the clinical signs of AD. The other 14 instruments identified are (currently) not recommended because of unclear or inadequate measurement properties. © 2013 American Academy of Allergy, Asthma & Immunology.


Guldner A.,University Hospital Dresden | Pelosi P.,University of Genoa | De Abreu M.G.,University Hospital Dresden
Current Opinion in Anaesthesiology | Year: 2013

Purpose of Review: In this review, we aimed at providing the most recent and relevant clinical evidence regarding the use of nonventilatory strategies to prevent postoperative pulmonary complications (PPCs) after noncardiac surgery. Recent Findings: Although nonavoidable, most comorbidities can be modified in order to reduce the incidence of pulmonary events postoperatively. The physical status of patients suffering from chronic obstructive pulmonary disease, asthma, obstructive sleep apnea, and congestive heart failure can be improved preoperatively, and a number of measures can be undertaken to prevent PPCs, including physiotherapy for pulmonary rehabilitation and drug therapies. Also, smokers may benefit from both short and long-term smoke cessation. Furthermore, the risk of PPCs may be reduced upon: choice of an adequate anesthesia strategy (e.g. regional vs. general); appropriate neuromuscular blockade and reversal; use of volatile instead of intravenous anesthetics in lung surgery; judicious intravascular volume expansion (restrictive vs. liberal strategy); regional instead of systemic analgesia after major surgery in high-risk patients; more strict indication for nasogastric decompression in order to avoid silent aspiration; and laparoscopic instead of open bariatric surgery. Summary: Nonventilatory strategies can play an important role in reducing PPCs and improving clinical outcome after noncardiac surgery, especially in high-risk patients. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Spieth P.M.,University Hospital Dresden | Zhang H.,University of Toronto
Current Opinion in Critical Care | Year: 2014

PURPOSE OF REVIEW: Despite recent advances in the management of patients with acute respiratory distress syndrome (ARDS) by using protective ventilator strategies, the mortality rate of ARDS remains high. The complexity of the pathogenesis and the heterogeneity of coexisting diseases in patients with ARDS require critical care physicians and researchers to search for multiple therapeutic approaches in order to further improve patient outcome. This review article therefore focuses on the recent studies in the field of pharmacological intervention in ARDS. RECENT FINDINGS: A number of approaches for pharmacological intervention have been evaluated in patients with ARDS, but most of them failed to reduce mortality or improve outcomes despite some promising observations seen in preclinical studies. Prior methods such as nitric oxide inhalation, neuromuscular blocking agents and corticosteroids may still have a place in the treatment, while novel therapeutic approaches including the use of angiotensin-converting enzyme inhibitors, statins and stem cells are currently under investigation. SUMMARY: Overall, there is no proven pharmacological therapy in ARDS, but some pharmacological interventions were associated with beneficial effects in certain subgroups of patients depending on the cause, underlying diseases, the concurrent supportive therapies and timing. Further clinical trials are warranted to assess multiple outcome measurement of the promising pharmacological interventions in selected patients with ARDS. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Rachner T.D.,University Hospital Dresden | Platzbecker U.,TU Dresden | Felsenberg D.,Charité - Medical University of Berlin | Hofbauer L.C.,TU Dresden
Mayo Clinic Proceedings | Year: 2013

Osteonecrosis of the jaw (ONJ) is a common and potentially severe complication of antiresorptive therapy for bone metastases. However, its occurrence in patients treated for osteoporosis is rare. Although poor oral hygiene and invasive dental procedures have been identified as potential triggers, little is known about the role of other systemic risk factors. We describe a patient who developed ONJ after her first treatment with denosumab, a monoclonal antibody against receptor activator of NF-kB ligand. This patient had several comorbidities that prompted us to assess the German ONJ registry for the incidence of comorbidities in patients with ONJ. In summary, almost half of the patients (35 of 86 [41%]) had 1 or more risk factors thought to increase the risk of ONJ. In conclusion, comorbidities or comedications may increase the susceptibility of developing ONJ during osteoporosis therapy. © 2013 Mayo Foundation for Medical Education and Research.


Deckert S.,University Hospital Dresden | Kopkow C.,University Hospital Dresden | Schmitt J.,University Hospital Dresden | Schmitt J.,TU Dresden
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

The aims of this overview are to synthesize the current evidence of published systematic reviews (SRs) on nonallergic comorbidities of atopic eczema (AE). EMBASE and MEDLINE were searched for SRs published from inception to November 2012. SRs were selected independently based on predefined inclusion criteria. Methodological quality of SRs included was assessed by two independent reviewers using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. Nine SRs met all inclusion criteria. Six reviews addressing the association between AE and cancer suggest a decreased risk of glioma, meningioma, and acute lymphoblastic leukemia in patients with current or previous AE. One SR reported a consistent positive association of AE with attention-deficit hyperactivity disorder (ADHD). Diabetes mellitus type 1 and multiple sclerosis (MS) were not significantly related to AE in reviews based on cross-sectional and case-control studies. Patients with AE appear to be at decreased risk of brain tumors. The relationship of AE with Th1- and Th17-mediated (auto-)inflammatory conditions such as diabetes mellitus type 1 and MS should be clarified in prospective observational studies. Children with AE are at increased risk of ADHD. SRs on the risk of depression and Th17-mediated disorders such as inflammatory bowel disease of patients with AE are missing. © 2013 John Wiley & Sons A/S.

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