Guckenberger M.,University of Würzburg |
Allgauer M.,Barmherzige Bruder |
Appold S.,Universitatsklinikum Dresden |
Dieckmann K.,University of Vienna |
And 9 more authors.
Journal of Thoracic Oncology | Year: 2013
INTRODUCTION: To evaluate safety and efficacy of stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) in a patterns-of-care and patterns-of-outcome analysis. METHODS: The working group "Extracranial Stereotactic Radiotherapy" of the German Society for Radiation Oncology performed a retrospective multicenter analysis of practice and outcome after SBRT for stage I NSCLC. Sixteen German and Austrian centers with experience in pulmonary SBRT were asked to participate. RESULTS: Data of 582 patients treated at 13 institutions between 1998 and 2011 were collected; all institutions, except one, were academic hospitals. A time trend to more advanced radiotherapy technologies and escalated irradiation doses was observed, but patient characteristics (age, performance status, pulmonary function) remained stable over time. Interinstitutional variability was substantial in all treatment characteristics but not in patient characteristics. After an average follow-up of 21 months, 3-year freedom from local progression (FFLP) and overall survival (OS) were 79.6% and 47.1%, respectively. The biological effective dose was the most significant factor influencing FFLP and OS: after more than 106 Gy biological effective dose as planning target volume encompassing dose (N = 164), 3-year FFLP and OS were 92.5% and 62.2%, respectively. No evidence of a learning curve or improvement of results with larger SBRT experience and implementation of new radiotherapy technologies was observed. CONCLUSION: SBRT for stage I NSCLC was safe and effective in this multi-institutional, academic environment, despite considerable interinstitutional variability and time trends in SBRT practice. Radiotherapy dose was identified as a major treatment factor influencing local tumor control and OS. © 2013 by the International Association for the Study of Lung Cancer.
Fitze G.,Universitatsklinikum Dresden
Trauma und Berufskrankheit | Year: 2017
Accidents are the main cause of death between the ages of 1 and 20 years. The abdomen is affected in up to 5% of cases and blunt abdominal trauma resulting in organ injuries is diagnosed in up to 20%. Thoracic trauma is a relatively uncommon injury in childhood, whereby lung contusions are the most frequent injuries of the lungs in childhood. In imaging diagnostics ultrasonography plays the most important role in childhood. The indications for abdominal contrast-enhanced computed tomography (CT) should be critically evaluated. With few exceptions, nonoperative management is the method of choice for these injuries in childhood. This approach has been evaluated for isolated injuries of the liver and spleen and is being used increasingly more for injuries of the kidneys. For injuries to the pancreas nonoperative management is also successful if the pancreatic duct is not involved. In contrast, injuries of the gastrointestinal tract nearly always necessitate a primary laparotomy; however, in general a laparotomy should be avoided. Preservation of organs is the primary aim of therapy. The indications for a primary surgical approach are circulation instability, perforation of an abdominal organ and peritonitis. Although the majority of thoracic injuries, such as fractures of the ribs and sternum as well as lung contusions are of moderate character and as a rule do not require surgical therapy, less common but more severe injuries in the tracheobronchial system, penetrating chest wounds and hematopneumothorax generally require emergency surgical interventions and are often associated with higher mortality due to mostly severe concomitant injuries. © 2017 Springer Medizin Verlag Berlin
Chemaly R.F.,University of Texas M. D. Anderson Cancer Center |
Ullmann A.J.,University Hospital Freiburg |
Stoelben S.,Mainz |
Richard M.P.,Mainz |
And 14 more authors.
New England Journal of Medicine | Year: 2014
BACKGROUND: Cytomegalovirus (CMV) infection is a leading cause of illness and death in patients who have undergone allogeneic hematopoietic-cell transplantation. Available treatments are restricted by clinically significant toxic effects and drug resistance. METHODS: In this phase 2 study, we evaluated the effect of letermovir (also known as AIC246), a new anti-CMV drug with a novel mechanism of action, on the incidence and time to onset of prophylaxis failure in CMV-seropositive recipients of allogeneic hematopoieticcell transplants from matched related or unrelated donors. From March 2010 through October 2011, we randomly assigned 131 transplant recipients in a 3:1 ratio to three sequential study cohorts according to a double-blind design. Patients received oral letermovir (at a dose of 60, 120, or 240 mg per day, or matching placebo) for 12 weeks after engraftment. The primary end point was all-cause prophylaxis failure, defined as discontinuation of the study drug because of CMV antigen or DNA detection, end-organ disease, or any other cause. Patients underwent weekly surveillance for CMV infection. RESULTS: The reduction in the incidence of all-cause prophylaxis failure was dose-dependent. The incidence of prophylaxis failure with letermovir, as compared with placebo, was 48% versus 64% at a daily letermovir dose of 60 mg (P = 0.32), 32% at a dose of 120 mg (P = 0.01), and 29% at a dose of 240 mg (P = 0.007). Kaplan-Meier time-to-onset profiles for prophylaxis failure showed a significant difference in the comparison of letermovir at a dose of 240 mg per day with placebo (P = 0.002). The safety profile of letermovir was similar to placebo, with no indication of hematologic toxicity or nephrotoxicity. CONCLUSIONS: Letermovir, as compared with placebo, was effective in reducing the incidence of CMV infection in recipients of allogeneic hematopoietic-cell transplants. The highest dose (240 mg per day) had the greatest anti-CMV activity, with an acceptable safety profile. Copyright © 2014 Massachusetts Medical Society.
Schaich M.,Universitatsklinikum Dresden
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013
To assess the treatment outcome benefit of multiagent consolidation in young adults with acute myeloid leukemia (AML) in a prospective, randomized, multicenter trial. Between December 2003 and November 2009, 1,179 patients (median age, 48 years; range, 16 to 60 years) with untreated AML were randomly assigned at diagnosis to receive either standard high-dose cytarabine consolidation with three cycles of 18 g/m(2) (3× HD-AraC) or multiagent consolidation with two cycles of mitoxantrone (30 mg/m(2)) plus cytarabine (12 g/m(2)) and one cycle of amsacrine (500 mg/m(2)) plus cytarabine (10 g/m(2); MAC/MAMAC/MAC). Allogeneic and autologous hematopoietic stem-cell transplantations were performed in a risk-adapted and priority-based manner. After double induction therapy using a 3 + 7 regimen including standard-dose cytarabine and daunorubicin, complete remission was achieved in 65% of patients. In the primary efficacy population of patients evaluable for consolidation outcomes, consolidation with either 3× HD-AraC or MAC/MAMC/MAC did not result in any significant difference in 3-year overall (69% v 64%; P = .18) or disease-free survival (46% v 48%; P = .99) according to the intention-to-treat analysis. Furthermore, MAC/MAMAC/MAC led to additional GI and hepatic toxicity and a higher rate of infection and bleeding, resulting in significantly shorter 3-year overall survival in the per-protocol analysis compared with 3× HD-AraC (63% v 72%; P = .04). In younger adults with AML, multiagent consolidation using mitoxantrone and amsacrine in combination with high-dose cytarabine does not improve treatment outcome and confers additional toxicity.
Gunther C.,Universitatsklinikum Dresden |
Beissert S.,Universitatsklinikum Dresden
Hautarzt | Year: 2015
Background: Lupus erythematosus is an autoimmune disease with a broad spectrum of cutaneous manifestations. The pathogenesis of lupus is based on a loss of tolerance against self antigens and can be mediated by defects in apoptosis, defects in eliminating cellular remnants and increased activation of the innate as well as the adaptive immune system. The increased activation of the innate immune system can be mediated by sensing of endogenous or exogenous nucleic acids, genetic variants in the components of the receptor cascade or disturbances in restriction of self nucleic acids. The inflammatory milieu is characterized by type I interferon expression and autoantibody production. The main trigger factors of the disease are sun exposure and viral infections. Treatment: Lupus erythematosus is effectively treated by glucocorticosteroids. Approved alternatives for long-term treatment are antimalarial agents and the B-cell inhibitor belimumab for patients with systemic lupus erythematosus. Conclusion: Future studies should more intensely analyse the effect of novel therapies on cutaneous manifestations to allow early detection of cutaneous lupus. Furthermore novel therapeutic strategies which specifically target the responsible pathogenetic mechanisms of the individual subtypes of lupus erythematosus are needed to improve the therapeutic success for this heterogeneous patient population. © 2015, Springer-Verlag Berlin Heidelberg.
Rollig C.,Universitatsklinikum Dresden |
Schmidt C.,Universitatsklinikum Dresden |
Bornhauser M.,Universitatsklinikum Dresden |
Ehninger G.,Universitatsklinikum Dresden |
And 2 more authors.
Journal of Immunotherapy | Year: 2011
Idiotype vaccines have shown both biological efficacy and clinical benefit in lymphoma. Circulating idiotype proteins (Id) in multiple myeloma patients offer a suitable target for immunotherapy. So far, specific immune responses after vaccination with Ids have been evaluated mostly in advanced myeloma. We explored the potential of dendritic-cell (DC)-based immunotherapy in 9 patients with stage-I disease. Mature monocyte-derived Id-pulsed DCs and keyhole limpet hemocyanin (KLH) were administered at dose levels between 2 and 20×10 6 cells. Patients received 5 immunizations every 4 weeks. A median number of 6.8×10 6 DCs were administered per vaccination. Five out of 9 patients (56%) developed Id-specific T cells as showed in proliferation assays and 8 out of 9 patients (89%) showed specific T-cell-mediated cytokine release after Id stimulation. The cytokine-secretion did not show a distinct Th1-type or Th2-type pattern. The M protein dropped slightly in 3 out of 9 patients. We could show that DC-based Id vaccination is a feasible way of inducing specific T-cell responses in stage-I myeloma patients. Further trials are needed to increase the rate of responses and to define the role of DC-based vaccination in the era of new pharmacologic therapies. © 2010 by Lippincott Williams & Wilkins.
Gunther C.,Universitatsklinikum Dresden
Hautarzt | Year: 2015
Lupus erythematosus is a prototypic autoimmune disease that can be triggered in genetically predisposed individuals by environmental exposures. The disease is based on an uncontrolled activation of the immune system that recognizes self antigens and induces inflammatory disease flares. The multifactorial pathogenesis is based on a polygenic model of inheritance with multiple various susceptibility genes elevating the disease risk. Many of these polymorphisms have been recently identified by genome-wide association studies. Monogenic forms of lupus erythematosus are rare. The identification of their underlying pathogenesis is important for the recognition of main mechanistic pathways in lupus as demonstrated by the history of defects in the complement system. The monogenic, autosomal dominant inherited familial chilblain lupus is characterized by cold-induced infiltrates on acral locations occurring in early childhood. Molecular exploration of the disease pathogenesis revealed that autoimmunity and especially lupus erythematosus can be induced by defects in intracellular elimination of nucleic acids and the subsequent type I-IFN-dependent activation of the innate immune system. This mechanism extends the concept of lupus pathogenesis: both defects in the extra- and intracellular elimination of autoantigens can lead to activation of the innate and adaptive immune system © 2015, Springer-Verlag Berlin Heidelberg.
Reiss M.,Elblandkliniken Meissen |
Reiss G.,Universitatsklinikum Dresden
Medizinische Monatsschrift fur Pharmazeuten | Year: 2010
The chronic otitis media is defined as a permanent perforation of the drum membrane, which does not close by itself, and an inflammatory reaction in the mucosa (mucositis) of the middle ear. Two main forms of the chronic otitis media are distinct: the suppurative otitis media and the cholesteatoma. The suppurative otitis media is often accompanied by secretion into the external ear canal (otorrhoe), but "dry ears" are also common. Other frequent, but not obligatory symptoms are hearing impairment, tinnitus, and aural pain or pressure. Although genetically determined microbial and immunological factors, as well as Eustachian tube characteristics, are supposed to be involved in the pathogenesis of chronic suppurative otitis media, many aspects of the pathogenesis still need to be clarified. Ear microscopy will show the perforation in the drum membrane. Further diagnostic tools are audiometry, vestibular testing, radiological examination (high-resolution computed tomography) and microbiological investigation. The curative treatment for chronic suppurative otitis media is surgery (tympanoplasty, i.e. closure of the perforation in the drum membrane and also - if necessary - the reconstruction of the ossicular chain), not conservative antimicrobial therapy.
Gunther C.,Universitatsklinikum Dresden
Hautarzt | Year: 2016
Autoimmune bullous diseases are characterized by intraepidermal or subepidermal autoantibody deposition that leads to blisters and secondary erosion. Mucous membranes are frequently affected in pemphigus vulgaris and always involved in cicatricial and mucosal pemphigoid. Mucosal lesions are detected less frequently in patients with bullous pemphigoid or epidermolysis bullosa acquisita. The diagnosis of autoimmune bullous disorders is based on determination of the subtype of autoantibodies bound in the skin and the clinical picture. Treatment is based on immunosuppression related to the type of disease and severity of the mucosal symptoms. Ocular involvement in mucosal pemphigoid and pemphigus vulgaris requires systemic treatment. © 2016 Springer-Verlag Berlin Heidelberg
Fitze G.,Universitatsklinikum Dresden
Trauma und Berufskrankheit | Year: 2016
Background: Accidents are the main cause of death between the ages of 1 and 20 years. Blunt abdominal trauma occurs in approximately 5 % of cases resulting in organ injury within the abdomen in about 25 %. The organs most involved are the kidneys and spleen followed by the liver, pancreas and the gastrointestinal (GI) tract. Diagnostics: In the field of radiological diagnostics ultrasound is the most important procedure in children. The indications for an abdominal computed tomography (CT) scan should be critically evaluated in the context of the clinical findings and the therapeutic consequences. Therapy: With only a few exceptions the non-operative management of abdominal organ injuries has become the established approach for children. This approach has been evaluated for spleen and liver injuries and is increasingly being applied for kidney injuries but in some rare cases a secondary nephrectomy is still necessary. For pancreatic injuries the non-operative management is also successful if the pancreatic duct is not involved. In contrast, in nearly all cases of injuries of the GI tract a primary laparotomy is necessary but generally, a laparotomy should be avoided. The preservation of the organ is the primary target of therapy. The indications for a surgical approach are circulation instability, perforation of the GI tract and peritonitis. © 2015, Springer-Verlag Berlin Heidelberg.