Karthaus M.,Klinikum Neuperlach |
Buchheidt D.,University of Mannheim
Current Pharmaceutical Design | Year: 2013
Aspergillus infections are a threat to in patients with hematological malignancies. Known risk factors are profound and long lasting neutropenia, uncontrolled graft versus host disease, continuous administration of steroids and environmental factors such as hospital construction. Numerous efforts have been undertaken for prophylaxis of invasive aspergillosis in high-risk populations. Most of them failed to demonstrate survival advantages. Prophylaxis makes sense, since diagnosis and treatment of invasive aspergillosis remain difficult. The introduction of non-culture based tools for the diagnosis of invasive aspergillosis is an important step forward for early and sensitive diagnosis of invasive aspergillosis. Early treatment is the cornerstone of a successful management of invasive aspergillosis. Substantial improvement came with the introduction of lipid formulations of amphotericin B in the early 1990s. Voriconazole was the first azole that improved the overall survival for patients with invasive aspergillosis. Newer azoles and the echinocandins were introduced for the treatment of invasive aspergillosis in the late 1990s. Voriconazole and liposomal amphotericin B allow a safer and more effective treatment of invasive aspergillosis when compared with amphotericin B-desoxycholate. Combination of antifungal agents has been introduced in clinical trials. Up to now no significant benefit has been obtained with antifungal combination compared to voriconazole alone. Because mortality of invasive aspergillosis remains up to more than 50%, prophylaxis, early diagnosis and early initiation of antifungal therapy are of utmost importance for the reduction of invasive aspergillosis related mortality. Despite all advances in the management of invasive aspergillosis important questions remain unresolved. This article reviews the current state and new insights in the management of invasive aspergillosis and points out clinicians unmet needs. © 2013 Bentham Science Publishers.
PubMed | Vivantes Klinikum Friedrichshain, Allgemein und Viszeralchirurgie, Franklin University, Friedrich - Alexander - University, Erlangen - Nuremberg and 6 more.
Type: Journal Article | Journal: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract | Year: 2016
Introduction of total mesorectal excision (TME) surgery for rectal cancer decreased local recurrence dramatically. Additional neoadjuvant chemoradiation (nCR) is frequently given in UICC II and III tumors based on TNM staging which is of limited accuracy. We aimed to evaluate determination of circumferential margin by magnetic resonance imaging (mrCRM) as an alternative criterium for nCR.Multicenter prospective cohort study which enrolled 642 patients in 13 centers with non-metastasized rectal adenocarcinoma. Patients with T4 tumors or patients with a mrCRM of 1 mm or less were treated by neoadjuvant chemoradiation. All others proceeded directly to surgery when inclusion criteria and no exclusion criteria were met. Quality of TME and accuracy of mrCRM determination were assessed during pathology workup.TME was complete in 381 of 389 patients after surgery without nCR (97.9%) and in 245 of 253 patients (96.8%) after nCR. Negative pathology circumferential margins (pCRM) were seen in 97.4% without nCR and in 89% of patients after nCR. Negative pCRM was predicted by negative mrCRM in 98.3% of rectal cancers. NCR was given to 253 of 642 patients (39.5%). Lymph node count was 23 (range 7-79; median/range) for surgery without nCR and 19 (range 2-56) for surgery after nCR.Surgical quality determined by pathology workup of specimen was very good in this study. Magnetic resonance imaging guided indication for nCR allows to achieve superb results concerning surrogate parameters for good oncological outcome. Thus, use of neoadjuvant chemoradiation with its potential detrimental side effects may be substantially reduced in selected patients.
Karthaus M.,Klinikum Neuperlach |
Tibor C.,G Hetenyi Hospital |
Lorusso V.,Instituto Tumori Giovanni Paolo II |
Singh-Arora R.,Sujan Surgical Cancer Hospital |
And 6 more authors.
Supportive Care in Cancer | Year: 2015
Purpose: This study aims to compare the efficacy and safety of oral palonosetron with intravenous (IV) palonosetron for the prevention of cisplatin-related chemotherapy-induced nausea and vomiting (CINV). Methods: A multinational, randomized, double-blind study enrolling adult chemotherapy-naive patients with malignant solid tumors scheduled to receive cisplatin-based highly emetogenic chemotherapy (HEC). Patients received oral palonosetron (0.50 mg) or IV palonosetron (0.25 mg), each with oral dexamethasone. The primary objective was to demonstrate non-inferiority in terms of patients with a complete response (CR, no emesis/no rescue medication) within the acute phase (0–24 h after chemotherapy administration). Results: Of the 743 patients randomized, 739 received study medications and 738 were included in the full analysis set. The CR rate in the acute phase was high for both groups (oral 89.4 %; IV 86.2 %). As this difference in proportions (stratum-adjusted Cochran-Mantel-Haenszel method) was 3.21 % (99 % confidence interval (CI) −2.74 to 9.17 %), non-inferiority was demonstrated (since the lower limit of the 99 % CI was closer to zero than the predefined margin of 15 %). Treatment-emergent adverse events (TEAEs) related to the study drug were rare (oral 3.2 %; IV 6.5 %). No TEAEs related to study drug leading to discontinuation were reported. Conclusion: Non-inferiority of oral versus IV palonosetron was demonstrated. The CR rate in the acute phase was >86 % in both patient groups. The safety profiles were comparable. © 2015, Springer-Verlag Berlin Heidelberg.
Glockner A.,BDH Klinik Greifswald GmbH |
Karthaus M.,Klinikum Neuperlach
Mycoses | Year: 2011
Sepsis is a leading cause of death in the intensive care unit (ICU), with Candida spp. in the forefront among the important pathogens. As recent studies have shown, survival outcome is strongly influenced by adequate antifungal therapy at an early stage that is often delayed by the time lag associated with microbiological diagnosis. Risk factor-based prediction models have a high negative predictive value, but positive prediction of candidaemia in the individual patient remains elusive. New antigen- or DNA-based methods for early diagnosis still await clinical validation. Their routine use is hampered by methodological issues. Species distribution of invasive Candida isolates in the ICU appears to be influenced primarily by age, previous hospitalisation and colonising species. In the context of the importance of adequate first-line treatment, recent guidelines favour the use of echinocandins in critically ill patients with symptoms evoking high suspicion of invasive candidiasis. This is supported by robust clinical trial data, a few interactions and low toxicity. Fluconazole is characterised by reduced activity against some important Candida species, elevated rates of persistent infection seen in comparative trials. Amphotericin B deoxycholate should be considered obsolete in ICU patients because of its high toxicity. Invasive aspergillosis (IA) is a rare devastating infection in the general ICU population, but some centres have reported elevated incidences and underdiagnosis as determined in autopsy-controlled studies. Treatment with mould-active agents such as voriconazole must be initiated early in patients with suspected IA. © 2010 Blackwell Verlag GmbH.
Rinninella E.,Catholic University of the Sacred Heart |
Kunda R.,Aarhus University Hospital |
Dollhopf M.,Klinikum Neuperlach |
Sanchez-Yague A.,Hospital Costa del Sol |
And 11 more authors.
Gastrointestinal Endoscopy | Year: 2015
Background and Aims A lumen-apposing, self-expanding metal stent incorporated in an electrocautery-enhanced delivery system for EUS-guided drainage of pancreatic fluid collections (PFCs) recently has become available. The aim of this study was to analyze the safety and clinical effectiveness of this newly developed device in this clinical setting. Methods This was a retrospective analysis of all consecutive patients with PFCs who underwent EUS-guided drainage using the study device in 13 European centers. Results Ninety-three patients with PFCs (80% with complex collections) underwent drainage using the study device. Penetration of the PFC was accomplished directly with the study device in 74.2% of patients, and successful stent placement was accomplished in all but 1 patient, mostly without fluoroscopic assistance. Direct endoscopic necrosectomy (DEN) was carried out in 31 of 52 cases (59.6%) of walled-off necrosis and in 2 of 4 cases (50%) of acute peripancreatic fluid collection. Complete resolution of the PFC was obtained in 86 cases (92.5%), with no recurrence during follow-up. Treatment failure occurred in 6 patients because of persistent infection requiring surgery (n = 3), perforation and massive bleeding caused by the nasocystic drainage catheter (NCDC) (n = 2), and the need for a larger opening to extract large necrotic tissue pieces (n = 1). Major adverse events occurred in 5 patients (perforation and massive bleeding caused by the NCDC in 2 patients, 1 pneumoperitoneum and 1 stent dislodgement during DEN, and 1 postdrainage infection) and were mostly not related to the drainage procedure. Conclusions EUS-guided drainage with the electrocautery-enhanced delivery system is a safe, easy to perform, and a highly effective minimally invasive treatment modality for PFCs. Copyright © 2015 by the American Society for Gastrointestinal Endoscopy.
Van Zanten A.R.H.,Gelderse Vallei Hospital |
Sztark F.,Bordeaux University Hospital Center |
Kaisers U.X.,University of Leipzig |
Zielmann S.,Heinrich Braun Klinikum |
And 13 more authors.
JAMA - Journal of the American Medical Association | Year: 2014
IMPORTANCE: Enteral administration of immune-modulating nutrients (eg, glutamine, omega-3 fatty acids, selenium, and antioxidants) has been suggested to reduce infections and improve recovery from critical illness. However, controversy exists on the use of immune-modulating enteral nutrition, reflected by lack of consensus in guidelines. OBJECTIVE: To determine whether high-protein enteral nutrition enriched with immune-modulating nutrients (IMHP) reduces the incidence of infections compared with standard high-protein enteral nutrition (HP) in mechanically ventilated critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: The MetaPlus study, a randomized, double-blind, multicenter trial, was conducted from February 2010 through April 2012 including a 6-month follow-up period in 14 intensive care units (ICUs) in the Netherlands, Germany, France, and Belgium. A total of 301 adult patients who were expected to be ventilated for more than 72 hours and to require enteral nutrition for more than 72 hours were randomized to the IMHP (n = 152) or HP (n = 149) group and included in an intention-to-treat analysis, performed for the total population as well as predefined medical, surgical, and trauma subpopulations. INTERVENTIONS: High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome measurewas incidence of new infections according to the Centers for Disease Control and Prevention (CDC) definitions. Secondary end points included mortality, Sequential Organ Failure Assessment (SOFA) scores, mechanical ventilation duration, ICU and hospital lengths of stay, and subtypes of infections according CDC definitions. RESULTS: There were no statistically significant differences in incidence of new infections between the groups: 53% (95% CI, 44%-61%) in the IMHP group vs 52% (95% CI, 44%-61%) in the HP group (P = .96). No statistically significant differences were observed in other end points, except for a higher 6-month mortality rate in the medical subgroup: 54% (95% CI, 40%-67%) in the IMHP group vs 35% (95% CI, 22%-49%) in the HP group (P = .04), with a hazard ratio of 1.57 (95% CI, 1.03-2.39; P = .04) for 6-month mortality adjusted for age and Acute Physiology and Chronic Health Evaluation II score comparing the groups. CONCLUSIONS AND RELEVANCE: Among adult patients breathing with the aid of mechanical ventilation in the ICU, IMHP compared with HP did not improve infectious complications or other clinical end points and may be harmful as suggested by increased adjusted mortality at 6 months. These findings do not support the use of IMHP nutrients in these patients. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2181.
Karthaus M.,Klinikum Neuperlach
European Journal of Medical Research | Year: 2011
Major progress for the management of invasive aspergillosis has come from the introduction of new antifungals since the late 1990s. Although mortality of invasive aspergillosis remains as high as 30-50%. Backbone of management are prophylaxis, early diagnosis and early initiation of antifungals for reduction of invasive aspergillosis related mortality. Randomized trials have been undertaken for the prophylaxis as well as treatment of invasive aspergillosis in the last two decades. Posaconazole is recommended for prophylaxis against aspergillosis in patients treated for acute myelogenous leukemia, myelodysplastic syndrome or patients with graft versus host disease after allogeneic transplantation. Efficacy has been shown for first-line therapy of invasive aspergillosis with voriconazole and liposomal amphotericin B. Gastrointestinal resorption for the azoles posaconazole, voriconazole and itraconazole differ considerably. While oral voriconazole resportion is reduced when taken with food, posaconazole has to be taken with fatty food for optimal intestinal resorption. Beside all advances in the management of invasive aspergillosis important questions remain unresolved. This article reviews the current state of prophylaxis and treatment of invasive aspergillosis and points out clinicians unmet needs. © I. Holzapfel Publishers 2011.
Montag M.,Ludwig Maximilians University of Munich |
Blankenstein T.J.F.,Ludwig Maximilians University of Munich |
Shabani N.,Klinikum Neuperlach |
Bruning A.,Ludwig Maximilians University of Munich |
Mylonas I.,Ludwig Maximilians University of Munich
Archives of Gynecology and Obstetrics | Year: 2011
Introduction The role of human papilloma virus (HPV) in the pathogenesis of anogenital dysplasia is now conclusive. However, HPV detection in formalin-fixed and paraffinembedded tissues remains controversial. Therefore, the aim of this study was to evaluate morphological changes directly in tissue specimens using a HPV-DNA detection system involving HPV in situ hybridisation. Materials and methods Samples from patients with cervical carcinoma were analysed using the GenPoint HPV DNA Probe Cocktail (Dako, Glostrup, Denmark) and the ZytoFast HPV Screening CISH-Kit (Zytomed, Berlin, Germany). Three cervical carcinoma cell lines with a welldefined HPV copy number per cell (SiHa, HeLa, and CaSki) served as positive controls for sensitivity testing, while two HPV-negative cell lines (AC-1M32, MCF-7) and brain tissue samples served as negative controls. Moreover, to assess the validity of the in situ hybridisation, the expression of HPV-16DNAin cell lines was demonstrated by HPV-16 E6- specific PCR. Results Both HPV-screening assays revealed strong signals of episomal and integrated HPV-DNA at a HPV copy number of more than 50 copies/cell. All cervical carcinoma samples were positive in the Dako assay, which identifies 13 high-risk HPV genotypes, whereas HPV-DNA could be detected in 9/10 cervical carcinoma samples using the Zytofast assay, identifying HPV 16, 18, 31, 33, and 35. Conclusion HPV in situ hybridisation is a convenient and powerful tool for detecting HPV-DNA in formalin-fixed and paraffin-embedded tissue samples. Therefore, this technique is suitable for analysis of a potential HPV infection using archival pathological slides. © Springer-Verlag 2010.
PubMed | Klinikum Neuperlach, University of Bern, University of Kiel and Cedars Sinai Medical Center
Type: Journal Article | Journal: Asian cardiovascular & thoracic annals | Year: 2016
Type A aortic dissection is a life-threatening disease requiring immediate surgical treatment. With emerging catheter-based technologies, endovascular stent-graft implantation to treat aneurysms and dissections has become a standardized procedure. However, endovascular treatment of the ascending aorta remains challenging. Thus we designed an ascending aortic dissection model to allow simulation of endovascular treatment.Five formalin-fixed human aortas were prepared. The ascending aorta was opened semicircularly in the middle portion and the medial layer was separated from the intima. The intimal tube was readapted using running monofilament sutures. The preparations were assessed by 128-slice computed tomography. A bare-metal stent was implanted for thoracic endovascular aortic repair in 4 of the aortic dissection models.Separation of the intimal and medial layer of the aorta was considered to be sufficient because computed tomography showed a clear image of the dissection membrane in each aorta. The dissection was located 3.91.4cm proximally from the aortic annulus, with a length of 4.60.9cm. Before stent implantation, the mean distance from the intimal flap to the aortic wall was measured as 0.630.163cm in the ascending aorta. After stent implantation, this distance decreased to 0.260.12cm.This model of aortic dissection of the ascending human aorta was reproducible with a comparable pathological and morphological appearance. The technique and model can be used to evaluate new stent-graft technologies to treat type A dissection and facilitate training for surgeons.
PubMed | Klinikum Neuperlach
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
4079 Background: LR is currently the curative approach of CLM. Validated PF are helpful for decisions regarding primary surgery and chemotherapy of CLM. The question of adjuvant ctx after LR is still open. The aim of the study was to analyze PF for survival after resection of CLM.Consecutive pts with CLM and LR were studied. Between 01/1990 and 12/2003 a total of 257 pts with CLM (colon 121, rectal ca 136) received LR in a Munich CRC center. 106 pts had synchrone and 151 had metachrone CLM. After LR of CLM 155 (60%) out of 257 received Ctx.Post-op mortality was 1.2% (3/257). Median survival after LR was 55.6 mo with a 5-ys of 47.1% and a 10-ys survival of 18.1 %. Median (55.8 vs 55.7 mo) and 5-ys OS (46.3 vs 47.6 mo) did not differ between syn- or metachrone LM. Initial LN status of pts with CLM was pN0 in 115/256 pts, while this was pN1 in 67 pts, pN2 in 43 and pN3 in 28. LN-status was associated with inferior OS. Median OS was 64.7 mo in pN0, while this was 53.8 in pN1, 41.2 in pN2 and 32.0 mo in pN3 pts with a 5-ys survival of 58% for pN0, 46.7% for pN1, 42.9% for pN2 and 21.4% for pN3 respectively (p=0.0025). A R0 LR of CLM was performed in 167/256, while this was R1 in 20, R2 in 11 and Rx in 59 pts. Pts with R0 resection had an OS of 65.4 mo, while this was significantly inferior in R1 (24.4 mo) and R2 resections (19.9 mo; p=0.0001). LM number (1 vs 2-3 vs >4) was associated with a worsening median (65.4 vs 48.1 vs 41.2 mo) and 5-ys survival (55.4 vs 37.9 vs 29.1 mo; p=0.0012). LM size ( <5 vs 5-10 >10 cm) was associated inversely with median (60.2% vs 42.9% vs 30.2%) and 5-ys OS (50.9% vs 39.8% vs 0%; p=0.0007). Adjuvant Ctx following LR improved median (63.6 vs 47.5 mo) as well as 5- ys OS (54.1% vs 39.1%). A total of 64 of 256 pts remained free of disease (med OS 136 mo) while 45 had new metachrone LM, 87 had LM and extrahepatic M and only 26 pts had a extrahepatic distant M.No difference in OS was observed between pts with syn- or metachrone CLM, while an increasing number and size of LM was associated with a worsening OS. Postoperative ctx after LR of CLM improved 5-ys survival and should be investigated in further trials. No significant financial relationships to disclose.