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Cross N.C.P.,University of Southampton | Cross N.C.P.,Wessex Regional Genetics Laboratory | White H.E.,Wessex Regional Genetics Laboratory | Muller M.C.,Universitatsmedizin Mannheim | And 2 more authors.
Leukemia | Year: 2012

The International Randomized Study of Interferon and STI571 (IRIS) demonstrated long-term cytogenetic responses in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with the tyrosine kinase inhibitor (TKI) imatinib. However, deep molecular responses (MRs), as measured by reductions in BCR-ABL transcript levels below the threshold of major MR, were achieved only by a small proportion of patients. With the advent of the second-generation TKIs nilotinib and dasatinib for the treatment of patients with newly diagnosed CML-CP, the proportion of patients who achieve the deepest levels of MR is likely to increase significantly. With these changes, the potential for patient eligibility in TKI cessations studies is becoming a more widely discussed topic and area for research. These developments highlight the need for robust, standardized and workable definitions of deep MRs. Specifically, it is critical that the measurement of MR is standardized in a manner to withstand both intra- and inter-laboratory variability, as well as new methodological developments. This review summarizes the relevant clinical background and proposes a framework within which standardization of MR can be taken forward. © 2012 Macmillan Publishers Limited.

Oettle H.,Charité - Medical University of Berlin | Neuhaus P.,Charité - Medical University of Berlin | Hochhaus A.,Universitatsklinikum Jena | Hartmann J.T.,University of Kiel | And 9 more authors.
JAMA - Journal of the American Medical Association | Year: 2013

IMPORTANCE: The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated. OBJECTIVE: To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival. DESIGN, SETTING, AND PATIENTS: CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012. INTERVENTIONS: After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up. RESULTS: A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0%[95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95%CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%). CONCLUSIONS AND RELEVANCE: Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting. TRIAL REGISTRATION: Identifier: ISRCTN34802808.

Li M.,Key Laboratory of Myopia | Zhou Z.,Yeshiva University | Shen Y.,Key Laboratory of Myopia | Knorz M.C.,Universitatsmedizin Mannheim | And 2 more authors.
Journal of Refractive Surgery | Year: 2014

PURPOSE: To compare the impact on corneal sensation after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (femto-LASIK) in patients with myopia. CopyrightMETHODS: In this prospective, nonrandomized comparative study, 71 subjects were enrolled. Thirty-eight eyes of 38 patients underwent SMILE and 33 eyes of 33 patients underwent femto-LASIK. Corneal sensation was tested with Cochet-Bonnet esthesiometry in five corneal areas preoperatively and at 1 week and 1, 3, and 6 months postoperatively. Comparison of corneal sensation was performed for the SMILE and femto-LASIK groups. Additionally, the correlations were evaluated between the postoperative corneal sensation, preoperative spherical equivalent, and ablation depth.RESULTS: All tested areas within the cap or flap demonstrated corneal hypoesthesia immediately after both surgeries. SMILE-treated eyes showed less compromised corneal sensation than femto-LASIK-treated eyes at all postoperative visits in the central, inferior, nasal, and temporal areas at the 1-week and 1-month visits. In the SMILE group, the inferior, nasal, and temporal quadrants recovered faster than other areas. In the femto-LASIK group, the sensation over the flap did not recover to preoperative levels by postoperative 6 months. There was no correlation between postoperative corneal sensation, preoperative spherical equivalent, and ablation depth in both groups.CONCLUSIONS: The impairment of corneal sensation was less significant in the SMILE group than in the femto-LASIK group and was independent of preoperative spherical equivalent or ablation depth. © SLACK Incorporated.

Children who require mechanical ventilation represent a high risk population with high morbidity and mortality. Experienced handling of conventional therapies, including high frequency oscillation ventilation and initiation of newer treatment options, such as therapy with surfactant or nitric oxide has led to some improvements. Nevertheless, extracorporeal membrane oxygenation (ECMO) is a life-saving technology for patients with respiratory failure refractory to maximum medical therapy. This article demonstrates the clinical management and selection criteria for ECMO in childhood contributing to the incidence and of acquired or inborn diseases which may lead to acute respiratory distress syndrome (ARDS). © 2011 Springer-Verlag.

Refractive surgery includes all procedures which are primarily targeted at changing the refractive power of the eye. Currently laser-assisted in situ keratomileusis (LASIK) is indicated to correct myopia of up to - 8 D, hyperopia up to + 3 D and astigmatism up to 5 D. Photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK) are primarily recommended for myopia up to - 6 D and for greater refractive errors, phakic intraocular lenses (IOL) are the first choice (myopia greater than - 6 D and hyperopia greater than + 3 D). If presbyopia is present in addition to the high refractive error, refractive lens exchange is another alternative. © Springer-Verlag Berlin Heidelberg 2013.

Hammes H.-P.,Universitatsmedizin Mannheim
Therapeutic Advances in Endocrinology and Metabolism | Year: 2013

Diabetic retinopathy (DRP) is a common complication caused by multiple biochemical abnormalities of the underlying metabolic disease. While the incidence of DRP appears to decline due to evidence-based changes in diabetes management, the predicted increase in patients affected in particular by type 2 diabetes may outweigh the positive trend. The diagnosis is based on the alterations of the vessels, usually indicating abnormalities of the blood-retinal barrier and increased vasoregression, but the neuroglial elements appear equally vulnerable to the diabetic condition. Control of blood glucose, blood pressure and timely identification of coincident nephropathy are important to prevent progression to vision-threatening stages. Guidelines give specific indications for laser photocoagulation, in particular when euglycemia is no longer effective in preventing progression to advanced stages. Intravitreal administration of antibodies directed against the single best characterized propagator of clinically significant macular edema, vascular endothelial growth factor (VEGF), has become popular despite uncertainty about the patient subgroups which benefit best and the optimum administration schedule. Multifactorial intervention beyond glycemic control includes antihypertensive, lipid-lowering and antiaggregatory and is effective in type 2 diabetic patients with high-risk profiles, in particular coincident nephropathy. © The Author(s), 2013.

Total knee arthroplasty (TKA) is one of the most common operations in orthopedic surgery worldwide but despite being mainly successful only 81% of patients are satisfied with the final result. The following systematic review compared patient satisfaction and analyzed the causal connections and influencing factors after TKA between 1990-1999 and 2000-2012. From 1990 to 1999 a total of 81.2% of patients were satisfied after TKA and in the period 2000-2012 patient satisfaction increased to 85%. Influencing factors on postoperative satisfaction derived from the 25 publications included in the study were consistently body-mass index, patient expectations, pain, joint function and mental factors. A lack of satisfaction scores and different designs resulted in difficulties in comparing the studies and were subsequently limitations of this study. © Springer-Verlag Berlin Heidelberg 2013.

Congenital diaphragmatic hernia (CDH) is a diagnosis with multiple, mostly unknown origin. Therefore its clinical presentation is highly variable. In case of prenatal detection prognosis and amount of interventions in neonatal intensive care is predictable. The results reported by high volume centres for CDH improved continuously during the last years. In neonates suffering from CDH without prenatal diagnosis severe respiratory distress is the leading clinical sign. Presenting symptom of late-onset CDH can also be gastrointestinal problems. Due to more subtle symptoms late presenting CDH is more difficult to diagnose. Prognosis is good, but it still requires surgical intervention to alleviate the symptoms. © Georg Thieme Verlag KG Stuttgart · New York.

Schwaab J.,Universitatsmedizin Mannheim
Blood | Year: 2013

To explore mechanisms contributing to the clinical heterogeneity of systemic mastocytosis (SM) and to suboptimal responses to diverse therapies, we analyzed 39 KIT D816V mutated patients with indolent SM (n = 10), smoldering SM (n = 2), SM with associated clonal hematologic nonmast cell lineage disorder (SM-AHNMD, n = 5), and aggressive SM (n = 15) or mast cell leukemia (n = 7) with (n = 18) or without (n = 4) AHNMD for additional molecular aberrations. We applied next-generation sequencing to investigate ASXL1, CBL, IDH1/2, JAK2, KRAS, MLL-PTD, NPM1, NRAS, TP53, SRSF2, SF3B1, SETBP1, U2AF1 at mutational hotspot regions, and analyzed complete coding regions of EZH2, ETV6, RUNX1, and TET2. We identified additional molecular aberrations in 24/27 (89%) patients with advanced SM (SM-AHNMD, 5/5; aggressive SM/mast cell leukemia, 19/22) whereas only 3/12 (25%) indolent SM/smoldering SM patients carried one additional mutation each (U2AF1, SETBP1, CBL) (P < .001). Most frequently affected genes were TET2, SRSF2, ASXL1, CBL, and RUNX1. In advanced SM, 21/27 patients (78%) carried ≥3 mutations, and 11/27 patients (41%) exhibited ≥5 mutations. Overall survival was significantly shorter in patients with additional aberrations as compared to those with KIT D816V only (P = .019). We conclude that biology and prognosis in SM are related to the pattern of mutated genes that are acquired during disease evolution.

Estimating the endotracheal tube size with the optimal internal diameter (ID) is of outstanding importance for airway management in pediatric patients. For many years different weight, height, and/or age-based formulas have been published. The aim of the present study was to identify and to compare published formulas to estimate optimal tube size in pediatric patients. A PubMed search was performed to identify published formulas for tube diameter in pediatric patients. The keywords "pediatric" or "paediatric", "anesthesia" or "anaesthesia", "anaesthesiology" or "anesthesiology", "size", "formula", "diameter", "tube" or "endotracheal tube" were used. Analysis was limited to articles published between 01.01.1951 and 30.06.2009. Additionally, similar publications retrieved from PubMed (related articles) and cited references were identified. Publications and formulas were assessed and classified by two independent colleagues. In the specified time-frame, 13 publications (11 original contributions and 2 letters to the editor) were identified with PubMed and 3 more formulas with the extended search. Altogether 22 formulas to estimate appropriate endotracheal tube size for pediatric patients (age 0-18 years) were identified: 12 age-based formulas for tubes without a cuff, 4 height-based formulas for tubes without a cuff, 2 weight-based formulas for tubes without a cuff and one multivariate formula for tubes without a cuff as well as 3 age-based formulas for cuffed endotracheal tubes. The identified formulas were comparatively simple to apply but were validated only for pediatric patients older than 1 year. Using tubes with a cuff can minimize the problem of optimal tube size. If a tube without a cuff is intended to be used other sizes should also be available.

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