Phase II study of neoadjuvant chemotherapy with gemcitabine and vinorelbine in resectable non-small cell lung cancer

OBJECTIVE: We assessed the efficacy of a non-platinum-containing doublet chemotherapy of gemcitabine and vinorelbine as induction therapy prior to surgical resection in patients with stage IB-IIIA and selected stage IIIB non-small cell lung cancer (NSCLC). The primary clinical end point was radiographic disease response rate, and the secondary end points were pathologic response rate, treatment-related toxicity, surgical resectability and outcome, and overall and disease-free survival. METHODS: Patients underwent staging with CT of the chest and upper-abdomen, whole-body F-18 fluorodeoxyglucose positron emission tomography, bronchoscopy, and mediastinoscopy. The patients had to have medically and surgically resectable disease. Chemotherapy consisted of gemcitabine, 1,000 mg/m(2), and vinorelbine, 25 mg/m(2), administered on days 1, 8, 22, and 29. Imaging studies were repeated between days 43 and 50. Disease response was assessed by response evaluation criteria in solid tumors, and patients with resectable disease were offered surgery between days 50 and 70. Patients were followed up every 3 months for 2 years with chest CT. RESULTS: Between January 2000 and March 2004, 27 patients with stage IB NSCLC, 15 patients with stage II NSCLC, and 20 patients with stage III NSCLC were entered. After induction chemotherapy 34% (95% confidence interval [CI], 23 to 48%) had an objective radiographic response, 2% had a complete pathologic response, 90% underwent thoracotomy, and 77% underwent a complete resection. There were four deaths in the 6-week period following surgery, and there were no deaths related to chemotherapy. There were no unexpected morbidities from surgery or chemotherapy. The 1-year and 2-year overall survival rates were 80% (95% CI, 68 to 88%) and 65% (95% CI, 50 to 76%), and the median overall survival was 38.2 months. CONCLUSIONS: Induction chemotherapy with gemcitabine and vinorelbine results in 1-year and 2-year survival rates and a median survival time comparable to those obtained with platinum-containing doublets. However, it appears to be less efficacious in terms of radiographic and pathologic response rates compared with platinum-containing chemotherapy doublets.     

Emergence of lyme arthritis after autologous chondrocyte transplantation

We report herein the first known incidence of the emergence of borrelial arthritis following autologous chondrocyte transplantation for repair of a cartilage defect. The patient had no recent manifestation of Lyme borreliosis, but 15 years earlier had had an expanding erythematous lesion after a tick bite. The current infection resulted in massive joint swelling, elevated body temperature, dissemination of the graft, and transplant failure. Results of routine bacteriologic studies were negative. A diagnosis of Lyme arthritis was first considered following the detection of Borrelia-specific serum antibodies. Additional evidence was provided when borrelial DNA sequences were detected in the synovial fluid through polymerase chain reaction. The diagnosis was confirmed by culture of Borrelia burgdorferi from the synovial fluid. The possibility of a dormant borrelial infection should be considered in patients who undergo repair of cartilage defects with autologous chondrocyte transplantation. We recommend that synovial fluid and joint tissue be screened for the presence of viable Borrelia before transplantation of an autologous graft.     

Lyme borreliosis

Lyme borreliosis is the most common tick-transmitted disease in the northern hemisphere and is caused by spirochaetes of the Borrelia burgdorferi species complex. A complete presentation of the disease is an extremely unusual observation in which a skin lesion results from a tick bite and is followed by heart and nervous system involvement, and later on by arthritis. Late involvement of eye, nervous system, joints, and skin can also occur. The only sign that enables a reliable clinical diagnosis of Lyme borreliosis is erythema migrans. Other features of some diagnostic value are earlobe lymphocytoma, meningoradiculoneuritis (Garin-Bujadoux-Bannwarth syndrome), and acrodermatitis chronica atrophicans. The many other symptoms and signs have little diagnostic value. Microbial or serological confirmation of borrelial infection is needed for all manifestations of the disease except for typical early skin lesions. However, even erythema migrans might not be pathognomonic for Lyme borreliosis, especially in the southern part of the USA where there is no microbiological evidence for infection with the agent. Treatment with antibiotics is beneficial for all stages of Lyme borreliosis, but is most successful early in the course of the illness. Prevention relies mainly on avoiding exposure to tick bites but there is some interest in chemoprophylaxis and also in vaccine development following initial disappointments.     

The outcome of the cementless tapered SL-Plus stem: an analysis of arthroplasty register data

Purpose

The aim of this study is to evaluate the outcome of the cementless SL-Plus stem in worldwide arthroplasty register datasets.

Methods

A structured analysis was conducted the registered data about the SL-Plus stem manufactured by Smith&;Nephew including published data from Australia as well as previously unpublished datasets from the Registers of Lombardia, Italy and Valdoltra, Slovenia. A total of 75% of the data analysed had not been published so far. The primary outcome measure was the revision rate, calculated in revisions per 100 observed component years. We evaluated a total of 10,684 primary and 122 revision surgeries with an average follow-up period of four years.

Results

All datasets showed good and reproducible results for treatment with the SL-Plus stem. An average of 0.31 revisions per 100 observed component years had been reported, which is considerably below the worldwide average (1.29) found for total hip arthroplasty independent of the product. The results of a large centre did not essentially deviate from the revision rates in Lombardia, where the numbers of cases per department are relatively low on average.

Conclusions

There were no indications for product defects or relevant errors in application. The SL-Plus stem can be considered a high-quality product that ensures good results also in the hands of less experienced surgeons. Data from even young registers can substantially contribute to the assessment of implants, even with the short follow-up periods. These datasets particularly allow for valid assessment of safety issues and can therefore make an essential contribution to the solution of problems of current relevance.     

Enteral application of an immunoglobulin-enriched colostrum milk preparation for reducing endotoxin translocation and acute phase response in patients undergoing coronary bypass surgery--a randomized placebo-controlled pilot trial

OBJECTIVE: To evaluate the influence of enteral application of an immunoglobulin enriched bovine milk preparation on endotoxin plasma levels, endotoxin neutralizing capacity of plasma (ENC) and the acute phase response (IL-6, CRP) during and after cardiac surgery, in a pilot study. DESIGN, PATIENTS AND METHODS: 60 patients who underwent coronary bypass operations, were evenly enrolled in a placebo-controlled randomized study. The patients were treated by enteral application of either 42 g of a bovine colostrum milk preparation per day or placebo, for 2 days preoperatively. Endotoxin and ENC were sequentially determined intra- and postoperatively by a chromogenic modification of the limulus amebocyte lysate test. Interleukin-6, CRP, transferrin, alpha-2-macroglobulin, albumin, apo-A, apo-B, IgG, IgA, IgM were determined by ELISA and nephelometrically. The clinical course was followed up by daily evaluation of the Apache-II-score. MAIN RESULTS: Demographic data were comparable in both groups. No differences of the Apache-II-score (verum group: 6.5 +/- 1.9 vs. controls: 6.8 +/- 1.8 on admission) were observed. Endotoxin and ENC levels were elevated at the end of the operation and seemed to have a trigger function for the acute phase response. However, there was no reduction (calculated as the area under the curve) in patients receiving the colostrum milk preparation throughout the observation period. Plasma levels of endotoxin binding proteins did not differ. Plasma IL-6 concentrations increased to maximal median values of 655 pg/ml in the verum and 786 pg/ml in the control group, respectively 2 and 6 h after surgery. In the colostrum group, there was a tendency to reduced IL-6 levels throughout the observation period. CRP-levels of all patients peaked 48 h after the operation but were lower (p = 0.034) in the verum group. CONCLUSION: This study revealed that endotoxemia occurs early in an elective non-intestinal surgical intervention, and is followed by a subsequent increase in mediators of the acute phase reaction. The prophylactic enteral application of a bovine milk preparation for two days in cardiac patients did reduce postoperative CRP-plasma levels but, contrary to a former double-blind study in abdominal surgery, failed to curtail perioperative endotoxemia. One reason could be the amount of colostrum preparation administered was too small.     

《国际功能、残疾和健康分类》:对物理和康复医学进行统一概念描述的模式

需要发展一个当代为国际上广泛接受的物理和康复医学（PRM）的概念描述。建立这种新的概念依赖于统一的概念模型和《国际功能、残疾和健康分类》（ICF）的分类体系。这种基于ICF的康复概念描述是将康复作为一种健康策略。欧盟医学专家委员会（UEMS）的康复专家正在致力于将ICF作为物理和康复医学的统一概念的模型，并依据此建立基于ICF的概念描述并给PRM下定义。根据此项目标，作者通过与欧盟物理和康复医学专业实践委员会成员的合作，对于属于医学专业的PRM作丁一个简明的定义。物理和康复医学是荩于功能评估的医学专业，包含健康状况的诊断和治疗，实旌、应用生物医学并结合其它更为广泛的干预方法，使残疾人或者可能经历残疾的人达到功能最佳化的目标。     

ICF Core Set for patients with cardiopulmonary conditions in early post-acute rehabilitation facilities

PURPOSE: The aim of this consensus process was to decide on a first version of the ICF Core Set for patients with cardiopulmonary conditions in early post-acute rehabilitation facilities. METHODS: The ICF Core Set development involved a formal decision-making and consensus process integrating evidence gathered from preliminary studies including focus groups of health professionals, a systematic review of the literature and empiric data collection from patients. RESULTS: Seventeen experts selected a total of 84 second-level categories. The largest number of categories was selected from the ICF component Body Functions (33 categories or 39% of all ICF Core Set categories). Four (5%) of the categories were selected from the component Body Structures, 23 (27%) from the component Activities and Participation, and 24 (29%) from the component Environmental Factors. CONCLUSIONS: The Post-acute ICF Core Set for patients with cardiopulmonary conditions is a clinical framework to comprehensively assess patients in early post-acute rehabilitation facilities, particularly in an interdisciplinary setting. This first ICF Core Set will be further tested through empiric studies in German-speaking countries and internationally.     

ICF Core Set for geriatric patients in early post-acute rehabilitation facilities

PURPOSE: The aim of this consensus process was to decide on a first version of the ICF Core Set for geriatric patients in early post-acute rehabilitation facilities. METHODS: The ICF Core Set development involved a formal decision-making and consensus process, integrating evidence gathered from preliminary studies including focus groups of health professionals, a systematic review of the literature and empiric data collection from patients. RESULTS: Fifteen experts selected a total of 123 second-level categories. The largest number of categories was selected from the ICF component Body Functions (51 categories or 41%). 14 (11%) of the categories were selected from the component Body Structures, 30 (29%) from the component Activities and Participation, and 28 (23%) from the component Environmental Factors. CONCLUSION: The Post-acute ICF Core Set for geriatric patients is a clinical framework to comprehensively assess patients in early post-acute rehabilitation facilities, particularly in an interdisciplinary setting. This first version of the ICF Core Set will be further tested through empiric studies in German-speaking countries and internationally.     

Treosulfan is an effective inducer of cell death in myeloma cell lines and primary myeloma cells from patients

Multiple myeloma is a non-curable haematological disease involving transformed plasma cells. High rates of complete remission can be achieved with autologous peripheral blood stem cell transplantation. Treosulfan is an alkylating substance that has been used in the treatment of ovarian carcinomas for many years. It has a favourable side-effect profile even at high-dose protocols. Thus, the objective of this study was to evaluate the effect of treosulfan on myeloma cells. The treatment of the myeloma cell lines, NCI-H929 and U266, with treosulfan led to apoptosis in both cell lines in a dose- and time-dependent manner. The induction of apoptosis was accompanied by cleavage of caspases -3 and -9 as well as downregulation of the antiapoptotic protein Mcl-1 and upregulation of the inhibitor of cyclin-dependent kinases, p21WAF1/CIP1. Furthermore, 100 micro mol/l treosulfan was capable of inducing cell death in 63.6 +/- 23.9% of primary myeloma cells, whereas treatment with the same concentration of melphalan showed 59.7 +/- 26% cell death. These in vitro concentrations were at least 10-fold lower than achievable plasma levels, even at conventional doses of treosulfan. Our results suggest that treosulfan might be an appropriate candidate for novel treatment protocols for patients with multiple myeloma.