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Current practice of methotrexate use for psoriasis: results of a worldwide survey among dermatologists 下载免费PDF全文
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A multicentre,randomized, placebo‐controlled trial establishing the treatment effect of TDT 068, a topical formulation containing drug‐free ultra‐deformable phospholipid vesicles,on the primary features of erythematotelangiectatic rosacea 下载免费PDF全文
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Ran Reshef Alex Ganetsky Edward P. Acosta Robin Blauser Lisa Crisalli Jessica McGraw Noelle V. Frey Elizabeth O. Hexner James A. Hoxie Alison W. Loren Selina M. Luger James Mangan Edward A. Stadtmauer Rosemarie Mick Robert H. Vonderheide David L. Porter 《Biology of blood and marrow transplantation》2019,25(3):515-521
Graft-versus-host disease (GVHD) remains the most common treatment-related complication after allogeneic hematopoietic cell transplantation (allo-HCT). Lymphocyte migration plays a critical role in the pathogenesis of GVHD. A previous phase I/II trial demonstrated that CCR5 blockade with maraviroc in the first 30days after allo-HCT resulted in a low incidence of early acute GVHD, primarily in visceral organs, but with no impact on late acute or chronic GVHD.We conducted a phase II trial to examine the efficacy of an extended course of maraviroc, administered through post-transplantation day +90 in addition to standard prophylaxis in 37 recipients of reduced-intensity-conditioned unrelated donor allo-HCT performed to treat hematologic malignancies.Extended maraviroc treatment was safe and feasible. The primary study endpoint, day +180 rate of grade II-IV acute GVHD, was 22 ± 7%, liver GVHD was not observed, and gut GVHD was uncommon. The day +180 rate of grade III-IV acute GVHD was 5 ± 4%. The 1-year rate of moderate to severe chronic GVHD was 8 ± 5% and that of disease relapse was 30 ± 8%. Overall survival at 1 year was 70 ± 8%. Compared with the previously studied short course of maraviroc, the extended course resulted in a significantly higher GVHD-free, relapse-free survival (adjusted hazard ratio [HR], .45; 95% confidence interval [CI], .25 to .82; P?=?.009) and overall survival (adjusted HR, .48; 95% CI, .24 to .96; P?=?.037). A combined analysis of both trials showed that high maraviroc trough concentrations on the day of hematopoietic cell infusion were associated with lower rates of acute GVHD.An extended course of maraviroc after reduced-intensity-conditioned unrelated donor allo-HCT is safe and effective in preventing acute and chronic GVHD and is associated with favorable survival. 相似文献
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We describe a case of 64-year-old female patient with ventricular tachycardia intractable to medical treatment and acute heart failure following myocardial infarction. Emergency surgical ventricular reconstruction and subendocardial resection was undertaken. We discuss the option of surgical intervention in this difficult and unusual clinical scenario. 相似文献
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Urothelial carcinoma of the bladder is difficult to treat in advanced and metastatic stages. Several factors play a role: age, multimorbidity including impaired renal function and neuropathy make access to life-prolonging chemotherapy impossible in many cases. Improvements of response rates and overall survival in the second-line setting are not much different compared to best supportive care. However, the therapeutic landscape has changed dramatically during the last 2 years. Immunotherapies represented by checkpoint inhibitors have showed positive trial outcomes and have been approved by EMA (European Medicines Agency). Both in second-line therapy after platinum-based chemotherapy and in first-line therapy in unfit patients, these drugs can be used. New concepts with combinations of immunotherapeutic compounds are currently being examined in various trials. If we follow the data of other malignancies (melanoma and non-small cell lung cancer), the future looks optimistic. 相似文献
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Lisa M. Crisalli Joanne T. Hinkle Christopher C. Walling Mary Sell Noelle V. Frey Elizabeth O. Hexner Alison W. Loren Selina M. Luger Edward A. Stadtmauer David L. Porter Ran Reshef 《Biology of blood and marrow transplantation》2018,24(6):1203-1208
Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a curative option for patients with hematologic malignancies who are unable to undergo myeloablative conditioning, but its success is limited by high rates of relapse. Several studies have suggested a role for T cell doses in peripheral blood stem cell grafts in RIC HSCT. Because T cell dose is typically not known until after the collection, and apheresis blood volume is easily modifiable, we hypothesized that higher donor apheresis blood volumes would improve transplantation outcomes through an effect on graft composition. Thus, we analyzed the relationships between apheresis volume, graft composition, and transplantation outcomes in 142 consecutive patients undergoing unrelated donor allogeneic RIC HSCT. We found that apheresis volume ≥15 L was associated with a significantly decreased risk of relapse (adjusted hazard ratio [aHR], .48; 95% confidence interval [CI], .28 to .84]; P?=?.01) and improved relapse-free survival (aHR, .56; 95% CI, .35 to .89; P?=?.02) and overall survival (aHR, .55; 95% CI, .34 to .91; P?=?.02). A high apheresis volume was not associated with increased rates of acute or chronic graft-versus-host disease. These results demonstrate that an apheresis volume of at least 15 L is independently predictive of improved transplantation outcomes after RIC allogeneic HSCT. 相似文献
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Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light 总被引:20,自引:4,他引:20 下载免费PDF全文
A K?ck T Schwarz R Kirnbauer A Urbanski P Perry J C Ansel T A Luger 《The Journal of experimental medicine》1990,172(6):1609-1614
Tumor necrosis factor alpha (TNF-alpha), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-alpha. Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-alpha-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF-alpha activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-alpha revealed a molecular mass of 17 kD for keratinocyte-derived TNF-alpha. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF-alpha in LPS- or ultraviolet B (UVB)-treated HNK and KB cells. In addition, increased TNF-alpha levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-alpha, which may gain access to the circulation. Thus, TNF-alpha in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation. 相似文献