Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients.

BackgroundKetoconazole is a well-known CYP17-targeted systemic treatment for castration-resistant prostate cancer (CRPC). However, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. Chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200-300 mg three times daily) had PSA response rate (>50% decline) of 21-62%. We hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the CRPC post-chemotherapy state.MethodsMen with CRPC and performance status 0-3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA response rate (>50% reduction from baseline) where a rate of 25% was to be considered promising for further study (versus a null rate of <5%); 25 patients were required. Secondary endpoints included PSA response >30% from baseline, progression-free survival (PFS), duration of stable disease and evaluation of adverse events (AEs).ResultsThirty patients were accrued with median age of 72 years (range 55-86) and median pre-treatment PSA of 73 ng ml(-1) (range 7-11,420). Twenty-nine patients were evaluable for response and toxicity. PSA response (>50% reduction) was seen in 48% of patients; PSA response (>30% reduction) was seen in 59%. Median PFS was 138 days; median duration of stable disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 grade 3 AEs, only 3 were attributed to treatment. None of the two grade 4 AEs were considered related to treatment.ConclusionsIn docetaxel pre-treated CRPC patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy

Design of automotive structural components using high strength sheet steels structural strength of cold-formed steel I-beams and hat sections subjected to web crippling load

INTRODUCTION When cold-formed steel beam webs are subjected to partial edge loading, they may fail by web crippling rather than bending of the beam. Web crippling is caused by a highly localized intensity of the load or reaction. Because of the complexity of the web crippling behavior, empirical expressions are presently used for the design of cold-formed steel beams in buildings and automotive structural components to prevent web crippling. 1,2,3. The research on the structural behavior of cold-formed steel beam webs subjected to web crippling has been conducted at Cornell University and the University of Missouri-Rolla (UMR) under the sponsorship of the American Iron and Steel Institute (AISI).4,5 Since 1982, additional work has been performed at the University of Missouri-Rolla, Inland Steel Company, and Ford Motor Company to investigate the web crippling strength of automotive structural components using high strength sheet steels. 6-9 The research findings of the UMR study were summarized in the Eighth Progress Report. 7 In the UMR Fifth and Eighth Progress Reports, it was noted that if the I-beam specimens are subjected to the end one-flange loading without connecting the beam flange to the bearing plate, the failure of all sections used in the pilot tests occured by cross-bending of the flange about the connector location as shown in Fig. 1 instead of the conventional web crippling. This type of failure will be referred to as a flange cross-bending mode of failure in this report. It seems to be dependent primarily on the bend radius, the thickness of the web, the location of connectors and other parameters. Figure 2 shows the failure of an I-beam subjected to end one-flange loading. The tested loads for the specimens having the flange cross-bending type of failure were lower than those caused by the conventional web crippling. The purpose of this brief study reported herein was to review the test results described in Ref. 6 for the flange cross-bending type of failure of cold-formed steel I-beams using high strength sheet steels and to develop some new design criteria, if possible. Because of the limited number of test results, the present investigation can only be treated as a preliminary study of the problem. An extensive experimental work will be needed for the development of general design criteria. Section II contains a review of the experimental research results described in Ref. 6. In Section III, an analytical study of this type of failure mode for cold-formed steel I-beams is presented by using the finite element method. The development of an empirical expression for predicting the ultimate load is discussed in Section IV. Also included in this section is the comparison of test results and predicted values based on the newly developed equations for flange cross-bending failure. In addition to the study of the web crippling strength of I-beams, this report also evaluates the results of 157 beam tests using hat sections. These tests were conducted recently at the Research Laboratories of Inland Steel Company. Section V includes the information on beam specimens 10 and comparisons of the tested and predicted failure loads on the basis of the design recommendations proposed in Ref. 7. Finally, conclusions are drawn in Section VI

Efficacy of combined glucocorticoid and hyperbaric oxygen therapy against delayed encephalopathy after carbon monoxide poisoning, and its effect on expression of immune-associated cytokines

Purpose: To study the efficacy of glucocorticoid combined with hyperbaric oxygen therapy for the treatment of delayed encephalopathy after carbon monoxide poisoning (DEACMP), and its effect on the expression of immune-associated cytokines.Methods: A total of 102 DEACMP patients in PLA General Hospital, Haidian, China were divided into two groups of 51 patients each, namely, observation group (glucocorticoid + hyperbaric oxygen therapy), and control group (hyperbaric oxygen only). The clinical data for each group was retrospectively analyzed. Clinical efficacy, improvement time, hospitalization time, cognitive function, activities associated with daily living, changes in immunity-associated cytokines, and incidence of adverse reactions were compared for the two groups.Results: Following treatment, the time taken for improvement, duration of hospitalization, cognitive function, daily living activity and total effectiveness in the observation group were significantly higher than those for the control group (p < 0.05). In addition, the levels of transforming growth factor beta 1 (TGF- β1), interleukin 4 (IL-4) and interferon-gamma (IFN-γ) in the observation group were significantly greater than for the corresponding control group levels (p <0.05). There was no significant difference in incidence of adverse reactions between the two groups (p > 0.05).Conclusion: These results suggest that a combination therapy of glucocorticoid and hyperbaric oxygen therapy for the treatment of DEACMP is more eutherapeutic in the improvement of cognitive function and activities of daily living in DEACMP patients than hyperbaric oxygen therapy. The mechanism of this combination therapy may be related to the improvement in immunity-related cytokine levels.Keywords: Glucocorticoid, Hyperbaric oxygen, Delayed encephalopathy after carbon monoxide poisoning, Efficacy, Immunit