In vitro study of the impact of drug ABX on primary human macrophages derived from peripheral blood monocytes in an inflammatory context : Involvement of microRNA 124
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Rosenblith and Stevens reported in 1953 that difference thresholds for frequency measured by an ABX procedure were at least twice as great as those measured by an AX procedure. Their report is consistent with the great bulk of the literature. The relationship has always been rationalized in terms of the greater physical and judgmental complexity of the ABX procedure. The present experiment was performed at 120 cps, 70 dB SPL, with two practiced subjects. For frequency differences of plus or minus 0.3 cps, or one-fourth of 1%, responses were 95% correct for ABX and 82% correct for AB. This result contradicts the usual finding, and suggests a need for an experimental analysis of frequency-judgment mechanisms. The experimental data were collected at the Massachusetts Institute of Technology Research Laboratory of Electronics.
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e17116 Background: There is emerging evidence that antibiotic (Abx) use may be associated with poor response to immune-checkpoint inhibitors (ICIs) in patients (pts) with some solid tumors. However, this has not been studied in metastatic urothelial carcinoma (mUC). We examined the effect of Abx use on outcomes in pts receiving ICIs for mUC. Methods: We retrospectively reviewed adult pts receiving ICIs for mUC treated at Cleveland Clinic between 2015 and 2020. Pts included in the study received > / = 3 cycles of ICI therapy with either azetolizumab or pembrolizumab. Abx use was defined as at least 3 days of Abx in the 60 days preceding or following ICI initiation. PFS and OS were estimated using the Kaplan-Meier method and a Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI). Results: A total of 69 pts with mUC receiving ICI therapy were included. The Abx-treated group consisted of 22 pts (32%) and the Abx-untreated group was 47 pts (68 %). 30 pts had Abx 60 days prior to ICI initiation and 20 patients had Abx within 60 days of ICI initiation. Abx use 60 days prior to ICI was not associated with PFS (HR = 0.91, 95% CI = 0.42-1.95) or OS (HR = 0.52, 95% CI = 0.33-1.68). Abx use during the first 60 days of ICI use was associated with decreased PFS (HR = 2.23, 95% CI = 1.03-4.86) but not OS (HR = 2.01, 95% CI = 0.89-4.53). Notably, there was no effect on response rates. The most commonly used Abx prior to treatment were: fluoroquinolones (30%); cephalosporins (26%); non-cephalosporin beta lactams (17%); and trimethoprim-sulfamethoxasole (13%). The most commonly used Abx after treatment initiation were: fluoroquinolones (17% of patients); cephalosporins (13%); non-cephalosporin beta lactams (12%); and trimethoprim-sulfamethoxasole (9%). Our study was insufficiently powered to address the effect of different antibiotic classes on outcomes. Conclusions: In our study, Abx use within first 60 days of treatment with ICIs was associated with decreased PFS and a trend toward decreased OS in pts with mUC but not in pts receiving Abx 60 days prior to ICI therapy. While the numbers are small, this is the first report exploring the effect of Abx on ICI response in mUC and further studies in larger databases are warranted.
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5045 Background: Although recent evidence has suggested that patients who receive antibiotics (ABX) during the course of ICI treatment might decrease overall survival (OS) (1), our previous analysis did not support a difference in OS in urothelial cancer patients who did and did not use ABX during the course of ICI treatment without regard to timing (2). This updated analysis aims to addresses the question of timing; specifically, use of ABX in the 30-day window pre- or post- initiation of ICI treatment. Methods: We pooled data from 7 trials that led to drug approval and which included 1747 patients with advanced urothelial cancer treated with an ICI. Five trials enrolled patients who received prior platinum and 2 enrolled cisplatin-ineligible patients. Concomitant medication datasets were searched for systemic ABX use. The association between ABX use and survival was evaluated using Kaplan-Meier estimates and Cox proportional hazards regression models stratified by study. Results: Overall, 56% of patients were exposed to antibiotics (ABX+) and 43% were not exposed (ABX-). In an exploratory analysis, median OS was similar between arms: 9.7 vs. 9.3 months in ABX+ vs. ABX- patients, respectively (HR 0.96). However, OS results differed in the 27% of patients who were exposed to antibiotics in the 30-day window pre- or post- initiation of ICI treatment, for whom median OS was 4.7 months vs. 11.5 months in the ABX+ vs. ABX- patients, respectively (HR 1.8). This remained true after controlling for baseline risk prognostic factors (Bajorin and Bellmunt scores). Similar trends were observed for progression-free survival (PFS). Conclusions: Patients treated with ABX while on therapy with an ICI for urothelial cancer had similar OS outcomes to those not treated with ABX. However, in an exploratory analysis looking at ABX use in the 30-day window pre- or post-initiation of ICI treatment, OS appeared decreased in ABX+ vs ABX- patients. Our exploratory analyses appear to show an association of OS/PFS with timing of antibiotics. References: 1) Routy B, Science (2017) 2) Weinstock C, ASCO 2019, abstract. [Table: see text]
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It is often reported that difference thresholds for frequency when measured by an ABX procedure are at least twice as great as those measured by an AB procedure. The relationship has always been rationalized in terms of the greater phsyical and judgmental complexity of the ABX procedure. The present experiment was performed at 120 cps, 70 dB SPL, with two practiced subjects. For frequency differences of plus or minus 0.3 cps, or 0.25%, responses were 95% correct for ABX, and 82% correct for AB. This result contradicts the usual findings, and suggests a need for a new analysis of frequency-judgment mechanisms.
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Abstract Objective: To (1) understand the role of antibiotic-associated adverse events (ABX-AEs) on antibiotic decision-making, (2) understand clinician preferences for ABX-AE feedback, and (3) identify ABX-AEs of greatest clinical concern. Design: Focus groups. Setting: Academic medical center. Participants: Medical and surgical house staff, attending physicians, and advanced practice practitioners. Methods: Focus groups were conducted from May 2022 to December 2022. Participants discussed the role of ABX-AEs in antibiotic decision-making and feedback preferences and evaluated the prespecified categorization of ABX-AEs based on degree of clinical concern. Thematic analysis was conducted using inductive coding. Results: Four focus groups were conducted ( n = 15). Six themes were identified. (1) ABX-AE risks during initial prescribing influence the antibiotic prescribed rather than the decision of whether to prescribe. (2) The occurrence of an ABX-AE leads to reassessment of the clinical indication for antibiotic therapy. (3) The impact of an ABX-AE on other management decisions is as important as the direct harm of the ABX-AE. (4) ABX-AEs may be overlooked because of limited feedback regarding the occurrence of ABX-AEs. (5) Clinicians are receptive to feedback regarding ABX-AEs but are concerned about it being punitive. (6) Feedback must be curated to prevent clinicians from being overwhelmed with data. Clinicians generally agreed with the prespecified categorizations of ABX-AEs by degree of clinical concern. Conclusions: The themes identified and assessment of ABX-AEs of greatest clinical concern may inform antibiotic stewardship initiatives that incorporate reporting of ABX-AEs as a strategy to reduce unnecessary antibiotic use.
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客观白朊界限 paclitaxel (abraxane， ABX ) 比常规 taxanes 有更有利的功效和更少的毒性。然而，在先进胃的癌症(自动增益控制) 的 ABX 的数据治疗是无法获得的。当前的学习被设计在与 ABX 对待自动增益控制病人总结我们的经验。从 2010 年 1 月 10 日在孙中山大学癌症中心收到了基于 ABX 的化疗的至少一个周期到 2012 年 5 月 14 日的有自动增益控制的病人的临床的数据回顾地被分析的方法……47 全部的结果 A 包含 ABX 政体骑车，与一 3 个周期中部(范围：18 个周期) ，予 14 个病人被以。五(35.7%) 部分回答并且 6 (42.9%) 稳定的疾病被获得，与 78.6% 的疾病控制率(DCR ) 。中部的前进免费幸存(PFS ) 和全面幸存(OS ) 分别地是 3.3 和 10.8 个月。有趣地，在首要的背景的病人完成了 100%(8/8 ) 的 DCR。嗜中性白血球减少症和 thrombocytopenia 是有在全部的 50% 的发生的不利事件组织的主要等级 3/4。然而，仅仅经历的 25% 病人(2/8 ) 分级 3 嗜中性白血球减少症什么时候在有 fluoropyrimidines 的联合的 ABX。结论当 ABX 与 fluoropyrimidines 结合了时，为有自动增益控制的病人的首要的治疗是显著的基于 ABX 的政体的活动，和毒性是温和的。为自动增益控制的首要的治疗强烈被期望的基于 ABX 的化疗的进一步未来的临床的试用。
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