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Shannon Gravely James F. Thrasher K. Michael Cummings Janine Ouimet Ann McNeill Gang Meng Eric N. Lindblom Ruth Loewen Richard J. OConnor Mary E. Thompson Sara C. Hitchman David Hammond Bryan W. Heckman Ron Borland Hua‐Hie Yong Tara Elton‐Marshall Maansi Bansal‐Travers Coral Gartner Geoffrey T. Fong 《Addiction (Abingdon, England)》2019,114(Z1):71-85
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Sergey Motov Stefan Mann Jefferson Drapkin Mahlaqa Butt Antonios Likourezos Elizabeth Yetter Jason Brady Nechama Rothberger Ankit Gohel Peter Flom Mo Mai Christian Fromm John Marshall 《The American journal of emergency medicine》2019,37(2):220-227
Study objective
We compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine (SDK) versus morphine in geriatric Emergency Department (ED) patients.Methods
This was a prospective, randomized, double-blind trial evaluating ED patients aged 65 and older experiencing moderate to severe acute abdominal, flank, musculoskeletal, or malignant pain. Patients were randomized to receive SDK at 0.3?mg/kg or morphine at 0.1?mg/kg by short intravenous infusion over 15?min. Evaluations occurred at 15, 30, 60, 90, and 120?min. Primary outcome was reduction in pain at 30?min. Secondary outcomes included overall rates of adverse effects and incidence of rescue analgesia.Results
Thirty patients per group were enrolled in the study. The primary change in mean pain scores was not significantly different in the ketamine and morphine groups: 9.0 versus 8.4 at baseline (mean difference 0.6; 95% CI ?0.30 to 1.43) and 4.2 versus 4.4 at 30?min (mean difference ?0.2; 95% CI ?1.93 to1.46). Patients in the SDK group reported higher rates of psychoperceptual adverse effects at 15, 30, and 60?min post drug administration. Two patients in the ketamine group and one in the morphine group experienced brief desaturation episodes. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication.Conclusion
SDK administered at 0.3?mg/kg over 15?min provides analgesic efficacy comparable to morphine for short-term treatment of acute pain in the geriatric ED patients but results in higher rates of psychoperceptual adverse effects.ClinicalTrials.gov Registration #: NCT02673372. 相似文献5.
Mohamed E. Salem J. Nicholas Bodor Alberto Puccini Joanne Xiu Richard M. Goldberg Axel Grothey W. Michael Korn Anthony F. Shields William M Worrilow Edward S. Kim Heinz-Josef Lenz John L. Marshall Michael J. Hall 《International journal of cancer. Journal international du cancer》2020,147(10):2948-2956
Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI. 相似文献
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Larisa T. McLoughlin Zack Shan Kathryn M. Broadhouse Natalie Winks Gabrielle Simcock Jim Lagopoulos Daniel F. Hermens 《Human brain mapping》2020,41(6):1495-1504
There is a dearth of research that has investigated the neural correlates of cyberbullying, using task‐based functional magnetic resonance imaging (fMRI) and, specifically, in a real‐time context such as observing cyberbullying scenarios. This article presents pilot data from a novel protocol designed to undertake such research with the overall aim being to elucidate the neurobiological underpinnings of cyberbullying via task‐based fMRI (tb‐fMRI)) in passive cyberbystanders. Young adults (N = 32, 18 to 25 years old) viewed six negative (cyberbullying) and six neutral stimuli from the Cyberbullying Picture Series (CyPicS) while undergoing tb‐fMRI. Our results revealed 12 clusters of significantly greater blood‐oxygenation‐level‐dependent (BOLD) responses (family wise error corrected p FWE < .05) in participants when viewing cyberbullying stimuli compared to neutral stimuli, across a distributed network of regions including left and right middle temporal gyrus, default mode network hubs, left and right posterior cerebellum/vermis, and putamen. Further analysis also revealed greater BOLD response in females compared to males, as well as in those with no prior experience of cyberbullying compared to those with prior experience (despite gender), when viewing the cyberbullying stimuli compared to the neutral stimuli. These results bring us closer to understanding the neurobiological underpinnings that may be associated with cybervictim/bully status and outcomes. 相似文献
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Nicole L. Stout DPT Justin C. Brown PhD Anna L. Schwartz PhD FNP Timothy F. Marshall PhD Anna M. Campbell PhD MBE Larissa Nekhlyudov MD MPH David S. Zucker MD PhD Karen M. Basen-Engquist PhD MPH Grace Campbell PhD MSW RN Jeffrey Meyerhardt MD MPH Andrea L. Cheville MD MSSE Kelley R. Covington MS Jennifer A. Ligibel MD Jonas M. Sokolof DO Kathryn H. Schmitz PhD MPH Catherine M. Alfano PhD 《Cancer》2020,126(12):2750-2758
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Ashley Di Meo Ihor Batruch Marshall D. Brown Chuance Yang Antonio Finelli Michael A. Jewett Eleftherios P. Diamandis George M. Yousef 《International journal of cancer. Journal international du cancer》2020,146(8):2315-2325
Renal cell carcinoma (RCC) is frequently diagnosed incidentally as an early-stage small renal mass (SRM; pT1a, ≤4 cm). Overtreatment of patients with benign or clinically indolent SRMs is increasingly common and has resulted in a recent shift in treatment recommendations. There are currently no available biomarkers that can accurately predict clinical behavior. Therefore, we set out to identify early biomarkers of RCC progression. We employed a quantitative label-free liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomics approach and targeted parallel-reaction monitoring to identify and validate early, noninvasive urinary biomarkers for RCC-SRMs. In total, we evaluated 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC (ccRCC)-SRM cases, in addition to 26 healthy controls. We identified six proteins, which displayed significantly elevated expression in clear cell RCC-SRMs (ccRCC-SRMs) relative to healthy controls. Proteins C12ORF49 and EHD4 showed significantly elevated expression in ccRCC-SRMs compared to renal oncocytoma (≤4 cm). Additionally, proteins EPS8L2, CHMP2A, PDCD6IP, CNDP2 and CEACAM1 displayed significantly elevated expression in progressive relative to nonprogressive ccRCC-SRMs. A two-protein signature (EPS8L2 and CCT6A) showed significant discriminatory ability (areas under the curve: 0.81, 95% CI: 0.70–0.93) in distinguishing progressive from nonprogressive ccRCC-SRMs. Patients (Stage I–IV) with EPS8L2 and CCT6A mRNA alterations showed significantly shorter overall survival (p = 1.407 × 10−6) compared to patients with no alterations. Our in-depth proteomic analysis identified novel biomarkers for early-stage RCC-SRMs. Pretreatment characterization of urinary proteins may provide insight into early RCC progression and could potentially help assign patients to appropriate management strategies. 相似文献