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1.
Stefano Cascinu György Bodoky Kei Muro Eric Van Cutsem Sang Cheul Oh Gunnar Folprecht Sumitra Ananda Gustavo Girotto Zev A. Wainberg Maria Luisa Limon Miron Jaffer Ajani Ran Wei Astra M. Liepa Roberto Carlesi Michael Emig Atsushi Ohtsu 《The oncologist》2021,26(3):e414-e424
BackgroundIn the intent‐to‐treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation.Materials and MethodsTumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the European Organization for Research and Treatment of Cancer Quality‐of‐Life Questionnaire‐Core 30 (EORTC QLQ‐C30) v3.0. Prespecified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR.ResultsIn both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs. 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved or stable QoL, with more tumor shrinkage associated with greater symptom palliation.ConclusionTreatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. Clinical trial identification number. .Implications for PracticeRamucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first‐line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with nonmeasurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits. NCT01170663相似文献
2.
Nina Vyas Kawa Manmi Qianxi Wang Ananda J. Jadhav Mostafa Barigou Rachel L. Sammons Sarah A. Kuehne A. Damien Walmsley 《Ultrasound in medicine & biology》2019,45(5):1044-1055
Bacterial biofilms are a cause of contamination in a wide range of medical and biological areas. Ultrasound is a mechanical energy that can remove these biofilms using cavitation and acoustic streaming, which generate shear forces to disrupt biofilm from a surface. The aim of this narrative review is to investigate the literature on the mechanical removal of biofilm using acoustic cavitation to identify the different operating parameters affecting its removal using this method. The properties of the liquid and the properties of the ultrasound have a large impact on the type of cavitation generated. These include gas content, temperature, surface tension, frequency of ultrasound and acoustic pressure. For many of these parameters, more research is required to understand their mechanisms in the area of ultrasonic biofilm removal, and further research will help to optimise this method for effective removal of biofilms from different surfaces. 相似文献
3.
Luciano Rodrigues Silva Lima Ananda Souza Pereira Marcoeli Silva de Moura Cacilda Castelo Branco Lima Saul Martins Paiva Lúcia de Ftima Almeida de Deus Moura Marina de Deus Moura de Lima 《International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children》2020,30(2):193-201
4.
5.
Beatriz Togoro Ferreira da Silva Livia Tosi Trevelin Ananda Carolina Schroeter Amanda Endres Willers Paulo Francisco Cesar Adriana Bona Matos 《European journal of oral sciences》2021,129(1):e12754
This study investigated the effect of irradiation with an erbium‐doped yttrium aluminium garnet (Er:YAG) laser and coating with silica on the surface characteristics, bond strength, and flexural strength of dental zirconia. Three hundred and forty‐three standard zirconia specimens were created, and 49 were assigned to each of seven surface treatment groups: (i) no treatment; Er:YAG laser (80 mJ/2 Hz) with pulse widths of 50 μs (ii), 100 μs (iii), 300 μs (iv), or 600 μs (v); or tribochemical silica coating at the partially sintered stage (vi) or after sintering was complete (vii). All specimens were sintered after the surface treatments, except for the group in which specimens were sintered before treatment. The study outcomes were roughness, surface loss, microshear bond strength (μSBS), and biaxial flexural strength (BFS). Mean roughness and surface loss values were significantly higher in specimens from irradiated groups than in those from silica‐coated groups. Regarding μSBS, after aging, specimens from all experimental groups presented very low and similar μSBS values, irrespective of the surface treatment. Silica coating after sintering yielded the highest BFS (1149.5 ± 167.6 MPa), while coating partially sintered specimens with silica resulted a BFS (826.9 ± 60.9 MPa) similar to that of the untreated control group (794.9 ± 101.7 MPa). Laser treatments, irrespective of pulse width used, significantly decreased the BFS. In the group treated with laser at 300 μs pulse width, specimens exhibited the lowest BFS value (514.1 ± 71.5 MPa). Adhesion to zirconia was not stable after aging, regardless of the surface treatment implemented. 相似文献
6.
Ilkka Liikanen Colette Lauhan Sara Quon Kyla Omilusik Anthony T. Phan Laura Barcel Bartrolí Amir Ferry John Goulding Joyce Chen James P. Scott-Browne Jason T. Yustein Nicole E. Scharping Deborah A. Witherden Ananda W. Goldrath 《The Journal of clinical investigation》2021,131(7)
Adoptive T cell therapies (ACTs) hold great promise in cancer treatment, but low overall response rates in patients with solid tumors underscore remaining challenges in realizing the potential of this cellular immunotherapy approach. Promoting CD8+ T cell adaptation to tissue residency represents an underutilized but promising strategy to improve tumor-infiltrating lymphocyte (TIL) function. Here, we report that deletion of the HIF negative regulator von Hippel-Lindau (VHL) in CD8+ T cells induced HIF-1α/HIF-2α–dependent differentiation of tissue-resident memory–like (Trm-like) TILs in mouse models of malignancy. VHL-deficient TILs accumulated in tumors and exhibited a core Trm signature despite an exhaustion-associated phenotype, which led to retained polyfunctionality and response to αPD-1 immunotherapy, resulting in tumor eradication and protective tissue-resident memory. VHL deficiency similarly facilitated enhanced accumulation of chimeric antigen receptor (CAR) T cells with a Trm-like phenotype in tumors. Thus, HIF activity in CD8+ TILs promotes accumulation and antitumor activity, providing a new strategy to enhance the efficacy of ACTs. 相似文献
7.
In a recent study published by the National Project Team on chronic kidney diseases of unknown origin in Sri Lanka, identified cadmium as a major risk factor but strong conclusions were not made as the identified environmental toxins were within the permissible levels.Sri Lankan food consumption pattern is different so that approach of total exposure of cadmium by food and water been calculated. Such calculation point out that total exposure of cadmium exceed the provisional tolerable weekly intake determined by international agencies. 相似文献
8.
Ravi Krupa Killen Annabel Alexander Angus Bell-Davies Frances Biganiro Sebintu James Brazeal Aurelia Butoyi Jean Marie Vianney Diaz Fabio Edgardo Drabile Romeo Fanny Marvin Fernie Lucila Gunawardana Shannon Hartley Emma Hawu Yolisa N. Hendron Holly Joseph Stephanie Alcine Lamahewage Ananda Mahagedera Ruwantha Manirambona Emery Morisho Benjamin Kitambala Muchunu Patrick Niyukuri Alliance Ntaganda Edmond Orliacq Francisco Orliacq Josefina Wobenjo Adili Young Pablo Lakhoo Kokila Ford Kathryn 《World journal of surgery》2022,46(3):476-485
World Journal of Surgery - The Global Initiative for Children's Surgery (GICS) group produced the Optimal Resources for Children’s Surgery (OReCS) document in 2019, listing standards of... 相似文献
9.
Christina M. Sheerin Mackenzie J. Lind Kaitlin E. Bountress Marisa E. Marraccini Ananda B. Amstadter Silviu-Alin Bacanu Nicole R. Nugent 《Journal of traumatic stress》2020,33(5):688-698
The hypothalamic-pituitary-adrenal (HPA) axis has been of interest in attempts to identify genetic vulnerability for posttraumatic stress disorder (PTSD). Although numerous HPA-axis genes have been implicated in candidate gene studies, the findings are mixed and interpretation is limited by study design and methodological inconsistencies. To address these inconsistencies in the PTSD candidate gene literature, we conducted meta-analyses of HPA-related genes from both a traditional single nucleotide polymorphism (SNP)–level analysis and a gene-level analysis, using novel methods aggregating markers in the same gene. Database searches (PubMed and PsycINFO) identified 24 unique articles examining six HPA-axis genes in PTSD; analyses were conducted on four genes (ADCYAP1R1, CRHR1, FKBP5, NR3C1) that met study eligibility criteria (original research, human subjects, main effect association study of selected genes, PTSD as an outcome, trauma-exposed control group) and had sufficient data and number of studies for use in meta-analysis, within 20 unique articles. Findings from SNP-level analyses indicated that two variants (rs9296158 in FKBP5 and rs258747 in NR3C1) were nominally associated with PTSD, ps = .001 and .001, respectively, following multiple testing correction. At the gene level, significant relations between PTSD and both NR3C1 and FKBP5 were detected and robust to sensitivity analyses. Although study limitations exist (e.g., varied outcomes, inability to test moderators), taken together, these results provide support for FKBP5 and NR3C1 in risk for PTSD. Overall, this work highlights the utility of meta-analyses in resolving discrepancies in the literature and the value of adopting gene-level approaches to investigate the etiology of PTSD. 相似文献
10.
Dana Dawson Diana Rinkevich Todd Belcik Ananda R Jayaweera Patrick Rafter Sanjiv Kaul Kevin Wei 《Journal of the American Society of Echocardiography》2003,16(11):1171-1177
BACKGROUND: The ability of high and low mechanical index (MI) imaging methods during myocardial contrast echocardiography (MCE) to assess the physiologic significance of coronary stenoses were compared with technetium 99m sestamibi single photon emission computed tomography (SPECT) in patients. METHODS: Intermittent ultraharmonic imaging (high MI) and power modulation angio (low MI) were performed during continuous infusions of the echo-enhancing contrast agent, Optison, at rest and after dipyridamole stress in 39 patients. Technetium 99m sestamibi SPECT was performed simultaneously. Images from the 3 apical windows were divided into 6 walls. Myocardial blood flow (MBF) velocity and MBF velocity reserve were quantified from pulsing interval versus acoustic intensity MCE curves in each wall using postprocessed images. RESULTS: Approximately 25% of the myocardial walls could not be analyzed from MCE because of artifacts. MBF velocity and MBF derived from both MCE methods increased significantly after dipyridamole in healthy patients (n = 143 and 129 walls for high and low MI, respectively), compared with those with either reversible (n = 11 and 10 walls for high and low MI, respectively) or fixed defects (n = 18 and 14 walls for high and low MI, respectively) on SPECT. Consequently, MBF velocity and MBF reserve were significantly greater for patients with normal perfusion. Receiver operator characteristic curves obtained for MBF velocity reserve provided a sensitivity and specificity of 82% and 87%, respectively, for high MI; versus 64% and 96%, respectively, for low MI imaging after uninterpretable images were excluded from analysis. CONCLUSIONS: Both high and low MI MCE imaging techniques can be used to determine the presence of perfusion defects as identified by technetium 99m sestamibi SPECT. Low MI imaging methods have a number of drawbacks that limit its sensitivity compared with high MI techniques. 相似文献