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Distinct roles but cooperative effect of TLR3/9 agonists and PD-1 blockade in converting the immunotolerant microenvironment of irreversible electroporation-ablated tumors

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Cellular & Molecular Immunology 2021年第12期18卷 2632-2647页

作者： Fatma Babikr Jiangbo Wan Aizhang Xu Zhaojia Wu Shahid Ahmed Andrew Freywald Rajni Chibbar Yue Wu Michael Moser gary groot Wenjun Zhang Bing Zhang Jim Xiang Saskatoon Cancer Center Saskatchewan Cancer AgencySaskatoonSKCanada Department of Oncology University of SaskatchewanSaskatoonSKCanada Department of Hematology Xinhua HospitalAffiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology University of SaskatchewanSaskatoonSKCanada Department of Surgery University of SaskatchewanSaskatoonSKCanada Department of Bioengineering University of SaskatchewanSaskatoonSKCanada Biomedical Science and Technology Research Center Shanghai UniversityShanghaiChina

Irreversible electroporation(IRE)is a new cancer ablation technology,but methods to improve IRE-induced therapeutic immunity are only beginning to be *** developed a mouse model bearing large primary(300 mm^(3))and medium distant(100 mm^(3))EG7 lymphomas engineered to express ovalbumin(OVA)as a nominal tumor *** established experimental protocols including IRE alone and IRE combined with Toll-like receptor(TLR)3/9 agonists(poly I:C/CpG)(IRE+pIC/CpG),PD-1 blockade(IRE+PD-1 blockade),or both(IRE+Combo)to investigate therapeutic effects on primary and distant EG7 tumors and conversion-promoting effects on the immunotolerant tumor microenvironment(TME).We demonstrated that IRE alone simulated very weak OVA-specific CD8^(+)T cell responses and did not inhibit primary tumor ***+pIC/CpG synergistically stimulated more efficient OVA-specific CD8^(+)T cell responses and primary tumor growth inhibition than IRE+PD-1 ***+pIC/CpG played a major role in the modulation of immune cell profiles but a minor role in the downregulation of PD-L1 expression in the TME and vice versa for IRE+PD-1 ***+Combo cooperatively induced potent OVA-specific CD8^(+)T cell immunity and rescued exhausted intratumoral CD8^(+)T cells,leading to eradication of not only primary tumors but also untreated concomitant distant tumors and lung ***+Combo efficiently modulated immune cell profiles,as evidenced by reductions in immunotolerant type-2(M2)macrophages,myeloid-derived suppressor-cells,plasmacytoid dendritic cells,and regulatory T cells and by increases in immunogenic M1 macrophages,CD169^(+)macrophages,type-1 conventional dendritic cells,and CD8^(+)T cells,leading to conversion of immunotolerance in not only primary TMEs but also untreated distant ***+Combo also showed effective therapeutic effects in two breast cancer ***,our results suggest that IRE+Combo is a promising strategy to improve IRE ablation therapy in cancer.

关键词： IRE ablation TLR3/9-agonists PD-1-blockade CD8+T-cell response antitumor immunity

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Electronic Synoptic Reporting of Thyroid Nodules: Potential for Reduction in Number of Patients Undergoing Thyroid Nodule Biopsies

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Open Journal of Radiology 2016年第3期6卷 233-242页

作者： Jimmy Tanche Wang Paul Babyn gary groot Rob Otani Department of Radiology University of Saskatchewan Faculty of Medicine Royal University of Hospital Saskatoon Canada Department of Surgery University of Saskatchewan Faculty of Medicine Royal University of Hospital Saskatoon Canada

Purpose: The objective of the study was to design and implement an electronic synoptic report for thyroid sonography that incorporates the thyroid imaging reporting and data system (TIRADS) and assess potential for reducing unnecessary fine needle aspiration biopsies (FNAB) of thyroid nodules. Methods: The electronic synoptic report was developed using a relational database based on elements from TIRADS and a multidisciplinary consensus statement for thyroid reporting. A retrospective analysis of 138 patients with previously reported thyroid sonographic exams was evaluated for the presence of these elements. The electronic synoptic report calculates the TIRADS score and generates a formal report. Using the TIRADS score the potential decrease in unnecessary FNAB was estimated. Results: Key TIRADS elements were variously reported ranging from 43% for the thyroid nodule’s architecture as solid or cystic. Thyroid nodule echogenicity and calcification was commented in 27% and 23%, respectively. Other features of the TIRADS score were commented in 0% to 8% of the official reports. Estimated reduction for potentially reduced need for FNAB was 34.5%. Conclusions: This study is the first implementation of synoptic reporting using a relational database for sonography of thyroid nodules. Implementation of an electronic standardized synoptic reporting system may facilitate more accurate, and more comprehensive reporting for thyroid ultrasound scanning of thyroid nodules. The use of TIRADS was estimated to be able to potentially reduce the need for FNAB which was significant.

关键词： Synoptic Reporting Thyroid Nodules Thyroid Cancer Fine Needle Aspiration Biopsy Thyroid Imaging Reporting and Data System

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The Role of a Pre-Fine Needle Aspiration Clinic in Improving the Quality of Thyroid Nodule Investigation in Saskatchewan

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Open Journal of Radiology 2020年第1期10卷 23-34页

作者： Paige Baldwin Terra Arnason Niomi Singh Robert Otani gary groot College of Medicine University of Saskatchewan Saskatoon Canada Department of Medicine Division of Endocrinology University of Saskatchewan Saskatoon Canada Department of Surgery University of Saskatchewan Saskatoon Canada Department of Radiology University of Saskatchewan Saskatoon Canada

Background: The Canadian province of Saskatchewan introduced a pre-fine needle aspiration (FNA) clinic to review adherence of referrals for thyroid biopsy based on the guidelines of the American College of Radiology’s (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) scoring system. The intention is to minimize low-yield biopsy rates by improving the quality of thyroid nodule investigation in Saskatchewan through this clinic. TI-RADS is a malignancy risk scoring system for thyroid nodules based on five sonographic characteristics: composition, echogenicity, shape, margin, and echogenic foci (calcium). Recommendations for intervention or clinical follow-up are further determined by the size of the nodule. Methods: Through a retrospective chart review of all thyroid biopsy referrals to the Royal University Hospital (RUH) in Saskatchewan between 22 March 2016 and 17 May 2018, the impact of the multidisciplinary pre-FNA clinic on appropriate thyroid biopsies in Saskatchewan was evaluated. Results: This study evaluated 252 referrals, 203 of which underwent FNA and 23 which received surgical biopsy. TI-RADS scores appended to thyroid biopsy referrals increased upon pre-FNA clinic initiation, yet score quality did not improve. Rates of malignant biopsies were lower than ACR-reporting suggesting inappropriate biopsy of low risk nodules perhaps by overcalling the TI-RADS score. The majority of FNA cytology matched final surgical pathology, with 78% of indeterminate FNAs being malignant, and all non-diagnostic FNAs being benign. Conclusions: The implementation of the pre-FNA clinic reduced the number of thyroid biopsies in Saskatchewan by 11% overall.

关键词： Thyroid Nodules Thyroid Cancer Fine Needle Aspiration Biopsy Thyroid Imaging Reporting and Data System (TIRADS)

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Online TI-RADS Calculator

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Open Journal of Radiology 2018年第3期8卷 175-180页

作者： Jimmy Tanche Wang Tasha Ellchuk Rob Otani gary groot Paul Babyn Department of Radiology Faculty of Medicine University of Saskatchewan Royal University of Hospital Saskatoon Canada Department of Surgery Faculty of Medicine University of Saskatchewan Royal University of Hospital Saskatoon Canada

Background: Thyroid nodules are common and fine needle aspiration (FNA) or surgery is used to assess for malignancy. Thyroid Imaging, Reporting and Data System (TI-RADS) use ultrasound for non-invasive risk stratification of thyroid nodules and reduce unnecessary biopsies. This project used an online calculator and education to facilitate the application of TI-RADS in clinical practice. Methods: Retrospective review defined the baseline reporting of thyroid nodule ultrasound features. Web-based resource and presentation were used to integrate TI-RADS in reporting thyroid ultrasounds and measure the improvements in comprehensive reporting of thyroid nodules and guiding management. Results: The percentage of thyroid ultrasound reporting using TI-RADS within six months increased from 0% to 27% during the project period. Reports with TI-RADS provided twice as many recommendations compared to reports without TI-RADS. Conclusion: Online TI-RADS calculator and education have successfully facilitated the integration of TI-RADS in thyroid ultrasound reporting to provide more accurate and comprehensive reports and guide management.

关键词： TI-RADS Thyroid Ultrasound

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Efficacy of telemedicine on glycaemic control in patients with type 2 diabetes:A meta-analysis

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World Journal of Diabetes 2021年第2期12卷 170-197页

作者： Julia De groot Dongjun Wu Declan Flynn Dylan Robertson gary Grant Jing Sun School of Medicine Griffith UniversityGold Coast 4222QueenslandAustralia School of Pharmacy and Pharmacology Griffith UniversityGold Coast 4222QueenslandAustralia School of Medicine and Menzies Health Institute Queensland Griffith UniversityBrisbane 4222QueenslandAustralia

BACKGROUND Telemedicine is defined as the delivery of health services via remote communication and *** is a convenient and cost-effective method of intervention,which has shown to be successful in improving glyceamic control for type 2 diabetes *** utility of a successful diabetes intervention is vital to reduce disease complications,hospital admissions and associated economic *** To evaluate the effects of telemedicine interventions on hemoglobin A1c(HbA1c),systolic blood pressure(SBP),diastolic blood pressure(DBP),body mass index(BMI),post-prandial glucose(PPG),fasting plasma glucose(FPG),weight,cholesterol,mental and physical quality of life(QoL)in patients with type 2 *** secondary aim of this study is to determine the effect of the following subgroups on HbA1c post-telemedicine intervention;telemedicine characteristics,patient characteristics and self-care *** PubMed Central,Cochrane Library,Embase and Scopus databases were searched from inception until 18th of June *** quality of the 43 included studies were assessed using the PEDro scale,and the random effects model was used to estimate outcomes and I2 for heterogeneity *** mean difference and standard deviation data were extracted for *** We found a significant reduction in HbA1c[-0.486%;95%confidence interval(CI)-0.561 to-0.410,P<0.001],DBP(-0.875 mmHg;95%CI-1.429 to-0.321,P<0.01),PPG(-1.458 mmol/L;95%CI-2.648 to-0.268,P<0.01),FPG(-0.577 mmol/L;95%CI-0.710 to-0.443,P<0.001),weight(-0.243 kg;95%CI-0.442 to-0.045,P<0.05),BMI(-0.304;95%CI-0.563 to-0.045,P<0.05),mental QoL(2.210;95%CI 0.053 to 4.367,P<0.05)and physical QoL(-1.312;95%CI 0.545 to 2.080,P<0.001)for patients following telemedicine interventions in comparison to control *** results of the meta-analysis did not show any significant reductions in SBP and cholesterol in the telemedicine interventions compared to the control *** telemedicine characteristic subgroup an

关键词： Telehealth Telemedicine Telemonitoring Behavioural change Selfmanagement Diabetes

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