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Biomarkers and a tailored approach for immune monitoring in kidney transplantation

World Journal of Transplantation 2017年第6期7卷 276-284页

作者： Francisco Salcido-Ochoa john carson allen jr Tregs and HLA Research Force Francisco Kidney and Medical CentreMount Elizabeth Novena Hospital Centre for Quantitative Medicine Duke-NUS Graduate Medical School

A literature review on immune monitoring in kidney transplantation produced dozens of research articles and a multitude of promising biomarkers,all in the quest for the much sought after-but perennially elusive-"holy grail" of kidney biomarkers able to unequivocally predict acute transplant rejection vs *** methodologies and study designs were many and *** the motivation for this editorial,which espouses the notion that in today's kidney transplantation milieu,the judicious use of disease classifiers tailored to specific patient immune risks may be more achievable and productive in the long run and confer a greater advantage for patient treatment than the pursuit of a single "omniscient" *** addition,we desire to direct attention toward greater scrutiny of biomarker publications and decisions to implement biomarkers in practice,standardization of methods in the development of biomarkers and consideration for adoption of "biomarker-driven" *** propose "biomarkerdriven" biopsies as an adjunctive to and/or alternative to random surveillance(protocol) biopsies or belated indication *** discovery of a single kidney transplantation biomarker would represent a major breakthrough in kidney transplantation practice,but until that occurs-if ever it does occur,other approaches offer substantial potential for unlocking prognostic,diagnostic and therapeutic *** conclude our editorial with suggestions and recommendations for productively incorporating current biomarkers into diagnostic algorithms and for testing future biomarkers of acute rejection in kidney transplantation.

关键词： Acute rejection Banff classification Biomarker Human leukocyte antigen matching Immune monitoring Immunological risk Kidney transplantation Protocol biopsy

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Multiparametric MRI reporting using Prostate Imaging Reporting and Data System version 2.0 (PI-RADSv2) retains clinical efficacy in a predominantly post-biopsy patient population

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Asian Journal of Urology 2019年第3期6卷 256-263页

作者： Edwin Jonathan Aslim Yan Mee Law Puay Hoon Tan john carson allen jr Lionel Tim-Ee Cheng Viswanath Anand Chidambaram Li Yan Khor Benjamin Yongcheng Tan Ernest Wencong Eu Christopher Wai Sam Cheng john Shyi Peng Yuen Henry Sun Sien Ho Lui Shiong Lee Department of Urology Singapore General HospitalSingapore Department of Diagnostic Radiology Singapore General HospitalSingapore Division of Pathology Singapore General HospitalSingapore Centre of Quantitative Medicine DUKE-NUS Medical SchoolSingapore Department of Anatomical Pathology Singapore General HospitalSingapore

Objective:To evaluate the efficacy of multiparametric magnetic resonance imaging(mp-MRI)using Prostate Imaging Reporting and Data System version 2.0(PI-RADSv2)definitions in detecting organ-confined prostate ***:All patients who underwent radical prostatectomy between January 1,2014 and December 30,2014 were *** underwent mp-MRI within 180 days before *** with prior pelvic irradiation or androgen deprivation therapy were *** embedded,whole-mount histopathology was centrally reviewed and correlated with imaging for tumour location,Gleason score(GS)and ***:There were 39 patients included,of which 35(90%)had mp-MRI done post-biopsy.A total of 93 cancer foci were identified on whole-mount pathology,of which mp-MRI detected 63(68%).Of those detected by mp-MRI,14 were PI-RADS 3(n=6 for GS 6,n=8 for GS 7,no GS≥8)and 49 were PI-RADS 4e5(nZ7 for GS 6,nZ33 for GS 7,and nZ9 for GS≥8).There were 30(32%)cancer foci missed by mp-MRI(n=15 for GS 6,n=13 for GS 7 and n=2 for GS≥8).A lesion classified as PI-RADS 4e5 predicted a higher grade cancer on pathology as compared to PI-RADS 3(for GS 7 lesions,odds ratio[OR]=3.53,95%CI:0.93e13.45,p=0.064).The mp-MRI size detection limit was 20 mm2 and 100 mm2 for 50%and 75%probability of cancer,*** associating with radiological and pathologic stage,the weighted Kappa value was 0.69(p<0.0001).The sensitivity and positive predictive values for this study were 68%(95%CI:57%e77%)and 78%(95%CI:67%e86%),***:In this predominantly post-biopsy cohort,mp-MRI using PI-RADSv2 reporting has a reasonably high diagnostic accuracy in detecting clinically significant prostate cancer.

关键词： Gleason score Histopathology Magnetic resonance imaging Prostatectomy Prostatic cancer

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Histopathological analysis of infiltrating T cell subsets in acute T cell-mediated rejection in the kidney transplant

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World Journal of Transplantation 2017年第4期7卷 222-234页

作者： Francisco Salcido-Ochoa Susan Swee-Shan Hue Siyu Peng Zhaoxiang Fan Reiko Lixiang Li Jabed Iqbal john carson allen jr Alwin Hwai Liang Loh Tregs and HLA Research Force and Renal Medicine Department Singapore General Hospital Tregs and HLA Research Force and Department of Pathology National University Hospital Tregs and HLA Research Force and Yong Loo Lin School of Medicine National University of Singapore Department of Pathology and Laboratory Medicine KK Women’s and Children’s Hospital Department of Pathology Singapore General Hospital Centre for Quantitative Medicine Duke-NUS Graduate Medical School

AIM To compare the differential immune T cell subset com-position in patients with acute T cell-mediated rejection in the kidney transplant with subset composition in the absence of rejection, and to explore the association of their respective immune profiles with kidney transplant *** A pilot cross-sectional histopathological analysis of the immune infiltrate was performed using immunohistochemistry in a cohort of 14 patients with acute T cellmediated rejection in the kidney transplant and 7 kidney transplant patients with no rejection subjected to biopsy to investigate acute kidney transplant dysfunction. All patients were recruited consecutively from 2012 to 2014 at the Singapore General Hospital. Association of the immune infiltrates with kidney transplant outcomes at up to 54 mo of follow up was also explored *** In a comparison to the absence of rejection, acute T cell-mediated rejection in the kidney transplant was characterised by numerical dominance of cytotoxic T lymphocytes over Foxp3^+ regulatory T cells, but did not reach statistical significance owing to the small sample size in our pilot study. There was no obvious difference in absolute numbers of infiltrating cytotoxic T lymphocytes, Foxp3^+ regulatory T cells and Th17 cells between the two patient groups when quantified separately. Our exploratory analysis on associations of T cell subset quantifications with kidney transplant outcomes revealed that the degree of Th17 cell infiltration was significantly associated with shorter time to doubling of creatinine and shorter time to transplant *** Although this was a small pilot study, results support our suspicion that in kidney transplant patients the immune balance in acute T cell-mediated rejection is tilted towards the pro-rejection forces and prompt larger and more sophisticated studies.

关键词： Acute T cell-mediated rejection in the kidney transplant Banff classification Cytotoxic T cell Regulatory T cell Th17 cell

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中国祝圣主教也许是符合传统的

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中国天主教 2006年第5期 9-10页

作者： john L allen jr 美国天主教报道周报

最近梵蒂冈和中国政府之间就祝圣五位新主教所产生的冲突,媒体普遍认为是世俗政权侵占教宗特权.西方评论家们通常认为,只有教宗享有任命主教的权力(见1月14日'美国天主教周报',以下简称NCR).

关键词：中国政府天主教传统世俗政权梵蒂冈评论家普遍

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