Synovial Fluid Biomarkers in the Osteoarthritic Knee: Differences in Concentration with Progression of Radiographic Severity

Objectives: The purpose of the current study was to analyze the synovial fluid concentrations of known inflammatory biomarkers in the setting of symptomatic osteoarthritis (OA) of the knee and assess for any differences in biomarker concentrations based on the extent of radiographic disease. Methods: Patients presenting with knee complaints were invited to provide synovial fluid samples from the symptomatic knee during their initial office visit. For this study, a subset of patients with OA was analyzed. The concentration of 16 synovial fluid biomarkers was measured, including TIMP-1, TIMP-2, TIMP-3, MMP-13, IL-6, MCP-1, MIP-1β, VEGF, bFGF, eotaxin, IL-1Ra, MMP-1, MMP-3, MMP-9, RANTES, and TSG-6. Samples were analyzed using a multiplex magnetic bead immunoassay. Patients were divided into a low-grade OA group (K-L ≤ 2 or OARSI ≤ 1) or a high-grade cartilage OA group (K-L ≥ 3 or OARSI ≥ 2). Results: 101 patients were included in this analysis. There was a significant difference in MIP-1β (p=0.025) and bFGF (p=0.015) concentrations between OARSI grade groups. Patients with high-grade joint space narrowing had significantly greater concentrations of MIP-1β (p=0.022) and bFGF (p=0.003). There was a significant difference in MIP-1β concentration between K-L grade groups (p=0.013). Patients in the high-grade K-L group had a significantly greater concentration of MIP-1β (p=0.020). Conclusions: The synovial fluid concentrations of two synovial fluid biomarkers were found to differ significantly based on the extent of radiographic OA present. MIP-1β is a pro-inflammatory growth factor known to induce the synthesis of other inflammatory factors including interleukins and TNF-α. bFGF is a growth factor that is known to promote chondrogenesis, angiogenesis, wound healing, and granulation tissue formation. Continued study of synovial fluid biomarkers in the setting of symptomatic OA may improve our understanding of the pathogenesis of disease and identify treatment targets in an attempt to halt disease progression.

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Low-Grade Squamous Intraepithelial Lesion or High-Grade Squamous Intraepithelial Lesion? Concordance Between the Interpretation of Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion in Papanicolaou Tests: Results From the College of American Pathologists PAP Education Program

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2018-0003-cp ◽

2018 ◽

Vol 143 (1) ◽

pp. 81-85 ◽

Cited By ~ 2

Author(s):

Barbara A. Crothers ◽

Mohiedean Ghofrani ◽

Chengquan Zhao ◽

Leslie G. Dodd ◽

Kelly Goodrich ◽

...

Keyword(s):

Education Program ◽

Repeated Measures ◽

False Negative ◽

Misclassification Rate ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Significant Difference ◽

Intraepithelial Lesion ◽

Diagnostic Concordance

Context.— Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. Objective.— To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. Design.— We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. Results.— There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL (P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). Conclusions.— More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.

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Urothelial carcinoma and its association with age and gender.

The Professional Medical Journal ◽

10.29309/tpmj/2019.26.10.3704 ◽

2019 ◽

Vol 26 (10) ◽

pp. 1719-1723

Author(s):

Rukhsana Parveen Samo ◽

Asim Mehmood ◽

Sana Kashif

Keyword(s):

Urothelial Carcinoma ◽

Male Gender ◽

Health Science ◽

P Value ◽

Low Grade ◽

High Grade ◽

Histological Grading ◽

Age And Gender ◽

Significant Difference ◽

And Gender

Objectives: To determine the urothelial carcinoma and its association with age and gender. Study Design: Retrospective study. Setting: Pathology department of Liaquat university of Medical and Health Science. Period: One year from January 2016 to December 2016. Material and Methods: Four micrometer thick paraffin-embedded and formalin-fixed sections were prepared from transurethral resection6of bladder6tumor (TURBT) samples of urothelial carcinoma patients and were examined. Histological grading was categorized as low and high grades. All the data was collected by self-made proforma. Data was analyzed by SPSS version 20. Results: Total 83 cases were enrolled in current study; their mean age was 49.19+12.33 years. Males were found in the majority 51(61.4%) and females were 32(38.6%). Most common age group was 46-60 years 36(43.4%). According to the histological grading high grade was most common as 65.10%, and low grade urothelial carcinoma was 34.90%. There was no significant difference according to age of histological grading. Male gender was most common, while progression of disease was higher among females in contrast to males as high grade carcinoma was significantly higher among females, p-value 0.014. Conclusion: It was concluded that male gender is the contributing factor of urothelial carcinoma, but disease progression significantly high among females. No significant association has been found according to age.

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Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000477 ◽

2015 ◽

Vol 25 (7) ◽

pp. 1201-1207 ◽

Cited By ~ 9

Author(s):

Esther Louise Moss ◽

Tim Evans ◽

Philippa Pearmain ◽

Sarah Askew ◽

Kavita Singh ◽

...

Keyword(s):

Overall Survival ◽

Clear Cell ◽

Stage Iii ◽

Serous Carcinoma ◽

Low Grade ◽

Type I ◽

High Grade ◽

Type Ii ◽

Ovarian Serous Carcinoma ◽

Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

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Synovial Fluid Biomarker Concentrations in Knees with Symptomatic Meniscus Injury Compared to Asymptomatic Contralateral Knees

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967119s00357 ◽

2019 ◽

Vol 7 (7_suppl5) ◽

pp. 2325967119S0035

Author(s):

Andrew Clair ◽

Matthew T. Kingery ◽

Utkarsh Anil ◽

Lena Kenny ◽

Eric Jason Strauss

Keyword(s):

Synovial Fluid ◽

Cartilage Damage ◽

Arthroscopic Surgery ◽

Low Grade ◽

Current Analysis ◽

Duration Of Symptoms ◽

Cartilage Lesions ◽

Meniscus Injury ◽

Symptomatic Knee ◽

Fluid Biomarker

Objectives: Changes in the joint microenvironment following an intra-articular injury have been implicated in the pathogenesis of knee osteoarthritis. Few studies have evaluated alterations in the joint microenvironment in the setting of meniscus injury. The purpose of the current study was to determine the changes in synovial fluid biomarker concentrations caused by meniscus pathology by comparing samples from injured, symptomatic knees to samples from asymptomatic contralateral knees. Methods: Patients undergoing surgery for unilateral meniscus injury were prospectively enrolled in this institutional review board approved study from October 2011 to December 2016. A cohort was formed consisting of patients that had synovial fluid samples collected from both the injured and contralateral uninjured knee at the time of arthroscopic surgery. Patients with ligamentous injury of the knee were excluded from the current analysis. Synovial fluid samples were collected just prior to incision and the concentrations of 10 biomarkers of interest were determined using a multiplex magnetic bread immunoassay. Results: The current analysis included synovial fluid samples from 82 knees (41 operative and 41 contralateral knees) from 41 patients undergoing arthroscopic surgery to treat a symptomatic meniscus injury. The mean age of patients was 49.86 +/- 11.75 years. Based on linear mixed effects models, there were significantly greater concentrations of 4 of the 5 pro-inflammatory biomarkers in symptomatic knees compared to asymptomatic knees when controlling for the duration of symptoms, BMI, age, and the random effects of by-patient variability. Knees with symptomatic meniscus injuries had 126.8 times greater concentration of IL-6, 2.7 times greater concentration of MCP-1, 2.0 times greater concentration of MIP-1beta, and 5.4 times greater concentration of MMP-3 compared to the contralateral, asymptomatic knee (Table 1). When controlling for the chronicity of the injury, presence of synovitis, and age of the patient, knees with concomitant high-grade cartilage lesions (ICRS 3 or 4) were associated with 2.1 times greater concentration of MCP-1, 1.9 times greater concentration of MIP-1beta, and 3.4 times greater concentration of VEGF compared to knees with concomitant low-grade cartilage lesions (ICRS 1 or 2). When controlling for the other variables, the presence of synovitis was associated with an 89.5% lower concentration of TIMP-1 compared to operative knees without synovitis. The age of the patient was found to affect the concentrations of IL-6, MCP-1, and VEGF. For all knees included in the study, each 1 year increase in age was associated with a 6% increase in IL-6, 3% increase in MCP-1, and 4% increase in VEGF (Figure 1). Conclusion: This study is the first that examines the synovial fluid biomarker concentrations in the setting of a symptomatic isolated meniscus injury. We demonstrated that 4 of the 5 proinflammatory biomarkers that were tested are found in greater concentration in the symptomatic knee. Furthermore, we described the effects of associated cartilage damage, synovitis, and patient age on biomarker concentrations. Understanding the implication of these alterations in the intra-articular microenvironment in the setting of meniscal pathology may hold the key to identifying treatment targets in an effort to prevent the onset of post-meniscectomy osteoarthritis. [Table: see text]

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Hormonal treatment of metastatic endometrial stromal sarcoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16576 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16576-e16576

Author(s):

K. Y. Terada ◽

J. Davis ◽

J. Kitayama ◽

D. Shimizu

Keyword(s):

Aromatase Inhibitors ◽

Stable Disease ◽

Progesterone Receptors ◽

Rank Test ◽

Low Grade ◽

Image Analyzer ◽

High Grade ◽

Estrogen And Progesterone Receptors ◽

Significant Difference

e16576 Background: Endometrial stromal sarcomas (ESS) traditionally have been classified as low grade or high grade based on mitotic activity and histologic appearance. High-grade tumors are currently referred to as undifferentiated uterine sarcomas and are not included in this series. ESS are known to have high expression of estrogen and progesterone receptors. This is a retrospective study of patients with metastatic ESS treated with hormonal therapy. Methods: Following approval by the institutional review board all patients diagnosed with ESS from 1987–2007 were identified. Clinical and demographic information were abstracted from the charts and all histologic materials were re-reviewed. Estrogen and progesterone receptor testing was performed utilizing mouse monoclonal antibodies and the Cell Analysis Systems 200 Image analyzer. Survival was calculated using the Kaplan-Meier method and comparisons utilized the log rank test. Results: Thirteen patients with ESS were identified during this period. Seven had disease confined to the uterus. Six had extrauterine disease; 5 patients presented with metastases and 1 patient presented with a pelvic recurrence 20 years following a hysterectomy. All underwent surgical resection except for 1 patient that declined surgery. All 6 patients with metastases had tumors that tested positive for estrogen and progesterone receptors; all were treated with megestrol acetate initially for a period of 1–4 years. Two patients were then changed to maintenance with medroxyprogesterone acetate. Three patients with persistent disease were changed to aromatase inhibitors; 1 to letrozole and 2 to anastrazole. One of these patients has had a complete response and 2 have had stable disease. One patient has been lost to follow-up. Follow-up for the 6 patients was 2–22 years; no known patients died of their disease. Actuarial 2- and 5-year survivals were 80% and 65%, respectively. There was no significant difference in survival between patients with metastases and without metastases. Conclusions: ESS tumors are relatively uncommon and there is an absence of studies to guide treatment of patients with metastases. This experience indicates that these tumors respond well to hormonal manipulation. Treatment with progestins or aromatase inhibitors may result in remission or stable disease. No significant financial relationships to disclose.

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Prognostic value of the volume time index (VTI) ratio for patients with appendiceal cancer with peritoneal carcinomatosis treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15704 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15704-e15704

Author(s):

Josh Karpes ◽

Daniel Dotta ◽

Oliver Fisher ◽

Raphael Shamavonian ◽

Nayef Alzahrani ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Peritoneal Dissemination ◽

Tumour Volume ◽

Peritoneal Metastases ◽

Low Grade ◽

High Grade ◽

Appendiceal Cancer ◽

Appendix Cancer ◽

Significant Difference

e15704 Background: Completeness of cytoreduction score (CC-score) and tumour volume (as expressed by the peritoneal cancer index (PCI)) have been demonstrated as important post-operative prognostic factors in those patients with appendix cancer with peritoneal metastases undergoing CRS/HIPEC. A previous analysis included a pre-operative factor and demonstrated the tumour marker to volume index (CA19-9/PCI) in patients who had low grade appendiceal cancer with peritoneal metastases was an independent prognostic factor for overall survival (OS). This analysis aims to evaluate VTI as a prognostic factor in low- and high-grade appendix neoplasms with peritoneal dissemination managed with CRS/HIPEC. Methods: A retrospective cohort study of all patients diagnosed with appendiceal cancer with peritoneal dissemination managed with CRS/IPC from 1996 to 2017 was performed by analysing the survival effect of the ratio of tumour volume to the time between initial tumour resection and CRS/HIPEC. VTI was stratified into low versus high groups, and tumour grade was divided into low grade: diffuse peritoneal adenomucinosis (DPAM); and high grade: peritoneal mucinous carcinomatosis (PMCA). Results: Two hundred and sixty-four patients were included. For both DPAM and PMCA, there was no statistically significant difference in overall survival between patients with a low versus high VTI. For both low and high VTI in DPAM, the median survival was not reached, p= 0.586. For PMCA, those with a low VTI had an overall survival of 63 months (95%CI 48-NR), versus those with a high VTI 69 months (95%CI 45-NR), p= 0.97. There was no statistically significant difference in the median recurrence free survival (RFS) between low and high VTI for both DPAM and PMCA. Conclusions: The volume to time ratio for appendix cancer with peritoneal dissemination was not an independent prognostic indicator for overall survival in patients undergoing CRS/HIPEC, suggesting that this index is not a valuable pre-operative planning tool.

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DNA Damage Response is Prominent in Ovarian High-Grade Serous Carcinomas, Especially Those with Rsf-1 (HBXAP) Overexpression

Journal of Oncology ◽

10.1155/2012/621685 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Malti Kshirsagar ◽

Wei Jiang ◽

Ie-Ming Shih

Keyword(s):

Dna Damage ◽

Chromatin Remodeling ◽

Dna Damage Response ◽

Surrogate Marker ◽

Serous Carcinoma ◽

Low Grade ◽

High Grade ◽

Significant Difference ◽

Damage Response ◽

Microenvironmental Stress

DNA damage commonly occurs in cancer cells as a result of endogenous and tumor microenvironmental stress. In this study, we applied immunohistochemistry to study the expression of phosphorylated Chk2 (pChk2), a surrogate marker of the DNA damage response, in high grade and low grade of ovarian serous carcinoma. A phospho-specific antibody specific for threonine 68 of Chk2 was used for immunohistochemistry on a total of 292 ovarian carcinoma tissues including 250 high-grade and 42 low-grade serous carcinomas. Immunostaining intensity was correlated with clinicopathological features. We found that there was a significant correlation between pChk2 immunostaining intensity and percentage of pChk2 positive cells in tumors and demonstrated that high-grade serous carcinomas expressed an elevated level of pChk2 as compared to low-grade serous carcinomas. Normal ovarian, fallopian tube, ovarian cyst, and serous borderline tumors did not show detectable pChk2 immunoreactivity. There was no significant difference in pChk2 immunoreactivity between primary and recurrent high-grade serous carcinomas. In high-grade serous carcinomas, a significant correlation (P<0.0001) in expression level (both in intensity and percentage) was found between pChk2 and Rsf-1 (HBXAP), a gene involved in chromatin remodeling that is amplified in high-grade serous carcinoma. Our results suggest that the DNA damage response is common in high-grade ovarian serous carcinomas, especially those with Rsf-1 overexpression, suggesting that Rsf-1 may be associated with DNA damage response in high-grade serous carcinomas.

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The Impact of Blastocyst Grade on Singleton Birthweight in Fresh Transplanted Cycles

10.21203/rs.3.rs-726950/v1 ◽

2021 ◽

Author(s):

Qiongyao Shi ◽

Senlin Shi ◽

Wenyan Song ◽

Feifei Zhao ◽

Haixia Jin ◽

...

Keyword(s):

Birth Weight ◽

Live Birth ◽

Cell Mass ◽

The Other ◽

Low Grade ◽

High Grade ◽

Significant Difference ◽

Group A ◽

Grade 3 ◽

The Impact

Abstract Background: A retrospectively cohort study was performed to compare the birth weight of different blastocyst grades in fresh transplantation cycle and explore the related factors affecting the birth weight. Methods: The 1301 fresh cycles of single blastocyst transplantation and single live birth profile were analyzed,four groups were divided according to the grade of transplanted blastocyst. There are 170 cycles in group A with AA blastocyst grade, 312 cycles in group B with AB/BA blastocyst grade, 559 cycles in group C with BB/CA/AC blastocyst grade and 260 cycles in group D with BC/CB blastocyst grade. Comparison were made among four groups of birth weight, general conditions, fertilization rate, embryo rate, cleavage rate and D5,D6 blastocyst formation rate and other laboratory indicators. And then comparison were performed among the birth weight of different groups which were divided by the degree of blastocyst expansion, and the classification of inner cell mass(ICM) and the trophectoderm(TE). Results: The study shows that the birth weight of group A is significantly higher than that of the other three groups (P < 0.05). And the high quality embryo rate and blastocyst rate of group A are significantly higher than those of the other three groups (P < 0.05). What’s more, the clinical pregnancy rate, implantation rate and live birth rate of high grade blastocyst are higher, but there are no significant difference in abortion rate. The birth weight of the degree of blastocyst expansion in grade 3 and below is significantly lower than that of those with grade 3 and above (P < 0.05). The birth weight of grade A of ICM is significantly higher than that of grade B (P < 0.05). The birth weight of grade B of TE is significantly heavier than that of grade C (P < 0.05). Conclusions: Our results indicate that high grade blastocyst transplantation can achieve better pregnancy outcome. Different blastocyst grades affect birth weight, and low grade blastocyst transplantation is associated with a single birth weight loss.

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Comparison of Diffusion and Perfusion Techniques in Differentiating High Versus Low Grade Pediatric Brain Tumors

Proceedings of IMPRS ◽

10.18060/24565 ◽

2020 ◽

Vol 3 ◽

Author(s):

Eric Chen ◽

Chang Ho ◽

Benjamin Gray ◽

Jason Parker ◽

Emily Diller ◽

...

Keyword(s):

Brain Tumors ◽

Tumor Grade ◽

Pediatric Brain Tumors ◽

Solid Cancer ◽

Low Grade ◽

Dynamic Susceptibility ◽

High Grade ◽

Dynamic Contrast Enhancement ◽

Significant Difference ◽

Pediatric Brain

Background/Objective: Brain tumors are the most common solid cancer in children and cause significant mortality and morbidity. We compare the effectiveness of different parameters in predicting tumor grade between dynamic contrast enhancement (DCE), intravoxel incoherent motion (IVIM), dynamic susceptibility contrast (DSC) perfusion and diffusion weighted imaging (DWI). Methods: A retrospective blinded review of pediatric brain tumors with DCE, IVIM, DWI, and DSC was performed. Parametric maps were registered to T2 weighted images. Volumetric regions of interest (ROI) were manually segmented from solid tumor components for each patient by a neuroradiologist (CH), neuroradiology fellow (BG), and medical student (EC). Resulting mean values for parameters from DCE (Ktrans, Kep, Ve, Vp,), IVIM (D, D*, f), DSC (rCBV) and DWI (ADC) were compared using Student’s t-test for high- and low-grade tumor groups based on WHO grading from pathology. For significant parameters, receiver operating characteristic (ROC) analysis with area under curve (AUC) was performed. Results: 20 subjects were included with 9 low grade and 11 high grade tumors. Significant differences between low versus high grade were demonstrated for D (10−3 mm2/s) (1.4±0.4 vs 0.9±0.2, p=0.01), f (0.04±0.02 vs 0.07±0.02, p=0.02), ADC (10−3 mm2/s) (1.4±0.4 vs 0.9±0.3, p=0.009) and rCBV (2.2±0.9 vs 4.7±2.1, p=0.003). No significant difference was found for D* or any DCE parameter. AUC from ROC was similar for all significant parameters [D (0.81, p=0.003); f (0.80, p=0.003); ADC (0.83, p=0.001); rCBV (0.83, p=0.0005)]. Conclusion: D and f parameters from IVIM can significantly differentiate high versus low grade pediatric brain tumors similar to ADC and rCBV. Conversely, no DCE parameter was significant. Scientific Implications: The results will assist the selection of MRI sequences that best predict tumor grade, as well as guide tumor biopsy for the most aggressive tumor portions. Further study of these techniques may correlate with molecular profiling and predict outcome.

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Ulcerative Colitis and Cytomegalovirus Infection: From A to Z

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa036 ◽

2020 ◽

Vol 14 (8) ◽

pp. 1162-1171 ◽

Cited By ~ 4

Author(s):

Fadi H Mourad ◽

Jana G Hashash ◽

Viraj C Kariyawasam ◽

Rupert W Leong

Keyword(s):

Ulcerative Colitis ◽

Inclusion Bodies ◽

Antiviral Treatment ◽

Low Grade ◽

High Grade ◽

Cmv Infection ◽

Significant Difference ◽

Cmv Colitis ◽

Cmv Disease ◽

Severe Colitis

Abstract Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed.

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