Miki Koroku ¹, Teppei Omori ¹, Harutaka Kambayashi ¹, Shun Murasugi ¹, Tomoko Kuriyama ¹, Yuichi Ikarashi ¹, Maria Yonezawa ¹, Ken Arimura ², Kazunori Karasawa ³, Norio Hanafusa ⁴, Masatoshi Kawana ⁵, Katsutoshi Tokushige 

Intest Res 2022 Jan;20(1):150-155. doi: 10.5217/ir.2020.00148. Epub 2021 Mar 12

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a pandemic. Although several treatment guidelines have been proposed for patients who have both inflammatory bowel disease and COVID-19, immunosuppressive therapy is essentially not recommended, and the treatment options are limited. Even in the COVID-19 pandemic, adjuvant adsorptive granulocyte and monocyte apheresis may safely bring ulcerative colitis (UC) into remission by removing activated myeloid cells without the use of immunosuppressive therapy. Our patient was a 25-year-old Japanese male with UC and COVID-19. This is the first case report of the induction of UC remission with granulocyte and monocyte apheresis treatment for active UC associated with COVID-19.

https://pubmed.ncbi.nlm.nih.gov/33902268/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831771/

Satoshi Tanidaa, b, Keiji Ozekia, Takuya Kannoa, Takahito Katanoa, Naomi Sugimuraa, Hirotada Nishiea, Hiroyasu Iwasakia, Mamoru Tanakaa, Takaya Shimuraa, Eiji Kubotaa, Hiromi Kataokaa, J Clin Med Res. 2021;13(10-11):510-514.

In conclusions, combination therapy with UST plus inten-sive GMA is helpful to ameliorate UC inflammation and clini-cally to reduce disease activities in refractory UC patients, and appears well tolerated.

https://www.jocmr.org/index.php/JOCMR/article/view/4625/25893489

Rish K Pai ¹, Douglas J Hartman ², Claudia Ramos Rivers ³, Miguel Regueiro ⁴, Marc Schwartz ³, David G Binion ³, Reetesh K Pai Clin Gastroenterol Hepatol 2020 Oct;18(11):2510-2517.e5. doi: 10.1016/j.cgh.2019.12.011. Epub 2019 Dec 14.

Background & aims: We investigated correlations between histologic features of the colonic mucosa in patients with ulcerative colitis (UC) and clinical outcomes during a 3-year follow-up period. Methods: We obtained baseline biopsies from all colorectal segments (n = 889) from 281 patients with UC enrolled in a prospective study at a single center from 2009 through 2013. Biopsies were assessed in a blinded manner using validated histologic scoring systems (the Geboes score, Nancy histopathologic index, and Robarts histopathologic index). Clinical, endoscopic, and histologic data were collected and tested for correlations with systemic corticosteroid use, hospitalization, and colectomy within 3 years of the index colonoscopy. Results: We found histologic evidence of UC activity (Geboes score ≥ 2B.1) in biopsies from 182 patients (65%) and endoscopic evidence of UC activity in 149 patients (53%) (substantial agreement, κ = 0.60). Histologic features of UC activity were associated with increased rates of systemic corticosteroid use, colectomy, and hospitalization in the entire cohort (P < .05 for all) and associated with increased rates of systemic corticosteroid use in an analysis limited to patients in endoscopic remission (P < .001). In patients in endoscopic remission, only histologic activity was independently associated with use of systemic corticosteroids (multivariate odds ratio, 6.34; 95% CI, 2.20-18.28; P = .001). Similar results were seen when the entire cohort was analyzed. Compared with patients without histologic evidence of UC activity, patients with only a small number of mucosal neutrophils still had higher rates of systemic corticosteroid use (P < .001). Conclusions: Histologic evidence of UC activity, including small numbers of neutrophils in the colonic mucosa, is the only factor independently associated with use of systemic corticosteroids. Complete resolution of neutrophil-associated inflammation should be a target for treatment of UC.

https://pubmed.ncbi.nlm.nih.gov/31843598/

https://www.cghjournal.org/article/S1542-3565(19)31438-7/fulltext

Xianyong Gui ^# 1, Alina Bazarova ^# 2 3, Rocìo Del Amor ^# 4, Michael Vieth  et al. Gut  2022 Feb 16;gutjnl-2021-326376. doi: 10.1136/gutjnl-2021-326376. Online ahead of print.

Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity. Methods: Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies. Results: PHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients’ risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy. Conclusions: PHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission.

https://pubmed.ncbi.nlm.nih.gov/35173041/#:~:text=artificial%20intelligence%20system-,PICaSSO%20Histologic%20Remission%20Index%20(PHRI)%20in%20ulcerative%20colitis%3A%20development,Gut.

https://gut.bmj.com/content/early/2022/02/23/gutjnl-2021-326376.long

Ailing Song, Hai Jiang, Liang Guo, Shanshan Wu, Am J Transl Res 2021;13(5):5156-5164

Objectives: The study discussed and analyzed the combined efficacy of adalimumab with granulocyte and monocyte adsorption apheresis (GMA) method on patients with ulcerative colitis (UC) and the repair of intestinal mucosal lesion. Methods: 60 UC patients in moderate-to-severe active phase that hospitalized from January 2017 to March 2020 were chosen and randomly classified into observation group (n=30) and control group (n=30). The control-group patients received GMA treatment, and the observation-group patients received combination therapy of GMA and adalimumab. The therapeutic efficacy, laboratory indicators, changes of serum inflammatory factors, and intestinal mucosal barrier impairment in two sets of participants were compared. Results: The comprehensive effective rate of clinical treatment was remarkably higher in observation group than that in control group (P<0.05). CRP and ESR of the two groups in post- treatment were notably lower than those before treatment (P<0.05), while Hb and ALB in post-treatment increased significantly than in pre-intervention (P<0.05); CRP in observation group after treatment was remarkably lower than that in control group (P<0.05), while no significant difference was noticed in ESR, ALB and Hb between the two groups (P>0.05). The serum inflammatory factors in observation group in post-treatment were significantly lower than those in the control group (P<0.05). The scores of PCT, DAO and intestinal mucosa in two sets of participants in post-treatment were dramatically lower than those in pre-treatment (P<0.05), and the scores in observation group after treatment were notably lower than those in the control group (P<0.05). Conclusions: The combined efficacy of adalimumab with GMA on UC patients can improve the clinical curative efficacy, effectively reduce the inflammatory factors, which is beneficial to the repair of intestinal mucosal barrier function, and worthy of clinical application.

https://pubmed.ncbi.nlm.nih.gov/34150104/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205815/pdf/ajtr0013-5156.pdf

Miki Koroku ¹, Teppei Omori ¹, Harutaka Kambayashi ¹, Shun Murasugi ¹, Tomoko Kuriyama ¹, Yuichi Ikarashi ¹, Maria Yonezawa ¹, Ken Arimura ², Kazunori Karasawa ³, Norio Hanafusa ⁴, Masatoshi Kawana ⁵, Katsutoshi Tokushige ¹ Intest Res. 2021 Mar 12. doi: 10.5217/ir.2020.00148.

In conclusion, our patient’s case indicates that GMA for a patient with both active UC and COVID-19 is a safe treatment option for active UC that could lead other patients in this condition to remission.

https://pubmed.ncbi.nlm.nih.gov/33902268/

https://irjournal.org/upload/pdf/ir-2020-00148.pdf

Nobuhiro Ueno, Yuya Sugiyama, Yu Kobayashi, Yuki Murakami et al DOI: https://doi.org/10.21203/rs.3.rs-154609/v1

In summary, we demonstrated the utility of FC as a biomarker for assessing ER after GMA and predicting CR at the early phase during GMA in patients with active UC. Assessing the baseline characteristics alone before GMA was not sufficient to predict CR. Our findings will benefit patients with active UC by allowing them to avoid undergoing unnecessary invasive procedures and will help establish new GMA therapeutic strategies.

https://www.researchsquare.com/article/rs-154609/v1

https://assets.researchsquare.com/files/rs-154609/v1/13c1025f-0cf0-4c37-8238-a76d8ff621a7.pdf

Szabolcs Kiss, Dávid Németh, Péter Hegyi , Mária Földi , Zsolt Szakács, Bálint Erőss , Benedek Tinusz , Péter Jenő Hegyi, Patrícia Sarlós , Hussain Alizadeh, BMJ Open 2021 May 19;11(5):e042374.

The results support the hypothesis that patients with active UC have a better chance of clinical remission if GMA is administered as an adjunctive therapy. As regards the frequency of AEs, we found no statistically significant difference between the two groups. With regard to remission maintenance, GMA was identified as an effective alternative therapeutic option

https://pubmed.ncbi.nlm.nih.gov/34011580/

e042374.full.pdf (bmj.com)

Chie Kurihara, Toshihide Ohmori, Kenichi Inaba, Nao Sugihara, Yoshinori Hanawa, Kazuki Horiuchi, Akinori Wada, Shin Nishii, Akinori Mizoguchi, Suguru Ito, Rina Tanemoto, Akira Tomioka, Yoshikiyo Okada, Yoshihiro Akita, Kazuyuki Narimatsu, Masaaki Higashiyama, Shunsuke Komoto, Kengo Tomita, Ryota Hokari

Background: Granulocyte and monocyte adsorptive apheresis (GMA) is non-pharmacological therapy which selective depletion of activated granulocytes and monocytes/macrophages from peripheral blood, and it is used as induction therapy for IBD. However, its therapeutic mechanism has not been well characterized. Recently, mucosal healing has been emerged as a therapeutic goal for IBD. It has been reported that growth factors play a role in improvement of mucosal repair and regeneration in animal colitis models, and tight junction proteins which impact mucosal permeability play a crucial role in mucosal healing. We investigated that changes in mRNA expression levels of these molecules in colonic mucosa of ulcerative colitis (UC) patients before and after GMA treatment in order to obtain further understanding of GMA therapeutic mechanisms. Methods: Thirty-two active UC patients (Mayo score ≥ 5 and Mayo endoscopic score ≥ 2) were enrolled in this study. All UC patients received 10-11 times of GMA, and colonoscopies were applied before the first GMA (preGMA) and after the last GMA (post-GMA). Assessment of GMA therapeutic efficacy and colonic mucosal healing were determined based on Mayo score. Growth factors such as EGF and HGF, and tight junction proteins such as occludin and ZO-1 mRNA expressions were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. Results: After GMA treatment, 11 patients (34.4%) achieved clinical remission, 17 patients (53.1%) showed clinical response and 4 patients (12.5%) showed non-response. All patients of the clinical remission group achieved mucosal healing, whereas none of patients in non-response group achieved mucosal healing. Baseline characteristics such as sex, location of disease, CRP, WBC and Mayo score were not significantly different according to GMA efficacy. In both pre-GMA and post-GMA, the clinical remission group showed significantly higher expressions of occludin, ZO-1 and EGF mRNA in mucosal tissue than those of the nonresponse group (P <0.05). Post-GMA, HGF mRNA expression tended to be lower in the remission group than those in non-response group. In the non-response group, levels of occludin and ZO-1 mRNA significantly decreased post-GMA compared to their pre-GMA levels (P <0.05), but they were not decreased in the clinical remission group. In contrast, HGF mRNA level decreased post-GMA compared to its pre-GMA level in the remission group, but it was not decreased in the non-response group. Conclusion: In UC patients who achieved clinical remission by GMA, expressions of EGF and tight junction molecules were higher significantly, and mRNA level of HGF decreased after GMA treatment. These results suggest that these molecules play an important role in mucosal healing, and could be helpful for choosing patients who are respond to GMA before treatment

https://www.gastrojournal.org/article/S0016-5085(21)01910-7/pdf

ISFA-EIFA-2021

Remission induction was more challenging in elderly UC patients. However, CAP was safe and effective for remission induction as a non-pharmacological treatment, even in elderly UC patients, after the incorporation of practical measures. Optimized and contrived CAP is still useful as the sole or concomitant treatment.

https://www.eventclass.org/contxt_eisfa2021/online-program/session?s=S-05