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Induction of mucosal healing by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids in patients with ulcerative colitis: long-term remission maintenance after induction by GMA and efficacy of GMA re-treatment upon relapse

Takumi Fukuchi Kousaku Kawashima Hideaki Koga Ran UtsunomiyaKohei Sugiyama Keiji Shimazu Takaaki Eguchi Shunji Ishihara J Clin Biochem Nutr. 2022 Mar;70(2):197-204. doi: 10.3164/jcbn.21-112. Epub 2021 Dec 25.

This study examined the long-term maintenance rate after inducing remission by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids (CS) and GMA re-treatment efficacy in the same patients upon relapse with ulcerative colitis. Patients who achieved clinical remission and mucosal healing (MH) by first-time intensive GMA (first GMA) without CS were enrolled. The cumulative non-relapse survival rate up to week 156 was calculated. Patients with relapse during the maintenance period underwent second-time intensive GMA (second GMA) without CS. Clinical remission and MH rates following second GMA were compared to those following first GMA in the same patients. Of the 84 patients enrolled, 78 were followed until week 156 and 34 demonstrated relapse. The cumulative non-relapse survival rate by week 156 was 56.4%. Clinical remission and MH rates after second GMA did not differ from those after first GMA in the same patients (week 6: clinical remission, 100% vs 88.4%, p = 0.134; MH, 100% vs 84.8%, p = 0.074). In conclusion, MH induction by intensive GMA without use of CS in ulcerative colitis patients contributes to subsequent long-term clinical remission maintenance. GMA re-treatment efficacy was comparable to that of first GMA in the same patients who had relapse.

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Efficacy of cytapheresis for induction therapy and extra-intestinal skin manifestations of ulcerative colitis

Tomoyoshi Shibuya,Osamu Nomura,Kei Nomura,Mayuko Haraikawa,Keiichi Haga,Dai Ishikawa,Taro Osada,Ken Yamaji,Shigaku Ikeda,Akihito Nagahara

Ther Apher Dial 2022 Mar 5. doi: 10.1111/1744-9987.13823. Online ahead of print.

Introduction: In recent years, the prevalence of inflammatory bowel diseases has been increasing in Japan due to the westernization of lifestyles. Many patients have been reported to have extra-intestinal manifestations (EIMs) at least once. Skin lesions occur with a high degree of frequency among EIMs, with erythema nodosum (EN) and pyoderma gangrenosum (PG) the main complications. Cytapheresis is again attracting attention as a treatment with few side effects. Methods: We investigated the therapeutic effect of cytapheresis on ulcerative colitis (UC) and cutaneous EIMs. Between 2008 and 2021, 240 patients with active UC had induction therapy by cytapheresis at our hospital. Results: Remission and response rates were 50.0% and 67.5%, respectively. Apheresis was performed on seven patients with PG and five patients with EN with a good response. Serious adverse events were not observed. Conclusion: This retrospective assessment of efficacy showed that EN and PG responded favorably to cytapheresis.

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Granulocytapheresis in ulcerative colitis (in Spanish)

Gerardo Prieto Bozano an. pedatr. contin.2012;10(5):286-9

  • Existen 2 dispositivos de granulocitoféresis: Cellsorba® (fibras de poliéster no tejidas), que fija granulocitos y linfocitos, y Adacolumn® (acetato de celulosa) que fija selectivamente granulocitos y monocitos.
  • Además de retirar leucocitos activados, la aféresis produce incremento del número de granulocitos CD10-negativos (inmaduros), disminución de citocinas proinflamatorias (factor de necrosis tumoral alfa [TNF-α], interleucina [IL-6],IL-8 e IL-1β) e incremento de citocinas inhibitorias (IL-1, IL-10)
  • La granulocitoféresis es un método razonablemente eficaz y seguro para obtener la remisión en niños con colitis ulcerosa corticodependiente o resistente, sobre todo en pacientes en el primer episodio, en enfermedad de corta evolución y en aquellos que no han recibido esteroides
  • El procedimiento requiere 2 accesos venosos de buen flujo. La pauta más habitual de tratamiento consiste en 1–2 sesiones semanales de 60min a un flujo de 30ml/min, hasta un total de 5–10 sesiones

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Combination Therapy With Ustekinumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis

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.

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Complete Resolution of Mucosal Neutrophils Associates With Improved Long-Term Clinical Outcomes of Patients With Ulcerative Colitis

Rish K Pai 1Douglas J Hartman 2Claudia Ramos Rivers 3Miguel Regueiro 4Marc Schwartz 3David G Binion 3Reetesh 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.

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PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system

Xianyong Gui # 1Alina Bazarova # 2 3Rocìo Del Amor # 4Michael 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.,PICaSSO%20Histologic%20Remission%20Index%20(PHRI)%20in%20ulcerative%20colitis%3A%20development,Gut.

Scientific corner

The combined efficacy of adalimumab with GMA method on the treatment of ulcerative colitis and repair of intestinal mucosal lesion

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.

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Granulocyte and monocyte apheresis therapy for patients with active ulcerative colitis associated with COVID-19

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

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Fecal Calprotectin is a Useful Biomarker for Predicting the Clinical Outcome of Granulocyte and Monocyte Adsorptive Apheresis in Ulcerative Colitis Patients: A Prospective Observation Study

Nobuhiro Ueno, Yuya Sugiyama, Yu Kobayashi, Yuki Murakami et al DOI:

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.

Scientific corner

Granulocyte and monocyte apheresis as an adjunctive therapy to induce and maintain clinical remission in ulcerative colitis: a systematic review and meta analysis

Szabolcs KissDávid NémethPéter Hegyi Mária Földi Zsolt SzakácsBálint Erőss Benedek Tinusz Péter Jenő HegyiPatrícia 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

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