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Tu1846 Higher Expression of MIP-1β and IL23 in Colonic Mucosa of Pretreatment may Predict Therapeutic Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Elderly Patients with Ulcerative Colitis

Chie Kurihara Toshihide Ohmori Shingo Kato Koji Yakabi Satoshi Mochida Soichiro Miura Gastroenterology 2017 152 (5) Suppl. S764

Background: The number of the elderly patients of ulcerative colitis (UC) is growing as the population ages. Because elderly patients with UC sometimes become refractory to treatment, it is important to select an appropriate induction therapy for elderly patients at the early phase of UC disease. To predict which therapy is effective before treatment will be useful for the decision of later therapeutic strategy. Granulocyte and monocyte adsorptive apheresis (GMA) that was developed for selective depletion of activated granulocytes and monocytes/
macrophages from peripheral blood is non-pharmacological therapy for inflammatory bowel disease. It is beneficial than the other therapy in the point that it has fewer side effects. GMA is effective and safe as induction therapy in UC, and commonly used in Asia and north Europe. GMA is one of hopeful candidate of elderly therapy. We investigated the relationship between therapeutic efficacy of GMA and age, and examined whether mRNA expressions of cytokines and chemokines in colonic mucosa showed presence of age-related change. Methods: Thirty-two active UC patients, mean age 36.7 years, range 14-70 years, were enrolled in this study. All patients received 10 or 11 times of GMA, and colonoscopies were applied before the first GMA and after the last GMA. Assessment of disease activity and colonic mucosal healing were determined based on Mayo score. In this study, elderly patients were defined as those >55 years of age. mRNA expressions of cytokines and chemokines were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. Results: There were no significant differences in sex, duration of disease, location of disease, CRP, WBC and Mayo score before the first GMA treatment between elderly group and non-elderly group. After the last GMA session, the ratios of mucosal healing in elderly group and non-elderly group were 2 of 6 (33.3%) and 16 of 26 (61.5%), respectively. In all patients, before treatment of GMA, mucosal healing group showed significantly higher mRNA expression of inflammatory cytokines and chemokines such as MIP-1β, TNFα, IL1β and IL8 in colonic mucosal tissue than that of non-mucosal healing group (P <0.05). In particular, in elderly group, the degree of mRNA expression of MIP-1β and IL23 in colonic mucosa before GMA treatment was higher in mucosal healing group than in non-mucosal healing group (P <0.05). High expressions of MIP-1β and IL23 showed sensitivity, specificity, positive predictive value and negative predictive value of 100% as a marker of mucosal healing after GMA in elderly group. Conclusion: Mucosal IL23 and MIP-1β mRNA expression before treatment in elderly were significantly higher in responder than non-responder to GMA treatment. We propose that measuring of expression of these molecules is useful to expect therapeutic efficacy of GMA in elderly patients with UC.

https://www.gastrojournal.org/action/doSearch?text1=mo1730&field1=AllField

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Granulocitoaféresis en 2017. Puesta al día (Spanish)

Cabriada, J.L., Rodríguez-Lago, I.

Enfermedad Inflamatoria Intestinal 20017 (16) 2, 62-69 DOI: 10.1016/j.eii.2016.12.001 

Granulocyte apheresis is a procedure that allows the removal of different activated leukocyte populations and it also modifies some circulating inflammatory mediators. These effects, along with its immunomodulatory potential, make it an attractive therapeutic option in inflammatory bowel disease. Previous studies with this technique have had significant limitations, but recent data is emerging about the ideal clinical setting in which granulocyte apheresis should be indicated. Most of the evidence supports its use in conditions that are dependent or refractory to corticosteroids, especially when treatments with immunomodulators or biologics has failed and when it is necessary to reduce or avoid the use of systemic corticosteroids. Its excellent safety profile gives it a role in cases of comorbidity or risk in the use of immunosuppressive drugs or in paediatric patients. In this review, we provide an update on the role of granulocyte apheresis in inflammatory bowel disease.

https://www.elsevier.es/es-revista-enfermedad-inflamatoria-intestinal-al-dia-220-articulo-granulocitoaferesis-2017-puesta-al-dia-S1696780116300999

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Therapeutic Apheresis in Pregnancy: Three Differential Indications With Positive Maternal and Fetal Outcome

Giuseppina Perrone 1, Roberto Brunelli 1, Eleonora Marcoccia 1, Ilaria Zannini 1, Miriam Candelieri 1, Maria Gozzer 2, Claudia Stefanutti 3

When approaching TA in pregnancy, clinicians have to consider the severity of disease, the strength of the indications, and the gestational age. Each case must be evaluated individually on the basis of existing evidence since, despite the increasing use, specific guidelines for apheresis in pregnancy are still lacking.

https://pubmed.ncbi.nlm.nih.gov/27412826/

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Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue.

Anand Padmanabhan 1, Laura Connelly-Smith 2, Nicole Aqui 3, Rasheed A Balogun 4, Reinhard Klingel 5, Erin Meyer 6, Huy P Pham 7, Jennifer Schneiderman 8, Volker Witt 9, Yanyun Wu 10, Nicole D Zantek 11, Nancy M Dunbar 12, Guest Editor Joseph Schwartz 13 , J Clin Apher. 2019 Jun;34(3):171-354.

The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

https://pubmed.ncbi.nlm.nih.gov/31180581/

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Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults.

Gerda C Leitner 1, Harald Vogelsang 1 , World J Gastrointest Pharmacol Ther. 2016 Feb 6;7(1):5-20.

As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.

https://pubmed.ncbi.nlm.nih.gov/26855808/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734954/pdf/WJGPT-7-5.pdf

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Immunological Mechanisms of Adsorptive Cytapheresis in Inflammatory Bowel Disease.

Esteban Sáez-González 1, Inés Moret 2 3 4, Diego Alvarez-Sotomayor 2, Francia Carolina Díaz-Jaime 2, Elena Cerrillo 2 3, Marisa Iborra 2 3 4, Pilar Nos 2 3 4, Belén Beltrán 2 3 4 , Dig Dis Sci. 2017 Jun;62(6):1417-1425.

The benefit of cytapheresis appears to rest upon its ability to reduce levels of certain immune cell populations; however, whether this depletion results in further changes in lymphocyte populations and cytokine production needs further clarification. In this review, we aim to summarize existing evidence on the role of cytapheresis in patients with IBD, its effect on cytokine levels and cellular populations, and to discuss its potential impact on disease activity.

https://pubmed.ncbi.nlm.nih.gov/28432476/

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Retrospective Single Center Study of Granulocyte Monocyte Adsorption Apheresis Treatment in Inflammatory Bowel Disease.

Kajsa Edfors 1, Dagny Ståhlberg 1, Charlotte Söderman 1 , Ther Apher Dial. 2016 Feb;20(1):79-85.

 Most frequently reported was headache (N = 4). GMA seems to be a valuable adjuvant treatment regime in the care of patients with refractory IBD.

https://pubmed.ncbi.nlm.nih.gov/26841133/

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Letter: The efficacy and safety of selective granulocyte and monocyte apheresis for inflammatory bowel disease: A meta-analysis.

Zhenfei Liu 1, Xueliang Jiang 2, Chengcheng Sun 3 , Eur J Intern Med. 2016 Dec;36:e26-e27. 

https://pubmed.ncbi.nlm.nih.gov/27614377/

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Efficacy and usefulness of new single-needle Intensive granulocyte and monocyte adsorptive apheresis in active ulcerative colitis patients without corticosteroids and biologics

Keiji Shimazu 1, Takumi Fukuchi 2, Insung Kim 3, Yuki Noguchi 3, Megumi Iwata 1, Shintaro Koyama 2 4, Satoshi Ubukata 2, Atsuo Tanaka 1 , Ther Apher Dial 2016 Aug;20(4):383-9.

Intensive granulocyte and monocyte adsorptive apheresis (GMA) twice weekly is effective and safe for patients with active ulcerative colitis (UC), but the requirement for maintaining two blood access routes is problematic. Here we compared the efficacy and safety of one-route blood access intensive GMA using a single-needle (SN) and conventional two-route blood access intensive GMA using a double-needle (DN) in patients with active UC not undergoing corticosteroid therapy. Among 80 active UC patients, 38 patients received SN intensive GMA and 42 patients received DN intensive GMA. The clinical remission ratio and mucosal healing ratio at 6 weeks, and the cumulative non-relapse ratio at 52 weeks did not differ significantly between groups. In addition, no serious or mild adverse effects were observed in SN intensive GMA. SN intensive GMA may be an adequate and novel therapeutic option for active UC as an alternative therapy before using corticosteroids.

https://pubmed.ncbi.nlm.nih.gov/27523079/

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Pyoderma Gangrenosum with Ulcerative Colitis Successfully Treated by the Combination of Granulocyte and Monocyte Adsorption Apheresis and Corticosteroids

Masashi Ohno 1, Shigeki Koyama, Mariko Ohara, Kazumi Shimamoto, Yu Kobayashi, Fumiyasu Nakamura, Kazuki Mitsuru, Akira Andoh

Intern Med.  2016;55(1):25-30. doi: 10.2169/internalmedicine.55.5422. Epub 2016 Jan 1.

A 36-year-old woman was admitted to our hospital due to swelling and redness of the left lateral malleolus and dorsum of the left foot with severe pain, with a flare-up of ulcerative colitis (UC). A pathologic examination by skin biopsy led to a diagnosis of pyoderma gangrenosum (PG). She was treated with the intravenous administration of prednisolone (60 mg/day), and granulocyte and monocyte adsorption apheresis (GMA) was performed twice-a-week for 5 weeks. This treatment dramatically improved both the skin and colonic mucosal lesions. These results suggest that a combination of GMA and corticosteroids might be recommendable to induce the remission of serious PG complicated with UC.

https://pubmed.ncbi.nlm.nih.gov/26726081/

https://www.jstage.jst.go.jp/article/internalmedicine/55/1/55_55.5422/_article

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