The effect of granulocytapheresis treatment on the mental health status of patients with inflammatory bowel disease

The effect of granulocytapheresis treatment on the mental health status of patients with inflammatory bowel disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The effect of granulocytapheresis treatment on the mental health status of patients with inflammatory bowel disease Selda Kahraman, Hakan Yüceyar, Evren Ozdemir This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9033099/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Studies on granulocytapheresis have emerged with the need for alternative treatments in patients with inflammatory bowel disease (IBD) refractory to conventional therapy.. In our study; It was aimed to examine the changes in the patients' quality of life, depression and anxiety after the granulocytapheresis procedure in patients with IBD. Our study included a total of 41 patients (14 female, 27 male), 22 active Ulcerative Colitis (UC), 19 Chrohn Diseases (CD), who underwent granulocytapheresis using Cellsorba E column between June 2021 and July 2022 in Medicana İzmir Hospital. The median age of the patients was 34 (19-66). Before the procedure, SF 36 , illness anxiety and Beck anxiety-depression, illness anxiety questionnaires, which show the patients' quality of life, anxiety and depression, were administered to all patients. The granulocytapheresis procedure was performed in 10 sessions (2 days a week / 5 weeks in total) with concomitant medications. The same questionnaires were repeated one week after the procedure was completed. Beck anxiety, Beck depression and illness anxiety scores were found to be statistically significantly lower after the application (p=0.018, p<0.001, p=0.005). The Physical Function score (p=0.017), general health perception (p=0.001), vitality (p=0.002), social functionality (p<0.001), mental health (p<0.001), health change (p=0.017). scores were found to be statistically significantly higher after the application. A more significant decrease was observed in Beck anxiety scores in women compared to men. (t:2,854, p: 0.008) In the disease anxiety scores, those with higher education level (t: 2.810, p: 0.010), non-smokers (t: 2.667, p: 0.013), non-antidepressant users (t: 2.650, p: 0.013) more significant decrease was observed. There was a significant increase in health change scores (t: 2.667, p: 0.013), mental health scores (t: 2.086, p: 0.044) in regularly working patients. In conclusion; After 10 sessions of granulocytapheresis in patients with IBD resistant to standard treatments, a significant improvement was observed in patients' quality of life, depression and anxiety. With the procedure, monocytes were significantly removed from the circulation, improvement was observed in the acute phase response such as sedimentation and CRP, and as a complication of the apheresis procedure, the hb, htc, and platelet values of the patients decreased partially at a level that did not require intervention. Ulcerative colitis Chrohn's disease Leukocytapheresis INTRODUCTION Inflammatory bowel diseases (IBD), including the Crohn's disease (CD) and ulcerative colitis (UC) represent the chronic recurring inflammatory conditions of the gastrointestinal system, characterized by uncertain etiology and unpredictable progress. ( 1 – 3 ) Although the etiology of the IBDs remains unknown, it is believed that genetic factors, intestinal flora and immune-mediated tissue damage are involved in its pathogenesis. ( 4 ) The number of granulocytes and macrophages in the mucous, cytokines ( 5 , 6 ), reactive oxygen derivatives ( 7 – 10 ) and catalytic proteases ( 11 ) play important roles in proinflammatory release. The therapeutic purpose of IBD treatments is to suppress disease activation to achieve clinical remission. ( 12 ) Agents commonly used to control disease activity for this purpose include 5-aminosalicylate (5-ASA) compounds, steroids, immunosuppressants (thiopurines), inhibitors of calcineurin (cyclosporin, tacrolimus) and anti-tumor necrosis factor alpha (TNF-α) inhibitors (infliximab, adalimumab) and biological agents such as and adhesion molecule inhibitor vedolizumab ( 12 – 14 ). Despite these treatments, proctocolectomy is required for about one-third of patients with a steroid-dependent or steroid-resistant medium to severe active UC. Despite multimodal medical treatments, including immune-modulating drugs and anti-TNF-alpha antibodies, IBD has no definitive treatment; the aim of treatments is to ameliorate the patient's symptoms and improve their quality of life. ( 15 – 18 ) In IBD, studies have emerged on leukocytapheresis with the need for alternative treatments in patients who are resistant to conventional treatment. Leukocytapheresis is a new non-pharmacological treatment approach in patients who are resistant to standard treatment approaches with active UC and CD, where leukocytes are mechanically removed from the circulatory system. Given the key role of granulocytes and macrophages in physiology, absorptive carrier-based granulocyte and monocyte apheresis instruments have been developed and their effects on inflammation have been proven in in-vivo and in-vitro environments. ( 19 ). The side effects of the drugs used have led to non-pharmacological treatment approaches with fewer side effects, including granulocyte and monocyte absorptive [GMA] apheresis [Adacolumn®, Otsuka Pharmaceuticals] and leukocytapheresis [GCAP; Cellsorba®, Asahi Medical] in patients with IBD. (20.21). IBD is associated with a significant psychosocial burden. IBD's course is chronic and unpredictable, accompanied by intense abdominal pain, diarrhea, deteriorated fecal control, fear of cancer, occasional need for surgical intervention, which make patients anxious about many aspects of life, tired and socially isolated. Therefore, pharmacological approaches and psychosocial support are widely used by patients with IBD. [22–24] Studies found that in patients with IBD, compared to healthy individuals, the rates of anxiety and depression were higher (anxiety: 9.6% vs. 19.1%, depression: 13.4% vs. 21.2%). ( 25 ) Business life can also be affected by the disease. Disease can lead to change in career choice, reduced working hours, irregular work, and financial difficulties. ( 26 – 28 ) Our study intended to examine the pre-treatment and post- leukocytapheresis changes in quality of life, depression and anxiety conditions of IBD patients who are resistant to standard treatments. METHOD STUDY DESIGN Our study was conducted at Medicana Izmir Hospital between June 2021 and July 2022 and included a total of 41 patients (14 women 27 men), 22 active UC and 19 CD, who underwent granulocytapheresis using the Medica la25 leucocyte adsorber device model 2020. Inclusion criteria for the study Those patients who were refractory or intolerant to steroid-dependent or active immune suppressors and/or biological agents were admitted into the study. Poor response was defined as continued disease activity, intolerance to previous treatments and allergic reaction after 3 months of 2.5 mg/kg of azathioprine or 1.5 mg/kg of 6-mercaptopurine use or 14 weeks after the start of anti-TNF-α treatment Exclusion criteria for the study , Those with active infection, those with inflammatory diseases under control, those who did not accept vascular intervention were excluded from the study. Hemogram, prothrombin time (PT), active partial thromboplastin time (APTT), international normalization ratio( INR), fibrinogen, ferritin, C-reactive protein (CRP) sedimentation values ​​of the patients were measured before and after the procedure. All blood of the patients was taken from the anterior cubital vein one hour before the first procedure and one hour after the last procedure. Questionnaires were conducted one hour before the first procedure and a week after the last procedure . Granulocytapheresis (GA) Procedures All patients received GA therapy on twice a week with the Adacolumn as previously described ( 43 ) Conventional medication was to be continued during the whole GA treatment . The 2020 model of the medica la 25 leukocyte adsorber device was used for this treatment Peripheral veins of the patients were evaluated. Peripheral vein was used in patients with suitable veins. A central venous catheter was inserted in patients with unsuitable veins and the GA was performed here. All procedures were carried out in accordance with relevant GA procedures and regulations.( 43 ) Consent was obtained from all patients for participation in the study, they filled a socio-demographic form and completed surveys with the face-to-face interview method. The ethics committee approval regarding the study was obtained from the ethics committee of Izmir Katip Çelebi University Non-Interventional Ethics Committee with the date 03.Jan.2021 and protocol number 104 GOA, decision number 150. Measures All patients underwent face-to-face interviews before GA and one week after the procedure, completing the Short Form-36 (SF-36) Quality of Life Scale, Illness Anxiety Inventory (HAI) Beck Anxiety Inventory (BAI), and Beck Depression Inventory.(BDI) Short Form-36 (SF-36) quality of life scale : The validity and reliability study of the Turkish version of the scale, which was developed by Ware and Sherbourne to assess quality of life, was conducted by Kocyigit et al. ( 29 , 30 ). This self-report scale is used for those with physical diseases with a higher priority, but it can also be used for those with a psychiatric disease ( 31 ). Its eight dimensions include physical functionality, social functionality, physical role difficulty, emotional role difficulty, mental health, energy, pain and overall perceived health, and it consists of 36 items: Subscales assess health between 0-100, where 0 indicates a poor health condition and 100 indicates a good health condition. In addition, the overall score of the scale is not used, and the sub-categories are evaluated among themselves. It was planned to use the Beck’s Anxiety Inventory (BAI) and Beck’s Depression Inventory (BDI) (Table 1) to determine the anxiety and depression conditions of the patients. With BDI depression was categorized into normal, mild mood disturbance, borderline clinical depression, moderate depression, severe depression and extreme depression. With the BAI anxiety was classified as mild, moderate and severe anxiety. These inventories are the ones developed by Beck in 1961, and the validity and reliability studies in Turkey were conducted by Tegin (1980) and Hisli (1988) ( 32 , 33 ). The Ilness Anxiety Inventory (HAI); is a reliable and valid assessment tool for assessing illness anxiety and will be useful in both clinical practice and research. The Illness Anxiety Inventory’s reliability and validity study for Turkish was conducted by Aydemir et al. in 2013. ( 34 ) Before the GA, all patients completed SF-36 quality of life, BAI, BDI and HAI, which indicated their quality of life, anxiety and depression conditions. With simultaneous medication, the patients underwent GA for 10 sessions (2 days per week/5 weeks in total). The same surveys were re-conducted a week after the GA completed. Statistical evaluation: All data were recorded to SPSS 15. The evaluations between different times (basal versus after 10 sessions of GA) between each other have been done non-parametric Mann-Whitney U test, whereas the correlation analysis has been done Pearson correlation analysis. P value less than 0.05 was considered statistically significant. RESULTS Our study was conducted at Medicana Izmir Hospital between June 2021 and July 2022 and included a total of 41 patients (14 women and 27 men), 22 active UC and 19 CH, who underwent GA using the Medica la25 leucocyte adsorber device model 2020. No complication requiring intervention occurred in any of the patients during the leukocytapheresis procedure. The patients’ median age was 34 (19-66). Those patients who were refractory or intolerant to steroid-dependent or active immune suppressors and/or biological agents were admitted into the study. Before the GA all patients completed SF-36 quality of life, BAI, BDI and HAI which indicated their quality of life, anxiety and depression conditions. With simultaneous medication, the patients underwent GA for 10 sessions (2 days per week/5 weeks in total). The same surveys were re-administered a week after the GA was completed. Demographic data of the patients are presented in Table 2. Nineteen patients (46.3%) were university graduates, 10 patients (24.4%) high school graduates, 7 patients (17.1%) secondary school graduates, and 5 patients (12.2%) were primary school graduates. Twenty-five patients (61%) were married, while 16 patients (39%) patients were single. Thirty-two patients (78%) were non-smokers, and 9 patients (22%) were smokers. While 24 patients (58.5%) were actively working, 17 patients (41.5%) were unemployed. Fifteen patients (36.6%) were receiving anti-TNF treatment, 33 patients were receiving steroids (80.5%), and 13 patients (31.7%) were receiving antidepressants. In 6 patients (14.6%), the GA was performed with the central venous catheter, and in 35 (85.4%) patients, the procedure was performed through peripheral vascular access. Regarding pre-operational BAI status of the patients, 12 patients (27.5%) had mild anxiety, 9 (22.5%) patients had moderate anxiety, and 4 patients (10%) presented severe anxiety, whereas 16 (40%) patients had no anxiety. As to the pre-operational BDI status of the patients, 7 patients (17%) had mild depression, 11 (26.8%) patients had moderate, 16 patients (39%) had moderate, 4 (9.9%) patients had severe depression, and 3 (7.3%) patients presented no depression. At the end of the 5-week procedure, the patient's clinical status was evaluated by gastroenterologists. Gastroenterologists evaluated the effectiveness of the GA procedure by looking at the patient's clinical complaints, physical examinations, and colonoscopy findings. The clinical activity indices of the patients showed 70% complete response and 25% partial response and %.5 had no response to the treatment. Table 3 provides comparative analysis results for the scores of surveys administered before and after the GA process. BAI, BDI and HAI scores significantly decreased after the process. (p=0.018, p<0.001, p=0.005). After the GA, the physical functionality score (p=0,017) and overall perceived health increased significantly. (p=0.001). Vitality (p=0.002), social functionality (p<0.001), mental health (p<0.001) and health change (p=0.017) scores increased after the procedure. In women, BAI scores were seen to drop more remarkably than in men. (t: 2.854, p:0.008) In terms of HAI scores, high-school and higher-level graduates (t: 2.810, p: 0.010), non-smokers (t: 2.667, p: 0.013), and those who did not receive antidepressants (t: 2.650, p: 0.013) presented a more remarkable decrease. Regularly employed patients had remarkably increased health change (t: 2.667, p: 0.013) and mental health scores (t: 2.086, p: 0.044). After 10 sessions of GA, the change in the blood parameters of patients is presented in Table 4. Hemoglobin (hb) (p=0.002), hematocrit (htc) (p=0.002), platelet (plt) (p<0.001), monocyte (p=0.006), CRP (p=0.024), and sedimentation levels (p=0.031) decreased significantly after the procedure. There was no statistically significant difference among leukocyte (p=0.813), neutrophile (p=0.619), lymphocyte (p=0.475), PT (p=0.310), APTT (p=0.145), INR (p=0.359), fibrinogen (p=0.070) and ferritin (p=0.111) levels DISCUSSION IBDs affect the quality of life due to chronic disease, indefinite prognosis, surgical operation and cancer development risks, causing anxiety and depression ( 35 – 37 ). In our study, regardless of disease activity, patients with potential depression and potential anxiety comprised, approximately, 51% and 55%, respectively. The prevalence of anxiety and/or depression during the recovery period in IBD is 29–35%, whereas the prevalence of anxiety and depression in the recurrence period is estimated to be 60% and 80%, respectively ( 38 , 39 ). In our study, anxiety and depression were found to be common among the patients with IBD, which was in line with the global literature. Regarding pre-operational BAI scores of the patients, 12 patients (27.5%) had mild anxiety, 9 (22.5%) patients had moderate anxiety, and 4 patients (10%) presented severe anxiety, whereas 16 (40%) patients had no anxiety. As to the pre-operational BDI status of the patients, 7 patients (17%) had mild depression, 11 (26.8%) patients had moderate, 16 patients (39%) had moderate, 4 (9.9%) patients had severe depression, and 3 (7.3%) patients presented no depression There are studies that compare quality of life, anxiety and depression conditions of IBD patients with healthy individuals. In our study, GA, an alternative treatment method, was administered to patients who were resistant to standard treatments. The aim was to examine the changes in quality of life, anxiety and depression conditions before and after the GA in the patients. . A study by Gerceker et al. reviewed the results of GA treatment in 6 patients with CD and 20 patients with active UC. With accompanying medications, the patients underwent GA (10 sessions for remission induction treatment, 6 sessions for maintenance treatment). In 30% of patients with active severe UC, intensive GA was employed (≥ 4 GA sessions in the first 2 weeks). The overall clinical remission rate for the patients with UC was 80% and the mucosal improvement rate was 65%. Patients were followed up for 24 months on average. Sixty-five percent of the patients with UC were found to have continued clinical remission. The follow-up indicated a mild recurrence in 3 patients with UC. In 5 patients with CD, significant clinical remission was achieved, except for one patient. ( 40 ) A meta-analysis involving seven randomized controlled studies in which GA procedures were analyzed found a more remarkably improved disease activity in UC. Significantly improved response rates and remission rates were achieved as a result of GA compared to traditional treatment ( 41 ). In another study by Habermalz et al., patients treated with GA for 12 weeks presented significantly higher remission rates compared to patients treated with traditional treatments ( 42 ). There are studies in the literature on anxiety-depression and quality of life in inflammatory bowel disease, as well as studies examining the effect of GA on the treatment of inflammatory bowel disease. Although there are studies in the literature that analyze the post-GA change in disease activity, there is no study that examines the change in quality of life, anxiety and depression conditions. In the present study, post-operational hb (p = 0.002), htc (p = 0.002), plt (p < 0.001) levels of the patients reduced significantly after 10 sessions of GA procedure. There was no statistically significant difference among leukocyte (p = 0.813), neutrophile (p = 0.619), lymphocyte (p = 0.475), PT (p = 0.310), APTT (p = 0.145), INR (p = 0.359), fibrinogen (p = 0.070) and ferritin (p = 0.111) levels. Monocyte (p = 0.006), CRP (p = 0.024), and sedimentation levels (p = 0.031), which are important markers of inflammation, decreased significantly after the procedure. Regarding anxiety and depression, BAI, BDI and HAI scores significantly decreased after the procedure. (p = 0.018, p < 0.001, p = 0.005 ). The physical functionality (p = 0.017) and overall perceived health, which are part of the sub-parameters of the SF36 quality of life survey, have increased significantly after the procedure. (p = 0.001). Vitality (p = 0.002), social functionality (p < 0.001), mental health (p < 0.001) and health change (p = 0.017) scores increased after the procedure. In women, BAI scores were seen to drop more remarkably than men. (t: 2.854, p:0.008) In terms of HAI scores, high-school and higher-level graduates (t: 2.810, p: 0.010), non-smokers (t: 2.667, p: 0.013), and those who did not receive antidepressants (t: 2.650, p: 0.013) presented a more remarkable decrease. Regularly employed patients had remarkably increased health change (t: 2.667, p: 0.013) and mental health scores (t: 2.086, p: 0.044). Given these results, post GA anxiety significantly decreased in female patients with higher levels of education, who are non-smokers, actively engaged in life and regularly employed. There are no studies in the literature examining the effects of GA on quality of life, depression, and anxiety in patients with inflammatory bowel disease. As the first study specifically designed for this field, we believe this study will make a significant contribution to the literature. CONCLUSION IBD patients resistant to standard treatments presented significant improvements in disease activity, quality of life, depression and anxiety levels after 10 sessions of GA procedure. With the process, monocytes were removed to a notable extent from circulation, improved acute phase response such as sedimentation and CRP were observed; and as a complication of the apheresis process, hb, htc, and platelet levels of the patients decreased to some extent, which required no intervention. For IBD patients who are resistant to standard treatments, GA should be considered an alternative treatment option. Abbreviations IBD: Inflammatory bowel diseases , CD: Crohn's disease UC: Ulcerative Colitis 5-ASA: 5-aminosalicylate Anti-TNF-α : Anti-tumor necrosis factor alpha GMA: Granulocyte monocyte apheresis PT: Prothrombin Time , APTT: Active partial thromboplastin time INR: International normalization ratio CRP: C-reactive protein SF-36 : Short Form-36 Hb: Hemoglobin Htc: hematocrit Plt: platelet Declarations Institutional Review Board Statement This study was approved by the Katip Çelebi University Non-Interventional Ethics Committee with the date 03.Jan.2021 and protocol number 104 GOA, decision number 150 Informed Consent Statement : Written informed consent has been obtained from the patients to publish this paper Conflicts of Interest : The authors declare no conflicts of interest Funding: This research received no external funding Author Contribution S.K. designed and planned the study, and E.Ö. and H.Y. enrolled patients in the outpatient clinic, took blood samples, evaluated the results, designed and wrote the manuscript, and calculated the statistics. S.K and E.Ö. planned of their treatment, and follow-up. All authors have read and agreed to the published version of the manuscript. Acknowledgments : The authors would like to thank all the patients and the lab team for their contributions. Data Availability The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author. References - Munkholm P, Langholz E, Davidsen M, Binder V. Disease activity courses in a regional cohort of Crohn’s disease patients. Scand J Gastroenterol. 1995;30:699–706. 10.3109/00365529509096316 . - Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet’s disease: a review. World J Gastroenterol. 2015;21:3801–12. 10.3748/wjg.v21.i13.3801 . - Stonnington CM, Phillips SF, Zinsmeister AR, Melton LJ 3rd. Prognosis of chronic ulcerative colitis in a community. Gut. 1987;28:1261–6. 10.1136/gut.28.10.1261 . Shanahan F. Crohn’s disease. Lancet. 2002; 359: 62–69 doi.10.1016/S0140-6736(02)07284-7. van Dullemen HM, van Deventer SJ, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J. Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology. 1995;109:129–35. 10.1016/0016-5085(95)90277-5 . - Lloyd AR, Oppenheim JJ. Poly’s lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. Immunol Today. 1992;13:169–72. 10.1016/0167-5699(92)90121-M . -Amada T, Volkmer C, Grisham MB. Antioxidant properties of 5-aminosalicylic acid: Potential mechanism for its antiinflammatory activity. Trends in Inflammatory Bowel Disease Therapy. CN Williams. (ed) Boston: Kluwer Academic; 1990. pp. 73–84. - Yamada T, Grisham MB. Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. Klin Wochenschr. 1991;69:988–94. 10.1007/BF01645144 . - Grisham MB, Yamada T. Neutrophils, nitrogen oxides, and inflammatory bowel disease. Ann N Y Acad Sci. 1992;664:103–15. 10.1111/j.1749-6632.1992.tb39753.x . - Kurtel H, Granger DN, Tso P, Grisham MB. Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Physiol. 1992;263:G573–8. 10.1152/ajpgi.1992.263.4.G573 . - Grisham MB, Granger N. Mechanisms of neutrophil mediated tissue injury. Inflammatory Bowel Disease. WF Stenson, editor New York: Elsevier,: RP MacDermott; 1992. pp. 225–39. Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012;6:991–1030. 10.1016/j.crohns.2012.09.002 . -. Bar F, Sina C, Fellermann K. Thiopurines in inflammatory bowel disease revisited. World J Gastroenterol. 2013;19:1699–706. 10.3748/wjg.v19.i11.1699 . Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710. 10.1056/NEJMoa1215734 . Bandzar S, Gupta S, Platt MO. Crohn’s disease: a review of treatment options and current research. Cell Immunol. 2013;286:45–52. 10.1016/j.cellimm.2013.11.003 . Lichtenstein GR, Hanauer SB, Sandborn WJ. Management of Crohn’s disease in adults. Am J Gastroenterol. 2009;104:465–83. 10.1038/ajg.2008.168 . quiz 464, 484. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105:501–23. 10.1038/ajg.2009.727 . quiz 524. Cohen LB, Nanau RM, Delzor F, Neuman MG. Biologic therapies in inflammatory bowel disease. Transl Res. 2014;163:533–56. 10.1016/j.trsl.2014.01.002 . Epub 2014 Jan 7. - Saniabadi AR, Hanai H, Takeuchi K, Umemura K, Nakashima M, Adachi T, Shima C, Bjarnason I, Loefberg R. Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003;7:48–59. 10.1046/j.1526-0968.2003.00012.x . - Saniabadi AR, Tanaka T, Ohmori T, Sawada K, Yamamoto T, Hanai H. Treating inflammatory bowel disease by adsorptive leucocytapheresis: a desire to treat without drugs. World J Gastroenterol. 2014;20:9699–715. 10.3748/wjg.v20.i29.9699 . Vecchi M, Vernia P, Riegler G, D’Inca R, Annese V, Bagnoli S. Therapeutic land scape for ulcerative colitis: where is the Adacolumn[R] system and where should it be? Clin Exp Gastroenterol. 2013;6:1–7. Epub 2013 Jan 4. Hilsden RJ, Scott CM, Verhoef MJ. Complementary medicine use by patients with inflammatory bowel disease. Am J Gastroenterol. 1998;93:697–701. 10.1111/j.1572-0241.1998.208_a.x . Langhorst J, Anthonisen IB, Steder-Neukamm U, et al. Amount of systemic steroid medication is a strong predictor for the use of complementary and alternative medicine in patients with inflammatory bowel disease: results from a German national survey. Inflamm Bowel Dis. 2005;11:287–95. 10.1097/01.mib.0000160771.71328.6c . Langhorst J, Anthonisen IB, Steder-Neukamm U, et al. Patterns of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease: perceived stress is a potential indicator for CAM use. Complement Ther Med. 2007;15:30–7. 10.1016/j.ctim.2006.03.008 . Mikocka-Walus A, Knowles SR, Keefer L, Graff L. Controversies revisited: a systematic review of the comorbidity of depression and anxiety with inflammatory bowel diseases. Inflamm Bowel Dis. 2016;22:752–62. 10.1097/MIB.0000000000000620 . - Restall GJ, Simms AM, Walker JR et al. Understanding work experiences of people with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:1688–97. doi.10.1097/MIB.0000000000000826. -. Lönnfors S, Vermeire S, Greco M, et al. IBD and health-related quality of life discovering the true impact. J Crohns Colitis. 2014;8:1281–86. 10.1016/j.crohns.2014.03.005 . Becker HM, Grigat D, Ghosh S, et al. Living with inflammatory bowel disease: a Crohn’s and colitis Canada survey. Can J Gastroenterol Hepatol. 2015;29:77–84. 10.1155/2015/815820 . Ware JE Jr, Sherbourne CD. The MOS 36-item short-form healthsurvey (SF-36). I. Conceptual framework and item selection. MedCare. 1992;30:473–83. Koçyiğit H, Aydemir Ö, Ölmez N, Memiş A. Kısa Form 36(KF-36)’nın Türkçe versiyonunun güvenilirliği ve geçerliliği. İlaç ve Tedavi Dergisi. 1999;12:102–6. Aydemir Ö. Konsültasyon-liyezon psikiyatrisinde yaşam kalitesi ölçümü: Kısa Form-36 (SF-36). 3P (Psikiyatri Psikoloji Psikofarmakoloji). Dergisi. 1999;7:14–22. Kılınç S, Torun F. Türkiye’de Klinikte Kullanılan Depresyon Değerlendirme Ölçekleri. Dirim Tıp Gazetesi. 2011;86:39–47. İsli N. Beck depresyon envanterinin üniversite öğrencileri için geçerliliği, güvenilirliği. Psikoloji Dergisi. 1989;7:3–13. - Ö, Aydemir İ, Kırpınar T, Uykur. C.Cengisiz Sağlık Anksiyetesi Ölçeği’nin Türkçe için Güvenilirlik ve Geçerlilik Çalışması Nöropsikiyatri Arşivi 2013; 50: 325–31, 10.4274/npa.y6383 -. Froch B, Zwolińska-Wcisło M, Bȩtkowska-Korpała B, Mach T. The dynamics of emotional reactions in patients with inflammatory bowel disease. Przeglad Gastroenterologiczny. 2009;4:141–6. Mikocka-Walus AA. Treatment of psychological comorbidities in common gastrointestinal and hepatologic disorders. World J Gastrointest Pharmacol Ther. 2010;1:64–71. 10.4292/wjgpt.v1.i2.64 . -Mikocka-Walus AA. Treatment of psychological co-morbidities in common gastrointestinal and hepatologic disorders. World J Gastrointest Pharmacol Ther. 2010;1(2):64–71. 10.4292/wjgpt.v1.i2.64] . [PMID: 21577298 doi:. Mittermaier C, Dejaco C, Waldhoer T, Oefferlbauer-Ernst A, Miehsler W, Beier M, et al. Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study. Psychosom Med. 2004;66:79–84. 10.1097/01.psy.0000106907.24881.f2 . Addolorato G, Capristo E, Stefanini GF, Gasbarrini G. inflammatory bowel disease: a study of the association between anxiety and depression, physical morbidity, and nutritional status. Scand J Gastroenterol. 1997;32:1013–21. 10.3109/00365529709011218 . - Gerçeker E, Yüceyar H, Kasap E, Demirci U, Ekti BC, Aydoğdu İ, Miskioğlu. Treatment of inflammatory bowel disease by leukocytapheresis. M Transfus Apher Sci. 2017;56(3):421–6. 10.1016/j.transci.2017.03.016 . -. Zhu M, Xu X, Nie F, Tong J, Xiao S, Ran Z. The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a metaanalysis. Int J Colorectal Dis. 2011;26:999–1007. 10.1007/s00384-011-1193-9 . Habermalz B, Sauerland S. Clinical effectiveness of selective granulocyte, monocyte adsorptive apheresis with the Adacolumn device in ulcerative colitis. Dig Dis Sci. 2010;55:1421–8. 10.1007/s10620-009-0845-x . -Suzuki Y, Yoshimura N, Saniabadi AR, Saito Y. Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative. colitis. a prospective uncontrolled study. Dig Dis Sci. 2004;49(4):565–71. Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files table1.doc table2.doc Table3.docx Table4.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 24 Apr, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers invited by journal 28 Mar, 2026 Editor assigned by journal 16 Mar, 2026 Submission checks completed at journal 14 Mar, 2026 First submitted to journal 14 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9033099","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":613855200,"identity":"b1d9fafd-9065-4d3f-8498-7c36458b6215","order_by":0,"name":"Selda Kahraman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYFAC5gYGBjYbBgYJ4rUwgrSkka7lMAla5NsbGxh+lJ1P7J/dfPABQ41NNEEtBmcONjD2nLudOOPOsWQDhmNpuQ0EtUgkNjDwtt1ObLiRYybB2HCYsBb5+Q8bGP+2nUucT7QWhhuMDcy8bQcSNxCtxeBMYgOzzLlk44030pINEojxi3z74QOMb8rsZOfdSD744EONDREOY2Bg/wEkHMEqE4hQDgf2pCgeBaNgFIyCEQYAhXNCR2Tw3xgAAAAASUVORK5CYII=","orcid":"","institution":"Medicana International Izmir Hospital,","correspondingAuthor":true,"prefix":"","firstName":"Selda","middleName":"","lastName":"Kahraman","suffix":""},{"id":613855201,"identity":"fa74488f-e002-4321-831d-0cb61ec70c2c","order_by":1,"name":"Hakan Yüceyar","email":"","orcid":"","institution":"Medicana International Izmir Hospital,","correspondingAuthor":false,"prefix":"","firstName":"Hakan","middleName":"","lastName":"Yüceyar","suffix":""},{"id":613855202,"identity":"17582c8c-13b5-4fc1-be6b-7ac1233418c9","order_by":2,"name":"Evren Ozdemir","email":"","orcid":"","institution":"Medicana International Izmir Hospital,","correspondingAuthor":false,"prefix":"","firstName":"Evren","middleName":"","lastName":"Ozdemir","suffix":""}],"badges":[],"createdAt":"2026-03-04 18:23:54","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9033099/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9033099/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106402141,"identity":"9066a88d-0f6d-439c-8eb5-fc2de83ab8a1","added_by":"auto","created_at":"2026-04-08 09:11:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":536193,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9033099/v1/345cd936-bc52-490e-a4d6-e4856f2f5ed6.pdf"},{"id":106045240,"identity":"93dcb8e6-789e-45a8-96d2-b37fcd1fd0e9","added_by":"auto","created_at":"2026-04-02 19:14:32","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":25600,"visible":true,"origin":"","legend":"","description":"","filename":"table1.doc","url":"https://assets-eu.researchsquare.com/files/rs-9033099/v1/db58eb5447d4718e290f728b.doc"},{"id":106094679,"identity":"04f61bbe-68ba-4bec-8d35-2894e3b1dd18","added_by":"auto","created_at":"2026-04-03 11:43:07","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":65024,"visible":true,"origin":"","legend":"","description":"","filename":"table2.doc","url":"https://assets-eu.researchsquare.com/files/rs-9033099/v1/8923bafac4352c1d9a83447d.doc"},{"id":106045237,"identity":"61809cf4-c36f-41f9-b696-498d5897f275","added_by":"auto","created_at":"2026-04-02 19:14:32","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":14954,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-9033099/v1/ab3ffc9a40799029c789eb05.docx"},{"id":106094050,"identity":"cc7d8e65-c58b-40f6-b1bb-369e89072fb8","added_by":"auto","created_at":"2026-04-03 11:40:53","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":15161,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.docx","url":"https://assets-eu.researchsquare.com/files/rs-9033099/v1/faf181131b6d8f2c6abe60ed.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effect of granulocytapheresis treatment on the mental health status of patients with inflammatory bowel disease","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eInflammatory bowel diseases (IBD), including the Crohn's disease (CD) and ulcerative colitis (UC) represent the chronic recurring inflammatory conditions of the gastrointestinal system, characterized by uncertain etiology and unpredictable progress. (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough the etiology of the IBDs remains unknown, it is believed that genetic factors, intestinal flora and immune-mediated tissue damage are involved in its pathogenesis. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The number of granulocytes and macrophages in the mucous, cytokines (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), reactive oxygen derivatives (\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) and catalytic proteases (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) play important roles in proinflammatory release.\u003c/p\u003e \u003cp\u003eThe therapeutic purpose of IBD treatments is to suppress disease activation to achieve clinical remission. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) Agents commonly used to control disease activity for this purpose include 5-aminosalicylate (5-ASA) compounds, steroids, immunosuppressants (thiopurines), inhibitors of calcineurin (cyclosporin, tacrolimus) and anti-tumor necrosis factor alpha (TNF-α) inhibitors (infliximab, adalimumab) and biological agents such as and adhesion molecule inhibitor vedolizumab (\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Despite these treatments, proctocolectomy is required for about one-third of patients with a steroid-dependent or steroid-resistant medium to severe active UC.\u003c/p\u003e \u003cp\u003eDespite multimodal medical treatments, including immune-modulating drugs and anti-TNF-alpha antibodies, IBD has no definitive treatment; the aim of treatments is to ameliorate the patient's symptoms and improve their quality of life. (\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn IBD, studies have emerged on leukocytapheresis with the need for alternative treatments in patients who are resistant to conventional treatment. Leukocytapheresis is a new non-pharmacological treatment approach in patients who are resistant to standard treatment approaches with active UC and CD, where leukocytes are mechanically removed from the circulatory system. Given the key role of granulocytes and macrophages in physiology, absorptive carrier-based granulocyte and monocyte apheresis instruments have been developed and their effects on inflammation have been proven in in-vivo and in-vitro environments. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe side effects of the drugs used have led to non-pharmacological treatment approaches with fewer side effects, including granulocyte and monocyte absorptive [GMA] apheresis [Adacolumn\u0026reg;, Otsuka Pharmaceuticals] and leukocytapheresis [GCAP; Cellsorba\u0026reg;, Asahi Medical] in patients with IBD. (20.21).\u003c/p\u003e \u003cp\u003eIBD is associated with a significant psychosocial burden. IBD's course is chronic and unpredictable, accompanied by intense abdominal pain, diarrhea, deteriorated fecal control, fear of cancer, occasional need for surgical intervention, which make patients anxious about many aspects of life, tired and socially isolated.\u003c/p\u003e \u003cp\u003eTherefore, pharmacological approaches and psychosocial support are widely used by patients with IBD. [22\u0026ndash;24]\u003c/p\u003e \u003cp\u003eStudies found that in patients with IBD, compared to healthy individuals, the rates of anxiety and depression were higher (anxiety: 9.6% vs. 19.1%, depression: 13.4% vs. 21.2%). (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) Business life can also be affected by the disease. Disease can lead to change in career choice, reduced working hours, irregular work, and financial difficulties. (\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOur study intended to examine the pre-treatment and post- leukocytapheresis changes in quality of life, depression and anxiety conditions of IBD patients who are resistant to standard treatments.\u003c/p\u003e"},{"header":"METHOD","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSTUDY DESIGN\u003c/h2\u003e \u003cp\u003eOur study was conducted at Medicana Izmir Hospital between June 2021 and July 2022 and included a total of 41 patients (14 women 27 men), 22 active UC and 19 CD, who underwent granulocytapheresis using the Medica la25 leucocyte adsorber device model 2020.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion criteria for the study\u003c/h3\u003e\n\u003cp\u003eThose patients who were refractory or intolerant to steroid-dependent or active immune suppressors and/or biological agents were admitted into the study. Poor response was defined as continued disease activity, intolerance to previous treatments and allergic reaction after 3 months of 2.5 mg/kg of azathioprine or 1.5 mg/kg of 6-mercaptopurine use or 14 weeks after the start of anti-TNF-α treatment\u003c/p\u003e \u003cp\u003e \u003cb\u003eExclusion criteria for the study\u003c/b\u003e ,\u003c/p\u003e \u003cp\u003eThose with active infection, those with inflammatory diseases under control, those who did not accept vascular intervention were excluded from the study.\u003c/p\u003e \u003cp\u003eHemogram, prothrombin time (PT), active partial thromboplastin time (APTT), international normalization ratio( INR), fibrinogen, ferritin, C-reactive protein (CRP) sedimentation values ​​of the patients were measured before and after the procedure.\u003c/p\u003e \u003cp\u003eAll blood of the patients was taken from the anterior cubital vein one hour before the first procedure and one hour after the last procedure. Questionnaires were conducted one hour before the first procedure and a week after the last procedure .\u003c/p\u003e\n\u003ch3\u003eGranulocytapheresis (GA) Procedures\u003c/h3\u003e\n\u003cp\u003eAll patients received GA therapy on twice a week with the Adacolumn as previously described (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e) Conventional medication was to be continued during the whole GA treatment .\u003c/p\u003e \u003cp\u003eThe 2020 model of the medica la 25 leukocyte adsorber device was used for this treatment Peripheral veins of the patients were evaluated. Peripheral vein was used in patients with suitable veins. A central venous catheter was inserted in patients with unsuitable veins and the GA was performed here. All procedures were carried out in accordance with relevant GA procedures and regulations.(\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e Consent was obtained from all patients for participation in the study, they filled a socio-demographic form and completed surveys with the face-to-face interview method. The ethics committee approval regarding the study was obtained from the ethics committee of Izmir Katip \u0026Ccedil;elebi University Non-Interventional Ethics Committee with the date 03.Jan.2021 and protocol number 104 GOA, decision number 150.\u003c/p\u003e\n\u003ch3\u003eMeasures\u003c/h3\u003e\n\u003cp\u003eAll patients underwent face-to-face interviews before GA and one week after the procedure, completing the Short Form-36 (SF-36) Quality of Life Scale, Illness Anxiety Inventory (HAI) Beck Anxiety Inventory (BAI), and Beck Depression Inventory.(BDI)\u003c/p\u003e \u003cp\u003e \u003cb\u003eShort Form-36 (SF-36) quality of life scale\u003c/b\u003e: The validity and reliability study of the Turkish version of the scale, which was developed by Ware and Sherbourne to assess quality of life, was conducted by Kocyigit et al. (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). This self-report scale is used for those with physical diseases with a higher priority, but it can also be used for those with a psychiatric disease (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Its eight dimensions include physical functionality, social functionality, physical role difficulty, emotional role difficulty, mental health, energy, pain and overall perceived health, and it consists of 36 items: Subscales assess health between 0-100, where 0 indicates a poor health condition and 100 indicates a good health condition. In addition, the overall score of the scale is not used, and the sub-categories are evaluated among themselves.\u003c/p\u003e \u003cp\u003eIt was planned to use the \u003cb\u003eBeck\u0026rsquo;s Anxiety Inventory (BAI)\u003c/b\u003e and \u003cb\u003eBeck\u0026rsquo;s Depression Inventory (BDI)\u003c/b\u003e (Table\u0026nbsp;1) to determine the anxiety and depression conditions of the patients. With BDI depression was categorized into normal, mild mood disturbance, borderline clinical depression, moderate depression, severe depression and extreme depression. With the BAI anxiety was classified as mild, moderate and severe anxiety. These inventories are the ones developed by Beck in 1961, and the validity and reliability studies in Turkey were conducted by Tegin (1980) and Hisli (1988) (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eThe Ilness Anxiety Inventory (HAI);\u003c/b\u003e is a reliable and valid assessment tool for assessing illness anxiety and will be useful in both clinical practice and research. The Illness Anxiety Inventory\u0026rsquo;s reliability and validity study for Turkish was conducted by Aydemir et al. in 2013. (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eBefore the GA, all patients completed SF-36 quality of life, BAI, BDI and HAI, which indicated their quality of life, anxiety and depression conditions. With simultaneous medication, the patients underwent GA for 10 sessions (2 days per week/5 weeks in total). The same surveys were re-conducted a week after the GA completed.\u003c/p\u003e\n\u003ch3\u003eStatistical evaluation:\u003c/h3\u003e\n\u003cp\u003eAll data were recorded to SPSS 15. The evaluations between different times (basal versus after 10 sessions of GA) between each other have been done non-parametric Mann-Whitney U test, whereas the correlation analysis has been done Pearson correlation analysis. P value less than 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOur study was conducted at Medicana Izmir Hospital between June 2021 and July 2022 and included a total of 41 patients (14 women and 27 men), 22 active UC and 19 CH, who underwent GA using the \u0026nbsp; Medica \u0026nbsp;la25 leucocyte adsorber device model 2020.\u0026nbsp;No complication requiring intervention occurred in any of the patients during the leukocytapheresis procedure.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The patients’ median age was 34 (19-66). Those patients who were refractory or intolerant to steroid-dependent or active immune suppressors and/or biological agents were admitted into the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore the GA all patients completed SF-36 quality of life, BAI, BDI and HAI which indicated their quality of life, anxiety and depression conditions. With simultaneous medication, the patients underwent GA \u0026nbsp; for 10 sessions (2 days per week/5 weeks in total). \u0026nbsp;The same surveys were re-administered a week after the GA \u0026nbsp;was completed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemographic data of the patients are presented \u0026nbsp;in Table 2. Nineteen patients (46.3%) were university graduates, 10 patients (24.4%) high school graduates, 7 patients (17.1%) secondary school graduates, and 5 patients (12.2%) were primary school graduates. Twenty-five patients (61%) were married, while 16 patients (39%) patients were single. Thirty-two patients (78%) were non-smokers, and 9 patients (22%) were smokers. While 24 patients (58.5%) were actively working, 17 patients (41.5%) were unemployed. Fifteen patients (36.6%) were receiving anti-TNF treatment, 33 patients were receiving steroids (80.5%), and 13 patients (31.7%) were receiving antidepressants. In 6 patients (14.6%), the GA was performed with the central venous catheter, and in 35 (85.4%) patients, the procedure was performed through peripheral vascular access.\u003c/p\u003e\n\u003cp\u003eRegarding pre-operational BAI status of the patients, 12 patients (27.5%) had mild anxiety, 9 (22.5%) patients had moderate anxiety, and 4 patients (10%) presented severe anxiety, whereas 16 (40%) patients had no anxiety.\u003c/p\u003e\n\u003cp\u003eAs to the pre-operational BDI status of the patients, 7 patients (17%) had mild depression, 11 (26.8%) patients had moderate, 16 patients (39%) had moderate, 4 (9.9%) patients had severe depression, and 3 (7.3%) patients presented no depression.\u003c/p\u003e\n\u003cp\u003eAt the end of the 5-week procedure, the patient's clinical status was evaluated by gastroenterologists. Gastroenterologists evaluated the effectiveness of the GA procedure by looking at the patient's clinical complaints, physical examinations, and colonoscopy findings. The clinical activity indices of the patients showed 70% complete \u0026nbsp;response and 25% partial response and %.5 had no response to the treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 provides comparative analysis results for the scores of surveys administered before and after the GA process. BAI, BDI and HAI scores significantly decreased after the process. (p=0.018, p\u0026lt;0.001, p=0.005). \u0026nbsp;After the GA, the physical functionality score (p=0,017) and overall perceived health increased significantly. (p=0.001). Vitality (p=0.002), social functionality (p\u0026lt;0.001), mental health (p\u0026lt;0.001) and health change (p=0.017) scores increased after the procedure. In women, BAI scores were seen to drop more remarkably than in men. (t: 2.854, p:0.008) In terms of HAI scores, high-school and higher-level graduates (t: 2.810, p: 0.010), non-smokers (t: 2.667, p: 0.013), and those who did not receive antidepressants (t: 2.650, p: 0.013) presented a more remarkable decrease. Regularly employed patients had remarkably increased health change (t: 2.667, p: 0.013) and mental health scores (t: 2.086, p: 0.044).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter 10 sessions of GA, the change in the blood parameters of patients is presented in Table 4. \u0026nbsp;Hemoglobin (hb) (p=0.002), hematocrit (htc) (p=0.002), platelet (plt) (p\u0026lt;0.001), monocyte (p=0.006), CRP (p=0.024), and sedimentation levels (p=0.031) decreased significantly after the procedure. There was no statistically significant difference among leukocyte (p=0.813), neutrophile (p=0.619), lymphocyte (p=0.475), PT \u0026nbsp; (p=0.310), APTT \u0026nbsp;(p=0.145), INR (p=0.359), fibrinogen (p=0.070) and ferritin (p=0.111) levels\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIBDs affect the quality of life due to chronic disease, indefinite prognosis, surgical operation and cancer development risks, causing anxiety and depression (\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). In our study, regardless of disease activity, patients with potential depression and potential anxiety comprised, approximately, 51% and 55%, respectively. The prevalence of anxiety and/or depression during the recovery period in IBD is 29\u0026ndash;35%, whereas the prevalence of anxiety and depression in the recurrence period is estimated to be 60% and 80%, respectively (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). In our study, anxiety and depression were found to be common among the patients with IBD, which was in line with the global literature. Regarding pre-operational BAI scores of the patients, 12 patients (27.5%) had mild anxiety, 9 (22.5%) patients had moderate anxiety, and 4 patients (10%) presented severe anxiety, whereas 16 (40%) patients had no anxiety.\u003c/p\u003e \u003cp\u003eAs to the pre-operational BDI status of the patients, 7 patients (17%) had mild depression, 11 (26.8%) patients had moderate, 16 patients (39%) had moderate, 4 (9.9%) patients had severe depression, and 3 (7.3%) patients presented no depression\u003c/p\u003e \u003cp\u003eThere are studies that compare quality of life, anxiety and depression conditions of IBD patients with healthy individuals. In our study, GA, an alternative treatment method, was administered to patients who were resistant to standard treatments. The aim was to examine the changes in quality of life, anxiety and depression conditions before and after the GA in the patients.\u003c/p\u003e \u003cp\u003e. A study by Gerceker et al. reviewed the results of GA treatment in 6 patients with CD and 20 patients with active UC. With accompanying medications, the patients underwent GA (10 sessions for remission induction treatment, 6 sessions for maintenance treatment). In 30% of patients with active severe UC, intensive GA was employed (\u0026ge;\u0026thinsp;4 GA sessions in the first 2 weeks). The overall clinical remission rate for the patients with UC was 80% and the mucosal improvement rate was 65%. Patients were followed up for 24 months on average. Sixty-five percent of the patients with UC were found to have continued clinical remission. The follow-up indicated a mild recurrence in 3 patients with UC. In 5 patients with CD, significant clinical remission was achieved, except for one patient. (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eA meta-analysis involving seven randomized controlled studies in which GA procedures were analyzed found a more remarkably improved disease activity in UC. Significantly improved response rates and remission rates were achieved as a result of GA compared to traditional treatment (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn another study by Habermalz et al., patients treated with GA for 12 weeks presented significantly higher remission rates compared to patients treated with traditional treatments (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere are studies in the literature on anxiety-depression and quality of life in inflammatory bowel disease, as well as studies examining the effect of GA on the treatment of inflammatory bowel disease.\u003c/p\u003e \u003cp\u003eAlthough there are studies in the literature that analyze the post-GA change in disease activity, there is no study that examines the change in quality of life, anxiety and depression conditions.\u003c/p\u003e \u003cp\u003eIn the present study, post-operational hb (p\u0026thinsp;=\u0026thinsp;0.002), htc (p\u0026thinsp;=\u0026thinsp;0.002), plt (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) levels of the patients reduced significantly after 10 sessions of GA procedure. There was no statistically significant difference among leukocyte (p\u0026thinsp;=\u0026thinsp;0.813), neutrophile (p\u0026thinsp;=\u0026thinsp;0.619), lymphocyte (p\u0026thinsp;=\u0026thinsp;0.475), PT (p\u0026thinsp;=\u0026thinsp;0.310), APTT (p\u0026thinsp;=\u0026thinsp;0.145), INR (p\u0026thinsp;=\u0026thinsp;0.359), fibrinogen (p\u0026thinsp;=\u0026thinsp;0.070) and ferritin (p\u0026thinsp;=\u0026thinsp;0.111) levels. Monocyte (p\u0026thinsp;=\u0026thinsp;0.006), CRP (p\u0026thinsp;=\u0026thinsp;0.024), and sedimentation levels (p\u0026thinsp;=\u0026thinsp;0.031), which are important markers of inflammation, decreased significantly after the procedure.\u003c/p\u003e \u003cp\u003eRegarding anxiety and depression, BAI, BDI and HAI scores significantly decreased after the procedure. (p\u0026thinsp;=\u0026thinsp;0.018, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;=\u0026thinsp;0.005 ). The physical functionality (p\u0026thinsp;=\u0026thinsp;0.017) and overall perceived health, which are part of the sub-parameters of the SF36 quality of life survey, have increased significantly after the procedure. (p\u0026thinsp;=\u0026thinsp;0.001). Vitality (p\u0026thinsp;=\u0026thinsp;0.002), social functionality (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), mental health (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and health change (p\u0026thinsp;=\u0026thinsp;0.017) scores increased after the procedure.\u003c/p\u003e \u003cp\u003eIn women, BAI scores were seen to drop more remarkably than men. (t: 2.854, p:0.008) In terms of HAI scores, high-school and higher-level graduates (t: 2.810, p: 0.010), non-smokers (t: 2.667, p: 0.013), and those who did not receive antidepressants (t: 2.650, p: 0.013) presented a more remarkable decrease.\u003c/p\u003e \u003cp\u003eRegularly employed patients had remarkably increased health change (t: 2.667, p: 0.013) and mental health scores (t: 2.086, p: 0.044).\u003c/p\u003e \u003cp\u003eGiven these results, post GA anxiety significantly decreased in female patients with higher levels of education, who are non-smokers, actively engaged in life and regularly employed.\u003c/p\u003e \u003cp\u003eThere are no studies in the literature examining the effects of GA on quality of life, depression, and anxiety in patients with inflammatory bowel disease. As the first study specifically designed for this field, we believe this study will make a significant contribution to the literature.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIBD patients resistant to standard treatments presented significant improvements in disease activity, quality of life, depression and anxiety levels after 10 sessions of GA procedure. With the process, monocytes were removed to a notable extent from circulation, improved acute phase response such as sedimentation and CRP were observed; and as a complication of the apheresis process, hb, htc, and platelet levels of the patients decreased to some extent, which required no intervention. For IBD patients who are resistant to standard treatments, GA should be considered an alternative treatment option.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIBD: Inflammatory bowel diseases ,\u003c/p\u003e\n\u003cp\u003eCD: \u0026nbsp;Crohn's disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;UC: Ulcerative Colitis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5-ASA: 5-aminosalicylate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Anti-TNF-α : Anti-tumor necrosis factor alpha\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGMA: \u0026nbsp;Granulocyte monocyte apheresis\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;PT: Prothrombin Time ,\u003c/p\u003e\n\u003cp\u003eAPTT: Active partial thromboplastin time\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eINR: International normalization ratio\u003c/p\u003e\n\u003cp\u003eCRP: \u0026nbsp;C-reactive protein\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSF-36 : Short Form-36\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHb: Hemoglobin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHtc: hematocrit\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePlt: platelet\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eInstitutional Review Board Statement\u003c/h2\u003e \u003cp\u003e This study was approved by the Katip \u0026Ccedil;elebi University Non-Interventional Ethics Committee with the date 03.Jan.2021 and protocol number 104 GOA, decision number 150\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eInformed Consent\u003c/strong\u003e \u003cp\u003e\u003cb\u003eStatement\u003c/b\u003e: Written informed consent has been obtained from the patients to publish this paper\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003e \u003cb\u003eConflicts of Interest\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eThe authors declare no conflicts of interest\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research received no external funding\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eS.K. designed and planned the study, and E.\u0026Ouml;. and H.Y. enrolled patients in the outpatient clinic, took blood samples, evaluated the results, designed and wrote the manuscript, and calculated the statistics. S.K and E.\u0026Ouml;. planned of their treatment, and follow-up. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments :\u003c/h2\u003e \u003cp\u003eThe authors would like to thank all the patients and the lab team for their contributions.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e- Munkholm P, Langholz E, Davidsen M, Binder V. Disease activity courses in a regional cohort of Crohn\u0026rsquo;s disease patients. Scand J Gastroenterol. 1995;30:699\u0026ndash;706. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/00365529509096316\u003c/span\u003e\u003cspan address=\"10.3109/00365529509096316\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet\u0026rsquo;s disease: a review. World J Gastroenterol. 2015;21:3801\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3748/wjg.v21.i13.3801\u003c/span\u003e\u003cspan address=\"10.3748/wjg.v21.i13.3801\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Stonnington CM, Phillips SF, Zinsmeister AR, Melton LJ 3rd. Prognosis of chronic ulcerative colitis in a community. Gut. 1987;28:1261\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/gut.28.10.1261\u003c/span\u003e\u003cspan address=\"10.1136/gut.28.10.1261\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShanahan F. Crohn\u0026rsquo;s disease. Lancet. 2002; 359: 62\u0026ndash;69 doi.10.1016/S0140-6736(02)07284-7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Dullemen HM, van Deventer SJ, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J. Treatment of Crohn\u0026rsquo;s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology. 1995;109:129\u0026ndash;35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0016-5085(95)90277-5\u003c/span\u003e\u003cspan address=\"10.1016/0016-5085(95)90277-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Lloyd AR, Oppenheim JJ. Poly\u0026rsquo;s lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. Immunol Today. 1992;13:169\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0167-5699(92)90121-M\u003c/span\u003e\u003cspan address=\"10.1016/0167-5699(92)90121-M\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e-Amada T, Volkmer C, Grisham MB. Antioxidant properties of 5-aminosalicylic acid: Potential mechanism for its antiinflammatory activity. Trends in Inflammatory Bowel Disease Therapy. CN Williams. (ed) Boston: Kluwer Academic; 1990. pp. 73\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Yamada T, Grisham MB. Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. Klin Wochenschr. 1991;69:988\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF01645144\u003c/span\u003e\u003cspan address=\"10.1007/BF01645144\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Grisham MB, Yamada T. Neutrophils, nitrogen oxides, and inflammatory bowel disease. Ann N Y Acad Sci. 1992;664:103\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1749-6632.1992.tb39753.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1749-6632.1992.tb39753.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Kurtel H, Granger DN, Tso P, Grisham MB. Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Physiol. 1992;263:G573\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1152/ajpgi.1992.263.4.G573\u003c/span\u003e\u003cspan address=\"10.1152/ajpgi.1992.263.4.G573\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Grisham MB, Granger N. Mechanisms of neutrophil mediated tissue injury. Inflammatory Bowel Disease. WF Stenson, editor New York: Elsevier,: RP MacDermott; 1992. pp. 225\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012;6:991\u0026ndash;1030. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.crohns.2012.09.002\u003c/span\u003e\u003cspan address=\"10.1016/j.crohns.2012.09.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e-. Bar F, Sina C, Fellermann K. Thiopurines in inflammatory bowel disease revisited. World J Gastroenterol. 2013;19:1699\u0026ndash;706. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3748/wjg.v19.i11.1699\u003c/span\u003e\u003cspan address=\"10.3748/wjg.v19.i11.1699\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699\u0026ndash;710. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1215734\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1215734\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBandzar S, Gupta S, Platt MO. Crohn\u0026rsquo;s disease: a review of treatment options and current research. Cell Immunol. 2013;286:45\u0026ndash;52. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cellimm.2013.11.003\u003c/span\u003e\u003cspan address=\"10.1016/j.cellimm.2013.11.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLichtenstein GR, Hanauer SB, Sandborn WJ. Management of Crohn\u0026rsquo;s disease in adults. Am J Gastroenterol. 2009;104:465\u0026ndash;83. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/ajg.2008.168\u003c/span\u003e\u003cspan address=\"10.1038/ajg.2008.168\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. quiz 464, 484.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105:501\u0026ndash;23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/ajg.2009.727\u003c/span\u003e\u003cspan address=\"10.1038/ajg.2009.727\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. quiz 524.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen LB, Nanau RM, Delzor F, Neuman MG. Biologic therapies in inflammatory bowel disease. Transl Res. 2014;163:533\u0026ndash;56. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.trsl.2014.01.002\u003c/span\u003e\u003cspan address=\"10.1016/j.trsl.2014.01.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2014 Jan 7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Saniabadi AR, Hanai H, Takeuchi K, Umemura K, Nakashima M, Adachi T, Shima C, Bjarnason I, Loefberg R. Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003;7:48\u0026ndash;59. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/j.1526-0968.2003.00012.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1526-0968.2003.00012.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Saniabadi AR, Tanaka T, Ohmori T, Sawada K, Yamamoto T, Hanai H. Treating inflammatory bowel disease by adsorptive leucocytapheresis: a desire to treat without drugs. World J Gastroenterol. 2014;20:9699\u0026ndash;715. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3748/wjg.v20.i29.9699\u003c/span\u003e\u003cspan address=\"10.3748/wjg.v20.i29.9699\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVecchi M, Vernia P, Riegler G, D\u0026rsquo;Inca R, Annese V, Bagnoli S. Therapeutic land scape for ulcerative colitis: where is the Adacolumn[R] system and where should it be? Clin Exp Gastroenterol. 2013;6:1\u0026ndash;7. Epub 2013 Jan 4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHilsden RJ, Scott CM, Verhoef MJ. Complementary medicine use by patients with inflammatory bowel disease. Am J Gastroenterol. 1998;93:697\u0026ndash;701. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1572-0241.1998.208_a.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1572-0241.1998.208_a.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLanghorst J, Anthonisen IB, Steder-Neukamm U, et al. Amount of systemic steroid medication is a strong predictor for the use of complementary and alternative medicine in patients with inflammatory bowel disease: results from a German national survey. Inflamm Bowel Dis. 2005;11:287\u0026ndash;95. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/01.mib.0000160771.71328.6c\u003c/span\u003e\u003cspan address=\"10.1097/01.mib.0000160771.71328.6c\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLanghorst J, Anthonisen IB, Steder-Neukamm U, et al. Patterns of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease: perceived stress is a potential indicator for CAM use. Complement Ther Med. 2007;15:30\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ctim.2006.03.008\u003c/span\u003e\u003cspan address=\"10.1016/j.ctim.2006.03.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMikocka-Walus A, Knowles SR, Keefer L, Graff L. Controversies revisited: a systematic review of the comorbidity of depression and anxiety with inflammatory bowel diseases. Inflamm Bowel Dis. 2016;22:752\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MIB.0000000000000620\u003c/span\u003e\u003cspan address=\"10.1097/MIB.0000000000000620\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Restall GJ, Simms AM, Walker JR et al. Understanding work experiences of people with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:1688\u0026ndash;97. doi.10.1097/MIB.0000000000000826.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e-. L\u0026ouml;nnfors S, Vermeire S, Greco M, et al. IBD and health-related quality of life discovering the true impact. J Crohns Colitis. 2014;8:1281\u0026ndash;86. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.crohns.2014.03.005\u003c/span\u003e\u003cspan address=\"10.1016/j.crohns.2014.03.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBecker HM, Grigat D, Ghosh S, et al. Living with inflammatory bowel disease: a Crohn\u0026rsquo;s and colitis Canada survey. Can J Gastroenterol Hepatol. 2015;29:77\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2015/815820\u003c/span\u003e\u003cspan address=\"10.1155/2015/815820\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWare JE Jr, Sherbourne CD. The MOS 36-item short-form healthsurvey (SF-36). I. Conceptual framework and item selection. MedCare. 1992;30:473\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKo\u0026ccedil;yiğit H, Aydemir \u0026Ouml;, \u0026Ouml;lmez N, Memiş A. Kısa Form 36(KF-36)\u0026rsquo;nın T\u0026uuml;rk\u0026ccedil;e versiyonunun g\u0026uuml;venilirliği ve ge\u0026ccedil;erliliği. İla\u0026ccedil; ve Tedavi Dergisi. 1999;12:102\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAydemir \u0026Ouml;. Kons\u0026uuml;ltasyon-liyezon psikiyatrisinde yaşam kalitesi \u0026ouml;l\u0026ccedil;\u0026uuml;m\u0026uuml;: Kısa Form-36 (SF-36). 3P (Psikiyatri Psikoloji Psikofarmakoloji). Dergisi. 1999;7:14\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKılın\u0026ccedil; S, Torun F. T\u0026uuml;rkiye\u0026rsquo;de Klinikte Kullanılan Depresyon Değerlendirme \u0026Ouml;l\u0026ccedil;ekleri. Dirim Tıp Gazetesi. 2011;86:39\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eİsli N. Beck depresyon envanterinin \u0026uuml;niversite \u0026ouml;ğrencileri i\u0026ccedil;in ge\u0026ccedil;erliliği, g\u0026uuml;venilirliği. Psikoloji Dergisi. 1989;7:3\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- \u0026Ouml;, Aydemir İ, Kırpınar T, Uykur. C.Cengisiz Sağlık Anksiyetesi \u0026Ouml;l\u0026ccedil;eği\u0026rsquo;nin T\u0026uuml;rk\u0026ccedil;e i\u0026ccedil;in G\u0026uuml;venilirlik ve Ge\u0026ccedil;erlilik \u0026Ccedil;alışması N\u0026ouml;ropsikiyatri Arşivi 2013; 50: 325\u0026ndash;31, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4274/npa.y6383\u003c/span\u003e\u003cspan address=\"10.4274/npa.y6383\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e-. Froch B, Zwolińska-Wcisło M, Bȩtkowska-Korpała B, Mach T. The dynamics of emotional reactions in patients with inflammatory bowel disease. Przeglad Gastroenterologiczny. 2009;4:141\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMikocka-Walus AA. Treatment of psychological comorbidities in common gastrointestinal and hepatologic disorders. World J Gastrointest Pharmacol Ther. 2010;1:64\u0026ndash;71. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4292/wjgpt.v1.i2.64\u003c/span\u003e\u003cspan address=\"10.4292/wjgpt.v1.i2.64\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e-Mikocka-Walus AA. Treatment of psychological co-morbidities in common gastrointestinal and hepatologic disorders. World J Gastrointest Pharmacol Ther. 2010;1(2):64\u0026ndash;71. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4292/wjgpt.v1.i2.64]\u003c/span\u003e\u003cspan address=\"10.4292/wjgpt.v1.i2.64]\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. [PMID: 21577298 doi:.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMittermaier C, Dejaco C, Waldhoer T, Oefferlbauer-Ernst A, Miehsler W, Beier M, et al. Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study. Psychosom Med. 2004;66:79\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/01.psy.0000106907.24881.f2\u003c/span\u003e\u003cspan address=\"10.1097/01.psy.0000106907.24881.f2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAddolorato G, Capristo E, Stefanini GF, Gasbarrini G. inflammatory bowel disease: a study of the association between anxiety and depression, physical morbidity, and nutritional status. Scand J Gastroenterol. 1997;32:1013\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/00365529709011218\u003c/span\u003e\u003cspan address=\"10.3109/00365529709011218\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e- Ger\u0026ccedil;eker E, Y\u0026uuml;ceyar H, Kasap E, Demirci U, Ekti BC, Aydoğdu İ, Miskioğlu. Treatment of inflammatory bowel disease by leukocytapheresis. M Transfus Apher Sci. 2017;56(3):421\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.transci.2017.03.016\u003c/span\u003e\u003cspan address=\"10.1016/j.transci.2017.03.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e-. Zhu M, Xu X, Nie F, Tong J, Xiao S, Ran Z. The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a metaanalysis. Int J Colorectal Dis. 2011;26:999\u0026ndash;1007. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00384-011-1193-9\u003c/span\u003e\u003cspan address=\"10.1007/s00384-011-1193-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHabermalz B, Sauerland S. Clinical effectiveness of selective granulocyte, monocyte adsorptive apheresis with the Adacolumn device in ulcerative colitis. Dig Dis Sci. 2010;55:1421\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10620-009-0845-x\u003c/span\u003e\u003cspan address=\"10.1007/s10620-009-0845-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e-Suzuki Y, Yoshimura N, Saniabadi AR, Saito Y. Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid na\u0026iuml;ve patients with active ulcerative.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ecolitis. a prospective uncontrolled study. Dig Dis Sci. 2004;49(4):565\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-psychology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"discpsy","sideBox":"Learn more about [Discover Psychology](https://www.springer.com/44202)","snPcode":"","submissionUrl":"","title":"Discover Psychology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ulcerative colitis, Chrohn's disease, Leukocytapheresis","lastPublishedDoi":"10.21203/rs.3.rs-9033099/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9033099/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eStudies on granulocytapheresis have emerged with the need for alternative treatments in patients with inflammatory bowel disease (IBD) refractory to conventional therapy..\u003c/p\u003e\n\u003cp\u003eIn our study; It was aimed to examine the changes in the patients' quality of life, depression and anxiety after the granulocytapheresis procedure in patients with IBD. Our study included a total of 41 patients (14 female, 27 male), 22 active Ulcerative Colitis (UC), 19 Chrohn Diseases (CD), who underwent granulocytapheresis using Cellsorba E column between June 2021 and July 2022 in Medicana İzmir Hospital. The median age of the patients was 34 (19-66). Before the procedure, SF 36 , illness anxiety and Beck anxiety-depression, illness anxiety questionnaires, which show the patients' quality of life, anxiety and depression, were administered to all patients. The granulocytapheresis procedure was performed in 10 sessions (2 days a week / 5 weeks in total) with concomitant medications. The same questionnaires were repeated one week after the procedure was completed.\u003c/p\u003e\n\u003cp\u003eBeck anxiety, Beck depression and illness anxiety scores were found to be statistically significantly lower after the application (p=0.018, p\u0026lt;0.001, p=0.005). The Physical Function score (p=0.017), general health perception (p=0.001), vitality (p=0.002), social functionality (p\u0026lt;0.001), mental health (p\u0026lt;0.001), health change (p=0.017). scores were found to be statistically significantly higher after the application. A more significant decrease was observed in Beck anxiety scores in women compared to men. (t:2,854, p: 0.008) In the disease anxiety scores, those with higher education level (t: 2.810, p: 0.010), non-smokers (t: 2.667, p: 0.013), non-antidepressant users (t: 2.650, p: 0.013) more significant decrease was observed. There was a significant increase in health change scores (t: 2.667, p: 0.013), mental health scores (t: 2.086, p: 0.044) in regularly working patients.\u003c/p\u003e\n\u003cp\u003eIn conclusion; After 10 sessions of granulocytapheresis in patients with IBD resistant to standard treatments, a significant improvement was observed in patients' quality of life, depression and anxiety. With the procedure, monocytes were significantly removed from the circulation, improvement was observed in the acute phase response such as sedimentation and CRP, and as a complication of the apheresis procedure, the hb, htc, and platelet values of the patients decreased partially at a level that did not require intervention.\u003c/p\u003e","manuscriptTitle":"The effect of granulocytapheresis treatment on the mental health status of patients with inflammatory bowel disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 19:14:28","doi":"10.21203/rs.3.rs-9033099/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-24T16:51:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"214715838059437861954258212929091552098","date":"2026-04-23T19:17:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-28T19:13:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-16T07:34:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-14T15:05:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Psychology","date":"2026-03-14T15:00:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-psychology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"discpsy","sideBox":"Learn more about [Discover Psychology](https://www.springer.com/44202)","snPcode":"","submissionUrl":"","title":"Discover Psychology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"15cf3d54-24e5-47e3-be8a-6b73688b00e7","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-02T19:14:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 19:14:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9033099","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9033099","identity":"rs-9033099","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}