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Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.
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Background/Aims@#We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). @*Methods@#Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. @*Results@#In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. @*Conclusions@#The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).
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Background/Aims@#Recently, 1 L of polyethylene glycol (PEG) plus ascorbic acid (Asc) has been introduced in Korea as a colonoscopy preparation agent. Data on its efficacy and safety in older adults have been limited. We aimed to evaluate the safety and efficacy of 1 L PEG/Asc in older adults by comparing it with oral sulfate solution (OSS). @*Methods@#A prospective multicenter randomized study was conducted with subjects aged ≥ 65 years who underwent colonoscopy. The participants were randomized to receive 1 L PEG/Asc or OSS. The primary endpoint was successful bowel preparation, defined as total Boston Bowel Preparation Scale ≥ 6, and ≥ 2 at each segment. Patient satisfaction, adverse events, and renal function changes were compared between the groups. @*Results@#Among the 106 patients, 104 were finally included in the analysis. Overall, successful bowel preparation was achieved in 96.2% of both 1 L PEG/Asc and OSS groups. The satisfaction scores for taste, total amount ingested, overall feeling, and willingness to repeat the same regimen were not significantly different between the groups. Adverse events of moderate or higher severity occurred in 16 and 10 cases in the 1 L PEG/Asc and OSS group, respectively. There were no significant changes in electrolyte levels or renal function from baseline. @*Conclusions@#The successful bowel preparation rate was > 90% in both groups without severe adverse effects and significant changes in renal function. As a new low-dose preparation regimen for colonoscopy in older adults, 1 L PEG/Asc, is as effective and safe as OSS.
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Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.
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Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD).Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.
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T-cell large granular lymphocyte (T-LGL) leukemia is characterized by clonal expansion of cytotoxic T cells resulting in cytopenia. The proliferation of clonal LGLs is caused by prolonged antigenic stimulation, which leads to apoptotic dysregulation owing mainly to the constitutive activation of survival pathways, notably the JAK/STAT pathway.Understanding how leukemic T-LGL persists can aid in the development of future immunosuppressive therapies. In this review, we summarize the diagnosis and current standard of therapy for T-LGL leukemia, as well as recent advances in clinical trials.
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Plasmacytoid dendritic cells (pDCs) are type I interferon-producing cells that modulate immune responses. There are two types of pDC neoplasms: 1) mature pDC proliferation (MPDCP) associated with myeloid neoplasm and 2) blastic pDC neoplasm (BPDCN).MPDCP is a clonal expansion of mature pDCs that is predominantly associated with chronic myelomonocytic leukemia. In contrast, BPDCN is a clinically aggressive myeloid malignancy involving the skin, bone marrow, lymphatic organs, and central nervous system. There are various types of skin lesions, ranging from solitary brown or violaceous to disseminated cutaneous lesions, which often spread throughout the body. The expression of CD4, CD56, CD123, and pDC markers (TCL-1, TCF4, CD303, and CD304, etc.) are typical immunophenotype of BPDCN. Historically, BPDCN treatment has been based on acute leukemia regimens and allogeneic hematopoietic cell transplantation in selected patients. Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632. Lastly, this review provides a comprehensive overview of pDC neoplasms.
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Background/Aims@#Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. @*Methods@#Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). @*Results@#Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). @*Conclusions@#Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.
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Background/Aims@#Fecal microbiota transplantation (FMT) represents a treatment option for recurrent Clostridioides difficile infection (CDI). Recently, FMT has been investigated in various clinical settings other than CDI. This study examined Korean physicians’ recognition of FMT and their attitudes toward this procedure @*Methods@#An online questionnaire included questions on indications for FMT, the FMT process, physicians’ attitudes toward FMT for the treatment of CDI and non-CDI diseases, and possible concerns. @*Results@#Finally, 107 physicians responded to this survey: 66 (61.7%) had experience of performing FMT, and 86 (80.4%) replied that they were willing to perform FMT for CDI. Two-thirds of physicians (63.6%, n = 68) would perform FMT for recurrent CDI on patients who had at least three recurrences. The most common obstacle to performing FMT for the treatment of CDI was the lack of regulations or guidelines (55.1%, n = 59). Seventy-seven (72.0%) physicians would consider FMT for non- CDI diseases when conventional treatment had failed. The most common obstacle for FMT for the treatment of non-CDI diseases was low treatment efficacy (57.0%, n = 61). @*Conclusions@#Two-thirds of Korean physicians had experience of performing FMT, and many performed FMT for recurrent CDI. The results of this study will prove useful to researchers and practitioners in FMT in Korea.
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Background@#Copeptin is the carboxyl-terminal part of the vasopressin precursor protein, and its concentration is an independent predictor of the onset of chronic kidney disease and a rapid decline in the glomerular filtration rate. The glomerular filtration rate is regarded as the best indicator of kidney transplant function and is a predictor of graft and patient survival. We investigated the clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients. @*Methods@#We measured serum creatinine, cystatin C, and copeptin concentrations in renal transplant recipients on the day of their operation, as well as on postoperative days 3, 7, 30, and 365. Acute rejection was defined as a sudden decrease in renal function accompanied by histological changes. @*Results@#Eight renal transplant recipients were enrolled in the study from July 2018 to December 2019. Four patients experienced histologically confirmed transplant rejection. All four cases involved acute T-cell rejection. No significant correlation was found between the copeptin level and the presence or absence of rejection at any time point. In subgroup analyses, changes in creatinine, the estimated glomerular filtration rate, cystatin, and copeptin did not show statistical significance. @*Conclusions@#We anticipated that copeptin would be useful to identify individuals at high risk of transplant rejection; however, our study failed to show an association. Further research will be needed to overcome the limitations of this study.
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Background@#This study aimed to assess the diagnostic feasibility of radiomics analysis based on magnetic resonance (MR)-proton density fat fraction (PDFF) for grading hepatic steatosis in patients with suspected non-alcoholic fatty liver disease (NAFLD). @*Methods@#This retrospective study included 106 patients with suspected NAFLD who underwent a hepatic parenchymal biopsy. MR-PDFF and MR spectroscopy were performed on all patients using a 3.0-T scanner. Following whole-volume segmentation of the MRPDFF images, 833 radiomic features were analyzed using a commercial program. Radiologic features were analyzed, including median and mean values of the multiple regions of interest and variable clinical features. A random forest regressor was used to extract the important radiomic, radiologic, and clinical features. The model was trained using 20 repeated 10-fold cross-validations to classify the NAFLD steatosis grade. The area under the receiver operating characteristic curve (AUROC) was evaluated using a classifier to diagnose steatosis grades. @*Results@#The levels of pathological hepatic steatosis were classified as low-grade steatosis (grade, 0–1; n = 82) and high-grade steatosis (grade, 2–3; n = 24). Fifteen important features were extracted from the radiomic analysis, with the three most important being wavelet-LLL neighboring gray tone difference matrix coarseness, original first-order mean, and 90th percentile. The MR spectroscopy mean value was extracted as a more important feature than the MR-PDFF mean or median in radiologic measures. Alanine aminotransferase has been identified as the most important clinical feature. The AUROC of the classifier using radiomics was comparable to that of radiologic measures (0.94 ± 0.09 and 0.96 ± 0.08, respectively). @*Conclusion@#MR-PDFF-derived radiomics may provide a comparable alternative for grading hepatic steatosis in patients with suspected NAFLD.
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Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is threatening global health worldwide with unprecedented contagiousness and severity. The best strategy to overcome COVID-19 is a vaccine. Various vaccines are currently being developed, and mass vaccination is in progress. Despite the very encouraging clinical trial results of these vaccines, there is insufficient information on the safety and efficacy of vaccines for inflammatory bowel disease (IBD) patients facing various issues. After reviewing current evidence and international guidelines, the Korean Association for the Study of Intestinal Diseases developed an expert consensus statement on COVID-19 vaccination issues for Korean IBD patients. This expert consensus statement emphasizes that severe acute respiratory syndrome coronavirus 2 vaccination be strongly recommended for IBD patients, and it is safe for IBD patients receiving immunomodulatory therapy.
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Background/Aims@#Improving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC. @*Methods@#A multicenter, hospital-based, prospective study was performed using a Moderateto-Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later. @*Results@#In a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p<0.01). Inflammatory markers such as C-reactive protein (CRP) or erythrocyte sedimentation rate also showed a negative correlation on HRQL (p<0.05). Patients whose IBDQ score improved by 16 or more (71.2%) in 1 year were younger, tended to be nonsmokers, and had a lower partial Mayo score and CRP than those whose IBDQ score did not. There was no significant association between HRQL and disease extent, treatments at diagnosis, or the highest treatment step during the 1-year period. @*Conclusions@#Optimally controlled disease status improves HRQL in patients with moderate-tosevere UC. The partial Mayo score and inflammatory markers may be potential indicators reflecting the influence of UC on patient`s daily lives.
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Fecal microbiota transplantation (FMT) is a highly efficacious and safe modality for the treatment of recurrent or refractory Clostridioides difficile infection (CDI), with overall success rates of 90%. Thus, FMT has been widely used for 10 years. The incidence and clinical characteristics of CDI, the main indication for FMT, differ between countries. To date, several guidelines have been published. However, most of them were published in Western countries and therefore cannot represent the Korean national healthcare systems. One of the barriers to performing FMT is a lack of national guidelines. Accordingly, multidisciplinary experts in this field have developed practical guidelines for FMT. The purpose of these guidelines is to aid physicians performing FMT, which can be adapted to treat CDI and other conditions.
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Background/Aims@#This study aimed to investigate the perceptions and behaviors of patients with inflammatory bowel disease (IBD) during the early coronavirus disease 2019 (COVID-19) pandemic in the major epidemic area in Korea. @*Methods@#Between April and May 2020, a cross-sectional survey was performed at two tertiary hospitals in Daegu, South Korea, on patients’ experiences, coping strategies and perceptions. @*Results@#Most of the 544 patients participating in the survey strictly adhered to personal protection guidance against COVID-19. In the early COVID-19 crisis, many patients canceled or postponed hospital visits (57.5%) and rescheduled biologics administrations (26.4%). Although 13.6% utilized telemedicine, the frequency of individuals leaving their homes remained unchanged. Although 50.4% were concerned about their susceptibility to COVID-19, 72.2% adhered to their treatment for IBD. In patients taking biologics or Janus kinase inhibitors, 86.8% disagreed that they should discontinue their medication as a preventative measure against COVID-19, but 21.9% actually discontinued their medications. Of those with discordance between the perception of IBD drug adherence and active behaviors, 5.4% of all and 39.4% of biologics or Janus kinase inhibitors withheld drugs specifically due to fear of COVID-19. Only 7% of all patients discussed drug safety with their physicians. The level of concern for COVID-19 depended on the type of drug used. @*Conclusions@#Patients with IBD showed concerns about the increased risk of COVID-19 due to IBD or their medications, and a considerable number of patients withheld their medications without consulting medical staff. Enhanced active communications with patients with IBD and appropriate health-related education should be provided.
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Gastric metastasis from renal cell carcinoma (RCC) is extremely rare, occurring in 0.2% of all RCC cases. Owing to its low prevalence, metachronous gastric metastasis from RCC may be underdiagnosed, and the imaging findings have not been well-established. Herein we present a case of metastatic RCC manifesting as a gastric polyp in a 70-year-old female along with a literature review on the imaging findings of gastric metastases from RCC. In patients presenting with gastric hyper-enhancing polypoid masses, metastasis from RCC should be considered as a differential diagnosis.
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Background/Aims@#The diagnosis of intestinal tuberculosis (Itbc) is often challenging. Therapeutic anti-tubercular trial (TATT) is sometimes used for the diagnosis of Itbc. We aimed to evaluate the changing pattern of fecal calprotectin (FC) levels during TATT in patients with Itbc. @*Methods@#A retrospective review was performed on the data of 39 patients who underwent TATT between September 2015 and November 2018 in five university hospitals in Daegu, South Korea. The analysis was performed for 33 patients with serial FC measurement reports. @*Results@#The mean age of the participants was 48.8 years. The final diagnosis of Itbc was confirmed in 30 patients based on complete mucosal healing on follow-up colonoscopy performed after 2 months of TATT. Before starting TATT, the mean FC level of the Itbc patients was 170.2 μg/g (range, 11.5-646.5). It dropped to 25.4 μg/g (range, 11.5-75.3) and then 23.3 μg/g (range, 11.5-172.2) after one and two months of TATT, respectively. The difference in mean FC before and one month after TATT was statistically significant (p<0.001), and FC levels decreased to below 100 μg/g in all patients after one month of TATT. @*Conclusions@#All Itbc patients showed FC decline after only 1 month of TATT, and this finding correlated with complete mucosal healing in the follow-up colonoscopy after 2 months of TATT.
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Purpose@#Endoscopic treatment and laparoscopic surgery are minimally invasive options for early treatment of colorectal cancer, however, more evidence of the long-term outcomes between the two procedures is needed to guide clinical decisions. Therefore, this study aimed to compare the oncologic outcomes between endoscopic and laparoscopic treatment for early colorectal cancer. @*Methods@#The study group included 60 patients who underwent endoscopic treatment and 38 patients who underwent laparoscopic surgery for early colorectal adenocarcinoma between January 2010 and December 2013 at a single study site. @*Results@#Histopathological diagnoses showed that 43 (78.3%) carcinomas in the endoscopic submucosal dissection group were mucosal to sm1, 13 (21.7%) were sm2 or deeper, and 17 high-risk cases (28.3%) in the endoscopic group underwent additional surgery. The median operation time, time to sips of water, and length of hospital stay were significantly shorter in the endoscopic group than in the laparoscopic group. The overall survival rates of patients in the endoscopic group and laparoscopic groups were 91.5% and 87.4%, respectively (P=0.391), and the disease-free survival rates were 90.4% and 87.4% (P=0.614), respectively. Systemic recurrences occurred in two patients (1.6%) in the endoscopic group and one patient (2.0%) in the laparoscopic group. Local recurrence combined with systemic recurrence in one patient (0.8%) in the endoscopic group. @*Conclusion@#Endoscopic resection for early colorectal cancer can be performed safely with better short-term outcomes and comparable longterm oncological outcomes compared to laparoscopic surgery.
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Purpose@#The aim of this multicenter study was to investigate the malignancy risk of minimally cystic thyroid nodules (MCTNs) using cyto-histopathologic diagnoses as the reference standard. @*Methods@#From June 2015 to September 2015, 5,601 thyroid nodules (≥1 cm) from 4,989 consecutive patients who underwent thyroid ultrasonography (US) at 26 institutions were retrospectively analyzed. Each thyroid nodule was categorized according to its cystic proportion: purely solid, minimally cystic (≤10%), and partially cystic (>10%). The malignancy risk of MCTNs was compared with those of purely solid nodules and partially cystic thyroid nodules (PCTNs). The malignancy risk of MCTNs was assessed according to echogenicity and the presence of suspicious US features. @*Results@#The prevalence of MCTNs was 22.5%. The overall malignancy risk of MCTNs was 8.8%, which was significantly lower than that of purely solid nodules (29.5%) (P0.05). MCTNs were associated with a higher risk of malignancy in hypoechoic nodules than in isohyperechoic nodules and in nodules with suspicious US features than in those without suspicious US features (all P<0.001). @*Conclusion@#The malignancy risk of MCTNs was significantly lower than that of purely solid nodules. MCTNs could be categorized as PCTNs rather than as solid nodules to increase the accuracy of the risk stratification system for thyroid nodules.
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The coronavirus disease 2019 (COVID-19) pandemic has reduced the ability to prevent or control chronic disease due to the concerns about safety in accessing health care. Inflammatory bowel disease (IBD) is a chronic condition requiring long- term sustained treatment, which is difficult in the current panedemic situation. The Korean Association for the Study of Intestinal Diseases (KASID) has developed an expert consensus statement on the clinical practice management of adult inflammatory bowel disease during the COVID-19 pandemic. This expert consensus statement is based on guidelines and clinical reports from several countries around the world. It provides recommendations to deal with the risk of COVID-19 and medication use in IBD patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and emphasizes the importance of right treatment approach to avoid worsening of the disease condition in IBD patients.