Efficacy and Safety of Infliximab in Intestinal Behçet’s Disease:A Multicenter, Phase 3 Study (BEGIN)

Background/Aims@#To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet’s disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. @*Methods@#This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. @*Results@#A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies. @*Conclusions@#This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568)

Clinical outcomes and predictors of response for adalimumab in patients with moderately to severely active ulcerative colitis: a KASID prospective multicenter cohort study

Background/Aims@#This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC). @*Methods@#A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score. @*Results@#A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients. @*Conclusions@#ADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.

An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response

PURPOSE: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in variability among test individuals, and do not mimic asthmatic responses accompanied by T-helper (Th) 17 and neutrophils. As dendritic cells (DCs) are known to play an important role in initiating and maintaining asthmatic inflammation, we developed an asthma model via adoptive transfer of allergen-loaded DCs.METHODS: Ovalbumin (OVA)-loaded bone marrow-derived DCs (BMDCs) (OVA-BMDCs) were injected intravenously 3 times into non-anesthetized C57BL/6 mice after intraperitoneal OVA-sensitization.RESULTS: OVA-BMDC-transferred mice developed severe asthmatic immune responses when compared with mice receiving conventional OVA challenge intranasally. Notably, remarkable increases in systemic immunoglobulin (Ig) E and IgG1 responses, Th2/Th17-associated cytokines (interleukin [IL]-5, IL-13 and IL-17), Th2/Th17-skewed T-cell responses, and cellular components, including eosinophils, neutrophils, and goblet cells, were observed in the lungs of OVA-BMDC-transferred mice. Moreover, the asthmatic immune responses and severity of inflammation were correlated with the number of OVA-BMDCs transferred, indicating that the disease severity and asthma type may be adjusted according to the experimental purpose by this method. Furthermore, this model exhibited less variation among the test individuals than the conventional model. In addition, this DCs-based asthma model was partially resistant to steroid treatment.CONCLUSIONS: A reliable murine model of asthma by intravenous (i.v.) transfer of OVA-BMDCs was successfully established without anesthesia. This model more accurately reflects heterogeneous human asthma, exhibiting a robust Th2/Th17-skewed response and eosinophilic/neutrophilic infiltration with good reproducibility and low variation among individuals. This model will be useful for understanding the pathogenesis of asthma and would serve as an alternative tool for immunological studies on the function of DCs, T-cell responses and new drugs.

Comparison of Effectiveness between Abdominal Vibration Stimulation and Walking Exercise for Bowel Cleansing before Therapeutic Colonoscopy

Background/Aims@#Adequate bowel preparation is important for successful colonoscopy. We aimed to evaluate the clinical feasibility and effectiveness of abdominal vibration stimulation in bowel preparation before therapeutic colonoscopy. @*Methods@#A single center, prospective, randomized, investigator-blinded study was performed between January 2016 and December 2016. Patients for therapeutic colonoscopy were prospectively enrolled and assigned to either the vibrator group or walking group. Patients who refused to participate in this study as part of the experimental group consented to register in the control group instead. During the preparation period, patients assigned to the walking group walked ≥3,000 steps, whereas those assigned to the vibrator group received abdominal vibrator stimulation and restricted walking. All patients received the same colon cleansing regimen: 4-L split-dose polyethylene glycol (PEG) solution. @*Results@#Three hundred patients who received PEG solution for therapeutic colonoscopy were finally enrolled in this study (n=100 per group). Bowel cleansing with abdominal vibration stimulation showed almost similar results to that with walking exercise (Boston Bowel Preparation Scale score for the entire colon: vibrator vs walking vs control, 7.38±1.55 vs 7.39±1.55 vs 6.17±1.15, p<0.001). There were no significant differences between the vibrator group and walking group regarding instances of diarrhea after taking PEG, time to first diarrhea after taking PEG, total procedure time, and patient satisfaction. @*Conclusions@#This study indicates that, compared with conventional walking exercise, abdominal vibration stimulation achieved similar rates of bowel cleansing adequacy and colonoscopy success without compromising safety or patient satisfaction.

Impact of previous metronidazole exposure on metronidazole-based second-line quadrupletherapy for Helicobacter pylori infection

Background/Aims@#The negative effects on the eradication success of Helicobacter pylori infection after previous exposure to macrolides, including clarithromycin on clarithromycin-based first-line therapy have been demonstrated. However,whether this is true for metronidazole-based second-line quadruple therapy remains unclear. We investigated the relationship between past administration of metronidazole and the failure of metronidazole-based second-line quadruple therapy in patients with H. pylori infection. Methods: Patients over 20 years of age who were diagnosed with H. pylori infection between January 1998 and March 2016 were enrolled in this study. The relationship between the clinical parameters and the results of a C13-urea breath test after metronidazole-based second-line quadruple therapy was analyzed in patients for whom clarithromycin-based triple therapy failed to eradicate H. pylori . @*Results@#The H. pylori eradication failure rate was significantly higher in patients with a history of metronidazole use than in patients without a history of metronidazole use ( p = 0.011). Multivariable analysis showed that the odds ratio of previous metronidazole use for eradication failure was 3.468 (95% confidence interval,1.391 to 8.649; p = 0.008). In the subgroup analysis of patients with a history of metronidazole use, the duration of metronidazole use and interval between its use and eradication therapy did not significantly affect H. pylori eradication failure. @*Conclusions@#Previous exposure to metronidazole was a significant risk factor for treatment failure of metronidazole-based second-line quadruple therapy; therefore, this should be considered when establishing a treatment strategy for patients with H. pylori infection.

Two Distinct Subsets Are Identified from the Peritoneal Myeloid Mononuclear Cells Expressing both CD11c and CD115

To this date, the criteria to distinguish peritoneal macrophages and dendritic cells (DCs) are not clear. Here we delineate the subsets of myeloid mononuclear cells in the mouse peritoneal cavity. Considering phenotypical, functional, and ontogenic features, peritoneal myeloid mononuclear cells are divided into 5 subsets: large peritoneal macrophages (LPMs), small peritoneal macrophages (SPMs), DCs, and 2 MHCII⁺CD11c⁺CD115⁺ subpopulations (i.e., MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ and MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺). Among them, 2 subsets of competent Ag presenting cells are demonstrated with distinct functional characteristics, one being DCs and the other being MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells. DCs are able to promote fully activated T cells and superior in expanding cytokine producing inflammatory T cells, whereas MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells generate partially activated T cells and possess a greater ability to induce Treg under TGF-β and retinoic acid conditions. While the development of DCs and MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells are responsive to the treatment of FLT3 ligand and GM-CSF, the number of LPMs, SPMs, and MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells are only influenced by the injection of GM-CSF. In addition, the analysis of gene expression profiles among MHCII⁺ peritoneal myeloid mononuclear cells reveals that MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells share high similarity with SPMs, whereas MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells are related to peritoneal DC2s. Collectively, our study identifies 2 distinct subpopulations of MHCII⁺CD11c⁺CD115⁺ cells, 1) MHCII⁺CD11c⁺CD115⁺CD14⁻CD206⁻ cells closely related to peritoneal DC2s and 2) MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells to SPMs.

A Proposal for Modification of the Barcelona Clinic Liver Cancer Staging System Considering the Prognostic Implication of Performance Status

BACKGROUND/AIMS: Barcelona Clinic Liver Cancer (BCLC) C stage demonstrates considerable heterogeneity because it includes patients with either symptomatic tumors (performance status [PS], 1–2) or with an invasive tumoral pattern reflected by the presence of vascular invasion (VI) or extrahepatic spread (EHS). This study aimed to derive a more relevant staging system by modification of the BCLC system considering the prognostic implication of PS. METHODS: A total of 7,501 subjects who were registered in the Korean multicenter hepatocellular carcinoma (HCC) registry database from 2008 to 2013 were analyzed. The relative goodness-of-fit between staging systems was compared using the Akaike information criterion (AIC) and integrated area under the curve (IAUC). Three modified BCLC (m-BCLC) systems (#1, #2, and #3) were devised by reducing the role of PS. RESULTS: As a result, the BCLC C stage, which includes patients with PS 1–2 without VI/EHS, was reassigned to stage 0, A, or B according to their tumor burden in the m-BCLC #2 model. This model was identified as the most explanatory and desirable model for HCC staging by demonstrating the smallest AIC (AIC=70,088.01) and the largest IAUC (IAUC=0.722), while the original BCLC showed the largest AIC (AIC=70,697.17) and the smallest IAUC (IAUC=0.705). The m-BCLC #2 stage C was further subclassified into C1, C2, C3, and C4 according to the Child-Pugh score, PS, presence of EHS, and tumor extent. The C1 to C4 subgroups showed significantly different overall survival distribution between groups (p<0.001). CONCLUSIONS: An accurate and relevant staging system for patients with HCC was derived though modification of the BCLC system based on PS.

Improvement of Nonalcoholic Fatty Liver Disease Reduces the Risk of Type 2 Diabetes Mellitus

BACKGROUND/AIMS: Little evidence is available about the effect of change in nonalcoholic fatty liver disease (NAFLD) status on risk of diabetes mellitus (DM) development. In this study, we tried to analyze the DM risk according to change in NAFLD status over time. METHODS: Among a total of 10,141 individuals for whom routine healthcare assessment was performed, 2,726 subjects were selected according to the inclusion/exclusion criteria. NAFLD status change was determined by using serial abdominal ultrasonography and fatty liver index (FLI) during the follow-up period. RESULTS: Subjects were categorized according to change in NAFLD status as follows: 670 subjects in the persistent NAFLD group, 155 subjects in the resolved NAFLD group, 498 subjects in the incident NAFLD group, and 1,403 subjects in the no NAFLD group. Multivariate Cox regression analysis revealed that incident NAFLD (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.08 to 3.50; p=0.026) and persistent NAFLD (HR, 3.59; 95% CI, 2.05 to 6.27; p<0.001) were independent risk factors for predicting DM development, whereas the risk with resolved NAFLD was not significantly different from that with no NAFLD. FLI could reproduce the results acquired by ultrasonography. CONCLUSIONS: This study demonstrated that future DM risk could be influenced by changes in NAFLD status over time. Resolution of NAFLD could reduce the risk of future DM development, while the development of new NAFLD could increase the risk of DM development.

Mycobacterium tuberculosis ESAT6 Drives the Activation and Maturation of Bone Marrow-Derived Dendritic Cells via TLR4-Mediated Signaling

6-kDa early secretory antigenic target (ESAT6), a virulent factor of Mycobacterium tuberculosis, is involved in immune regulation. However, the underlying mechanism behind the activation and maturation of dendritic cells (DCs) by ESAT6 remains unclear. In this study, we investigated the effect on TLRs signaling on the regulation of ESAT6-induced activation and maturation of DCs. ESAT6 induced production of IL-6, TNF-α, and IL-12p40 in bone marrow-derived dendritic cells (BMDCs) from wild-type and TLR2-deficient mice, with this induction abolished in TLR4-deficient cells. NF-κB is essential for the ESAT6-induced production of the cytokines in BMDCs. TLR4 was also required for ESAT6-induced activation of NF-κB and MAPKs in BMDCs. ESAT6 additionally upregulated the expression of surface molecules CD80, CD86, and MHC-II, and also promoted the ability of CD4⁺ T cells to secrete IFN-γ via the TLR4-dependent pathway. Our findings suggest that TLR4 is critical in the activation and maturation of DCs in response to ESAT6.

Three-year colonoscopy surveillance after polypectomy in Korea: a Korean Association for the Study of Intestinal Diseases (KASID) multicenter prospective study

BACKGROUND/AIMS: Colonoscopic surveillance is currently recommended after polypectomy owing to the risk of newly developed colonic neoplasia. However, few studies have investigated colonoscopy surveillance in Asia. This multicenter and prospective study was undertaken to assess the incidence of advanced adenoma based on baseline adenoma findings at 3 years after colonoscopic polypectomy. METHODS: A total of 1,323 patients undergoing colonoscopic polypectomy were prospectively assigned to 3-year colonoscopy surveillance at 11 tertiary endoscopic centers. Relative risks for advanced adenoma after 3 years were calculated according to baseline adenoma characteristics. RESULTS: Among 1,323 patients enrolled, 387 patients (29.3%) were followed up, and the mean follow-up interval was 31.0±9.8 months. The percentage of patients with advanced adenoma on baseline colonoscopy was higher in the surveillance group compared to the non-surveillance group (34.4% vs. 25.7%). Advanced adenoma recurrence was observed in 17 patients (4.4%) at follow-up. The risk of advanced adenoma recurrence was 2 times greater in patients with baseline advanced adenoma than in those with baseline non-advanced adenoma, though the difference was not statistically significant (6.8% [9/133] vs. 3.1% [8/254], P=0.09). Advanced adenoma recurrence was observed only in males and in subjects aged ≥50 years. In contrast, adenoma recurrence was observed in 187 patients (48.3%) at follow-up. Male sex, older age (≥50 years), and multiple adenomas (≥3) at baseline were independent risk factors for adenoma recurrence. CONCLUSIONS: A colonoscopy surveillance interval of 3 years in patients with baseline advanced adenoma can be considered appropriate.

Negative Histology after Endoscopic Resection: An Endoscopist's Aspect / 대한Helicobacter연구학회지

Endoscopic submucosal dissection (ESD) is accepted as the standard treatment for gastric epithelial dysplasia or early gastric cancer because it enables curative en bloc resection and complete histopathological assessment of the specimen. However, occasionally, a tumorous lesion may not be detected, and histopathological discrepancies can occur after ESD. Reportedly, the prevalence of negative histopathological results after endoscopic resection is 2.0~4.4%. Negative histopathological results after endoscopic resection are commonly attributable to complete removal of the lesion via an endoscopic forceps biopsy (EFB) at the time of the initial diagnostic endoscopic examination, an initial histopathological overestimation of the EFB specimen, and incorrect localization of the original tumor with subsequent ESD performed at a wrong site. A small tumor size and surface area are known to be significant endoscopic predictors of negative histopathological results after ESD. Therefore, clinicians should be mindful of the fact that negative histopathological findings observed after endoscopic resection warrant a comprehensive review of all pre-ESD data and an adequate follow-up to determine the cause of these findings and to detect any possibility of local recurrence.

Cytomegalovirus Gastric Ulcer Complicated with Pyloric Obstruction in a Patient with Ulcerative Colitis / 대한소화기학회지

In patients with inflammatory bowel disease (IBD), cytomegalovirus (CMV) infections could aggravate the course of IBD but it is difficult to distinguish CMV infection from IBD exacerbation endoscopically. Usually, CMV tends to localize to the colon and other organic involvements were reported very rare in the IBD patients. Herein, we report a case that CMV gastric ulcer complicated with pyloric obstruction in a patient with ulcerative colitis during ganciclovir therapy, which was resolved by surgical gastrojejunostomy with review of literature.

Diagnostic Yield and Clinical Impact of Video Capsule Endoscopy in Patients with Chronic Diarrhea: A Korean Multicenter CAPENTRY Study

BACKGROUND/AIMS: In some cases, chronic diarrhea is unexplained, and small bowel disorders may be one of the causes. The aim of this study was to assess the diagnostic yield and clinical impact of video capsule endoscopy (VCE) in patients with chronic diarrhea. METHODS: We retrospectively analyzed records from October 2002 to August 2013 in the VCE nationwide database registry (n=2,964). Ninety-one patients from 15 medical centers (60 males and 31 females; mean age, 47±19 years) were evaluated for VCE as a result of chronic diarrhea. RESULTS: The duration of chronic diarrhea was 8.3±14.7 months. The positive diagnostic yield of VCE was 42.9% (39/91). However, 15.4% (14/91) exhibited an inconsistent result, and 41.8% (38/91) were negative. Abnormal findings consistent with chronic diarrhea included erosions/aphthous ulcers (19.8%), ulcers (17.6%), mucosal erythema (3.3%), edema (1.1%), and luminal narrowing (1.1%). The most common diagnoses were functional diarrhea associated with irritable bowel syndrome in 37 patients (40.7%) and Crohn’s disease in 18 patients (19.8%). After VCE examination, the diagnosis was changed in 34.1% of the patients (31/91). Hematochezia (odds ratio [OR], 8.802; 95% confidence interval [CI], 2.126 to 36.441) and hypoalbuminemia (OR, 4.811; 95% CI, 1.241 to 18.655) are predictive factors of a positive diagnostic yield. CONCLUSIONS: VCE had a favorable diagnostic yield and clinical impact on the management of patients with chronic diarrhea.

Down-Regulation of Serum High-Mobility Group Box 1 Protein in Patients with Pulmonary Tuberculosis and Nontuberculous Mycobacterial Lung Disease / 결핵및호흡기질환

BACKGROUND: Recently, increased levels of high-mobility group box 1 protein (HMGB1) have been identified in various inflammatory conditions and infections. However, no studies have evaluated the HMGB1 level in nontuberculous mycobacterial (NTM) lung disease, and compared it to mycobacterial lung disease. METHODS: A total of 60 patients newly diagnosed with NTM lung disease, 44 culture-positive pulmonary tuberculosis (TB) patients, and 34 healthy controls, were included in this study. The serum HMGB1 concentrations were quantified using HMGB1 enzyme-linked immunosorbent assay kits. RESULTS: Serum HMGB1 level in patients with pulmonary TB or NTM lung disease, was significantly lower than that of the healthy controls. In addition, the serum HMGB1 level in TB patients was significantly lower than patients with NTM lung disease. However, the levels in NTM patient subgroups did not differ according to the causative species, disease progression, and disease phenotype. CONCLUSION: Although low levels of serum HMGB1 has the potential to be a marker of mycobacterial lung disease, these levels were unable to differentiate disease progression and disease phenotype in NTM lung diseases.

Non-steroidal anti-inflammatory drug-induced enteropathy

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to be associated with serious upper gastrointestinal complications, such as peptic ulcer, bleeding, perforation, and obstruction. Recently, attention has been mainly focused on the small bowel injuries caused by NSAIDs, and new endoscopic techniques such as capsule endoscopy and double balloon endoscopy can help in detecting such injuries. This article reviewed the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of small bowel injuries caused by NSAIDs. Small bowel injures by NSAIDs might occur with a similar frequency and extent as those observed in the upper gastrointestinal tract. The pathogenesis of NSAID-induced enteropathy is complex and not clearly understood. The various lesions observed in the small bowel, including petechiae, reddened folds, loss of villi, erosions, and ulcers can be detected by capsule endoscopy. A drug that could prevent or treat NSAID-induced enteropathy has not yet been developed. Therefore, further investigations should be performed to elucidate the pathogenesis of such enteropathy and develop suitable preventive and treatment strategies.

New Colonoscopy Devices to Improve Colon Neoplasm Detection / 대한소화기학회지

Early detection and removal of adenomatous polyps can prevent the development of colorectal cancer. However, it is fairly common—up to 20%—for polyps to be undetected in a colonoscopy due to poor visualization of the proximal aspect of colonic folds and anatomical flexures. To overcome these limitations, many new endoscopes and accessories have been developed. A wide-angle colonoscopy did not improve the detection of adenoma compared with the standard colonoscopy. An extra-wide angle and Retroview colonoscopies showed a significantly lower miss rate of polyps in the colon model. However, clinical trials are mandatory in the future. The recently introduced full spectrum endoscopy system showed a significantly higher adenoma detection rate than the standard forward-viewing colonoscopy. In accessories, The cap-assisted colonoscopy showed only a marginal or no benefit on the detection of polyps and adenomas. In contrast, a colonoscopy with Endocuff, EndoRings, and G-eye have showed significantly lower adenoma miss rates. The Third Eye, which provides additional retrograde viewing, has revealed a significant improvement in the detection of adenoma and polyp. However, the Third Eye Retroscope was limited by its deployment through the working channel of the scope. Recently, the Third Eye Panoramic cap, which was designed to overcome the limitation of the Third Eye Retroscope, was introduced. In the future, this would be needed to evaluate the effectiveness, efficiency and safety for these new colonoscopies and accessories.

Efficacy and Safety of Infliximab Therapy and Predictors of Response in Korean Patients with Crohn's Disease: A Nationwide, Multicenter Study

PURPOSE: Infliximab is currently used for the treatment of active Crohn's disease (CD). We aimed to assess the efficacy and safety of infliximab therapy and to determine the predictors of response in Korean patients with CD. MATERIALS AND METHODS: A total of 317 patients who received at least one infliximab infusion for active luminal CD (n=198) and fistulizing CD (n=86) or both (n=33) were reviewed retrospectively in 29 Korean referral centers. Clinical outcomes of induction and maintenance therapy with infliximab, predictors of response, and adverse events were evaluated. RESULTS: In patients with luminal CD, the rates of clinical response and remission at week 14 were 89.2% and 60.0%, respectively. Male gender and isolated colonic disease were associated with higher remission rates at week 14. In week-14 responders, the probabilities of sustained response and remission were 96.2% and 93.3% at week 30 and 88.0% and 77.0% at week 54, respectively. In patients with fistulizing CD, clinical response and remission were observed in 85.0% and 56.2% of patients, respectively, at week 14. In week-14 responders, the probabilities of sustained response and remission were 94.0% and 97.1%, respectively, at both week 30 and week 54. Thirty-nine patients (12.3%) experienced adverse events related to infliximab. Serious adverse events developed in 19 (6.0%) patients including seven cases of active pulmonary tuberculosis. CONCLUSION: Infliximab induction and maintenance therapy are effective and well tolerable in Korean patients with luminal and fistulizing CD. However, clinicians must be aware of the risk of rare yet critical adverse events.

Apoptotic Effect of Macrophages against Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) causing tuberculosis as an intracellular pathogen initially infects alveolar macrophages following aerosol inhalation. Thus, macrophages play a critical role in the establishment of Mtb infection and macrophage cell death, a common outcome during Mtb infection, may initiate host- or pathogen-favored immune responses, resulting in facilitating protection or pathogenesis, respectively. In addition, virulent Mtb strains are known to inhibit apoptosis and consequently down-regulates immune response using a variety of strategies. In many recent studies have shown that virulent Mtb can either augment or reduce apoptosis by regulating expression of pro-apoptotic and anti-apoptotic proteins belonging to Bcl-2 family proteins. In this review, we will discuss and dissect the apoptotic pathways of Bcl-2 family proteins in Mtb-infected macrophages.

Immunomodulatory Roles of PE/PPE Proteins and Their Implications in Genomic Features of Mycobacterium tuberculosis

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a notorious cause of human death worldwide. A deeper understanding of the proline-glutamate (PE) and proline-proline-glutamate (PPE) families, which compromise 10% of the coding regions in the Mtb genome, has uncovered their unique roles in host-pathogen interactions. Further, comparative genomic analysis of different Mtb strains has proposed that Mtb has acquired diverse gene sets that play immunomodulatory roles in host-pathogen interactions. This review delineates the various immunomodulatory roles of PE/PPE antigens and discusses their implications in the development of the improved diagnostic tools and vaccines.

Nontuberculous Mycobacterial Lung Disease Caused by Mycobacterium shinjukuense: The First Reported Case in Korea / 결핵및호흡기질환

Mycobacterium shinjukuense is a novel species of nontuberculous mycobacteria (NTM) that was first reported in Japan in 2011. It is a slow-growing NTM pathogen that can cause chronic pulmonary infections. There are only a few reported cases of M. shinjukuense infections, all of which are from Japan. We reported a case of chronic lung disease caused by M. shinjukuense. The organism was identified by 16S rRNA, rpoB, and hsp65 gene sequencing. To the best of our knowledge, this was the first confirmed case of lung disease caused by M. shinjukuense outside of Japan.