Sniper2L is a high-fidelity Cas9 variant with high activity.

Although several high-fidelity SpCas9 variants have been reported, it has been observed that this increased specificity is associated with reduced on-target activity, limiting the applications of the high-fidelity variants when efficient genome editing is required. Here, we developed an improved version of Sniper-Cas9, Sniper2L, which represents an exception to this trade-off trend as it showed higher specificity with retained high activity. We evaluated Sniper2L activities at a large number of target sequences and developed DeepSniper, a deep learning model that can predict the activity of Sniper2L. We also confirmed that Sniper2L can induce highly efficient and specific editing at a large number of target sequences when it is delivered as a ribonucleoprotein complex. Mechanically, the high specificity of Sniper2L originates from its superior ability to avoid unwinding a target DNA containing even a single mismatch. We envision that Sniper2L will be useful when efficient and specific genome editing is required.

Risk factors and management of iatrogenic colorectal perforation in diagnostic colonoscopy: a single-center cohort study.

BACKGROUND AND AIMS: Diagnostic colonoscopy plays a central role in colorectal cancer screening programs. We analyzed the risk factors for perforation during diagnostic colonoscopy and discussed the treatment outcomes. METHODS: We performed a retrospective analysis of risk factors and treatment outcomes of perforation during 74,426 diagnostic colonoscopies between 2013 and 2018 in a tertiary hospital. RESULTS: A total of 19 perforations were identified after 74,426 diagnostic colonoscopies or sigmoidoscopies, resulting in a standardized incidence rate of 0.025% or 2.5 per 10,000 colonoscopies. The majority (15 out of 19, 79%) were found at the sigmoid colon and recto-sigmoid junction. Perforation occurred mostly in less than 1000 cases of colonoscopy (16 out of 19, 84%). In particular, the incidence of perforation was higher in more than 200 cases undergoing slightly advanced colonoscopy rather than beginners who had just learned colonoscopy. Old age (≥ 70 years), inpatient setting, low body mass index (BMI), and sedation status were significantly associated with increased risk of perforation. Nine (47%) of the patients underwent operative treatment and ten (53%) were managed non-operatively. Patients who underwent surgery were often diagnosed with delayed or concomitant abdominal pain. Perforations of rectum tended to be successfully treated with endoscopic clipping. CONCLUSIONS: Additional precautions are required to prevent perforation in elderly patients, hospital settings, low BMI, sedated patients, or by a doctor with slight familiarity with endoscopies (but still insufficient experience). Endoscopic treatment should be actively considered if diagnosis is prompt, abdominal pain absent, and especially the rectal perforation is present.

Determination of Gait Events and Temporal Gait Parameters for Persons with a Knee-Ankle-Foot Orthosis.

Gait event detection is essential for controlling an orthosis and assessing the patient's gait. In this study, patients wearing an electromechanical (EM) knee-ankle-foot orthosis (KAFO) with a single IMU embedded in the thigh were subjected to gait event detection. The algorithm detected four essential gait events (initial contact (IC), toe off (TO), opposite initial contact (OIC), and opposite toe off (OTO)) and determined important temporal gait parameters such as stance/swing time, symmetry, and single/double limb support. These gait events were evaluated through gait experiments using four force plates on healthy adults and a hemiplegic patient who wore a one-way clutch KAFO and a pneumatic cylinder KAFO. Results showed that the smallest error in gait event detection was found at IC, and the largest error rate was observed at opposite toe off (OTO) with an error rate of -2.8 ± 1.5% in the patient group. Errors in OTO detection resulted in the largest error in determining the single limb support of the patient with an error of 5.0 ± 1.5%. The present study would be beneficial for the real-time continuous monitoring of gait events and temporal gait parameters for persons with an EM KAFO.

Measurements of Electrodermal Activity, Tissue Oxygen Saturation, and Visual Analog Scale for Different Cuff Pressures.

The quantification of comfort in binding parts, essential human-machine interfaces (HMI) for the functioning of rehabilitation robots, is necessary to reduce physical strain on the user despite great achievements in their structure and control. This study aims to investigate the physiological impacts of binding parts by measuring electrodermal activity (EDA) and tissue oxygen saturation (StO2). In Experiment 1, EDA was measured from 13 healthy subjects under three different pressure conditions (10, 20, and 30 kPa) for 1 min using a pneumatic cuff on the right thigh. In Experiment 2, EDA and StO2 were measured from 10 healthy subjects for 5 min. To analyze the correlation between EDA parameters and the decrease in StO2, a survey using the visual analog scale (VAS) was conducted to assess the level of discomfort at each pressure. The EDA signal was decomposed into phasic and tonic components, and the EDA parameters were extracted from these two components. RM ANOVA and a post hoc paired t-test were used to determine significant differences in parameters as the pressure increased. The results showed that EDA parameters and the decrease in StO2 significantly increased with the pressure increase. Among the extracted parameters, the decrease in StO2 and the mean SCL proved to be effective indicators. Such analysis outcomes would be highly beneficial for studies focusing on the comfort assessment of the binding parts of rehabilitation robots.

Can balloon-assisted enteroscopy predict disease outcomes in patients with small-bowel Crohn's disease?

There are limited studies on the endoscopic assessment of disease activity using balloon-assisted enteroscopy (BAE) and its predictive role for long-term outcomes of patients with small bowel Crohn's disease (CD). We sought to investigate the value of BAE as a predictor of long-term outcomes in patients with small-bowel CD. A total of 111 patients with small-bowel CD whose endoscopic disease activity was assessed using BAE based on the small-bowel simple endoscopic score for Crohn's disease (small-bowel SES-CD) at Samsung Medical Center were retrospectively selected from January 2014 to August 2020. The outcome was an evaluation of the risk of surgery according to a small-bowel SES-CD of 0-6 vs. ≥ 7 and endoscopic findings (presence of any ulcer and degree of stricture) using the Cox proportional hazards model. The risk of surgery was significantly increased in patients with a small-bowel SES-CD of ≥ 7 compared to a small-bowel SES-CD of 0-6 [hazard ratio (HR) 6.31; 95% confidence interval (CI) 1.48-26.91; p = 0.013]. In addition, the risk of surgery was significantly increased in patients with stenosis with "cannot be passed" compared to the cases without stenosis (HR 12.34; 95% CI 1.66-91.92; p = 0.014), whereas there was no significance in any ulcer. The present study demonstrated the role of BAE in the endoscopic assessment of disease activity and its predictive value for the risk of surgery in small-bowel CD patients. Further optimization of BAE utilization for the assessment of disease activity is warranted in clinical practice.

Effectiveness and safety of adalimumab in patients with intestinal Behçet's disease: a real-world prospective observational study in South Korea.

BACKGROUND: Intestinal Behçet's disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. METHODS: This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet's disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). RESULTS: A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953-0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). CONCLUSION: Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.

Violent Event Severity Tool for Reporting Violent Incidents.

OBJECTIVES: To explore the usefulness of the Violent Event Severity Tool (VEST). BACKGROUND: The Joint Commission and many governing bodies require establishing workplace violence prevention programs in hospitals. Inconsistent processes have hampered the efficacy evaluation of such programs for collecting and reporting violence. The VEST was developed as a standardized tool for capturing violence data. METHODS: Ninety-six healthcare workers attending the 2022 Magnet® conference completed the survey. The VEST includes 6 types and 4 intensities of violent incidents. RESULTS: Most participants reported that the VEST is easy to use (79%), relevant (85%), and useful (85%). Fewer than half were satisfied with their incident report filing processes. Only 38% of participants experiencing grade 1 physical assault filed an incident report, whereas 70% and 100% experiencing grades 3 and 4 physical assaults filed. CONCLUSIONS: The VEST appears to be a useful and relevant tool for consistent collection and reporting of various violence types and severities.

Quantification of Comfort for the Development of Binding Parts in a Standing Rehabilitation Robot.

Human-machine interfaces (HMI) refer to the physical interaction between a user and rehabilitation robots. A persisting excessive load leads to soft tissue damage, such as pressure ulcers. Therefore, it is necessary to define a comfortable binding part for a rehabilitation robot with the subject in a standing posture. The purpose of this study was to quantify the comfort at the binding parts of the standing rehabilitation robot. In Experiment 1, cuff pressures of 10-40 kPa were applied to the thigh, shank, and knee of standing subjects, and the interface pressure and pain scale were obtained. In Experiment 2, cuff pressures of 10-20 kPa were applied to the thigh, and the tissue oxygen saturation and the skin temperature were measured. Questionnaire responses regarding comfort during compression were obtained from the subjects using the visual analog scale and the Likert scale. The greatest pain was perceived in the thigh. The musculoskeletal configuration affected the pressure distribution. The interface pressure distribution by the binding part showed higher pressure at the intermuscular septum. Tissue oxygen saturation (StO2) increased to 111.9 ± 6.7% when a cuff pressure of 10 kPa was applied and decreased to 92.2 ± 16.9% for a cuff pressure of 20 kPa. A skin temperature variation greater than 0.2 °C occurred in the compressed leg. These findings would help evaluate and improve the comfort of rehabilitation robots.

TinyFallNet: A Lightweight Pre-Impact Fall Detection Model.

Falls represent a significant health concern for the elderly. While studies on deep learning-based preimpact fall detection have been conducted to mitigate fall-related injuries, additional efforts are needed for embedding in microcomputer units (MCUs). In this study, ConvLSTM, the state-of-the-art model, was benchmarked, and we attempted to lightweight it by leveraging features from image-classification models VGGNet and ResNet while maintaining performance for wearable airbags. The models were developed and evaluated using data from young subjects in the KFall public dataset based on an inertial measurement unit (IMU), leading to the proposal of TinyFallNet based on ResNet. Despite exhibiting higher accuracy (97.37% < 98.00%) than the benchmarked ConvLSTM, the proposed model requires lower memory (1.58 MB > 0.70 MB). Additionally, data on the elderly from the fall data of the FARSEEING dataset and activities of daily living (ADLs) data of the KFall dataset were analyzed for algorithm validation. This study demonstrated the applicability of image-classification models to preimpact fall detection using IMU and showed that additional tuning for lightweighting is possible due to the different data types. This research is expected to contribute to the lightweighting of deep learning models based on IMU and the development of applications based on IMU data.

Specificity of clinical decision support tools for vedolizumab and ustekinumab in biologically naïve patients with Crohn's disease.

BACKGROUND AND AIMS: Clinical decision support tools (CDST) were developed to predict drug response to various biological treatments for Crohn's disease (CD). This study investigated whether CDSTs for vedolizumab (V-CDST) and ustekinumab (U-CDST) can be used as prognostic or drug-specific markers to predict response. METHODS: A hypothetical scenario involving 872 patients with CD who were exposed to the first biological therapy at Samsung Medical Center between 1995 and 2020 is presented. V-CDST & U-CDST were calculated based on clinical and laboratory data immediately before the first biologic was initiated. The Cumulative Link Mixed Model (CLMM) test, weighted Kappa and plot, and Spearman's correlation was used to determine the degree of agreement and difference between the two tools. RESULTS: 25% of all patients diagnosed with biologically naïve CD were categorized into different probability groups using V-CDST and U-CDST. The difference between the two tools was significantly based on a two-sample paired ordinal test with Cumulative Link Mixed Model (CLMM) (p-value < .001). Concordance between the two tools with a total of 654 subjects (75% of all patients) showed a similar probability (weighted Kappa: 0.47, 95% CI: 0.41-0.52). CONCLUSIONS: V-CDST and U-CDST are useful in selecting vedolizumab or ustekinumab in 25% of biologically naïve CD patients in our hypothetical scenario.

Fall-from-Height Detection Using Deep Learning Based on IMU Sensor Data for Accident Prevention at Construction Sites.

Workers at construction sites are prone to fall-from-height (FFH) accidents. The severity of injury can be represented by the acceleration peak value. In the study, a risk prediction against FFH was made using IMU sensor data for accident prevention at construction sites. Fifteen general working movements (NF: non-fall), five low-hazard-fall movements, (LF), and five high-hazard-FFH movements (HF) were performed by twenty male subjects and a dummy. An IMU sensor was attached to the T7 position of the subject to measure the three-axis acceleration and angular velocity. The peak acceleration value, calculated from the IMU data, was 4 g or less in general work movements and 9 g or more in FFHs. Regression analysis was performed by applying various deep learning models, including 1D-CNN, 2D-CNN, LSTM, and Conv-LSTM, to the risk prediction, and then comparing them in terms of their mean absolute error (MAE) and mean squared error (MSE). The FFH risk level was estimated based on the predicted peak acceleration. The Conv-LSTM model trained by MAE showed the smallest error (MAE: 1.36 g), and the classification with the predicted peak acceleration showed the best accuracy (97.6%). This study successfully predicted the FFH risk levels and could be helpful to reduce fatal injuries at construction sites.

sEMG-Based Hand Posture Recognition and Visual Feedback Training for the Forearm Amputee.

sEMG-based gesture recognition is useful for human-computer interactions, especially for technology supporting rehabilitation training and the control of electric prostheses. However, high variability in the sEMG signals of untrained users degrades the performance of gesture recognition algorithms. In this study, the hand posture recognition algorithm and radar plot-based visual feedback training were developed using multichannel sEMG sensors. Ten healthy adults and one bilateral forearm amputee participated by repeating twelve hand postures ten times. The visual feedback training was performed for two days and five days in healthy adults and a forearm amputee, respectively. Artificial neural network classifiers were trained with two types of feature vectors: a single feature vector and a combination of feature vectors. The classification accuracy of the forearm amputee increased significantly after three days of hand posture training. These results indicate that the visual feedback training efficiently improved the performance of sEMG-based hand posture recognition by reducing variability in the sEMG signal. Furthermore, a bilateral forearm amputee was able to participate in the rehabilitation training by using a radar plot, and the radar plot-based visual feedback training would help the amputees to control various electric prostheses.

Recurrence pattern and surveillance strategy for rectal neuroendocrine tumors after endoscopic resection.

BACKGROUND AND AIM: Endoscopic resection is highly effective treatment option for rectal neuroendocrine tumors (NETs) as they usually present as small localized tumors. However, there are no well-established surveillance strategies following endoscopic resection. We established our own protocol for the surveillance of rectal NETs after endoscopic resection since 2013. This study aimed to assess the outcome and to optimize the surveillance strategies after endoscopic resection. METHODS: We retrospectively analyzed the data of patients with endoscopically treated rectal NETs between January 2013 and April 2018 at Samsung Medical Center. We analyzed 337 patients with a median follow-up duration of 35.0 months (min-max: 12.0-88.3). RESULTS: A total of 329 (97.6%) patients had tumors ≤ 1 cm in size, and eight (2.4%) patients had tumors > 1 cm in diameter. Synchronous rectal NETs were diagnosed in nine (2.7%) patients. Thirteen (3.9%) patients were identified as having positive resection margins. Regardless of the salvage treatment, none of these patients developed recurrence. Metachronous rectal NETs were diagnosed in nine (2.7%) patients. Metachronous lesions were associated with the number of synchronous lesions at initial diagnosis (P < 0.001, hazard ratio = 1.75, 95% confidence interval = 1.38-2.23). Extracolonic metastasis was not detected in this study. CONCLUSION: Although initial screening for detecting metastatic lesions using computed tomography is recommended, repeated imaging for detecting extracolonic recurrence was not necessary for small non-metastatic rectal NETs. However, regular endoscopic follow-up seems reasonable, especially in case of synchronous rectal NETs, for detecting metachronous rectal NETs.

The Performance of Post-Fall Detection Using the Cross-Dataset: Feature Vectors, Classifiers and Processing Conditions.

In this study, algorithms to detect post-falls were evaluated using the cross-dataset according to feature vectors (time-series and discrete data), classifiers (ANN and SVM), and four different processing conditions (normalization, equalization, increase in the number of training data, and additional training with external data). Three-axis acceleration and angular velocity data were obtained from 30 healthy male subjects by attaching an IMU to the middle of the left and right anterior superior iliac spines (ASIS). Internal and external tests were performed using our lab dataset and SisFall public dataset, respectively. The results showed that ANN and SVM were suitable for the time-series and discrete data, respectively. The classification performance generally decreased, and thus, specific feature vectors from the raw data were necessary when untrained motions were tested using a public dataset. Normalization made SVM and ANN more and less effective, respectively. Equalization increased the sensitivity, even though it did not improve the overall performance. The increase in the number of training data also improved the classification performance. Machine learning was vulnerable to untrained motions, and data of various movements were needed for the training.

sEMG-Based Hand Posture Recognition Considering Electrode Shift, Feature Vectors, and Posture Groups.

Surface electromyography (sEMG)-based gesture recognition systems provide the intuitive and accurate recognition of various gestures in human-computer interaction. In this study, an sEMG-based hand posture recognition algorithm was developed, considering three main problems: electrode shift, feature vectors, and posture groups. The sEMG signal was measured using an armband sensor with the electrode shift. An artificial neural network classifier was trained using 21 feature vectors for seven different posture groups. The inter-session and inter-feature Pearson correlation coefficients (PCCs) were calculated. The results indicate that the classification performance improved with the number of training sessions of the electrode shift. The number of sessions necessary for efficient training was four, and the feature vectors with a high inter-session PCC (r > 0.7) exhibited high classification accuracy. Similarities between postures in a posture group decreased the classification accuracy. Our results indicate that the classification accuracy could be improved with the addition of more electrode shift training sessions and that the PCC is useful for selecting the feature vector. Furthermore, hand posture selection was as important as feature vector selection. These findings will help in optimizing the sEMG-based pattern recognition algorithm more easily and quickly.

Epithelial Regeneration Ability of Crohn's Disease Assessed Using Patient-Derived Intestinal Organoids.

Little is known about the ability for epithelial regeneration and wound healing in patients with inflammatory bowel diseases. We evaluated the epithelial proliferation and wound healing ability of patients with Crohn's disease (CD) using patient-derived intestinal organoids. Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < 0.001). Long-term cultured organoids (≥6 passages) derived from controls and CD patients showed an indistinguishable microscopic appearance and culturing behavior. Under TNFα-enriched conditions (30 ng/mL), the organoid reconstitution rate and cell viability of CD patient-derived organoids were significantly lower than those of the control organoids (p < 0.05 for each). The number of EdU+ cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < 0.05). In a wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < 0.001). The wound healing ability of CD patient-derived organoids is reduced in TNFα-enriched conditions, due to reduced cell proliferation. Epithelial regeneration ability may be impaired in patients with CD.

Association between sensitization and allergic diseases in 7-years-old Korean children.

BACKGROUND: Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children. OBJECTIVE: We characterized the association between sensitization patterns and allergic diseases. METHODS: A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. RESULTS: The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. CONCLUSIONS: The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Effects of a weight control intervention based on the transtheoretical model on physical activity and psychological variables in middle-aged obese women.

The study examined the effect of a weight control intervention on BMI, physical activity levels, and psychological variables toward physical activity. Thirty-three middle-aged obese women participated in the 16-week weight control intervention. Results indicated that the participants' BMI significantly decreased and physical activity levels significantly increased over the intervention. Moreover, exercise self-efficacy and perceived benefits toward physical activity significantly increased, but perceived barriers of physical activity gradually decreased over the intervention. The study suggests that it is important to consider not only physical activity itself, but also the various psychological variables when planning and implementing the weight control program.

Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea.

OBJECTIVE: No population-based study has evaluated the natural course of UC over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based cohort. DESIGN: This Korean population-based, Songpa-Kangdong IBD cohort included all patients (n=1013) newly diagnosed with UC during 1986-2015. Disease outcomes and their predictors were evaluated. RESULTS: During the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines and antitumour necrosis factor (anti-TNF) agents was 40.8%, 13.9% and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20 and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1% and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (HR 8.249, 95% CI 2.394 to 28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440 to 28.773) and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057 to 0.886) were independent predictors of colectomy. The standardised mortality ratio in patients with UC was 0.725 (95% CI 0.508 to 1.004). CONCLUSION: Korean patients with UC may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.

Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study.

BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.