Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges.

RNA has emerged as a revolutionary and important tool in the battle against emerging infectious diseases, with roles extending beyond its applications in vaccines, in which it is used in the response to the COVID-19 pandemic. Since their development in the 1990s, RNA interference (RNAi) therapeutics have demonstrated potential in reducing the expression of disease-associated genes. Nucleic acid-based therapeutics, including RNAi therapies, that degrade viral genomes and rapidly adapt to viral mutations, have emerged as alternative treatments. RNAi is a robust technique frequently employed to selectively suppress gene expression in a sequence-specific manner. The swift adaptability of nucleic acid-based therapeutics such as RNAi therapies endows them with a significant advantage over other antiviral medications. For example, small interfering RNAs (siRNAs) are produced on the basis of sequence complementarity to target and degrade viral RNA, a novel approach to combat viral infections. The precision of siRNAs in targeting and degrading viral RNA has led to the development of siRNA-based treatments for diverse diseases. However, despite the promising therapeutic benefits of siRNAs, several problems, including impaired long-term protein expression, siRNA instability, off-target effects, immunological responses, and drug resistance, have been considerable obstacles to the use of siRNA-based antiviral therapies. This review provides an encompassing summary of the siRNA-based therapeutic approaches against viruses while also addressing the obstacles that need to be overcome for their effective application. Furthermore, we present potential solutions to mitigate major challenges.

Effect of protein fouling on filtrate flux and virus breakthrough behaviors during virus filtration process.

Virus filtration process is used to ensure viral safety in the biopharmaceutical downstream processes with high virus removal capacity (i.e., >4 log10 ). However, it is still constrained by protein fouling, which results in reduced filtration capacity and possible virus breakthrough. This study investigated the effects of protein fouling on filtrate flux and virus breakthrough using commercial membranes that had different symmetricity, nominal pore size, and pore size gradients. Flux decay tendency due to protein fouling was influenced by hydrodynamic drag force and protein concentration. As the results of prediction with the classical fouling model, standard blocking was suitable for most virus filters. Undesired virus breakthrough was observed in the membranes having relatively a large pore diameter of the retentive region. The study found that elevated levels of protein solution reduced virus removal performance. However, the impact of prefouled membranes was minimal. These findings shed light on the factors that influence protein fouling during the virus filtration process of biopharmaceutical production.

Improving the Separation Properties of Polybenzimidazole Membranes by Adding Acetonitrile for Organic Solvent Nanofiltration.

In research on membranes, the addition of co-solvents to the polymer dope solution is a common method for tuning the morphology and separation performance. For organic solvent nanofiltration (OSN) applications, we synthesized polybenzimidazole (PBI) membranes with high separation properties and stability by adding acetonitrile (MeCN) to the dope solution, followed by crosslinking with dibromo-p-xylene. Accordingly, changes in the membrane structure and separation properties were investigated when MeCN was added. PBI/MeCN membranes with a dense and thick active layer and narrow finger-like macrovoids exhibited superior rejection properties in the ethanol solution compared with the pristine PBI membrane. After crosslinking, they displayed superior rejection properties (96.56% rejection of 366-g/mol polypropylene glycol). In addition, the membranes demonstrated stable permeances for various organic solvents, including acetone, methanol, ethanol, toluene, and isopropyl alcohol. Furthermore, to evaluate the feasibility of the modified PBI OSN membranes, ecamsule, a chemical product in the fine chemical industry, was recovered. Correspondingly, the efficient recovery of ecamsule from a toluene/methanol solution using the OSN process with PBI/MeCN membranes demonstrated their applicability in many fine chemical industries.

Comparative Evaluation of the Performance of Sterile Filters for Bioburden Protection and Final Fill in Biopharmaceutical Processes.

Sterile filtration processes are widely used in the production of biotherapeutics for microorganism removal and product sterility. Sterile filtration processes can be applied to buffer preparation and cell culture media preparation in biotherapeutics processes, and to final sterilization or final filling in downstream processes. Owing to their broad range of applications in bioprocessing, various 0.2/0.22 µm sterile filters with different polymer materials (i.e., hydrophilic PVDF and PES) and nominal pore sizes are commercially available. The objective of this study was to evaluate two different commercial sterile filters in terms of filtration performance in various sterile filtration processes of biopharmaceutical production. The results demonstrate the importance of choosing the appropriate filter considering the process type and target removal/transport product to ensure efficient sterile filtration in the production of biotherapeutics.

Poly(ethylene-co-vinyl alcohol) Electrospun Nanofiber Membranes for Gravity-Driven Oil/Water Separation.

Fabrication of highly efficient oil/water separation membranes is attractive and challenging work for the actual application of the membranes in the treatment of oily wastewater and cleaning up oil spills/oil leakage accidents. In this study, hydrophilic poly(ethylene-co-polyvinyl alcohol) (EVOH) nanofiber membranes were made using an electrospinning technique for oil/water separation. The as-prepared EVOH electrospun nanofiber membranes (ENMs) exhibited a super-hydrophilic property (water contact angle 33.74°) without further treatment. As prepared, ENMs can provide continuous separation of surfactant-free and surfactant-stabilized water-in-oil emulsions with high efficiency (i.e., flux 8200 L m−2 h−1 (LMH), separation efficiency: >99.9%). In addition, their high stability (i.e., reusable, mechanically robust) would broaden the conditions under which they can be employed in the real field oil/water separation applications. Various characterization techniques (including morphology investigation, pore size, porosity, mechanical properties, and performance test) for gravity-driven oil/water separation were employed to evaluate the newly prepared EVOH ENMs.

Isoporous Polyvinylidene Fluoride Membranes with Selective Skin Layers via a Thermal-Vapor Assisted Phase Separation Method for Industrial Purification Applications.

The membrane filtration process is the most widely used purification process in various industries due to its high separation efficiency, process simplicity, and low cost. Although there is a wide range of membrane products with diverse materials and pore sizes on the market, there is a technological gap between microfiltration and ultrafiltration membranes. Here we developed highly porous polyvinylidene fluoride (PVDF) membranes with a selective skin layer with a pore size range of 20 to 80 nm by using a thermal-vapor assisted phase separation method. Porous and bi-continuous sublayers were generated from spinodal decomposition induced by cooling. The overall membrane structure and pore size changed with the dope composition, while the pore size and thickness of the selective skin layer were effectively controlled by water vapor exposure. The excellent nanoparticle removal efficiencies of the prepared PVDF membranes were confirmed, indicating their potential application in high-level purification processes to remove small trace organic or inorganic impurities from various industrial fluids.

Ceramide NPs derived from natural oils of Korean traditional plants enhance skin barrier functions and stimulate expressions of genes for epidermal homeostasis.

BACKGROUND: New ceramide (CER) NPs were prepared by linking fatty acids derived from oils of Korean traditional plants to phytosphingosine (PHS). The oils of Korean traditional plants were extracted from the seeds of Panax ginseng, Camellia sinensis, Glycine max napjakong, Glycine max seoritae, and Camellia japonica as sources of diverse fatty acids. AIMS: The aim of this study was to investigate signaling bioactivities of HP-C. sinensis ceramide NP that was column purified to remove any residual PHS and to evaluate the skin barrier functions of the HP-C. sinensis ceramide NP in human skin. METHODS: The expressions of genes related to epidermal differentiation were analyzed in vitro by qPCR. Human studies were also performed to determine the skin barrier functions with respect to TEWL and SC cohesion. RESULTS: The HP-C. sinensis CER NP significantly enhanced the expressions of FLG, CASP14, and INV indicates that the signaling biological activities of oil-derived ceramide NPs could be different depend on the natural oils. The control ceramide, C18-CER NP, had no effect on the expression of the three genes. HP-C. sinensis CER NP was selected for the in vivo human studies. Application of 0.5% HP-C. sinensis CER NP cream stimulated significantly faster recovery of a disrupted skin barrier than that of the control C18-CER NP. A significant enhancement of SC cohesion of the skin treated with 0.5% HP-C. sinensis CER NP was also observed. CONCLUSION: Taken all together, our results clearly demonstrate that HP-C. sinensis CER NP, P. ginseng CER NP, and other oil-derived CER NP could be a better choice for developing moisturizers to improve skin barrier function as they more closely mimic the endogenous CER composition of the actual human skin barrier.

A Review on Polymer Precursors of Carbon Molecular Sieve Membranes for Olefin/Paraffin Separation.

Carbon molecular sieve (CMS) membranes have been developed to replace or support energy-intensive cryogenic distillation for olefin/paraffin separation. Olefin and paraffin have similar molecular properties, but can be separated effectively by a CMS membrane with a rigid, slit-like pore structure. A variety of polymer precursors can give rise to different outcomes in terms of the structure and performance of CMS membranes. Herein, for olefin/paraffin separation, the CMS membranes derived from a number of polymer precursors (such as polyimides, phenolic resin, and polymers of intrinsic microporosity, PIM) are introduced, and olefin/paraffin separation properties of those membranes are summarized. The effects from incorporation of inorganic materials into polymer precursors and from a pyrolysis process on the properties of CMS membranes are also reviewed. Finally, the prospects and future directions of CMS membranes for olefin/paraffin separation and aging issues are discussed.

Deep radiomics-based survival prediction in patients with chronic obstructive pulmonary disease.

Heterogeneous clinical manifestations and progression of chronic obstructive pulmonary disease (COPD) affect patient health risk assessment, stratification, and management. Pulmonary function tests are used to diagnose and classify the severity of COPD, but they cannot fully represent the type or range of pathophysiologic abnormalities of the disease. To evaluate whether deep radiomics from chest computed tomography (CT) images can predict mortality in patients with COPD, we designed a convolutional neural network (CNN) model for extracting representative features from CT images and then performed random survival forest to predict survival in COPD patients. We trained CNN-based binary classifier based on six-minute walk distance results (> 440 m or not) and extracted high-throughput image features (i.e., deep radiomics) directly from the last fully connected layer of it. The various sizes of fully connected layers and combinations of deep features were experimented using a discovery cohort with 344 patients from the Korean Obstructive Lung Disease cohort and an external validation cohort with 102 patients from Penang General Hospital in Malaysia. In the integrative analysis of discovery and external validation cohorts, with combining 256 deep features from the coronal slice of the vertebral body and two sagittal slices of the left/right lung, deep radiomics for survival prediction achieved concordance indices of 0.8008 (95% CI, 0.7642-0.8373) and 0.7156 (95% CI, 0.7024-0.7288), respectively. Deep radiomics from CT images could be used to predict mortality in COPD patients.

Radiomics approach for survival prediction in chronic obstructive pulmonary disease.

OBJECTIVES: To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS). METHODS: This study included 344 patients from the Korean Obstructive Lung Disease (KOLD) cohort. External validation was performed on a cohort of 112 patients. In total, 525 chest CT-based radiomics features were semi-automatically extracted. The five most useful features for survival prediction were selected by least absolute shrinkage and selection operation (LASSO) Cox regression analysis and used to generate a RS. The ability of the RS for classifying COPD patients into high or low mortality risk groups was evaluated with the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. RESULTS: The five features remaining after the LASSO analysis were %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm. The RS demonstrated a C-index of 0.774 in the discovery group and 0.805 in the validation group. Patients with a RS greater than 1.053 were classified into the high-risk group and demonstrated worse overall survival than those in the low-risk group in both the discovery (log-rank test, < 0.001; hazard ratio [HR], 5.265) and validation groups (log-rank test, < 0.001; HR, 5.223). For both groups, RS was significantly associated with overall survival after adjustments for patient age and body mass index. CONCLUSIONS: A radiomics approach for survival prediction and risk stratification in COPD patients is feasible, and the constructed radiomics model demonstrated acceptable performance. The RS derived from chest CT data of COPD patients was able to effectively identify those at increased risk of mortality. KEY POINTS: • A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm were selected to generate a radiomics model. • A radiomics model for predicting survival of COPD patients demonstrated reliable performance with a C-index of 0.774 in the discovery group and 0.805 in the validation group. • Radiomics approach was able to effectively identify COPD patients with an increased risk of mortality, and patients assigned to the high-risk group demonstrated worse overall survival in both the discovery and validation groups.

Defect Engineering in Metal-Organic Frameworks Towards Advanced Mixed Matrix Membranes for Efficient Propylene/Propane Separation.

Highly permselective and durable membrane materials have been sought for energy-efficient C3 H6 /C3 H8 separation. Mixed-matrix membranes (MMMs) comprising a polymer matrix and metal-organic frameworks (MOFs) are promising candidates for this application; however, rational matching of filler-matrix is challenging and their separation performances need to be further improved. Here, we propose a novel strategy of "defect engineering" in MOFs as an additional degree of freedom to design advanced MMMs. MMMs incorporated with defect-engineered MOFs exhibit exceptionally high C3 H6 permeability and maintained C3 H6 /C3 H8 selectivity, especially with enhanced stability under industrial mixed-gas conditions. The gas transport, sorption, and material characterizations reveal that the defect sites in MOFs provide the resulting MMMs with not only ultrafast diffusion pathways but also favorable C3 H6 sorption by forming complexation with unsaturated open metal sites, confirmed by in situ FT-IR studies. Most importantly, the concept is also valid for different polymer matrices and gas pairs, demonstrating its versatile potential in other fields.

Metal-Contact Improvement in a Multilayer WSe2 Transistor through Strong Hot Carrier Injection.

Hot carrier injection (HCI), occurring when the horizontal electric field is strongly applied, usually affects the degradation of nanoelectronic devices. In addition, metal contacts play a significant role in nanoelectronic devices. In this study, Schottky contacts in multilayer tungsten diselenide (WSe2) field-effect transistors (FETs) by hot carrier injection (HCI), occurring when a high drain voltage is applied, is investigated. A small number of hot carriers with high energy reduces the Schottky barrier height and improves the performance of FETs effectively rather than damaging the channel. Thermal annealing at the end of the fabrication process increases device performance by causing interfacial reactions of the source/drain electrodes. HCI causes a significant enhancement in the local asymmetry, especially in the subthreshold region. The subthreshold swing (SS) of the thermally annealed FETs is significantly improved from 9.66 to 0.562 V dec-1 through the energy of HCI generated by a strong horizontal electric field. In addition, the contact resistances (RSD), also called series resistances, extracted by a four-probe measurement and a Y-function method were also improved by decreasing to a 10th through the energy of HCI. To understand the asymmetrical characteristics of the channel after the stress, we performed electrical analysis, electrostatic force microscopy (EFM), and Raman spectroscopy.

Defect spectroscopy of sidewall interfaces in gate-all-around silicon nanosheet FET.

Through time-dependent defect spectroscopy and low-frequency noise measurements, we investigate and characterize the differences of carrier trapping processes occurred by different interfaces (top/sidewall) of the gate-all-around silicon nanosheet field-effect transistor (GAA SiNS FET). In a GAA SiNS FET fabricated by the top-down process, the traps at the sidewall interface significantly affect the device performance as the width decreases. Compare to expectations, as the width of the device decreases, the subthreshold swing (SS) increases from 120 to 230 mV/dec, resulting in less gate controllability. In narrow-width devices, the effect of traps located at the sidewall interface is significantly dominant, and the 1/f 2 noise, also known as generation-recombination (G-R) noise, is clearly appeared with an increased time constant (τ i ). In addition, the probability density distributions for the normalized current fluctuations (ΔI D) show only one Gaussian in wide-width devices, whereas they are separated into four Gaussians with increased in narrow-width devices. Therefore, fitting is performed through the carrier number fluctuation-correlated with mobility fluctuations model that separately considered the effects of sidewall. In narrow-width GAA SiNS FETs, consequently, the extracted interface trap densities (N T ) distribution becomes more dominant, and the scattering parameter ([Formula: see text]) distribution increases by more than double.

Data stratification toward advanced flood waste estimation: A case study in South Korea.

Flood waste management is important for reducing the damage and secondary environmental pollution caused by delays in disaster recovery. One key issue related to flood waste management concerns estimating the precise quantity of waste to plan recovery strategies and policies. In this study, an advanced flood waste estimation technique was devised using data stratification. In total 90 flood cases in South Korea were sorted by three strata characteristics: administrative region (AR; equivalent to special city or province), urbanization rate (UR), and disaster type and coastal accessibility (DC). According to the results, such data stratification led to flood waste prediction improvement not only by the single-stage stratification but also by successive stratifications. Data stratification was effective both for identifying groups with similar contexts and for eliminating disparities in the dataset that impede accurate waste prediction. Among the stratification sequences tested, the order resulted in the most improvement in flood waste prediction was UR, AR, and DC. This stratification order yielded enhanced waste prediction in 74 cases. Since this study deals with a strategy to resolve gaps in disaster data, which is a crucial issue in many countries, it is envisaged that this strategy can be transferred to other countries.

Real-time effect of electron beam on MoS2 field-effect transistors.

Irradiation of MoS2 field-effect transistors (FETs) fabricated on Si/SiO2 substrates with electron beams (e-beams) below 30 keV creates electron-hole pairs (EHP) in the SiO2, which increase the interface trap density (Nit ) and change the current path in the channel, resulting in performance changes. In situ measurements of the electrical characteristics of the FET performed using a nano-probe system mounted inside a scanning electron microscope show that e-beam irradiation enables both multilayer and monolayer MoS2 channels act as conductors. The e-beams mostly penetrate the channel owing to their large kinetic energy, while the EHPs formed in the SiO2 layer can contribute to the conductance by flowing into the MoS2 channel or inducing the gate bias effect. The analysis of the device parameters in the initial state and the vent-evacuation state after e-beam irradiation can clarify the effect of the interplay between the e-beam-induced EHPs and ambient adsorbates on the carrier behavior, which depends on the thickness of the MoS2 layer. DC and low frequency noise analysis reveals that the e-beam-induced EHPs increase Nit from 109-1010 to 1011 cm-2 eV-1 in both monolayer and multilayer devices, while the interfacial Coulomb scattering parameter αSC increases by three times in the monolayer and decreases to one-tenth of its original value in the multilayer. In other words, an MoS2 layer with a thickness of ∼30 nm is less sensitive to adsorbates by surface screening. Thus, the carrier mobility in the monolayer device decreases from 45.7 to 40 cm2 V-1 s-1, while in the 30 nm-thick multilayer device, it increases from 4.9 to 5.6 cm2 V-1 s-1. This is further evidenced by simulations of the distribution of interface traps and channel carriers in the MoS2 FET before and after e-beam irradiation, demonstrating that Coulomb scattering decreases as the effective channel moves away from the interface.

Origin of CO2-philic Sorption by Graphene Oxide Layered Nanosheets and Their Derivatives.

Graphene oxide (GO) is a promising 2D material for adsorbents and membranes, in particular, for the CO2 separation process. However, CO2 diffusion and sorption in GO and its layered structures are still not well understood because of its heterogeneous structure. Here we report CO2 sorption in GO and its derivatives (e.g., reduced GO (rGO)) in powders and films. These CO2 sorption behaviors reveal that GO is highly CO2-philic via complex CO2-functional-group-surface interactions, as compared with graphite and rGOs. Even in highly interlocked, lamellar GO films, CO2 molecules above a certain threshold pressure can diffuse into GO interlayers, causing GO films to swell and leading to dramatic increases in CO2 sorption. Intercalated water in GO interlayers can be removed by preferential CO2 sorption without any changes in the GO chemical structure. This finding helps to explain the origin of CO2 affinity with GO and has implications for preparing anhydrous GO assemblies for various applications.

Chest CT imaging features for prediction of treatment response in cryptogenic and connective tissue disease-related organizing pneumonia.

OBJECTIVES: To investigate CT imaging features associated with poor clinical outcome after corticosteroid treatment in patients diagnosed with cryptogenic organizing pneumonia (COP) and connective tissue disease-related organizing pneumonia (CTD-OP) and to assess the difference in CT findings and treatment responses between COP and CTD-OP. METHODS: Chest CT images from 166 patients (COP, 131; CTD-OP, 35) with pathologically proven organizing pneumonia were reviewed by two thoracic radiologists. The type, distribution pattern, and extent of parenchymal abnormalities, along with other associated imaging features, were assessed for each patient. Logistic regression analyses were used to identify features associated with poor clinical outcomes such as residual disease (RD) and disease relapse. The differences between COP and CTD-OP were also analyzed. RESULTS: Consolidation involving more than 10% of parenchyma (hazard ratio [HR], 2.27), detectable bronchiectasis (HR, 3.59), and diagnosis of CTD-OP (HR, 4.31) were associated with a higher risk of RD after adjustments for patient age and sex. More than 10% consolidation involvement (HR, 2.54) and diagnosis of CTD-OP (HR, 6.42) were also associated with a higher risk of disease relapse. Compared with COP, CTD-OP demonstrated a greater extent of parenchymal abnormalities, especially consolidation, and was less likely to show a peribronchovascular distribution pattern. CONCLUSION: Bronchiectasis and a greater extent of consolidation were associated with RD, with the latter also being associated with disease relapse. Compared with COP, CTD-OP was associated with worse treatment outcomes and demonstrated a greater extent of parenchymal abnormalities, which were also less likely to show a peribronchovascular pattern. KEY POINTS: • The presence of bronchiectasis and a high parenchymal involvement of consolidation on initial chest CT were associated with a worse response to corticosteroids in patients with organizing pneumonia. • Connective tissue disease-related organizing pneumonia (CTD-OP) was associated with worse treatment outcomes than its idiopathic counterpart cryptogenic organizing pneumonia (COP). • Compared with COP, CTD-OP generally demonstrated a greater extent of parenchymal abnormalities, especially consolidation, and was less likely to show a peribronchovascular distribution pattern.

Blood Oxygenation Using Fluoropolymer-Based Artificial Lung Membranes.

Artificial lung (AL) membranes are used for blood oxygenation for patients undergoing open-heart surgery or acute lung failures. Current AL technology employs polypropylene and polymethylpentene membranes. Although effective, these membranes suffer from low biocompatibility, leading to undesired blood coagulation and hemolysis over a long term. In this work, we propose a new generation of AL membranes based on amphiphobic fluoropolymers. We employed poly(vinylidene-co-hexafluoropropylene), or PVDF-co-HFP, to fabricate macrovoid-free membranes with an optimal pore size range of 30-50 nm. The phase inversion behavior of PVDF-co-HFP was investigated in detail for structural optimization. To improve the wetting stability of the membranes, the fabricated membranes were coated using Hyflon AD60X, a type of fluoropolymer with an extremely low surface energy. Hyflon-coated materials displayed very low protein adsorption and a high contact angle for both water and blood. In the hydrophobic spectrum, the data showed an inverse relationship between the surface free energy and protein adsorption, suggesting an appropriate direction with respect to biocompatibility for AL research. The blood oxygenation performance was assessed using animal sheep blood, and the fabricated fluoropolymer membranes showed competitive performance to that of commercial polyolefin membranes without any detectable hemolysis. The data also confirmed that the bottleneck in the blood oxygenation performance was not the membrane permeance but rather the rate of mass transfer in the blood phase, highlighting the importance of efficient module design.

A Curriculum Learning Strategy to Enhance the Accuracy of Classification of Various Lesions in Chest-PA X-ray Screening for Pulmonary Abnormalities.

We evaluated the efficacy of a curriculum learning strategy using two steps to detect pulmonary abnormalities including nodule[s], consolidation, interstitial opacity, pleural effusion, and pneumothorax with chest-PA X-ray (CXR) images from two centres. CXR images of 6069 healthy subjects and 3417 patients at AMC and 1035 healthy subjects and 4404 patients at SNUBH were obtained. Our approach involved two steps. First, the regional patterns of thoracic abnormalities were identified by initial learning of patch images around abnormal lesions. Second, Resnet-50 was fine-tuned using the entire images. The network was weakly trained and modified to detect various disease patterns. Finally, class activation maps (CAM) were extracted to localise and visualise the abnormal patterns. For average disease, the sensitivity, specificity, and area under the curve (AUC) were 85.4%, 99.8%, and 0.947, respectively, in the AMC dataset and 97.9%, 100.0%, and 0.983, respectively, in the SNUBH dataset. This curriculum learning and weak labelling with high-scale CXR images requires less preparation to train the system and could be easily extended to include various diseases in actual clinical environments. This algorithm performed well for the detection and classification of five disease patterns in CXR images and could be helpful in image interpretation.

Use of Anti-TNF Alpha Blockers Can Reduce Operation Rate and Lead to Growth Gain in Pediatric Crohn's Disease.

PURPOSE: Pediatric Crohn's disease (CD) is directly related to growth and has a high probability of requiring surgical intervention(s); therefore, more active treatment for CD is required for children. This study investigated the impact of biologics on growth and disease course associated with surgery. METHODS: This was a retrospective cohort study involving patients diagnosed with CD at the Seoul National University Children's Hospital (Seoul, Korea) between January 2006 and October 2017. The aim was to determine the characteristics of pediatric patients with CD and whether biologics affected growth and the surgical disease course. RESULTS: Among patients who underwent surgery for CD, the mean number of operations per patient was 1.89. The mean time from initial diagnosis to surgery was 19.3 months. The most common procedure was fistulectomy (34%), followed by incision and drainage (25%). In all patients, the use of biologics increased the height (p=0.002) and body mass index (BMI) (p=0.005). Among patients who underwent surgery, height (p=0.004) and BMI (p=0.048) were increased in the group using biologics. Patients who used biologics exhibited a low operation rate only within 2 years after diagnosis, with no differences thereafter (p=0.027). CONCLUSION: Although biologics could not mitigate the operation rate in pediatric patients who underwent surgery for CD, biological therapy delayed disease progression within 2 years of disease onset. Additionally, biologics conferred growth and BMI benefits in this window period. Therefore, it may be helpful to use biologics for optimal growth in pediatric patients with a high probability of undergoing future surgery.