Binding affinity screening of polyphenolic compounds in Stachys affinis extract (SAE) for their potential antioxidant and anti-inflammatory effects.

Free radical is a marker in various inflammatory diseases. The antioxidant effect protects us from this damage, which also plays an essential role in preventing inflammation. Inflammation protects the body from biological stimuli, and pro-inflammatory mediators are negatively affected in the immune system. Inflammation caused by LPS is an endotoxin found in the outer membrane of Gram-negative bacteria, which induces immune cells to produce inflammatory cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase. Based on this, the antioxidant and anti-inflammatory effects of plant extracts were investigated. First, the main phenolic compounds for the five peaks obtained from Stachys affinis extract (SAE) were identified. The antioxidant effect of each phenolic compound was confirmed through HPLC analysis before and after the competitive binding reaction between DPPH and the extract. Afterward, the anti-inflammatory effect of each phenolic compound was confirmed through competitive binding between COX2 and the extract in HPLC analysis. Lastly, the anti-inflammatory effect of SAE was confirmed through in vitro experiments and also confirmed in terms of structural binding through molecular docking. This study confirmed that phenolic compounds in SAE extract have potential antioxidant and anti-inflammatory effects, and may provide information for primary screening of medicinal plants.

Choroidal thickening induced by pioglitazone in diabetic patients.

Purpose: This study aimed to determine the changes in choroidal thickness induced by pioglitazone in diabetic patients. Methods: A total of 261 patients diagnosed with type 2 diabetes who had taken oral pioglitazone for more than 6 months were included in the study. After excluding patients who did not undergo regular eye examinations or who had ophthalmic surgery/interventions during the treatment period, a total of 40 eyes were included. The study examined the duration and dosage of pioglitazone, patient age, ocular axial length, refraction, glycated hemoglobin, systolic blood pressure, corrected visual acuity, macular thickness, choroidal thickness, and choroid vascular index. Patients were categorized into a high dose group if their pioglitazone dose was 30mg or more per day, and a low dose group if it was 15mg or less. Choroidal thickness was measured below the subfovea and a 500 µm radius nasal and temporal to that location. Results: Choroidal thickness significantly increased after 6 and 12 months of pioglitazone in all subjects (6.70µm, 13.65µm, each). When stratified by pioglitazone dosage, choroidal thickness increased at 6 and 12 months in both the high (4.48µm, 0.84µm, each) and low dose groups (6.85µm, 21.45µm, each), with a greater change observed in low dose group (p<0.05, respectively). Based on the location of choroidal thickness measurements, a significant increase in choroidal thickness was observed at 6 and 12 months of pioglitazone treatment in the subfoveal (7.00µm, 13.15µm, each) and nasal regions (6.43µm, 19.24µm, each), while a significant increase was only observed after 6 months of treatment in the temporal region (8.53µm) (p<0.05, respectively). The largest increase in choroidal thickness was observed in the nasal side. Conclusion: This study found that choroidal thickness increased in diabetic patients after taking pioglitazone. Regular eye examinations are recommended for diabetic patients who are on pioglitazone.

Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY).

BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).

Potential Antioxidant and Anti-Inflammatory Properties of Polyphenolic Compounds from Cirsium japonicum Extract.

Cirsium japonicum is a medicinal plant that has been used due to its beneficial properties. However, extensive information regarding its therapeutic potential is scarce in the scientific literature. The antioxidant and anti-inflammatory potential of polyphenols derived from the Cirsium japonicum extracts (CJE) was systematically analyzed. High-performance liquid chromatography (HPLC) with mass spectrometry (MS) was used to examine the compounds in CJE. A total of six peaks of polyphenol compounds were identified in the extract, and their MS data were also confirmed. These bioactive compounds were subjected to ultrafiltration with LC analysis to assess their potential for targeting cyclooxygenase-2 (COX2) and DPPH. The outcomes showed which primary compounds had the highest affinity for binding both COX2 and DPPH. This suggests that components that showed excellent binding ability to DPPH and COX2 can be considered significant active substances. Additionally, in vitro analysis of CJE was carried out in macrophage cells after inducing inflammation with lipopolysaccharide (LPS). As a result, it downregulated the expression of two critical pro-inflammatory cytokines, COX2 and inducible nitric oxide synthase (iNOS). In addition, we found a solid binding ability through the molecular docking analysis of the selected compounds with inflammatory mediators. In conclusion, we identified polyphenolic compounds in CJE extract and confirmed their potential antioxidant and anti-inflammatory effects. These results may provide primary data for the application of CJE in the food and pharmaceutical industries with further analysis.

Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa.

Most mutations in retinitis pigmentosa (RP) arise in rod photoreceptors, but cone photoreceptors, responsible for high-resolution daylight and color vision, are subsequently affected, causing the most debilitating features of the disease. We used mass spectroscopy to follow 13C metabolites delivered to the outer retina and single-cell RNA sequencing to assess photoreceptor transcriptomes. The S cone metabolic transcriptome suggests engagement of the TCA cycle and ongoing response to ROS characteristic of oxidative phosphorylation, which we link to their histone modification transcriptome. Tumor necrosis factor (TNF) and its downstream effector RIP3, which drive ROS generation via mitochondrial dysfunction, are induced and activated as S cones undergo early apoptosis in RP. The long/medium-wavelength (L/M) cone transcriptome shows enhanced glycolytic capacity, which maintains their function as RP progresses. Then, as extracellular glucose eventually diminishes, L/M cones are sustained in long-term dormancy by lactate metabolism.

Six-Year Survival Outcomes for Patients with HER2-Positive Early Breast Cancer Treated with CT-P6 or Reference Trastuzumab: Observational Follow-Up Study of a Phase 3 Randomised Controlled Trial.

BACKGROUND: The Phase 3 CT-P6 3.2 study demonstrated equivalent efficacy and comparable safety between CT-P6 and reference trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer after up to 3 years' follow-up. OBJECTIVE: To investigate long-term survival with CT-P6 and reference trastuzumab. METHODS: In the CT-P6 3.2 study, patients with HER2-positive early breast cancer were randomised to neoadjuvant chemotherapy with CT-P6 or reference trastuzumab, surgery, and adjuvant CT-P6 or reference trastuzumab before a 3-year post-treatment follow-up. Patients who completed the study could enter a 3-year extension (CT-P6 4.2 study). Data were collected every 6 months to assess overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). RESULTS: Of 549 patients enrolled in the CT-P6 3.2 study, 216 (39.3%) patients continued in the CT-P6 4.2 study (CT-P6, 107; reference trastuzumab, 109) (intention-to-treat extension set). Median follow-up was 76.4 months for both groups. Medians were not reached for time-to-event parameters; estimated hazard ratios (95% confidence intervals) for CT-P6 versus reference trastuzumab were 0.59 (0.17-2.02) for OS, 1.07 (0.50-2.32) for DFS, and 1.08 (0.50-2.34) for PFS. Corresponding 6-year survival rates in the CT-P6 and reference trastuzumab groups, respectively, were 0.96 (0.90-0.99) and 0.94 (0.87-0.97), 0.87 (0.78-0.92) and 0.89 (0.81-0.94), and 0.87 (0.78-0.92) and 0.89 (0.82-0.94). CONCLUSIONS: Data from this extended follow-up of the CT-P6 3.2 study demonstrate the comparable long-term efficacy of CT-P6 and reference trastuzumab up to 6 years. EUDRACT NUMBER: 2019-003518-15 (retrospectively registered 10 March 2020).

Conversion of Hazardous Diesel Soot Particles into a Novel Highly Efficient 3D Hydrogel for Solar Desalination and Wastewater Purification.

Diesel particulate matter (DPM) generated as vehicular exhaust is one of the main sources of atmospheric soot. These soot particles have been known to cause adverse health problems in humans and cause acute environmental problems. Despite great efforts for minimizing soot production, research on the disposal and recycling of inevitable diesel soot is scarce. However, DPM consists mainly of carbonaceous soot (DS) that can be easily utilized as a photothermal material for solar desalination. Recently, interfacial solar steam generation using three-dimensional (3D) structures has gained extensive attention. 3D-structured hydrogels have exhibited incredible performance in solar desalination owing to their tunable physicochemical properties, hydrophilicity, intrinsic heat localization, and excellent water transport capability. Herein, a novel DS-incorporated 3D polyvinyl alcohol (PVA)-based hydrogel is proposed for highly efficient solar desalination. The polymer network incorporated with purified DS (DSH) achieved an excellent evaporation rate of 3.01 kg m-2 h-1 under 1 sun illumination due to its vertically aligned water channels, hydrophilicity, and intrinsic porous structure. In addition, the DSH-PVA hydrogel could generate desalinated water efficiently (2.5 kg m-2 h-1) with anti-salt fouling properties. The present results would motivate the utilization and recycling of waste materials like DS as photothermal materials for efficient, low-cost, and sustainable solar desalination.

An Outbreak of Fungal Endophthalmitis After Cataract Surgery in South Korea.

Importance: Fungal endophthalmitis caused by contaminated medical products is extremely rare; it follows an intractable clinical course with a poor visual prognosis. Objective: To report the epidemiologic and clinical features and treatment outcomes of a nationwide fungal endophthalmitis outbreak after cataract surgery as a result of contaminated viscoelastic agents in South Korea. Design, Setting, and Participants: This was a retrospective case series analysis of clinical data from multiple institutions in South Korea conducted from September 1, 2020, to October 31, 2021. Data were collected through nationwide surveys in May and October 2021 from the 100 members of the Korean Retinal Society. Patients were diagnosed with fungal endophthalmitis resulting from the use of the viscoelastic material sodium hyaluronate (Unial [Unimed Pharmaceutical Inc]). Data were analyzed from November 1, 2021, to May 30, 2022. Main Outcomes and Measures: The clinical features and causative species were identified, and treatment outcomes were analyzed for patients who underwent 6 months of follow-up. Results: The fungal endophthalmitis outbreak developed between September 1, 2020, and June 30, 2021, and peaked in November 2020. An official investigation by the Korea Disease Control and Prevention Agency confirmed contamination of viscoelastic material. All 281 eyes of 265 patients (mean [SD] age, 65.4 [10.8] years; 153 female individuals [57.7%]) were diagnosed with fungal endophthalmitis, based on clinical examinations and supportive culture results. The mean (SD) time period between cataract surgery and diagnosis was 24.7 (17.3) days. Patients exhibited characteristic clinical features of fungal endophthalmitis, including vitreous opacity (212 of 281 [75.4%]), infiltration into the intraocular lens (143 of 281 [50.9%]), and ciliary infiltration (55 of 281 [19.6%]). Cultures were performed in 260 eyes, and fungal presence was confirmed in 103 eyes (39.6%). Among them, Fusarium species were identified in 89 eyes (86.4%). Among the 228 eyes included in the treatment outcome analysis, the mean (SD) best-corrected visual acuity improved from 0.78 (0.74) logMAR (Snellen equivalent, 20/120 [7.3 lines]) to 0.36 (0.49) logMAR (Snellen equivalent, 20/45 [4.9 lines]) at 6 months. Furthermore, disease remission with no signs of fungal endophthalmitis (or cells in the anterior chamber milder than grade 1) was noted in 214 eyes (93.9%). Conclusions and Relevance: This was a retrospectively reviewed case series of a fungal endophthalmitis outbreak resulting from contaminated viscoelastic material. Findings of this case series study support the potential benefit of prompt, aggressive surgical intervention that may reduce treatment burden and improve prognosis of fungal endophthalmitis caused by contaminated medical products.

Delayed-onset endophthalmitis associated with Achromobacter species developed in acute form several months after cataract surgery: Three case reports.

BACKGROUND: Achromobacter species-associated endophthalmitis is rare and may present as either acute or chronic postoperative endophthalmitis. Delayed-onset Achromobacter species endophthalmitis appearing in acute presentation that develops more than several months after cataract surgery is very rare. Intraocular lens (IOL) removal is commonly recommended to treat Achromobacter species endophthalmitis, which is based on previous studies. Here, we report the results of surgery without IOL removal when treating patients with delayed-onset postoperative Achromobacter species endophthalmitis that developed in an acute form. CASE SUMMARY: Three patients visited our ophthalmology clinic due to visual impairment that began 2-3 d earlier. They had undergone cataract surgery 5-18 mo prior. Best-corrected visual acuity of the diseased eye was between counting fingers at 30 cm to non-light perception. They showed conjunctival injection, inflammation in the anterior chamber (cell reaction 4+) and hypopyon formation. The patients were diagnosed with infectious endophthalmitis and immediately underwent pars plana vitrectomy, anterior chamber irrigation and intravitreal injection of ceftazidime and vancomycin. Before fluid infusion, a vitreous specimen was obtained. In all cases, the IOLs were not removed. Achromobacter species was detected on vitreous specimen culture. After surgery, the vitreous opacity decreased gradually and there was little retinal damage. At 1 mo after treatment, the best-corrected visual acuity had improved to 20/50 and 20/40. CONCLUSION: Delayed onset postoperative endophthalmitis caused by Achromobacter species can appear in an acute form. All patients responded well to early vitrectomy and administration of empirical antibiotics including ceftazidime. There was no need for IOL removal during surgery.

Effect of prophylactic anti-VEGF injections on the prevention of recurrent vitreous hemorrhage in PDR patients after PRP.

We evaluated the effectiveness of intravitreal anti-vascular endothelial growth factor (anti-VEGF) antibody injection (IVAI) for the prevention of recurrent vitreous hemorrhage (VH) due to neovascularization on disc (NVD) in patients with proliferative diabetic retinopathy (PDR) after panretinal photocoagulation (PRP). This retrospective case series reviewed the medical records of 12 PDR patients with recurrent VH after PRP from NVD. The interval between IVAIs was decided on the basis of the interval between VH recurrences after the initial IVAI, and NVD regression/recurrence during follow-up. We recorded the success rate of VH prevention, and the interval between IVAIs. Fundus examination revealed NVD regression at 1 month after the injection. However, NVD progressed gradually and VH recurred after 3-4 months. Thereafter, IVAIs were administered every 3-4 months; VH did not recur and visual acuity remained stable during the treatment period. In one case, NVD did not recur after 4 years of periodic injections. No systemic or ocular complications of IVAI were observed. In conclusion, proactive and periodic IVAIs (at 3-4-month intervals) may prevent recurrent VH in association with NVD in PDR patients after PRP.

Effective Icephobicity of Silicone Oil-Infused Oleamide-Polydimethylsiloxane with Enhanced Lubrication Lifetime.

Icing and freezing phenomena in cold weather cause serious damage and economic losses. Thus, the development of a new effective icephobic surface with low ice adhesion strength (τice) that can easily remove ice by wind or gravity force is essentially required. In this study, we propose a silicone oil-infused oleamide-polydimethylsiloxane (SiOP) by a facile fabrication method to achieve the effective icephobic performance with enhanced lubrication lifetime. The proposed SiOP is composed of a composite containing oleamide and polydimethylsiloxane (PDMS) and silicone oil impregnated into the polymeric networks of the composite. Oleamide has been used as a slip agent in industries to reduce the skin friction of polymer films. The weight of the oil impregnated in SiOP is approximately three times higher than that of silicone oil-infused PDMS (SiPDMS). Different from the SiPDMS surface on which oil dries easily, a slippery oil layer is stably formed on the SiOP surface. The fabricated SiOP surfaces have very low τice values of approximately 1 kPa, which is much smaller than that of the SiPDMS surface. The SiOP with an oleamide content of 5 wt % exhibits the smallest τice value of 0.88 kPa. The fabricated SiOP surfaces maintain their superior icephobicity for more than 30 icing/deicing cycles, demonstrating their enhanced lubrication lifetime. In addition, the ice freezing time of a water droplet of 7 µL in volume is significantly delayed on the SiOP surface compared with that on the SiPDMS surface. The present results demonstrate that the proposed SiOP surface can help provide superior icephobic performance with the aid of the incorporation of oleamide into the conventional SiPDMS. The developed icephobic SiOP can be utilized to satisfactorily resolve the lubricant drought problem of conventional icephobic surfaces by empolying oleamide as a complementary slip agent.

Optimization of adipose tissue-derived mesenchymal stromal cells transplantation for bone marrow repopulation following irradiation.

BACKGROUND: Bone marrow (BM) suppression is one of the most common side effects of radiotherapy and the primary cause of death following exposure to irradiation. Despite concerted efforts, there is no definitive treatment method available. Recent studies have reported using mesenchymal stromal cells (MSCs), but their therapeutic effects are contested. AIM: We administered and examined the effects of various amounts of adipose-derived MSCs (ADSCs) in mice with radiation-induced BM suppression. METHODS: Mice were divided into three groups: Normal control group, irradiated (RT) group, and stem cell-treated group following whole-body irradiation (WBI). Mouse ADSCs (mADSCs) were transplanted into the peritoneal cavity either once or three times at 5 × 105 cells/200 µL. The white blood cell count and the levels of, plasma cytokines, BM mRNA, and BM surface markers were compared between the three groups. Human BM-derived CD34+ hematopoietic progenitor cells were co-cultured with human ADSCs (hADSCs) or incubated in the presence of hADSCs conditioned media to investigate the effect on human cells in vitro. RESULTS: The survival rate of mice that received one transplant of mADSCs was higher than that of mice that received three transplants. Multiple transplantations of ADSCs delayed the repopulation of BM hematopoietic stem cells. Anti-inflammatory effects and M2 polarization by intraperitoneal ADSCs might suppress erythropoiesis and induce myelopoiesis in sub-lethally RT mice. CONCLUSION: The results suggested that an optimal amount of MSCs could improve survival rates post-WBI.

Bioinspired Fatty Acid Amide-Based Slippery Oleogels for Shear-Stable Lubrication.

Liquid-repellent technology is an efficient means of energy-saving and biofouling avoidance. However, liquid-repellent surfaces suffer from inefficient lubricant retention under shear flow and fouling problem in marine environment. Here, the authors demonstrate a fatty acid amide (FAA)-based oleogel for stable and sustainable lubrication in marine environment. The lubrication management of marine creatures is emulated in synthetic oleogels by incorporating solid (FAA) and liquid lubricants into the molecular meshes of polymeric networks, with the nature-derived solid lubricant providing multifunctional synergistic effects with liquid oil molecules for slippery property and remarkable anti-biofouling. The lubricant-confining gel achieves shear-stable lubricity with efficient oil management. The oleogel provides continued lubrication without biofouling for approximately 4 months in marine field tests. The gel design provides a new paradigm for sustainable and shear-stable lubrication in marine environment.

Care and Management of Voice Change in Thyroid Surgery: Korean Society of Laryngology, Phoniatrics and Logopedics Clinical Practice Guideline.

Voice change is a common complaint after thyroid surgery and has a significant impact on quality of life. The Korean Society of Laryngology, Phoniatrics and Logopedics assembled a task force to establish guideline recommendations on education, care, and management related to thyroid surgery. The guideline recommendations encompass preoperative voice education, management of anticipated voice change during surgery, and comprehensive voice care after thyroid surgery, and include in-depth information and up-to-date knowledge based on validated literature. The committee constructed 14 key questions (KQs) in three categories-preoperative (KQ 1-2), intraoperative (KQ 3-8), and postoperative (KQ 9-14) management-and developed 18 evidence-based recommendations. The Delphi survey reached an agreement on each recommendation. A detailed evidence profile is presented for each recommendation. The level of evidence for each recommendation was classified as high-quality, moderate-quality, or low-quality. The strength of each recommendation was designated as strong or weak considering the level of evidence supporting the recommendation. The guidelines are primarily targeted toward physicians who treat thyroid surgery patients and speech-language pathologists participating in patient care. These guidelines will also help primary care physicians, nurses, healthcare policymakers, and patients improve their understanding of voice changes and voice care after thyroid surgery.

Nicotine Affects Murine Aortic Stiffness and Fatigue Response During Supraphysiological Cycling.

Nicotine exposure is a major risk factor for several cardiovascular diseases. Although the deleterious effects of nicotine on aortic remodeling processes have been studied to some extent, the biophysical consequences are not fully elucidated. In this investigation, we applied quasi-static and dynamic loading to quantify ways in which exposure to nicotine affects the mechanical behavior of murine arterial tissue. Segments of thoracic aortas from C57BL/6 mice exposed to 25 mg/kg/day of subcutaneous nicotine for 28 days were subjected to uniaxial tensile loading in an open-circumferential configuration. Comparing aorta segments from nicotine-treated mice relative to an equal number of control counterparts, stiffness in the circumferential direction was nearly twofold higher (377 kPa ± 165 kPa versus 191 kPa ± 65 kPa, n = 5, p = 0.03) at 50% strain. Using a degradative power-law fit to fatigue data at supraphysiological loading, we observed that nicotine-treated aortas exhibited significantly higher peak stress, greater loss of tension, and wider oscillation band than control aortas (p ≤ 0.01 for all three variables). Compared to simple stress relaxation tests, fatigue cycling is shown to be more sensitive and versatile in discerning nicotine-induced changes in mechanical behavior over many cycles. Supraphysiological fatigue cycling thus may have broader potential to reveal subtle changes in vascular mechanics caused by other exogenous toxins or pathological conditions.

Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis.

OBJECTIVE: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA. METHODS: This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0-W24 results were previously reported; we present W26-W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity. RESULTS: Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive. CONCLUSION: Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292.

Efficacy and Safety of CT-P10 Versus Rituximab in Untreated Low-Tumor-Burden Follicular Lymphoma: Final Results of a Randomized Phase III Study.

INTRODUCTION: This double-blind, parallel-group, active-controlled phase III trial (NCT02260804) assessed CT-P10 and rituximab safety and efficacy in patients with previously untreated low-tumor-burden follicular lymphoma (LTBFL), including after a single switch from rituximab to CT-P10. PATIENTS AND METHODS: LTBFL patients were randomized (1:1) to receive CT-P10 or rituximab (375 mg/m2 intravenously; day 1 of 4 7-day cycles). Patients achieving disease control entered a 2-year maintenance period. CT-P10 or rituximab were administered every 8 weeks (6 cycles) in year 1; all patients could receive CT-P10 (every 8 weeks; 6 cycles) in year 2. Secondary endpoints (reported here) were overall response rate (ORR) during the study period, progression-free survival (PFS), time to progression (TTP), and overall survival (OS). Safety and immunogenicity were evaluated. RESULTS: Between  November 9, 2015 and  January 4, 2018, 258 patients were randomized (130 for CT-P10; 128 for rituximab). ORR was similar between groups over the study period (CT-P10: 88%; rituximab: 87%). After 29.2 months' median follow-up, median PFS, TTP, and OS were not estimable; 24-month Kaplan-Meier estimates suggested similarity between groups. Overall, 114 (CT-P10: 88%), and 104 (rituximab: 81%) patients experienced treatment-emergent adverse events. The single switch was well tolerated. CONCLUSION: These updated data support therapeutic similarity of CT-P10 and rituximab and support the use of CT-P10 monotherapy for previously untreated LTBFL.

An automatic screening method for strabismus detection based on image processing.

PURPOSE: This study aims to provide an automatic strabismus screening method for people who live in remote areas with poor medical accessibility. MATERIALS AND METHODS: The proposed method first utilizes a pretrained convolutional neural network-based face-detection model and a detector for 68 facial landmarks to extract the eye region for a frontal facial image. Second, Otsu's binarization and the HSV color model are applied to the image to eliminate the influence of eyelashes and canthi. Then, the method samples all of the pixel points on the limbus and applies the least square method to obtain the coordinate of the pupil center. Lastly, we calculated the distances from the pupil center to the medial and lateral canthus to measure the deviation of the positional similarity of two eyes for strabismus screening. RESULT: We used a total of 60 frontal facial images (30 strabismus images, 30 normal images) to validate the proposed method. The average value of the iris positional similarity of normal images was smaller than one of the strabismus images via the method (p-value<0.001). The sample mean and sample standard deviation of the positional similarity of the normal and strabismus images were 1.073 ± 0.014 and 0.039, as well as 1.924 ± 0.169 and 0.472, respectively. CONCLUSION: The experimental results of 60 images show that the proposed method is a promising automatic strabismus screening method for people living in remote areas with poor medical accessibility.

Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial.

PURPOSE: Equivalent efficacy was demonstrated for the biosimilar CT-P6 and trastuzumab following neoadjuvant therapy for patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Following adjuvant treatment, efficacy and safety were comparable between treatments. We report updated safety and efficacy data after up to 3 years' follow-up. METHODS: Following neoadjuvant chemotherapy with CT-P6/trastuzumab, patients underwent surgery and continued receiving adjuvant CT-P6/trastuzumab. The primary endpoint (previously reported) was pathological complete response. Time-to-event analyses (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]), study drug-related and cardiac adverse events, and immunogenicity were assessed during post-treatment follow-up. RESULTS: Most patients entered the follow-up period (CT-P6: 259 [95.6%]; trastuzumab: 269 [96.8%]). After a median follow-up of 38.7 (CT-P6) and 39.6 (trastuzumab) months, medians were not reached for time-to-event parameters; estimated hazard ratios (HRs) and 3-year survival rates were similar between groups. Estimated HRs (95% confidence intervals) for CT-P6 versus trastuzumab were 1.23 (0.78-1.93) for DFS, 1.31 (0.86-2.01) for PFS, and 1.10 (0.57-2.13) for OS (intention-to-treat population). Safety findings were comparable between groups for the overall study and follow-up period, including study drug-related cardiac disorders (CT-P6: 22 [8.1%] patients; trastuzumab: 24 [8.6%] patients [overall]) and decreases in left ventricular ejection fraction. Immunogenicity was similar between groups. CONCLUSION: The similarity of the time-to-event analyses between CT-P6 and trastuzumab supports the equivalence in terms of efficacy established for the primary endpoint. CT-P6 was well tolerated, with comparable safety and immunogenicity to trastuzumab. ClinicalTrials.gov: NCT02162667 (registered June 13, 2014).

Comparative efficacy of subcutaneous (CT-P13) and intravenous infliximab in adult patients with rheumatoid arthritis: a network meta-regression of individual patient data from two randomised trials.

BACKGROUND: A subcutaneous (SC) formulation of infliximab biosimilar CT-P13 is approved in Europe for the treatment of adult patients with rheumatoid arthritis (RA). It may offer improved efficacy versus intravenous (IV) infliximab formulations. METHODS: A network meta-regression was conducted using individual patient data from two randomised trials in patients with RA, which compared CT-P13 SC with CT-P13 IV, and CT-P13 IV with reference infliximab IV. In this analysis, CT-P13 SC was compared with CT-P13 IV, reference infliximab IV and pooled data for both reference infliximab IV and CT-P13 IV. Outcomes included changes from baseline in 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI), and rates of remission, low disease activity or clinically meaningful improvement in functional disability per Health Assessment Questionnaire-Disability Index (HAQ-DI). RESULTS: The two studies enrolled 949 patients with RA; pooled data for 840 and 751 patients were evaluable at weeks 30 and 54, respectively. For the CT-P13 SC versus pooled IV treatment arm comparison, differences in changes from baseline in DAS28-CRP (- 0.578; 95% confidence interval [CI] - 0.831, - 0.325; p < 0.0001), CDAI (- 3.502; 95% CI - 5.715, - 1.289; p = 0.002) and SDAI (- 4.031; 95% CI - 6.385, - 1.677; p = 0.0008) scores at 30 weeks were statistically significant in favour of CT-P13 SC. From weeks 30 to 54, the magnitude of the differences increased and remained statistically significant in favour of CT-P13 SC. Similar results were observed for the comparison of CT-P13 SC with CT-P13 IV and with reference infliximab IV. Statistically significant differences at week 30 favoured CT-P13 SC over the pooled IV treatment arms for the proportions of patients achieving EULAR-CRP good response, American College of Rheumatology (ACR) 50 and ACR70 responses, DAS28-CRP-defined remission, low disease activity (DAS28-CRP, CDAI and SDAI criteria) and clinically meaningful HAQ-DI improvement. CONCLUSIONS: CT-P13 SC was associated with greater improvements in DAS28-CRP, CDAI and SDAI scores and higher rates of clinical response, low disease activity and clinically meaningful improvement in functional disability, compared with CT-P13 IV and reference infliximab IV. TRIAL REGISTRATION: EudraCT, 2016-002125-11 , registered 1 July 2016; EudraCT 2010-018646-31 , registered 23 June 2010.