The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam.

OBJECTIVES: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. METHODS: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan-Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). RESULTS: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. CONCLUSION: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam / El impacto de COVID-19 y otros factores en el estado de uso de las terapias farmacológicas biológicas para la artritis reumatoide: un estudio de Vietnam

Objectives: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. Methods: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan–Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). Results: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. Conclusion: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.(AU)

Objetivos: Describir el estado del uso de fármacos antirreumáticos modificadores de la enfermedad biológica (bDMARD) para tratar la artritis reumatoide (AR) y los factores relacionados. Además, el estudio determinó el impacto de COVID-19 en el uso de bDMARD. Métodos: Este es un estudio transversal que incluyó a 219 pacientes con AR mayores de 18 años. El método Kaplan-Meier y la prueba Log-rank (p<0,05) se usaron para estimar el tiempo de retención y compararlo entre diferentes tiempos. El análisis de regresión de Cox se utilizó para determinar los factores que afectan el tiempo de retención de los medicamentos biológicos (p<0,05). Resultados: De 1.967 cursos de tratamiento, hubo 149 (7,6%) interrupciones del fármaco, 760 (38,6%) extensiones de dosis y 64 (3,3%) cambios de fármaco. Nivel de enfermedad moderado y elección del factor de necrosis tumoral (TNF) inhibidores inicialmente se asociaron con el tiempo de retención de COVID-19. Las discontinuaciones de los medicamentos y las extensiones de las dosis aumentaron después de la aparición de COVID-19. El tiempo de retención durante COVID-19 fue significativamente diferente del pre-COVID-19. Género, tipo de bDMARD de primer uso, convencional DMARD sintéticos (csDMARDs) y el estado de uso de corticoides, los niveles de actividad de la enfermedad se asociaron con el tiempo de retención. Conclusión: La presencia de COVID-19 tiene un efecto significativo en el estado de uso del medicamento biológico. Se necesitan más estudios longitudinales para aclarar la relación entre COVID-19 y el uso de fármacos, así como los factores relacionados.(AU)

Atherosclerosis in Vietnamese patients with systemic sclerosis and its relationship to disease and traditional risk factors.

Objective: The aim of this study was to determine the frequency of clinical and subclinical atherosclerosis in Vietnamese patients with SSc and the risk factors for subclinical atherosclerosis. Methods: A case-control study of 46 patients with SSc who met the ACR criteria for the disease and 42 healthy age- and sex-matched controls of Kinh ethnicity was conducted. Clinical data including cardiovascular disease (CVD) events were collected. Serum levels of blood lipids and high-sensitivity CRP were determined. Carotid artery intima-media thickness (IMT) and carotid plaques were measured by carotid Doppler ultrasonography. Results: Patients with SSc, of whom 96% had dcSSc, reported a higher number of CVD events compared with the controls (21.7 vs 0%; P = 0.0065). They exhibited low serum levels of high-density lipoprotein cholesterol and high levels of total cholesterol compared with controls (P = 0.01 and P = 0.03, respectively). Common carotid artery IMT was significantly higher in SSc patients compared with controls [mean (s.d.): 0.61 (0.12) vs 0.47 (0.07) mm; P < 0.0001]. Carotid artery IMT in SSc showed significant positive correlations with age, disease duration, total cholesterol and low-density lipoprotein cholesterol (P < 0.05). Thirteen patients with SSc (28.3%) but no controls had carotid atherosclerotic plaques. Patients with plaque had a higher mean modified Rodnan skin score and higher mean IMT compared with patients without plaque. Conclusion: We confirmed an increased risk of CVD events and signs of subclinical atherosclerosis in patients with SSc of Kinh ethnicity and both traditional and disease-related risk factors for CVD.

Nanohybrid biodegradable scaffolds for TGF-ß3 release for the chondrogenic differentiation of human mesenchymal stem cells.

An ideal scaffold for bone tissue engineering should have chondroinductive, biodegradable, and biocompatible properties, as well as the ability to absorb and slowly release the biological molecules. In order to develop such a system to support bone tissue regeneration, in the present study, we developed a three-dimensional poly(L-lactic-co-glycolic acid) (PLGA)/Polycaprolactone (PCL) nanohybrid scaffold embedded with PLGA macroparticles (MPs) conjugated with TGF-ß3 for the growth and chondrogenic differentiation of human mesenchymal stem cells (hMSCs). First, a microfluidic device was used to fabricate porous PLGA MPs with the sizes ranging from 10 to 50 µm. Next, the PLGA MPs were loaded with TGF-ß3, mixed with PCL solution, and then electrospun to obtain PLGA-TGF-ß3 MPs/PCL nanohybrid scaffold. Our results demonstrated that PLGA MPs fabricated using a microfluidic-based approach exhibited enhanced conjugation of TGF-ß3 with over 80% loading efficiency and sustained release of TGF-ß3. Furthermore, the results of glycosaminoglycan (GAG) content measurement and Safranin O staining revealed that the PLGA-TGF-ß3 MPs and PLGA-TGF-ß3 MPs/PCL nanohybrid scaffold can promote the proliferation and chondrogenic differentiation of hMSCs in vitro. Therefore, the PLGA-TGF-ß3 MPs/PCL nanohybrid scaffold could pave the way for cartilage regeneration and have wide applications in regenerative medicine.

Microfluidic Approach to Generate a Tadpole-Egg-Shaped Alginate Fiber and Its Application in Tissue Engineering.

Herein, we introduce a facile microfluidic technique to produce a hybrid alginate fiber with a tadpole-egg shape. A triple-flow polydimethylsiloxane microfluidic device was constructed to allow the formation of oil droplets inside the alginate stream and was instantaneously gelated with the coaxially adjacent CaCl2. The fiber entrapping the uniform oil droplets was dehydrated, leading to the formation of a distinct tadpole-egg-shaped structure. A series of diverse fiber architectures was fabricated in a controlled manner based on the flow rates of the relevant flows. The tadpole-egg-shaped alginate fibers were employed as building blocks to create a three-dimensional microwell template for cell cultures. First, the tadpole-egg-shaped alginate fibers containing the oil droplets were half-dipped into a melted agarose solution. After the solidification of the agarose gel, the alginate fibers were degraded by an ethylenediaminetetraacetic acid (EDTA) solution to generate the hemispherical microwells. Mesenchymal stem cells (MSCs) were cultured in the microwells to generate spheroids, which were induced into chondrocytes using transforming growth factor-ß3. The formed MSC spheroids exhibited a relatively high ratio of cell viability with more than 95% live cells after 14 days of culture. The success of the chondrogenic differentiation was proven based on staining (Safranin O) and the glycosaminoglycan levels. The latter was significantly higher in spheroids that were induced to form chondrocytes compared to those that were not induced after 21 days of differentiation. Second, we investigated the potential of the tadpole-egg-shaped alginate fibers as microcarriers for applications in drug delivery and implantable technologies. It was revealed that the degradation of the Ca-alginate wall of the hybrid fibers to release the oil droplets required an EDTA solution with a concentration of 500 mM for a 15 min period. This result can be used to further develop the tadpole-egg-shaped alginate fibers as uniform microcarriers with multiple compartments.

Adipose Tissue Stem Cells for Therapy: An Update on the Progress of Isolation, Culture, Storage, and Clinical Application.

Adipose tissue stem cells (ASCs), known as multipotent stem cells, are most commonly used in the clinical applications in recent years. Adipose tissues (AT) have the advantage in the harvesting, isolation, and expansion of ASCs, especially an abundant amount of stem cells compared to bone marrow. ASCs can be found in stromal vascular fractions (SVF) which are easily obtained from the dissociation of adipose tissue. Both SVFs and culture-expanded ASCs exhibit the stem cell characteristics such as differentiation into multiple cell types, regeneration, and immune regulators. Therefore, SVFs and ASCs have been researched to evaluate the safety and benefits for human use. In fact, the number of clinical trials on ASCs is going to increase by years; however, most trials are in phase I and II, and lack phase III and IV. This systemic review highlights and updates the process of the harvesting, characteristics, isolation, culture, storage, and application of ASCs, as well as provides further directions on the therapeutic use of ASCs.

Safety of a quadrivalent meningococcal conjugate vaccine in healthy subjects aged 9 months to 55 years in Vietnam.

PURPOSE: Meningococcal disease is a major global health concern due to its severe and sudden clinical manifestations, devastating long-term sequelae, and predominance in younger age groups. This study evaluated the safety of a quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D; Menactra) in participants aged 9 months to 55 years in Vietnam. METHODS: This was an open-label, single-arm study conducted between June and December 2016. Participants received one 0.5-mL dose of the vaccine, and those aged 9 to 23 months received a second 0.5-mL dose 3 months later. Participants (or their parents or legal guardians) reported adverse events during the 28 days after each dose. RESULTS: The study included 112 participants aged 9 to 23 months and 112 participants aged 2 to 55 years. Of these 224 participants, 100 (44.6%) had one or more solicited reactions within 7 days following any MenACWY-D dose, mostly injection site pain, lost appetite (in 9 to 23-month-olds), and malaise (in 2 to 55-year-olds). Most solicited reactions were of mild or moderate intensity and resolved within 3 days. Five participants had unsolicited adverse reactions (ARs), two of which (tonsillitis and febrile convulsion), in 9 to 23-month-olds, were considered by the investigator as serious adverse events related to the vaccine. No immediate unsolicited ARs, severe unsolicited nonserious ARs, or unsolicited injection site reactions were reported, and both participants who experienced vaccine-related serious adverse events recovered. CONCLUSION: Consistent with studies in other countries, MenACWY-D had an acceptable safety profile in individuals from Vietnam aged 9 months to 55 years (WHO Universal Trial Number: U1111-1143-9207).

Microfluidic approach for the fabrication of cell-laden hollow fibers for endothelial barrier research.

This study reports an advanced approach to effectively generate hollow fibers in a triple-flow polydimethylsiloxane (PDMS) microfluidic device based on the gelation of alginate induced with CaCl2 inside a coaxial flow system. Two PDMS replicas with a semi-cylindrical microchannel were assembled to obtain a complete microchannel with a circular cross-section, which allowed the formation of mild and continuous coaxial flows for the fabrication of hollow fibers without employing complex glass microcapillaries. Mineral oil was introduced into the central flow to serve as an inert space inside the Ca-alginate wall. This was used to maintain the consistent formation of the hollow core of the microfiber and to easily transport fluid through the lumen structure in subsequent applications. The hollow fibers exhibited characteristics such as flexibility while showing robust mechanical strength, high permeability, and biocompatibility, and were used as scaffolds for the attachment and proliferation of human umbilical vein endothelial cells (HUVECs) to mimic a blood vessel. The fully covered HUVEC fibers were further integrated into a neurovascular system and co-cultured with astrocytes forming an on-chip blood brain barrier (BBB) platform. The use of this neurovascular model for drug testing will pave the way for developing or synthesizing a new drug that can cross the BBB in the human brain.