Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review

Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.     

甲氨蝶呤皮下注射治疗应用与展望

【摘要】 研究表明，甲氨蝶呤皮下注射较口服途径可以获得更快、更好的吸收和更高的血药浓度以及较低的生物利用度变异度。在类风湿关节炎患者和银屑病患者，甲氨蝶呤皮下注射的疗效显著优于口服途径，并且胃肠道不良反应发生率更低。对于甲氨蝶呤口服疗效欠佳或者不耐受的患者，改为皮下注射后仍然可以获得较好的治疗反应。甲氨蝶呤皮下注射可以作为生物制剂使用前的治疗选择，可节省大量费用。总之，甲氨蝶呤皮下注射具有较好的临床应用前景。     

输卵管妊娠治疗方式及其对未来生育影响的研究进展

输卵管妊娠是一种临床常见的妇科急腹症。输卵管妊娠如能在包块尚未破裂前早期诊断，其相关的病死率大大降低。输卵管妊娠的治疗方式有很多，无论哪种治疗方式，都会导致患者生育功能的下降。临床中对于有生育要求的患者，选择哪种治疗方式更好地保护患者的生育功能并减少并发症仍是有争议的话题。近年有学者做了大量研究比较输卵管妊娠不同治疗方式的并发症及其对患者未来生育前景的影响，甚至提出更新的治疗方式以弥补传统治疗方式的不足。现就输卵管妊娠的治疗方式、并发症及对未来生育的影响的研究进展进行综述。     

CD8-positive T-cell lymphoproliferative disorder associated with Epstein-Barr virus-infected B-cells in a rheumatoid arthritis patient under methotrexate treatment

We report a 48-year-old female who developed lymphoproliferative disorder (LPD) during treatment of rheumatoid arthritis (RA) with methotrexate (MTX). She presented with multiple tumors in the cervical lymph nodes (LNs), multiple lung shadows and round shadows in both kidneys with pancytopenia and a high CRP level. The LN showed CD8-positive T-cell LPD associated with Epstein-Barr (EB) virus-infected B-cells. Clonality assays for immunoglobulin (Ig) heavy chain and T-cell receptor gamma (TCRγ) were negative. The cessation of MTX without chemotherapy resulted in the complete disappearance of the tumors and abnormal clinical features. We compared this case with previously published ones and discuss the pathological findings, presuming that the proliferation of CD8 T-cells was a reactive manifestation to reactivated EB virus-infected B-cells.     

Rheumatoid arthritis: Perioperative management of biologics and DMARDs

ObjectiveArthroplasty remains prevalent for patients with rheumatoid arthritis (RA), but outcomes are not equivalent to patients with osteoarthritis, and complications including infection are increased. The objective of this article is to review the current evidence supporting perioperative medication management. Challenges are discussed such as continuing potent disease-modifying therapy (DMARDs) and biologics, which may increase infection risk, versus withholding these medications, which may result in disease flares.MethodsPublished literature regarding arthroplasty in RA has been reviewed and discussed.ResultsSome DMARDs such as methotrexate and hydroxychloroquine appear safe in the perioperative period. Anti-TNFα biologics should be withheld due to increase in infection risk, while the impact of rituximab and abatacept on infection risk has not been as clearly defined.ConclusionThis article provides an overview of arthroplasty in RA, summarizes the evidence supporting perioperative medication management including corticosteroids, and identifies areas where further study is needed.