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Journal of Translational Medicine Dec 2023Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy...
BACKGROUND
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy resistance. Cirsiliol is a recently found flavonoid with anti-tumor effects in various tumors. However, the effects of cirsiliol in the regulation of aggressive behaviors of OS remain unknown.
METHODS
The effect of cirsiliol on the proliferation of OS cells was detected using a cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining, while cell apoptosis was detected using flow cytometry. Immunofluorescence was applied to visualize the expression level of the mitochondria, lysosomes and microtubule-associated protein light chain 3 (LC3). A computational molecular docking technique was used to predict the interaction between cirsiliol and the AKT protein. The impact of cirsiliol on resistance was investigated by comparing it between a methotrexate (MTX)-sensitive OS cell line, U2OS, and a MTX-resistant OS cell line, U2OS/MTX. Finally, in situ xenogeneic tumor models were used to validate the anti-tumor effect of cirsiliol in OS.
RESULTS
Cirsiliol inhibited cell proliferation and induced apoptosis in both U2OS and U2OS/MTX300 OS cells. In addition, treatment with cirsiliol resulted in G2 phase arrest in U2OS/MTX300 and U2OS cells. Cell fluorescence probe staining results showed impaired mitochondria and increased autophagy in OS cells after treatment with cirsiliol. Mechanistically, it was found that cirsiliol targeted AKT by reducing the phosphorylation of AKT, which further activated the transcriptional activity of forkhead Box O transcription factor 1 (FOXO1), ultimately affecting the function of OS cells. Moreover, in situ tumorigenesis experiments showed that cirsiliol inhibited the tumorigenesis and progression of OS in vivo.
CONCLUSIONS
Cirsiliol inhibits OS cell growth and induces cell apoptosis by reducing AKT phosphorylation and further promotes FOXO1 expression. These phenomena indicate that cirsiliol is a promising treatment option for OS.
Topics: Child; Humans; Adolescent; Methotrexate; Proto-Oncogene Proteins c-akt; Molecular Docking Simulation; Cell Line, Tumor; Osteosarcoma; Apoptosis; Cell Proliferation; Bone Neoplasms; Carcinogenesis; Autophagy; Mitochondria; Forkhead Box Protein O1
PubMed: 38087310
DOI: 10.1186/s12967-023-04682-7 -
Drug and Therapeutics Bulletin Nov 2023Medicines and Healthcare products Regulatory Agency. Methotrexate: advise patients to take precautions in the sun to avoid photosensitivity reactions. 2023;17:2.
Medicines and Healthcare products Regulatory Agency. Methotrexate: advise patients to take precautions in the sun to avoid photosensitivity reactions. 2023;17:2.
Topics: Humans; Methotrexate; Drug-Related Side Effects and Adverse Reactions; Government Agencies
PubMed: 37845001
DOI: 10.1136/dtb.2023.000056 -
Alimentary Pharmacology & Therapeutics Jan 2024
Topics: Humans; Crohn Disease; Methotrexate; Immunosuppressive Agents; Polyglutamic Acid
PubMed: 38085937
DOI: 10.1111/apt.17743 -
Journal of the American Academy of... Jun 2024For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies...
Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.
BACKGROUND
For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis.
OBJECTIVE
To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines.
METHODS
Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts.
RESULTS
Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination.
LIMITATIONS
Studies regarding infection rates after vaccination are lacking.
CONCLUSION
Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.
Topics: Humans; Psoriasis; Arthritis, Psoriatic; Delphi Technique; Biological Products; Administration, Oral; Consensus; Vaccination; Adult; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Methotrexate; Dermatologic Agents
PubMed: 38331098
DOI: 10.1016/j.jaad.2023.12.070 -
Clinical Gastroenterology and... Aug 2023Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes (early pregnancy loss [EPL], preterm birth [PB], congenital malformations [CM]).
METHODS
We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios (ORs) of outcomes were pooled and analyzed using a random effects model.
RESULTS
Ten studies reporting semen parameters (268 patients with IBD) and 16 studies reporting adverse pregnancy outcomes (over 25,000 patients with IBD) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared with nonexposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to nonexposed patients (5%). Biologic use was not associated with risk of EPL (OR, 1.26; I = 0%; P = .12), PB (OR, 1.10; I = 0%; P = .17), or CM (OR, 1.03; I = 0%; P = .69). Thiopurine use was not associated with risk of EPL (OR, 1.31; I = 19%; P = .17), PB (OR, 1.05; I = 0%; P = .20), or CM (OR, 1.07; I = 7%; P = .34). Methotrexate use was not associated with risk of PB (OR, 1.06; I = 0%; P = .62) or CM (OR, 1.03; I = 0%; P = .81).
CONCLUSIONS
Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.
Topics: Pregnancy; Female; Male; Humans; Infant, Newborn; Methotrexate; Premature Birth; Semen; Inflammatory Bowel Diseases; Abortion, Spontaneous; Fertility
PubMed: 35870769
DOI: 10.1016/j.cgh.2022.07.008 -
Acta Obstetricia Et Gynecologica... Sep 2023Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment.
MATERIAL AND METHODS
We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times.
TRIAL REGISTRATION NUMBER
PROSPERO: CRD42021214093.
RESULTS
1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group.
CONCLUSIONS
Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
Topics: Pregnancy; Humans; Female; Methotrexate; Watchful Waiting; Pregnancy, Tubal; Pregnancy, Ectopic; Chorionic Gonadotropin; Abortifacient Agents, Nonsteroidal; Retrospective Studies
PubMed: 37345445
DOI: 10.1111/aogs.14617 -
Seminars in Arthritis and Rheumatism Feb 2024IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the... (Review)
Review
INTRODUCTION
IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the orbit and ocular adnexa. Although a few cases of uveitis have been reported, the exact pattern of IgG4-related intraocular manifestations remains unclear. Here, we report on a nationwide French multicenter cohort of patients with IgG4-RD and uveitis and conducted a literature review.
METHODS
Patients with uveitis and a concomitant definite diagnosis of IgG4-RD (Revised Comprehensive Diagnostic criteria, American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD, International Consensus Diagnostic Criteria for auto-immune pancreatitis, or diagnostic criteria for IgG4-related hypophysitis), were screened from our national IgG4-RD and systemic fibrosis database. Concomitantly, we conducted a PubMed literature review and selected cases of definite IgG4-RD with uveitis.
RESULTS
We reported on 16 patients (8 from our database and 8 from the literature) and a total of 30 episodes of uveitis. Uveitis cases represented 3 % of total IgG4-RD patients in the national database on IgG4-RD and systemic fibrosis. Uveitis was inaugural in IgG4-RD in 4/16 cases (25 %) (appearing before any other IgG4-related symptom, at a median of 9 months), occurred concurrently to other IgG4-related symptoms in 9/16 cases (56 %) (at a median of 15 months before IgG4-RD diagnosis), and appeared during follow up in 3/16 patients (19 %) (at a median of 57 months after first IgG4-related symptoms). When uveitis occurred during follow up, it was associated with IgG4-RD manifestations in other organs in 6/9 patients (67 %). Uveitis was bilateral in 8/16 cases (50 %) and granulomatous in 5/10 cases (50 %). It was anterior in 8/13 (62 %), intermediate in 3/13 (23 %), and global (panuveitis) in 4/13 patients (31 %). Median serum IgG4 at diagnosis was 3.2 g/L. Median follow up time was of 6 years, during which 8/16 patients (50 %) experienced at least one relapse of uveitis. Treatment data was available for 29/30 uveitis flares. Steroids were used in 28/29 episodes of uveitis (97 %), leading to remission of uveitis in 16/28 cases (57 %). Methotrexate and rituximab (in combination with systemic steroids) were administered as second- or third-line therapy in 6/29 (21 %) and 5/29 (17 %) episodes of uveitis, respectively, and led to remission of uveitis in 4/6 cases (67 %) and 4/5 cases (80 %), respectively. One third of uveitides required at least two different lines of treatment for remission induction (mainly a combination of both systemic steroids and methotrexate or rituximab).
DISCUSSION AND CONCLUSIONS
Uveitis may be one of the initial symptoms of IgG4-RD, and IgG4-RD should be considered in the diagnostic workup of uveitis. Its early onset in IgG4-RD may help with early diagnosis and treatment of the disease. Steroid monotherapy may be sufficient to treat IgG4-related uveitis, yet relapses were frequent (50 %) and ultimately a third of patients required at least two lines of treatment. Hence, steroid-sparing agents can be considered at early stages of the disease, particularly for patients with a high risk of relapse or steroid-related complications.
Topics: Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Rituximab; Methotrexate; Uveitis; Fibrosis; Recurrence; Steroids; Multicenter Studies as Topic
PubMed: 38000318
DOI: 10.1016/j.semarthrit.2023.152278 -
Expert Opinion on Pharmacotherapy 2024Rheumatoid arthritis (RA) is a complex autoimmune disease that affects millions of people worldwide, with a systemic impact. This review explores the role of... (Review)
Review
INTRODUCTION
Rheumatoid arthritis (RA) is a complex autoimmune disease that affects millions of people worldwide, with a systemic impact. This review explores the role of non-biological conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in its management.
AREAS COVERED
We discuss the effectiveness and safety of key csDMARDs such as Nonsteroidal anti-inflammatory drugs, corticosteroids, Hydroxychloroquine, Sulfasalazine, Methotrexate, and Leflunomide in relieving symptoms and slowing the progression of the disease. We also highlight the importance of combination therapy using csDMARDs, supported by clinical studies demonstrating the benefits of various csDMARD combinations. Early intervention with these drugs is emphasized to prevent joint damage, improve clinical symptoms, and enhance patient outcomes.
EXPERT OPINION
Overall, csDMARDs have proven pivotal in managing RA, providing cost-effective and versatile treatment options. We acknowledge the advantages of biologics but highlight the associated challenges, making the choice between non-biological and biological drugs a personalized decision. This comprehensive overview aims to provide a deeper understanding of RA treatment strategies, contributing to improving the quality of life for patients with this chronic condition.
Topics: Humans; Biological Products; Quality of Life; Arthritis, Rheumatoid; Antirheumatic Agents; Methotrexate; Drug Therapy, Combination; Treatment Outcome
PubMed: 38126739
DOI: 10.1080/14656566.2023.2297798 -
PloS One 2023Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective treatment for RA, the effects that bDMARDs have on integumentary, cardiac, and immune systems and the high costs associated with these treatments, make that mesenchymal stem cell-based therapies (MSCs) for RA are being considered potential treatment methods. This work analyses the performance in safety and efficacy terms of MSCs techniques.
METHODS AND FINDING
A literature search was performed in PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey databases from inception to October 28, 2022. Three randomized controlled trials (RCTs) and one non-randomized controlled trial (non-RCTs), including 358 patients met our inclusion criteria and were included in qualitative synthesis; only RCTs were eligible for quantitative synthesis (meta-analysis). Meta-analysis of adverse events (AE) in RCTs showed no significant differences in the incidence of AE in the MSCs group compared to the control group (Risk ratio: 2.35; 95% CI, 0.58 to 9.58; I2 = 58.80%). The pooled Risk ratio for non-serious and serious adverse events showed no statistical difference between intervention and control groups concerning the incidence of non-serious and serious adverse events (Risk ratio: 2.35; 95% CI, 0.58 to 9.51; I2 = 58.62%) and (Risk ratio: 1.10; 95% CI, 0.15 to 7.97; I2 = 0.0%) respectively. The Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS28) decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed; however, this improvement was not shown in the studies after 12 months of follow-up without continuous treatment administration.
CONCLUSION
This Systematic review and meta-analysis showed a favorable safety profile, without life-threatening events in subjects with RA, and a trend toward clinical efficacy that must be confirmed through high-quality RCTs, considerable sample size, and extended follow-up in subjects with RA.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Methotrexate; Treatment Outcome; Controlled Clinical Trials as Topic
PubMed: 37498842
DOI: 10.1371/journal.pone.0284828 -
Journal of Cutaneous Medicine and... 2024Prurigo nodularis (PN) is a complex chronic skin disease characterized by severe pruritic nodules. PN is often associated with mental health disorders and chronic...
BACKGROUND
Prurigo nodularis (PN) is a complex chronic skin disease characterized by severe pruritic nodules. PN is often associated with mental health disorders and chronic medical comorbidities. Until recently, PN treatment has been challenging and difficult.
OBJECTIVES
This study aims to describe the demographic, clinical characteristics, and comorbidities associated with PN. Also, we aim to describe the effectiveness of systemic therapies, including methotrexate, cyclosporine, and narrow band ultraviolet (NB-UVB) in adult patients with PN.
METHODS
This is a retrospective chart review of adult patients diagnosed with PN at Hamilton Health Science Center and/or McMaster University in Hamilton, Ontario, between 2015 and 2023.
RESULTS
The study included 81 patients (57% female). The mean age was 52.8 years, and the mean age of PN diagnosis was 50 years. Reported symptoms included: itching (100%), dry skin (53%), pain (17%), and burning sensation (5%). Lower and upper extremities were the most common areas involved in 93% and 69%, respectively. Mental health disorders were present in 79% of patients, with depression (58%) and anxiety (52%) being the most common. Atopic dermatitis was the most common skin comorbidity noted. Treatments used included cyclosporine, and NB-UVB, and MTX, which resulted in significant improvement of pruritus in 38%, 35%, and 31% of patients, respectively, at week 16.
CONCLUSIONS
PN is associated with increased risk of mental health disorders and other medical comorbidities. Cyclosporine, methotrexate, and NB-UVB therapy may be effective treatment options, however clinicians must consider the potential short- and long-term adverse effects of these treatments.
Topics: Adult; Humans; Female; Middle Aged; Male; Retrospective Studies; Prurigo; Methotrexate; Pruritus; Treatment Outcome; Cyclosporins
PubMed: 38281092
DOI: 10.1177/12034754241227808