Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn's disease: a Korean nationwide population-based study.

Background: Although immunomodulators are widely prescribed in patients with Crohn's disease (CD), it is unclear whether there is a difference in treatment outcomes between thiopurines and methotrexate (MTX). Objective: To compare the risk of clinical failure between thiopurines and MTX in bio-naïve patients with CD. Design: Nationwide, population-based study. Methods: We used claims data from the Korean National Health Insurance Service. After inverse probability of treatment weighting, logistic regression and Cox proportional hazard analyses were used to evaluate the risk of clinical failure in bio-naïve patients with CD treated with thiopurine (thiopurine group) or MTX (MTX group). Results: Overall, 10,296 adult and pediatric patients with CD [9912 (96.3%) and 384 (3.7%) in the thiopurine and MTX groups, respectively] were included. The odds ratios (ORs) of failure to induce remission were significantly higher in the MTX group than in the thiopurine group [adjusted OR (aOR), 1.115; 95% confidence interval (CI), 1.045-1.190; p = 0.001]. However, the opposite result was observed only in patients without concomitant steroid use: the MTX group had a lower risk of induction failure than the thiopurine group (aOR, 0.740; 95% CI, 0.673-0.813; p < 0.001). The risk of overall maintenance failure was higher in the MTX group than in the thiopurine group [adjusted hazard ratio (aHR), 1.117; 95% CI, 1.047-1.191; p = 0.001]. The risk of overall maintenance failure was higher in the standard-dose MTX group than in the low-dose MTX group (aHR, 1.296; 95% CI, 1.134-1.480; p < 0.001). There was no significant difference in the risk of maintenance failure according to the administration route of MTX. Conclusion: Thiopurine is more effective than MTX in inducing and maintaining remission in bio-naïve patients with CD; however, the concomitant use of steroids influences inducing remission.

Differences in treatment efficacy between thiopurine and methotrexate in patients with Crohn's disease who were not treated with biologics Immunomodulators (IMMs) used in the treatment of Crohn's disease (CD) include medications such as thiopurine and methotrexate (MTX). Although IMMs are widely prescribed for patients with CD, it remains unclear whether treatment outcomes differ according to the specific types and dosages of IMMs and administration routes of MTX. In this study, we investigated the risk of treatment failure between thiopurines and MTX in CD patients not undergoing biologic treatment. Patients treated with MTX had a higher risk of maintenance failure than those treated with thiopurines. There was no difference in the risk of treatment failure according to the dosage of thiopurine. However, the risk of maintenance failure was higher in patients receiving standard-dose MTX than in those receiving low-dose MTX. There was no difference in the risk of maintenance failure according to the administration route of MTX. Our study enriches the knowledge regarding the treatment efficacy of thiopurines and MTX for patients with CD and may help clinicians develop appropriate treatment plans.

Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

Psoriasis is a skin condition that not only affects the skin but is also linked to issues in the body's fat tissue, which can lead to inflammation and heart problems. The fat tissue in people with psoriasis contains various immune cells, contributing to obesity and insulin resistance. Research has found a strong connection between inflammation in fat tissues and cardiovascular problems in people with psoriasis. Specific substances released by fat tissue, like leptin, resistin, and adiponectin, can impact inflammation and cardiovascular health. Psoriasis patients often show increased levels of these substances. Treatment for psoriasis may influence cardiovascular health. Some studies suggest that certain medications, like methotrexate or TNF inhibitors, may lower the risk of heart events. However, there are also concerns about potential adverse effects, and further research is needed to fully understand how psoriasis treatments affect cardiovascular outcomes. To manage the cardiovascular risks associated with psoriasis, regular screening for heart-related issues is recommended. Lifestyle changes, such as a healthy diet, stress management, and smoking cessation, are also essential. Additionally, specific medications, like statins and metformin, may be beneficial in controlling cardiovascular risk factors in people with psoriasis. Despite advancements in understanding the relationship between psoriasis and cardiovascular health, there are still challenges. Research is ongoing to develop better screening guidelines and treatment strategies. Collaboration between dermatologists, rheumatologists, and cardiologists is crucial to address the complex nature of this condition and its impact on the heart.

Ameliorated in vitro anti-cancer efficacy of methotrexate loaded zinc oxide nanoparticles in breast cancer cell lines MCF-7 & MDA-MB-231 and its acute toxicity study.

Traditional therapies often struggle with specificity and resistance in case of cancer treatments. It is therefore important to investigate new approaches for cancer treatment based on nanotechnology. Zinc oxide nanoparticles (ZnONPs) are known to exhibit anti-cancer properties by inducing oxidative stress, apoptosis, and cell cycle arrest. Methotrexate (MTX) known anti-folate shows specificity to folate receptors (FR) and interrupts healthy functioning of cells. This study proposes the use of previously characterized biocompatible Methotrexate loaded Zinc oxide nanoparticles (MTX-ZnONPs) as a dual action therapeutic strategy against breast cancer cell lines, MCF-7 (MTX-sensitive) and MDA-MB-231 (MTX-resistant). To elucidate the cytotoxicity mechanism of MTX-ZnONPs in depth In-vitro study was carried out. In vitro assays, including cell cycle analysis, apoptosis assay, and western blot analysis to study the protein expression were performed. Results of these assays, further supported the anti-cancer activity of MTX-ZnONPs showing apoptotic and necrotic activity in MCF-7 and MDA-MB-231 cell line respectively. In vivo acute oral toxicity study to identify the LD50 in animals revealed no signs of toxicity and mortality up to 550 mg/kg body weight of animal, significantly higher LD50 values than anticipated therapeutic levels and safety of the synthesized nanosystem. The study concludes that MTX-ZnONPs exhibit anti-cancer potential against breast cancer cells offering a promising strategy for overcoming resistance.

Long-term clinical course of two rare cases of synovitis-acne-pustulosis-hyperostosis-osteomyelitis syndrome involving only unilateral femur.

Synovitis-acne-pustulosis-hyperostosis-osteomyelitis (SAPHO) syndrome is characterised by aseptic osteitis and is often complicated by pustular dermatitis, such as palmoplantar pustulosis or acne. Although bone lesions are most found in the anterior thoracic region or spine, femoral lesions are not well documented in the literature. There is no established treatment for this condition, and few reports have described its long-term course. Here, we describe two cases of SAPHO syndrome involving the femur and discuss their long-term follow-up. A 40-year-old man (Case 1) presented with right thigh pain. Fifteen years after the initial diagnosis, the pain could be controlled with minomycin, salazosulfapyridine, and methotrexate. X-rays of the femur showed gradual cortical thickening. Although there were waves of pain, it gradually improved with the adjustment of drugs 25 years following the initial diagnosis. A 35-year-old man (Case 2) with right thigh pain was prescribed salazosulfapyridine and methotrexate; however, these were ineffective. Alendronate and guselkumab also proved ineffective. Ultimately, infliximab was started 9 years following disease onset, and pain became manageable. X-rays of the femur showed cortical thickening. SAPHO syndrome can be managed with drug therapies, such as nonsteroidal anti-inflammatory drugs, methotrexate, and conventional synthetic disease-modifying antirheumatic drugs; however, there are occasional treatment-resistant cases.

Statin-induced, immune-mediated necrotising myopathy triggered by malignancy successfully treated with immunosuppression.

Statin-induced immune-mediated necrotising myopathy (IMNM) is an inflammatory myopathy that can present as proximal muscle weakness and, in some cases, as dysphagia and respiratory distress. In this report, we present a case of statin-induced IMNM in a 78-year-old male. The patient had significantly high levels of creatinine kinase and myoglobinuria and experienced gradual weakness in the proximal muscles for 1 month after initiating a 20 mg dose of Atorvastatin 10 months before admission. Rapid clinical improvement was observed with the use of high-dose glucocorticoids in conjunction with methotrexate.

The role of upfront lenalidomide maintenance for primary central nervous system lymphoma following first-line methotrexate treatment: A retrospective study.

BACKGROUND: Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown encouraging results in older patients with PCNSL. Herein, we performed a retrospective, single-center analysis to evaluate the effect of lenalidomide maintenance on the duration of response in patients with newly-diagnosed PCNSL. METHODS: Sixty-nine adult patients with PCNSL who achieved complete remission or partial remission (PR) after induction therapy were enrolled. The median age of patients was 58.0 years. The maintenance group (n = 35) received oral lenalidomide (25 mg/day) for 21 days, every 28 days for 24 months; the observation group did not undergo any further treatment. RESULTS: After a median follow-up of 32.6 months, the maintenance group experienced fewer relapse events. However, the median progression-free survival (PFS) was similar between groups (36.1 vs. 30.6 months; hazard ratio, 0.78; 95% confidence interval, 0.446). Lenalidomide maintenance significantly improved PFS and overall survival (OS) only among patients who experienced PR after induction. The median duration of lenalidomide maintenance was 18 months; lenalidomide was well tolerated and minimally impacted the quality of life. CONCLUSIONS: The present study was the first to evaluate lenalidomide maintenance as a frontline treatment among patients with PCNSL, PFS and OS did not improve, although the safety profile was satisfactory.

A rare case of extraluminal interstitial pregnancy treated with laparoscopic cornuotomy.

We report an extremely rare case of an extraluminal interstitial pregnancy. A 36-year-old nulliparous woman visited our hospital during the fifth week of gestation. Although no intrauterine gestational sac (GS) was identified, transabdominal ultrasonography revealed a GS-like cyst was detected in the right uterine horn. She underwent laparoscopic surgery for a suspected interstitial ectopic pregnancy. After laparoscopic cornuotomy, dye leakage was observed from the fimbria rather than the incision site. Finally, the patient was diagnosed with a right extraluminal interstitial pregnancy. Hysterosalpingography performed at three postoperative months revealed bilateral tubal passage. She conceived 7 months after surgery, with safe delivery by elective cesarean section at 38 weeks.

Adherence to low-dose methotrexate in children with juvenile idiopathic arthritis using a sensitive methotrexate assay.

BACKGROUND: Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined. METHODS: This was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy. RESULTS: Plasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher's Exact). CONCLUSIONS: Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.

From Treatment to Tragedy: Severe Methotrexate Toxicity With Mucocutaneous Ulcers, Myelosuppression, and Nephropathy.

Methotrexate (MTX) is a well-established drug for the use of various neoplastic disorders. Recently, it has been widely used as a disease-modifying antirheumatic drug (DMARD) in low doses, mainly for rheumatoid arthritis (RA) and psoriasis. The drug is known to cause renal damage as well as be excreted via the kidneys, thus causing a higher incidence of adverse effects in patients with impaired renal function. The side effects of MTX toxicity range from mucocutaneous ulcers to nephrotoxicity and bone marrow depression, all of which are seen in this case. Here, we report an elderly male in his late 60s who was prescribed MTX 15 mg once a week along with folic acid 5 mg for RA by a general practitioner. Despite being prescribed once weekly, he continued to take MTX daily without following up with a physician for a span of five months. Following this, he presented to the medicine outpatient department with odynophagia due to oral ulcers for 10 days. He was diagnosed with MTX toxicity, causing nephropathy, myelosuppression, and mucocutaneous ulcerations. He was treated with injectable leucovorin 100 mg thrice a day until the toxicity subsided, leading to his eventual recovery.

Inhibition of QDPR synergistically modulates intracellular tetrahydrobiopterin profiles in cooperation with methotrexate.

Tetrahydrobiopterin (BH4) is an essential cofactor for dopamine and serotonin synthesis in monoaminergic neurons, phenylalanine metabolism in hepatocytes, and nitric oxide synthesis in endothelial and immune cells. BH4 is consumed as a cofactor or is readily oxidized by autooxidation. Quinonoid dihydropteridine reductase (QDPR) is an enzyme that reduces quinonoid dihydrobiopterin (qBH2) back to BH4, and we have previously demonstrated the significance of QDPR in maintaining BH4 in vivo using Qdpr-KO mice. In addition to the levels of BH4 in the cells, the ratios of oxidized to reduced forms of BH4 are supposed to be important for regulating nitric oxide synthase (NOS) via the so-called uncoupling of NOS. However, previous studies were limited due to the absence of specific and high-affinity inhibitors against QDPR. Here, we performed a high-throughput screening for a QDPR inhibitor and identified Compound 9b with an IC50 of 0.72 µM. To understand the inhibition mechanism, we performed kinetic analyses and molecular dynamics simulations. Treatment with 9b combined with methotrexate (MTX), an inhibitor of another BH4-reducing enzyme, dihydrofolate reductase (DHFR), significantly oxidized intracellular redox states in HepG2, Jurkat, SH-SY5Y, and PC12D cells. Collectively, these findings suggest that 9b may enhance the anticancer and anti-autoimmune effects of MTX.

Can failure be predicted in methotrexate treatment with the modified parameter?

OBJECTIVE: The objective of the study was to increase the prediction of success of single-dose methotrexate therapy in ectopic pregnancy patients with modified parameters obtained from complete blood count and beta-human chorionic gonadotropin (ß-hCG) parameters. In this way, it was aimed to predict patients whose methotrexate treatment may fail and rupture, to avoid unnecessary methotrexate treatment, to shorten the duration of hospital stay and to reduce patient mortality. MATERIALS AND METHODS: 233 patients diagnosed with ectopic pregnancy between January 1, 2017, and March 01, 2022, in the obstetrics and gynecology service of a tertiary center were included in the study. RESULTS: The mean of ß-hCG was 1976 in the methotrexate group and 2358 in the surgery group (p < 0.05). The ROC curve determined the effect of BW (ß-hCGxWBC/1000) and BP (ß-hCGx1000/PLT) markers in diagnosing patients who will need surgery in ectopic pregnancy. The areas under the ROC curve for ß-hCG, BW and BP were 0.86, 0.99 and 0.94, respectively (p < 0.05). ß-hCG > 2139.03, BW > 30.96 and BP > 10.17 values were significantly associated with the need for surgery in ectopic pregnancy patients (p < 0.05). Logistic regression analysis revealed that a 1-unit increase in BP caused a statistically significant 1.77-fold increase in surgical need in patients with ectopic pregnancy. In contrast, a 1-unit increase in BW caused a 2.34-fold increase in surgical need (p < 0.05). CONCLUSION: The study results showed that BW and BP values together with ß-hCG are effective in predicting ectopic pregnancy patients who may undergo surgery.

Case report: Effectiveness of low-dose methotrexate monotherapy in post-essential thrombocythemia myelofibrosis.

JAK/STAT pathway signalling is associated with both chronic inflammatory conditions such as psoriasis and haematological malignancies such as the myeloproliferative neoplasms (MPNs). Here we describe a 73yo female patient with a history of chronic plaque psoriasis, post-essential thrombocythemia myelofibrosis (MF) and a quality of life substantially impacted by both conditions. We report that 15 mg oral Methotrexate (MTX) weekly as a monotherapy is well tolerated, provides a substantial clinical improvement for both conditions and significantly improves quality of life. We suggest that the recently identified mechanism of action of MTX as a JAK inhibitor is likely to explain this efficacy and suggest that repurposing MTX for MPNs may represent a clinical- and cost-effective therapeutic option.

Contribution of aldehyde oxidase to methotrexate-induced hepatotoxicity: In Vitro and pharmacoepidemiological approaches.

BACKGROUND: Methotrexate (MTX) is partially metabolized by aldehyde oxidase (AOX) in the liver and its clinical impact remains unclear. In this study, we aimed to demonstrate how AOX contributes to MTX-induced hepatotoxicity in vitro and clarify the relationship between concomitant AOX inhibitor use and MTX-associated liver injury development using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We assessed intracellular MTX accumulation and cytotoxicity using HepG2 cells. We used the FAERS database to detect reporting odds ratio (ROR)-based MTX-related hepatotoxicity event signals. RESULTS: AOX inhibition by AOX inhibitor raloxifene and siRNA increased the MTX accumulation in HepG2 cells and enhanced the MTX-induced cell viability reduction. In the FAERS analysis, the ROR for MTX-related hepatotoxicity increased with non-overlap of 95% confidence interval when co-administered with drugs with higher Imax, u (maximum unbound plasma concentration)/IC50 (half-maximal inhibitory concentration for inhibition of AOX) calculated based on reported pharmacokinetic data. CONCLUSION: AOX inhibition contributed to MTX accumulation in the liver, resulting in increased hepatotoxicity. Our study raises concerns regarding MTX-related hepatotoxicity when co-administered with drugs that possibly inhibit AOX activity at clinical concentrations.

Should All Patients Trial Subcutaneous Methotrexate Prior to Commencing Biologic Therapy? A Real World Study.

Introduction: Methotrexate (MTX) is the bed rock of inflammatory arthritis management. However, intolerance is a limiting factor for drug optimisation and retention. There is data to suggest subcutaneous (SC) MTX is better tolerated. It is less clear whether this strategy is effective in those where the oral preparation is inefficacious and its potential to avoid escalation to biologic therapy. Objectives: To analyse the reasons for switching to SC MTX in a real-world setting, clinical outcomes achieved and proportion requiring biologic prescription. Materials and Methods: A retrospective survey of patients prescribed SC MTX in a university teaching hospital identified 352 patients. 298 switched from oral to SC MTX- 164 stopped oral MTX due to side effects, 134 stopped due to inefficacy, and 54 started SC MTX as first line therapy. 103 patients progressed to biologic therapy. Rheumatoid arthritis (RA): DAS-28 improved from a mean of 4.06 (0.63-8.06) to 2.83 (0.14-7.32) following the switch (p<0.0001). Psoriatic arthritis (PsA): total joint count improved from a mean of 7 (0-42) to 2 (0-25) (p<0.0001). Swollen joint count improved from a mean of 2 (0-26) to 1 (0-6) (p=0.09). Discussion: SC MTX is an effective solution for RA and PsA, irrespective of whether oral MTX is inefficacious or intolerable. Where oral MTX was ineffective, a switch to SC achieved low disease activity despite multi-morbidity, long disease course and protracted oral MTX exposure. This intervention prevented over two-thirds of patients requiring biologics. SC MTX is a durable strategy with excellent disease outcomes and substantial economic benefits.

The Role of Etanercept in Controlling Clinical and Radiological Progression in Rheumatoid Arthritis: A Systematic Review.

Etanercept (ETN) is a disease-modifying anti-rheumatic drug (DMARD) used in the treatment of rheumatoid arthritis (RA) that works as a tumor necrosis factor inhibitor (TNF inhibitor) by blocking the effects of naturally occurring TNF. This review will evaluate the effect of ETN as a monotherapy or combination therapy with methotrexate (MTX) in the treatment of RA. This systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. A systematic search was done on PubMed and Google Scholar from 1999 to 2023. Predefined eligibility criteria were set for selected studies, which include: free full-text articles published; randomized control trials (RCTs); systematic reviews and meta-analyses; and observational studies in a patient with RA treated with ETN as initial therapy or as an add-on to conventional disease-modified therapy. Hence, the data had been extracted, and a quality assessment of each study was done by two individual authors. When comparing patients who received 15-25 mg of MTX with those who also received 25 mg of ETN in combination, 71% achieved American College of Rheumatology 20 (ACR20) by 24 weeks, compared to 27% in the MTX and placebo groups (p<0.001), and 39% achieved American College of Rheumatology 50 (ACR50), compared to 3% in the placebo + MTX group (p<0.001). Low disease activity (DAS 28) was more common in patients who had both MTX and ETN (64.5% with DAS <2.4 and 56.3% with DAS 28 <3.2) compared to patients who received only one medication (44.4% with DAS <2.4 and 33.2% with DAS 28 <3.2 for ETN and 38.6% with DAS <2.4 and 28.5% with DAS 28 <3.2 for MTX, with P<0.01). ETN demonstrated smaller changes from baseline in the modified Sharp score (TSS) and erosion scores (ES) at 12 months and two years, as well as a decreased change in the ES score at one year (with a trend of P value = 0.06 for the TSS score), in comparison to those receiving DMARD. Reactions at the injection site (42% vs. 7%, P<0.001) were the only events that occurred significantly more frequently in the ETN plus-MTX group. Combining ETN and MTX appears to help control RA symptoms by decreasing the American College of Rheumatology (ACR) response and DAS score, as well as halting the disease's progression on X-rays. The most common adverse effects were reactions to ETN administered alone at the injection site, likely because of patient awareness of the treatment received. There was also concern about tuberculosis and malignancy, but no recent data is available. Therefore, a larger clinical trial with longer follow-up is required to ascertain long-term safety and benefits.

A Case of Femoral Artery Aneurysm Caused by Methotrexate Associated Lymphoproliferative Disease.

An 82-year-old man with left leg edema was referred to our department after an ultrasound examination by his previous physician, which revealed deep vein thrombosis (DVT) in the left superficial femoral vein and a left common femoral artery aneurysm (CFAA). The DVT was caused by the CFAA. The patient was adjudged to be at high risk of peripheral embolization due to the irregular shape of the varicose vein and a large amount of mural thrombus. Surgery was performed to replace the artificial blood vessel. The patient displayed firm adhesion to the surrounding area, marked lymph node swelling, and a large amount of mural thrombus in the mass. The superficial femoral artery (SFA) demonstrated severe intimal thickening and partial dissection. The postoperative course was good, and the patient was undergoing rehabilitation to be discharged home; however, B-cell lymphoma was suspected based on the pathology results of the mass wall submitted intraoperatively. The patient had a history of rheumatoid arthritis and was treated with methotrexate (MTX). During the course of his illness, a subcutaneous mass was found on his right forearm, and a skin biopsy revealed MTX-associated lymphoproliferative disease (MTX-LPD), which had resolved with MTX withdrawal. The histopathological results of the skin biopsy matched those of the CFAA mural thrombus, and Epstein-Barr virus-positive cells were also observed, leading to the diagnosis of MTX-LPD, which was considered to be the cause of CFAA. No MTX-LPD was identified in the vessel walls or intramural thrombus. We herein report a case of CFAA with an extremely rare etiology and clinical presentation.

NIR-Responsive Methotrexate-Modified Iron Selenide Nanorods for Synergistic Magnetic Hyperthermic, Photothermal, and Chemodynamic Therapy.

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

Comparison of methotrexate and azathioprine as the first-line steroid-sparing immunosuppressive agents in patients with Takayasu's arteritis.

BACKGROUND: Immunosuppressive (IS) agents are recommended for the first-line treatment of patients with active Takayasu's arteritis (TAK) together with glucocorticoids (GCs). However, there is limited data comparing the efficacy and outcomes of different IS agents for this purpose. OBJECTIVES: In this study, we aimed to compare the outcomes of two most frequently used first-line IS agents, namely methotrexate (MTX) and azathioprine (AZA) in TAK patients. METHODS: TAK patients who received any IS agent in addition to GCs as the initial therapy were included in this multicentre, retrospective cohort study. Clinical, laboratory and imaging data of the patients were assessed. In addition, a matched analysis (cc match) using variables 'age', 'gender' and 'diffuse aortic involvement' was performed between patients who received MTX or AZA as the first-line IS treatment. RESULTS: We recruited 301 patients (F/M: 260/41, mean age: 42.2 ± 13.3 years) from 10 tertiary centres. As the first-line IS agent, 204 (67.8 %) patients received MTX, and 77 (25.6 %) received AZA. Less frequently used IS agents included cyclophosphamide in 17 (5.6 %), leflunomide in 2 (0.5 %) and mycophenolate mofetil in one patient. The remission, relapse, radiographic progression and adverse effect rates were similar between patients who received MTX and AZA as the first-line IS agent. Vascular surgery rate was significantly higher in the AZA group (23% vs. 9 %, p = 0.001), whereas the frequency of patients receiving ≤5 mg/day GCs at the end of the follow-up was significantly higher in the MTX group (76% vs 62 %, p = 0.034). Similarly, the rate of vascular surgery was higher in AZA group in matched analysis. Drug survival was similar between MTX and AZA groups (median 48 months, MTX vs AZA: 32% vs 42 %, p = 0.34). IS therapy was discontinued in 18 (12 MTX, 6 AZA) patients during the follow-up period due to remission. Among those patients, two patients had a relapse at 2 and 6 months, while 16 patients were still on remission at the end of a mean 69.4 (±50.9) months of follow-up. CONCLUSIONS: Remission, relapse, radiographic progression and drug survival rates of AZA and MTX were similar for patients with TAK receiving an IS agent as the first-line f therapy. The rate of vascular surgery was higher and the rate of GC dose reduction was lower with AZA compared to MTX at the end of the follow-up.

An observational study of root-cause analysis of medication errors in elderly with methotrexate toxicity.

INTRODUCTION: Medication errors are inherent in a healthcare system. This results in both time and cost burdens for both the patient and the health system. The aim of this study was to conduct a root-cause analysis of medication errors in elderly patients with methotrexate toxicity, analyze associated factors, and propose solutions. METHODS: This single-center prospective study was designed to identify medication errors in cases of methotrexate toxicity between November 2022 to May 2023. Categorical data and free-text data are used to describe incidents. Harm assessment, factors related to medication errors, and preventability were evaluated for each case. Possible strategies to prevent similar occurrences are discussed. RESULTS: Out of a total of 15 patients who presented during the study period, nine suffered from methotrexate toxicity due to medication errors. Most medication errors occurred during prescribing or dispensing (seven cases). Inadequate knowledge about medication and dosage, inadequate communication was identified as a contributing factor for all medication errors. Patients on long-term methotrexate treatment are at high risk of methotrexate toxicity. CONCLUSION: This study highlights the challenges of health literacy and lacking communication between healthcare providers and patients that can be met through community pharmacy programs for the elderly in lower-middle-income countries.