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Chinese Medical Journal Feb 2023The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients.... (Review)
Review
The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.
Topics: Humans; Arthritis, Rheumatoid; Methotrexate; Lung Diseases, Interstitial; Prognosis; Lung
PubMed: 36689640
DOI: 10.1097/CM9.0000000000002577 -
CMAJ : Canadian Medical Association... Jan 2021
Topics: Female; Hand; Humans; Methotrexate; Middle Aged; Psoriasis
PubMed: 33667188
DOI: 10.1503/cmaj.200517-f -
Nature Communications Mar 2023Folate is an essential vitamin for vertebrate embryo development. Methotrexate (MTX) is a folate antagonist that is widely prescribed for autoimmune diseases, blood and...
Folate is an essential vitamin for vertebrate embryo development. Methotrexate (MTX) is a folate antagonist that is widely prescribed for autoimmune diseases, blood and solid organ malignancies, and dermatologic diseases. Although it is highly contraindicated for pregnant women, because it is associated with an increased risk of multiple birth defects, the effect of paternal MTX exposure on their offspring has been largely unexplored. Here, we found MTX treatment of adult medaka male fish (Oryzias latipes) causes cranial cartilage defects in their offspring. Small non-coding RNA (sncRNAs) sequencing in the sperm of MTX treated males identify differential expression of a subset of tRNAs, with higher abundance for specific 5' tRNA halves. Sperm RNA methylation analysis on MTX treated males shows that m5C is the most abundant and differential modification found in RNAs ranging in size from 50 to 90 nucleotides, predominantly tRNAs, and that it correlates with greater testicular Dnmt2 methyltransferase expression. Injection of sperm small RNA fractions from MTX-treated males into normal fertilized eggs generated cranial cartilage defects in the offspring. Overall, our data suggest that paternal MTX exposure alters sperm sncRNAs expression and modifications that may contribute to developmental defects in their offspring.
Topics: Animals; Male; Pregnancy; Humans; Female; Methotrexate; Semen; Spermatozoa; Folic Acid; RNA, Small Untranslated; RNA, Transfer
PubMed: 36959185
DOI: 10.1038/s41467-023-37427-7 -
RMD Open Apr 2023
Topics: Humans; Methotrexate; Immunosuppressive Agents; Antirheumatic Agents; Vaccination
PubMed: 37015758
DOI: 10.1136/rmdopen-2022-002798 -
Medicina (Kaunas, Lithuania) Jun 2020Cervical pregnancy (CP) is a rare form of ectopic pregnancy (EP) in which the embryo implants and grows inside the endocervical canal. Early diagnosis is essential in... (Observational Study)
Observational Study
Cervical pregnancy (CP) is a rare form of ectopic pregnancy (EP) in which the embryo implants and grows inside the endocervical canal. Early diagnosis is essential in order to allow conservative medical and surgical treatments. Although many treatment approaches are disponible, the most effective is still unclear. The aim of this study is to evaluate the efficacy of hysteroscopic management in early CP in order to preserve future fertility. This is a retrospective observational case series. Five patients with a diagnosis of CP, hemodynamically stables and managed conservatively between 2014 and 2019 at the Institute of Child and Maternal Health Burlo Garofolo in Trieste, Italy, were included. Four patients, with βhCG levels >5000 mUi/mL were managed by hysteroscopy, with or without a previous systemic Methotrexate (MTX). One case with βhCG levels <5000 mUi/mL was treated using MTX combined to Mifepristone and Misoprostol. In one patient treated by hysteroscopy alone it occurred a profuse vaginal bleeding with necessity for blood transfusion. Haemorrhage was controlled by a second hysteroscopic procedure. No complications, such as vaginal bleeding, were recorded in the other cases. Serum β-hCG levels become undetectable in a range of 15-40 days after hysteroscopic management; after medical treatment it become undetectable after 35 days. Serum βhCG levels had a faster drop the day after hysteroscopy than post medical management. The onset of a spontaneous pregnancy at the normal implantation site occurred after five months in one case treated by hysteroscopy. Many therapeutic approaches are effective for CP treatment. Hysteroscopy, alone or in combination with MTX, may provide a greater effect on the descent of βhCG, leading to a reduction of the hospitalization stay, decreasing costs and period for attempt pregnancy. Further prospective studies on larger samples are needed to define therapeutic protocols for CP management.
Topics: Abortifacient Agents, Nonsteroidal; Adult; Female; Fertility; Humans; Hysteroscopy; Italy; Methotrexate; Pregnancy; Pregnancy, Ectopic; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 32545627
DOI: 10.3390/medicina56060293 -
Folia Morphologica 2021The intention of the present study was to assess the structural affection of the lung following methotrexate (MTX) overdose. The proposed underlying mechanisms involved...
BACKGROUND
The intention of the present study was to assess the structural affection of the lung following methotrexate (MTX) overdose. The proposed underlying mechanisms involved in lung affection were studied. The possible modulation role of febuxostat over such affection was studied.
MATERIALS AND METHODS
Twenty-four rats were divided into three groups: control, MTX-treated, febuxostat-treated. The study was continued for 2 weeks. Lung was processed for histological and immunohistochemical (inducible nitric oxide synthase [iNOS] and cyclooxygenase [COX]-2) studies. Inflammatory markers (tumour necrosis factor alpha [TNF-a], interleukin 1 [IL-1]), Western blot evaluation of nuclear factor kappa B (NF-kB) and oxidative/antioxidative markers were done.
RESULTS
Methotrexate-treated group exhibited inflammatory cellular infiltrations, thickened interalveolar septa, dilated congested blood vessels, extravasated blood, and apoptosis. The collagen fibres content increased 3-fold. MTX induced lung affection through oxidative stress (increase MDA/decrease GSH, SOD) and apoptosis. It induced sterile inflammation through an increase of NF-kB (2-fold), IL-1 (3-fold) and TNF-a (3-fold), COX-2 cells (2.5-fold) and iNOS (6-fold). With the use of febuxostat, the normal lung architecture was observed with a bit thickened interalveolar septum and extravasated blood. The collagen fibres content was minimal. Decrement of oxidative stress and sterile inflammation (COX-2 cells and iNOS were comparable to the control group. NF-kB, IL-1 and TNF-a became higher by 34%, 64% and 100%).
CONCLUSIONS
The overdose of MTX displays inflammatory lung affection with residual fibrosis. It induces lung affection through oxidative stress, apoptosis and sterile inflammation. With the use of febuxostat, the normal lung architecture was preserved with a little structural affection or fibrotic residue. Febuxostat exerts its lung protection through its anti-inflammatory and antioxidant features.
Topics: Animals; Antioxidants; Febuxostat; Lung; Methotrexate; Oxidative Stress; Rats
PubMed: 32644182
DOI: 10.5603/FM.a2020.0075 -
Skin Therapy Letter Nov 2019Methotrexate (MTX), an agent originally intended for anti-neoplastic use, has been successfully employed in the treatment of a variety of dermatologic conditions. In... (Review)
Review
Methotrexate (MTX), an agent originally intended for anti-neoplastic use, has been successfully employed in the treatment of a variety of dermatologic conditions. In addition to its multiple clinical indications, variable dosing and modes of administration make it a viable option for patients of all ages and most comorbidities. MTX is a folate analog that antagonizes dihydrofolate reductase, thus inhibiting thymidylate synthesis and, ultimately, the production of pyrimidine. Depending on dosage, MTX can function as an anti-inflammatory agent, immunomodulator, or antimetabolite. Patients suffering from psoriasis have benefited from MTX in addition to those with atopic dermatitis, chronic urticaria, pemphigus vulgaris, bullous pemphigoid, cutaneous lupus erythematosus, cutaneous sarcoidosis, and mycosis fungoides. Although patients with these conditions can benefit from MTX treatment, the drug can cause adverse sequelae, including hematologic, pulmonary, gastrointestinal, and hepatic side effects. Therefore, the drug should be administered under careful physician supervision.
Topics: Dermatologic Agents; Humans; Methotrexate; Skin Diseases
PubMed: 31801013
DOI: No ID Found -
Ophthalmic Surgery, Lasers & Imaging... Mar 2023Proliferative vitreoretinopathy (PVR) has been mitigated by intravitreal methotrexate (MTX) 400 μg/0.1 mL in several studies. Here, we evaluate the results from a lower...
BACKGROUND AND OBJECTIVE
Proliferative vitreoretinopathy (PVR) has been mitigated by intravitreal methotrexate (MTX) 400 μg/0.1 mL in several studies. Here, we evaluate the results from a lower dose of MTX, 200 μg/0.05 mL.
MATERIALS AND METHODS
We identified and reviewed records of patients with grade ≥C1 PVR who were treated with 200 μg/0.05 mL MTX injections: during PVR surgery and every 2 weeks thereafter.
RESULTS
Twenty-four eyes met inclusion criteria with a mean of 5.6 injections and follow-up ranging 6 to 56 months. The retina was reattached in 19 of 24 eyes (79%) after a single surgery and in 5 of 24 eyes (21%) after one additional PVR surgery. Visual acuity improved from baseline logMAR 1.63 to 0.97 at 12 months ( < .001), with 5 of 20 achieving 20/60 or better and 16 of 20 achieving 20/200 or better. One eye developed a transient corneal abrasion that resolved within 1 week.
CONCLUSION
Low-dose MTX (200 μg/0.05 mL) during and after PVR surgery resulted in good rates of retinal reattachment and visual acuity recovery. .
Topics: Humans; Methotrexate; Vitreoretinopathy, Proliferative; Retinal Detachment; Vitrectomy; Retina
PubMed: 36944071
DOI: 10.3928/23258160-20230220-01 -
The Journal of Dermatological Treatment Dec 2024Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing... (Review)
Review
Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing and increased risk of side effects. This systematic review summarizes the available evidence on dosing regimens.A literature search was conducted, screening all randomized controlled trials (RCTs) and guidelines published up to 6 July 2023, in the MEDLINE, Embase, and Cochrane Library databases.Five RCTs and 21 guidelines were included. RCTs compared methotrexate with other treatments rather than different methotrexate dosing regimens. The start and maintenance doses in RCTs varied between 7.5-15 mg/week and 14.5-25 mg/week, respectively. Despite varied dosing, all RCTs demonstrated efficacy in improving atopic dermatitis signs and symptoms. Guidelines exhibited substantial heterogeneity but predominantly proposed starting doses of 5-15 mg/week for adults and 10-15 mg/m/week for children. Maintenance doses suggested were 7.5-25 mg/week for adults and 0.2-0.7 mg/kg/week for children. One guideline suggested a test dose and nearly half advised folic acid supplementation.This systematic review highlights the lack of methotrexate dosing guidelines for atopic dermatitis. It identifies commonly recommended and utilized dosing regimens, serving as a valuable resource for clinicians prescribing methotrexate off-label and providing input for an upcoming consensus study.
Topics: Adult; Child; Humans; Methotrexate; Dermatitis, Atopic
PubMed: 38124505
DOI: 10.1080/09546634.2023.2292962 -
Life Science Alliance Nov 2023Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including...
Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including methotrexate and 5-fluorouracil that are commonly applied for the treatment of leukemia and colorectal cancer (CRC), respectively. Despite high success rates, therapy-induced resistance causes relapse at later disease stages. Depletion of folylpolyglutamate synthetase (FPGS), which normally promotes intracellular accumulation and activity of natural folates and methotrexate, is linked to methotrexate and 5-fluorouracil resistance and its association with relapse illustrates the need for improved intervention strategies. Here, we describe a novel antifolate (C1) that, like methotrexate, potently inhibits dihydrofolate reductase and downstream one-carbon metabolism. Contrary to methotrexate, C1 displays optimal efficacy in FPGS-deficient contexts, due to decreased competition with intracellular folates for interaction with dihydrofolate reductase. We show that FPGS-deficient patient-derived CRC organoids display enhanced sensitivity to C1, whereas FPGS-high CRC organoids are more sensitive to methotrexate. Our results argue that polyglutamylation-independent antifolates can be applied to exert selective pressure on FPGS-deficient cells during chemotherapy, using a vulnerability created by polyglutamylation deficiency.
Topics: Humans; Folic Acid Antagonists; Methotrexate; Tetrahydrofolate Dehydrogenase; Folic Acid; Fluorouracil
PubMed: 37591722
DOI: 10.26508/lsa.202302058