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  1. Destiani DP, Naja S, Dewi S, Rahmadi AR, Sulaiman SAS, Abdulah R
    Osteoporos Int, 2021 May;32(5):805-816.
    PMID: 33210179 DOI: 10.1007/s00198-020-05743-z
    Even though new drugs for the treatment of rheumatoid arthritis (RA) have been developed, methotrexate (MTX) remains a commonly used drug for RA management. In addition to monitoring disease activity during RA treatment, bone erosion should be closely assessed throughout long-term RA management. In this review article, we present a systematic review of MTX effectiveness in reducing the risk of bone erosion. We reviewed randomized controlled trial studies that involved MTX monotherapy or MTX in combination with placebo. Evaluation of the progression of bone erosion was examined by radiographic assessment such as total Sharp score (TSS) or van der Heijde score (SvdH or vdH TSS), joint space narrowing (JSN), erosion score (ERO), and proportion of radiographic nonprogressors. Several key factors were found to influence the response to MTX treatment, such as gene polymorphism. The exact mechanism of the prevention of bone erosion by MTX remains unclear, which warrants future investigations. The variability of RA disease activity in study subjects resulted in variations in the results reported by individual studies. Collective analysis suggests that MTX could slow down the progression of bone erosion based on a radiographic score of less than 0.5-1/year.
    Matched MeSH terms: Methotrexate/therapeutic use
  2. Bin Ahmad MZ, Mat Nasir N, Md Yasin M, Yusof ANM, Bakrin IH, Lim SC
    Am J Case Rep, 2023 May 19;24:e940148.
    PMID: 37202915 DOI: 10.12659/AJCR.940148
    BACKGROUND This case illustrates the challenges in diagnosing linear scleroderma (LS) in a child who presented to a primary care setting. Diagnosis of LS is easily missed due to the lack of prominent symptoms, subtle visible skin changes, and under-recognition of this condition. CASE REPORT A 7-year-old boy presented with a linear, painless, non-itchy rash at the center of his forehead, which has been present for 6 months. The rash extends vertically from the hairline to the bridge of the nose. The color gradually evolved from reddish to purplish-grey and shiny within 3 months. He had underlying eczema, allergic rhinitis, and allergic conjunctivitis since birth. His condition remained unrecognized despite consultations with various medical specialties, including family medicine specialist, ophthalmologist, otorhinolaryngologist, and a general pediatrician. Six months after the onset of his lesion, he was subsequently referred to a pediatric dermatologist and pediatric rheumatologist, who made the diagnosis of LS. Laboratory investigations for autoimmune disease showed that negative antinuclear antibodies (ANA) and inflammatory markers, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were normal. Skin biopsy provided a tissue confirmation of the diagnosis. MRI of the lesion showed no extension into the underlying muscle or bone erosions. The patient was initially treated with intravenous (IV) methylprednisolone for 3 days, followed by oral methotrexate weekly and prednisolone. The lesion improved after 1 month of treatment, and after 15 months it was less pigmented and less noticeable. CONCLUSIONS LS is the commonest form of localized scleroderma in children. LS on the forehead can erode into the underlying tissues and is sometimes associated with extensive hemifacial atrophy. Treatment should be instituted early to prevent late irreversible fibrotic sequelae. This report aims to highlight the importance of early diagnosis and treatment of an uncommon but potentially disfiguring condition.
    Matched MeSH terms: Methotrexate/therapeutic use
  3. Ng BK, Lim PS, Ahmad S, Kampan NC, Abdul Karim AK, Omar MH
    Taiwan J Obstet Gynecol, 2015 Apr;54(2):208-10.
    PMID: 25951734 DOI: 10.1016/j.tjog.2014.11.022
    Matched MeSH terms: Methotrexate/therapeutic use
  4. Khanijow VK, Prasad U, Chang CM
    Med J Malaysia, 1989 Dec;44(4):329-33.
    PMID: 2520043
    Nasopharyngeal carcinoma (NPC) is one of the commonest presentation of head and neck cancers in Malaysia, especially in the Chinese. The standard treatment is radical radiotherapy to the post-nasal space and the neck. Chemotherapy is given to patients with primary advanced disease and to patients with recurrence. The study reviews results of chemotherapy given to 33 patients at the University Hospital, Kuala Lumpur, over the last four years.
    Matched MeSH terms: Methotrexate/therapeutic use
  5. Adam BA
    Med J Malaysia, 1973 Mar;27(3):192-4.
    PMID: 4268922
    Matched MeSH terms: Methotrexate/therapeutic use
  6. Sakthiswary R, Suresh E
    Lupus, 2014 Mar;23(3):225-35.
    PMID: 24399812 DOI: 10.1177/0961203313519159
    OBJECTIVE: The objective of this review is to evaluate the evidence for efficacy of methotrexate (MTX) in systemic lupus erythematosus (SLE).
    METHODS: A comprehensive, computerized search was performed in MEDLINE (PubMed), EMBASE and the Cochrane Controlled Trials registry to screen for studies that examined the efficacy of MTX in adult SLE patients. The Jadad scoring system was used to assess study quality, and data were pooled using the random effects model.
    RESULTS: Of the 53 articles that were identified, 44 were excluded. Nine studies (including three randomized controlled and six observational) were eligible for inclusion. All of the included studies predominantly involved patients with arthritis or mucocutaneous features. There was significant reduction of the SLE Disease Activity Index (SLEDAI) among MTX-treated patients when compared with controls (p = 0.001, odds ratio (OR) 0.444, 95% confidence interval (CI) 0.279 to 0.707). There was also significant reduction in the average dose of corticosteroids among MTX-treated patients when compared with controls (p = 0.001, OR 0.335, 95% CI 0.202 to 0.558). The effect of MTX on laboratory and serological markers, including erythrocyte sedimentation rate, anti-dsDNA and complement levels (C3 and C4), could not be determined because of the limited numbers of controlled trials.
    CONCLUSION: The use of MTX is associated with significant reductions in SLEDAI and the average dose of corticosteroids in adult patients with SLE.
    KEYWORDS: SLE; Systemic lupus erythematosus; efficacy; lupus; methotrexate
    Matched MeSH terms: Methotrexate/therapeutic use*
  7. Leong CF, Azma RZ, Cheong SK, Salwati S, Sharifah NA
    Malays J Pathol, 2005 Jun;27(1):45-50.
    PMID: 16676693
    A 25-year-old man was referred to Hospital UKM with a 2-week history of fever, productive cough and loss of appetite. Physical examination revealed an ill-looking, tachypnoeic young man. No obvious lymphadenopathy or organomegaly was noted. Examination of the respiratory system revealed right pleural effusion. Full blood picture demonstrated leukocytosis with 90% blasts, and bone marrow examination confirmed the diagnosis of acute myeloid leukemia (AML) French-American-British (FAB) classification of M4 with eosinophilia. His chromosome karyotyping showed complex karyotypic abnormalities. Cytological examination of the pleural fluid demonstrated numerous blast cells indicating leukemic infiltration of the lungs, which is a rare presentation in AML. He was then started on induction chemotherapy with intravenous daunorubicin and cytarabine. In the midst of treatment, he developed an episode of seizure and cerebro-spinal fluid cytology confirmed central nervous system (CNS) leukaemic infiltration. Additional intrathecal methotraxate was given. Repeat bone marrow examination done on day 15 of chemotherapy showed persistence of excess blasts indicating refractory AML. He was then reinduced with high dose cytarabine but to no avail. The disease progressed and he succumbed about 8 weeks after the initial diagnosis was made. We highlight here a case of AML-M4Eo with complex karyoyptic abnormalities presenting with leukaemic infiltration of the lungs and CNS which had imparted a bad prognosis for this subtype of AML, AML-M4Eo.
    Matched MeSH terms: Methotrexate/therapeutic use
  8. Ti TK, Yong NK
    Med J Malaysia, 1974 Mar;28(3):165-70.
    PMID: 4278036
    Matched MeSH terms: Methotrexate/therapeutic use
  9. Salari N, Kazeminia M, Shohaimi S, Nankali AA, Mohammadi M
    Reprod Biol Endocrinol, 2020 Nov 09;18(1):108.
    PMID: 33168010 DOI: 10.1186/s12958-020-00666-0
    BACKGROUND: Previous caesarean scar pregnancy is one type of ectopic pregnancy in myometrium and fibrous tissue of previous caesarean scar. One of the therapeutic methods of this type of ectopic pregnancy is treatment with methotrexate. Given various findings on the treatment of caesarean scar pregnancy with methotrexate and lack of global report in this regard, we aimed to achieve a global report on the treatment of CSP with methotrexate through related literature review and analysis of the results of the studies, to enable more precise planning to reduce complications of CSP.

    METHOD: This review study extracted information through searching national and international databases of SID،, Embase, ScienceDirect, ، Scopus, ، PubMed, Web of Science (ISI) between 2003 and January 2020. To perform the meta-analysis, random-effects model and heterogeneity of the studies with I2 index were investigated. Data were sanalysed using Comprehensive Meta-Analysis version 2.

    RESULTS: In total, 26 articles with a sample size of 600 individuals were enrolled in the meta-analysis. According to the results of the study, the mean level of β-hCG was 28,744.98 ± 4425.1 mIU/ml before the intervention and was 23,836.78 ± 4533.1 mIU/ml after the intervention. The mean intraoperative blood loss (ml) was 4.8 ± 3.76 ml, mean hospital stay (days) was 11.7 ± 1.2 days, mean time for serum-hCG normalization (days) was 41.6 ± 3.2 days, success was 90.7% (95% CI: 86.7-93.5%), and complication was 9% (95% CI: 6.3-12.8%).

    CONCLUSION: The results of the current study show methotrexate significantly reduces β-hCG levels and can be effective in treating caesarean scar pregnancy and its complications.

    Matched MeSH terms: Methotrexate/therapeutic use*
  10. Koh KT, Teh CL, Cheah CK, Ling GR, Yong MC, Hong HC, et al.
    Reumatismo, 2016 Sep 09;68(2):90-6.
    PMID: 27608797 DOI: 10.4081/reumatismo.2016.872
    The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.
    Matched MeSH terms: Methotrexate/therapeutic use*
  11. Mak JWY, Tang W, Yip TCF, Ran ZH, Wei SC, Ahuja V, et al.
    Aliment Pharmacol Ther, 2019 12;50(11-12):1195-1203.
    PMID: 31638274 DOI: 10.1111/apt.15547
    BACKGROUND: Little is known of the outcome of patients with perianal Crohn's disease after stopping anti-tumour necrosis factor (TNF) therapy.

    AIM: To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti-TNF therapy.

    METHODS: Consecutive perianal CD patients treated with anti-TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan-Meier method.

    RESULTS: After a median follow-up of 89 months (interquartile range [IQR]: 65-173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti-TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti-TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01-1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti-TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58-2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti-TNF therapy after a median of 6 months.

    CONCLUSIONS: More than half of the perianal CD patients developed relapse after stopping anti-TNF therapy. Most regained response after resuming anti-TNF. However, more than one-fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti-TNF is crucial in perianal CD.

    Matched MeSH terms: Methotrexate/therapeutic use
  12. Sivalingam N, Mak FK
    Singapore Med J, 2000 Dec;41(12):599-601.
    PMID: 11296786
    Cervical pregnancy is an uncommon variety of ectopic gestation. The aetiology is obscure. Diagnosis can be missed unless early evaluation is done by experienced personnel utilising pelvic ultrasonography. Three cases of cervical pregnancy managed at this hospital are described illustrating difficulties in early diagnosis and possible association with previous uterine scar and prior curettage of the uterus for retained products of conception. Treatment options vary according to the clinical state of the patient at the time of diagnosis. Non-surgical methods including systemic methotrexate administration in one and surgical evacuation of products of conception with subsequent cervical cerclage in another are discussed. Surgical interventions like total abdominal hysterectomy with internal iliac artery ligation to arrest life-threatening pelvic haemorrhage is also described. Other treatment options include potassium chloride (KCl) alone or in combination with methotrexate.
    Matched MeSH terms: Methotrexate/therapeutic use*
  13. Sakthiswary R, Chan GY, Koh ET, Leong KP, Thong BY
    ScientificWorldJournal, 2014;2014:823763.
    PMID: 24971392 DOI: 10.1155/2014/823763
    BACKGROUND: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore.
    METHODS: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis.
    RESULTS: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512).
    CONCLUSION: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

    Study site: Tan Tock Seng Hospital, Singapore
    Matched MeSH terms: Methotrexate/therapeutic use
  14. Ibrahim SB, Yashodhara BM, Umakanth S, Kanagasabai S
    BMJ Case Rep, 2012;2012.
    PMID: 22744241 DOI: 10.1136/bcr.02.2012.5850
    A 23-year-old pregnant woman in her second trimester of pregnancy presented with blisters on the face, abdomen and the leg. Based on the clinical presentation and skin biopsy (histopathology and direct immunofluorescence) the diagnosis of pemphigus vulgaris was established. The child born to this patient also had similar skin lesions. The lesions in the mother and the child improved after treatment. The authors report a rare case of pemphigus vulgaris in a pregnant lady and neonatal pemphigus in her child, both of whom were treated successfully.
    Matched MeSH terms: Methotrexate/therapeutic use
  15. Esther LSY, Chew KT, Rahman RA, Zainuddin AA, Hing EY, Kampan N
    Horm Mol Biol Clin Investig, 2020 Mar 13;41(2).
    PMID: 32167930 DOI: 10.1515/hmbci-2020-0001
    Intramyometrial ectopic pregnancy (IMEP) is a rare form of ectopic pregnancy. It is defined as a conceptus implanted within the myometrium and is completely surrounded by myometrium with clear separation from both the uterine cavity and tubes. IMEP possesses not only diagnostic but also therapeutic challenge. The majority of reported cases were managed by hysterectomy. Early management of unruptured IMEP using methotrexate may help to preserve fertility. We, for the first time, report a case of ruptured IMEP managed successfully using suction and curettage followed by Bakri balloon tamponade and avoiding hysterectomy. Post-procedure, the patient received two doses of intramuscular methotrexate 50 mg/m2 due to plateauing serial beta human chorionic gonadotropin (β-hCG) levels and subsequently achieved undetectable level 10 weeks post-methotrexate. She also had complete resolution of the ectopic intramyometrial mass.
    Matched MeSH terms: Methotrexate/therapeutic use
  16. Sen DK, Sivanesaratnam V, Chuah CY, Ch'ng SL, Singh J, Paramsothy M
    Acta Obstet Gynecol Scand, 1987;66(5):425-8.
    PMID: 3425244
    Of 36 cases of choriocarcinoma treated at the University Hospital Kuala Lumpur during 1980-84 inclusive, 6 patients were found to have cerebral metastases. Intrathecal methotrexate and combination chemotherapy were started in all cases, with monitoring of tumor growth by serial beta-HCG assays and CT scanning of brain and lung. Chemotherapy was reduced because of severe toxicity in 2 patients, one of whom received radiotherapy to the brain. Four patients (66%) have now been in remission for 2.5-6 years. Two did not respond to therapy and died. The factors involved in therapy and response are discussed.
    Matched MeSH terms: Methotrexate/therapeutic use
  17. Naqvi AA, Hassali MA, Aftab MT
    J Pak Med Assoc, 2019 Mar;69(3):389-398.
    PMID: 30890833
    OBJECTIVE: The study aimed to evaluate literature on rheumatoid arthritis disease in Pakistani patients, to have an understanding about its epidemiology, clinical aspects and socio-economic determinants.

    METHODS: The review study was conducted from December 2017, to May 2018. An online search was conducted in international and local health databases using appropriate search keywords as well as scanning reference lists of related articles. Literature published after year 2000 that reported epidemiological, demographic, clinical and socioeconomic data of Pakistani rheumatoid arthritis patients was included. Meta-analysis was performed where possible. This systematic review was registered on the international prospective register of systematic reviews PROSPERO (CRD42018090582).

    RESULTS: Of the 334 research articles found, 29 (8.7%) were selected. Patients were mostly females, but no study explored impact of disease on household and family role functioning of rheumatoid arthritis-affected women in Pakistan. Most patients were uneducated (55%) and unemployed; had low disease knowledge (N = 149, 74.5%) and poor adherence to disease-modifying anti-rheumatic drugs (N = 23, 23%). Point prevalence of rheumatoid arthritis reported from Karachi was high at 26.9%. Moderate disease activity, i.e., 4.5}0.7 and mild functional disability (N = 66, 51.6%) were seen in RA patients. Almost half (N = 799, 46.9%) had comorbidities. Almost a fifth proportion of RA patients had dyslipidaemia as a comorbidity (N = 134, 16.77%) and higher cardiovascular risk score as modifiable risk factor. Undiagnosed depression (N = 134, 58.3%) and low bone mineral density (N = 93, 40.6%) were reported in RA patients. Direct monthly treatment cost of disease was significantly high considering patients' socio-economic status, i.e., USD 16.47 - 100.68. Most commonly used drug was methotrexate.

    CONCLUSIONS: There is a paucity of data on Pakistani rheumatoid arthritis patients' demographic and socio-economic parameters, especially the gender element.

    Matched MeSH terms: Methotrexate/therapeutic use
  18. Devaraj NK
    Ethiop J Health Sci, 2019 Jan;29(1):957-958.
    PMID: 30700964 DOI: 10.4314/ejhs.v29i1.18
    The diagnosis of rheumatologic problem can be difficult, especially if not all the diagnostic criteria or typical clinical features are seen. This includes conditions such as rheumatoid arthritis which needs early diagnosis to start disease modifying drugs (DMARDs) which can improve the prognosis and prevent further joint erosion and organ damage. This case report focused on a similar scenario in an elderly woman initially thought to have osteoarthritis but was diagnosed later with rheumatoid arthritis which brought much relief to her current predicament.
    Matched MeSH terms: Methotrexate/therapeutic use
  19. Suthandiram S, Gan GG, Zain SM, Bee PC, Lian LH, Chang KM, et al.
    Pharmacogenomics, 2014 Aug;15(11):1479-94.
    PMID: 25303299 DOI: 10.2217/pgs.14.97
    Pharmacogenetics of methotrexate (MTX) contributes to interindividual differences in toxicity. We aimed to evaluate the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 h following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma.
    Matched MeSH terms: Methotrexate/therapeutic use*
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