Administration Of Methotrexate Research Articles

Amlodipine Protects against Methotrexate-Induced Acute Kidney Injury in Rats

Background Methotrexate (MTX) is a commonly used chemotherapy drug with known nephrotoxic effects, including the potential for acute kidney injury. However, the precise mechanism through which MTX induces nephrotoxicity remains unclear, though oxidative stress and direct toxic effects on renal tubules are believed to play key roles. Recent studies suggest that calcium channel blockers may offer promise in slowing down the progression of chronic kidney diseases. Objective The purpose of this study was to explore the potential of Amlodipine, a calcium channel blocker, to alleviate acute kidney injury caused by the administration of MTX in rats. Methods Three groups of twenty-four male Wistar rats were randomly assigned: Group 1—the control group was given normal saline orally. Group II, underwent five days of continuous administration of a single intraperitoneal (IP) dosage of 20 mg/kg MTX. The same dosage of MTX was given to Group III followed by an oral dose of Amlodipine at 5 mg/kg over the same period. Upon completion of the experiment, serum biochemical parameters, renal damage markers, oxidative stress, inflammatory markers, and kidney tissue histology were assessed. Results The results indicate that MTX administration significantly increased the levels of serum biochemical parameters, renal damage markers, inflammatory markers, oxidative stress markers, and induced alterations in kidney histology. However, the administration of Amlodipine following MTX treatment protected against these changes. Conclusion Amlodipine exhibits therapeutic potential in mitigating MTX-induced kidney injury in rats and its associated side effects.

E077 Evaluation of group education for patients with large vessel vasculitis prescribed subcutaneous methotrexate

Abstract Background/Aims Patient education in rheumatology is of proven value to educate as well as to reduce demand on health care services. This can be delivered in a multitude of ways, in person and more recently with the use of multi-media modalities. There is limited evidence to specifically demonstrate the benefit of patient education for patients with vasculitis. Education needs to be adapted to meet patient needs. In addition to one-to-one appointments, we have been conducting in-person group education for this patient group. We present our experience. Methods Patients prescribed subcutaneous methotrexate for large vessel vasculitis were given the opportunity to attend a group education session run by the specialist nurse. The sessions were held over a 4-month period, in groups of 3-5 individuals. Patients were provided with written information including the links to online resources prior to attending the group education session which consisted of a verbal presentation and a short video. Patients also had the opportunity to ask questions during the group session. If patients were happy to proceed with the planned treatment, a prescription for the subcutaneous methotrexate was provided and initial blood monitoring commenced. After attending the group session, patients were given an evaluation form to complete Results The responses from the evaluation forms are shown in the following table: Conclusion Group education has proved to be a successful way of providing education to patients with large vessel vasculitis needing to learn about the indications for use, along with the safe handling and administration of subcutaneous methotrexate. Disclosure G. Ducker: None. C.B. Mukhtyar: None.

Fisetin ameliorates methotrexate induced liver fibrosis.

Methotrexate (MTX), a widely used chemotherapeutic and immunosuppressive agent, is associated with hepatotoxicity, leading to liver fibrosis and cirrhosis. This study explores the regenerative and reparative effects of fisetin, a flavonoid with known antioxidant and anti-inflammatory properties, on MTX-induced liver fibrosis in a rat model. Thirty-six male Wistar albino rats were divided into normal, MTX and saline, and MTX and fisetin. Liver injury was induced in the latter two groups using a single intraperitoneal dose of MTX (20 mg/kg). Fisetin (50 mg/kg/day) or saline was administered intraperitoneally for ten days. After sacrifice, liver tissues were subjected to histopathological evaluation and biochemical analyses, including Transforming Growth Factor-β1 (TGF-beta), sirtuins-1 (SIRT-1), malondialdehyde (MDA), cytokeratin 18, thrombospondin 1, and alanine transaminase (ALT) levels. MTX administration significantly increased liver injury markers, including TGF-beta, MDA, cytokeratin 18, thrombospondin 1, and ALT, while reducing SIRT-1 levels. Fisetin treatment attenuated these effects, demonstrating its potential therapeutic impact. Histopathological analysis confirmed that fisetin mitigated MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. This study proves that fisetin administration can alleviate MTX-induced liver damage in rats. The reduction in oxidative stress, inflammation, and apoptosis, along with the histological improvements, suggests fisetin's potential as a therapeutic agent against MTX-induced hepatotoxicity. Further investigations and clinical studies are warranted to validate these findings and assess fisetin's translational potential in human cases of MTX-induced liver damage.

CLINICAL CASE OF KERATOACANTHOMA

Keratoacanthoma is a common, rapidly growing skin tumour that has long been considered benign due to its staged course and ability to spontaneously regress. However, according to the latest World Health Organization classification, keratoacanthoma is classified as a well-differentiated form of squamous cell carcinoma.
 Despite its long history keratoacanthoma remains a subject of controversy with regard to epidemiology, diagnosis, prognosis, and treatment.
 The etiology and pathogenesis of keratoacanthoma are also not clearly defined. However, a number of factors have been identified that are highly likely to lead to the development of a tumour. In particular, these are ultraviolet and X-ray radiation, thermal and traumatic injuries, chemical carcinogens, genetic and immunological predictors, human papillomaviruses and certain drugs (sorafenib, infliximab, etc.).
 Clinically, keratoacanthoma appears on the skin as a single or multiple crater-like nodule. Dermoscopy can be used for early diagnosis and differentiation from other tumour formations. The choice of therapy varies widely and depends on the location, stage of development, and size of the tumour.
 The publication presents a number of cases which demonstrate the clinical, dermoscopic, and histological picture of keratoacanthomas.
 Case presentation. Patient A, 44 years old, skin with signs of photodamage. A single dense nodule, up to 0.5 cm in diameter, on the anterior surface of the right lower leg. It appeared and grew rapidly over the past month.
 Dermoscopy with photographic fixation was performed. A non-pigmented dome-shaped lesion with central yellow-brown keratinous masses, sporadic haemorrhages, and white structureless areas was observed. The vascular pattern was represented by looped, glomerular and helical vessels in a radial arrangement. The lesion was surgically excised. A pathohistological study was carried out. The conclusion was a well-differentiated squamous cell carcinoma of the skin.
 In typical cases, the diagnosis of keratoacanthoma is not difficult. However, the combination with other skin lesions can distort the clinical picture. For example, in Patient B, keratoacanthoma developed against the background of seborrheic keratosis. In such cases, the use of dermoscopy can provide additional clues to the diagnosis and, accordingly, influence treatment methods.
 Considering keratoacanthoma as a well-differentiated squamous cell carcinoma, surgical excision is preferred. The metastatic potential of this tumour is not significant, but in high-risk areas such as the lip or ear, it can reach 30%. At the same time, surgery reduces the risk of local recurrence. Other approaches include electrodissection and curettage, cryodestruction, intratumoural administration of methotrexate, 5-fluorouracil, bleomycin, and photodynamic therapy. These methods are appropriate in cases where the size or location of the tumour do not allow achieving the desired aesthetic effect.
 Conclusions: 1. Keratoacanthoma is a well-differentiated squamous cell carcinoma with a low potential for metastasis. 2. Central yellow-brown keratinous masses, sporadic haemorrhages, white structureless areas, in combination with looped and glomerular vessels in radial disposition seen during dermoscopy of a nodule, may be a sign of keratoacanthoma. 3. The choice of treatment method for keratoacanthoma depends on its location and size; surgical excision of the tumour should be preferred.

Dilatation and Curettage after Uterine Artery Embolization versus Methotrexate Injection for the Treatment of Cesarean Scar Pregnancy: A Single-Center Experience.

Background and Objectives: Cesarean scar pregnancy (CSP) represents a type of ectopic pregnancy in which the embryo implants inside the scar of a previous cesarean section. This condition can lead to maternal morbidity and mortality. The best therapeutic approach in terms of clinical effectiveness and patient safety for CSP has not been described yet, although different therapeutic strategies are currently available. The purpose of the present study was to analyze the success rate of two different treatments in a single institution. Materials and Methods: A retrospective study was performed among patients diagnosed with CSP at the Gynecology and Obstetrics Department of the "Cannizzaro" Hospital in Catania (University of Enna-Italy) from January 2016 to December 2022. The diagnosis was made by 2D/3D transvaginal ultrasound, following Timor-Tritsch criteria. Two treatment strategies were performed: local and systemic methotrexate (MTX) injection and uterine artery embolization (UAE) with subsequent dilatation and curettage (D&C). All treated women underwent subsequent clinical and sonographic follow-up. Complete recovery was defined as the reduction of β-HCG values until it was undetectable and the disappearance of the mass in the uterine scar on ultrasound. Results: Nineteen patients were included; nine were in the MTX group and ten were in the UAE + D&C group. No significant differences were found between the two groups in terms of clinical parameters. Treatment was successful in 4 of 10 (44%) patients in the MTX group and 10 of 10 (100%) in the UAE + D&C group (p = 0.01); the length of hospital stay was significantly shorter in the latter group (p < 0.0001). Conclusions: In our experience, administration of MTX is not recommended as the primary treatment or pre-treatment. Dilatation and curettage after uterine artery embolization are better than methotrexate injection for the treatment of cesarean scar pregnancy in a single-institution series in terms of complete recovery and length of hospital stay.

The incidence and prognosis of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of the lung related to methotrexate: A retrospective study

Background and objectiveOther iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung. MethodsPatients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed. ResultsAmong the 51 patients with OIIA-LPD, 16 (31.3%, 7 men, 9 women) had OIIA-LPD of the lung (median age, 69 [range, 63–82] years). Peripheral lesions were observed in 10 (62.5%), central lesions in two (12.5%), and both lesions in four (25.0%) patients. Nine of the 16 patients underwent bronchoscopic biopsy, seven were diagnosed (diagnostic yield, 77.8%) and, re-biopsy was performed in 2 patients. Eight (50.0%) patients had LPD and six (37.5%) had diffuse large B-cell lymphoma. In the 14 patients with confirmed treatment efficacy, the overall response rate to MTX withdrawal was 71.4%. However, chemotherapy was required in case of larger lesions (three patients). Death related to OIIA-LPD occurred in only one patient, and 11 of the 14 patients were alive during the study period (median follow-up time, 53.7 [range, 4.3–84.2] months). ConclusionThe incidence of OIIA-LPD of the lung is 31.3% and higher than that reported previously. The treatment effect of MTX withdrawal seems to be sufficient; however, in some cases, chemotherapy may be required from the beginning.

Prevalence of methotrexate intolerance among patients with rheumatoid arthritis in Erbil city using methotrexate intolerance severity score

Background and objectives: Rheumatoid arthritis is classified as an autoimmune disease characterized by inflammation of the joints and membranes surrounding the joints. The aim of this study was to find the frequency of methotrexate intolerance among rheumatoid arthritis patients and to detect factors contributing to intolerance. Methods: An observational cross-sectional study was conducted in Rizgary and Hawler Teaching Hospital in Erbil/ Iraq. The study period started from the 1st of July 2021 to the 1st of July 2022. A convenient sample of hundred patients was included in the study. A validated version of the methotrexate intolerance severity score questionnaire was used for data collection. Each element in the methotrexate intolerance severity score questionnaire was given a score ranging from 0-3 depending on the absence of symptoms or the presence of mild, moderate or severe symptoms. The intolerance was diagnosed based on a cut-off score of 6 and more. Results: Females constituted 93% of the sample, 49% were obese, and only 13% were smokers. Among the rheumatoid arthritis patients, 66% tolerated Methotrexate, and only 34% did not tolerate the treatment. The oral dose was tolerated by 71%, and the only significant relation(p=0.050) was reported for the route of Methotrexate administration. The differences were significant for restlessness (p&lt;0.001), crying (p=0.002), irritability(p&lt;0.001), and not taking medication. Conclusions: The study concluded that Methotrexate intolerance is prevalent among Rheumatoid arthritis patients in Erbil city. The prevalence of intolerance was significant among steroid users.

Methotrexate treatment strategies for rheumatoid arthritis: a scoping review on doses and administration routes

BackgroundTo describe the evidence of methotrexate (MTX) initiation strategies in patients with rheumatoid arthritis (RA) and, in the case of non-responders, analyse the efficacy and safety of route and dose optimisation.MethodsWe conducted a comprehensive scoping review of randomised controlled trials according to PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O’Malley. PubMed, EMBASE, and Cochrane were searched without language restriction, and hand searches of relevant articles were examined.ResultsWe identified 1,367 potentially eligible studies, of which 12 were selected based on the titles and abstracts and then on the full-length articles. In naïve-MTX patients, a linear dose-response relationship for starting dose was found between 5 mg/m2/week (7.5–10 mg/week) and 10 mg/m2/week (15–22 mg/week), without toxicity correlation. A higher initial dose of MTX (25 mg vs. 15 mg) was more effective, resulting in fewer dose increases due to ineffectiveness and more dose reductions due to higher remission rates. There was also a trend towards increased gastrointestinal toxicity. Comparing different routes of administration of MTX, subcutaneous MTX showed a statistically higher ACR20 response (85%) in comparison with oral MTX (77%) (p < 0.05). The clinical efficacy and safety of accelerated and conventional start MTX regimens were comparable between 7.5 and 15 mg with a 2,5 mg dose increase every two weeks. In RA patients who have failed the initial treatment with MTX, the stepwise increase in MTX doses is associated with a higher ACR20 response and sustained remission rate than other strategies. In MTX non-responders, optimisation to SC MTX was associated with improvements in ACR20 and ACR50 rates with similar toxicity between groups. In the early RA patients subgroup, SC MTX showed higher ACR20 response rates than oral MTX, and intensive oral methods have a much higher sustained remission rate, shorter mean time to remission, and better clinical disease activity measures than conventional treatments.ConclusionsHigher starting doses of MTX and initial subcutaneous MTX made better performance in improving the ACR20 response, although the clinical effectiveness and safety of other MTX start regimens are comparable. This scoping review provides evidence in support of optimising MTX treatment in terms of route and dose prior to concluding that MTX treatment in RA patients has failed.

Cost-effectiveness analysis of expectant vs active management for treatment of persistent pregnancies of unknown location

BackgroundPersistent pregnancies of unknown location (PUL) are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. ObjectiveThis study was designed to assess the cost-effectiveness between three primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical two-dose methotrexate, (3) uterine evacuation followed by methotrexate, if indicated. Study DesignWe conducted a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location (ACT or NOT) multicenter randomized trial conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, two-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon following randomization. Costs were expressed in 2018 U.S. dollars. Effectiveness was measured in quality-adjusted life-years (QALYs) and the rate of salpingectomy. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. ResultsMethotrexate had the lowest mean cost, $875, followed by expectant management $1085, and uterine evacuation $1902 (p=0.001). Expectant management had the highest mean QALY (0.1043) followed by methotrexate (0.1031) and uterine evacuation (0.0992) (p=0.0001). Salpingectomy rate was higher for expectant management compared to methotrexate (9.4% vs 1.2%; p=0.02) and expectant management compared to uterine evacuation (9.4% vs 8.1%; p=0.04). Uterine evacuation, with highest costs and lowest QALYs, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared to methotrexate at a willingness-to-pay of $150,000/QALY given an ICER of $175,083/QALY gained (95% CI, -$1,666,825-2,676,375). Threshold analysis demonstrated methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Expectant management would also be favorable in lower risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability expectant management was cost-effective compared to methotrexate at a willingness-to-pay of $150,000/QALY gained was 50%. Results were dependent on the cost of surgical intervention, and the expected rate of methotrexate failure. ConclusionManagement of pregnancies of unknown location with a two-dose methotrexate protocol may be cost-effective compared to expectant management and uterine evacuation. While uterine evacuation was dominated, expectant management versus methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.

Rechallenge With High-Dose Methotrexate After Treatment With Glucarpidase in Adult Patients With Lymphoma.

Limited evidence exists regarding methotrexate (MTX) resumption after patients with lymphoma receive glucarpidase for toxic MTX levels and acute kidney injury (AKI). This retrospective review included adults with lymphoma treated with glucarpidase after MTX at Mayo Clinic between January 31, 2020, and October 10, 2022. Descriptive statistics summarize patient characteristics and clinical outcomes. Of 11 patients treated with glucarpidase after MTX, seven (64%) were rechallenged with MTX. Indications for MTX rechallenge included confirmed CNS disease (n = 6, 86%) and intravascular lymphoma (n = 1, 14%). Compared with the nonrechallenged subgroup, before receiving MTX that required glucarpidase rescue, the rechallenged patients had lower median pretreatment serum creatinine (Scr; 0.7 v 1.2 mg/dL), and none had AKI with previous MTX doses, n = 0 (0%) versus n = 2 (50%). During the MTX dose requiring glucarpidase rescue, the rechallenged group had lower median peak Scr (1.26 v 3.32 mg/dL) and lower incidence of AKI stage III (n = 1 [14%] v n = 3 [75%]), and none of the rechallenged patients required renal replacement therapy (RRT; n = 0 [0%] v n = 1 [25%]). At the first rechallenge after glucarpidase administration, the median MTX dose reduction was 56% (range, 46%-75%), and the lowest used dose when prescribed according to each treatment protocol schedule was 1.5 g/m2. Two (29%) patients experienced AKI (n = 1 stage I, n = 1 stage II) after MTX rechallenge. Zero patients required RRT, and zero required another glucarpidase administration. Six (86%) patients completed all recommended MTX doses. In selected adults with lymphoma who required glucarpidase for toxic MTX levels after administration of high-dose MTX, resumption of MTX therapy at lower doses is safe. Patients selected for MTX resumption had experienced less severe AKI during the previous cycle compared with those not selected for MTX resumption.

The Protective Effect of Roflumilast Against Acute Hepatotoxicity Caused by Methotrexate in Wistar Rats: In vivo Evaluation.

Methotrexate (MTX) is one of the most widely used drugs in cancer chemotherapy and treating rheumatoid arthritis. The hepatotoxicity of MTX is one of its major side effects. Roflumilast (ROF) has been recognized to have antioxidant and anti-inflammatory activity in in-vivo and in-vitro models. The present study aimed to explore the potential protective effects of roflumilast against MTX-induced liver toxicity in male Wistar rats. High dose of 5 mg/kg for 4 consecutive days subcutaneous (S.C) injection of methotrexate for induction of acute liver injury. A total of 24 Wistar rats, rats were used in four different groups. The NS injections were given S.C to the control group once a day for 4 consecutive days. SC injections of MTX (5 mg/kg) were given to the MTX group daily for four days. At 5 mg/kg once daily for four days, the roflumilast group was given daily oral roflumilast. An injection of MTX and oral roflumilast were given to the MTX + roflumilast group once daily for four consecutive days. Administration of high dose MTX (5 mg/kg) today 4 produced a significant decrease in hepatic glutathione (GSH) levels and a significant increase in ALT and AST liver enzymes, hepatic malondialdehyde (MDA), tumor suppressor protein (p53), interleukin 6, interleukin 1 levels compared to the control group. Treatment with roflumilast for 4 days significantly attenuated unfavorable changes in these parameters. According to histopathological findings, Roflumilast significantly reduced MTX-induced inflammation and degeneration in the liver. In conclusion, the findings indicate that roflumilast may have a potential therapeutic benefit in treating rats with MTX-induced liver toxicity by mitigating its effects. The aim of this study is to investigate the potential protective effects of roflumilast against MTX-induced liver toxicity in Wistar rats.

A Pilot Study to Assess the Suitability of Riboflavin as A Surrogate Marker of Breast Cancer Resistance Protein (BCRP) in Healthy Participants.

We recently showed that riboflavin is a selected substrate of BCRP over P-gp and demonstrated its prediction performance in preclinical DDI studies. The aim of this study was to investigate the suitability of riboflavin to assess BCRP inhibition in humans. First, we assessed the substrate potential of riboflavin towards other major drug transporters using established transfected cell systems. Riboflavin is a substrate for OAT1, OAT3, and MATE2-K with uptake ratios ranging from 2.69 to 11.6 but riboflavin is not a substrate of OATP1B1, OATP1B3, OCT2, and MATE1. The effects of BMS-986371, a potent in vitro inhibitor of BCRP (IC 50 0.40 µM), on the pharmacokinetics of riboflavin, isobutyryl carnitine, and arginine were then examined in healthy male adults (N = 14 or 16) following oral administration of methotrexate (MTX) (7.5 mg) and enteric coated (EC) sulfasalazine (SSZ) (1,000 mg) alone or in combination with BMS-986371 (150 mg). Oral administration of BMS-986371 increased the AUCs of rosuvastatin and immediate-release (IR) SSZ to 1.38- and 1.51-fold , respectively, and significantly increased AUC(0-4h), AUC(0-24h), and C max of riboflavin by 1.25-, 1.14-, and 1.11-fold (P-values of 0.003, 0.009, and 0.025, respectively) compared to the MTX/SSZ EC alone group. In contrast, BMS-986371 did not significantly influence the AUC(0-24h) and C max values of isobutyryl carnitine and arginine (0.96- to 1.07-fold, respectively; P > 0.05). Overall, these data indicate that plasma riboflavin is a promising biomarker of BCRP that may offer a possibility to assess drug candidate as a BCRP modulator in early drug development. Significance Statement Endogenous compounds that serve as biomarkers for clinical inhibition of BCRP are not currently available. This study provides the initial evidence that riboflavin is a promising BCRP biomarker in humans. For the first time, the value of leveraging the substrate of BCRP with acceptable prediction performance in clinical studies is shown. Additional clinical investigations with known BCRP inhibitors are needed to fully validate and showcase the utility of this biomarker.

Polymyalgia rheumatica-Achallenge in geriatrics : Interdisciplinary presentation of diagnostics and treatment

Polymyalgia rheumatica is the second most frequent inflammatory rheumatic disease in people aged over 50years, after rheumatoid arthritis. It is characterized by pain and morning stiffness in the region of the shoulders, hip girdle and neck. It can be associated with giant cell arteritis (CGA). Treatment with glucocorticoids is indispensable. The duration of treatment varies and often exceeds 1year. The additive administration of methotrexate is an option for saving glucocorticoids. The biologicals tocilizumab or secukinumab are very promising alternatives. The course of treatment should be closely monitored for inflammation parameters, glucocorticoid side effects, pain, visual acuity, depression, activities of daily living and especially related to functions of the upper extremities. The geriatric assessment plays an important role in the management of this condition.

Safety of methotrexate administration in women with pregnancy of unknown location deemed to have high risk of ectopic pregnancy.

This study evaluates the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have high risk of underlying ectopic pregnancy (EP) and to investigate whether this would result in inadvertent exposure of MTX to viable intra-uterine pregnancy (IUP). A retrospective observational study was conducted on clinically stable women who were classified PUL at Early Pregnancy Unit, Nepean Hospital, between 2007 and 2021. PUL is defined as when a woman presents with a positive pregnancy test but has no signs of IUP or EP on the transvaginal ultrasound (TVS). If patients with a PUL behave biochemically like an EP but the location is not confirmed on ultrasound, these women are eligible for MTX to minimize the risk of subsequent tubal rupture.Criteria discussed in the guidelines of American College of Obstetricians and Gynaecologists (ACOG),American Society for Reproductive Medicine (ASRM),Royal College of Obstetricians & Gynaecologists(RCOG)and National Institute for Health Care Excellence (NICE)were applied to the collected PUL database. The number of patients eligible to receive MTX and the number of women with underlying viable IUP who would be inadvertently given MTX were calculated. A total of 816 consecutive women with PUL were reviewed, and 724 had complete data and were included in the final analysis. 6 patients were persistent PULs,and 718 fell among outcomes of 4 subgroups: viable IUP, non-viable IUP, EP, failed PUL. According to the ACOG, ASRM, RCOG and NICE, the rate of possible MTX administration among patients with a PUL is 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no single persistent-PUL would have received MTX according to the above protocols, and majority of the MTX treatment were unnecessary because those patients were classified as NVIUP or FPUL later. More importantly, ACOG and ASRM could theoretically result in inadvertent MTX administration to women with an underlying IVUP at rates of 4.1/1000 (3/724). Current guidelines used to predict high risk of EP among PUL population are not safe enough to avoid inadvertent MTX administration to women with an underlying viable IUP.These guidelines need to be wisely used to ensure that no wanted pregnancy is exposed to MTX. Women with PULs should be carefully monitored and MTX should be used with judicious care when the location of pregnancy is yet to be confirmed. This article is protected by copyright. All rights reserved.

Search for predictors of methotrexate toxicity in rheumatoid arthritis

Aim. To determine prognostic markers of methotrexate (MT) toxicity in rheumatoid arthritis (RA).Materials and methods. The study included 294 patients with RA who were prescribed MT at a dose of 10 to 25 mg per week for the first time as basic anti-inflammatory therapy (BPVT). The following adverse events (AEs) were recorded: hepatotoxicity, toxicity from the gastrointestinal tract, blood system. Qualitative parameters were considered as possible predictors of MT intolerance: gender, obesity, smoking, systemic manifestations, as well as rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (ACCP), intake of glucocorticosteroids (GCS), form of administration of MT; and quantitative: age of RA onset, baseline disease activity according to DAS28 (Disease Activity Score 28) and HAQ (Health Assessment Questionnaire), MT dose. Statistical processing was performed by one-factor methods using Pearson’s χ2 test with Yates correction, Fisher’s exact two-tailed test, Mann–Whitney U-test, and Student’s t-test. Multivariate analysis was carried out by binary logistic regression.Results. In a univariate analysis, significant results were obtained for hepatotoxicity: a direct correlation with the use of corticosteroids at the onset (odds ratio (OR) 2.0; 95 % confidence interval (CI) 1.1–3.8, p = 0.03), inversely correlated with MT tablet intake (OR 0.5, 95 % CI 0.2–0.95, p = 0.03). According to the results of multivariate analysis, hepatotoxicity was recorded more often when taking GCS in the debut 2.01 times (95 % CI 1.02–3.96, p = 0.043), and in the presence of ACCP – 3.16 times (95 % CI 1.06–9.45, p = 0.039); and less frequently when taking tableted MT by 2.62 times (95 % CI 0.17–0.84, p = 0.017). Gastrointestinal toxicity tends to be associated with a younger age of RA onset (p = 0.06) and greater RA HAQ activity at onset (p = 0.07).Conclusions. Hepatotoxicity is more expected in patients seropositive for ACCP and GCS treatment in the onset of RA, but is less common when taking MT tablets. AEs from the gastrointestinal tract are associated with a younger age of onset of the disease and a greater degree of activity according to the HAQ index.

Evaluación de los niveles de adropina en el tejido renal después del tratamiento con Metotrexato en ratas: un estudio experimental prospectivo

In this study, it was aimed to investigate Adropin levels in kidney tissues after Methotrexate (MTX) administration to identify potential changes following administration of agents with antioxidant/anti–inflammatory potential. Twenty four adult rats male albino Wistar rats were used in this study, and randomly divided into four groups. Control: These rats did not receive any treatment during the 14–day (d) experiment. N–acetylcysteine (NAC): These rats were administered 100 mg·kg-1·day-1 NAC intraperitoneally (i.p.) for 14 d. MTX: A single dose of 20 mg·kg-1 MTX was administered i.p. at the beginning of the study. MTX+ NAC: A single dose of 20 mg·kg-1 MTX was administered i.p. at the beginning of the study, and the rats were given 100 mg·kg-1·day-1 NAC i.p. for 14 d. Total antioxidant, and serum Adropin levels were found to be the lowest in the MTX group while the oxidant levels were significantly lower in the MTX group than in the MTX+NAC group (P&lt;0.001). TUNEL positivity was similar among the groups, and no significant differences were observed. It was considered that these findings have shed light on the role of Adropin in the development of kidney failure following MTX administration.

The Prospective Effect of Green Tea versus Pomegranate Peels Extracts on Submandibular Salivary Glands of Albino Rats after Methotrexate Administration (Histological and Immunohistochemical Study).

There is curiosity in the use of substances that can stop cell damage. Antioxidants are substances that can prevent free radicals from damaging cells, and they can be used to treat and avoid a wide variety of illnesses. The current investigation set out to evaluate the histological changes brought on by a single high dose of methotrexate in the submandibular glands of rats treated with green tea and pomegranate peel extract, both are well-known as antioxidants. Forty-eight healthy Albino rats were used in the current study. Animals were divided into six groups. Group 1: Vehicle group which is control group, Group 2: methotrexate treated group, Group 3: green tea control group, Group 4: pomegranate peel extract control group, Group 5: green tea + methotrexate group, and Group 6: pomegranate peel extract + methotrexate group. Rats of all groups were left 1 week after the end of the treatment. Cervical dislocation was used to kill all of the rats. Samples were gained from the rats' submandibular salivary glands of different groups for histological and immunohistochemical evaluation. Green tea + methotrexate group showed improvement in the histological picture of the submandibular salivary gland compared to methotrexate group and the pomegranate peel extract + methotrexate group. The antioxidant activity of green tea is more potent than that of pomegranate peels extract in blocking methotrexate that induced cytotoxicity in the submandibular salivary glands of rats. As a result, it can be administered to people undergoing cancer treatment as a safeguard for their salivary glands.

Remission of Cardiac Sarcoidosis after the Administration of Methotrexate as First-line Drug Therapy

Remission of Cardiac Sarcoidosis after the Administration of Methotrexate as First-line Drug Therapy

Effect of vitamin B12 on methotrexate-induced cardiotoxicity in rats.

Methotrexate (MTX) is a drug with anti-inflammatory and immunosuppressive effects and is also a folic acid antagonist. Our aim in this study is to determine the molecular mechanisms of cardiotoxicity caused by MTX, a chemotherapeutic drug, and to evaluate the protective effects of vitamin B12 on this toxicity. A total of 32 rats were used in our study and 4 groups were formed. Control group, Vit B12 group (3 μg/kg B12 for 15 days, IP), MTX group (20 mg/kg MTX single dose on day 8 of the experiment, IP), MTX +Vit B12 group (3 μg/kg, IP ), Vit B12 throughout the 15 days, and a single dose of 20 mg/kg MTX (IP) on day 8 of the experiment. Immunohistochemically, expressions of hypoxia-inducible factor 1α (HIF1-α), vascular endothelial growth factor receptor-2 (VEGFR-2), erythropoietin (EPO), and interleukin-6 (IL-6) were evaluated in the heart tissue. Total catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the heart tissue. At the same time, ANP and NT-proBNP levels were measured in the blood serum. In the study, the expression of HIF1-α and VEGFR-2 increased significantly in the MTX group, while IL-6 and EPO significantly decreased. At the same time, CAT and SOD levels were significantly decreased and MDA levels increased significantly in the MTX group. While vitamin B12 significantly corrected all these values, it also greatly reduced the increases in ANP and NT-proBNP levels caused by MTX. It is important to use Vit B12 before and after MTX administration to replace the folate that MTX has reduced.

ВЛИЯНИЕ ПРИМЕНЕНИЯ МЕТОТРЕКСАТА НА СОСТОЯНИЕ МИЕЛОПОЭЗА И ТРОМБОЦИТОПОЭЗА У ДЕТЕЙ С ИДИОПАТИЧЕСКИМ АРТРИТОМ

Methotrexate is the mainstay drug in the treatment of juvenile idiopathic arthritis (JIA). The effect of methotrexate on the hematopoietic system manifests itself in the form of its inhibition, contributing to the development of aplastic anemia, leukopenia, neutropenia and thrombocytopenia. The purpose of the study was to study the effect of methotrexate on the state of the leukocyte and megakaryocyte pool of cells in patients with JIA. Material and methods. The study was carried out on the basis of the 2nd City Children's Clinical Hospital in Minsk. A study of the state of hematopoiesis was carried out in 82 children with JIA who received only methotrexate. The comparison group consisted of 40 patients who were diagnosed with JIA and had a complete blood count performed before starting methotrexate therapy. Results. Statistically significant differences were identified in both the megakaryocyte and leukocyte series. Against the background of an increase in the number of platelets before the start of basic therapy, there was a decrease in the average volume of platelets (p&lt;0.01) and, accordingly, the distribution of platelets by volume (p&lt;0.001). Changes in the white blood cell count (WBC) were manifested in a gradual decrease in the number of leukocytes during long-term use of methotrexate (p &lt; 0.001). Conclusion. The use of methotrexate in patients with JIA contributes to a significant decrease in the content of platelets, leukocytes, neutrophils, lymphocytes, and monocytes, which is due to the relief of the inflammatory process. The duration of methotrexate administration did not affect the content of lymphocytes and basophils.