Methotrexate Therapy Research Articles

Intralesional or intraorbital rituximab injection for the management of biopsy-proven idiopathic orbital inflammation involving the lacrimal gland

ObjectifMesurer l'efficacité de l'injection intralésionnelle de rituximab dans la prise en charge de l'inflammation orbitaire idiopathique (IOI) touchant la glande lacrymale, soit le sous-type le plus fréquent. MéthodeOn a inclus 18 patients consécutifs qui présentaient une IOI touchant la glande lacrymale objectivée par biopsie et auxquels on a administré le rituximab (50 mg/5 mL) directement dans la lésion une fois par mois. RésultatsDu point de vue clinique, tous les patients présentaient un œdème et une ptose de la paupière supérieure. La plupart d'entre eux (56 %) avaient en outre une douleur périoculaire et une masse supéro-temporale palpable. Les biopsies ont fait ressortir une inflammation chronique sans fibrose chez 14 patients (78 %) et une inflammation chronique s'accompagnant de fibrose chez 4 patients (22 %). Ainsi, 1 patient (6 %) a reçu une seule dose de rituximab par voie intralésionnelle parce qu'il a bénéficié d'une réponse complète après la première injection; 11 patients (61 %) ont reçu 2 doses tandis que 6 patients (33 %) ont reçu 3 doses en raison d'une réponse partielle après les 2 premières injections. Après un suivi moyen de 33 mois (médiane : 33 mois; fourchette : 11–59 mois), 16 patients (89 %) ont eu une réponse clinique, dont 14 patients (78 %) chez lesquels la réponse était complète (soit la disparition de toutes les lésions) et 2 patients (11 %) chez lesquels la réponse était partielle (soit une diminution de ≤ 30 % du diamètre de la lésion). Par ailleurs, 2 patients (11 %) n'ont eu aucune réponse après 3 injections et ont dû entreprendre un traitement par voie générale associant un corticostéroïde et le méthotrexate. Enfin, 2 des patients (11 %) qui avaient eu une réponse complète ont subi une récurrence 12 et 49 mois après la dernière injection. Ces 2 patients ont reçu 2 doses supplémentaires de rituximab, espacées de 1 mois, et affichaient une réponse complète lors de l'examen de suivi 27 et 11 mois après le traitement, respectivement. ConclusionL'injection intralésionnelle de rituximab peut constituer un traitement efficace de l'IOI touchant la glande lacrymale, le taux de réponse complète ayant atteint 78 % dans notre série de cas. L'administration locale de rituximab permet d’éviter les éventuels effets indésirables oculaires et systémiques typiques des corticostéroïdes et des immunosuppresseurs administrés par voie générale.

Methotrexate Polyglutamate Concentrations as a Possible Predictive Marker for Effectiveness of Methotrexate Therapy in Patients with Sarcoidosis: A Pilot Study.

Methotrexate (MTX), a folate antagonist, is often used as second-line treatment in patients with sarcoidosis. Effectiveness of MTX has large inter-patient variability and at present therapeutic drug monitoring (TDM) of MTX is not possible. Upon administration, MTX is actively transported into cells and metabolized to its active forms by adding glutamate residues forming MTXPG(n=1-5) resulting in enhanced cellular retention. In this study we address the question whether different MTXPG(n) concentrations in red blood cells (RBC) of patients with sarcoidosis after 3months of MTX therapy correlate with response to treatment. We retrospectively included patients with sarcoidosis that had started on MTX therapy and from whom blood samples and FDG-PET/CT were available 3 and 6-12months after MTX initiation, respectively. FDG-uptake was measured by SUVmax in the heart, lungs and thoracic lymph nodes. Changes in SUVmax was used to determine anti-inflammatory response after 6-12months of MTX therapy. MTXPG(n) concentrations were measured from whole blood RBC using an LC-MS/MS method. Pearson correlation coefficients were calculated to evaluate the relationship betweenchanges in the SUVmax andMTXPG(n) concentrations. We included 42 sarcoidosis patients treated with MTX (15mg/week); 31 with cardiac sarcoidosis and 11 with pulmonary sarcoidosis. In MTXPG3 and MTXPG4 a significant negative relation between the absolute changes in SUVmax and MTXPG(n) was found r = - 0.312 (n = 42, p = 0.047) for MTXPG3 and r = - 0.336 (n = 42, p = 0.031 for MTXPG4). The other MTXPG(n) did not correlate to changes in SUVmax. These results suggest a relation between MTXPG(n) concentrations and the anti-inflammatory effect in patients with sarcoidosis. Further prospective validation is warranted, but if measuring MTXPG concentrations could predict treatment effect of MTX this would be a step in the direction of personalized medicine.

Management of non-tubal ectopic pregnancy: A case series

The aim of this study is to review the various modalities used for management of non-tubal ectopic pregnancies. Ectopic pregnancy is a rare occurrence comprising 1-2% of all pregnancies. However, the most common site for ectopic implantation is fallopian tube. Tubal ectopic pregnancies 95% of all ectopic pregnancies while rest 5% are non-tubal pregnancies. Common sites for non-tubal ectopic pregnancy are cervical, cornual, interstitial, caesarean scar, ovarian and abdominal. Often misdiagnosed, however, detailed history taking, clinical examination and ultrasound helps to establish diagnosis. In this article, we discuss various cases of non-tubal ectopic pregnancy managed with medical treatment using methotrexate or surgical intervention or a combination of both. This study is a retrospective study carried out at MGM Medical College, Navi Mumbai, India between the years 2020-2022A total of 10 patients were diagnosed using clinical, laboratory and radiological methods and were then managed using medical and surgical management modalities ranging from methotrexate therapy to obstetric hysterectomy.There should be a clear protocol for management of non-tubal ectopic pregnancies in hospitals since there is an anticipated rise in the near future because of an increased rate of risk factors.

Methotrexate therapy for adult and paediatric moderate-to-severe atopic dermatitis: A PRISMA-compliant meta-analysis of data from daily practice.

Of the 15 eligible studies identified via electronic searches in MEDLINE, EMBASE and CENTRAL in November 2022 for methotrexate therapy of moderate-to-severe atopic dermatitis, 12 were non-randomized controlled trial (non-RCT) studies with data from 437 patients (235 adults and 202 children). The response rates for short-term therapy were 77% [95% CI 55-99] (four studies; adults) - comparable to 81% [54-100] of RCTs (two studies; adults) (p = 0.63) - and 61% [43-79] (two studies; children), and for medium/long-term therapy were 88.9% [74.3-100.0] (four studies; adults) and 77.7% [61.5-94.0] (three studies; children). Children had a markedly lower rate of treatment discontinuation due to side effects [2.0% (five studies; children) vs. 14.9% (six studies; adults)], but were more likely to experience gastrointestinal disorders {relative risk (RR) 2.0 [1.44-2.71]}, fatigue (RR 2.3 [1.35-3.72]), headache (RR 2.8 [1.23-5.61]), and infections (RR 2.9 [2.18-3.58]). Other adverse events (children vs. adults) included hepatic disorders (32/176 vs. 35/305) and blood and lymphatic system/bone marrow disorders (25/148 vs. 19/184). Four serious adverse events were reported (children). Evidence from daily practice was limited by bias in the selection of participants in the study.

Abstract 11916: An Elusive and Unusual Diagnosis of Cardiac Sarcoidosis

Introduction: Cardiac sarcoidosis (CS) can present heterogeneously; presentations are often related to conduction system abnormalities in the form of AV block or ventricular arrhythmia, or heart failure. There are not yet widely accepted diagnostic guidelines for CS although diagnostic pathways such as the Japanese Ministry of Health and Welfare and the Heart Rhythm Society criteria exist. Methods: A 65 year old female with a history of hypertension, HFpEF, CAD with remote DES to RCA, CKD3a, Obesity and biopsy proven pulmonary sarcoidosis presented with 3 days of sudden onset dyspnea and hypoxia. Labs included aa pro-BNP of 16,754 pg/mL (0-299) and high-sensitivity troponin of 35 ng/L (0-14). EKG showed sinus rhythm with left axis and QTc of 499 ms. Chest Xray revealed pulmonary edema consistent with heart failure exacerbation Echocardiogram revealed EF 60-64%, normal LV and RV wall motion and thickness, and GLS of-17.2%. Left heart catheterization revealed patent RCA stent and non-obstructive CAD. She was diuresed to euvolemic state. Inpatient cardiac monitoring, repeat EKGs, and an 8 day holter monitor showed no arrhythmia or conduction abnormality. Although clinical suspicion for CS was low due lack of arrhythmia, preserved EF and several independent risk factors for HFpEF. FDG-PET was performed to rule out CS and revealed defects in basal anteroseptal and apical lateral regions consistent with sarcoid related fibrosis (Figure 1). Disseminated disease was seen in mediastinal and splenic regions. The patient was started on prednisone and methotrexate therapy for immunosuppressive treatment of CS. Conclusions: In patients with known sarcoidosis, a high index of suspicion for CS is required due to lack of clear diagnostic guidelines. Although diagnostic criteria frequently highlight systolic heart failure and arrhythmias, CS can present in patients with HFpEF, and the presence of other risk factors for diastolic heart failure should not preclude CS investigation.

Erythrocyte Folyl Polyglutamate Synthetase Activity Profiling as a Potential Tool for the Prediction of Methotrexate Efficacy and Toxicity in Rheumatoid Arthritis

Methotrexate (MTX) is the cornerstone of therapy in the treatment of rheumatoid arthritis (RA). However, its efficacy and toxicity are variable and remain unpredictable. Interindividual variation in the metabolism of MTX by the enzyme folyl polyglutamate synthetase (FPGS) has been associated with response variability in RA. In this work, we propose the development of a FPGS phenotyping assay that can be evaluated as a tool for the prediction of efficacy and toxicity in patients with RA prior to initiating MTX therapy. FPGS activity was measured in erythrocyte lysate by monitoring methotrexate polyglutamate (MTX + Glun) formation using ultra-performance liquid chromatography tandem–mass spectrometry (UPLC/MS/MS). Erythrocyte FPGS activity was measured in newly diagnosed RA (n = 35) and osteoarthritis (n = 7) patients. The enzymatic assay was optimized for measuring FPGS activity in 25 µL of packed erythrocytes over two hours. The coefficient of variation for intra- and inter-day analysis was found to be 5% and 12%, respectively. The method was used to measure FPGS enzyme kinetics, resulting in a mean (SD) Km of 30.3 (4.8) µM and a Vmax of 612 (193) pmol MTX + Glu2/h/mL of packed erythrocytes. Mean (SD) erythrocyte FPGS activity in patients with RA was found to be 445.93 (344.50) pmol MTX + Glu2/h/mL and with a 26-fold difference in the range (range: 83–2179 pmol MTX + Glu2/h/mL) whereas for patients with OA, it was found to be 409.80 (157.66) pmol MTX + Glu2/h/mL with a 3.5-fold difference in the range (range: 200.95–683.93 pmol MTX + Glu2/h/mL). Monitoring erythrocyte FPGS activity may be a feasible strategy of phenotyping for methotrexate efficacy and toxicity in patients with RA.

Mycosis fungoides with spongiosis: a case report

BackgroundMycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). CTCL are an uncommon, heterogeneous group of non-Hodgkin lymphomas (NHLs) of T- and B-cell origin where the skin is the primary organ of involvement. It is characterized by malignant CD4+ T-cells infiltrating the skin and other organs, leading to progressive skin and systemic involvement. Histopathologically, MF is characterized by atypical lymphocytes demonstrating epidermotropism without spongiosis. Spongiosis is the histological hallmark of intercellular epidermal edema, viewed as clear spaces within the epidermis, and is very common in benign inflammatory dermatoses. Very few studies have reported MF in sub-Saharan Africa (SSA). We are reporting a case of MF with a rare presentation of spongiosis treated successfully with a low dose total skin electron beam therapy (TSEBT) followed by maintenance therapy of low dose Methotrexate (MT) at the Ocean Road Cancer Institute (ORCI) in Tanzania. This is the first case of MF to be managed with low-dose TSEBT in Tanzania. The authors wish to create awareness of the disease among physicians and pathologists and expand on the data paucity in SSA.Case descriptionWe are reporting a case of a 31-year-old male of African origin who self-referred to our oncology center with a 4-year history of skin rashes throughout the body, which was unresponsive to topical steroid treatment. The biopsy was taken, and the patient was diagnosed with MF CD 3 positive with spongiosis. The patient was treated with radiotherapy, whereby he received low dose total skin electron beam therapy (TSEBT) 12 Gy in 3 fractions at a daily dose of 4 Gy, followed by maintenance therapy of low dose Methotrexate and attained an excellent therapeutic response.ConclusionSpongiosis is an infrequent presentation of MF. Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with MF, which could be administered safely multiple times during a patient's disease with an acceptable toxicity profile. Lack of tendency to perform skin biopsies and cost constraints in assessing multiple immunophenotypic markers lead to missing the diagnosis. Diagnosis and treatment of MF in resource-limited countries is challenging.

Primary Central Nervous System Lymphoma and Contemporary Clinical Prognostication

Background: Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma with two-year overall survival (OS) rates of 66-70% reported in prospective clinical trials. Induction therapy with high-dose methotrexate (HD-MTX) followed by consolidation has become the mainstay of treatment, however, there are few contemporary and robust prognostication indices widely available for clinical use. Some of the most used indices were developed prior to the routine use of rituximab and include the International Extranodal Lymphoma Study Group (IELSG; 1980-1999), Memorial Sloan-Kettering Cancer Center (MSKCC; 1983-2003), Nottingham/Barcelona (NB; 1986-2001), and Taipei Score (TS; 2003-2015). Herein, we describe a contemporary comparison of clinical prognostication indices using a single-center cohort of PCNSL patients treated at the Mayo Clinic. Methods: Patients with a diagnosis of PCNSL who received HD-MTX as part of induction therapy at Mayo Clinic between October 2010 and June 2022 were identified and retrospectively reviewed. Patients with prior or concurrent systemic lymphoma were excluded. Primary endpoints were progression-free survival (PFS) defined as time from diagnosis to relapse, progression, or death due to any cause; and OS defined as time from diagnosis to death due to any cause. PFS and OS were evaluated using Kaplan-Meier curves and compared by risk scores using a log-rank test. The association between baseline characteristics and survival outcome were assessed in univariate Cox regression models. Any characteristics showing significant (p-value <0.05) association with outcome were combined using a multivariate Cox regression model. All characteristics that maintained significant association with outcome were combined into a new prognostic model. We compared the performance of each prognostic index model using Harrell's C (HC). Results: A total of 148 patients were identified (50.7% female) with median age at diagnosis of 66 years (range 29-85), with 48 patients (32.4%) age >70 (Table 1). Most had multifocal disease (60.1%) and deep brain involvement (67.6%) at diagnosis with elevated CSF protein (58.1%) but no documented CSF involvement (93.9%). In total, 117 patients (79.1%) received methotrexate, rituximab, and temozolomide (MRT) induction therapy, and the remaining 31 patients (20.9%) received methotrexate and rituximab (MR) induction therapy with various consolidation strategies. The median follow-up for all patients was 4.5 years and the two-year OS was 79% (95% CI: 73-86%). This cohort was stratified using previously published prognostication indices (Table 1). Upon analysis, PFS was not accurately predicted using the IELSG (score 4-5: HR 0.7 (CI 0.3-2.0); HC 0.6), MSKCC (3: 1.3 (0.4-4.0); 0.5), NB (3: 0.9 (0.4-2.5); 0.6), or TS (3: 0.9 (0.1-7.2); 0.5) prognostication indices. Furthermore, OS was not accurately predicted using the IELSG (4-5: 1.5 (0.6-4.0); 0.6), MSKCC (3: 1.2 (0.5-3.2); 0.6), NB (3: 1.2 (0.5-3.2); 0.6), or TS (3: 1.3 (0.2-9.8); 0.6) prognostication indices. Upon multivariate analysis, no variables listed in Table 1 were associated with PFS within this cohort. The two variables predicting a worsened OS were an ECOG performance status of 2 or more (1.9 (1.01-3.6)) and an MR induction regimen instead of MRT (2.1 (1.05-4.3)) (Figure 1). The two-year OS with no risk factors was 86.1% (95% CI: 78.8-94.1%), one risk factor was 75.7% (95% CI: 63.6-90.1%), and two risk factors was 61% (95% CI: 43-86%) (Figure 1). Conclusions: This study reports overall improved outcomes in patients with PCNSL compared to prior prospective and retrospective cohorts, likely in part due to treatment advances and supportive care strategies. This single-center, retrospective cohort of rituximab-exposed patients with PCNSL were not well prognosticated using previously published indices, indicating that further study and more sophisticated approaches to prognostication are warranted. Although multivariate analysis did not demonstrate any variables associated with PFS, it did demonstrate an inferior OS with a performance score of 2 or more and in patients treated with MR rather than MRT.

An Unusual Cause of Bilateral Adrenal Incidentaloma: A Case Report of Primary Adrenal Lymphoma

Primary adrenal lymphoma (PAL) is an extremely rare among the causes of adrenal incidentaloma. Most were diagnosed with adrenal insufficiency and B symptoms (unexplained weight loss, night sweats, fever). This article presented a 57-year-old woman who was investigated for bilateral adrenal masses found incidentally on computed tomography (CT). Physical examination and laboratory tests revealed no evidence of adrenal insufficiency or B symptoms. Only 24-hour urinary metanephrine and normetanephrine excretion were increased. Tumour F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) scan showed the greatest dimension was 14 cm in the left adrenal mass and the maximum standardized uptake value (SUV max) was 26.1 (relative to mean SUV in the normal liver parenchyma, which was 2). An adrenal biopsy was performed after taking adequate precautions against the possibility of a catecholamine crisis. Histopathology revealed high-grade B-cell lymphoma. Bone marrow involvement and brain metastasis were not observed. She received the R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen and intrathecal methotrexate therapy as central nervous system prophylaxis. The patient responded well to treatment, and close clinical follow-up continues. PAL should always be considered when a bilateral adrenal mass is detected.

Chronic hepatitis B in hospitalized rheumatologic patients: problems of screening and reactivation of infection

Objective: to evaluate the completeness of screening for hepatitis B virus (HBV) infection in HBsAg-positive patients admitted to a rheumatology hospital and to follow the history of HBV reactivation/seroversion during antirheumatic therapy. Material and methods. The results of initial and repeated (if applicable) hospitalizations were analyzed in 80 patients with rheumatic diseases (RD), including 55 (69%) women and 25 (31 %) men, with Australian surface antigen (HBsAg), admitted to the V.A. Nasonova Institute of Rheumatology from January 1, 2020 to July 20, 2022 (30 months). Results and discussion. The total number of hospitalizations to the clinic during the observation period, including repeat admissions, was 13,681. The number of hospitalizations in 80 patients with HBV infection during the observation period, including repeat admissions, was 144, of which for systemic vasculitis – 6 (8 %), other systemic connective tissue diseases – 16 (20 %), osteoarthritis and post-traumatic changes of joints – 14 (15 %), inflammatory joint diseases – 42 (54 %). Cases of HBV reactivation/seroverion, both in anamnesis and during observation, were detected in 9 (11 %) patients, and most frequently (n = 5) they were registered during methotrexate therapy. Conclusion. HBV infection in patients with RD leads to significant difficulties in the selection of drug therapy, due to the risk of reactivation of the infection. The results obtained indicate incomplete screening of patients with RD for HBV infection during the preclinical phase. Further investigation is needed to develop clear recommendations for the management of patients with RD infected with HBV.

Granulomatosis with polyangiitis: The wily masquerader of cavitary pulmonary lesions

Background: Granulomatosis with Polyangiitis (GPA) is a small and medium vessel vasculitis with predominant respiratory and renal involvement that causes florid presentation of the disease entity with varying spectrum of illness at different time intervals. Case: We report the case of a 42-years-old female patient with symptoms of low-grade fever, productive cough and significant loss of weight with multiple cavitary lesions on Chest radiograph. The patient was initially suspected to have tuberculosis which was eventually ruled out. A diagnosis of vasculitis was suspected as patient gave history of repeated hospitalisations with symptoms of upper respiratory tract involvement, left facial nerve palsy and sensorineural hearing loss, A diagnosis of limited GPA was made when the cytoplasmic Antineutrophil Cytoplasmic Antibodies, (c-ANCA) and antiproteinase-3 antibodies (anti-PR3) was elevated. The patient was treated with combination immunosuppressive therapy of prednisolone and methotrexate which induced clinical remission within one month and complete radiological remission within 4 months. Conclusion: GPA is an important non infective cause of cavitary pulmonary lesions that presents with extrapulmonary clinical spectrum (recurrent sinusitis, ear infections, renal dysfunction and neurological disease). Multifocal presentation of the disease at different time intervals results in considerable delay in diagnosis and adds to the morbidity of the disease entity.

НЕПЕРЕНОСИМОСТЬ МЕТОТРЕКСАТА У ДЕТЕЙ С ЮВЕНИЛЬНЫМ ИДИОПАТИЧЕСКИМ АРТРИТОМ ПО ДАННЫМ ОПРОСНИКА MISS (METHOTREXATE INTOLERANCE SEVERITY SCORE): ОДНОМОМЕНТНОЕ ИССЛЕДОВАНИЕ

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. First-line therapy is the prescription of Methotrexate (MTX) though this drug can cause undesirable effects which in its turn dictates the need for the use of diagnostic techniques that would allow early detection of intolerance to MTX. One of such diagnostic approaches is the Methotrexate Intolerance Severity Score (MISS) questionnaire. The purpose of this research was to evaluate the frequency of MTX intolerance in children with JIA using the Russian-language adaptation of the MISS questionnaire. Materials and methods used: a single-center, single-stage study of children aged 3 to 17 y/o with a non-systemic variant of JIA who were prescribed MTX was conducted using the 2011 MISS questionnaire in Russian. The MTX intolerance was determined if the patient scored 6 points and above. Results: 250 patients (78 boys and 172 girls) were included in the study. MTX intolerance using the MISS questionnaire was identified in 30% of patients; the most common complaint was MTX-associated nausea. The cut-off point for the questionnaire was estimated using the ROC analysis. The area under the ROC curve was 0.945. Patients scoring 6 points with a sensitivity of 94% (95% CI 78-97) and specificity of 100% (95% CI 80-100) were intolerant to MTX. The validity of using the questionnaire to identify individuals with MTX intolerance has been demonstrated therefore the questionnaire can be recommended for wider use. Conclusion: MTX intolerance, which was determined by the total score (6 points and above) was identified in 75 patients on MTX therapy.

Ocular toxoplasmosis following anti-tumour necrosis factor-α therapy combined with oral methotrexate therapy: A case report and review of literature.

Purpose: To report a case of ocular toxoplasmosis following long-term treatment with adalimumab and review the literature on ocular toxoplasmosis following anti-Tumour necrosis factor-α therapy. Method: A retrospective chart review of A 21-year-old male who developed retinochoroiditis in his left eye following adalimumab therapy combined with oral methotrexate. Result: A known patient of juvenile idiopathic arthritis (JIA) on adalimumab and oral methotrexate for the last four years presented to us with a blurring of vision for the last 15 days. Fundus examination of the left eye revealed severe vitritis and two patches of retinochoroiditis in the inferior part of the fundus. Subsequent investigations confirmed it to be a case of toxoplasma retinochoroiditis, and he responded to anti-toxoplasma treatment. A review of literature on a similar topic revealed five such cases, and the index case was the first such report in patients with JIA. Conclusion: The index case highlights the importance of early recognition and management of opportunistic infections in patients receiving biologicals.

The effect of the plasma methotrexate concentration during high-dose methotrexate therapy in childhood acute lymphoblastic leukemia

Two hundred and thirty-one acute lymphoblastic leukemia (ALL) children with 1376 high-dose methotrexate (HD-MTX) courses (3–5 g/m2) were enrolled to analyze the influence of the plasma MTX concentration (C MTX) in ALL. The 24-h target peak C MTX (C 24h) was set at 33 μmol/l for low-risk (LR) and 65 μmol/l for intermediate/high-risk (IR/HR) groups. The median C 24h was 42.0 μmol/l and 69.7 μmol/l for LR and IR/HR groups, respectively. MTX excretion delay was observed in 14.6% of courses, which was more frequent in IR/HR groups (56.9% vs. LR group 40.2%, p = .014) and T-ALL patients (82.6% vs. B-ALL 47.1%, p = .001). MTX-related toxicities were more common in courses with MTX excretion delay. However, survival between the patients who failed to reach the target C 24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, C MTX does not exert an independent influence on the prognosis of childhood ALL.

UTERUS PRESERVING TREATMENT MODALITIES FOR ABNORMAL INVASIVE PLACENTA: A SYSTEMATIC REVIEW

Background: When a focal accreta is identified, conservative intervention may be considered, such as preserving the uterus and placenta and then enduring methotrexate therapy or pelvic artery embolisation. In spite of this, surgical treatment remains the gold standard for the condition. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 401 articles, whereas the results of our search on SagePub brought up 289 articles. The results of the search conducted for the last year of 2013 yielded a total 43 articles for PubMed and 31 articles for SagePub. In the end, we compiled a total of 20 papers, 12 of which came from PubMed and 8 of which came from SagePub. We included seven research that met the criteria. Conclusion: Due to the intricacy of surgery, conservative management should be reserved for individuals who are interested in preserving their fertility as well as those who have major disease.

Risks of malignant lymphoma in rheumatoid arthritis patients receiving methotrexate-alone and in combination therapy compared with the general population: A study based on a Japanese medical claims database.

The risk of malignancy in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) and biological disease-modifying antirheumatic drug (bDMARD) combination therapy is unknown. This study aimed to clarify the incidence of malignancy and the recommended monitoring period in patients receiving this combination therapy. A retrospective, observational study based on a large Japanese medical claims database was conducted between April 2013 and February 2020. Patients with RA were classified into MTX-alone and combination therapy groups, and the standardized incidence rates (SIR) of malignancy were calculated. The time of onset of malignancy in both groups was calculated. In total, 2,052 patients received MTX-alone and 782 received combination therapy. The incidence of malignant lymphoma was significantly higher with MTX-alone therapy (SIR: 6.09, 95% confidence interval (CI): 1.58-10.61) and combination therapy (SIR: 20.86, 95% CI: 8.53-33.19) than in the general Japanese population. Furthermore, the combination therapy had a significantly higher risk of malignant lymphoma than the MTX-alone therapy (adjusted odds ratio: 4.27, 95% CI: 1.64-11.12). The median time from MTX prescription to the onset of malignant lymphoma was 3.58 years (interquartile range (IQR): 2.00-5.34 years) for MTX-alone and 3.42 years (IQR: 1.25-4.92 years) for combination therapy. The incidence of malignant lymphoma in the combination therapy group was extensively higher than that in the general Japanese population. Special attention is required for early symptoms of malignant lymphoma, particularly in the 3rd - 4th year after initiating MTX therapy.

P30 An unusual infective cause of inflammatory arthritis

P30 An unusual infective cause of inflammatory arthritis

Early clinical indicators of acute kidney injury caused by administering high-dose methotrexate therapy to juvenile pigs.

Early identification of compromised renal clearance caused by high-dose methotrexate (HDMTX) is essential for initiating timely interventions that can reduce acute kidney injury and MTX-induced systemic toxicity. We induced acute kidney injury (AKI) by infusing 42 juvenile pigs with 4 g/kg (80 g/m2) of MTX over 4 hours without high-volume alkalinizing hydration therapy. Concentrations of serum creatinine and MTX were measured at 15 time points up to 148 hours, with 10 samples collected during the first 24 hours after the start of the HDMTX infusion. During the first 28 hours, 81% of the pigs had increases in the concentrations of serum creatinine in one or more samples indicative of AKI (i.e., > 0.3g/dL increase). A rate of plasma MTX clearance of less than 90% during the initial 4 hours after the HDMTX infusion and a total serum creatinine increase at 6 and 8 hours after starting the infusion greater than 0.3 g/dL were predictive of AKI at 28 hours (p < 0.05 and p < 0.001, respectively). At conclusion of the infusion, pigs with a creatinine concentration more than 0.3 g/dL higher than baseline or serum MTX greater than 5,000 μmol/L had an increased risk of severe AKI. Our findings suggest that serum samples collected at conclusion and shortly after HDMTX infusion can be used to predict impending AKI. The pig model can be used to identify biological, environmental, and iatrogenic risk factors for HDMTX-induced AKI and to evaluate interventions to preserve renal functions, minimize acute kidney injury, and reduce systemic toxicity.

The potential protectivity of honey and olive oil in methotrexate induced renal damage in rats

Methotrexate (MTX) is an antimetabolite used to treat inflammatory diseases, autoimmune disorders and some malignancies. However, it has some life-threatening side effects such as nephrotoxicity which limit its clinical applications. That motivated the attention to seek for a defensive material to improve the outcomes of methotrexate while minimizing both renal and non-renal toxicity. Both honey (H) and olive oil (OO) are bioactive substances widely used as nutraceuticals that exhibited a potent therapeutic and antioxidant properties. This study aimed to assess the possible protective effect of H and OO intake either singly or together against the biochemical and structural Methotrexate-induced nephrotoxicity in rats. The study was conducted on 56 adult albino rats, they were divided into seven groups (n = 8): group 1 received only distelled water (negative control), group 2 received H (1.2 g/kg/day), group 3 received OO (1.25 ml/kg/day), group 4 received a single intraperitoneal injection of MTX (20 mg/kg), group 5 received MTX and H, group 6 received MTX and OO, group 7 received MTX, H and OO together. At the end of the experiment (2 weeks), all rats were sacrificed, and blood samples were assessed for kidney function tests. Kidney tissues were evaluated for several antioxidant parameters including Malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Tissues were also processed for histological and immunohistochemical assessments. Results revealed that both H and OO improved the kidney function markers, histopathological and immunohistological changes due to Methotrexate-induced renal damage. Additionally, both substances also redeemed the oxidative damage of the kidney by decreasing MDA and increasing anti-oxidant enzymatic activities. Such effects were more apparent when the two substances were given together. Ultimately, our results proof that H and OO amiolerate the Methotrexate-induced nephrotoxicity in rats, thus they can be used as an adjuvant supplements for patients requiring methotrexate therapy.

The impact of maternal electrolyte and albumin levels on the efficacy of single-dose methotrexate treatment for ectopic pregnancies.

This study aims to investigate the impact of maternal albumin and serum electrolyte levels on the efficacy of single-dose methotrexate (SDMtx) therapy for ectopic pregnancies. Building on previous research, recommendations are provided to enhance the success of SD-Mtx therapy in the management of ectopic pregnancy. Conducted at a tertiary center gynecology clinic, the study included 353 patients diagnosed with ectopic pregnancy and treated with SD-Mtx from 2012 to 2023. Patients who responded positively to SD-Mtx treatment comprised Group 1 (n=313), while those requiring surgical intervention due to failed SD-Mtx therapy constituted Group 2 (n=40). Through the hospital's digital database, patient data including complete blood count, biochemistry, and hormone test results were retrospectively examined. The mean β-hCG value was 1996 IU/mL for Group 1 in contrast to 2058 IU/mL for Group 2. There was no statistically significant difference in β-hCG levels between the two groups. Notably, Group 1 patients exhibited lower serum magnesium levels but higher potassium levels compared to Group 2 patients, with statistically significant differences. Furthermore, Group 1 patients had higher albumin levels than those in Group 2, with a statistically significant difference. Successful SD-Mtx treatment was associated with lower maternal serum magnesium levels and higher potassium and albumin levels. Considering electrolyte levels before administering SD-Mtx and addressing any imbalances could potentially enhance treatment success. Additionally, restoring low albumin levels might improve the efficacy of SD-Mtx treatment for ectopic pregnancies. While this study suggests these trends, further extensive studies with a larger sample size are necessary to establish more definitive evidence.