Dose Methotrexate Research Articles

Hysteroscopic resection vs ultrasound-guided dilation and evacuation for treatment of cesarean scar ectopic pregnancy: a randomized clinical trial

Cesarean scar ectopic pregnancy is a type of ectopic pregnancy in which the fertilized egg is implanted in the muscle or fibrous tissue of the scar after a previous cesarean delivery. The condition can be catastrophic if not managed on time and can lead to significant morbidity and mortality. Several approaches have been studied for the management of cesarean scar ectopic pregnancy in women who opted for termination of pregnancy with no consensus on the best treatment modality reached so far. This study aimed to compare the success rate of hysteroscopic resection vs ultrasound-guided dilation and evacuation for the treatment of cesarean scar ectopic pregnancy. This was a parallel group, nonblinded, randomized clinical trial conducted at a single center in Italy. Women with singleton gestations at <8 weeks and 6 days of gestation were included in the study. Inclusion criteria were women with a cesarean scar ectopic pregnancy with positive embryonic heart activity who opted for termination of pregnancy. Patients were randomized 1:1 to receive either hysteroscopic resection (ie, intervention group) or ultrasound-guided dilation and evacuation (ie, control group). Both groups received 50 mg/m2 of methotrexate intramuscularly at the time of randomization (day 1) and another dose at day 3. A third dose of methotrexate was planned in case of persistence of positive fetal heart activity at day 5. Participants received either ultrasound-guided dilation and evacuation or hysteroscopic resection from 1 to 5 days after the last dose of methotrexate. Hysteroscopic resection was performed under spinal anesthesia using a 15 Fr bipolar mini-resectoscope. Dilation and evacuation were performed by vacuum aspiration with a Karman cannula, followed by sharp curettage, if necessary, under ultrasound guidance. The primary outcome was the success rate of the treatment protocol, defined as no further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. Resolution of the cesarean scar ectopic pregnancy was evaluated based on decline of beta-hCG and the absence of residual gestational material in the endometrial cavity. Treatment failure was defined as the necessity for further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. A sample size calculation indicated that 54 participants were required to test the hypothesis RESULTS: A total of 54 women were enrolled and randomized. Number of previous cesarean deliveries ranged from 1 to 3. Overall, 10 women received a third dose of methotrexate with 7 of 27 (25.9%) participants in the hysteroscopic resection group and 3 of 27 (11.1%) in the dilation and evacuation group. The success rate was 100% (27/27) in the hysteroscopic resection group and 81.5% (22/27) in the dilation and evacuation group (relative risk, 1.22; 95% confidence interval, 1.01-1.48). Additional procedures were required in 5 cases of the control group, namely 3 hysterectomies, 1 laparotomic uterine segmental resection, and 1 hysteroscopic resection. The length of stay in the hospital was 9.0±2.9 days in the intervention group and 10.0±3.5 days in the control group (mean difference,-1.00 days; 95% confidence interval,-2.71 to 0.71). No cases of admission to intensive care unit or maternal death were reported. Hysteroscopic resection was associated with an increased success rate in the treatment of cesarean scar ectopic pregnancy when compared with ultrasound-guided dilation and evacuation.

PO-01-087 A RARE CASE OF BI-ATRIAL FDG-UPTAKE: PRESENTING AS NEW ONSET ATRIAL FIBRILLATION

Isolated atrial myocarditis is rare, with presenting symptoms that are non-specific. Prior reports have suggested association with atrial arrythmias and increased risk of stroke due to atrial dysfunction. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) CT scan is considered as a goal standard test for the diagnosis of myocarditis. To present a case highlighting that isolated atrial myocarditis had higher incidence atrial arrythmias and oral anticoagulation should be considered in such cases. N/A A 55yo male with no prior medical history presented with non-specific symptoms of fatigue, shortness of breath and frequent palpitations. He underwent 2D echocardiogram showed LVEF of 50-55% with mild bi-atrial dilatation with no regional wall motion abnormalities and was diagnosed with incidental atrial fibrillation during the procedure. He was referred to cardiac electrophysiology for further work up. During his initial EP clinic visit, 12 lead ECG demonstrated normal sinus rhythm with premature atrial contractions and premature ventricular contractions. Due to symptomatic, dual chamber arrythmias, cardiac MRI (CMR) and FDG-PET CT was ordered to rule out myocarditis. The CMR was negative for any LGE however, high-fat dietary preparation FDG-PET CT scan revealed uptake on bi-atrial walls (figure) and interatrial septum with SUV max of 3.1. There was no LV myocardial FDG uptake noted. Patient was diagnosed with isolated atrial myocarditis and was started on dronedarone, OAC (CHADS2VASc =0) for stroke prophylaxis and immunosuppressive therapy (methotrexate and low dose prednisone). Invasive atrial myocardial biopsy was not considered due good response to therapy. Isolated atrial myocarditis is an uncommon presentation of acute myocarditis and is associated with atrial arrythmias. FDG PET-CT or CMR imaging may be useful to aid diagnosis. Long-term response to immunosuppressive therapy may need further investigations. OAC should be considered for stroke prophylaxis, despite low CHADS2VASc due to unknown long-term implications of atrial dysfunction.

Tripterygium wilfordii Hook F combination therapy with methotrexate for rheumatoid arthritis: An updated meta-analysis.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory arthropathy. Tripterygium wilfordii Hook F (TwHF) is common herbal medicine for the treatment of RA in China. However, many important issues, such as efficacy, safety and optimal doses of the combination therapy of TwHF and Methotrexate (MTX) for RA remain to be evaluated. This study aims to evaluate the efficacy and safety of combination therapy of TwHF and MTX for RA by meta-analysis of randomized clinical trials (RCTs). Relevant literature was searched from English (PubMed, Web of Science, EMBASE, and Cochrane library) and Chinese databases (WanFang, VIP, CNKI) until December 2021. Response rates and rates of adverse events (AEs) were independently extracted and analyzed. Fourteen randomized controlled trials (RCTs) were included with a total of 1446 patients, which included eight new RCTs with a total of 803 new patients when compared with the previous meta-analysis (Wang et al., 2017). Compared to MTX monotherapy, TwHF+MTX was revealed a higher effective rate (RR=1.15, 95% CI: 1.10, 1.21), partial remission rate (RR=1.27, 95% CI: 1.15, 1.40) and remission rate (RR=1.31, 95% CI: 1.11, 1.55). The addition of TwHF benefited the clinical symptoms (such as tender joint count) and most laboratory indexes (such as the tumor necrosis factor-α). According to the subgroup analyses, the efficacy of the TwHF+MTX seems to be positively associated with the dose of TwHF (10mg/d vs 30-60mg/d), negatively related to the dose of MTX (∼10 mg/w vs ∼15 mg/w) and methodological risk of bias of included RCTs, and unrelated to the duration of therapy (12-week vs 24-week). For safety, the addition of TwHF did not increase the risk of most AEs and even reduced the risk of infection and liver AEs. Combining TwHF with MTX may be a superior strategy in the treatment of RA compared with MTX monotherapy. The optimal combination of TwHF+MTX therapy might be TwHF at 30-60mg/d with MTX (∼10 mg/w). Further high-quality double-blind RCTs may be able to change the conclusions of our study, which are still warranted.

The importance of β-hCG values in prediction of the effectiveness of single dose methotrexate therapy in tubal ectopic pregnancy.

To investigate the importance of β-hCG values on the day of onset and on the fourth and seventh day after treatment in the effectiveness of treatment in tubal ectopic pregnancies treated with a single dose of methotrexate (MTX). One hundred sixty-two patients with tubal ectopic pregnancy treated with a single dose MTX treatment were retrospectively evaluated. β-hCG values and changes on Days 0, 4 and 7 of the MTX treatment successful group and the unsuccessful group were analyzed. MTX treatment was successful in 125 (77.2%) and unsuccessful in 37. When the β-hCG values on Days 0, 4 and 7 were compared in pairs, the differences between groups were statistically significant (p < 0.001). The mean β-hCG value was 783.0 in the MTX successful group and 1802.0 in unsuccessful group (p < 0.001). There was a 21.6% decrease in β-hCG values between Days 0 and day 4 in the MTX successful group and a 25.7% increase in the MTX unsuccessful group (p < 0.001). On Days 0, 4 and 7, ROC curve analysis's values are , respectively; 755/939/486 for cut off, 86.49/83.78/94.59% for sensitivity and 48.80/69.60/72.36% for specificity. Success rates of single-dose MTX treatment increase in tubal ectopic pregnancies with low initial β-hCG value. Patients with a decrease in β-hCG value and/or a cut-off decrease of 20% or more on the fourth day of treatment can be called for weekly β-hCG monitoring without the need for close follow-up. The change in β-hCG between Day 0 and Day 4 can be used to predict the efficacy of treatment.

P062 Immune responses to mRNA vaccines against SARS-CoV2 in patients with immune-mediated inflammatory rheumatic diseases

Abstract Background/Aims Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccinés immunogenicity. Methods Humoral, CD4 and CD8 immune responses were investigated in 147 SARS-Cov2-naïve patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and disease-matched IMRD patients not receiving immunosuppressors and with healthy controls Results IMRD patients showed decreased seroconversion rates (63% vs 100%, p = 0.04) and cellular immune responses (59% vs 100%, p = 0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide. Conclusion IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity. Disclosure C. Sieiro Santos: None. S. Calleja Antolín: None. C. Moriano Morales: None. C. Álvarez Castro: None. E. Díez Álvarez: None. J. Garcia Ruiz de Morales: None.

Risk factors associated with relapse after methotrexate dose reduction in patients with rheumatoid arthritis receiving golimumab and methotrexate combination therapy.

To identify risk factors for relapse after methotrexate (MTX) dose reduction in rheumatoid arthritis (RA) patients receiving golimumab (GLM)/MTX combination therapy. Data on RA patients ≥20 years old receiving GLM (50 mg) + MTX for ≥6 months were retrospectively collected. MTX dose reduction was defined as a reduction of ≥12 mg from the total dose within 12 weeks of the maximum dose (≥1 mg/wk average). Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline. A total of 304 eligible patients were included. Among the MTX-reduction group (n = 125), 16.8% of patients relapsed. Age, duration from diagnosis to the initiation of GLM, baseline MTX dose, and DAS28-CRP were comparable between relapse and no-relapse groups. The adjusted odds ratio (aOR) of relapse after MTX reduction was 4.37 (95% CI 1.16-16.38, P = 0.03) for prior use of non-steroidal anti-inflammatory drugs (NSAIDs), and the aORs for cardiovascular disease (CVD), gastrointestinal disease and liver disease were 2.36, 2.28, and 3.03, respectively. Compared to the non-reduction group, the MTX-reduction group had a higher proportion of patients with CVD (17.6% vs 7.3%, P = 0.02) and a lower proportion of prior use of biologic disease-modifying antirheumatic drugs (11.2% vs. 24.0%, P = 0.0076). Attention should be given to RA patients with history of CVD, gastrointestinal disease, liver disease, or prior NSAIDs-use when considering MTX dose reduction to ensure benefits outweigh the risks of relapse.

Treatment of Cesarean Scar and Cervical Pregnancies Using the Ovum Aspiration Set for Intrachorial Methotrexate Injection as a Conservative, Fertility-Preserving Procedure.

Background and Objectives: Cesarean scar and cervical pregnancies are rare forms of ectopic pregnancies, occurring in 1 in 2000 and 1 in 9000 pregnancies, respectively. Both entities are medically challenging due to their high morbidity and mortality potential. Materials and Methods: In this retrospective study, we analyzed all cesarean scar and cervical pregnancies from 2010 to 2019 in the Department of Gynecology and Obstetrics of the University Hospital Freiburg, treated with both intrachorial (using the ovum aspiration set) and systemic methotrexate application. Results: We identified seven patients with a cesarean scar and four patients with cervical pregnancies. At diagnosis, the median gestational age was 7 + 1 (range: 5 + 5-9 + 5) weeks and the mean value of ß-hCG was 43,536 (range: 5132-87842) mlU/mL. On average, one dose of intrachorial and two doses of systemic methotrexate were administered per patient. The efficacy rate was 72.7% with three patients (27.3%) needing an additional surgical or interventional procedure. The uterus was preserved in 100% of the patients. Out of the eight patients with follow-up data, five reported subsequent pregnancies (62.5%) that resulted in six live births. None had recurrent cesarean scars or cervical pregnancies. In the subgroup analyses, when comparing cesarean scar pregnancies to cervical pregnancies, patient characteristics, treatment modality, and the outcome did not differ significantly, except for parity (2 versus 0, p = 0.02) and the duration since the last pregnancy (3 vs. 0.75 years, p = 0.048). When comparing cases with successful and failed methotrexate-only treatments, the maternal age was significantly higher in the successful group (34 vs. 27 years, p = 0.02). Localization of the gestation, gestational and maternal age, ß-hCG, and history of preceding pregnancies were non-predictive for the efficacy of the treatment. Conclusions: The combined application of intrachorial and systemic methotrexate for the treatment of cesarean scar and cervical pregnancies has been proven effective, well-tolerated, organ- and fertility-conserving with a low complication rate.

Effect of two additional doses of intrathecal methotrexate during induction therapy on serious infectious toxicity in pediatric patients with acute lymphoblastic leukemia.

Although initial central nervous system (CNS) involvement is rarely detected in childhood acute lymphoblastic leukemia (ALL), risk-adapted CNS-directed therapy is essential for all patients. Treatment intensity depends on the initial CNS status. In the AIEOP-BFM ALL 2009 trial, patients with cytomorphologic detection of leukemic blasts in initial cerebrospinal fluid were classified as CNS2 or CNS3 and received five intrathecal doses of methotrexate (MTX) in induction therapy compared to patients with CNS1 status (no blasts detected) who received three doses. The impact of additional intrathecal (IT) MTX on systemic toxicity in induction therapy is unknown. Between June 1st 2010 and February 28th 2017, a total of 6,136 ALL patients aged 1-17 years were enrolled onto the AIEOP-BFM ALL 2009 trial. The effect of three versus five doses of IT MTX during induction therapy on the incidence of severe infectious complications was analyzed. Among 4,706 patients treated with three IT MTX doses, 77 (1.6%) had a life-threatening infection during induction as compared to 59 of 1,350 (4.4%) patients treated with five doses (P<0.001; Odds Ratio 2.86 [95% Confidence Interval 1.99-4.13]). In a multivariate regression model, treatment with additional IT MTX proved to be the strongest risk factor for life-threatening infections (Odds Ratio 2.85 [1.96-4.14]). Fatal infections occurred in 16 (0.3%) and 38 (1.6%) patients treated with three or five IT MTX doses, respectively (P<0.001). As the relevance of additional intrathecal MTX in induction for relapse prevention in CNS2 patients is unclear, doses of intrathecal therapy have been reduced for these patients. (Clinicaltrials.gov identifiers: NCT01117441 and NCT00613457).

Impacts of Valproic Acid on Systemic Bone Loss Associated with Experimental Model of Rheumatoid Arthritis in Rats

Background: Valproic acid (VA) is a compound used for many neurological disorders, which is also known as a histone deacetylase inhibitor. The impacts of VA on adjuvant-induced arthritis (AIA) in rats were investigated. Objectives: To investigate the possible osteoprotective and anti-inflammatory effects of VA in rheumatoid arthritis (RA). Materials and Methods: AIA was achieved through subdermal injection of complete Freund’s adjuvant (CFA) into the rat hindpaw. Forty Swiss albino rats were recruited in this study. These rats were divided into four groups: the normal control group received 0.1 mL phosphate buffer saline intraperitoneally each day, the positive control group received 0.75 mg/kg intraperitoneal once weekly dose of methotrexate, the AIA group received CFA without treatment, and the VA group received 300 mg/kg/day intraperitoneal dose of VA. Statistical analysis was done, and a P value of less than 0.05 was considered as statistically significant. Results: VA (300 mg/kg body weight) administered intraperitoneally could significantly reverse the effect of adjuvant arthritis on bone mineral density and bone mineral content in addition to an improvement in bone formation markers (osteoprotegerin, osteoprotegerin/RANKL ratio). Serum levels of tumor necrosis factor and interleukin 1b were significantly reduced by VA treatment. Reduced serum malondialdehyde with the elevated superoxide dismutase level was also achieved. Conclusion: These findings support the evidence that VA has a positive effect on bone anabolism and its anti-inflammatory properties could be considered as a bonus in inflammatory disorders induced bone loss such as RA.

Management of ectopic pregnancy in a tertiary hospital: a retrospective cohort study.

The goal of this study was to manage the treatment modalities of ectopic pregnancy. This retrospective study included 1,103 women diagnosed and treated for ectopic pregnancy at Kanuni Sultan Suleyman Training and Research Hospital between January 1, 2017, and December 31, 2020. Serial beta-human chorionic gonadotropin (β-Hcg) measurements and transvaginal ultrasound (TV USG) findings were used to establish the diagnosis of an ectopic pregnancy. They were divided into four groups: expectant treatment, single-dose methotrexate, multidose methotrexate, and surgical treatment. All data analyses were performed using SPSS version 24.0. A receiver operating characteristic (ROC) analysis was used to determine the cut-off for change in beta-human chorionic gonadotropin (β-hCG) levels between the first and fourth day. There were significant differences between groups in terms of gestational age and β-hCG changes (p < 0.001). In patients receiving expectant treatment, the decrease in β-hCG values on the fourth day was 35.19%, while patients receiving single-dose methotrexate treatment showed a decrease of 24%. The most common risk factor for ectopic pregnancy was the absence of risk factors. Comparison of the surgical treatment group with the other groups revealed significant differences in terms of the presence of free fluid in the abdomen, the average diameter of the ectopic pregnancy mass, and the presence of fetal cardiac activity. A single dose of methotrexate was effective in patients with β-hCG levels lower than 1,227.5 mIU/ml, with a 68.5% sensitivity and 69.1% specificity. An increase in gestational age also leads to an increase in β-hCG values and the diameter of the ectopic focus. As the diagnosis period progresses, the need for surgical intervention increases.

Methotrexate therapy associated with a reduced rate of new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis

ObjectiveTo study the effect of methotrexate (MTX) therapy on new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis (JIA).MethodsIn this matched case–control study, we compared MTX exposure between cases with...

Efficacy and Safety of CMAB008 Compared with Innovator Infliximab in Patients with Moderate-to-Severe Rheumatoid Arthritis Receiving Concomitant Methotrexate: A Randomized, Double-blind, Multi-center, Phase III Non-inferiority Study.

The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3mg/kg or innovator infliximab 3mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than -15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were - 4.6% and the lower limit of one-sided 97.5% confidence interval was - 14.29%, not less than the lower limit of the non-inferiority margin (- 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference - 4.6%, 95% CI - 14.29% to 5.12%) and PPS (difference - 3.3%, 95% CI - 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. NCT03478111.

Etanercept for patients with juvenile idiopathic arthritis: drug levels and influence of concomitant methotrexate: observational study

BackgroundEtanercept (ETN) is widely used tumour necrosis factor (TNF) blocker in the treatment of juvenile idiopathic arthritis (JIA) when traditional synthetic disease modifying antirheumatic drug (sDMARD) therapy is not sufficient. There is limited information about the effects of methotrexate (MTX) on serum ETN concentration in children with JIA. We aimed to investigate whether ETN dose and concomitant MTX would effect ETN serum trough levels in JIA patients, and whether concomitant MTX have an influence on the clinical response in patients with JIA receiving ETN.MethodsIn this study, we collected the medical record data of 180 JIA patients from eight Finnish pediatric rheumatological centres. All these patients were treated with ETN monotherapy or combination therapy with DMARD. To evaluate the ETN concentrations, blood samples of the patients were collected between injections right before the subsequent drug. Free ETN level was measured from serum.ResultsNinety-seven (54%) of the patients used concomitant MTX, and 83 (46%) received either ETN monotherapy or used sDMARDs other than MTX. A significant correlation was noted between ETN dose and drug level [r = 0.45 (95% CI: 0.33–0.56)]. The ETN dose and serum drug level were correlated (p = 0.030) in both subgroups – in MTX group [r = 0.35 (95% CI: 0.14–0.52)] and in non-MTX group [r = 0.54 (95% CI: 0.39–0.67)].ConclusionIn the present study, we found that concomitant MTX had no effect on serum ETN concentration or on clinical response. In addition, a significant correlation was detected between ETN dose and ETN concentration.

Cesarean Scar Pregnancy Treated by Systemic or Local Methotrexate Administration Followed by Hysteroscopic Removal: A Comparative Pilot Study

Background: Cesarean Scar Pregnancy (CSP) is a life-threatening condition following an ectopic implantation within the scar of a previous cesarean delivery and no guideline is shared about optimal treatment options. Methods: We present a retrospective study comparing the outcomes of patients with CSP diagnosed before the 10th week of gestation treated by systemic or local Methotrexate (MTX) for pregnancy termination, followed by hysteroscopic placental removal. After MTX administration, the weekly decrease-rate of beta Human Chorionic Gonadotropin subunit (β-HCG) was adopted as criterion to indicate a repeated MTX dose (less than 25% decline after 2 weeks) and to surgery timing (50% decline in two consecutive assessments). Results: Fourteen patients satisfied the inclusion criteria. Eight and six of them underwent systemic (group A) and local (group B) MTX administration, respectively. No significant difference was found in pre-treatment and intra-operative variables. Group B showed significantly accelerated times in weekly halving of β-HCG with respect to group A (p-value = 0.005). Accordingly, the elapsing time between MTX and surgery was found to be significantly longer in the group A than in the group B (p-value = 0.016). In group B no patient required further MTX administration whereas 3 out of 8 patients from group A required an additional MTX dose. In all patients hysteroscopic surgery resulted uneventful and no further treatment was required. Conclusions: When followed by hysteroscopic placental removal, systemic or local MTX administration resulted effective to treat CSP. Local MTX allows quicker trophoblastic demise, leading to significant anticipation of surgery with respect to systemic administration.

Protective effects of sitagliptin on methotrexate-induced nephrotoxicity in rats

Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers. However, its use has been limited by its life-threatening side effects, including nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the protective effect of sitagliptin on methotrexate (MTX)-induced nephrotoxicity in rats. Twenty-four rats were divided into four groups: control group, which received the vehicle for 6 days; MTX group, which received a single dose of MTX, followed by five daily doses of vehicle dosing; MTX + sitagliptin group, which received a single dose of MTX 1 h after the first sitagliptin treatment and six daily doses of sitagliptin; and sitagliptin group, which received sitagliptin for 6 days. Both MTX and sitagliptin were given as intraperitoneal injections at a dose of 20 mg/kg body weight. All rats were euthanized on the seventh day of the study. Kidney tissues were harvested and blood samples were collected. Serum levels of blood urea nitrogen (BUN) and creatinine were evaluated. Furthermore, catalase, glutathione peroxidase, superoxide dismutase activities, and malondialdehyde (MDA) levels were determined in kidney tissue. In addition, histopathological analysis was conducted. Histopathological evaluation showed that MTX-induced marked kidney injury. Biochemical analysis revealed a significant increase of BUN and creatinine in the serum of the MTX group. Furthermore, oxidative stress and depressed antioxidant system of the kidney tissues were evident in the MTX group. Sitagliptin did not affect these endpoints when administered alone, but it significantly attenuated the observed MTX-induced effects. These results suggest that sitagliptin exhibits potent anti-oxidant properties against the nephrotoxicity induced by MTX in rats.

Early prediction of the failure of methotrexate treatment by Days 1–4 serum β-hCG change and 48-hour pre-treatment increment inβ-hCG

To determine whether the change of serum β-hCG levels between Days 1 and 4 and 48-h pre-treatment increment in β-hCG can early predict treatment failure of single-dose methotrexate (MTX) in tubal ectopic pregnancies (EP), a retrospective study of 1120 ectopic pregnancies treated with a regimen of a single dose of MTX was conducted in the Department of Obstetrics and Gynaecology, Shanghai First Maternity and Infant Hospital. Treatment failure was defined by an obligation to proceed to surgery or have an additional doses of methotrexate.1350 files were reviewed, with 1120 included for final analysis .64% (722/1120) had β-hCG levels increase on Day 4 after MTX treatment, while 36% (398/1120) had β-hCG levels fall. In this cohort, the treatment failure rate with a single dose of MTX was 15.7% (113/722), and the significant features in the logistic regression model of diagnosing the results of MTX treatment were the ratio of Day 1 to Day 48-h pre-treatment β-hCG values (Odds Ratio (OR) 1.221, 95% Confidence interval (CI) 1.159–1.294), the ratio of Day 4 to Day 1 β-hCG serum values (OR 1.098, 95% CI 1.014–1.226), and β-hCG values on Day 1 (OR 1.070, 95% CI 1.016–1.156). The decision tree model was developed by using increment of β-hCG in 48 h before treatment > =19%, the ratio of Day 4 to Day 1 β-hCG serum values > =36%, and β-hCG values on Day 1> =728 mIU/L to predict the failure of MTX treatment. The diagnostic accuracy, sensitivity and specificity in the test group were 97.22%, 100%, and 96.9%, respectively. IMPACT STATEMENT What is already known on this subject? A decrease of 15% β-hCG levels between Days 4 and 7 is a common protocol for predicting the success of a single-dose methotrexate therapy of an ectopic pregnancy. What do the results of this study add? This clinical study offers the cut-off values points for prediction of single-dose methotrexate treatment failure. What are the implications of these findings for clinical practice and/or further research? We identified the importance of β-hCG increase between Days 1 and 4 and β-hCG increment in 48 h pre-treatment for predicting the failure of single-dose methotrexate therapy. It can be used to aid the clinician to optimise the selection of the most appropriate treatment methods during a follow-up evaluation after MTX treatment.

Recurrence of methotrexate-induced leukoencephalopathy after methotrexate rechallenge: A case report and literature review

Methotrexate (MTX) is potent chemotherapeutic agent, often administered intrathecally to treat or prevent central nervous system involvement in lymphomas and leukemias, particularly T-cell lymphoblastic leukemia (T-LBL). MTX has been linked to adverse neurologic effects that mimic acute stroke, including facial drooping, hemiplegia, impaired consciousness, and seizures, as well as changes on imaging-known as MTX-induced leukoencephalopathy (LE). We report a case of a 17-year-old male diagnosed with T-LBL, who had been receiving MTX chemotherapy for 4 months. After receiving his fourth dose of MTX, he presented to the emergency department with fever, facial drooping, and acute left-sided weakness. Brain magnetic resonance imaging (MRI) revealed bilateral deep white matter T2 hyperintense foci, increased on the right, with associated diffusion restriction in the right centrum semiovale-consistent with MTX-induced LE. After his symptoms resolved, he was discharged on leucovorin. Six months afterward, he was rechallenged with MTX and developed recurrence of symptoms. Repeat MRI showed well-defined T2/FLAIR hyperintensities in the right centrum semiovale without corresponding diffusion restriction. The left centrum semiovale hyperintensity became less conspicuous in comparison to the previous MRI study. We report a rare case of recurrence of LE after MTX rechallenge and discuss mechanisms, best imaging modalities, and possible treatment options for MTX-induced LE. Given the ominous presentation of MTX-induced LE, we urge clinicians to maintain a high index of suspicion for this condition. Further research is necessary to understand why only certain patients develop recurrence of LE after subsequent doses of MTX.

Low-Dose Intravitreal Methotrexate for Proliferative Vitreoretinopathy

Proliferative vitreoretinopathy (PVR) has been mitigated by intravitreal methotrexate (MTX) 400 μg/0.1 mL in several studies. Here, we evaluate the results from a lower dose of MTX, 200 μg/0.05 mL. We identified and reviewed records of patients with grade ≥C1 PVR who were treated with 200 μg/0.05 mL MTX injections: during PVR surgery and every 2 weeks thereafter. Twenty-four eyes met inclusion criteria with a mean of 5.6 injections and follow-up ranging 6 to 56 months. The retina was reattached in 19 of 24 eyes (79%) after a single surgery and in 5 of 24 eyes (21%) after one additional PVR surgery. Visual acuity improved from baseline logMAR 1.63 to 0.97 at 12 months (P < .001), with 5 of 20 achieving 20/60 or better and 16 of 20 achieving 20/200 or better. One eye developed a transient corneal abrasion that resolved within 1 week. Low-dose MTX (200 μg/0.05 mL) during and after PVR surgery resulted in good rates of retinal reattachment and visual acuity recovery. [Ophthalmic Surg Lasers Imaging Retina 2023;54(3):139-146.].

Prophylactic Chemotherapy for the Prevention of Gestational Trophoblastic Neoplasia- A descriptive study

Background: Gestational trophoblastic neoplasia develops from the trophoblastic cells which later form the placenta. It ranges from the relatively benign partial and complete hydatidiform mole while choriocarcinoma and the rare placental site trophoblastic tumor are its malignant variants. The risk of developing gestational trophoblastic neoplasia (GTN) is 15-17% after complete mole and 3.5-4% after partial mole1,2. This risk is more in patients with high-risk molar pregnancy1,2. Aim: To evaluate the role of prophylactic chemotherapy in prevention of gestational trophoblastic neoplasia in patients who fall in high-risk molar category. Place and duration of study: Ghurki Trust Teaching Hospital and Surgimed Hospital, 2016-2020 (4 years duration) Study design: Descriptive case series Methodology: Twenty three patients who presented with high-risk molar pregnancy in the study period were included in this study after takinginformed consent.These patients were divided into two groups. Group A included those patients who underwent suction evacuation followed by prophylactic chemotherapy; they were 13 in number, while group B had 10 patients and they underwent suction and evacuation only. Single dose of methotrexate 1mg/kg body weight was given to the patients in group A. Patients were asked about the history of excessive vaginal bleeding and serial beta hcg levels were carried out on follow up. Results: The patients average age was 32 years with the range between 25-42 years.14 patients (61%) were more than 40 years old while 9 patients (39%) were less than 40 years old. Three patients had beta hcg levels above 100,000 IU/ml. Patients were followed up withserial beta hcg levels till they became negative.No patient (0%) in group A developed gestational trophoblastic neoplasia while two patients (15.3%) in group B developed persistent vaginal bleeding and 1 patient (7%) developed choriocarcinoma involving the brain. Conclusion: Prophylactic chemotherapy reduces the risk of development of gestational trophoblastic neoplasia as concluded by thisstudy. However, only 16% of patients in high-risk molar category develop gestational trophoblastic neoplasia2 which means this will expose 84% patients to unnecessary chemotherapy. This will increase the cost of treatment also. Keywords: Molar pregnancy, Prophylactic chemotherapy, Gestational trophoblastic neoplasia

Novel and replicated clinical and genetic risk factors for toxicity from high-dose methotrexate in pediatric acute lymphoblastic leukemia.

Methotrexate (MTX) is a key component of treatment for high-risk pediatric acute lymphoblastic leukemia (ALL) but may cause acute kidney injury and prolonged hospitalization due to delayed clearance. The purpose of this study is to identify clinical and genetic factors that may predict which children are at risk for creatinine increase and prolonged MTX clearance. We conducted a single-center, retrospective cohort study of pediatric patients with ALL who received 4000-5000 mg/m2 of MTX. Measurements We performed germline genotyping to determine genetic ancestry and allele status for 49 single nucleotide polymorphisms (SNPs) identified from the literature as related to MTX disposition. Bayesian hierarchical ordinal regression models for creatinine increase and for prolonged MTX clearance were developed. Hispanic ethnicity, body mass index (BMI) < 3%, BMI between 85%-95%, and Native American genetic ancestry were found to be associated with an increased risk for creatinine elevation. Older age, Black race, and use of the intensive monitoring protocol were associated with a decreased risk for creatinine elevation. Older age, B- compared to T-ALL, and the minor alleles of rs2838958/SLC19A1 and rs7317112/ABCC4 were associated with an increased risk for delayed clearance. Black race, MTX dose reduction, and the minor allele of rs2306283/SLCO1B1 were found to be associated with a decreased risk for delayed clearance. These predictors of MTX toxicities may allow for more precise individualized toxicity risk prediction.