Use Of Methotrexate Research Articles

Cutaneous spectrum of lupus erythematosus: A cohort of patients from a referral-center in Colombia

IntroductionTo date, few epidemiological studies compare the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE). The information is even more scarce in Latin America. The aim of this study is to describe the phenotype of CLE in a reference center in Colombia. Materials and methodsA retrospective cross-sectional study was carried out. SLE was confirmed according to EULAR/ACR 2019 classification criteria and patients were simultaneously evaluated in the rheumatology and dermatology clinics. A descriptive and bivariate analysis was carried out. The institutional committee approved the study. ResultsThirty participants were diagnosed with SLE and CLE. Most patients were female (83.3%), with a mean age of 37±13 years. Chronic CLE was the most prevalent subtype (46.7%), followed by acute (30%) and subacute (16.7%) CLE. There were statistically significant differences when comparing acute CLE and reduced C4 (p=.032); in subacute CLE and interstitial lung disease (p=.010); and in lymphopenia (p=.012) and thrombocytopenia (p=.046). Finally, there was a difference in patients with chronic CLE and the use of topical corticosteroid (p=.026), methotrexate (p=.036), and SLEDAI>3 points (p=.025). ConclusionThis study provides valuable insights into the phenotypic characteristics and associations of CLE with systemic manifestations in the Colombian population, contributing to the understanding and managing of this complex autoimmune disease.

Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.

To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Analysis of factors influencing target PASI responses and side effects of methotrexate monotherapy in plaque psoriasis: a multicenter study of 1521 patients.

Methotrexate (MTX) is commonly used as first-line systemic treatment agent in psoriasis. We aimed to evaluate the clinical characteristics and treatment responses of patients with psoriasis undergoing MTX monotherapy. Data from adult patients with plaque psoriasis who received MTX monotherapy for at least 3months between April 2012 and April 2022 were retrospectively evaluated in 19 tertiary care centers. Our study included 722 female and 799 male patients, a total of 1521 participants. The average age of the patients was 44.3 ± 15.5years. Mode of treatment was oral in 20.4% of patients while in 79.4% it was subcutaneous. The median treatment duration was 8months (IQR = 5-15). The median weekly dose was 15mg (IQR = 11-15). 1448 (95.2%) patients were taking folic acid supplementation. At week 12, 16.3% of the patients achieved PASI (Psoriasis Area and Severity Index) 90 response while at week 24, 37.3% achieved it. Logistic regression analysis for week 12 identified the following independent factors affecting PASI 90 achievement positively: median weekly MTX dose ≤ 15mg (P = 0.011), subcutaneous administration (P = 0.005), no prior systemic treatment (< 0.001) and folic acid use (0.021). In logistic regression analysis for week 24; median weekly MTX dose ≤ 15mg (P = 0.001), baseline PASI ≥ 10 (P < 0.001), no prior systemic treatment (P < 0.004), folic acid use (P = 0.001) and absence of comorbidities (P = 0.009) were determined as independent factors affecting the achievement of PASI 90. Adverse effects were observed in 38.8% of the patients, with nausea/vomiting (23.9%) and transaminase elevation (13%) being the most common. The most common reasons for interruptions (15.3%) and discontinuations (27.1%) of the treatment were patient related individual factors. The use of MTX as the first systemic treatment agent, at doses ≤ 15mg/week and concurrent folic acid application are positive predictive factors for achieving the target PASI response both at weeks 12 and 24. In our study, which is one of the most comprehensive studies on MTX treatment in psoriasis, we observed that MTX is an effective and safe treatment option.

Protective Role of Hesperidin Nanoparticles and Hesperidin against Methotrexate-Induced Reproductive System Toxicity in Male Albino Rats

Background: In light of the widespread use of the drug methotrexate in the medical field and the lack of awareness of its side effects and its impact on fertility, it was necessary to search for some treatments that do not contain side effects. Objective: find effective substances from medical plants to reduce the effect of the drug’s side effects on fertility. Materials and Methods: The study involved a group of 30 adult male rats, rats were divided into five groups: control group These animals were dosed with Normal Saline ,second group animals that were dosed orally with Methotrexate at 1 mg/kg once a week for two consecutive months ,third group dosed orally with hesperidin (62mg/kg). The fourth group were dosed simultaneously with the hesperidin (62mg/kg) and with the 1 mg/kg Methotrexate. The fifth group were dosed with(62mg/kg) hesperidin nanoparticles and simultaneously with 1 mg/kg methotrexate orally for 60 days. The dosage amount was also chosen based on previous research, and an experiment was conducted on hemolysis and antioxidant activity to determine the safety of the dosage concentration. Results: The Methotrexate caused a decrease in the level of sex hormones and had a negative effect on the level of sperm count and morphology, while hesperidin had a clear effect in raising the level of LH, FSH and testosterone and also sperm count and reducing abnormalities in the sperm, while on the histological level it was found that Methotrexate displays a distorted structure of the testicular tissue. This is characterized by an enlargement of the spaces between the seminiferous tubules, resulting in increased diameters. Additionally, there is a decrease in the size of the epithelial cell layer, cell necrosis, and a scarcity or absence of sperm. The cohort administered with the active compound hesperidin had a typical configuration of testicular tissue, characterized by the presence of tubules. Sperm has an oval morphology and exhibit a consistent and organized arrangement. The tubules are enveloped by a basement membrane that is composed of sperm-generating cells, including dispersed Sertoli cells with triangular nuclei. In close proximity to the cavity, the cells exhibited a larger size and had black, round nuclei, accompanied by spermatids that displayed a round or rectangular form. The presence of sperm was discovered within the interior spaces of the seminal tubules. Conclusion: The hesperidin nanoparticles had the best effect on increasing fertility, Hesperidin played a role in reducing the amount of damage caused by the drug Methotrexate on the tissues of the reproductive system. Hesperidin had a role in restoring the level of reproductive hormones to a level similar to normal, while the nanoparticles of hesperidin had a greater role in maintaining the level of hormones in a way similar to the control groups and in protecting the reproductive tissues from the damage caused by methotrexate.

Progressive multifocal leukoencephalopathy reports in rheumatoid arthritis concerning different treatment patterns-an exploratory assessment using the food and drug administration adverse event reporting system

Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare but potentially life-threatening brain infection caused by the John Cunningham virus. PML is a known adverse effect associated with molecular-targeted drugs and immunosuppressive agents. Recent concerns have emerged regarding the link between methotrexate (MTX) and PML. However, limited information exists on the influence of concomitant drug use in rheumatoid arthritis (RA) treatment, where various medications are often used together.Methods: To explore treatment patterns and patient background that affect PML reporting in RA, we analyzed data on RA cases from the Food and Drug Administration Adverse Event Reporting System (FAERS; JAPIC AERS) database between 1997 and 2019.Results and Discussion: Our analysis revealed significantly elevated crude and adjusted reporting odds ratios (aROR) for MTX, rituximab (RIT), azathioprine, and cyclophosphamide. When considering treatment patterns, the concomitant use of MTX and RIT showed a higher aROR than using MTX or RIT alone. Additional TNF-α inhibitors or glucocorticoids did not increase PML reports. Moreover, male sex and older age were associated with increased PML reports. While limitations are inherent in studies using spontaneous reporting data, our exploratory assessment suggests an association between PML and the combination of MTX and RIT and a higher risk in men and older patients. These findings help enhance our understanding of PML risk factors in the context of RA treatment.

Incident Use of Hydroxychloroquine for the Treatment of Rheumatoid Arthritis and Systemic Lupus Erythematosus During the COVID-19 Pandemic.

We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We used US claims data (IQVIA PHARMETRICS®Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d'Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control. More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment. Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States.

Methotrexate Use and Risk of Interstitial Lung Disease in Dermatomyositis

This cohort study examines the association between methotrexate use and interstitial lung disease in patients with dermatomyositis.

Three- and five-year outcomes of an inception cohort of Australian children with juvenile idiopathic arthritis.

To describe the 3- and 5-year outcomes of an inception cohort of Australian children with JIA for whom 1-year outcomes have previously been published. Data regarding clinical outcomes of the original cohort of 134 patients at 3 and 5 years were sought. Relevant clinical features and medication exposures entered prospectively into an electronic record were collected and analyzed using descriptive statistics. Data were available for 110 and 98 patients at 3 and 5 years, respectively. The proportion of patients with active joints progressively decreased from 34% at 12 months to 21% at 3 years and 16% at 5 years. Cumulative exposure to methotrexate increased between 3 and 5 years (75%-80%), however, point prevalence use decreased (45%-41%). Cumulative exposure and point prevalence use of bDMARDS both increased between 3 and 5 years; 30%-42% and 29%-33%, respectively. Thirty-five percent of patients had inactive joint disease off medications at 5 years, which occurred most frequently in patients with sJIA and oligoarthritis. Five-year outcomes of Australian children with JIA are good, with only a small minority having ongoing active joint disease at 5 years. bDMARDS play an increasing role in management over time; however, methotrexate use remains significant. A majority of children remain on medications at 5 years.

Rare complication of rheumatoid arthritis: Charcot Neuro-osteoarthropathy

BackgroundRheumatoid arthritis (RA) is an autoimmune disease.However, there are few cases of Charcot Neuro-osteoarthropathy (CN) caused by rheumatoid diseases in clinical reports. It is not easy to pay attention to the diagnosis of CN in the complications of rheumatoid disease, which greatly increases the probability of misdiagnosis and missed diagnosis. This case reported a rare complication of rheumatoid arthritis, Charcot arthritis, and the molecular mechanism and diagnosis and treatment of CN caused by RA were systematically discussed.Case presentationThe patient, a 79-year-old woman, was hospitalized due to bilateral shoulder pain, limited activity for half a year, aggravated for 4 months to the hospital. During this period, the symptoms did not improve after treatment with acupuncture and Chinese medicine. The patient was previously diagnosed with rheumatoid arthritis for more than 3 years and intermittent irregular use of methylprednisolone and methotrexate for 2 years. She had a history of osteoporosis. Physical examination: symmetrical malformed swelling of the finger joints of both hands; Bilateral supraspinatus and deltoid muscle atrophy, tenderness at the acromion, and attachment of the long head tendon of the biceps brachii were observed. The left Dugas test and the right Dugas test were positive.Blood test: anti-cyclic citrullinated peptide antibody (A-CCP) 33.10U/ml (normal range: 0-5RU/ml); antinuclear antibody quantification (ANA) 47.40AU/ml (normal range: Negative or < 32); anti-double stranded DNA IgG antibody quantification (dsDNA) 31.00 IU/ml (normal range: 0-100 IU/ml); D-Dimer 6.43 µg/ml (normal range: 0–0.5 mg/L); erythrocyte sedimentation rate (ESR) was 27 mm/h (normal range: < 20 mm/60 min). C-reactive protein (CRP) 39.06 mg/L(0.068-8 mg/L).MRI 3.0 T enhancement of bilateral shoulder joints, cervical spine and thoracic spine showed: 1.Large bone destruction, cartilage injury, multiple effusion, synovitis, obvious on the right side. 2.Intervertebral disc degeneration, cervical 3/4, 4/5, 5/6, 6/7 disc herniation, with cervical 3/4 obvious, posterior central herniation;ConclusionsRheumatoid arthritis complicated with Charcot's joint is rare. Clinically, patients with rheumatoid diseases should not ignore Charcot's joint complications because of rareness. Early blood inflammatory markers, neuro electrophysiology, and imaging MRI of rheumatoid CN are of great significance for the diagnosis of this mild or early neurovascular inflammation. Early diagnosis and treatment are helpful to prevent further joint injury. The clinical diagnosis, treatment, and molecular mechanism of osteolysis in RA and peripheral sensory nerve injury remain to be further revealed.

Relationship of Hematological Profiles with the Serum Complement System in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes.

New-onset or relapse of uveitis after rapid spreading of COVID-19 infection in China and risk factor analysis for relapse

BackgroundThe aim of this study was to report the clinical profile of new-onset and relapse of uveitis following rapid spreading of coronavirus disease 2019 (COVID-19) infection due to change of anti-COVID-19 policies in China and investigate potential risk factors for inflammation relapse.MethodsIn this retrospective case-control study, patients with new-onset or a history of uveitis between December 23, 2022, and February 28, 2023, were included to assess the influence of COVID-19 infection on uveitis. Detailed information on demographic data, clinical characteristics, treatment measures, treatment response, and ocular inflammatory status before and after COVID-19 infection was collected.ResultsThis study included 349 patients with a history of uveitis. The uveitis relapse rate was higher (28.8%, n = 288) in those with COVID-19 infection than in patients without COVID-19 infection (14.8%, n = 61) (P = 0.024). Among the relapse cases, 50.8% experienced a relapse of anterior uveitis, while 49.2% had a relapse of uveitis involving the posterior segment. Multivariable regression analysis indicated a positive correlation between disease duration and uveitis relapse, while the last relapse exceeding one year before COVID-19 infection and the use of methotrexate during COVID-19 infection were negatively correlated with relapse of uveitis. Thirteen patients who developed new-onset uveitis following COVID-19 infection were included; among them, three (23.1%) had anterior uveitis and 10 (76.9%) had uveitis affecting the posterior segment. Regarding cases involving the posterior segment, four patients (30.8%) were diagnosed with Vogt-Koyanagi-Harada disease.ConclusionsCOVID-19 infection increases the rate of uveitis relapse. Long disease duration is a risk factor, while time since the last relapse more than 1 year and methotrexate use are protective factors against uveitis relapse.

Extensive extra genital Csillag’s disease: a rare case report

Lichen sclerosus et atrophicus (LSA), also called as Csillag’s disease, is characterized by small, shiny, porcelain white, sclerotic papules, plaques and atrophic patches that can occur at any site on the skin including the mucosa. Most commonly found in genitalia, rarely occurring on extragenital skin. Predominantly seen in women with bimodal age distribution. Predominantly an interface dermatoses histopathologically consisting of epidermal atrophy, sclerosis /homogenization of collagen fibers and lichenoid inflammatory infiltrates in dermis. No effective treatment till date although topical steroids, calcineurin inhibitors, topical retinoids and systemic agents like hydroxychloroquine, mexthotrexate, PUVA shows varying inconsistent results. Here we report a case of 36-year-old female having LSA with extensive extra vulval involvement including face. No any other co-existing skin disorders. She showed partial improvement use of physical sunscreens, systemic antimalarials, oral methotrexate and antioxidants.

Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

Rheumatology: What You May Have Missed in 2023.

Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.

The temporal association between adverse drug reactions and antirheumatic drugs utilisation in Western Australia: a retrospective study from real-world data (1995-2015).

Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with antirheumatic medications, this study aims to analyse and compare ADR reporting for these drugs in the pharmacovigilance datasets of Western Australia (WA) and the United States (US). Therapeutic Goods Administration provided WA pharmacovigilance data of selected antirheumatic drugs to from 1995 to 2015. The proportional reporting ratio (PRR) for WA case reports was compared to corresponding USA pharmacovigilance data by assessing the disproportionality of each ADR. clinically significant or true ADRs were determined using the Evans 2001 criteria (n > 2, chi-square > 4, PRR > 2). A total of 232 reports were found in WA, mostly on sixty-nine women aged 45 to 69. Methotrexate, leflunomide, azathioprine, sulfasalazine, and infliximab had the highest reported ADRs, related to gastrointestinal disorders. Patients who used biological agents in WA had 2.7 times the likelihood of reporting true ADRs compared to conventional antirheumatic drugs. The ADR rates in the two datasets were comparable over the study period. The PRR values of ADRs were consistent between WA and US databases. Methotrexate and infliximab use were commonly associated with ADR reports in WA females, with incidence rates comparable to the US; while patients using biological agents were more likely to report true ADRs than those on conventional antirheumatic drugs in WA.

Assessment of Risk Factors for Acute Kidney Injury with Machine Learning Tools in Children Undergoing Hematopoietic Stem Cell Transplantation.

Background: Although acute kidney injury (AKI) is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT), its prophylaxis remains a clinical challenge. Attempts at prevention or early diagnosis focus on various methods for the identification of factors influencing the incidence of AKI. Our aim was to test the artificial intelligence (AI) potential in the construction of a model defining parameters predicting AKI development. Methods: The analysis covered the clinical data of children followed up for 6 months after HSCT. Kidney function was assessed before conditioning therapy, 24 h after HSCT, 1, 2, 3, 4, and 8 weeks after transplantation, and, finally, 3 and 6 months post-transplant. The type of donor, conditioning protocol, and complications were incorporated into the model. Results: A random forest classifier (RFC) labeled the 93 patients according to presence or absence of AKI. The RFC model revealed that the values of the estimated glomerular filtration rate (eGFR) before and just after HSCT, as well as methotrexate use, acute graft versus host disease (GvHD), and viral infection occurrence, were the major determinants of AKI incidence within the 6-month post-transplant observation period. Conclusions: Artificial intelligence seems a promising tool in predicting the potential risk of developing AKI, even before HSCT or just after the procedure.

Methotrexate and the Risk of Dementia: A Two-Sample Mendelian Randomization Study.

Recent studies have suggested a potential association between methotrexate use and an increased risk of dementia. However, the causal relationship between methotrexate and dementia remains unclear. This study aims to investigate the potential causal effect of methotrexate use on the risk of dementia using a two-sample Mendelian randomization (TSMR) approach. We conducted a TSMR study using summary statistics from genome-wide association studies (GWAS) of methotrexate use and dementia. We obtained genetic instruments for methotrexate use from a large-scale GWAS meta-analysis and genetic instruments for dementia from a separate GWAS meta-analysis. We performed several statistical analyses, including inverse-variance weighted (IVW), weighted median (WM1), weighted mode (WM2), and MR-Egger regression methods, to estimate the causal effect of methotrexate on dementia risk. Our TSMR analysis showed a significant positive association between genetic predisposition to methotrexate use and dementia risk. The IVW method estimated a causal odds ratio (OR) of 0.476 [95% confidence interval (CI) 0.362-0.626] per unit increase in the log odds ratio of methotrexate use. WM1, WM2, and MR-Egger methods provided consistent results. The findings of this mendelian randomization (MR) study suggest a potential causal effect of methotrexate use on the risk of dementia. However, further research is needed to validate these findings and explore the underlying mechanisms. Since methotrexate is widely prescribed for various autoimmune diseases, a better understanding of its potential impact on dementia risk is crucial for optimizing treatment strategies and addressing potential adverse effects.

Protective Effect of Green Chiretta (Andrographis paniculata) against Methotrexate-induced Cardio and Spleen Toxicity: In-vitro and In-vivo

Background:: Methotrexate (MTX) is a widely used medication for treating various conditions, including skin infections, inflammatory diseases, autoimmune disorders, and malignancies. However, prolonged and extreme use of MTX can lead to detrimental effects on multiple organs. Green Chiretta (GC) is a traditional medicinal plant known for its anti-inflammatory, antioxidant, and immunostimulatory properties. Objective:: The objective of this study is to examine the antioxidant potential of GC through in-vitro analysis and to assess the potential protective effects of aqueous leaf extracts of GC against MTXinduced cardiac and spleen toxicity. Methods:: In-vitro antioxidant activity was assessed by measuring total phenolic content, DPPH, catalase and peroxidase activity. We divided rats into five groups (n=6), and after the study, rats were euthanized and the levels of antioxidants (SOD, CAT &amp; GSH) and lipid peroxidase (MDA), as well as histopathology modification of the heart and spleen tissues were examined. Results:: Our study's findings highlight the superiority of the aqueous GC extract's antioxidant capacity relative to other solvents (ethanol and methanol). Moreover, the aqueous GC extract's administration to rats yielded significant progress in antioxidant levels (Superoxide dismutase, catalase, glutathione), a reduction in lipid peroxidation (MDA), and the restoration of cardiac and spleen histoarchitecture against MTX-induced toxicity. These results collectively emphasize the extract's potential as a valuable therapeutic option against oxidative stress and tissue damage. Conclusion:: The present study revealed that the aqueous GC extract demonstrated its protective efficacy against MTX-induced cardio and spleen toxicity in Wistar albino rats

PULMONARY FUNCTION IN RHEUMATOID ARTHRITS: A CROSS-SECTIONAL STUDY

Objective: Rheumatoid arthritis (RA) is an autoimmune disease with many extraarticular manifestations. Pulmonary involvement is seen in 60-80% cases with and without symptoms. This research studies the pattern of PFT (Pulmonary Function Test) in RA and find the correlation between PFT and Disease activity. Secondary objectives were to evaluate the effect of use of Methotrexate (MTx) on disease activity and PFT.&#x0D; Methods: An outpatient-based descriptive cross-sectional study was conducted in General Medicine department at a tertiary centre among 100 eligible patients. Disease activity score was recorded using DAS-28 (Disease Activity Score-28) and CDAI (Clinical Disease Activity Index). Patients underwent PFT by Spirometry thereafter.&#x0D; Results: 45 % patients had restrictive pattern and 55% had normal PFT. None had an obstructive pattern. The mean FVC (Forced Vital Capacity), FEV1 (Forced Expiratory Volume in the first second), FEV1/FVC ratio, PEFR (Peak Expiratory Flow Rate) and FEF 25-75% (Forced mid expiratory flow) were 78.83±14.37, 79.24±16.96, 103.56±11.03, 71.73±22.39 and 76.56±23.72 respectively. Both FVC and FEV1 were found to be significantly associated with age, disease duration, CDAI score, MTx dose and duration (P&lt;0.05). Age, ESR(erythrocyte sedimentation rate) and MTx dose were significantly associated with FEV1/FVC ratio (P&lt;0.05). Age, duration of disease, ESR. MTx dose and duration were significantly associated with PEFR (P&lt;0.05). Lastly age, CDAI score, MTx dose and duration were significantly associated with FEF 25-75% (P&lt;0.05).&#x0D; Conclusion: Restrictive pattern (45%) was the most common defect on PFT among RA patients. Severity of lung disease depends on age, MTx dose, disease activity (ESR, CDAI), duration of disease and MTx duration.

Liver Elastography for the Detection of Methotrexate-Induced Liver Injury: A Retrospective Study

Background: Liver biopsy, the gold standard for monitoring of methotrexate-induced liver injury, is associated with significant morbidity and mortality. Transient elastography (TE) has been used as a non-invasive alternative to detect liver stiffness. Aim: To assess the utility of TE in detecting liver fibrosis in patients with methotrexate use. Methods: A retrospective chart review was performed for 35 patients referred to the liver clinic for evaluation of suspected methotrexate-induced liver injury. Demographic, clinical, histopathological, and elastographic data were collected and interpreted. Liver stiffness measurement (LSM) and controlled attenuation parameter were recorded from TE results. Results: Thirty-five patients with a mean age of 58 years, including 23 females (66%), were included. The median LSM by TE was 10.8 kPa and the median controlled attenuation parameter was 303 dB/m. A total of 12 out of 35 patients (34%) had evidence of clinical and pathological advanced fibrosis. Using a cut-off elastography value of 10 kPa, the TE yielded 92% sensitivity and 93% negative predictive value for ruling out methotrexate-induced advanced liver fibrosis. Using a higher LSM cut-off point of kPa ≥15.0, specificity was calculated at 87% and positive predictive value at 80%. Area under the receiver operating characteristic curve was 0.80 (95% confidence interval). Conclusion: FibroScan® (Echosens, Paris, France) has a high sensitivity and specificity for kPa 10 and 15, respectively, for detecting advanced liver fibrosis in patients on methotrexate.