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2.
Reprod Health ; 21(1): 95, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956582

ABSTRACT

BACKGROUND: Non-tubal ectopic pregnancies account for < 10% of all ectopic pregnancies. Due to its rarity and wide variation in clinical practice, there is no guideline or consensus for its management. We reported our 20-year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital. METHODS: This is a retrospective review of all women admitted for non-tubal ectopic pregnancies from January 2003 to December 2022 in a tertiary hospital. Women with non-tubal ectopic pregnancies diagnosed by ultrasound or operation were included for analysis. RESULTS: Within the study period, 180 women were diagnosed to have non-tubal ectopic pregnancies at a mean gestation of 6.8 weeks. 16.7% (30/180) were conceived via assisted reproduction. Medical treatment was the first-line management option for 81 women, of which 75 (92.1%) women received intralesional methotrexate administered under transvaginal ultrasound guidance. The success rate of intralesional methotrexate ranges from 76.5% to 92.3%. Intralesional methotrexate was successful even in cases with a positive fetal pulsation or with high human chorionic gonadotrophin levels up to 252605U/L. Twenty seven women were managed expectantly and 40 underwent surgery. Nine (11.1%), two (6.1%), and one (2.3%) women required surgery due to massive or recurrent bleeding following medical, expectant, or surgical treatment. Hysterotomy and uterine artery embolization were necessary to control bleeding in one Caesarean scar and one cervical pregnancy. CONCLUSIONS: Intralesional methotrexate is more effective than systemic methotrexate and should be considered as first line medical treatment for non-tubal ectopic pregnancies. It has a high success rate in the management of unruptured non-tubal ectopic pregnancies even in the presence of fetal pulsations or high human chorionic gonadotrophin levels, but patients may require a prolonged period of monitoring. Close surveillance and readily available surgery were required due to the risk of heavy post-procedural intra-abdominal bleeding.


Subject(s)
Abortifacient Agents, Nonsteroidal , Methotrexate , Pregnancy, Ectopic , Tertiary Care Centers , Humans , Female , Pregnancy , Retrospective Studies , Pregnancy, Ectopic/therapy , Pregnancy, Ectopic/surgery , Adult , Methotrexate/therapeutic use , Methotrexate/administration & dosage , Abortifacient Agents, Nonsteroidal/therapeutic use , Abortifacient Agents, Nonsteroidal/administration & dosage
3.
Neurology ; 102(12): e209527, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38830184

ABSTRACT

OBJECTIVES: Despite a high response rate at the first evaluation during induction chemotherapy, the risk of early relapse remains high and unpredictable in primary CNS lymphomas (PCSNLs). We aimed to assess the prognostic value of early IL-10 levels in CSF (e-IL-10) after 2 months of induction chemotherapy. METHODS: We retrospectively selected from the LOC (Lymphomes Oculo-Cérébraux) network database patients with PCSNLs who had complete or partial response at the 2-month evaluation of a high-dose methotrexate-based first-line chemotherapy for whom e-IL-10 was available. RESULTS: Thirty patients (median age: 62 years, brain involvement in 30/30, CSF involvement in 10/30, median baseline CSF IL-10: 27.5 pg/mL) met the selection criteria. e-IL-10 was undetectable in 22 patients and detectable in 8 patients. At the end of induction treatment, 7 of 8 and 4 of 22 of the patients with detectable and undetectable e-IL-10 had experienced progressive disease, respectively (p = 0.001, OR: 26.8, 95% CI 2-1,478). The median progression-free survival times were 5.8 months (95% CI 2.8-8.8) and 28.7 months (95% CI 13.4-43.9) in the groups with detectable and undetectable e-IL-10, respectively (p < 0.001). DISCUSSION: Our results suggest that despite an objective response, the persistence of detectable e-IL-10 is associated with a high risk of early relapse in PCNSL. A closer follow-up of such patients is warranted.


Subject(s)
Central Nervous System Neoplasms , Induction Chemotherapy , Interleukin-10 , Humans , Middle Aged , Female , Male , Interleukin-10/cerebrospinal fluid , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/drug therapy , Aged , Retrospective Studies , Prognosis , Adult , Lymphoma/cerebrospinal fluid , Lymphoma/drug therapy , Methotrexate/therapeutic use , Methotrexate/administration & dosage
4.
Arch Dermatol Res ; 316(7): 400, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878177

ABSTRACT

BACKGROUND: Keratoacanthoma (KA) is a benign neoplasm that affects mainly photodamaged skin. It is locally destructive and may rarely spread. Surgery is not always suitable and usually disfiguring. Thus, non-operative modalities represent good alternatives. OBJECTIVE: To assess and compare the efficacy of intralesional methotrexate (MTX) and 5-flurouracil (5-FU) in the treatment of KA. PATIENTS AND METHODS: Randomized controlled trial included 20 patients with biopsy proven KA divided into 2 equal groups; group (A) received intralesional MTX, 25 mg/ml and group (B) received intralesional 5-FU, 50 mg/ml every 2 weeks till complete clearance or for a maximum 5 sessions. RESULTS: In the MTX group, complete clearance was observed in 7 patients (70%) compared to 8 patients (80%) in the 5- FU group with no statistically significant difference. However, the median number of injections needed to achieve complete response in the MTX group was 3 sessions versus only 2 sessions in the 5-FU group. LIMITATIONS: the small sample size due to the relatively low incidence of KAs in our population. CONCLUSION: Intralesional therapy is a good alternative to surgery in selected cases of KA. Both drugs showed comparable efficacy, but 5-FU may give faster results, hence increasing patient satisfaction and compliance.


Subject(s)
Fluorouracil , Injections, Intralesional , Keratoacanthoma , Methotrexate , Humans , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Keratoacanthoma/drug therapy , Keratoacanthoma/pathology , Female , Male , Middle Aged , Aged , Treatment Outcome , Adult , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Aged, 80 and over
5.
Arch Dermatol Res ; 316(6): 316, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822884

ABSTRACT

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.


Subject(s)
Drug Liberation , Emulsions , Gels , Methotrexate , Skin Absorption , Methotrexate/administration & dosage , Methotrexate/chemistry , Methotrexate/pharmacokinetics , Humans , Skin Absorption/drug effects , Rheology , Lipids/chemistry , Administration, Cutaneous , Skin/metabolism , Skin/drug effects , Administration, Topical , Drug Delivery Systems/methods , Animals , Particle Size , Drug Carriers/chemistry , Nanogels/chemistry
6.
Reumatismo ; 76(2)2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38916170

ABSTRACT

OBJECTIVE: Data from trials demonstrated that abatacept (ABA) has a good safety and efficacy profile in treating rheumatoid arthritis. We have studied the retention rate of ABA in a real-life cohort of patients with rheumatoid arthritis. METHODS: This is a monocentric, retrospective study including patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism 2010 criteria who started treatment with ABA. The Kaplan-Meier method was applied to evaluate the ABA retention rate. RESULTS: This analysis was conducted on 161 patients [male/female 21/140, median age 65 years, interquartile range (IQR) 18.7, median disease duration 169 months, IQR 144.0]. 111 patients (68.9%) received ABA subcutaneously. ABA was associated with methotrexate in 61.9% of patients and was the first biological disease-modifying antirheumatic drug in 41%. We observed a median ABA survival of 66 months [95% confidence interval (CI) 57.3-74.7], with a retention rate of 88% at 6 months and 50.9% at 5 years. Drug survival was significantly higher in patients treated with ABA subcutaneously and in male patients (p=0.039 and p=0.018, respectively). Adjusted for main confounders, female gender was the main predictor of withdrawal (hazard ratio 5.1, 95% CI 1.2-21.3). CONCLUSIONS: Our study shows that better survival is associated with subcutaneous administration and male gender, confirming ABA effectiveness.


Subject(s)
Abatacept , Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Abatacept/therapeutic use , Arthritis, Rheumatoid/drug therapy , Male , Female , Retrospective Studies , Aged , Antirheumatic Agents/therapeutic use , Middle Aged , Methotrexate/therapeutic use , Methotrexate/administration & dosage , Treatment Outcome , Kaplan-Meier Estimate , Drug Therapy, Combination , Cohort Studies
7.
Ann Saudi Med ; 44(3): 141-145, 2024.
Article in English | MEDLINE | ID: mdl-38853473

ABSTRACT

BACKGROUND: Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to its effectiveness, the main concern is to limit the risk of relapse and preserve fertility. OBJECTIVES: Determine the impact of medical or surgical treatment for ectopic pregnancy on future fertility. DESIGN: Retrospective. SETTING: Department of obstrtrics and gynecolgy at Ankara Etlik Zübeyde Hanim Women's Health Training and Research Hospital, Ankara, Turkey. PATIENTS AND METHODS: Patients who were treated for ectopic pregnancy between June 2016 and November 2019 were allocated into two groups. Expectant approach or medical treatment by methotrexate constituted the conservative treatment group while salpingectomy by laparoscopy indicated the surgical treatment group. MAIN OUTCOME MEASURES: Fertility rates within two years following treatment were evaluated according to treatment options. SAMPLE SIZE: 202 patients. RESULTS: Of the 202 patients, 128 had medical treatment and 74 patients had surgical treatment for ectopic pregnancy. Of 272 diagnosed with ectopic pregnancy, 70 were excluded for various reasons. Parity and unemployment rate was significantly higher in the surgical treatment (P=.006 and P=.12, respectively). Moreover, ectopic mass size and serum ß-hCG levels were significantly higher in the surgical treatment group (P<.001 and P<.001, respectively). There were no significant differences between the conservative and surgical treatment groups in time to pregnancy (17.0 months vs 19.0 months, P=.255). Similarly, there was no significant difference between the conservative and surgical treatment groups with respect to history of infertility (P=.12). There were no significant differences between the conservative and surgical treatment groups in terms of live birth (51.6% vs 44.6%) and ectopic pregnancy (2.3% vs 1.4%) (P=.72 for both). There was no significant difference between the conservative and surgical treatment groups with respect to infertility rate (35.9% vs 41.9%, P=.72) and admittance to the IVF program (3.9% vs 6.8%, P=.39) following ectopic pregnancy treatment. CONCLUSIONS: Reproductive outcomes did not differ significantly in women undergoing expectant management, medical treatment, and surgery for ectopic pregnancy. This finding suggests that clinicians should not hesitate to act in favor of surgical treatment for ectopic pregnancy even if there were concerns for future fertility. LIMITATIONS: Retrospective study.


Subject(s)
Abortifacient Agents, Nonsteroidal , Conservative Treatment , Laparoscopy , Methotrexate , Pregnancy, Tubal , Salpingectomy , Humans , Female , Pregnancy , Retrospective Studies , Adult , Methotrexate/therapeutic use , Methotrexate/administration & dosage , Salpingectomy/methods , Conservative Treatment/methods , Pregnancy, Tubal/surgery , Laparoscopy/methods , Abortifacient Agents, Nonsteroidal/administration & dosage , Abortifacient Agents, Nonsteroidal/therapeutic use , Turkey , Fertility , Chorionic Gonadotropin, beta Subunit, Human/blood , Fertility Preservation/methods
8.
Article in Russian | MEDLINE | ID: mdl-38881013

ABSTRACT

Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases. OBJECTIVE: To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer. MATERIAL AND METHODS: Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity). RESULTS: The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months. CONCLUSION: Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.


Subject(s)
Breast Neoplasms , Injections, Spinal , Meningeal Neoplasms , Methotrexate , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Middle Aged , Adult , Meningeal Neoplasms/secondary , Meningeal Neoplasms/drug therapy , Methotrexate/administration & dosage , Aged , Meningeal Carcinomatosis/drug therapy , Meningeal Carcinomatosis/secondary , Antimetabolites, Antineoplastic/administration & dosage
9.
BMJ Case Rep ; 17(6)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38901855

ABSTRACT

Takayasu arteritis is an inflammatory disease of unknown aetiology affecting large vessels. Medium vessel involvement is also well documented; however, neuropathy as a presenting manifestation is rare. In this case report, a young woman in her 20s presented with an 8-month history of intermittent claudication in the right upper limb progressing to rest pain with allodynia in C5-C8 distribution and painless right axillary mass. On examination, she had absent pulses in the right radial, brachial and subclavian artery with audible bruit in the right subclavian and abdominal aorta. CT angiogram showed features suggestive of Takayasu arteritis with a partially thrombosed aneurysm arising from the right axillary artery leading to compression of the right brachial plexus. This patient received treatment with methotrexate and oral corticosteroids. At 3 months follow-up, there was a reduction in the size of the aneurysm, resolution of compressive symptoms and normalisation of inflammatory markers.


Subject(s)
Aneurysm , Axillary Artery , Brachial Plexus Neuropathies , Takayasu Arteritis , Humans , Takayasu Arteritis/complications , Takayasu Arteritis/diagnosis , Takayasu Arteritis/drug therapy , Female , Axillary Artery/diagnostic imaging , Aneurysm/etiology , Aneurysm/diagnostic imaging , Aneurysm/complications , Brachial Plexus Neuropathies/etiology , Brachial Plexus Neuropathies/diagnosis , Adult , Computed Tomography Angiography , Methotrexate/therapeutic use , Methotrexate/administration & dosage
10.
Article in English | MEDLINE | ID: mdl-38708770

ABSTRACT

Hailey‒Hailey disease is a rare chronic autosomal-dominant blistering disease characterized by erosions, fissures, and vegetations occurring in intertriginous regions. To date, there is no specific treatment and there are no therapeutic guidelines, which makes management of the disease challenging. We present the case of a 43-year-old man unsuccessfully treated for Hailey‒Hailey disease with topical and systemic corticosteroids, antibiotics, and surgical debridement. At presentation he had erosions, vegetations, and infection in the axillae and groin. We introduced oral methotrexate, 10 mg weekly, and complete remission was achieved in 3 weeks. After 8 weeks, we decided to discontinue methotrexate due to lesion absence. Over 3 years of follow-up, mild flares were effectively managed with topical miconazole or mild steroid creams. We conclude that oral methotrexate is safe and effective for achieving long-term remission in Hailey‒Hailey disease.


Subject(s)
Methotrexate , Pemphigus, Benign Familial , Humans , Pemphigus, Benign Familial/drug therapy , Male , Adult , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Administration, Oral , Dermatologic Agents/therapeutic use , Dermatologic Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/administration & dosage , Treatment Outcome
12.
Arch Dermatol Res ; 316(6): 278, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796658

ABSTRACT

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 3 months 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 ± 15.5 years. Mode of treatment was oral in 20.4% of patients while in 79.4% it was subcutaneous. The median treatment duration was 8 months (IQR = 5-15). The median weekly dose was 15 mg (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 ≤ 15 mg (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 ≤ 15 mg (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 ≤ 15 mg/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.


Subject(s)
Folic Acid , Methotrexate , Psoriasis , Severity of Illness Index , Humans , Methotrexate/therapeutic use , Methotrexate/administration & dosage , Methotrexate/adverse effects , Psoriasis/drug therapy , Psoriasis/diagnosis , Female , Male , Adult , Middle Aged , Retrospective Studies , Treatment Outcome , Folic Acid/administration & dosage , Folic Acid/therapeutic use , Administration, Oral , Dermatologic Agents/adverse effects , Dermatologic Agents/administration & dosage , Dermatologic Agents/therapeutic use , Injections, Subcutaneous
14.
Biomater Sci ; 12(13): 3335-3344, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38787761

ABSTRACT

Rheumatoid arthritis (RA) is a systemic immune disorder marked by synovitis, bone damage, and cartilage erosion, leading to increased socio-economic burdens and reduced quality of life. Despite its unknown cause, advancements in understanding its pathophysiology have facilitated novel therapeutic approaches. Current treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and biologics, often result in low efficacy and unnecessary side effects. To address the limitations of these drugs, carrier-based drug delivery systems, such as nanomicelles, have emerged as a promising solution. In this study, nanomicelles were synthesised utilizing PLGA (poly(lactic-co-glycolic acid)) as a backbone; this backbone is conjugated with chlorogenic acid (CGA), which is known for suppressing inflammation, and incorporates methotrexate (MTX), a model drug that is established for RA treatment. The nanomicelles were extensively characterized in terms of size, charge, drug loading, and drug-release behaviour. The in vivo assessment of MTX-PLGA-b-CGA nanomicelles in a collagen-induced arthritis model demonstrated a remarkable reduction in joint swelling, cartilage erosion, and disease severity. Furthermore, histological findings confirmed cartilage integrity and reduced expression of key pro-inflammatory markers, including receptor activator of nuclear factor kappa beta ligand (RANKL) and tumor necrosis factor (TNF-α). The approach based on the MTX-PLGA-b-CGA nanomicelles presents a biocompatible and potentially effective therapeutic strategy for management of the severity and progression of RA, providing a hopeful alternative for RA treatment.


Subject(s)
Arthritis, Experimental , Chlorogenic Acid , Methotrexate , Micelles , Polylactic Acid-Polyglycolic Acid Copolymer , Animals , Chlorogenic Acid/chemistry , Chlorogenic Acid/pharmacology , Chlorogenic Acid/administration & dosage , Methotrexate/chemistry , Methotrexate/pharmacology , Methotrexate/administration & dosage , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Mice , Drug Carriers/chemistry , Male , Drug Liberation , Nanoparticles/chemistry , Arthritis, Rheumatoid/drug therapy
15.
RMD Open ; 10(2)2024 May 20.
Article in English | MEDLINE | ID: mdl-38772677

ABSTRACT

OBJECTIVES: Non-adherence to rheumatoid arthritis (RA) treatments must be identified. A methotrexate (MTX) urinary dosage (METU) was recently developed. The aim of our study was to assess adherence to MTX in RA using METU in real-life conditions and to compare it with indirect adherence measurement technics. METHODS: We performed a cross-sectional study at Reims University Hospital. We included over 18-year-old patients with RA treated by MTX for more than 6 months. Patients were invited to complete demographic, clinical and psychological questionnaires and adherence measurement technics (Compliance Questionnaire of Rheumatology (CQR) and Medication Possession Ratio (MPR)). A urinary sample was collected to measure MTX and information about tolerance was evaluated through Methotrexate Intolerance Severity Score. RESULTS: 84 patients were included, 26 using oral MTX, 58 subcutaneous (SC) MTX. Among them, 73% were female, mean age was 61.5 years, MTX mean dose was 15 mg/week and 61.9% were treated by biological DMARDs (Disease Modifying Antirheumatic Drugs). 77 patients (91.7%) were adherent to treatment according to METU, whereas MPR and CQR reported less adherence (69.5% and 61.9%, respectively). MPR and METU were not significantly different in SC MTX users (p=0.059). Non-adherent patients had a higher number of tender joints and C reactive protein value (p<0.05). CONCLUSION: This is the first largest study evaluating MTX adherence in patients with RA using a urinary dosage. We identified that indirect adherence measurements did not reflect real-life adherence. It would be appreciable to realise METU, in a new study, in patients with RA with unexplained response to treatment, to consider it before escalating therapeutic strategy.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Medication Adherence , Methotrexate , Humans , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/urine , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Methotrexate/adverse effects , Female , Male , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/administration & dosage , Cross-Sectional Studies , Middle Aged , Aged , Surveys and Questionnaires , Adult , Biomarkers/urine
16.
Eur J Obstet Gynecol Reprod Biol ; 298: 171-174, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38762953

ABSTRACT

OBJECTIVE: The use of various methotrexate (MTX) protocols for the treatment of ectopic pregnancy is well established. This study aimed to evaluate the efficacy of single- and double-dose MTX protocols for the treatment of pregnancy of unknown location (PUL). STUDY DESIGN: This retrospective study was conducted in the Department of Gynaecological Endocrinology, University Hospital, Krakow, Poland. Haemodynamically stable women with PUL were enrolled between January 2014 and September 2023. Demographics, gestational age and treatment outcomes were compared between women in the single-dose MTX group and women in the double-dose MTX group. The primary outcome was the success rate, measured as the number of women treated without surgical intervention. The secondary outcome was the number of days of MTX needed to achieve an appropriate decrease in beta-human chorionic gonadotrophin (ß-hCG). RESULTS: Two hundred and eleven women (mean age 33 ± 1.8 years) with PUL were enrolled in the study, with an overall success rate of 89.1 %. Single- and double-dose MTX protocols were found to have comparable treatment success rates (93 % and 95 %, respectively). Women with lower initial serum ß-hCG (<2000 mIU/ml) had higher treatment efficacy compared with women with higher initial serum ß-hCG (96.5 % vs 71.4 %), regardless of protocol type. The length of hospital stay for the women treated with the single-dose MTX protocol was 1 day shorter compared with that for the women treated with the double-dose MTX protocol. CONCLUSION: Single- and double-dose MTX protocols have comparable efficacy and safety, and should be equally considered in women with PUL with initial ß-hCG < 2000 mIU/ml.


Subject(s)
Abortifacient Agents, Nonsteroidal , Methotrexate , Pregnancy, Ectopic , Humans , Female , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Pregnancy , Adult , Retrospective Studies , Abortifacient Agents, Nonsteroidal/administration & dosage , Pregnancy, Ectopic/drug therapy , Chorionic Gonadotropin, beta Subunit, Human/blood , Treatment Outcome
17.
J Control Release ; 370: 747-762, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38740094

ABSTRACT

Rheumatoid arthritis (RA) is a progressive autoimmune disease and drug therapy has been restricted due to poor therapeutic efficacy and adverse effects. In RA synovium, dendritic cells present self-antigens to activate cascade immune pathway. Furthermore, downstream macrophages secrete high levels of pro-inflammatory cytokines; Hyperplasia of activated synovial fibroblasts (FLS) is responsible for hypoxic synovium microenvironment, secretion of cytokines/chemokines and erosion of bone/cartilage tissues. Positive feedback loop of inflammation between macrophages and FLS independent of antigen-presentation is constructed. Herein, an injectable pH-sensitive peptide hydrogel encapsulating siRNA/Methotrexate-polyethyleneimine (siMP, including sip65MP, sip38MP, siCD86MP) and Bismuthene nanosheet/Methotrexate-polyethyleneimine (BiMP) is successfully developed. Among them, siCD86MP reduces protein level of co-stimulatory molecule CD86 while sip65MP and sip38MP separately inhibit NF-κB and MAPK-p38 pathways of macrophages and FLS to suppress secretion of cytokines and MMPs. Meanwhile, reduction in anti-apoptotic property of FLS induced by inhibition of NF-κB pathway has a synergistic effect with photodynamic therapy (PDT) and photothermal therapy (PTT) mediated by BiMP for FLS elimination, effectively ameliorating hypoxic synovium microenvironment. After being injected into synovium, hydrogel responds to acidic microenvironment and serves as a reservoir for sustained drug release and inherent retention capacity of which enables cationic nanoparticles to bypass tissue barrier for precise synovium targeting. This brand-new drug delivery system combines modulating cascade immune pathway from beginning to end by RNAi and eliminating FLS for improving synovium microenvironment by phototherapy together, providing a robust strategy for clinical RA treatment.


Subject(s)
Arthritis, Rheumatoid , Fibroblasts , Hydrogels , Methotrexate , Synovial Membrane , Fibroblasts/drug effects , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/therapy , Hydrogels/administration & dosage , Synovial Membrane/immunology , Animals , Methotrexate/administration & dosage , Methotrexate/pharmacology , RNA, Small Interfering/administration & dosage , Photochemotherapy/methods , Mice , Humans , Macrophages/drug effects , Macrophages/immunology , RAW 264.7 Cells , Cytokines/metabolism , Antirheumatic Agents/administration & dosage , Cellular Microenvironment/drug effects , NF-kappa B/metabolism , Phototherapy/methods , Peptides/administration & dosage
18.
Pediatr Rheumatol Online J ; 22(1): 52, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715014

ABSTRACT

BACKGROUND: Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined. METHODS: This was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy. RESULTS: Plasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher's Exact). CONCLUSIONS: Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.


Subject(s)
Antirheumatic Agents , Arthritis, Juvenile , Medication Adherence , Methotrexate , Humans , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Methotrexate/blood , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/blood , Retrospective Studies , Child , Female , Medication Adherence/statistics & numerical data , Male , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/blood , Antirheumatic Agents/therapeutic use , Adolescent , Child, Preschool , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods
19.
Sci Rep ; 14(1): 12073, 2024 05 27.
Article in English | MEDLINE | ID: mdl-38802442

ABSTRACT

Carbon nanotubes (CNTs) have the potential to serve as delivery systems for medicinal substances and gene treatments, particularly in cancer treatment. Co-delivery of curcumin (CUR) and Methotrexate (MTX) has shown promise in cancer treatment, as it uses fewer drugs and has fewer side effects. This study used MTX-conjugated albumin (BSA)-based nanoparticles (BSA-MTX) to enhance and assess the efficiency of CUR. In-vitro cytotoxicity tests, DLS, TEM, FTIR, UV/Vis, SEM, and DSC studies assessed the formulations' physical and chemical properties. The Proteinase K enzyme was used to severe amidic linkages between MTX and BSA. The findings demonstrated the efficacy of using ƒ-MWCNT-CUR-BSA-MTX as a vehicle for efficient co-delivery of CUR and MTX in cancer treatment. The MTT colorimetric method was used to evaluate the effect of chemical and medicinal compounds. Cell division was studied using the MTT method to investigate the effect of pure MWCNT, pure CUR, MTX-BSA, and ƒ-MWCNT-CUR-MTX-BSA. Studies on cell lines have shown that the combination of curcumin and MTX with CNT can increase and improve the effectiveness of both drugs against cancer. A combination of drugs curcumin and methotrexate simultaneously had a synergistic effect on MCF-7 cells, which indicated that these drugs could potentially be used as a strategy for both prevention and treatment of breast cancer. Also, ƒ-MWCNT-CUR-MTX-BSA was found to have a significant effect on cancer treatment with minimal toxicity compared to pure curcumin, pure MTX-BSA, MTX, and ƒ-MWCNT alone. Unique properties such as a high ratio of specific surface area to volume, high chemical stability, chemical adsorption ability, high capacity of drug and biomolecules of carbon nanotubes, as well as multiple drug loading at the same time The combination of ƒ-MWCNT-CUR-BSA MTX significantly impacts cancer therapy), are desirable as an alternative option for targeted drug delivery and high therapeutic efficiency.


Subject(s)
Curcumin , Methotrexate , Nanotubes, Carbon , Nanotubes, Carbon/chemistry , Methotrexate/chemistry , Methotrexate/pharmacology , Methotrexate/administration & dosage , Humans , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/administration & dosage , Nanoparticles/chemistry , Drug Delivery Systems , Serum Albumin, Bovine/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , MCF-7 Cells , Drug Carriers/chemistry , Cell Survival/drug effects , Cell Line, Tumor
20.
Tidsskr Nor Laegeforen ; 144(6)2024 May 14.
Article in English, Norwegian | MEDLINE | ID: mdl-38747669

ABSTRACT

Background: A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review. Case presentation: The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level. Interpretation: Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.


Subject(s)
Medication Errors , Methotrexate , Humans , Female , Methotrexate/adverse effects , Methotrexate/administration & dosage , Aged , Dyspnea/chemically induced , Leucovorin/adverse effects , Leucovorin/administration & dosage , Antidotes/administration & dosage , Antidotes/therapeutic use , Antirheumatic Agents/adverse effects , Antirheumatic Agents/administration & dosage
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