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Asian Pacific Journal of Cancer... May 2024Several studies of multi-drug regimens for osteosarcoma have shown different efficacies and are still controversial. Meanwhile, chemotherapy options have remained... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies of multi-drug regimens for osteosarcoma have shown different efficacies and are still controversial. Meanwhile, chemotherapy options have remained largely unchanged over a couple of decades. This study is designed to ascertain the outcome and safety of Methotrexate, Doxorubicin, and Cisplatin regimen for chemotherapy in osteosarcoma patients through the utilization of meta-analysis.
METHODS
We interrogated trials that compared the MAP regimen with other regimens as chemotherapy for osteosarcoma from several databases encompassing PubMed, Science Direct, and grey literature (Google Scholar) until December 2022. The analyzed outcomes including Event-Free Survival (EFS), Overall Survival (OS), Tumor Necrosis (TN) rate, and Adverse Event (AE) were then analyzed using RevMan 5.4 software in fixed or random effect models.
RESULTS
Our meta-analysis comprised 8 prospective articles that evaluated a cumulative number of 2920 OS patients. The analysis results indicated no meaningful difference in 5-year EFS (OR=0.99, 95% CI=0.77-1.27, [P = 0.91]) and neoadjuvant chemotherapy response (TN) (OR=0.76, 95% CI=0.49-1.17, [P = 0.22]) between the MAP and control groups. Furthermore, 5-year OS analysis revealed a significant association in the control group (OR=0.82, 95% CI=0.68-0.99, [P = 0.04]). However, the control group was associated with statistically meaningful AE compared to the MAP group, particularly in thrombocytopenia (OR=0.46, 95% CI=0.23-0.90, [P = 0.02]) and fever (OR=0.34, 95% CI=0.26-0.46, [P < 0.00001]).
CONCLUSION
The present meta-analysis showed that the MAP regimen remains preferable in treating osteosarcoma patients despite no significant outcome compared to the other regimens considering the less frequent AE in the MAP regimen.
Topics: Osteosarcoma; Humans; Methotrexate; Doxorubicin; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Patient Safety; Prognosis; Survival Rate; Treatment Outcome
PubMed: 38809621
DOI: 10.31557/APJCP.2024.25.5.1497 -
BMC Oral Health May 2024This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate. (Comparative Study)
Comparative Study
OBJECTIVE
This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate.
METHODS
One hundred twenty-five rats were divided into five equal groups of twenty-five each. The rats in Group I received basic diets, while those in Groups II, III, IV, and V received 20 mg/kg MTX as a single intraperitoneal dose on day one. Group III received 10 mg/kg CVM dissolved in saline orally and daily, and the other two groups aqueous suspension of GA. Therefore, Group IV received 2 ml/kg suspension orally and daily, while Group V received 3 ml/kg suspension orally and daily. After 9 days, the parotid glands were dissected carefully and prepared for hematoxylin and eosin (H&E) staining as a routine histological stain and caspase-3 and Ki67 immunohistochemical staining. Quantitative data from α-Caspase-3 staining and Ki67 staining were statistically analysed using one-way ANOVA followed by Tukey's multiple comparisons post hoc test.
RESULTS
Regarding caspase-3 and Ki67 immunohistochemical staining, one-way ANOVA revealed a significant difference among the five groups. For Caspase-3, the highest mean value was for group II (54.21 ± 6.90), and the lowest mean value was for group I (15.75 ± 3.67). The other three groups had mean values of 31.09 ± 5.90, 30.76 ± 5.82, and 20.65 ± 3.47 for groups III, IV, and V, respectively. For Ki67, the highest mean value was for group I (61.70 ± 6.58), and the lowest value was for group II (18.14a ± 5.16). The other three groups had mean values of 34.4 ± 9.27, 48.03 ± 8.40, and 50.63 ± 8.27 for groups III, IV, and V, respectively.
CONCLUSION
GA, rather than the normally used drug CVM, had a desirable effect on the salivary glands of patients with xerostomia.
Topics: Animals; Rats; Xerostomia; Parotid Gland; Ki-67 Antigen; Methotrexate; Gum Arabic; Thiophenes; Caspase 3; Male; Rats, Wistar; Quinuclidines
PubMed: 38807094
DOI: 10.1186/s12903-024-04374-8 -
BMJ Case Reports May 2024Pityriasis rubra pilaris (PRP) is a rare dermatological condition which may present with ocular manifestations. We report a case of recurrent cicatricial ectropion (CE)...
Pityriasis rubra pilaris (PRP) is a rare dermatological condition which may present with ocular manifestations. We report a case of recurrent cicatricial ectropion (CE) with topical beta-blocker use in the rare dermatological condition PRP. The patient underwent release of scar tissue, lateral tarsal strip and full-thickness supraclavicular skin graft for CE following immunosuppression with methotrexate for 3 months. Postoperatively, CE recurred, with skin graft shrinkage and resumption of periocular disease activity, 8 weeks following the introduction of topical timolol. The patient was referred for further immunosuppression and substitution of timolol before consideration for further surgery. PRP has a variety of potential ocular complications. Surgery has a high risk of recurrence and should be performed when the overall disease is quiescent and drugs, which could trigger reactivation, have been discontinued and/or substituted. Skin grafts should be oversized to off-set shrinkage.
Topics: Humans; Pityriasis Rubra Pilaris; Ectropion; Skin Transplantation; Timolol; Male; Recurrence; Adrenergic beta-Antagonists; Female; Methotrexate; Middle Aged; Cicatrix
PubMed: 38806396
DOI: 10.1136/bcr-2023-256445 -
RMD Open May 2024To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years.
METHODS
Patients with rheumatoid arthritis and inadequate response to methotrexate were randomised to receive upadacitinib 15 mg once daily, placebo or adalimumab 40 mg every other week, all with concomitant methotrexate. By week 26, patients with insufficient response to randomised treatment were rescued; patients remaining on placebo switched to upadacitinib. Patients completing the 48-week double-blind period could enter a long-term extension. Safety and efficacy were assessed through week 264, with radiographic progression analysed through week 192. Safety was assessed by treatment-emergent adverse events (TEAEs). Efficacy was analysed by randomised group (non-responder imputation (NRI)) or treatment sequence (as observed).
RESULTS
Rates of TEAEs were generally similar with upadacitinib versus adalimumab, although numerically higher rates of herpes zoster, lymphopenia, creatine phosphokinase elevation, hepatic disorder and non-melanoma skin cancer were reported with upadacitinib. Numerically greater proportions of patients randomised to upadacitinib versus adalimumab achieved clinical responses (NRI); Clinical Disease Activity Index remission (≤2.8) and Disease Activity Score based on C reactive protein <2.6 were achieved by 24.6% vs 18.7% (nominal p=0.042) and 31.8% vs 23.2% (nominal p=0.006), respectively. Radiographic progression was numerically lower with continuous upadacitinib versus adalimumab at week 192.
CONCLUSION
The safety profile of upadacitinib through 5 years was consistent with the known safety profile of upadacitinib, with no new safety risks. Clinical responses were numerically higher with upadacitinib versus adalimumab at 5 years. Upadacitinib demonstrates a favourable benefit-risk profile for long-term rheumatoid arthritis treatment.
TRIAL REGISTRATION NUMBER
NCT02629159.
Topics: Humans; Arthritis, Rheumatoid; Adalimumab; Heterocyclic Compounds, 3-Ring; Female; Antirheumatic Agents; Male; Middle Aged; Treatment Outcome; Double-Blind Method; Adult; Methotrexate; Aged; Drug Therapy, Combination
PubMed: 38806190
DOI: 10.1136/rmdopen-2023-004007 -
Clinical Rheumatology Jul 2024Immunosuppressants, such as methotrexate (MTX), can suppress the COVID-19 vaccine response in patients with autoimmune diseases. Thus, this study aims to evaluate the... (Meta-Analysis)
Meta-Analysis Review
Immunosuppressants, such as methotrexate (MTX), can suppress the COVID-19 vaccine response in patients with autoimmune diseases. Thus, this study aims to evaluate the effects of MTX hold following COVID-19 vaccination on vaccine efficacy response. A systematic review and meta-analysis of relevant studies retrieved from Web of Science, SCOPUS, PubMed, and CENTRAL from inception until Oct 1, 2023, was conducted. Covidence was used to screen the eligible articles, and all relevant outcomes data were synthesized using risk ratios (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) in meta-analysis models within RevMan 5.4. PROSPERO ID: CRD42024511628. Four studies with a total of 762 patients with autoimmune inflammatory disorders were included. Holding MTX following the COVID-19 vaccination for approximately 2 weeks was associated with significantly higher antibody titer (SMD: 0.70, 95% CI [0.54, 0.87], P < 0.00001). However, the flare rate was significantly higher in the MTX hold group based on CDAI > 10 or DAS28-CRP > 1.2 either after 1st dose (RR: 2.49 with 95% CI [1.39, 4.47], P = 0.002) or 2nd dose (RR: 2.16 with 95% CI [1.37, 3.41], P = 0.0009) and self-reported disease flare (RR: 1.71 with 95% CI [1.35, 2.17], P < 0.00001). Holding MTX for 2 weeks after the COVID-19 vaccination resulted in significantly higher antibody titer but also had a higher disease flare rate, necessitating cautious clinical monitoring during this period. There is still a need to investigate safer MTX hold duration, considering patients' vulnerability to COVID-19, disease status, and demographics while adopting this strategy.
Topics: Humans; Methotrexate; COVID-19 Vaccines; COVID-19; Autoimmune Diseases; Immunosuppressive Agents; SARS-CoV-2; Vaccine Efficacy
PubMed: 38802670
DOI: 10.1007/s10067-024-07013-3 -
Scientific Reports May 2024Carbon nanotubes (CNTs) have the potential to serve as delivery systems for medicinal substances and gene treatments, particularly in cancer treatment. Co-delivery of...
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.
Topics: Nanotubes, Carbon; Methotrexate; Humans; Curcumin; Nanoparticles; Drug Delivery Systems; Serum Albumin, Bovine; Antineoplastic Agents; MCF-7 Cells; Drug Carriers; Cell Survival; Cell Line, Tumor
PubMed: 38802442
DOI: 10.1038/s41598-024-59745-6 -
The Western Journal of Emergency... May 2024Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic...
INTRODUCTION
Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic gonadotropin (β-hCG) level to qualify for diagnostic testing (pelvic ultrasound) can delay diagnosis and treatment. In this study we sought to determine the relationship between β-hCG level and the size of ectopic pregnancy with associated outcomes.
METHODS
We performed a retrospective case review of patients diagnosed with ectopic pregnancy in an urban, academic emergency department specializing in obstetrical care, from January 1, 2015-December 31, 2017. Variables extracted included presentation, treatment, adverse outcomes, and rates of rupture.
RESULTS
We identified 519 unique ectopic pregnancies. Of those ectopic pregnancies, 22.9% presented with evidence of rupture on ultrasound, and 14.4% showed evidence of hemodynamic instability (pulse >100 beats per minute; systolic blood pressure <90 millimeters of mercury; or evidence of significant blood loss) on presentation. Medical management outcomes were as follows: of 177 patients who received single-dose methotrexate, 14.7% failed medical management and required surgical intervention; of 46 who received multi-dose methotrexate, 36.9% failed medical management and required surgical intervention. Ultimately, 55.7% of patients required operative management of their ectopic pregnancy. Mean β-hCG level at initial presentation was 7,096 milli-international units per milliliter (mIU/mL) (SD 88,872 mIU/mL) with a median of 1,289 mIU/mL; 50.4% of ectopic pregnancies presented with β-hCG levels less than the standard discriminatory zone of 1,500 mIU/mL. Additionally, 44% of the patients who presented with evidence of rupture had β-hCG levels less than 1,500 mIU/mL. Comparison of size of ectopic pregnancy (based on maximum dimension in millimeters) to β-hCG levels revealed a very weak correlation (r = 0.144, ), and detection of ectopic pregnancies by ultrasound was independent of β-hCG levels.
CONCLUSION
Levels of β-hCG do not correlate with the presence or size of an ectopic pregnancy, indicating need for diagnostic imaging regardless of β-hCG level in patients with clinical suspicion for ectopic pregnancy. Almost one-sixth of patients presented with evidence of hemodynamic instability, and approximately one quarter of patients presented with evidence of rupture requiring emergent operative management. Ultimately, more than half of patients required an operative procedure to definitively manage their ectopic pregnancy.
Topics: Humans; Female; Pregnancy; Pregnancy, Ectopic; Retrospective Studies; Chorionic Gonadotropin, beta Subunit, Human; Adult; Emergency Service, Hospital; Methotrexate; Abortifacient Agents, Nonsteroidal; Pregnancy Trimester, First; Ultrasonography, Prenatal
PubMed: 38801051
DOI: 10.5811/westjem.18396 -
Toxicology and Applied Pharmacology Jul 2024Hepatotoxicity is the main off-target effect of methotrexate (MTX) limiting its effective clinical use. Besides, MDA-MB231 breast cancer cells show chemoresistance,...
PI3K inhibitor "alpelisib" alleviates methotrexate induced liver injury in mice and potentiates its cytotoxic effect against MDA-MB-231 triple negative breast cancer cell line.
Hepatotoxicity is the main off-target effect of methotrexate (MTX) limiting its effective clinical use. Besides, MDA-MB231 breast cancer cells show chemoresistance, partly via PI3K/AKT pathway. Therefore, we investigated the ameliorative potentials of the PI3K inhibitor, alpelisib (ALP) on MTX-induced hepatotoxicity (in vivo) and the restraining potentials of ALP on MDA-MB231 chemoresistance to MTX (in vitro). Twenty-eight male BALB/c mice were divided into 4 groups. In treatment groups, mice were administered ALP (2.5 and 5 mg/kg) for 5 days and MTX (20 mg/kg) from day 2 till day 5. The results showed that ALP restored hepatic architecture, reduced immune cell infiltration (F4/80, Ly6G and MPO) and repressed the rise in liver enzymes (AST and ALT) induced by MTX. Additionally, ALP rectified the MTX-induced disruption of cellular oxidant status by boosting antioxidant defense systems (HO-1 and GSH) and repressing lipid peroxidation (MDA and 4-HNE). Finally, ALP curbed MTX-induced hepatocyte apoptosis (NF-κB and BAX) and shifted the cytokine milieu away from inflammation (IL-17, IL-22, IL-6 and IL- 10). The results of the in vitro experiments revealed that ALP alone and in combination with MTX, synergistically, reduced cancer cell viability (MTT assay), migration (wound healing assay) and their capacity to establish colonies (colony formation assay) as compared to MTX alone. RT-PCR revealed the antiproliferative (Bcl-2) and proapoptotic (BAX) potentials of ALP and ALP/MTX combination especially after 24 h. In conclusion, targeting PI3K/AKT pathway is a promising strategy in triple negative breast cancer patients by ameliorating hepatotoxicity and restraining chemoresistance to chemotherapy.
Topics: Animals; Methotrexate; Mice, Inbred BALB C; Chemical and Drug Induced Liver Injury; Male; Triple Negative Breast Neoplasms; Mice; Humans; Cell Line, Tumor; Phosphoinositide-3 Kinase Inhibitors; Apoptosis; Drug Synergism; Signal Transduction; Female; Antimetabolites, Antineoplastic; Liver; Phosphatidylinositol 3-Kinases; Oxidative Stress; Proto-Oncogene Proteins c-akt
PubMed: 38797265
DOI: 10.1016/j.taap.2024.116979 -
Archives of Dermatological Research May 2024Methotrexate (MTX) is commonly used as first-line systemic treatment agent in psoriasis. We aimed to evaluate the clinical characteristics and treatment responses of...
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.
Topics: Humans; Methotrexate; Psoriasis; Female; Male; Adult; Middle Aged; Retrospective Studies; Treatment Outcome; Folic Acid; Severity of Illness Index; Administration, Oral; Dermatologic Agents; Injections, Subcutaneous
PubMed: 38796658
DOI: 10.1007/s00403-024-03066-1 -
Dermatologic Clinics Jul 2024Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents,... (Review)
Review
Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents, such as apremilast, deucravacitinib, and oral interleukin-23 receptor antagonists. Patients may prefer oral therapies to injectable therapies based on the route of administration. Both older and newer oral psoriasis therapies can be utilized effectively in the treatment of psoriasis. Here, we will review oral agents used in the treatment of psoriasis as well as provide commentary on their role in our current, evolving psoriasis treatment paradigm.
Topics: Humans; Psoriasis; Administration, Oral; Thalidomide; Acitretin; Immunosuppressive Agents; Methotrexate; Cyclosporine; Dermatologic Agents; Piperidines; Pyrazoles; Pyrimidines; Pyrroles; Antibodies, Monoclonal, Humanized; Keratolytic Agents; Indoles; Nicotinic Acids; Antibodies, Monoclonal
PubMed: 38796267
DOI: 10.1016/j.det.2024.02.013