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Annals of Saudi Medicine 2024Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to...
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 Hanım 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 (=.006 and =.12, respectively). Moreover, ectopic mass size and serum β-hCG levels were significantly higher in the surgical treatment group (<.001 and <.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, =.255). Similarly, there was no significant difference between the conservative and surgical treatment groups with respect to history of infertility (=.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%) (=.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%, =.72) and admittance to the IVF program (3.9% vs 6.8%, =.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.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Adult; Methotrexate; Salpingectomy; Conservative Treatment; Pregnancy, Tubal; Laparoscopy; Abortifacient Agents, Nonsteroidal; Turkey; Fertility; Chorionic Gonadotropin, beta Subunit, Human; Fertility Preservation
PubMed: 38853473
DOI: 10.5144/0256-4947.2024.141 -
The Brazilian Journal of Infectious... 2024We report an autochthonous case of mild unifocal chronic pulmonary paracoccidioidomycosis in a 48-year-old previously healthy woman with no history of possible...
We report an autochthonous case of mild unifocal chronic pulmonary paracoccidioidomycosis in a 48-year-old previously healthy woman with no history of possible environmental exposures in endemic rural areas, supposedly resulting from reactivation of a latent pulmonary focus secondary to the use of methotrexate for the control of Chikungunya arthropathy. Laboratory investigation ruled out other immunosuppression. Her only symptoms were a dry cough and chest pain. Diagnosis confirmed by needle lung biopsy. There were no abnormalities on physical examination nor evidence of central nervous system involvement. MRI of the total abdomen showed no involvement of other organs. Computed chest tomography showed a favorable evolution under the use of itraconazole (200 mg/day). Different tomographic presentations findings are highlighted when performed before and after treatment. CONCLUSIONS: PCM should be considered even in a woman without a history of consistent environmental exposure and in a non-endemic geographic area.
Topics: Humans; Female; Paracoccidioidomycosis; Middle Aged; Methotrexate; Lung Diseases, Fungal; Chronic Disease; Itraconazole; Tomography, X-Ray Computed; Antifungal Agents; Immunosuppressive Agents
PubMed: 38851212
DOI: 10.1016/j.bjid.2024.103768 -
Medicine Jun 2024The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1... (Observational Study)
Observational Study
Impact of TYMS gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients - identification of novel single nucleotide polymorphism: Cross-sectional study.
The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1 [877 bp, 657,220-658,096 bp]) and the therapeutic outcomes for rheumatoid arthritis (RA) Iraqi patients. An observational cross-sectional study involving 95 RA patients with established RA patients based on their methotrexate treatment responsiveness. Genetic sequencing of the TYMS gene was performed for all patients according to the instruction manuals of the sequencing company (Macrogen Inc. Geumchen, South Korea). Four polymorphisms were identified by sequencing 95 randomly selected patients in the noncoding region of TYMS. Three of these polymorphisms were found in the NCBI database's dbSNP (rs2853741, rs2606241, and rs2853742 SNPs), and one SNP polymorphism is novel (657334). The CTAT (657334, rs2853741, rs2606241, and rs2853742 SNPs) haplotype was significantly associated with responder with odd ratio, 95% confidence interval: 0.506, 0.281-0.912 (P value = .022). In contrast, the other haplotypes were not associated with MTX responsiveness. In the multivariate analysis, after adjusting to the effect of age, sex, smoking, and disease duration, the TCrs2853741 genotype was associated with non-responders (P value = .030). In contrast, the ACrs260641 genotype, after adjusting to the effect of age, sex, and smoking, was associated with non-responders (P value = .035). Genetic polymorphism of the TYMS gene, especially in TCrs2853741 and ACrs260641, predicts non-responder to MTX treatment in RA, while the presence of the CTAT haplotype predicts a good response to MTX treatment.
Topics: Humans; Cross-Sectional Studies; Polymorphism, Single Nucleotide; Male; Arthritis, Rheumatoid; Female; Methotrexate; Middle Aged; Antirheumatic Agents; Adult; Iraq; Thymidylate Synthase; Haplotypes; Treatment Outcome
PubMed: 38847705
DOI: 10.1097/MD.0000000000038448 -
Frontiers in Endocrinology 2024Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to...
OBJECTIVE
Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level.
METHODS
A two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels (<5×10) were selected as instrumental variables (IVs). Data concerning PCOS were obtained from the Apollo database. The primary method of causal estimation was inverse variance weighting (IVW), complemented by sensitivity analyses to validate the results.
RESULTS
The study found no genetic evidence to suggest a causal association between plasma levels of Hcy, folate, vitamin B12, vitamin B6, and PCOS. The effect sizes, determined through random-effect IVW, were as follows: Hcy per standard deviation increase, OR = 1.117, 95%CI: (0.842, 1.483), = 0.442; folate per standard deviation increase, OR = 1.008, CI: (0.546, 1.860), = 0.981; vitamin B12 per standard deviation increase, OR = 0.978, CI: (0.808, 1.185), = 0.823; and vitamin B6 per standard deviation increase, OR = 0.967, CI: (0.925, 1.012), = 0.145. The fixed-effect IVW results for each nutrient exposure and PCOS were consistent with the random-effect IVW findings, with additional sensitivity analyses reinforcing these outcomes.
CONCLUSION
Our findings indicate no causal link between Hcy, folate, vitamin B12, vitamin B6 levels, and PCOS.
Topics: Humans; Polycystic Ovary Syndrome; Female; Mendelian Randomization Analysis; Homocysteine; Polymorphism, Single Nucleotide; Vitamin B Complex; Folic Acid; Vitamin B 12; Genome-Wide Association Study; Vitamin B 6; Adult
PubMed: 38841299
DOI: 10.3389/fendo.2024.1393847 -
Frontiers in Immunology 2024Antigen-presenting dendritic cells (DCs) and monocytes play an essential role in rheumatoid arthritis (RA) pathogenesis, however, their tolerogenic potential remains...
OBJECTIVE
Antigen-presenting dendritic cells (DCs) and monocytes play an essential role in rheumatoid arthritis (RA) pathogenesis, however, their tolerogenic potential remains unclear. Herein, the tolerogenic profiles of DCs are characterized in treatment-naïve RA patients to determine their role to inflammatory arthritis management.
METHODS
Thirty-six treatment-naïve RA patients were enrolled, of which 62% were non-responders to methotrexate (MTX) monotherapy based on disease activity score (DAS) after 6-months of therapy. DC and monocyte subset frequencies, activation (CD40, CD86, CD209 expression), and tolerogenic profile (intracellular indoleamine-2,3-dioxygenase [IDO1] and cytotoxic T lymphocyte antigen 4 [CTLA-4] expression) were examined in the baseline peripheral blood by multicolor flow-cytometry. Soluble CTLA-4 (sCTLA-4) levels in plasma were measured.
RESULTS
DC subsets were decreased in RA compared to healthy controls (HC), and the frequency of conventional DCs (cDC) inversely correlated with inflammatory markers and improvement in disease activity. CD141 cDC1s were the major IDO1-expressing cells. IDO1cDC1s were reduced in RA patients compared to HC. The baseline frequency of IDO1cDC1s inversely correlated with improvement in disease activity. CTLA-4 expression in CD1c cDC2s and monocytes was lower in RA patients compared to HC. Moreover, MTX-responders had a significantly lower frequency of IDO1cDC1 cells and higher level of sCTLA-4 in the plasma compared to MTX non-responders. There was a strong predictive association of low IDO1cDC1 cells, low sCTLA-4 and non-response to MTX.
CONCLUSIONS
Our findings reveal altered DC and monocytes immunophenotypes that are associated with RA pathology and treatment response. The frequencies of tolerogenic IDO1cDC1s and the low level of sCTLA-4 are strongly associated with MTX non-responsiveness and therapeutic outcome. These results suggest that investigation of the association IDO1cDC1 and sCTLA-4 with response to treatment may be more generalizable to other autoimmune diseases.
Topics: Humans; Arthritis, Rheumatoid; Dendritic Cells; Indoleamine-Pyrrole 2,3,-Dioxygenase; Methotrexate; Female; Male; Middle Aged; CTLA-4 Antigen; Adult; Antirheumatic Agents; Aged; Monocytes; Treatment Outcome; Biomarkers
PubMed: 38840915
DOI: 10.3389/fimmu.2024.1352251 -
Frontiers in Immunology 2024Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in...
INTRODUCTION
Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms.
METHODS
To assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation.
RESULTS
Administration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1β in MTX-induced rats.
DISCUSSION
Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Methotrexate; Rats; Rats, Sprague-Dawley; Male; Enteritis; Anti-Inflammatory Agents; Cytokines; Glucosides; Disease Models, Animal
PubMed: 38835771
DOI: 10.3389/fimmu.2024.1405084 -
Journal of Medical Case Reports Jun 2024Immunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to...
BACKGROUND
Immunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to 1.39 per 10 person-years. Sinonasal immunoglobulin G4-related disease is atypical and exceedingly uncommon in the existing literature, frequently manifesting clinically as chronic rhinosinusitis, epistaxis, and facial pain.
CASE PRESENTATION
This report describes a 25-year-old Iraqi female who has been suffering from symptoms of chronic rhinosinusitis for 8 years. Despite undergoing several surgeries, there has been no improvement in her symptoms. A tissue biopsy that revealed dense lymphoplasmocytosis with noticeable plasma cell infiltration, storiform fibrosis, and obliterative angitis, along with positive immunohistochemical staining for Immunoglobulin G4 plasma cells, finally confirmed the diagnosis of sinonasal immunoglobulin G4-related disease. The patient responded well to oral prednisolone and methotrexate treatments.
CONCLUSIONS
The main objective of the current report is to raise awareness among physicians about the significance of promptly identifying and diagnosing this rarity, thus preventing the adverse consequences linked to delayed diagnosis and treatment initiation.
Topics: Humans; Female; Immunoglobulin G4-Related Disease; Adult; Sinusitis; Prednisolone; Rhinitis; Methotrexate; Chronic Disease; Biopsy; Treatment Outcome
PubMed: 38835063
DOI: 10.1186/s13256-024-04594-0 -
PloS One 2024Clinical studies showed that prolonged infusion of methotrexate (MTX) leads to more severe adverse reactions than short infusion of MTX at the same dose. We hypothesized...
BACKGROUND AND PURPOSE
Clinical studies showed that prolonged infusion of methotrexate (MTX) leads to more severe adverse reactions than short infusion of MTX at the same dose. We hypothesized that it is the saturation of folate polyglutamate synthetase (FPGS) at high MTX concentration that limits the intracellular synthesis rate of methotrexate polyglutamate (MTX-PG). Due to a similar accumulation rate, a longer infusion duration may increase the concentration of MTX-PG and, result in more serious adverse reactions. In this study, we validated this hypothesis.
EXPERIMENTAL APPROACH
A549, BEL-7402 and MHCC97H cell lines were treated with MTX at gradient concentrations. Liquid chromatograph-mass spectrometer (UPLC-MS/MS) was used to quantify the intracellular concentration of MTX-PG and the abundance of FPGS and γ-glutamyl hydrolase (GGH). High quality data were used to fit the cell pharmacokinetic model.
KEY RESULTS
Both cell growth inhibition rate and intracellular MTX-PG concentration showed a nonlinear relationship with MTX concentration. The parameter Vmax in the model, which represents the synthesis rate of MTX-PG, showed a strong correlation with the abundance of intracellular FPGS.
CONCLUSION AND IMPLICATIONS
According to the model fitting results, it was confirmed that the abundance of FPGS is a decisive factor limiting the synthesis rate of MTX-PG. The proposed hypothesis was verified in this study. In addition, based on the intracellular metabolism, a reasonable explanation was provided for the correlation between the severity of adverse reactions of MTX and infusion time. This study provides a new strategy for the individualized treatment and prediction of efficacy/side effects of MTX.
Topics: Methotrexate; gamma-Glutamyl Hydrolase; Peptide Synthases; Humans; Cell Line, Tumor; Polyglutamic Acid; Tandem Mass Spectrometry; Cell Proliferation; Antimetabolites, Antineoplastic
PubMed: 38833640
DOI: 10.1371/journal.pone.0302663 -
Environmental Health : a Global Access... Jun 2024Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies...
BACKGROUND
Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother's arsenic exposure, folic acid, and spina bifida risk in Bangladesh.
METHODS
We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure.
RESULTS
We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother's arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82).
CONCLUSIONS
Mother's arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.
Topics: Humans; Folic Acid; Bangladesh; Spinal Dysraphism; Case-Control Studies; Female; Arsenic; Infant; Male; Adult; Infant, Newborn; Pregnancy; Water Pollutants, Chemical; Maternal Exposure; Young Adult; Drinking Water
PubMed: 38831396
DOI: 10.1186/s12940-024-01091-1 -
International Journal of Biological... Jun 2024Cellulose nanofibres (CNFs), also known as nano-fibrillated cellulose, have emerged as highly promising sustainable biomaterials owing to their numerous advantages,...
Cellulose nanofibres (CNFs), also known as nano-fibrillated cellulose, have emerged as highly promising sustainable biomaterials owing to their numerous advantages, including high accessibility, long-term sustainability, low toxicity, and mechanical properties. Recently, marine organisms have been explored as novel and environmentally friendly sources of cellulose fibers (CFs) due to their easy cultivation, extraction and biocompatibility. Dinoflagellates, a group of marine phytoplankton, have gained particular attention due to their unique cellulosic morphology and lignin-free biomass. Previously, we showed that the unique amorphous nature of dinoflagellate-derived cellulose offers various benefits. This study further explores the potential of dinoflagellate-derived CFs as a sustainable and versatile CNF source. Extracted dinoflagellate cellulose is effectively converted into CNFs via one-step TEMPO oxidation without significant polymer degradation. In addition, the biological compatibility of the CNFs is improved by amine-grafting using putrescine and folic acid. The products are characterised by conductometric titration, zeta potential measurements, TGA, GPC, FTIR, SEM/TEM, XRD, and XPS. Finally, in a proof-of-principle study, the application of the functionalised CNFs in drug delivery is tested using methylene blue as a drug model. Our findings suggest that dinoflagellate-derived CNFs provide an eco-friendly platform that can be easily functionalised for various applications, including drug delivery.
Topics: Dinoflagellida; Cellulose; Nanofibers; Cyclic N-Oxides; Folic Acid
PubMed: 38825272
DOI: 10.1016/j.ijbiomac.2024.132804