Silent ovarian ectopic pregnancy: a case report

In clinical practice, an ovarian pregnancy is considered one of the most challenging diagnoses faced by an obstetrician/gynecologist. In this article, we report a 31-year-old Asian-Pakistani female, who presented to the ObsGynae clinic with 8 weeks of amenorrhea, a positive urine pregnancy test, and very high serum ?-hCG levels. Transvaginal ultrasonography ruled out a tubal pregnancy, and the patient was sent for repeat ?-hCG levels. The patient was hemodynamically stable and displayed no characteristic signs and symptoms of an ectopic pregnancy. Upon repeat scans and ?-hCG levels, a diagnosis of ovarian ectopic pregnancy was made. The patient was managed on medication; a single dose of I/M 50 mg/m2 methotrexate was administered and the resultant decline in ?-hCG levels proved the success of conservative treatment in this case. An ovarian ectopic can present as a life-threatening condition, and a high index of suspicion can prevent morbidity as well as mortality. Ovarian pregnancy, without any alarming signs despite very high ?-hCG levels, as reported in this case, is one of the rarest clinical cases observed.

A successful conservative management of cervical ectopic pregnancy

Cervical ectopic pregnancy is a rare life-threatening condition with an incidence of less than 1% among all ectopic pregnancies. A 27-year-old primigravida presented with spotting per vaginum following 4 weeks 5 days of amenorrhea. Transvaginal ultrasound done at 4 weeks 5 days showed a gestational sac located in the anterior wall of cervix, diagnosis of cervical ectopic pregnancy was made. Initial serum beta hCG titre was 4106 mIU/ml. Serial monitoring of serum beta hCG done showed increasing values. Hence, decided for medical management with single dose of injection methotrexate, as the diagnosis was made at an early gestation and patient was hemodynamically stable. On follow up, serum beta hCG did not fall significantly, hence multidose methotrexate regimen was initiated. She responded to it, but she continued to have persistent bleeding per vaginum with fall in hemoglobin levels, hence sorted for surgical management which included suction and evacuation, after ligation of descending cervical artery and subsequently cervical tamponade. Intraoperative period was uneventful. On follow-up, patient was asymptomatic and vitals stable. Serum beta hCG done 2 weeks post procedure was below 5 mIU/ml and resumed spontaneous cycles after a month. Thus, early detection and accurate diagnosis of cervical ectopic pregnancy using ultrasound and serial beta hCG titre monitoring becomes a cornerstone of management. We present this case as it was her index pregnancy, with a need to preserve future fertility, successful conservative management of Cervical ectopic pregnancy with combination of medical and surgical intervention.

A rare case report on cervical pregnancy

Cervical pregnancy is a rare type of ectopic pregnancy and it represents <1% of all ectopic pregnancies. Tubal ectopic, Interstital, caesarean scar pregnancy, cornual, ovarian, Intramural are other types of ectopic pregnancy. Timely diagnosis and Treatment are key to management any type of ectopic pregnancy. Cervical ectopic pregnancy is the implantation of blastocyst in the intracervical canal. Cervical pregnancy are high risk cases as they may present with an unexpected life-threatening hemorrhage secondary to the erosion of cervical blood vessels, which may require hysterectomy to save the patient. Here is case of 22yr old primi patient with 6 weeks and 2 days of cervical ectopic pregnancy planned for dilatation and evacuation followed by medical management span; Improved ultrasound resolution and earlier detection of these pregnancies have led to the development of more conservative treatments that attempt to limit morbidity and preserve fertility.

Diagnosis and management of cases of ectopic pregnancy in a tertiary care centre: our experience

Background: Ectopic pregnancy is a leading cause of maternal morbidity and mortality. With our study, we aim to highlight the importance of risk factors and effect of clinical presentation on the management modalities of ectopic pregnancy and study changing trends of modern management from radical surgical methods to medical and laparoscopic management of ectopic pregnancies.Methods: This prospective study was undertaken at a tertiary care hospital between May 2021 and May 2022.Results: The most common age group of presentation was 26-30 years. The most common risk factor was history of previous abortion. Amenorrhoea and abdominal pain were the most commonly encountered symptoms in this study. Cervical motion tenderness was significantly associated with ruptured ectopic pregnancy. Conservative medical management with injection methotrexate (Mtx), which was successful in 50% cases. Success rate was 100% for laparoscopic management and 100% for laparotomy in this study. No maternal mortality was observed during the present study.Conclusions: Our hospital being a tertiary centre, had to manage a number of cases as surgical emergencies by laparotomy and not conservatively, as they brought in either diagnosed cases of ruptured ectopic pregnancy, or failure of medical management. It is important that in the face of this diagnostic dilemma, all physicians should be should maintain a high level of suspicion and be sensitive to the fact that in the reproductive age group any woman presenting with pain in the lower abdomen, diagnosis of ectopic pregnancy should be considered irrespective of the presence or absence of amenorrhea or tubal sterilisation.

Variations in Genetic Factors Impacting the Effectiveness and Side Effects of Methotrexate with Rheumatoid Arthritis

This review provides a comprehensive overview of genetic variations influencing the effectiveness and side effects of methotrexate (MTX) treatment in rheumatoid arthritis (RA) patients. It synthesizes findings on associations between genetic polymorphisms and MTX therapy outcomes, aiming to identify potential genetic markers for enhancing treatment and personalized strategies in RA. The review highlights genetic variations associated with MTX therapy effects. Variants in genes involved in MTX transport, including reduced folate carrier 1 (RFC1) and ABC transporters, correlate with treatment response. Specific RFC1 and ABCB1 variants are linked to improved MTX efficacy. Polymorphisms in genes regulating MTX metabolism, such as thymidylate synthase (TYMS) and methylenetetrahydrofolate reductase (MTHFR), predict effectiveness and toxicity risks of MTX. Additionally, genes influencing MTX's mechanistic pathways, like the adenosine signaling cascade, impact clinical outcomes. While the evidence is preliminary, this review suggests the potential of genetic testing to guide personalized MTX therapy in RA, leading to improved effectiveness and reduced adverse events. However, further research with diverse cohorts is necessary to validate these findings and establish the utility of pharmacogenomic-based treatment approaches for RA patients receiving MTX. RA is a chronic autoimmune disease treated with MTX as the cornerstone therapy, but patient responses vary. This comprehensive review examines genetic variations influencing MTX's efficacy and toxicity in RA patients. Through a rigorous literature review using databases like PubMed and Web of Science, this study synthesizes findings from pharmacogenetic research on genetic polymorphisms and MTX outcomes.

Successful multiple-dose methotrexate therapy for unruptured repeat ectopic pregnancy with high ?-human chorionic gonadotropin value: a case report

Successfully managing an unruptured ectopic pregnancy necessitates prioritizing the preservation of fertility as the primary objective. Medical management is traditionally considered to be more successful at lower �- human chorionic gonadotropin (HCG) values. However, there is emerging evidence that successful treatment can be achieved with modification of dosage regimen in the presence of high ?-HCG value. We reported the successful management of a case of unruptured repeat ectopic pregnancy in a patient with high ?-HCG. Mrs PA is a 25-year-old G4P0+3 with previous right salpingectomy due to ruptured ectopic gestation who presented with an ultrasound diagnosis of unruptured left tubal ectopic gestation at a gestational age of 6 weeks. The pre-treatment quantitative ?-HCG level was 7066 IU/l. She had multiple dose methotrexate therapy which was well tolerated with normalization of ?-HCG levels within 44 days. Hysterosalpingography done six (6) months post-treatment demonstrated patent left fallopian tube. She subsequently had spontaneous conception of an intrauterine pregnancy 16-months post-treatment. The pregnancy was carried to term and culminated in successful delivery at term. Multiple-dose chemotherapy was successful in this patient with high ?-HCG level with no reported adverse effect.

Mucositis oral como efecto adverso al uso del metotrexato en el tratamiento de la artritis reumatoide: una revisión sistematizada de casos / Oral mucositis as an adverse effect of the use of methotrexate in the treatment of rheumatoid arthritis: a systematized review of cases

Introducción: el metotrexato se usa ampliamente para el tratamiento de una variedad de enfermedades neoplásicas y autoinmunes. Sin embargo, como todo fármaco, su eficacia viene marcada por cierto grado de toxicidad debido a la farmacocinética del medicamento. El metotrexato se creó como un fármaco anticancerígeno; sin embargo, se ha convertido en el tratamiento de elección contra la artritis reumatoide. Principalmente, el metotrexato causa inflamación de las mucosas epiteliales. La mayoría de los efectos secundarios del metotrexato se pueden detectar de forma temprana y son reversibles. La mucositis del tracto alimentario es el principal efecto secundario de la quimioterapia contra el cáncer. Se le conoce colectivamente como lesión de la mucosa inducida por quimioterapia, afecta todo el canal alimentario desde la boca hasta el ano, ocasionando la mucositis oral y la mucositis intestinal. Material y métodos: se buscaron casos clínicos en los que se reporte mucositis causada por metotrexato en tratamiento de artritis reumatoide. Se empleó un diagrama de flujo, PRISMA modificado para la búsqueda de artículos. Finalmente, se cotejó que los casos clínicos cumplieran con los fundamentos de la CARE guide, para manejar una correcta estructura y bajo riesgo a sesgo. Conclusiones: una correcta anamnesis y exploración clínica oral es lo más importante de la medicina oral. Es relevante indagar sobre las enfermedades que presentan los pacientes, así como la historia de medicamentos que se administren, especialmente en pacientes mayores, con mayores padecimientos de enfermedades sistémicas (AU)

Introduction: methotrexate is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, like all drugs its efficacy is marked by a certain degree of toxicity due to the pharmacokinetics of the drug. Methotrexate was developed as an anticancer drug, however, it has become the treatment of choice for rheumatoid arthritis. Methotrexate primarily causes inflammation of the epithelial mucous membranes. Most of the side effects of methotrexate can be detected early and are reversible. Mucositis of the alimentary tract is the main side effect of cancer chemotherapy. It is collectively known as chemotherapy-induced mucosal injury, affecting the entire alimentary canal from the mouth to the anus, where oral mucositis and intestinal mucositis are both common. Material and methods: we searched for clinical cases reporting mucositis caused by methotrexate in the treatment of rheumatoid arthritis, using a modified PRISMA flowchart to search for articles. Finally, the clinical cases were checked for compliance with the fundamentals of the CARE guide, in order to manage a correct approach to oral medicine. It is important to inquire about the diseases the patients present, as well as the history of medications administered, especially in older patients, with more systemic disease conditions, structure, and low risk of bias. Conclusion: a correct anamnesis and oral clinical examination is the most important aspect of oral medicine. It is important to inquire about the diseases that the patients present, as well as the history of medications that are administered, especially in older patients with major systemic diseases (AU)

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

Experiencia en el manejo del embarazo ectópico cornual / Experience in the management of cornual ectopic pregnancy

RESUMEN Antecedentes: El embarazo ectópico cornual representa del 2 al 4% de los embarazos ectópicos y es potencialmente mortal debido al riesgo de rotura uterina y consecuente hemorragia masiva, con una tasa de mortalidad de hasta 2,5%. No existe consenso sobre el manejo más adecuado de esta patología. Objetivo: Describir la experiencia en el manejo del embarazo ectópico cornual en el Instituto Nacional Materno Perinatal de Lima, Perú. Metodología: Estudio descriptivo y retrospectivo de pacientes con diagnóstico de embarazo ectópico cornual durante el año 2022. Los datos se obtuvieron de los registros en las historias clínicas. El análisis estadístico se procesó en el programa SPSS 19. Resultados: De 9 casos de embarazo ectópico cornual registrados, 7 cumplieron los criterios de inclusión. La edad promedio fue de 31 años y la edad gestacional promedio 7,3 semanas de amenorrea. El 71,4% de los casos no tenía factores de riesgo. La mayoría presentó sangrado vaginal asociado a dolor pélvico (71,4%). El valor promedio inicial de la hCG-β fue 8,262,3 mUI/mL. El tamaño promedio de la tumoración fue 36,7 mm y 28,6% de los casos se complicó con rotura uterina. El 57,1% recibió tratamiento quirúrgico consistente en resección cornual, cornuostomía o inyección local de metotrexato. Conclusiones La cirugía es el tratamiento más utilizado en el embarazo ectópico cornual. En lo últimos años, la laparoscopia es una opción quirúrgica importante con ciertas ventajas sobre la laparotomía.

ABSTRACT Background: Cornual ectopic pregnancy accounts for 2%-4% of ectopic pregnancies and is potentially fatal due to uterine rupture and consequent massive hemorrhage, with a mortality rate of up to 2.5%. There is no consensus on the most appropriate management of this pathology. Objective: To describe the experience in the management of cornual ectopic pregnancy at the Instituto Nacional Materno Perinatal, Lima, Peru. Methods: Descriptive and retrospective study of patients with a diagnosis of cornual ectopic pregnancy during the year 2022. Data were obtained from medical records. Statistical analysis was processed in the SPSS 19 program. Results: Out of 9 cases of cornual ectopic pregnancy registered, 7 met the inclusion criteria. The mean age was 31 years and the mean gestational age 7.3 weeks. Of the cases 71.4% had no risk factors. The majority presented vaginal bleeding associated with pelvic pain (71.4%). The average initial value of β-hCG was 8,262.3 mIU/mL. The average size of the tumor was 36.7 mm and 28.6% of the cases presented uterine rupture. 57.1% had surgical treatment consisting of cornual resection, cornuostomy or local injection of methotrexate. Conclusions: Surgery is the most commonly used treatment for cornual ectopic pregnancy. In recent years, laparoscopy has become an important surgical option with certain advantages over laparotomy.

Effect of Bushen Quhan Huashi Prescription Combined with Methotrexate on Disease Activity and Serum Core-Binding Factor a1 Level in Patients with Ankylosing Spondylitis / 广州中医药大学学报

Objective To investigate the effects of the Bushen Quhan Huashi Prescription(mainly composed of Drynariae Rhizoma,Eucommiae Cortex,Dipsaci Radix,Notopterygii Rhizoma et Radix,Zingiberis Rhizoma Recens,Coicis Semen,and Achyranthis Bidentatae Radix)in combination with Methotrexate on the disease activity and serum core-binding factor a1(Cbfa1)level of patients with ankylosing spondylitis(AS)of kidney deficiency and governor-vessel cold type.Methods Ninety AS patients with kidney deficiency and governor-vessel cold type were randomly divided into a trial group and a control group,with 45 patients in each group.The control group was given Methotrexate treatment,and the trial group was treated with Bushen Quhan Huashi Prescription on the basis of treatment for the control group.The course of treatment in the two groups lasted for 3 months.The changes of Bath ankylosing spondylitis disease activity index(BASDAI)scores,Bath ankylosing spondylitis function index(BASFI)scores and serum levels of Cbfa1,type I collagen carboxy-terminal peptide(CTX-Ⅰ)and Dickkopf1 protein(DKK1)of the two groups were observed before and after treatment.After treatment,the clinical efficacy and the incidence of adverse effects were compared between the two groups.Results(1)After 3 months of treatment,the total effective rate of the trial group was 97.78%(44/45)and that of the control group was 82.22%(37/45).The intergroup comparison by chi-square test)showed that the therapeutic efficacy of the trial group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the disease activity scores of BASDAI and BASFI in the two groups of patients were significantly decreased compared with those before treatment(P＜0.05),and the trial group's reduction of BASDAI scores and BASFI scores were significantly superior to those of the control group,and the differences were statistically significant(P＜0.01).(3)After treatment,the serum levels of serological indicators of Cbfa1,CTX-Ⅰ,and DKK1 in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of Cbfa1,CTX-Ⅰ and DKK1 levels in the trial group was significantly superior to that in the control group,the differences being all statistically significant(P＜0.01).(4)During the treatment,the incidence of adverse reactions in the trial group was 6.66%(3/45)and that in the control group was 11.11%(5/45),and the difference of the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Bushen Quhan Huashi Prescription combined with Methotrexate exerts certain effect in treating AS patients with kidney deficiency and governor-vessel cold type,and the therapy can effectively control the disease activity and reduce the level of serum Cbfa1 expression in the patients.

Effects of MTHFR gene polymorphism on the adverse reactions in osteosarcoma patients after the first high-dose methotrexate treatment / 中国药房

OBJECTIVE To explore the effects of 5，10-methylenetetetrahydrofolate reductase （MTHFR） gene polymorphism on the adverse reactions in patients with osteosarcoma after the first high-dose methotrexate （HD-MTX） treatment. METHODS A prospective study was conducted to include 53 patients with osteosarcoma treated with HD-MTX at the first admission in General Hospital of Eastern Theater Command. The dose of MTX was evaluated according to the polymorphism of rs1801133 in the METHFR gene and demographic factors， then whole pharmaceutical monitoring was conducted. The data on liver toxicity， renal toxicity， hematological toxicity， and gastrointestinal reaction were collected after the first chemotherapy cycle. Single factor analysis and binary Logistic regression analysis were used to analyze the correlation between MTX dose， 24 h blood drug concentration， and rs1801133 locus genotype with four adverse reactions. RESULTS The MTX dosage in patients with CC wild type was significantly higher than that in TT mutant type （7.97 g/m2 vs. 6.98 g/m2， P＝0.030）， but this difference did not affect the 0 h and 24 h blood drug concentrations of MTX. The above four adverse reactions were not related to the dose of MTX. The results of binary Logistic regression analysis showed that carrying one T allele increased the risk of developing hematological toxicity by 4.13 times（95% confidence interval：1.35-12.62，P＝0.013）. When 24 h plasma concentration threshold of MTX was set to 2.65 µmol/L， the sensitivity and specificity of predicting liver function damage were 53.33% and 86.96%， respectively； when the threshold was set to 7.28 μmol/L， the sensitivity and specificity of predicting renal damage were 100% and 81.63%. CONCLUSIONS The polymorphism of the rs1801133 in the MTHFR gene is associated with hematological toxicity of MTX. Patients who take HD-MTX for the first time and carry the T allele have a high risk of hematological toxicity. The 24 h plasma concentration of MTX is related to liver toxicity and renal toxicity. In addition， monitoring the 24 h blood drug concentration can predict liver and renal toxicity， and take early intervention.

Association of reduced folate carrier 1 gene polymorphism with methotrexate efficacy, plasma concentration and adverse reactions in patients with rheumatoid arthritis / 中华检验医学杂志

Objective:To explore the relationship between reduced folate carrier 1(RFC1) gene polymorphism a curative effect, plasma concentration and adverse reaction of methotrexate (MTX) in patients with rheumatoid arthritis (RA).Methods:A total of 268 RA patients with 82 males and 186 females, aged (52.47±10.29) years, who received MTX treatment in the First People's Hospital of Shangqiu, from Jan 20, 2018 to Jan 20, 2021 were collected by case-control study. The genotype of RFC1 G80A locus were detected. The plasma concentration of MTX were detected after initial administration for 48 hours. The curative effect and adverse reactions were observed and counted after treatment for 6 months. The differences of RFC1 G80A genotype among different groups were compared. Collinearity diagnosis and logistic regression were used to analyze the influencing factors of MTX efficacy and plasma concentration. The incidences of adverse reactions among patients with different genotype were compared by Chi-square test.Results:The distribution of RFC1 G80A genotype (GG/GA/AA) and gene frequency (G/A) showed statistically significant differences between the effective group and the ineffective group (χ 2=6.583, P=0.037; χ 2=6.249, P=0.012), and the effective rate of AA type [59.26% (32/54)] was higher than that of GG type [36.49% (27/74)] (χ 2=6.516, P=0.011). Logistic regression analysis showed that the OR (95% CI) value of MTX response rate in AA genotype patients versus GG genotype patients was 2.491(1.206-5.144). The 48 hour plasma drug concentration of AA type patients was 1.15 (0.75, 1.35) μmol/L. Compared with GG type [0.74 (0.61, 1.18) μmol/L] and GA type [0.84 (0.69, 0.99) μmol/L], the difference was statistically significant(χ 2=7.152, P=0.028). Logistic regression analysis showed that the probability of high 48 hour plasma drug concentration in patients with AA type was approximately 2.583 (1.238-5.390) times higher than that in patients with GG type. There was a statistically significant difference in the incidence of liver function injury among three different genotypes (GG/GA/AA) (χ 2=12.606, P=0.002). Conclusion:RFC1 G80A locus polymorphism can affect the MTX efficacy, blood drug concentration and liver function damage in RA patients. AA type patients have better efficacy and higher blood drug concentration compared to GG type patients, but the rate of liver function damage is also higher.

Advances in mechanism of methotrexate on toxicity in various organs / 中国药理学通报

As a widely used anti-tumor drug and anti-rheumatic drug in clinic, methotrexate (MTX) has many toxic and side effects, including gastrointestinal mucosa injury, central nervous system injury, liver and kidney function injury, etc. They often bring great trouble to the follow-up treatment of patients. The clarification of the mechanism of MTX toxicity to various organs has become the key to rescue the toxicity. The purpose of the article is to review the toxicity mechanism of MTX in various organs, so as to save the patients from the adverse reactions in clinical treatment.

Network meta-analysis on efficacy and safety of different biological agents in treatment of rheumatoid arthritis / 中国组织工程研究

OBJECTIVE:There are many kinds of biological agents for the treatment of rheumatoid arthritis in clinic,but the differences in therapeutic efficacy and safety are still unclear.The purpose of this study is to compare the differences in effectiveness and safety of different biological agents for the treatment of rheumatoid arthritis. METHODS:CNKI,VIP,WanFang,China Biomedical Literature System,PubMed,Cochrane Library,Web of Science,and Embase databases were searched to collect the randomized controlled trials on biological agents for rheumatoid arthritis that meet the requirements from inception to October 1,2022.The literature was selected by EndNote software,and the quality of the included literature was evaluated by RevMan 5.3 software.The software Stata 14.2 was used for direct meta-analysis and network meta-analysis of ACR20(American College of Rheumatology 20%response),ACR50(American College of Rheumatology 50%response),ACR70(American College of Rheumatology 70%response),erythrocyte sedimentation rate,and adverse reactions. RESULTS:Totally 39 articles were included,including 5 low-risk articles,4 high-risk articles,and the remaining 30 articles contained unknown risk bias,with a total of 13 treatment measures.The results of network meta-analysis:(1)In ACR20,infliximab combined with methotrexate(OR=5.54,95%CI:1.33-23.01,P<0.05),abatacept+methotrexate tablets(OR=3.21,95%CI:1.13-9.10,P<0.05),and tocilizumab(OR=2.95,95%CI:1.61-5.44,P<0.05)were better than methotrexate tablets.The probabilistic ranking of ACR20 was:infliximab+methotrexate tablets>abatacept+methotrexate tablets>tocilizumab>certlizumab>etanercept+methotrexate tablets.(2)In the aspect of ACR50,etanercept combined with methotrexate tablets(OR=4.04,95%CI:2.13-7.66,P<0.05),infliximab combined with methotrexate tablets(OR=4.79,95%CI:1.19-19.26,P<0.05),and tocilizumab combined with methotrexate tablets(OR=3.54,95%CI:1.36-9.22,P<0.05)had better therapeutic effects than methotrexate tablets.The probabilistic ranking of ACR50 was:etanercept+methotrexate tablets>infliximab+methotrexate tablets>tocilizumab+methotrexate tablets>tocilizumab>certlizumab+methotrexate tablets.(3)In terms of ACR70,the therapeutic effects of infliximab combined with methotrexate tablets(OR=8.00,95%CI:2.31-27.69,P<0.05),etanercept combined with methotrexate tablets(OR=4.26,95%CI:2.51-7.21,P<0.05),and tocilizumab combined with methotrexate tablets(OR=3.51,95%CI:1.82-6.80,P<0.05)were better than methotrexate tablets.The probabilistic ranking of ACR70 was infliximab+methotrexate tablets>etanercept+methotrexate tablets>tocilizumab+methotrexate tablets>certlizumab>adalimumab+methotrexate tablets.(4)In erythrocyte sedimentation rate,etanercept combined with methotrexate tablets(SMD=-9.23,95%CI:-16.55 to-1.92,P<0.05)was better than etanercept and methotrexate tablets(SMD=14.59,95%CI:7.28-21.91,P<0.05).The probabilistic ranking of erythrocyte sedimentation rate was etanercept+methotrexate tablets>infliximab+methotrexate tablets>etanercept>adalimumab+methotrexate tablets>methotrexate tablets.(5)In terms of adverse reactions,placebo(OR=0.62,95%CI:0.39-0.99,P<0.05)was better than infliximab and certlizumab(OR=0.44,95%CI:0.25-0.78,P<0.05).The probabilistic ranking of adverse reactions was placebo>infliximab>etanercept+methotrexate tablets>certlizumab>etanercept. CONCLUSION:Based on evidence from 39 randomized controlled trials,infliximab combined with methotrexate tablets(highly recommended)can be the first choice in clinic,and etanercept combined with methotrexate tablets(highly recommended)can be the second choice in terms of good effectiveness and safety.

Synthesis, characterization and protection effect of black rice anthocyanins nano-composite against hepatotoxicity induced by methotrexate in rats

Abstract The present study aimed to investigate the beneficial of prepared black rice anthocyanins nano-composite (An-AgNps) against hepatotoxicity induced by methotrexate (MTX) in rats. Anthocyanins nano-composite was prepared by silver as the metallic ion reduction and were characterized by IR and SEM. The rats in our experiment were divided into five groups. Serum lipid profile, serum transaminases (ALT and AST), ALP, LDH, TBA, GSH and SOD were examined. The results show that SEM of An-AgNps has average particle size from 70 to 130nm. In the group treated with MTX; TC, TG, LDL-c, ALT, AST, ALP, LDH and TBA levels were significantly (P0.05) increased than NC, while, HDL-c, SOD and GSH levels were significantly (P0.05) decreased. On the other hand, An-AgNps + MTX treated groups were reversed the levels of all biomarkers similar to NC. In conclusion, the results show that An-AgNps has a protective effect on MTX-induced hepatotoxicity and oxidative stress.

Resumo O presente estudo teve como objetivo investigar o benefício de nanocompósito de antocianinas de arroz preto preparado (An-AgNps) contra a hepatotoxicidade induzida por metotrexato (MTX) em ratos. O nanocompósito de antocianinas foi preparado a partir da prata por meio da redução do íon metálico e caracterizado por IR e SEM. Os ratos em nosso experimento foram divididos em cinco grupos, e foram examinados o perfil lipídico sérico, as transaminases séricas (ALT e AST), ALP, LDH, TBA, GSH e SOD. Os resultados mostram que SEM de An-AgNps tem tamanho médio de partícula de 70 a 130 nm. No grupo tratado com MTX, os níveis de TC, TG, LDL-c, ALT, AST, ALP, LDH e TBA aumentaram significativamente (P 0,05) do que NC, enquanto os níveis de HDL-c, SOD e GSH diminuíram significativamente (P 0,05). Por outro lado, nos grupos tratados com An-AgNps + MTX, foram revertidos os níveis de todos os biomarcadores semelhantes ao NC. Em conclusão, os resultados mostram que o An-AgNps tem um efeito protetor contra a hepatotoxicidade induzida pelo MTX e o estresse oxidativo.

Pacientes con embarazo en cicatriz de cesárea tratadas con metotrexato. Serie de casos de terapia combinada sistémica y percutánea en un centro de tercer nivel de Colombia / Management of cesarean scar pregnancy with methotrexate. A case series of combined systemic and percutaneous therapy in a III level center in Colombia

Resumen OBJETIVO: Describir un esquema de atención no quirúrgica en pacientes con embarazo en cicatriz de cesárea en el contexto de un sistema de salud con bajos recursos. Además, describir la tolerancia, vigilancia, evolución y desenlace de cada una de las pacientes tratadas con el esquema propuesto. MATERIALES Y MÉTODOS: Estudio retrospectivo, descriptivo de serie de casos de pacientes que acudieron al servicio de Urgencias de una institución de tercer nivel de atención en Barranquilla, Colombia, entre los meses de mayo de 2020 a marzo 2023 debido a síntomas obstétricos o fueron remitidas a la institución con diagnóstico, confirmado por ultrasonografía, de embarazo en cicatriz de cesárea. Parámetros de estudio: medición de variables sociodemográficas, obstétricas, de evolución clínica y complicaciones maternas. Se efectuó el análisis descriptivo de los datos. RESULTADOS: Se documentaron 11 pacientes que dieron una incidencia de 1.85 casos por cada 5000 embarazos. El dolor pélvico y el sangrado fueron los síntomas más prevalentes. Cinco pacientes tuvieron dos o más cesáreas, el resto una sola previa y cinco antecedente de legrado obstétrico. Nueve de 11 pacientes se atendieron con menos de 8 semanas de embarazo. La tasa de éxito alcanzada fue en las 11 pacientes, con negativización de la beta hCG a los 38.7 días en promedio. No se registraron complicaciones severas ni requerimiento de atención quirúrgica. CONCLUSIONES: Se describió la implementación de un esquema combinado sistémico y local con metotrexato que resultó seguro y efectivo, con preservación de la fertilidad.

Abstract OBJECTIVE: To report a scheme of non-surgical care in patients with cesarean scar pregnancy in the context of a health system with low resources. In addition, to describe the tolerance, monitoring, evolution and outcome of each of the patients treated with the proposed scheme. MATERIALS AND METHODS: Descriptive study of a case series of patients who, between May 2020 and March 2023, attended the emergency room of a tertiary care institution in Barranquilla, Colombia, because of obstetric symptoms or were referred to the institution with a diagnosis of cesarean scar pregnancy confirmed by ultrasound. Study parameters: measurement of sociodemographic, obstetric, clinical evolution and maternal complication variables. Descriptive analysis of data was performed. Results: Eleven patients were documented, giving an incidence of 1.85 cases per 5000 pregnancies. Pelvic pain and bleeding were the most common symptoms. Five patients had two or more previous cesarean sections, the remainder had only one previous cesarean section, and five had a history of obstetric curettage. Nine of the 11 patients were treated at less than 8 weeks'; gestation. The success rate was 100%, with a mean beta-hCG negativity of 38.7 days. There were no major complications and no surgical intervention was required. CONCLUSIONS: We describe the implementation of a combined systemic and local regimen with methotrexate that was safe and effective, with preservation of fertility.

Manejo de la neoplasia trofoblástica gestacional. A propósito de un caso

La enfermedad trofoblástica gestacional es definida como un grupo heterogéneo de lesiones, las cuales surgen a partir del epitelio trofoblástico de la placenta luego de una fertilización anormal. Se presenta el caso de una paciente de 35 años de edad, con diagnóstico de neoplasia trofoblástica gestacional posmolar en etapa I, que se detectó tras estudios imagenológicos de seguimiento y determinación de la hormona gonadotropina coriónica humana, para lo cual llevó tratamiento con quimioterapia y terapéutica de mantenimiento con metotrexato por 5 días o metotrexato/ácido folínico por 8 días, hasta la normalización de la gonadotropina coriónica humana. Lo más relevante es que, aunque estos tumores abarcan menos del 1 % de los tumores ginecológicos, representan una amenaza para la vida de las mujeres en edad reproductiva.

Gestational trophoblastic disease is defined as a heterogeneous group of lesions, which arise from the trophoblastic epithelium of the placenta after abnormal fertilization. The case of a 35-year-old female patient is presented with a diagnosis of posmolar gestational trophoblastic neoplasia in stage I, which was detected after follow-up imaging studies and determination of human chorionic gonadotropin, for which she underwent chemotherapy treatment and maintenance therapy with methotrexate for 5 days or methotrexate/folinic acid for 8 days, until normalization of human chorionic gonadotropin The most relevant thing is that, although these tumors comprise less than 1% of gynecological tumors, they represent a threat to the life of women of reproductive age.

Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Avaliação da esteatose e da fibrose hepática em pacientes com psoríase: o papel do metotrexate, da síndrome metabólica, de fatores genéticos e a associação com o risco cardiovascular / Assessment of hepatic steatosis and fibrosis in patients with psoriasis: the role of methotrexate, metabolic syndrome, genetic factors and the association with cardiovascular risk

Introdução: Uma alta prevalência de doença hepática esteatótica metabólica (MASLD) tem sido descrita na psoríase. A influência da presença de fatores metabólicos, dos polimorfismos dos genes PNPLA3 e TM6SF2 e da dose acumulada de metotrexate (MTX) na progressão da doença esteatótica necessita melhor avaliação. O risco cardiovascular também é aumentado na MASLD e a presença de ateroesclerose subclínica pode representar um marcador do processo inflamatório que une os componentes da hipótese do eixo hepato-dérmico na psoríase. Objetivos: Avaliar o impacto dos polimorfismos dos genes PNPLA3 e TM6SF2, dos parâmetros metabólicos e da dose cumulativa de MTX na esteatose e fibrose hepática avançada em pacientes com psoríase. Avaliar a associação de esteatose e fibrose hepática avançada com ateroesclerose subclínica nestes pacientes. Métodos: Estudo transversal com inclusão prospectiva de pacientes ambulatoriais com psoríase, submetidos a análise clínica e laboratorial, elastografia hepática transitória (TE) com controlled atenuated parameter (CAP) com o equipamento FibroScan® (Echosens,Fr). Todos os pacientes realizaram a genotipagem para os polimorfismos PNPLA3/TM6SF2. A medida da velocidade de onda de pulso carótido-femoral (VOP-cf) foi adotada como medida de rigidez aórtica (rAO). A esteatose foi definida por CAP ≥275 dB/m, fibrose hepática avançada como rigidez hepática ≥10 kPa, aumento da rAo como VOP-cf ≥10m/s. Dose cumulativa significativa de metotrexato foi definida por ≥1500 mg (MTX1500). A análise de regressão logística avaliou as variáveis independentes relacionadas à esteatose e fibrose hepática avançada e ao aumento da rigidez aórtica; valor de p<0,05 foi considerado significativo. Resultados: Foram incluídos 199 pacientes (idade 54,6 ±12,6 anos, 57,3% mulheres). A prevalência de síndrome metabólica (SM), esteatose e fibrose hepática avançada foi de 55,8%, 54,8% e 9%, respectivamente. As frequências dos genótipos PNPLA3 e TM6SF2 foram CC 42,3%/CG 49,5%/GG 8,2% e CC 88,7%/ CT 11,3%/TT 0%. SM (OR3,01 IC95% 1,51- 5,98; p=0,002) e índice de massa corporal (OR1,17 IC95% 1,08-1,26; p<0,01) foram independentemente associados à esteatose. Diabetes Mellitus tipo 2 (DM2) (OR10,76 IC95% 2,42-47,87; p=0,002) e a presença de pelo menos um alelo PNPLA3 G (OR5,66 IC95% 1,08-29,52; p=0,039) foram associados à fibrose hepática avançada, mas não o polimorfismo TM6SF2 ou dose cumulativa de MTX. Para a análise das variáveis relacionadas com o aumento da rAo, um sub-grupo com 80 pacientes (idade 56,2±11,5 anos, 57,5% mulheres, IMC 28,6±5,3kg/m2), com prevalências de SM, DM2, dislipidemia, hipertensão arterial sistêmica, esteatose e fibrose hepática avançada de 57,5%, 40,0%, 67,5%, 70,0%, 50,0% e 16,3%, respectivamente, foi avaliado. Com relação ao tratamento da psoríase, 45% receberam dose de MTX≥1500 mg e 33,8%, tratamento imunobiológico. Neste grupo, a prevalência deVOP-cf≥10m/s foi de 21,2%. Na análise de regressão logística, a idade foi independentemente relacionada com o aumento da rAo (OR: 1,21; IC95%:1,06-1,38; p=0,003), mas não a esteatose ou fibrose hepática avançada. MTX1500 foi um fator protetor cardiovascular (OR: 0,18; IC95%: 0,038-0,87; p=0,033), mas não a terapia imunobiológica. Conclusões: Em indivíduos com psoríase, SM e DM2 conferem maiores chances de esteatose e fibrose avançada, respectivamente. O alelo PNPLA3 G, mas não o polimorfismo TM6SF2, impacta em risco 5 vezes maior de fibrose hepática avançada. O aumento da rAo é associado à idade, mas não à esteatose ou fibrose avançada. Um efeito cardiovascular protetor do MTX foi encontrado em uma população psoríase com alta prevalência de SM e seus componentes.(AU)

Introduction: A high prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been described in psoriasis. The influence of the presence of metabolic factors, PNPLA3 and TM6SF2 gene polymorphisms and the cumulative dose of methotrexate (MTX) on the progression of steatotic disease requires further evaluation. Cardiovascular risk is also increased in MASLD and the presence of subclinical atherosclerosis may represent a marker of the inflammatory process that joins the components of the hepato-dermal axis hypothesis in psoriasis. Objectives: To evaluate the impact of PNPLA3 and TM6SF2 gene polymorphisms, metabolic parameters and cumulative MTX dose on steatosis and advanced liver fibrosis in patients with psoriasis. To evaluate the association of steatosis and advanced fibrosis with subclinical atherosclerosis. Methods: Cross-sectional study with prospective inclusion of outpatients with psoriasis, submitted to clinical and laboratory analysis, transient elastography (TE) with controlled attenuated parameter (CAP), with FibroScan® (Echosens,Fr). All patients underwent genotyping for PNPLA3/TM6SF2 polymorphisms. The measurement of carotid-femoral pulse wave velocity (PWV-cf) was adopted as a measure of aortic stiffness (AoS). Steatosis was defined by CAP ≥275 dB/m, advanced liver fibrosis as liver stiffness ≥10 kPa, increased AoS as PWV-cf ≥10m/s. Significant cumulative dose of methotrexate was defined as ≥1500 mg (MTX1500). Logistic regression analysis evaluated the independent variables related to to steatosis and advanced liver fibrosis and increased AoS; p value <0.05 was considered significant. Results: 199 patients were included (age 54.6 ±12.6 years, 57.3% feminine). The prevalence of metabolic syndrome (MetS), steatosis and advanced liver fibrosis was 55.8%, 54.8% and 9%, respectively. The frequencies of the PNPLA3 and TM6SF2 genotypes were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/CT 11.3%/TT 0%. MetS (OR3.01 95% CI 1.51-5.98; p=0.002) and body mass index (OR1.17 95% CI 1.08-1.26; p<0.01) were independently associated with steatosis. Type 2 Diabetes Mellitus (DM2) (OR10.76 95% CI 2.42-47.87; p=0.002) and the presence of at least one PNPLA3 G allele (OR5.66 95% CI 1.08-29.52; p =0.039) were associated with advanced liver fibrosis, but not the TM6SF2 polymorphism or cumulative dose of MTX. To analyze the variables related to increased AoS, a sub-group with 80 patients (age 56.2±11.5 years, 57.5% feminine, BMI 28.6±5.3kg/m2), with prevalences of MetS, DM2, dyslipidemia, systemic arterial hypertension, steatosis and advanced liver fibrosis of 57.5%, 40.0%, 67.5%, 70.0%, 50.0% and 16.3%, respectively, was evaluated. Regarding psoriasis treatment, in this group, 45% received a dose of MTX≥1500 mg and 33.8%, immunobiological treatment. The prevalence of PWVcf≥10m/s was 21.2%. In the logistic regression analysis, age was independently related to increased AoS (OR: 1.21; 95% CI: 1.06-1.38; p=0.003), but not steatosis or advanced liver fibrosis. MTX1500 was a cardiovascular protective factor (OR: 0.18; 95% CI: 0.038-0.87; p=0.033), but not immunobiological therapy. Conclusions: In individuals with psoriasis, MetS and DM2 confer a greater risk for steatosis and advanced fibrosis, respectively. The PNPLA3 G allele, but not the TM6SF2 polymorphism, impacts a 5-fold increased risk of advanced liver fibrosis. Increased AoS is associated with age, but not with steatosis or advanced fibrosis. A protective cardiovascular effect of MTX was found in a psoriasis population with a high prevalence of MetS and its components.(AU)

Application of the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice: a retrospective analysis apart from the clinical trial at two centers in Brazil

ABSTRACT Introduction: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. Methods: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. Results: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. Conclusion: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.