Vol 22, No 4 (2020)

ORIGINAL ARTICLE
A predictive model to calculate the probability of placental abruption in patients with initially low obstetric risk
Frolova N.I., Belokrinitskaya T.E.
Abstract

Aim. To develop a predictive model to calculate the probability of placental abruption development in patients with initially low obstetric risk by using a multidimensional mathematical analysis of anamnestic, clinical, and genetic data.

Materials and methods. This logistic model is based on 212 observations. This study included two groups of healthy women aged 18–35 years without a history of spontaneous abortion, preterm labor, stillbirth, preeclampsia, or other complications. The first group was comprised of 112 women with a history of a placental abruption (patient group), and the second group consisted of 100 women with non-complicated pregnancy (control group). Gene polymorphisms were detected using the polymerase chain reaction-real time technique. The data was analyzed using binary and multifactorial statistical mathematics. Our analysis of the predictive models was performed by using logistic regression. To determine the diagnostic value of the predictive models used, the ROC-curve is followed by determining the area under it (AUC).

Results. The 24 anamnestic, clinical, and genotypic characteristics were examined as placental abruption predictors using multifactorial analysis. We were able to determine what the nine most informative predictors of placental abruption were according to Wald Chi-Square criteria (÷2, р): fetal growth restriction (13.143; р<0.001), placental insufficiency (9.629; р=0.002), male sex of the fetus (6.965; р=0.008), preeclampsia (6.779; р=0.009), combination of genotypes PAI-1-5G4G/FV-1691GA (6.613; р=0.010) or PAI-1-5G4G/MTHFR-677CT (6.158; р=0.013), pathology of amnion (4.497; р=0.034), infectious diseases in pregnancy (4.277; р=0.039), tobacco smoking (3.963; р=0.047). ROC analysis identified a high specificity (82.64%) and sensitivity (77.42%) of the model, and the integral index of the effectiveness of predictive markers (AUC=0.836), according to the expert scale of values which is indicative of a very high quality model.

Conclusion. It is recommended to use this elaborated predictive model in clinical practice for the purpose of individual risk assessment of placental abruption in healthy patients with initially low obstetric risk.

Gynecology. 2020;22(4):6-10
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Analysis of morbidity and mortality of cervical cancer in Zabaikalskii krai
Bogomazova T.V., Chimitdorzhieva T.N.
Abstract

Relevance. Currently, noncommunicable diseases are responsible for the majority of deaths worldwide. Cervical cancer (СС) is actual medical and social problem. Comparative analysis of morbidity, mortality and state of oncological care in Zabaikalskii krai and Russian Federation was purpose of this study.

Aim. Estimation of morbidity and mortality from cervical cancer in the Zabaikalskii krai in dynamics over 10 years.

Materials and methods. The assessment was carried out on the basis of an analysis of statistical data concerning the burden of morbidity and mortality from cancer in the territory of the Zabaikalskii krai and the Russian Federation. Statistical analysis was performed using the Statistica 10 software. Standardized indicators were used to analyze morbidity and mortality. Differences were considered statistically significant at an error level of p<0.05.

Results. Analysis cervical cancer incidence of the Zabaikalskii krai and the Russian Federation in dynamics from 2007–2017 (100 000 female population) demonstrates a significant increase in the incidence of cervical cancer. On the territory of the Russian Federation, there is a steady increase on average by 2.26% annually, the growth dynamics over this period amounted to 25.81%, and in 2017 amounted to 15.76‰. In the Zabaikalskii krai in 2017, the incidence of cervical cancer was 41.54‰. In dynamics over the past 10 years, this indicator increased by 46.42%, which is significantly higher than in the Russian Federation (p<0.01). The analysis of standardized indicators of mortality from cervical cancer in the structure of mortality from cancer in Russia in 2017 amounted to 5.18%, which corresponds to 10th place. Mortality in the first year since diagnosis was 14.6%. In the group of women of reproductive age 30–39 years, mortality from cervical cancer was also maximum (23.6%) compared with other age groups. Mortality from cervical cancer in the Zabaikalskii krai was 7.17‰ in 2017. This indicator is higher than the all-Russian values by 38.41% (p<0.01). In dynamics over 10 years, a decrease in mortality in the Zabaikalskii krai by 6.39% is noted.

Conclusion. It should be noted that a significant increase in the incidence of cervical cancer, and a decrease in mortality from this pathology, may indicate some success in the diagnosis and treatment of this pathology. In this regard, the search for new diagnostic, prognostic and predictive markers at this stage is relevant in solving this all-Russian medical and social problem.

Gynecology. 2020;22(4):11-16
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Recurrent cystitis and bacterial vaginosis: how to avoid polypharmacy
Kulchavenya E.V., Breusoff A.A.
Abstract

Background. The structure of lower urinary tract infections has clear sex-based differences. The vaginal microbiota is a key factor in the pathogenesis of lower urinary tract infections: aerobic vaginitis predisposes to infection and increases the incidence of cystitis by 2.9 times.

Aim. To determine the effectiveness of Nifuratel as monotherapy in patients with chronic cystitis and concomitant bacterial vaginosis (BV).

Materials and methods. Study design: an open-label, non-comparative, pilot, single-center, prospective study, which included 23 patients with recurrent cystitis and BV. All women received monotherapy with Nifuratel (Macmiror manufactured by Doppel Farmaceutici S.r.l., Italy) in tablets of 200 mg 3 times a day for 7 days. Control visits were performed in 7.90 and 180 days.

Results. BV was diagnosed in all patients; 19 (82.6%) women also had vaginal candidiasis. At the end of therapy, 17 (73.9%) patients showed an excellent outcome, 4 (17.4%) – a significant improvement, 2 (8.7%) – no effect. After the end of three-month therapy, 18 (81.8%) out of 22 patients who left in the study had no complaints of urinary disorders or vaginal discharge. Their urinalyses were normal. Molecular genetic analysis of the vaginal biocenosis showed moderate dysbiosis; Candida spp. was revealed only in 3 (13.6%) cases. 18 patients came for the 4th visit. Within six months after the end of monotherapy with Nifuratel, the patients had no complaints. They all achieved the recovery of vaginal normocenosis with a sufficient amount of Lactobacillus spp.

Conclusion. Monotherapy in patients with recurrent cystitis and BV is highly effective for both diseases: 73.9% of women achieved stable normalization of urine and vaginal microbiota analyzes, removal of bacteriuria. The bi-directional action of Nifuratel allows to avoid polypharmacy in this category of patients.

Gynecology. 2020;22(4):17-21
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Clinical and morphological stages vulvar lichen sclerosus
Sokolova A.V., Apolikhina I.A., Zaitsev N.V., Chernukha L.V.
Abstract

Aim. To determine leading clinical symptoms and risk factors for vulvar lichen sclerosus, identify the features of the disease in the early and late stages.

Materials and methods. The investigation included 102 patients with clinical symptoms of aged 21 to 79 (the average age was 50.6±13.9 years), 67/102 (66%) conducted punch biopsy of vulva. The control group consisted of 113 women without signs of vulvar lichen sclerosus according to clinical and anamnestic examination.

Results and discussion. Patients with VLS are overweight and obese 1 degree (BMI³26.5), have a low level of physical activity and sleep durations≤ 6.6 hours, experience stress and have low resistance to stress factors. Among gynecological diseases, patients with VLS are more often diagnosed with uterine myoma (42%) and genital endometriosis (29%). Among extragenital diseases, endocrine (54%), autoimmune (53%), diseases of the urinary system (54%) and skin (14%), benign diseases of the mammary glands (28.57%) prevail. Scars and deformations of the perineum, as a risk factor for VLS, are observed in 46.21%; 5% of women have a family history of VLS.

Conclusion. Vulvar lichen sclerosus is a multifactorial disease, divided into early and late stages. Subjective symptoms of VLS are not related to age, duration and stage of the disease. Mucosal edema is characteristic of the early stage, and the late stage is characterized by a change in the architectonics of the external genitalia. In 11% of cases, the disease has no visual changes on the vulva. In this case, the most exact diagnostic method for VLS is a histological examination, which allows doctors to establish a diagnosis even at an early stage.

Gynecology. 2020;22(4):22-27
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Use of a drug containing ornidazole-neomycin–prednisolone–econazole for the empirical treatment of vaginal infections
Volkov V.G., Zakharova T.V.
Abstract

Relevance. Empirical treatment of vaginitis is indicated due to its polymicrobial etiology and limited microbiological analysis. The aim of the study was to study the combination of ornidazole–neomycin–prednisolone–econazole (ONPE, Elzhina®) as a first-line drug for local treatment of patients with various forms of non-specific vaginitis.

Materials and methods. The study included 55 non-pregnant women aged 18 to 50 years (38±1.5 years) who had clinical and laboratory signs of acute vaginitis.

Results. All patients at the initial treatment complained of pathological discharge, 47 (85.5%) noted itching, burning, pain in the genital area of various degrees of severity, 17 (30.9%) – discomfort when urinating, 9 (16.4%) – unpleasant smell, 8 (14.5%) – dyspareunia, 4 (2.2%)– complained of sensations of a foreign body in the vagina. The clinical and laboratory effectiveness of treatment was 89.1% (49). In 6 (10.9%) patients, clinical improvement was noted, with the remaining laboratory signs of aerobic vaginitis.

Conclusion. The new combination of ornidazole–neomycin–prednisolone–econazole (ONPE, Elzhina® ) has a good efficacy and safety profile and can be used to initiate empirical treatment of non-specific inflammatory diseases of the lower genital tract.

Gynecology. 2020;22(4):28-32
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Influence of preoperative preparation on the vaginal architectonics of postmenopausal women with severe genital prolapse
Lazukina M.V., Mikhelson A.A., Bashmakova N.V., Melkozerova O.A., Chistyakova G.N., Grishkina A.A.
Abstract

Patients with severe postmenopausal genital prolapse (GP) are the most clinically difficult group of women, in which surgical treatment with mesh implants presents significant difficulties due to the duration of lesions amid pronounced structural changes in the tissues of the urogenital tract under conditions of hormone deficiency. That is why it is of particular importance to study the histological characteristics of the vaginal mucosa in women with GP, who must conduct surgical treatment of vaginal access.

Aim. To study the histological features of the vaginal mucosa in postmenopausal women with severe GP in preparation for surgical treatment with vaginal access.

Materials and methods. The study involved 70 postmenopausal women suffering from GP of stage III, IV in combination with genitourinary menopausal syndrome. Patients were randomized blindly into two groups. The therapy was carried out using vaginal forms of estrogen and progesterone preparations in combination with lactobacilli. In the comparison group, preoperative preparation was not performed. All patients underwent clinical and laboratory examination: general examination and gynecological examination, morphological examination of biopsy samples of the mucous membrane of the anterior vaginal wall, which were obtained during subsequent surgical treatment of GP. Methods of parametric statistics were used.

Results. It was established that focal dystrophy, acanthotic severity, keratinization of the vaginal epithelium, moderate inflammation are characteristic morphological changes in the vaginal mucosa in women with postmenopausal GP. Application at the stage of preparation for surgical treatment using vaginal forms, as a result of which estrogen and progesterone enhance the inflammatory process in the ulcerative vagina, reduce dystrophic changes and their severity in relation to complex changes and differentiation of the vaginal epithelium and activation of regeneration processes in tissues.

Conclusion. Reducing inflammation and the severity of dystrophic processes in vaginal enemas at the stage of preoperative preparation of women with postmenopausal GP favorably affects the regeneration processes, which in the first place can improve the outcome of surgical treatment.

Gynecology. 2020;22(4):33-38
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Potential predictive marker of treatment effectiveness in patients with osteopenic syndrome after surgical menopause
Zaydieva Y.Z., Kruchinina E.V., Gorenkova O.S., Polyakova E.Y., Kareva E.N., Kurguzova D.O., Kochina N.A., Krasnoshchok K.V., Serebrova S.Y.
Abstract

Introduction. Patients with surgical menopause have a risk for osteopenic syndrome (OS). Menopausal hormone therapy (MHT) in combination with calcium and vitamin D promotes increase in bone mineral density (BMD). The expression level of vitamin D receptor in mononuclear fraction cells (MNFC) of blood can be considered as a predictive marker of effectiveness of OS therapy.

Aim. To search a molecular predictive marker of the effectiveness of OS treatment.

Materials and methods. The study included 100 women aged 40–55 years with a duration of surgical menopause from 12 months to 6 years. The criterion for including patients in the study was the absence of contraindications to the use of MHT. The subject of the study was the determination of BMD by dual-energy X-ray absorptiometry, polymerase chain reaction diagnostics of the level of expression of vitamin D genes, estradiol and progesterone receptors, determination of 25-OH vitamin D in the blood.

Results. Analysis of 12-month OS therapy effectiveness evaluated with a surrogate marker BMD. The increase in BMD up to 3–4% per year was treated as absence of negative dynamics, more than 4% per year as positive one. Significant effect of combination therapy compared with MHT on BMD in patients with surgical menopause with a low baseline level of BMD (due to hypovitaminosis D) is associated with the anti-inflammatory, bone-protective effect of vitamin D. In both groups of patients not responding; to the prescribed therapy we were able to conduct a comparative analysis of expression level of the target molecules in the MNFC before the start of treatment. The efficacy of MHT and combination therapy for BMD disorders is positively associated with the expression level of vitamin D receptors in MNFC before treatment. Therefore, the vitDR mRNA level is a potential predictive marker of the effectiveness of OS treatment. The expression levels of nuclear estradiol beta receptor and membrane receptor for progesterone in MNFC before treatment showed an upward trend in women responding to therapy.

Conclusion. The expression level of the vitamin D receptor in MNFC of blood is significantly lower in the group of women with no/insufficient effect on 12-month combined therapy. This indicator can be considered as a predictive marker of the effectiveness of OS therapy.

Gynecology. 2020;22(4):39-42
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The role of 7-hydroxymatairezinol in modulation of estrogen metabolism and therapy for mastopathy
Rubashkina A.N., Lapochkina N.P., Torshin I.Y., Gromova O.A.
Abstract

Quantitative estimates of the effect of 7-hydroxymatairesinol (7-HMR) intake on estrogen balance and clinical aspects of the course of fibrocystic mastopathy have been carried out.

Aim. Assessment of effects 7-HMR on metabolism of estrogen (16a-OHE1, 2-OHE2, 2-OHE1, 2-OMEE1, 4-OMEE2, 4-OHE1, a ratio 2-OHE1/16a-OHE1, 2-OHE1/2-OMeE1 and 4-OHE1/4-OMeE1) and progesterone in daily urine at patients with fibrous and cystous mastopathy in the post-menopausal period.

Materials and methods. The analysis of metabolites of estrogen (16a-OHE1, 2-OHE2, 2-OHE1, 2-OMEE1, 4-OMEE2, 4-OHE1, ratios 2-OHE1/16a-OHE1, 2-OHE1/2-OMeE1 and 4-OHE1/4-OMeE1) and progesterone in daily urine with use of solid-phase immunofermental set (IFA) of «Amerscham International» on the analyzer of Amerkard by means of standard sets is carried out. Statistical 10.0 and Microsoft Excel spreadsheets were used in statistical material processing.

Results. It was found that taking 7-HMR (60 mg/day, 1 month) contributes to normalizing estrogen metabolism (decreasing estradiol, estrone, estriol, 16a-OHE1) and improves the clinical symptoms of mastopathy.

Conclusions. In patients with FCM, 7-HMR contributes to a decrease in hyperestrogenia-related tumor risks by lowering estrogen metabolites levels.

Gynecology. 2020;22(4):43-48
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Modern view on management tactics of patients with endometrial pathologic processes in the perimenopausal period and postmenopause
Pestrikova T.Y., Yurasova E.A., Kovaleva T.D., Yurasov I.V., Knyazeva T.P., Adamyan E.S., Mashtagova K.M.
Abstract

Aim. To evaluate the effectiveness of combination therapy of pathological endometrial processes (benign forms) based on the determination of one of the variants of etiopathogenesis in patients of perimenopausal age and in postmenopause.

Materials and methods. The examination included 34 patients with a diagnosis of endometrial hyperplastic processes in the perimenopausal period and in postmenopause. To verify the diagnosis, in addition to the results of a clinical examination (general and gynecological), the patients underwent laboratory (microscopic and molecular biological studies using real-time polymerase chain reaction method of aspirates from the uterine cavity), diagnostic (ultrasound, hysteroscopy) and morphological examination methods.

Results. Conducting combined antimicrobial and antiviral therapy in patients with endometrial hyperplastic processes, endometrial polyp in combination with chronic endometritis, allowed us to eliminate microbial agents from the endometrium before starting hormonal therapy. A positive result of the combined approach showed the absence of recurrence of endometrial hyperplastic processes within 2 years in 91.17% of patients of the examination group.

Conclusion. In our study, we evaluated the effectiveness of the combined treatment of endometrial hyperplastic processes in patients in the perimenopausal period and in postmenopause, against a background of chronic endometritis, using systemic therapy with antibiotics and antiviral drugs, followed by hormonal therapy. A clinical study allows us to formulate recommendations on the management of patients with endometrial hyperplastic processes, endometrial polyps in the perimenopausal period and in postmenopause.

Gynecology. 2020;22(4):49-54
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REVIEW
Adenomyosis: clinical aspects, impact on fertility and pregnancy outcome
Gabidullina R.I., Kuptsova A.I., Koshelnikova E.A., Nuhbala F.R., Bagirli R.R., Mingaleva E.R., Khaliullina E.A.
Abstract

Aim. To investigate the modern condition of the problem of adenomyosis and its impact on women’s reproductive function.

Material and methods. The article presents a systematic literature review on the results of research search in electronic databases MEDLINE, PubMed, EMBASE, Cochrane Library and Elibrary.

Results. Adenomyosis is a common but insufficiently studied disease. Modern imaging methods, such as transvaginal ultrasound and MRI, make it possible to diagnose adenomyosis at the early stages of the disease and perform the organ-preserving surgery. A medical treatment of adenomyosis requires to develop a lifelong management plan, the choice depends on the woman’s age, reproductive status and clinical symptoms. Currently, there is evidence of a negative impact of adenomyosis on fertility and pregnancy outcomes. Dienogest, a 19-norsteroid derivative, is a progestin with high selectivity to progesterone receptors, it exerts a hypogonadotropic effect and an antiproliferative effect on the endometrium. A mild regime of supression of ovarian function provides adequate conditions for blood supply to the uterus before planning a pregnancy. The immunomodulating effect of progestin may be useful for implantation and fetal protection to pregnancies occurring after treatment. Dienogest treatment increases the effectiveness of IVF cycles for adenomyosis of varying severity.

Conclusion. The review summarizes the aspects of prevalence, comorbidity, risk factors, classification, mechanism of pathogenesis, clinical manifestations, diagnosis, treatment of adenomyosis, impact on fertility and pregnancy outcomes.

Gynecology. 2020;22(4):55-61
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Genital herpes: modern views and prospects for the treatment
Khryanin A.A., Knorring G.Y.
Abstract

The review focuses on the clinical and epidemiological characteristics of herpes viral infection, in particular genital herpes. The current treatment options for recurrent ­genital herpes are presented. A detailed description of valaciclovir is given.

Gynecology. 2020;22(4):62-67
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Experience in the treatment of chronic endometritis
Tapilskaya N.I., Savicheva A.M., Shalepo K.V., Kopylova A.A.
Abstract

At present, bacterial biofilms play a significant role in chronic endometritis. In our clinical case, a patient with a history of infertility has had no sex life for several years, but bacterial vaginosis recurs monthly. Ascending bacterial infection with chronic endometritis was confirmed by immunohistochemistry data (detection of CD138), as well as microbiological data (detection of anaerobic microorganisms, including Gardnerella vaginalis and Atopobium vagine, in the endometrium). To treat chronic endometritis, we used antibiotic moxifloxacin, followed by administration of bovhyaluronidase azoximer (Longidaza®) in the form of rectal suppositories. As a result of complex therapy, the patient’s endometrium improved (CD138 and anaerobic bacteria revealed), subsequent repeated insemination with donor sperm led to the onset of progressive pregnancy.

Gynecology. 2020;22(4):68-70
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CLINICAL CASE
A clinical case of sulodexide usage in infertility of unknown origin
Kurtov I.V., Osadchuk A.M., Fatenkova E.S., Kurtova A.I., Davydkin I.L.
Abstract

The article shows the possible use of sulodexidi in a patient with primary infertility of unknown origin associated with an excess of the plasminogen activator type 1 inhibitor. This method illustrates the possibility of pregnancy when taking sulodexidi at the stage of pregravidar preparation in a woman with hypofibrinolysis.

Gynecology. 2020;22(4):72-74
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Possibilities of using neodymium laser (Nd:YAG) in patients with concomitant diseases which are accompanied by pathological discharge from the genital tract
Pauzina O.A., Apolikhina I.A., Malyshkina D.A.
Abstract

Background. Pathological vaginal discharge is the most common disorder in women after giving birth who have vaginal relaxation syndrome and vaginal wall prolapse, as well as in women during menopause. To date, there are no clear treatment regimens for mixed vulvovaginal infections, and the use of only drug therapy in patients with pelvic organ prolapse and genitourinary syndrome of menopause in combination with diseases which are accompanied by pathological vaginal discharge does not give a long lasting result and is characterized by frequent relapses. In this regard, the use of laser methods in combination with drug therapy may lead to the recovery of vaginal microbiocenosis and a decrease in the number of relapses of diseases which are accompanied by pathological discharge from the genital tract.

Results. Description. This article presents a clinical case and description of the experience of using a neodymium laser for the treatment of a patient with recurrent mixed vulvovaginitis, 2nd- degree vaginal wall prolapse, loss of pelvic floor muscle tone, vaginal relaxation syndrome and sexual dysfunction using neodymium laser. The woman received 3 procedures of exposure to a neodymium laser with an interval of 28–30 days. After 3 procedures of exposure to a neodymium laser, the patient has a good clinical efficacy in the recovery of vaginal microbiocenosis.

Conclusions. An innovative technique of exposure to Nd:YAG neodymium laser in the practice of a gynecologist has shown high clinical efficiency in the treatment of not only pelvic floor dysfunction, but also mixed vulvovaginitis. And, despite this aspect of the use of laser technologies requires further study, we can use a neodymium laser in combination with traditional drug therapy to treat diseases which are accompanied by pathological discharge from the genital tract in cases of ineffective drug monotherapy and frequent relapses.

Gynecology. 2020;22(4):75-81
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IN AID OF THE CLINICIAN
Vulvovaginitis of mixed etiology and real clinical practice
Prilepskaya V.N., Abakarova P.R., Donnikov A.E.
Abstract

Lower genital tract inflammatory diseases, caused by opportunistic and pathogenic microorganisms (vulvovaginitis), occupy a leading place among gynecological diseases and are one of the most common reasons for women to consult an obstetrician-gynecologist. Vulvovaginitis is rarely caused by a single pathogen. In recent years, lower genital tract inflammatory diseases are characterized by the predominance of mixed infections, which, on the one hand, can lead to a more severe and prolonged course, frequent relapses, an ascending infection, and, on the other hand, can be asymptomatic, till the development of complications, and represent certain difficulties in the diagnosis and choice of therapy. Opportunistic pathogens and anaerobes-bacteroides play a major role in manifestations of mixed infections. Currently, in the treatment of mixed vulvovaginitis, preference is given to combined drugs that have an effect on a wide range of pathogenic microorganisms. One of them is Metromicon-Neo®, which features of action and our experience of its use along with the features of mixed vulvovaginitis are summarized in the article.

Gynecology. 2020;22(4):82-87
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