Dimitar Metodiev

Dr. Dimitar Metodiev

MHAT Hospital for Women Health Nadezhda

Research Focus & Metrics

Academic Career Length

6Years (2021-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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22 November 2021 in Clinics and Practice
Verified
Journal Article
Open access
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Stoyan KostovStoyan Kostov
Stoyan Kostov
YKYavor Kornovski
Yavor Kornovski
VIVesela Ivanova
Vesela Ivanova
DDDeyan Dzhenkov
Deyan Dzhenkov
DMDimitar Metodiev
Dimitar Metodiev
angel yordanovangel yordanov
angel yordanov
Sarcomas of the uterine corpus are rare malignant neoplasms, which are further classified into mesenchymal tumors, and mixed (epithelial plus mesenchymal) tumors. The main issues concerning these neoplasms are the small number of clinical trials, insufficient data from evidence-based medicine, insignificant interest from the pharmaceutical industry, all of which close a vicious circle. The low frequency of these malignancies implies insufficient experience in the diagnosis, hence incomplete surgical and complex treatment. Additionally, the rarity of these sarcomas makes it very difficult to develop clinical practice guidelines. Preoperative diagnosis, neoadjuvant and adjuvant chemoradiation, target and hormone therapies still raise many controversies. Disagreements about the role and type of surgical treatment are also often observed in medical literature. There are still insufficient data about the role of pelvic lymph node dissection and fertility-sparing surgery. Pathologists’ experience is of paramount importance for an accurate diagnosis. Additionally, genetics examinations become part of diagnosis in some sarcomas of the uterine corpus. Some gene mutations observed in uterine sarcomas are associated with different outcomes. Therefore, a development of molecular classification of uterine sarcomas should be considered in the future. In this review, we focus on the epidemiology, pathogenesis, pathology, diagnosis and treatment of the following sarcomas of the uterine corpus: leiomyosarcoma, low- and high-grade endometrial stromal sarcomas, undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are excluded as they represent an epithelial tumor rather than a true sarcoma.

24 January 2023 in Journal of Reproductive Immunology
Verified
Journal Article
Closed access
RGRumiana Ganeva
Rumiana Ganeva
PDParvanov Dimitar
Parvanov Dimitar
NVNina Vidolova
Nina Vidolova
MRMargarita Ruseva
Margarita Ruseva
MHMaria Handzhiyska
Maria Handzhiyska
SGStamenov Georgi
Stamenov Georgi

26 July 2022 in Clinics and Practice
Verified
Journal Article
Open access
PDF file
DMDimitar Metodiev
Dimitar Metodiev
MRMargarita Ruseva
Margarita Ruseva
PDParvanov Dimitar
Parvanov Dimitar
RGRumiana Ganeva
Rumiana Ganeva
MHMaria Handzhiyska
Maria Handzhiyska
SGStamenov Georgi
Stamenov Georgi
It is an acknowledged fact that SARS-CoV-2 exhibits tropism for the human placenta. A possible mechanism of SARS-CoV-2 entry into host cells is via angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in trophoblasts, endothelial cells, and macrophages. The present study describes a case of spontaneous miscarriage in the 20th gestational week after maternal SARS-CoV-2 infection. The placenta and various fetal organs were examined for structural alterations and expression of the viral nucleocapsid protein and several immune cell markers via immunohistochemistry (IHC). Histopathological examination of the placenta revealed acute chorioamnionitis, acute subamnionic placentitis, multiple intervillous thrombi, increased fibrinoid deposition, and necrotic changes of the chorionic villi. Immunohistochemistry confirmed the presence of SARS-CoV-2 nucleocapsid protein regions predominantly in the syncytiotrophoblast. Staining of the placental tissue for different markers helped elucidate the distribution of immune cells. Pathomorphological examination of the fetal organs demonstrated changes in microcirculation with the presence of sludge phenomenon and diapedesis haemorrhages, mostly in the lungs, brain, and myocardium. IHC staining of fetal organs revealed expression of SARS-CoV-2 nucleocapsid protein, which was detected to the highest extent in the brain, lungs, and liver. The findings of the present report support the hypothesis of possible vertical transmission of SARS-CoV-2 from mother to fetus.

1 June 2026 in Immuno
Verified
Journal Article
Open access
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RGRumiana Ganeva
Rumiana Ganeva
TPTeodora Tihomirova Pankova
Teodora Tihomirova Pankova
PDParvanov Dimitar
Parvanov Dimitar
MRMargarita Ruseva
Margarita Ruseva
MHMaria Handzhiyska
Maria Handzhiyska
SHSavina Petrova Hadjidekova
Savina Petrova Hadjidekova
The aim of this study was to investigate the association between the endometrial microbiome and local immune cell composition during the implantation window. We conducted a single-center prospective observational study including endometrial samples from 58 women without endometrial pathology. All samples were obtained during the mid-secretory phase (day 5 post-ovulation). Endometrial stromal CD3+ T cells, CD4+ T helpers, CD56+ NK cells and CD68+ macrophages were identified by immunohistochemistry and quantified as a percentage of stromal cells using HALO image analysis software. Microbiome composition was assessed by 16S rRNA gene sequencing (V4–V5 region). Lactobacillus dominance (LD) was defined as the genus with the highest centered log-ratio value within each sample. Endometrial immune cell composition showed a median 2.28% CD3+ T cells of stromal cells, 1.75% CD56+ NK cells, 1.44% CD68+ macrophages and 0.29% CD4+ T helpers. Lactobacillus-dominated microbiota was identified in 51.7% (30/58) of samples. Correlation analysis showed that Lactobacillus-related taxa were negatively associated with NK/T ratios and positively with T helper-related ratios. LD samples exhibited reduced NK cell abundance (1.17% vs. 2.12%, p = 0.006, q = 0.023) and a lower NK/T ratio (0.52 vs. 1.05, p = 0.004, q = 0.023) compared to non-LD samples. This study provides evidence for a link between microbial composition and local immune regulation in the endometrium.

23 October 2025 in Diagnostics
Verified
Journal Article
Open access
PDF file
PDParvanov Dimitar
Parvanov Dimitar
RGRumiana Ganeva
Rumiana Ganeva
MRMargarita Ruseva
Margarita Ruseva
MHMaria Handzhiyska
Maria Handzhiyska
JSJinahn Safir
Jinahn Safir
SHSavina Petrova Hadjidekova
Savina Petrova Hadjidekova
Background/Objectives: Senescent cells contribute to endometrial remodeling during the implantation window, but their spatial organization within the stroma remains poorly understood. This study aimed to characterize the distribution of senescent (p16-positive) cells in the functional layer of the endometrium and to evaluate their spatial relationships with immune cell subsets. Methods: Endometrial biopsies from 68 women undergoing IVF were collected during the mid-luteal phase (LH+7, corresponding to the implantation window). Samples were analyzed by immunohistochemistry for p16 and immune markers (CD3, CD4, CD8, CD14, CD68, CD56, CD79α). Images from adjacent serial sections were digitally aligned, and senescent cell density, clustering, and nearest-neighbor distances to immune cells were quantified using HALO Image Analysis software (v3.4). Ratios of senescent-to-immune cell abundance were also calculated to account for stromal variability. Results: Senescent cells were heterogeneously dispersed within the stroma, with occasional high-density clusters. Quantitative analysis revealed that their abundance was lower than that of monocytes, macrophages, and total T cells, but higher than that of T-helper and B cells. Across patients, median senescent-to-immune cell ratios were approximately 1, indicating comparable abundances, except for CD4+ and CD79α+ subsets, where ratios were significantly elevated. Nearest-neighbor analysis showed that macrophages and monocytes localized in closest proximity to senescent cells (45 ± 20 μm and 45 ± 25 μm), while T-helper and NK cells were positioned at greater distances from senescent cells (102 ± 42 μm and 53 ± 23 μm, respectively). B cells showed the greatest separation (211 ± 66 μm). Correlation analysis confirmed density-driven proximity for most immune subsets, with CD4+ and CD56+ cells as exceptions, displaying limited spatial association with senescent cells. Conclusions: Senescent cells in the endometrium during the implantation window display heterogeneous distribution and selective spatial associations with immune subsets. Their preferential distancing from T-helper and NK cells suggests impaired local immune–senescence crosstalk, highlighting spatial profiling of senescent cells as a potential diagnostic marker of endometrial receptivity.

24 October 2025 in Immuno
Verified
Journal Article
Open access
PDF file
MRMargarita Ruseva
Margarita Ruseva
PDParvanov Dimitar
Parvanov Dimitar
RGRumiana Ganeva
Rumiana Ganeva
MHMaria Handzhiyska
Maria Handzhiyska
JSJinahn Safir
Jinahn Safir
SHSavina Petrova Hadjidekova
Savina Petrova Hadjidekova
Embryo implantation requires a finely tuned immune balance at the maternal–fetal interface. Interferon tau (IFN-τ), a key immunomodulator in ruminant implantation, may have therapeutic potential in human reproduction. This study investigated its effects on peripheral blood mononuclear cells (PBMCs) in vitro and the subsequent impact on endometrial immune composition following intrauterine administration of these cells. The work was conducted in two stages. First, in vitro assays were performed with PBMCs from 20 patients with recurrent implantation failure (RIF) cultured with or without IFN-τ for 24 h. Cytokines (IL-10, IL-4, TNF-α, IL-6) were measured by ELISA, and T cell subsets (Th, cytT, Th1, Th2, Th9, Tfh, Th17, Treg) were analyzed by flow cytometry. IFN-τ increased IL-4 and reduced TNF-α and IL-6, indicating a Th2 profile shift. T-cell analysis revealed fewer cytT, Th1, Th9, and Th17 cells, more Th2 cells, and improved Th/Tk, Th1/Th2, and Th17/Treg ratios after IFN-τ. A second clinical study included 55 RIF patients who received intrauterine IFN-τ-modulated PBMCs. Post-treatment endometrial biopsies revealed more helper T cells and macrophages, with higher Th/total T, Th/cytT, and Th/macrophage ratios, suggesting a tolerogenic environment. Overall, IFN-τ modulates PBMCs in vitro and promotes a favorable endometrial immune profile in vivo, highlighting its potential as an immunotherapy in assisted reproduction.