Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide. Detecting different biomarkers together on single cells by novel method mass cytometry could contribute to more precise screening. Liquid-based cytology (LBC) cervical samples were collected (N = 53) from women categorized as normal and precancerous lesions. Human papillomavirus was genotyped by polymerase chain reaction, while simultaneous examination of the expression of 29 proteins was done by mass cytometry (CyTOF). Differences in cluster abundances were assessed with Spearman's rank correlation as well as high dimensional data analysis (t-SNE, FlowSOM). Cytokeratin (ITGA6, Ck5, Ck10/13, Ck14, Ck7) expression patterns allowed determining the presence of different cells in the cervical epithelium. FlowSOM analysis enabled to phenotype cervical cells in five different metaclusters and find new markers that could be important in CC screening. The markers Ck18, Ck18, and CD63 (Metacluster 3) showed significantly increasing associated with severity of the precancerous lesions (Spearman rank correlation rho 0.304, p = 0.0271), while CD71, KLF4, LRIG1, E-cadherin, Nanog and p53 (Metacluster 1) decreased with severity of the precancerous lesions (Spearman rank correlation rho -0.401, p = 0.0029). Other metaclusters did not show significant correlation, but metacluster 2 (Ck17, MCM, MMP7, CD29, E-cadherin, Nanog, p53) showed higher abundance in low- and high-grade intraepithelial lesion cases. CyTOF appears feasible and should be considered when examining novel biomarkers on cervical LBC samples. This study enabled us to characterize different cells in the cervical epithelium and find markers and populations that could distinguish precancerous lesions.

• MeSH
• Cervix Uteri pathology   metabolism   MeSH
• Adult MeSH
• Uterine Cervical Dysplasia diagnosis   pathology   MeSH
• Papillomavirus Infections pathology   diagnosis   virology   MeSH
• Kruppel-Like Factor 4 * MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor * genetics   metabolism   MeSH
• Uterine Cervical Neoplasms * diagnosis   pathology   genetics   MeSH
• Precancerous Conditions * pathology   diagnosis   MeSH
• Flow Cytometry * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The aim of this study was to determine whether the presence and extent of lymphovascular invasion (LVI) is prognostic in surgical stage I cervical squamous cell carcinoma (SCC). All available tumour slides and/or paraffin blocks from 426 patients with stage I cervical SCC treated surgically with curative intent were collected from 18 institutions and retrospectively analysed. Presence and extent of LVI (focal <5 spaces, extensive ≥5 spaces) were assessed on scanning magnification in large haematoxylin and eosin slide sets in 366 cases. Progression-free survival (PFS) was calculated as the time from surgery to first progression or death or last follow-up, whichever occurred first. Overall survival (OS) was defined as the time from surgery to death or last follow-up. Clinicopathological and statistical analyses were performed on 97 patients with the International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IA and 329 patients with stage IB SCC of the cervix. LVI, both focal and extensive, was more frequent in stage IB than in stage IA (p<0.001). Patients with stage IB carcinomas with extensive LVI had worse PFS [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.49, 5.49; p=0.005] and OS (HR 2.88; 95% CI 1.38, 6.02; p=0.012) than those with focal or no LVI. In stage IA, in contrast, the presence and extent of LVI did not associate with PFS (p=0.926) or OS. Extensive LVI was not statistically correlated with PFS and OS in substages IA1, IA2 or IB2. PFS (HR 3.7; 95% CI 1.61, 8.46; p<0.001) and OS (HR 4.18; 95% CI 1.58, 11.04; p=0.002) in stage IB1, and PFS (HR 7.78; 95% CI 0.87, 69.82; p=0.039) in stage IB3 were diminished in the presence of extensive LVI. In conclusion, in patients with FIGO stage I cervical SCC, the presence and extent of LVI has prognostic significance in stage IB carcinoma, and quantifying LVI is recommended.

• MeSH
• Cervix Uteri pathology   surgery   MeSH
• Adult MeSH
• Neoplasm Invasiveness MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphatic Metastasis pathology   MeSH
• Uterine Cervical Neoplasms * pathology   surgery   mortality   MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Carcinoma, Squamous Cell * pathology   surgery   mortality   MeSH
• Neoplasm Staging * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Endometriosis, a complex inflammatory disease, affects a significant proportion of women of reproductive age, approximately 10-15%. The disease involves the growth of endometrial glands and stroma outside the uterine cavity, leading to tissue remodeling and fibrosis. Hormonal imbalances, accompanied by local and general inflammation and pain, are key features of endometriosis. Endometriotic lesions are associated with the overproduction of cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, and extracellular vesicles. Genetic predisposition and cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast cells, Th1 in the early phase, Th2 in the late phase, and T regulatory cells play a crucial role in endometriosis. Reduced NK cell function and impaired immune vigilance contribute to endometrial growth. The strong inflammatory condition of the endometrium poses a barrier to the proper implantation of the zygote, contributing to the infertility of these patients. Cytokines from various cell types vary with the severity of the disease. The role of microbiota in endometriosis is still under study. Endometriosis is associated with autoimmunity and ovarian cancer. Hormonal treatments and surgery are commonly used; however, recent interest focuses on anti-inflammatory and immunomodulatory therapies, including cytokine and anti-cytokine antibodies. Modulating the immune response has proven critical; however, more research is needed to optimize treatment for these patients.

• MeSH
• Cytokines metabolism   immunology   MeSH
• Endometriosis * immunology   therapy   pathology   etiology   MeSH
• Endometrium immunology   pathology   MeSH
• Humans MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Úvod a cíl studie: Uterinní NK (uNK) buňky jsou specializovanou subpopulací NK (natural killer) lymfocytů nacházejících se v endometriu. Hrají klíčovou roli v regulaci imunitní odpovědi a v procesu implantace embrya. Cílem této studie je retrospektivní analýza výsledků léčby metodou in vitro fertilizace (IVF) v souboru žen, které podstoupily imunofenotypizaci uNK buněk a na základě výsledků tohoto vyšetření byly, nebo nebyly léčeny imunomodulační terapií. Metody: Studie zahrnovala 122 pacientek, které podstoupily imunofenotypizaci uNK buněk v období od dubna do prosince 2023. Imunofenotypizace byla provedena metodou průtokové cytometrie. Pacientky byly roztříděny do čtyř skupin dle fenotypu uNK buněk: normální nálezy, nízké absolutní a relativní počty uNK (LOW-IMMUNE profil), nízké počty uNK v kombinaci s nežádoucím posunem směrem k cytotoxickému uNKdim imunofenotypu (MIXED-IMMUNE profil) a normální počty uNK, ale nežádoucí posun v poměru cytotoxických a regulačních uNK s cytotoxickým fenotypem (OVER-IMMUNE profil). Byly hodnoceny výsledky embryotransferu a výskyt potratů do ukončeného 12. týdne těhotenství v jednotlivých skupinách. Výsledky: Nejvyšší míra dosažení klinické gravidity byla nalezena v léčené skupině OVER- -IMMUNE (70 %), následované skupinou MIXED-IMMUNE (60 %). Skupina LOW-IMMUNE se od neléčené NORMAL skupiny signifikantně nelišila (p = 0,205). Nedostatečná imunitní aktivace (LOW-IMMUNE profil) byla signifikantně nejčastěji sdružena s prvotrimestrální těhotenskou ztrátou (p < 0,0001). Závěr: Tato studie přináší nové poznatky o potenciálu imunofenotypizace uNK buněk a následné imunomodulační terapie v léčbě poruch plodnosti. Ačkoli výsledky naznačují možné klinické přínosy, je zapotřebí dalšího výzkumu k potvrzení těchto zjištění a k objasnění mechanizmů, které vedou ke zlepšení výsledků léčby technikami asistované reprodukce.

Introduction and objective: Uterine NK (uNK) cells, a specialized subpopulation of natural killer (NK) lymphocytes located in the endometrium, play a crucial role in regulating the immune response and in the process of embryo implantation. This study aims to retrospectively analyze the outcomes of in vitro fertilization (IVF) treatment in a cohort of women who underwent uNK cell immunophenotyping with subsequent immunomodulatory therapy applied based on the results. Methods: The study included 122 patients who underwent uNK cell immunophenotyping between April and December 2023. Immunophenotyping was performed using flow cytometry. Patients were categorized into four groups according to their uNK cell phenotypes: normal findings, low absolute and relative numbers of uNK cells (LOW-IMMUNE profile), low numbers of uNK cells combined with the shift towards the cytotoxic uNKc dim immunophenotype (MIXED-IMMUNE profile), and normal numbers of uNK cells, but an undesirable shift in the ratio of cytotoxic to regulatory uNK cells towards the cytotoxic uNK dim phenotype (OVER-IMMUNE profile). Embryo transfer outcomes and the occurrence of miscarriages up to the 12th week of pregnancy were evaluated in each group. Results: The highest clinical pregnancy rate was observed in the treated OVER-IMMUNE group (70%), fol lowed by the MIXED-IMMUNE group (60%). The LOW-IMMUNE group did not differ significantly from the untreated NORMAL group (P = 0.205). Insufficient immune activation (LOW-IMMUNE profile) was significantly associated with first-trimester pregnancy loss (P < 0.0001). Conclusion: This study provides new insights into the potential benefits of uNK cell immunophenotyping and subsequent immunomodulatory therapy in treating fertility disorders. While the results indicate possible clinical advantages, further research is necessary to confirm these findings and elucidate the mechanisms leading to improved outcomes in assisted reproductive techniques.

• Keywords
• uterinní NK buňky, imunofenotypizace lymfocytů, opakované selhání implantace,
• MeSH
• Killer Cells, Natural MeSH
• Endometrium cytology   MeSH
• Fertilization in Vitro * MeSH
• Abortion, Habitual MeSH
• Immunophenotyping MeSH
• Immunomodulation MeSH
• Humans MeSH
• Flow Cytometry methods   MeSH
• Retrospective Studies MeSH
• Infertility, Female * MeSH
• Check Tag
• Humans MeSH
• Female MeSH

Torze dělohy je pro svou ojedinělost velmi nebezpečná komplikace těhotenství a porodu, často opomíjená, a může v některých případech ohrozit na životě jak rodičku, tak i její dítě. V našem případě bylo termínové těhotenství ukončeno akutním císařským řezem kvůli podezření na HELLP syndrom s peroperačním nálezem torze dělohy o 120°. Děloha byla derotována a zbytek operace byl proveden dle standardního postupu. Následky vzniklého stavu tak byly pro rodičku a její dítě zcela minimální a pooperační stav stabilní a nekomplikovaný. Zařazením i této raritní komplikace do diferenciální diagnostiky akutně vzniklých obtíží s bolestmi epigastria a zvracením v těhotenství můžeme včasně zabránit někdy až fatálním komplikacím pro matku i dítě.

Uterine torsion belongs to one of the most dangerous labor complications also because of its rarity. As it is not common for an obstetrician to come across this state, it is usually not at the very top of the differential diagnostics list when solving acute child delivery complications. However, it is serious enough to pose a lethal threat to both mother and child. In this case, the term gravidity was ended by acute cesarean section because of HELLP syndrome. During the operation, as well as after a complicated delivery and hysterotomy suture uterine torsion of 120 degrees to the right, the patient was diagnosed with detorsion. The rest of the operation was done according to normal standards. Thanks to this very prompt procedure, the aftermath of the described state meant little to no harm to the mother and her child. This case study should highlight the importance of including uterine torsion into differential diagnostics of acute abdominal pain and vomiting to prevent fatal labor complications for the mother and her child.

• Keywords
• torze dělohy,
• MeSH
• Cesarean Section MeSH
• Adult MeSH
• HELLP Syndrome * physiopathology   MeSH
• Pregnancy Complications * MeSH
• Humans MeSH
• Pregnancy MeSH
• Uterus pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Antiphospholipid syndrome (APS) is associated with recurrent pregnancy morbidity, yet the underlying mechanisms remain elusive. We performed multifaceted characterization of the biological and transcriptomic signatures of mouse placenta and uterine natural killer (uNK) cells in APS. Histological analysis of APS placentas unveiled placental abnormalities, including disturbed angiogenesis, occasional necrotic areas, fibrin deposition, and nucleated red blood cell enrichment. Analyses of APS placentas showed a reduced cell proliferation, lower protein content and thinning of endothelial cells. Disturbances in APS trophoblast cells were linked to a cell cycle shift in cytotrophoblast cells, and a reduced number of spiral artery-associated trophoblast giant cells (SpA-TGC). Transcriptomic profiling of placental tissue highlighted disruptions in cell cycle regulation with notable downregulation of genes involved in developmental or signaling processes. Cellular senescence, metabolic and p53-related pathways were also enriched, suggesting potential mechanisms underlying placental dysfunction in APS. Thrombotic events, though occasionally detected, appeared to have no significant impact on the overall pathological changes. The increased number of dysfunctional uNK cells was not associated with enhanced cytotoxic capabilities. Transcriptomic data corroborated these findings, showing prominent suppression of NK cell secretory capacity and cytokine signaling pathways. Our study highlights the multifactorial nature of APS-associated placental pathologies, which involve disrupted angiogenesis, cell cycle regulation, and NK cell functionality.

• MeSH
• Antiphospholipid Syndrome * immunology   pathology   MeSH
• Killer Cells, Natural * immunology   metabolism   MeSH
• Disease Models, Animal * MeSH
• Mice MeSH
• Placenta * metabolism   pathology   MeSH
• Cell Proliferation MeSH
• Gene Expression Profiling MeSH
• Pregnancy MeSH
• Transcriptome MeSH
• Trophoblasts metabolism   pathology   immunology   MeSH
• Uterus * pathology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Circulating endometrial cells (CECs) have emerged as a new biomarker of advanced disease in women with endometriosis. The identification of several subtypes of CECs (e.g., stem cell-like, epithelial, glandular, stromal) has opened the way for characterization of endometriosis-associated CECs. This study focused on the isolation and characterization of CECs and disseminated endometrial cells (DECs) in patients with spontaneous pneumothorax (SP). The primary objective was to differentiate between cancer and non-cancer cells in patients with no previous cancer diagnosis. The MetaCell® size-based separation protocol was used to enrich CECs/DECs. Evaluation of the captured cells by 3D microscopy was performed using a NANOLIVETM microscope using a holographic approach. Based on gene expression analysis (GEA), we can conclude that mitochondria are much more active in primary tumors compared to endometriosis tissue (e.g. MT-ND1, MT-ATP6 genes). The culture of DECs is made of stromal, stem and immune cells. In vitro culture of DECs is characterized by an increase in the epithelial marker KRT18. Similarly, NFE2L2, a proerythroid factor, is also elevated. Further, a significant decrease in the amount of stem and immune cells was observed in the cell culture of DECs. The data presented here show how morphologically plastic the changes in the mitochondrial network can be and how cells can reflect them at the level of gene expression. The markers identified could help in the accompanying diagnostic process of the spontaneous pneumothorax in women of reproductive age.

• MeSH
• Adult MeSH
• Endometriosis * pathology   diagnosis   genetics   MeSH
• Endometrium pathology   metabolism   MeSH
• Humans MeSH
• Mitochondria * metabolism   pathology   MeSH
• Pneumothorax * pathology   diagnosis   MeSH
• Gene Expression Profiling methods   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Předkládáme raritní kazuistiku pacientky, která spontánně otěhotněla a dokončila úspěšně těhotenství po peripartální hysterektomii jedné dělohy při vrozených vývojových vadách dělohy (uterus duplex). Důvodem peripartální hysterektomie bylo život ohrožující krvácení s hemoperitoneem po císařském řezu.

We present a rare case report of a patient with a congenital uterine anomaly – uterus didelphys. Who spontaneously became pregnant and completed the pregnancy successfully after peripartum hysterectomy of one uterus. The reason for the peripartum hysterectomy was a life-threatening hemorrhage with hemoperitoneum after cesarean delivery.

• MeSH
• Cesarean Section methods   MeSH
• Gravidity * MeSH
• Hysterectomy classification   methods   MeSH
• Humans MeSH
• Young Adult MeSH
• Peripartum Period MeSH
• Pregnant People MeSH
• Uterine Didelphys * surgery   diagnosis   complications   MeSH
• Uterus abnormalities   surgery   MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: This study aimed to determine the differences in the cervical load and prevalence of Lactobacillus crispatus DNA, Lactobacillus iners DNA, Gardnerella vaginalis DNA, Sneathia sanguinegens DNA, and Ureaplasma species DNA between pregnant women with preterm prelabor rupture of membranes (PPROM) with and without a history of cervical excisional treatment. We also assessed the changes in the cervical load and prevalence of L. crispatus DNA, L. iners DNA, G. vaginalis DNA, S. sanguinegens DNA, and U. spp DNA. according to the cone length. METHODS: This retrospective study included 132 women with singleton pregnancies complicated by PPROM. For all women, information about the cervical loads of bacterial DNA corresponding to L. crispatus, L. iners, G. vaginalis, S. sanguinegens, and U. spp., which was assessed using PCR, was available. RESULTS: Women with a history of cervical excisional treatment had a higher cervical load of L. iners DNA (4.4 × 106 copies DNA/mL vs. 3.5 × 105 copies DNA/mL, p = .04) and a higher load and prevalence of U. spp. DNA (1.1 × 105 copies DNA/mL vs. 9.6 × 104 copies DNA/mL, p = .03; 2.7% vs. 0.5%, p = .04) than those without a history of cervical excisional treatment. In the subset of women with a history of cervical excisional treatment, those with a cone length 18 mm and more had a lower relative abundance of L. crispatus DNA (6% vs. 89%, p = .02), a higher load and relative abundance of L. iners DNA (1.1 × 107 copies DNA/mL vs. 8.2 × 105 copies DNA/mL, p = .04; 91% vs. 35%, p = .04), and higher loads of G. vaginalis DNA (7.6 × 104 copies DNA/mL vs. 3.2 × 102 copies DNA/mL, p = .02) than those with cone length < 18 mm. CONCLUSIONS: A history of cervical excisional treatment was associated with alterations in the cervical microbiota composition in pregnant women with PPROM.

• MeSH
• Cervix Uteri * microbiology   surgery   MeSH
• DNA, Bacterial analysis   isolation & purification   MeSH
• Adult MeSH
• Gardnerella vaginalis isolation & purification   genetics   MeSH
• Lactobacillus isolation & purification   genetics   MeSH
• Humans MeSH
• Microbiota MeSH
• Fetal Membranes, Premature Rupture * microbiology   epidemiology   MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Ureaplasma isolation & purification   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: The anatomic descriptions and extents of radical hysterectomy often vary across the literature and operative reports worldwide. The same nomenclature is often used to describe varying procedures, and different nomenclature is often used to describe the same procedure despite the availability of guideline and classification systems. This makes it difficult to interpret retrospective surgical reports, analyze surgical databases, understand technique descriptions, and interpret the findings of surgical studies. OBJECTIVE: In collaboration with international experts in gynecologic oncology, the purpose of this study was to establish a consensus in defining and interpreting the 2017 updated Querleu-Morrow classification of radical hysterectomies. STUDY DESIGN: The anatomic templates of type A, B, and C radical hysterectomy were documented through a set of 13 images taken at the time of cadaver dissection. An online survey related to radical hysterectomy nomenclature and definitions or descriptions of the associated procedures was circulated among international experts in radical hysterectomy. A 3-step modified Delphi method was used to establish consensus. Image legends were amended according to the experts' responses and then redistributed as part of a second round of the survey. Consensus was defined by a yes response to a question concerning a specific image. Anyone who responded no to a question was welcome to comment and provide justification. A final set of images and legends were compiled to anatomically illustrate and define or describe a lateral, ventral, and dorsal excision of the tissues surrounding the cervix. RESULTS: In total, there were 13 questions to review, and 29 experts completed the whole process. Final consensus exceeded 90% for all questions except 1 (86%). Questions with relatively lower consensus rates concerned the definitions of types A and B2 radical hysterectomy, which were the main innovations of the 2017 updated version of the 2008 Querleu-Morrow classification. Questions with the highest consensus rates concerned the definitions of types B1 and C, which are the most frequently performed radical hysterectomies. CONCLUSION: The 2017 version of the Querleu-Morrow classification proved to be a robust tool for defining and describing the extent of radical hysterectomies with a high level of consensus among international experts in gynecologic oncology. Knowledge and implementation of the exact definitions of hysterectomy radicality are imperative in clinical practice and clinical research.

• MeSH
• Cervix Uteri MeSH
• Hysterectomy methods   MeSH
• Consensus MeSH
• Humans MeSH
• Genital Neoplasms, Female * MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH