Extreme Case of Surgical Port Metastasis in Ovarian Cancer.

Ovarian cancer accounts for more deaths than any other malignancy of the female reproductive system. Early diagnosis of this disease is difficult because there are no systematic opportunistic screening methods. At advanced stages, diagnostic laparoscopy is the first step in confirming disease advancement and obtaining samples for genetic and pathologic examination needed to start chemotherapy. Swiftly starting oncological treatment is crucial for increasing the survival rate in these patients. We present the case of a 51-year-old woman with metastatic International Federation of Gynecology and Obstetrics (FIGO) stage IIIC ovarian cancer who had delayed her therapy after initial laparoscopy due to COVID-19 infection and presented with an extreme case of surgical port metastasis.

Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, COSA): study protocol for a multicentre, non-blinded, randomised controlled trial.

INTRODUCTION: Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation. METHODS AND ANALYSIS: This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78. ETHICS AND DISSEMINATION: The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal. TRIAL REGISTRATION: NCT05268640.

Soluble Forms of Immune Checkpoints and Their Ligands as Potential Biomarkers in the Diagnosis of Recurrent Pregnancy Loss-A Preliminary Study.

Immune checkpoints (ICPs) serve as regulatory switches on immune-competent cells. Soluble ICPs consist of fragments derived from ICP molecules typically located on cell membranes. Research has demonstrated that they perform similar functions to their membrane-bound counterparts but are directly present in the bloodstream. Effective control of the maternal immune system is vital for a successful pregnancy due to genetic differences between the mother and fetus. Abnormalities in the immune response are widely acknowledged as the primary cause of spontaneous abortions. In our research, we introduce a novel approach to understanding the immune-mediated mechanisms underlying recurrent miscarriages and explore new possibilities for diagnosing and preventing pregnancy loss. The female participants in the study were divided into three groups: RSA (recurrent spontaneous abortion), pregnant, and non-pregnant women. The analysis of soluble forms of immune checkpoints and their ligands in the serum of the study groups was conducted using the Luminex method Statistically significant differences in the concentrations of (ICPs) were observed between physiological pregnancies and the RSA group. Among patients with RSA, we noted reduced concentrations of sGalectin-9, sTIM-3, and sCD155, along with elevated concentrations of LAG-3, sCD80, and sCD86 ICPs, in comparison to physiological pregnancies. Our study indicates that sGalectin-9, TIM-3, sLAG-3, sCD80, sCD86, sVISTA, sNectin-2, and sCD155 could potentially serve as biological markers of a healthy, physiological pregnancy. These findings suggest that changes in the concentrations of soluble immune checkpoints may have the potential to act as markers for early pregnancy loss.

The Intersection of Human and Veterinary Medicine-A Possible Direction towards the Improvement of Cell Therapy Protocols in the Treatment of Perianal Fistulas.

The effective treatment of perianal fistulizing Crohn's disease is still a challenge. Local administration of mesenchymal stromal cells (MSCs) is becoming a part of accepted treatment options. However, as a fledgling technique, it still can be optimized. A new trend in translational research, which is in line with "One Health" approach, bases on exploiting parallels between naturally occurring diseases affecting humans and companion animals. Canine anal furunculosis (AF) has been indicated as condition analogous to human perianal Crohn's disease (pCD). This narrative review provides the first comprehensive comparative analysis of these two diseases based on the published data. The paper also outlines the molecular mechanisms of action of MSCs which are likely to have a role in modulating the perianal fistula niche in humans, and refers them to the current knowledge on the immunomodulatory properties of canine MSCs. Generally, the pathogenesis of both diseases shares main determinants such as the presence of genetic predispositions, dysregulation of immune response and the relation to intestine microbiota. However, we also identified many aspects which should be further specified, such as determining the frequency of true fistulas formation in AF patients, elucidating the role of TNF and Th17 pathway in the pathogenesis of AF, or clarifying the role of epithelial-to-mesenchymal transition phenomenon in the formation of canine fistulae. Nevertheless, the available data support the hypothesis that the results from testing cell therapies in dogs with anal furunculosis have a significant translational value in optimizing MSC transplants procedures in pCD patients.

sFlt-1/PlGF Ratio Is Not a Good Predictor of Severe COVID-19 nor of Adverse Outcome in Pregnant Women with SARS-CoV-2 Infection-A Case-Control Study.

BACKGROUND: Elevated serum levels of sFlt-1 were found in non-pregnant severe COVID-19 patients. The aim was to investigate sFlt-1/PlGF ratio as a predictor of severe disease and adverse outcome in pregnant women with COVID-19. METHODS: A single-center case-control study was conducted in pregnant women with SARS-CoV-2 infection. SARS-CoV-2-negative pregnant women served as controls. Serum sFlt-1/PlGF ratio was assessed. The primary outcome was severe COVID-19 and the secondary outcome comprised adverse outcomes including severe COVID-19, intensive care unit admission, maternal multiple organ failure, preterm delivery, fetal demise, preeclampsia or hypertension diagnosed after COVID-19, maternal death. RESULTS: 138 women with SARS-CoV-2 infection and 140 controls were included. sFlt-1/PlGF ratio was higher in infected patients (11.2 vs. 24; p < 0.01) and in women with severe disease (50.8 vs. 16.2; p < 0.01). However, it was similar in women with adverse and non-adverse outcome (29.8 vs. 20; p = 0.2). The AUC of sFlt-1/PlGF ratio was 0.66 (95% CI 0.56-0.76) for the prediction of severe COVID-19, and 0.72 (95% CI 0.63-0.79) for the prediction of adverse outcome. CONCLUSIONS: sFlt-1 and sFlt-1/PlGF ratio are related to SARS-CoV-2 infection and the severity of COVID-19 during pregnancy. However, sFlt-1/PlGF ratio is not a good predictor of severe COVID-19 or adverse outcome.

Trends in Diagnosis and Surgical Treatment of Bone Metastases among Orthopedic Surgeons.

BACKGROUND: The proper diagnosis and treatment of bone metastases are essential for patient survival. However, several strategies for the treatment are practiced. Therefore, the aim of the study was to analyze what factors influence the choice of a method of treatment. METHODS: An online survey was conducted within the Polish Society of Orthopedics and Traumatology. It consisted of 45 questions and was divided into four main parts: Participant Characteristics, Diagnosis and Qualification, Treatment, and Clinical Cases. RESULTS: A total number of 104 responses were collected. The most frequently chosen methods were: Intramedullary nail (IMN) + Resection + Polymethyl methacrylate (PMMA) (30.47%) and IMN without tumor resection (42.13%), and in third place, modular endoprosthesis (17.25%). The less experienced group of orthopedic surgeons more often (47.5% vs. 39.5%) decided to perform IMN without tumor resection than the more experienced group (p = 0.046). Surgeons from district hospitals less frequently (13.7% vs. 23.1%) would decide to use modular endoprosthesis than surgeons from university hospitals (p = 0.000076). Orthopedists who performed ≥ 11 bone metastases surgeries per year would more often use modular endoprosthesis (34.8% vs. 13.2%) than those who performed ≤ 10 operations per year (p = 0.000114). CONCLUSION: Experience, place of work, and the number of metastasis surgeries performed during a year may influence the choice of treatment method in patients with bone metastases.

Video-Based Microsurgical Education versus Stationary Basic Microsurgical Course: A Noninferiority Randomized Controlled Study.

BACKGROUND: Repetitive training is essential for microsurgical performance. This study aimed to compare the improvement in basic microsurgical skills using two learning methods: stationary microsurgical course with tutor supervision and self-learning based on digital instructional materials. We hypothesized that video-based training provides noninferior improvement in basic microsurgical skills. METHODS: In this prospective study, 80 participants with no prior microsurgical experience were randomly divided into two groups: the control group, trained under the supervision of a microsurgical tutor, and the intervention group, where knowledge was based on commonly available online instructional videos without tutor supervision. Three blinded expert microsurgeons evaluated the improvement in basic microsurgical skills in both groups. The evaluation included an end-to-end anastomosis test using the Ten-Point Microsurgical Anastomosis Rating Scale (MARS10) and a six-stitch test on a latex glove. Statistically significant differences between groups were identified using standard noninferiority analysis, chi-square, and t-tests. RESULTS: Seventy-seven participants completed the course. Baseline test scores did not differ significantly between groups. After the 4-day microsurgical course, both groups showed statistically significant improvement in microsurgical skills measured using the MARS10. The performed tests showed that data for self-learning using digital resources provides noninferior data for course with surpervision on the initial stage of microsurgical training (7.84; standard deviation [SD], 1.92; 95% confidence interval [CI], 7.25-8.44) to (7.72; SD, 2.09; 95% CI, 7.07-8.36). CONCLUSION: Video-based microsurgical training on its initial step provides noninferior improvement in microsurgical skills to training with a dedicated instructor.

Recent Advances in Assessment and Treatment in Kienböck's Disease.

Kienböck's disease is a rare disease described as progressive avascular osteonecrosis of the lunate. The typical manifestations include a unilateral reduction in wrist motion with accompanying pain and swelling. Besides recent advances in treatment options, the etiology and pathophysiology of the disease remain poorly understood. Common risk factors include anatomical features including ulnar variance, differences in blood supply, increased intraosseous pressure along with direct trauma, and environmental influence. The staging of Kienböck's disease depends mainly on radiographic characteristics assessed according to the modified Lichtman scale. The selection of treatment options is often challenging, as radiographic features may not correspond directly to initial clinical symptoms and differ among age groups. At the earliest stages of Kienböck disease, the nonoperative, unloading management is generally preferred. Patients with negative ulnar variance are usually treated with radial shortening osteotomy. For patients with positive or neutral ulnar variance, a capitate shortening osteotomy is a recommended option. One of the most recent surgical techniques used in Stage III Kienböck cases is vascularized bone grafting. One of the most promising procedures is a vascularized, pedicled, scaphoid graft combined with partial radioscaphoid arthrodesis. This technique provides excellent pain management and prevents carpal collapse. In stage IV, salvage procedures including total wrist fusion or total wrist arthroplasty are often required.

Evaluation of the Optimal Manufacturing Protocols and Therapeutic Properties of Mesenchymal Stem/Stromal Cells Derived from Wharton's Jelly.

Wharton's jelly (WJ) from the umbilical cord (UC) is a good source of mesenchymal stem/stromal cells (MSCs), which can be isolated and used in therapy. Current knowledge shows that even small changes in the cell environment may result in obtaining a subpopulation of cells with different therapeutic properties. For this reason, the conditions of UC transportation, cell isolation, and cultivation and the banking of cells destined for clinical use should be unified and optimized. In this project, we tried various protocols for cell vs. bioptat isolation, banking, and transport in order to determine the most optimal. The most efficient isolation method of WJ-MSCs was chopping the whole umbilical matrix with a scalpel after vessel and lining membrane removal. The optimal solution for short term cell transportation was a multi-electrolyte fluid without glucose. Considering the use of WJ-MSCs in cell therapies, it was important to investigate the soluble secretome of both WJ bioptats and WJ-MSCs. WJ-MSCs secreted higher levels of cytokines and chemokines than WJ bioptats. WJ-MSCs secreted HGF, CCL2, ICAM-1, BDNF, and VEGF. Since these cells might be used in treating neurodegenerative disorders, we investigated the impact of cerebrospinal fluid (CSF) on WJ-MSCs' features. In the presence of CSF, the cells expressed consecutive neural markers both at the protein and gene level: nestin, ß-III-tubulin, S-100-ß, GFAP, and doublecortin. Based on the obtained results, a protocol for manufacturing an advanced-therapy medicinal product was composed.

Interaction between Macrophages and Human Mesenchymal Stromal Cells Derived from Bone Marrow and Wharton's Jelly-A Comparative Study.

Despite intensive clinical research on the use of mesenchymal stromal cells (MSCs), further basic research in this field is still required. Herein, we compared human bone marrow MSCs (BM-MSCs, n = 6) and Wharton's jelly MSCs (WJ-MSCs, n = 6) in their ability to interact with human primary macrophages. Evaluation of secretory potential revealed that under pro-inflammatory stimulation, WJ-MSCs secreted significantly more IL-6 than BM-MSCs (2-fold). This difference did not translate into the effect of MSCs on macrophages: both types of MSCs significantly directed M1-like macrophages toward the M2 phenotype (based on CD206 expression) to a similar extent. This observation was consistent both in flow cytometry analysis and immunocytochemical assessment. The effect of MSCs on macrophages was sustained when IL-6 signaling was blocked with Tocilizumab. Macrophages, regardless of polarization status, enhanced chemotaxis of both BM-MSCs and WJ-MSCs (p < 0.01; trans-well assay), with WJ-MSCs being significantly more responsive to M1-derived chemotactic signals than BM-MSCs. Furthermore, WJ-MSCs increased their motility (scratch assay) when exposed to macrophage-conditioned medium while BM-MSCs did not. These results indicate that although both BM-MSCs and WJ-MSCs have the ability to reciprocally interact with macrophages, the source of MSCs could slightly but significantly modify the response under clinical settings.

Microsurgical Anastomosis Rating Scale (MARS10): A Final Product Scoring System for Initial Microsurgical Training.

BACKGROUND: High cost and ethical controversy of using living models in microsurgical training made non-living models more popular. However, non-living models don't provide appropriate feedback of microsurgical performance. Currently existing Global Rating Scales used for advanced microsurgical skills validation are difficult to apply on non-living model. This study presents a simple instrument for basic assessment of microsurgical anastomosis on non-living model. METHODS: Seventy medical students were divided into 2 groups depending on their prior microsurgical experience. Each participant performed 3 end-to-end anastomoses on chicken femoral artery model. Anastomoses were reviewed by 3 blinded experts and then photographed. Evaluation included a patency tests, longitudinal cut of anastomosis, and the newly proposed tool 10 Point Microsurgical Anastomosis Rating Scale (MARS10). Presented scale consists of 5 factors important for anastomosis closure (anastomosis closure, suture spacing, bites size, knot tying, and cut ends length), graded on 3 point scale (0-2 points). Results were analyzed with analysis of variance, Spearman correlation, and t Student test. RESULTS: Anastomoses evaluated by experts as patent significantly correlated with a high summary score in MARS10 scale (r = 0.73 P < .0001). There was a significant difference in MARS10 score between groups (P < .0001). There were no significant inter-rater differences in scoring among all 3 evaluators (p > .05). CONCLUSIONS: 10 Point Microsurgical Anastomosis Rating Scale is a quick, valid, and reliable tool to assess microsurgical end-to-end arterial anastomoses on non-living model.

HISTORIQUE: Le coût élevé et la controverse éthique liés à l'utilisation de modèles vivants pendant la formation en microchirurgie ont popularisé l'utilisation des modèles non vivants. Cependant, les modèles non vivants ne donnent pas de commentaires appropriés sur l'exécution de la microchirurgie. Les échelles d'évaluation mondiales actuellement utilisées pour valider les habiletés microchirurgicales avancées sont difficiles à appliquer sur des modèles non vivants. La présente étude propose un simple instrument d'évaluation fondamentale de l'anastomose microchirurgicale sur un modèle non vivant. MÉTHODOLOGIE: Les chercheurs ont divisé 70 étudiants en médecine en deux groupes d'après leur expérience microchirurgicale. Chaque participant a effectué trois anastomoses bout à bout sur un modèle d'artère fémorale de poulet. Trois experts ont examiné les anastomoses en aveugle puis les ont photographiées. L'évaluation incluait un test de perméabilité, la coupe longitudinale de l'anastomose et la nouvelle échelle d'évaluation de l'anastomose microchirurgicale en 10 points (MARS10). Cette échelle est composée de cinq facteurs importants pour fermer l'anastomose (fermeture de l'anastomose, espace entre les sutures, dimension des piqûres d'aiguille, exécution des nœuds et longueur des extrémités de fils), classés sur une échelle de trois points (de 0 à 2). Les chercheurs ont analysé les résultats avec l'analyse de variance, la corrélation de Spearman et le test de Student. RÉSULTATS: Les anastomoses évaluées comme perméables par les experts étaient corrélées par un sommaire de cotation élevé dans l'échelle de MARS10 (r = 0,73 P < 0,0001). Il y avait une différence significative du score MARS10 entre les groupes (p < 0,0001). Il n'y avait pas de différences interévaluateur significatives dans les scores des trois évaluateurs (p > 0,05). CONCLUSIONS: L'échelle de MARS10 est un outil rapide, valide et fiable pour évaluer les anastomoses artérielles microchirurgicales bout à bout sur des modèles non vivants.

Differences in Immune Checkpoints Expression (TIM-3 and PD-1) on T Cells in Women with Recurrent Miscarriages-Preliminary Studies.

BACKGROUND: Immune checkpoints are molecules that regulate the function of immune cells and control inflammation processes. An important role in this regard is played by TIM-3/Gal-9 and PD-1/PDL-1 interactions. Previous research performed in a mouse model of pregnancy loss confirmed that blocking TIM-3 could induce fetal loss. Similarly, the PD-1 molecule maintains protective interactions between the mother's immune cells and the fetus. The purpose of this study was to assess the expression of these molecules on a range of T lymphocyte subpopulations from non-pregnant women with recurrent spontaneous abortion (RSA) versus healthy fertile women. METHODS: PBMCs were isolated by gradient centrifugation of blood obtained from 12 healthy women and 24 women with RSA and immediately stained for flow cytometry analysis. Standard immunophenotyping of PBMC was performed with the antibodies against classical lymphocyte markers: CD3, CD4, CD8, and CD56. Immune checkpoints were investigated using antibodies against PD-1(CD279) and TIM-3(CD366). RESULTS: We found that expression of TIM-3 was significantly decreased on CD8+ T lymphocytes in the RSA group, and expression of PD-1 was upregulated on CD4+ T lymphocytes in the RSA group in comparison to the healthy controls. CONCLUSIONS: Considering our findings, therapeutic intervention towards immune checkpoints may be a promising treatment option for recurrent spontaneous abortion.

Endometriotic Peritoneal Fluid Stimulates Recruitment of CD4+CD25highFOXP3+ Treg Cells.

Endometriosis is a common gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus. The disease is associated with disturbed local and systemic immunity. It has been reported that the proportion of CD4+CD25highFOXP3+ Treg cells may be significantly increased in the peritoneal fluid of patients with endometriosis. Therefore, the aim of our study was to investigate whether the proportions of Treg cells in the peritoneal cavity of patients with endometriosis are related to the chemotactic and stimulatory activity of the local peritoneal milieu. The peritoneal fluid was collected from 13 women with ovarian endometriosis and 12 control women without the disease. T cell populations were analyzed by flow cytometry, cytokines and chemokines were evaluated using the cytometric bead kit, and cell chemotaxis was studied by cell migration assay. We confirmed that the proportions of Treg cells are increased in the peritoneal fluid of women with endometriosis as compared to the control women. Endometriosis was also associated with elevated concentrations of IL-6, IL-10, and TGF-ß1/2 as well as CCL20, CXCL8, CXCL9, and CXCL10. We did not reveal any changes in the proportion of peritoneal Th17 cells and concentrations of IL-17A. Peritoneal Treg cells positively correlated with concentrations of TGF-ß, IL-10, and CCL20. Endometriotic peritoneal fluid stimulated chemotaxis of both CD4+ and Treg cells. This chemotactic activity positively correlated with concentrations of CCL20. CCL20 stimulated the migration of Treg cells, and the chemotactic activity of the endometriotic peritoneal fluid was inhibited by neutralizing anti-CCL20 antibodies. These results imply that increased proportions of the peritoneal Treg cells in women with endometriosis may result from attraction and activation by local chemokines and cytokines, especially CCL20 and TGF-ß. Since Treg cells contribute to the immunopathogenesis of endometriosis, their chemotaxis and activation may be considered as a target for therapeutic intervention.

Peritoneal Fluid from Patients with Ovarian Endometriosis Displays Immunosuppressive Potential and Stimulates Th2 Response.

Endometriosis is a common gynaecological disorder characterized by the ectopic growth of endometrial tissue outside the uterine cavity. It is associated with chronic pelvic inflammation and autoimmune reactivity manifesting by autoantibody production and abrogated cellular immune responses. Endometriotic peritoneal fluid contains various infiltrating leucocyte populations and a bulk of proinflammatory and immunoregulatory cytokines. However, the nature and significance of the peritoneal milieu in women with endometriosis still remains obscure. Therefore, the aim of the present study was to investigate the immunoregulatory activity of the peritoneal fluid (PF) from women with endometriosis. The peritoneal fluid samples were collected during laparoscopic surgery from 30 women with and without endometriosis. Immunoregulatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) and chemokines (CCL2, CCL5, CXCL8 and CXCL9) were evaluated in PF and culture supernatants generated by unstimulated and CD3/CD28/IL-2-stimulated CD4+ T cells cultured in the presence of PF. The effect of PF on the generation of Treg and Th17 cells in CD4+ T cell cultures, as well as the natural cytotoxic activity of peripheral blood mononuclear cells, was also investigated. Concentrations of IL-6, IL-10, CCL2, CXCL8 and CXCL9 were significantly upregulated in the PF from women with endometriosis when compared to control women, whereas concentrations of other cytokines and chemokines were unaffected. The culturing of unstimulated and CD3/CD28/IL-2-stimulated CD4+ T cells in the presence of endometriotic PF resulted in the downregulation of their IL-2, IFN-γ, IL-17A and TNF production as compared to culture medium alone. On the other side, endometriotic PF significantly stimulated the production of IL-4 and IL-10. Endometriotic PF also stimulated the release of CCL2 and CXCL8, whereas the production of CCL5 and CXCL9 was downregulated. Endometriotic PF stimulated the generation of Treg cells and had an inhibitory effect on the generation of Th17 cells in cultures of CD4+ T cells. It also inhibited the NK cell cytotoxic activity of the peripheral blood lymphocytes. These results strongly imply that the PF from patients with endometriosis has immunoregulatory/immunosuppressive activity and shifts the Th1/Th2 cytokine balance toward the Th2 response, which may account for deviation of local and systemic immune responses. However, a similar trend, albeit not a statistically significant one, was also observed in case of PF from women without endometriosis, thus suggesting that peritoneal milieu may in general display some immunoregulatory/immunosuppressive properties. It should be stressed, however, that our present observations were made on a relatively small number of PF samples and further studies are needed to reveal possible mechanism(s) responsible for this phenomenon.

Recombinant activated factor VII administration in a patient with congenital lack of factor VII undergoing laparoscopic hysterectomy: A case report.

INTRODUCTION AND IMPORTANCE: Case report of patient with congenital lack of factor VII, suffering from recurrent hematomas and massive menstrual bleedings resulting in severe anemia and multiple hospitalization. CASE PRESENTATION: Patient was diagnosed with endometrial hyperplasia and not responding to hormonal treatment and substitution with recombinant factor VII was not effective to reduce the bleedings. This case describes successful laparoscopic technique of using bipolar coagulation and non-absorbable clips. CLINICAL DISCUSSION: We describe premedication and post-surgical management - which we had to modify from this found in very scarce literature. Despite previous vaginal deliveries without any complications during the puerperium, 20 days after the surgery patient presented with intraperitoneal bleeding after stopping rFVIIa therapy. It was treated medically without the need for re-laparoscopy. CONCLUSION: Laparoscopic surgery is possible in patients with lack and deficiency of FVIIa, but they need close post-operative surveillance and prolonged supplementation with recombinant FVIIa.

Maternal and neonatal serum expression of the vascular growth factors in hyperglycemia in pregnancy.

INTRODUCTION: Hyperglycemia in pregnancy (HIP) occurs in up to 8-17% of pregnancies. Unfavorable impact of the pregnancy induced hyperglycemia on both maternal and fetal tissues is associated with adverse pregnancy outcomes. Vascular growth factors, especially in the early phase of gestation, are considered as one of the most significant molecules that regulate pregnancy course and their serum expression may be altered in patients affected with HIP. MATERIAL AND METHODS: Fifty-five consecutive pregnant patients who underwent elective cesarean section were incorporated into this study. During the surgery, maternal and cord blood samples were collected. Serum expression levels of vascular growth factors: PlGF, VEGF, THBS-2 and Ang-2 were compared among non-HIP and pregnancies affected by gestational diabetes. Subsequently, laboratory results were correlated with obstetric outcomes. RESULTS: There were no statistical differences in maternal characteristics, neonatal outcomes and maternal or neonatal serum levels between study and control groups. However, our results revealed significant differences between fetal and maternal levels of VEGF (p = .028 and .0001), THBS-2 (p = .013 and .0014) and Ang-2 (p = .035 and .048) for HIP and non-HIP group, respectively. CONCLUSIONS: Similar serum expressions of vascular growth factors in and non-HIP and HIP pregnancies point that normal glycemia due to thorough prenatal surveillance may result in normal angio- and vasculogenesis associated with good pregnancy outcomes.

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs).

Tuning stem cells microenvironment in vitro may influence their regenerative properties. In this study Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) were encapsulated in 3D hydrogels derived from human fibrin (FB) or platelet lysate (PL) and the oxygen level was adjusted to physiological normoxia (5% O2). The influence of the type of the scaffold and physiological normoxia conditions was tested on the WJ-MSCs' survivability, proliferation, migratory potential, the level of expression of selected trophic factors, cytokines, and neural markers. Encapsulated WJ-MSCs revealed high survivability, stable proliferation rate, and ability to migrate out of the hydrogel and the up-regulated expression of all tested factors, as well as the increased expression of neural differentiation markers. Physiological normoxia stimulated proliferation of encapsulated WJ-MSCs and significantly enhanced their neuronal, but not glial, differentiation. Ex vivo studies with indirect co-culture of organotypic hippocampal slices and cell-hydrogel bio-constructs revealed strong neuroprotective effect of WJ-MSCs against neuronal death in the CA1 region of the rat hippocampus. This effect was potentiated further by FB scaffolds under 5% O2 conditions. Our results indicating significant effect of oxygen and 3D cytoarchitecture suggest the urgent need for further optimization of the microenvironmental conditions to improve therapeutical competence of the WJ-MSCs population.

Pregnancy Weight Gain as a Predictor of Fetal Wellbeing in Liver Transplant Recipients.

BACKGROUND Gestational weight gain (GWG) is an important index influencing perinatal outcomes. Inappropriate weight gain during pregnancy is strongly associated with multiple pregnancy complications. In pregnant liver transplant recipients whose risk of adverse pregnancy outcomes is already high, this aspect may be even more significant. The present study analyzed the gestational weight gain in female liver transplant recipients and its effect on neonatal complications. MATERIAL AND METHODS A cohort study of retrospective data was performed in the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw. There were 23 patients who fulfilled all inclusion criteria. The gestational weight gain was analyzed in the context of pre-pregnancy BMI, immunosuppression, and perinatal outcomes. RESULTS The preterm delivery rate was 39.13% and GWG increased according to the duration of pregnancy. The model adjusted to week of delivery revealed no association between weight gain and the length of pregnancy (p=0.82). GWG in liver transplant recipients did not affect hypotrophy incidence, adverse perinatal outcomes, or caesarian delivery rate. A positive correlation between GWG and neonatal birth weight was observed (p=0.06). One patient, with coexisting PIH, had a stillbirth at 23 weeks. In all other cases, the 5-min Apgar score was 10 points. CONCLUSIONS Current obstetrical recommendations do not consider patients with chronic diseases undergoing immunosuppressive treatment. Proper counselling and preparing liver transplant recipients for pregnancy, especially optimizing maternal pre-pregnancy BMI, may be an important element in improving perinatal outcomes by lowering the risk of maternal complications. GWG itself is not relevant as a predictor of term gestation, but it might be important in achieving eutrophic fetus growth.

The association between serum metalloproteinase concentration, obesity, and hormone levels in reproductive-aged women.

INTRODUCTION: Increased levels and activity of some matrix metalloproteinases (MMPs) are described in obesity-related vascular diseases. Factors that influence MMP blood concentration are still being investigated. This research aims to evaluate the concentration of most types of MMPs: collagenases (MMP-1, -3, -8, -13), matrilysin (MMP-7), gelatinase (MMP-9), and metalloelastase (MMP-12) in serum of women in reproductive age in relation with their body mass index (BMI), age, oestradiol, and progesterone concentrations. MATERIAL AND METHODS: Blood samples were taken from 54 healthy reproductive-aged women with normal menstrual cycles. The weight and height of all women were measured, and body mass index (BMI) was calculated. Concentration of MMP-1, -3, -7, -8, -9, -12, and MMP-13 was evaluated using a Procarta Immunoassay Kit. Serum concentrations of oestradiol and progesterone were evaluated by immunochemiluminescence (32 in the proliferative and 20 in the secretory phase of menstrual cycle). The results of the study were statistically calculated using Pearson, Spearman, and Kruskal-Wallis tests. RESULTS: Positive correlation between MMP-7, -8, -9, -12, and -13 levels and BMI was demonstrated. Significantly higher concentrations of MMPs were found especially in obese women compared to women with normal BMI. In healthy, regularly menstruating premenopausal women, MMP levels did not correlate with oestradiol and progesterone concentrations. CONCLUSIONS: The results suggest that body mass can influence MMP serum concentration in women with regular menstrual cycles.

Basal and metoclopramide induced prolactin secretion in lean PCOS women.

Polycystic ovary syndrome (PCOS) as well as hyperprolactinemia can cause infertility. In retrospective study the prolactin levels during the oral metoclopramide test among lean PCOS woman according to four phenotypes and free androgen index (FAI) were compared. The study population consisted of 314 lean PCOS women. The population was divided into four groups according to the FAI and menstrual cycle regularity. The group A consisted 126 women with FAI≥5 and irregular menstruation, the group B- 53 patients with FAI≥5 and regular menstruation. Group C- 70 patients with FAI<5 and irregular menstruation, group D - 65 patients with FAI<5 and regular menstruation. The ratio of prolactin value in 120th minute in the metoclopramide test to the basal prolactin value was higher in group D than in groups A and B. The prolactin basal concentration was higher in patients with FAI≥5 than in patients with FAI<5, (262.9 vs 228.9 µIU/ml; p<0.001). The ratio of prolactin in 60th minute (12.3 vs 16.7; p=0.006) and in the 120th minute (10.9 versus 13.3; p<0.001) of the metoclopramide test to the basal prolactin were lower in patients with FAI≥5. The prolactin secretion in lean PCOS women may be associated with their FAI.