Hemostasis in Pre-Eclamptic Women and Their Offspring: Current Knowledge and Hemostasis Assessment with Viscoelastic Tests.

Pre-eclampsia (PE) is a placenta-mediated disease and remains a major cause of maternal and neonatal mortality and morbidity. As PE develops, normal pregnancy's hypercoagulable balance is disrupted, leading to platelet hyperactivation, excessive pathological hypercoagulability, and perturbed fibrinolysis. This narrative review aims to summarize the current knowledge regarding hemostasis in PE compared with healthy gestation and the potential effects of maternal PE on neonatal hemostasis. Finally, it aims to discuss hemostasis assessments for normal pregnancies and PE, emphasizing the role of viscoelastic tests, namely, thromboelastography (TEG) and thromboelastometry (ROTEM), for monitoring PE-associated hemostatic alterations. The use of TEG/ROTEM for assessing the hemostatic profile of PE women has been little considered, even though conventional coagulation tests (CCTs) have not helped to monitor hemostasis in this population. Compared with normal pregnancy, TEG/ROTEM in PE reveals an excessive hypercoagulability analogous with the severity of the disease, characterized by higher-stability fibrin clots. The TEG/ROTEM parameters can reflect PE severity and may be used for monitoring and as predictive markers for the disease.

Rate of Leiomyosarcomas during Surgery for Uterine Fibroids: 8-Year Experience of a Single Center.

The aim of this study is to investigate the prevalence of occult malignant mesenchymal tumors in patients operated on for uterine fibroids in relation to the surgical approach and type of operation. A retrospective review of all patients that underwent surgery for uterine fibroids (January 2011-December 2018) at the 1st Department of Obstetrics & Gynecology at "Papageorgiou" Hospital. The surgical approach and clinicopathological characteristics were analyzed. A total of 803 patients were operated on: 603 (75.1%) with laparotomy, 187 (23.3%) laparoscopically, and 13 (1.6%) vaginally. Furthermore, 423 (52.7%) patients underwent hysterectomy and 380 (47.3%) myomectomies. Laparoscopy and myomectomy were offered to younger patients with fewer smaller uterine fibroids and were associated with statistically significant shorter hospitalization. The pathological reports revealed: 690 (86%) benign leiomyomas, 32 (4%) cellular leiomyomas, 29 (3.6%) degenerated leiomyomas, 22 (2.7%) adenomyomas, 18 (2.2%) atypical-bizarre leiomyomas, 1 (0.1%) STUMP, 5 (0.65%) endometrial stromal sarcomas, and 6 (0.75%) cases of leiomyosarcomas (LMS). All LMS were preoperatively characterized as suspicious and underwent abdominal hysterectomy. Morcellation was offered in two cases of atypical leiomyomas, with no morcellation-associated complication. Laparoscopy as a valuable surgical approach for young patients with fewer in number and smaller in size fibroids is associated with shorter hospitalization. The risk of unintended morcellation of LMS seems to be very low and can be reduced with careful preoperative work-up but not eliminated.

Modified Nonlinear Hysteresis Approach for a Tactile Sensor.

Soft tactile sensors based on piezoresistive materials have large-area sensing applications. However, their accuracy is often affected by hysteresis which poses a significant challenge during operation. This paper introduces a novel approach that employs a backpropagation (BP) neural network to address the hysteresis nonlinearity in conductive fiber-based tactile sensors. To assess the effectiveness of the proposed method, four sensor units were designed. These sensor units underwent force sequences to collect corresponding output resistance. A backpropagation network was trained using these sequences, thereby correcting the resistance values. The training process exhibited excellent convergence, effectively adjusting the network's parameters to minimize the error between predicted and actual resistance values. As a result, the trained BP network accurately predicted the output resistances. Several validation experiments were conducted to highlight the primary contribution of this research. The proposed method reduced the maximum hysteresis error from 24.2% of the sensor's full-scale output to 13.5%. This improvement established the approach as a promising solution for enhancing the accuracy of soft tactile sensors based on piezoresistive materials. By effectively mitigating hysteresis nonlinearity, the capabilities of soft tactile sensors in various applications can be enhanced. These sensors become more reliable and more efficient tools for the measurement and control of force, particularly in the fields of soft robotics and wearable technology. Consequently, their widespread applications extend to robotics, medical devices, consumer electronics, and gaming. Though the complete elimination of hysteresis in tactile sensors may not be feasible, the proposed method effectively modifies the hysteresis nonlinearity, leading to improved sensor output accuracy.

Combined Anticoagulant Therapy for Prevention of Preeclampsia and Small for Gestational Age Neonates: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review and meta-analysis (SRMA) aims to compare the efficacy of combining low molecular weight heparin (LMWH) and aspirin against aspirin alone in preventing preeclampsia (PE) and small for gestational age (SGA) neonates in women at moderate and high risks. STUDY DESIGN: The included studies were nonrandomized and randomized clinical trials (RCTs) enrolling women at moderate and high risks for developing preeclampsia. PubMed/Medline, Cochrane Library, Embase, and Grey literature (including ClinicalTrials.gov) were searched. RESULTS: Out of 4,762 records, 7 nonrandomized studies and 12 RCTs (enrolling 545 and 1,677 women, respectively) were selected. Although the studies were clinically heterogeneous, the conduction of quantitative analysis was feasible. Regarding RCTs, the odds of early-onset preeclampsia was reduced by 89% (pooled odds ratio [OR] = 0.11, 95% confidence interval [CI]: 0.01-0.93, p = 0.04) in women with thrombophilia, the incidence of SGA neonates below the 5th percentile by 48% (pooled OR = 0.52, 95% CI: 0.28-0.96, p = 0.04) in women with a history of preeclampsia and/or SGA neonates, and the incidence of SGA neonates below the 10th percentile by 31% (pooled OR = 0.69, 95% CI: 0.50-0.96, p = 0.03) in the whole population. CONCLUSION: Concerning the whole studied population, combined anticoagulant therapy is not superior to aspirin alone. However, it may be more effective in preventing early-onset preeclampsia regarding women with thrombophilia, SGA neonates below the 5th percentile regarding women with a history of preeclampsia and/or SGA, and SGA neonates below the 10th percentile in moderate- or high-risk women. The above mixed but promising results need to be envisaged with caution due to the clinical heterogeneity of the included studies which is the main limitation of our research. Nevertheless, the strict and narrow inclusion search criteria, and the appropriate subgroup analysis are its main strengths. More RCTs with homogeneous populations and stricter inclusion criteria are needed to confirm these results. KEY POINTS: · Combined therapy is not superior to aspirin alone.. · Combined therapy in women with thrombophilia may protect against early-onset preeclampsia.. · Combined therapy in moderate/high-risk women may protect against SGA <10th percentile neonates..

Humanin and diabetes mellitus: A review of in vitro and in vivo studies.

Humanin (HN) is a 24-amino acid mitochondrial-derived polypeptide with cyto-protective and anti-apoptotic effects that regulates the mitochondrial functions under stress conditions. Accumulating evidence suggests the role of HN against age-related diseases, such as Alzheimer's disease. The decline in insulin action is a metabolic feature of aging and thus, type 2 diabetes mellitus is considered an age-related disease, as well. It has been suggested that HN increases insulin sensitivity, improves the survival of pancreatic beta cells, and delays the onset of diabetes, actions that could be deployed in the treatment of diabetes. The aim of this review is to present the in vitro and in vivo studies that examined the role of HN in insulin resistance and diabetes and to discuss its newly emerging role as a therapeutic option against those conditions.

Contrast enhanced computed tomography assessment of superficial inguinal lymph node metastasis in canine mammary gland tumors.

Mammary gland neoplasms are predominant in dogs. However, sentinel lymph node (SLN) status assessment criteria have not been established for these cases. In this retrospective, secondary analysis, diagnostic case control study, CT images of 65 superficial inguinal SLNs were obtained before and 1, 3, 5, and 10 min after intravenous administration of contrast agent (iopamidol 370 mgI/mL). The presence and degree of postcontrast enhancement were assessed, by means of the median absolute density value and the maximum absolute density value at any time point in the center and in the periphery of each SLN measured in Hounsfield units (HU), before and after contrast agent administration. These values were compared with histopathological findings postsurgical excision. Receiver operating characteristic analysis was conducted. The absolute density values ranged widely at each time point and within each group of nodes (negative, positive, control group). At all time points, the median density value in the center and in the periphery was significantly higher in metastatic than in non-metastatic SLNs (P ≤ .014). Among the parameters tested, the median absolute density value measured in the periphery of the SLN 3 min after injection showed the highest sensitivity, specificity, and accuracy (AUC) (87.5%, 82.1%, and 92.1% respectively), with a cutoff value of 50.9 HU. The maximum absolute density value at any time point in the center and periphery of the SLNs was also significantly higher in metastatic SLNs compared to non-metastatic (P ≤ .001). With a cutoff value of 59.5 HU, the maximum absolute density value in the periphery of the SLN displayed high sensitivity and specificity (87.5% and 89.3%, respectively). The results of this study support the hypothesis that contrast enhanced CT imaging may aid in the assessment of SLN metastasis in dogs with mammary gland neoplasms.

Are neonatal outcomes of triplet pregnancies different from those of singletons according to gestational age?

OBJECTIVES: Multiple pregnancies sustain the high pace of extreme prematurity. Little evidence is available about triplet gestation given the evolution in their management during the last decades. The aim of the study was to compare the neonatal outcomes of triplets with those of matched singletons in a cohort study. METHODS: An observational retrospective cohort study of triplets and matched singletons born between 2004 and 2017 matched by gestational age was conducted. Additionally, the investigation performed in regard to data from the overall Greek population of interest. The primary outcome was mortality or severe neonatal morbidity based on pregnancy type. RESULTS: A total of 237 triplets of 24-36 weeks' gestation and 482 matched singletons were included. No differences in the primary outcome between triplets and singletons were found. Rates of severe neonatal morbidities did not differ significantly between triplets and singletons. A threshold of 1000 gr for birthweight and 28 weeks' gestation for gestational age determined survival on triplets [OR: 0.08 (95% CI: 0.02-0.40, p=0.0020) and OR: 0.13 (95% CI: 0.03-0.57, p=0.0020) for gestational age and birthweight respectively]. In Greece stillbirths in triplets was 8 times higher than that of singletons (OR: 8.5, 95% CI: 6.9-10.5). From 3,375 triplets, 94 were stillborn, whereas in singletons, 4,659 out of 1,388,273. In our center 5 times more triplets than the expected average in Greece were delivered with no significant difference in stillbirths' rates. CONCLUSIONS: No significant differences were identified in mortality or major neonatal morbidities between triplets and matched singletons highlighting the significance of prematurity and birthweight for these outcomes.

DNA methylation patterns of RAR-ß2 and RASSF1A gene promoters in FNAB samples from Greek population with benign or malignant breast lesions.

BACKGROUND: Promoter hypermethylation is common in Breast Cancer (BC) with studies mainly in histological specimens showing frequent methylation of tumor suppressor genes (TSGs) compared with normal tissues. The aim of this study was to estimate the frequency of promoter methylation of RAR-ß2 and RASSF1A genes in breast FNAB material aiming to evaluate the methylation status of these two genes as biomarker for detecting BC in Greek population. METHODS: FNAB material from 104 patients was collected for cytological evaluation and epigenetic analysis. DNA was extracted and subjected to bisulfite conversion. A methylation-specific PCR was carried out and the final products were separated with electrophoresis in 2% agarose gels. RESULTS: From 104 samples, RASSF1A hypermethylation was observed in 78 (75%) and RAR-ß2 hypermethylation in 64 (61.6%). 84% and 78% of the cases diagnosed with breast malignancy (n = 50) were methylated for RASSF1A and RAR-ß2, respectively. Methylated RASSF1A and RAR-ß2 were also detected in 88.3% and 76.5% in samples diagnosed as suspicious for malignancy (n = 17) and in 57.2% of samples diagnosed with atypia (n = 14). The Odds Ratio for breast malignancy was 4.545 in patients with RASSF1A hypermethylation and 9.167 in patients with RAR-ß2 hypermethylation underlying their promoter's methylation positive correlation with breast malignancy. CONCLUSION: To optimize the sensitivity and specificity of this epigenetic setting, more TSGs related to BC should be gradually imported in our evaluated methylation panel and be validated in a larger study sample with the aim that the obtained epigenetic profiles will provide clinicians with valuable tools for management of BC patients in Greece.

Bilothorax Associated with Bile Peritonitis in a Dog with No Diaphragmatic Disruption: A Case Report.

A 4-year-old intact male mixed-breed dog was presented with vomiting and severe depression of 6-day duration after being struck by a car 2 weeks before presentation. Clinical examination revealed hypothermia, respiratory difficulty, jaundice, and a bicavitary (pleural and peritoneal) effusion. Hematological and biochemical abnormalities included neutrophilic leukocytosis, increased total bilirubin concentration, and increased serum lipase activity. Biochemical and cytological evaluation of both abdominal and thoracic fluids were suggestive of bilious effusions. During celiotomy, a rupture of the cystic duct was observed, which necessitated cholecystectomy. A diaphragmatic rupture was not found. A thoracostomy tube was inserted in the right pleural space, and continuous suction was maintained for 48 hours. The dog was discharged 20 days after surgery and no abnormalities were detected on either blood tests or ultrasonographic examinations of the thorax and abdomen on follow-up examination 7 months after surgery. The presence of a bilothorax should be considered in animals with bile peritonitis, grossly intact diaphragm and pleural effusion. The exact mechanisms of the development of bilothorax are unclear, but the transport of bile through microscopic congenital or acquired weaknesses or defects of the diaphragm, via abdominal lymphatics penetrating the diaphragm and draining into the thoracic lymphatics represent the most probable route.

Psychological stress reduces the immunological benefits of breast milk.

Our study aimed to assess the impact of maternal psychological stress on the immunological components of breast milk. Eighty-nine women participated in the study. We assessed general stress, postpartum-specific stress, negative affectivity, salivary cortisol of mother, and secretory immunoglobulin A (sIgA) levels of breast milk 4-6 weeks after delivery. Controlling for the effects of women's age, weight, number, and duration of feedings, postpartum-specific stress was related to reduced sIgA concentration (R2 = .206, beta = -.275, p = .020). This study suggests that the established link between psychological stress and immunity may also extend to the immunity of the newborn by reducing the immunological benefits of breast milk. It also suggests that breastfeeding might be a potential mechanism of the relationship between maternal stress and the health of the offspring. Findings highlight the need for interventions addressing women during the postpartum period, in order to ensure the mother's well-being and the infant's optimal development.

Surgical management of congenital uterine anomalies (including indications and surgical techniques).

The prevalence of congenital uterine anomalies (CUA) is reported to be 4.3-6.7% in the general population, 3.4%-8% in the infertile population, and 12.6-18.2% of those with recurrent miscarriages. They are the result of abnormal formation, differentiation, and fusion of the Müllerian or paramesonephric ducts during fetal life. To date, various classification systems have been proposed for the categorization of CUA, but the recently introduced ESHRE/ESGE classification seems to be a new, clear, and systematic categorization, which could be the basis for clinicians to rely on when they refer to CUA and their clinical impact either generally or concerning pregnancy outcomes. CUA are apparently related to an impaired reproductive outcome, while their exact clinical impact as well as the effectiveness of their treatment remain considered controversial. Surgery is indicated in women presenting with symptoms related to specific uterine anomalies, especially in those with fertility problems. In this review, indications, surgical techniques for the repair of CUA according to their classification, and fertility and pregnancy outcomes before and after surgery will be thoroughly reviewed.

Three-dimensional ultrasound in the diagnosis and the classification of congenital uterine anomalies using the ESHRE/ESGE classification: a diagnostic accuracy study.

STUDY OBJECTIVE: To estimate the diagnostic accuracy of three-dimensional ultrasonography (3D US) compared to hysteroscopy/laparoscopy, in the investigation of uterine congenital anomalies using the ESHRE/ESGE classification of female genital tract congenital anomalies. DESIGN: Prospective blind, comparative, cohort study. SETTING: University Tertiary Hospital and affiliated private Hospital. PATIENTS AND METHODS: Sixty-two women consecutively referred with a suspected diagnosis of uterine congenital anomalies. The ESHRE/ESGE classification of congenital anomalies of the female genital tract was used for the description of abnormal findings. INTERVENTIONS: All patients underwent (1) 3D US and (2) hysteroscopy with laparoscopy to establish the final diagnosis. RESULTS: Concordance between 3D US and hysteroscopy with laparoscopy about the type and the classification of uterine anomaly was verified in 61 cases, including all those with septate uterus, dysmorphic uterus, bicorporeal, hemi-uterus or unicorporeal, and aplastic uterus and one out of two with normal uterus. For the diagnosis of septate uteri, which was the most common anomaly, the sensitivity of 3D US was 100%, the specificity was 92.3%, the PPV was 98% and the NPV was 100%, with kappa index 0.950. For bicorporeal, dysmorphic uterus, hemi-uteri or unicorporeal and aplastic uterus the sensitivity, specificity, PPV and NPV were all 100% with K = 1.00. Overall, 3D US showed perfect diagnostic accuracy (Kappa index = 0.945) in the detection of congenital uterine anomalies. CONCLUSION: 3D US appears to be a very accurate method for the diagnosis of congenital uterine anomalies.

Efficacy of the National Thalassaemia and Sickle Cell Disease Prevention Programme in Northern Greece: 15-Year Experience, Practice and Policy Gaps for Natives and Migrants.

Hemoglobinopathies constitute the most frequent monogenic disorders worldwide and in Greece. In Greece, carrier frequency is estimated at about 8.0%, resulting in a heavy disease burden in the past. Therefore, the implementation of a national prevention program of the disease was an urgent necessity. Moreover, due to migration flow from different geographic areas in the last two decades, the observed spectrum of underlying mutations was expanded, leading to the adaptation of diagnostic approaches. We report the results of the National Thalassaemia Prevention Programme in Northern Greece, over a 15-year period (2001-2015). In total 33,837 healthy at-risk individuals (individuals or couples, 91.0% Greeks) were screened. We have screened 1598 pregnancies in 371 (23.0%) (10.0% non Greeks), of whom both parents carried gene defects and were offered genetic counseling. Seventy-six fetuses (23.0%) were predicted to be affected by severe forms of the disease. Following informed parental choices, 73 of the above pregnancies were terminated. Meanwhile, within the study period, 58 new thalassemic babies (five non Greeks) were referred to the Thalassaemia and Sickle Cell Disease Care Unit of Northern Greece, reflecting mostly parental unawareness, choice or the program failure. Based on the region's population, the birth rate and the prevalence of the disease, the anticipated number of new cases is about 45 annually. According to our data, four thalassemic newborns were registered annually at a stable rate in the last 15 years, reaching a reduction of 90.0% of new affected births. Overall, the National Thalassaemia Prevention Programme effectively decreased the incidence of affected newborns in our region.

Compound Heterozygosity for Hb Adana (HBA2: c.179G>A) and the -α3.7/αα Thalassemia Deletion in Greece: Clinical Phenotype and Genetic Counseling.

Hb Adana (HBA2: c.179G>A) is found worldwide but is extremely rare and carriers are asymptomatic, with red cell indices similar to α+-thalassemia (α+-thal) carriers. First line screening tests are unable to detect the unstable hemoglobin (Hb). Coinheritance with the α-thal (-α3.7) deletion is herein presented and the challenges involving genetic counseling of couples carrying the mutations are discussed.

First Report of a Coincidental Discovery of Hb Shimonoseki [α54(E3)Gln→Arg, HBA2: c.164A > G (or HBA1)] in a Greek Family.

The rare Hb Shimonoseki [α54(E3)Gln→Arg, HBA2: c.164A > G (or HBA1)] has been reported in Western Japan. Hb Shimonoseki seems to be an innocuous variant and few published data are available. Heterozygous carriers have no clinical or hematological findings. The abnormal hemoglobin (Hb) was detected by high performance liquid chromatography (HPLC) and classic electrophoresis or capillary electrophoresis (CE), but confirmation of the variant is based on molecular studies. This is the first description of Hb Shimonoseki heterozygosity in a Greek family.

Myomas and Adenomyosis: Impact on Reproductive Outcome.

Among uterine structural abnormalities, myomas and adenomyosis represent two distinct, though frequently coexistent entities, with a remarkable prevalence in women of reproductive age. Various mechanisms have been proposed to explain the impact of each of them on reproductive outcome. In respect to myomas, current evidence implies that submucosal ones have an adverse effect on conception and early pregnancy. A similar effect yet is not quite clear and has been suggested for intramural myomas. Still, it seems reasonable that intramural myomas greater than 4 cm in diameter may negatively impair reproductive outcome. On the contrary, subserosal myomas do not seem to have a significant impact, if any, on reproduction. The presence of submucosal and/or large intramural myomas has also been linked to adverse pregnancy outcomes. In particular increased risk for miscarriage, fetal malpresentation, placenta previa, preterm birth, placenta abruption, postpartum hemorrhage, and cesarean section has been reported. With regard to adenomyosis, besides the tentative coexistence of adenomyosis and infertility, to date a causal relationship among these conditions has not been fully confirmed. Preterm birth and preterm premature rupture of membranes, uterine rupture, postpartum hemorrhage due to uterine atony, and ectopic pregnancy have all been reported in association with adenomyosis. Further research on the impact of adenomyosis on reproductive outcome is welcome.

Management of atypical polypoid adenomyomas. A case series.

OBJECTIVE: Atypical polypoid adenomyomas (APAs) are endometrial, non-malignant, focal, and non-invasive lesions that are intriguing for their histological resemblence to invasive endometrioid adenocarcinoma or malignant mixed Müllerian tumor. The aim of this study was to present our clinical experience, regarding the reproductive outcome, the recurrence rate, and the association with hyperplasia and cancer, in a small series of patients with APA. STUDY DESIGN: Retrospective case series of patients treated for APA in a single private hospital setting from 1998 to 2016. All patients underwent diagnostic hysteroscopy and hysteroscopic removal of the lesion. Follow-up was performed annually with endovaginal ultrasonography and hysteroscopy when necessary. RESULTS: Nine patients (mean age: 37.9 years-old ±8.3years) were treated because of menorrhagia, infertility, and incidental asymptomatic endometrial lesions with operative hysteroscopy. Mean follow-up was 10.0 years (±5.8years). Three patients intended for pregnancy and 2 of them had achieved a full term delivery. There were 2 recurrences (22.2%), two cases of atypical endometrial hyperplasia (22.2%), and 2 patients with endometrioid adenocarcinoma (22.2%), all within the first 5 years. CONCLUSIONS: It appears that APAs exhibit a significant recurrence rate and they may be related both to atypical endometrial hyperplasia and endometrial adenocarcinoma; therefore, clinicians should be aware of these lesions in order to individualize treatment according to the patent's age and fertility history.