Monitoring Humoral Response Following BNT162b2 mRNA Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplantation Patients: A Single-Center Prospective Study along with a Brief Review of Current Literature.

Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients-mostly autologous from a single Unit-along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated-p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era.

Application of Biomarkers in Obese Infertile Women: A Genetic Tool for a Personalized Treatment.

This study investigates links between CART and leptin gene expression, FSH receptor Asn680Ser polymorphism, and reproductive hormones in morbidly obese patients under 40 years old, facing infertility, and undergoing bariatric surgery. A total of 29 women were included in this study. A hormonal profile along with detection of CART and leptin gene expression was evaluated before and after bariatric surgery. Additionally, the presence or absence of Asn680Ser of the FSHR gene was studied. Following bariatric surgery, a mean reduction in BMI (16.03 kg/m2) was observed in all women. FSH levels preoperatively varied significantly among genotypes, with medians of 8.1, 9.5, and 10.3 for individuals without polymorphism, heterozygotes, and homozygotes, respectively (p = 0.0408). Post surgery, marginal differences in FSH levels were observed (5.8, 7.1, and 8.2, respectively) (p = 0.0356). E2 and LH levels exhibited no significant genotype-based differences pre and post surgery. Presurgical E2 levels were 29.6, 29.8, and 29.6, respectively (p = 0.91634), while postsurgical levels were 51.2, 47.8, and 47 (p = 0.7720). LH levels followed similar patterns. Our findings highlight bariatric surgery's positive impact on BMI reduction and its potential connection to genetic markers, hormones, and infertility. This suggests personalized treatments and offers a valuable genetic tool for better fertility outcomes in obese individuals.

Prospective Study on the Correlation between CART and Leptin Gene Expression, Obesity, and Reproductive Hormones in Individuals Undergoing Bariatric Surgery.

Obesity, a global health concern affecting 650 million individuals of all ages worldwide, prompts health complications, including fertility issues. This research investigates the impact of bariatric surgery on morbidly obese females under 40, examining the relationship between CART and leptin gene expressions and reproductive hormones. Post-surgery, a significant reduction in BMI (16.03 kg/m2, n = 29) was observed, accompanied by notable hormonal changes. FSH levels showed a mean difference of 3.18 ± 1.19 pre- and post-surgery (p < 0.001), LH levels exhibited a mean difference of 2.62 ± 1.1 (p < 0.001), E2 levels demonstrated a mean difference of 18.62 ± 5.02 (p < 0.001), and AMH levels showed a mean difference of 3.18 ± 1.19 (p < 0.001). High CART and leptin expressions before treatment correlated with lower expressions after treatment. These findings, rooted in statistically significant correlations (CART: rs = 0.51, p = 0.005; leptin: rs = 0.75, p < 0.001), shed light on potential molecular pathways connecting gene expressions with reproductive hormones post-bariatric surgery. Our study uniquely investigates the interplay between genetic markers, infertility, and bariatric surgery in women. It stands out by providing distinctive insights into the development of personalized treatment strategies for obesity-related infertility, contributing to a deeper understanding of this complex medical issue.

MicroRNAs Can Influence Ovarian Cancer Progression by Dysregulating Integrin Activity.

Ovarian cancer is a deadly disease that affects thousands of women worldwide. Integrins, transmembrane receptors that mediate cell adhesion and signaling, play important roles in ovarian cancer progression, metastasis, and drug resistance. Dysregulated expression of integrins is implicated in various cellular processes, such as cell migration, invasion, and proliferation. Emerging evidence suggests that microRNAs (miRNAs) can regulate integrin expression and function, thus affecting various physiological and pathological processes, including ovarian cancer. In this article, we review the current understanding of integrin-mediated cellular processes in ovarian cancer and the roles of miRNAs in regulating integrins. We also discuss the therapeutic potential of targeting miRNAs that regulate integrins for the treatment of ovarian cancer. Targeting miRNAs that regulate integrins or downstream signaling pathways of integrins may provide novel therapeutic strategies for inhibiting integrin-mediated ovarian cancer progression.

Expression of Stemness Markers in the Cervical Smear of Patients with Cervical Insufficiency.

The presence of stem cells has been previously described in human precancerous and malignant cervical cultures. Previous studies have shown a direct interplay of the stem cell niche, which is present in practically every tissue with the extracellular matrix. In the present study, we sought to determine the expression of stemness markers in cytological specimens collected from the ectocervix among women with cervical insufficiency during the second trimester of pregnancy and women with normal cervical length. A prospective cohort of 59 women was enrolled of whom 41 were diagnosed with cervical insufficiency. The expression of OCT-4 and NANOG was higher in the cervical insufficiency group compared to the control group (-5.03 (-6.27, -3.72) vs. -5.81 (-7.67, -5.02) p = 0.040 for OCT4) and (-7.47 (-8.78, -6.27) vs. -8.5 (-10.75, -7.14), p = 0.035 for NANOG. Differences in the DAZL gene were not significantly different (5.94 (4.82, 7.14) vs. 6.98 (5.87, 7.43) p = 0.097). Pearson correlation analysis indicated the existence of a moderate correlation of OCT-4 and Nanog with cervical length. Considering this information, the enhanced activity of stemness biomarkers among pregnant women diagnosed with cervical insufficiency may be predisposed to cervical insufficiency, and its predictive accuracy remains to be noted in larger population sizes.

Pre-Operative Neutrophil-to-Lymphocyte Ratio as a Predictor of Post-Operative Infectious Morbidity in Gynecologic Oncology Patients.

Background: Neutrophil-to-lymphocyte ratio (NLR) has been described as a predictor of progression-free and overall survival, and in the field of peri-operative care it seems to be a factor that can help discriminate patients at risk of developing post-operative complications. In the present study we sought to determine whether NLR is useful as a biomarker in predictive models that aim to identify patients with gynecologic cancer undergoing surgery at risk of developing post-operative infectious morbidity. Patients and Methods: We designed a prospective cohort study that enrolled 208 patients with gynecologic cancer. Post-operative infectious morbidity was evaluated based on a 30-day follow-up interval from the procedure. Results: Forty-three patients (20.5%) developed post-operative infectious morbidity. Using an optimal cutoff value of 1.7 for the pre-operative NLR we observed that the sensitivity of the biomarker was 76.7% and the specificity 73.3% with a produced area under the curve of 0.760 (95% confidence interval [CI], 0.680-0.839). Univariable logistic regression indicated that NLR is a predictor of post-operative morbidity. Cox regression analysis revealed that NLR was the only factor that was associated with the timing of infectious morbidity (hazard ratio [HR], 1.339; 95% CI, 1.180-1.519; p < 0.001). Using random forest analysis and decision trees we achieved a diagnostic accuracy of the predictive model that exceeded 90%. Conclusions: Neutrophil-to-lymphocyte ratio may be a factor that could potentially help evaluate the risk of post-operative morbidity in patients with gynecologic cancer.

The effect of the delivery mode on the evolution of cervical intraepithelial lesions during pregnancy. A meta-analysis.

OBJECTIVE: The aim of the present study was to evaluate the impact of the mode of delivery on the natural evolution of cervical squamous intraepithelial lesions in pregnant patients. METHODS: Α systematic search was conducted in Medline (1966-2021), Cochrane Central Register of Controlled Trials CENTRAL (1999-2021), Scopus (2004-2021), Google Scholar (2004-2021) and Clinicaltrials.gov (2008-2021) along with the reference lists of electronically retrieved full-text papers. All the studies that investigated the correlation of the mode of delivery with the natural evolution of cervical squamous intraepithelial lesions of patients during pregnancy, were included in the present meta-analysis. RESULTS: Eight retrospective studies were finally included, comprising 813 patients whose premalignant lesions were evaluated cytologically, of whom 685 delivered via the vaginal route, and 233 patients whose squamous intraepithelial lesions were evaluated histologically, of whom 162 delivered vaginally. The methodological quality of the included studies ranged between moderate and serious. Regression rates were comparable among women that delivered with caesarean section compared to patients that delivered vaginally, both in the cytological (OR 1.32, 95% CI 0.56, 3.12) and in the histological evaluation (OR 1.87, 95% CI 0.50, 6.96) of the lesions. Subgroup analysis revealed consistent results for all subgroups of premalignant lesions. Finally, the results observed for both the persistence and the progression rates of these lesions were proportional. CONCLUSION: Our meta-analysis suggests that the delivery mode does not alter the natural evolution of squamous intraepithelial lesions in pregnant women and therefore their presence should not determine the mode of delivery.

Cephalad-caudad versus transverse blunt expansion of the low transverse hysterotomy during cesarean delivery decreases maternal morbidity: a meta-analysis.

OBJECTIVE: Cesarean delivery is the most prevalent surgical procedure worldwide, reaching approximately 29.7 million cases in 2015. It is directly associated with an increased risk of maternal and neonatal morbidity rates in the absence of malpresentation. Several techniques have been investigated, and there is evidence that cephalad-caudad expansion of the uterine incision might be associated with improved maternal outcomes compared with traditional transverse blunt expansion. The purpose of this meta-analysis was to evaluate the impact of cephalad-caudad expansion on adverse maternal outcomes, including intraoperative blood loss, risk of uterine vessel injury, and tearing of the lower uterine segment. DATA SOURCES: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials, Google Scholar, and Clinicaltrials.gov databases from inception to January 2021. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that assessed the impact of the cephalad-caudad blunt expansion of the low transverse uterine incision during cesarean delivery rather than those of transverse blunt expansion were selected for inclusion. METHODS: Effect sizes were calculated with the Hartung-Knapp-Sidik-Jonkman random-effects model in R. Trial sequential analysis was performed to evaluate the adequacy of sample sizes. RESULTS: Cephalad-caudad blunt expansion of the uterine incision was associated with a lower prevalence of unintended incision extension (relative risk, 0.62; 95% confidence interval, 0.45-0.86) and uterine vessel injury (relative risk, 0.55; 95% confidence interval 0.41-0.73). However, these complications were not accompanied by the increased need for additional suture placement (relative risk, 0.62; 95% confidence interval, 0.31-4.12) or transfusion rates (relative risk, 0.75; 95% confidence interval, 0.28-2.03). Similarly, the intraoperative duration was comparable with cases treated with transverse blunt expansion (mean difference = -0.45 minutes; 95% confidence interval -2.12 to 1.21) and the risk of intentional incision extension in the form of an inverted T (relative risk, 0.38; 95% confidence interval, 0.09-1.52). Trial sequential analysis revealed that the required sample size was reached in the unintended incision extension and uterine vessel injury outcomes. CONCLUSION: The findings of our study suggested that cephalad-caudad blunt expansion of the uterine incision is superior to transverse expansion in terms of reducing unintended incision extension and uterine vessel injury.

Galectins-1, -3, -7, -8 and -9 as prognostic markers for survival in epithelial ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: Galectins are a family of proteins that have recently emerged as regulators of cancer biology. OBJECTIVES: To investigate the impact of peritumoral and tumoral galectin expression on ovarian cancer prognosis. SEARCH STRATEGY: We searched Medline, Cochrane, and EMBASE databases from inception until March 22, 2020. SELECTION CRITERIA: All studies correlating galectins and ovarian cancer prognosis were selected. DATA COLLECTION AND ANALYSIS: The literature search presented 11 studies, which contained 1034 patients. Meta-analysis was performed with RevMan 5.3 software. MAIN RESULTS: Studies were stratified into two groups depending on the location of galectin expression (peritumoral stroma or nucleus/cytoplasm of tumor cells). Tumoral galectin-7 and galectin-9 expression was significantly associated with poor overall survival (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.32-3.21, P = 0.001; OR 1.71, 95% CI 1.27-2.30, P < 0.001, respectively). The total effect of high tumoral expression of galectins in overall survival and progression-free survival was significant (OR 1.51, 95% CI 1.02-2.23, P = 0.04; OR 2.76, 95% CI 1.73-4.40, P < 0.001, respectively). CONCLUSIONS: Our results suggest that galectins are implicated in ovarian cancer prognosis; however, further research is needed to ascertain their actual importance as well as their diagnostic accuracy.

PIK3CA Mutations and Their Impact on Survival Outcomes of Patients with Cervical Cancer: A Systematic Review.

INTRODUCTION: Several studies have implicated the PIK3/AKT pathway in the pathophysiology of cancer progression as its activation seems to be aberrant in several forms of cancer. The purpose of the present systematic review is to evaluate the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer. METHODS: We used the Medline (1966-2020), Scopus (2004-2020), ClinicalTrials.gov (2008-2020), EMBASE (1980-2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2020), and Google Scholar (2004-2020) databases in our primary search along with the reference lists of electronically retrieved full-text papers. Statistical meta-analysis was performed with the RevMan 5.3 software. RESULTS: Overall, 12 articles were included in the present study that comprised 2,196 women with cervical cancer. Of those, 3 studies did not report significant differences in survival outcomes among patients with mutated versus wild-type PIK3CA tumors, 5 studies reported decreased survival outcomes, and 3 studies revealed increased survival rates. The meta-analysis revealed that patients with the mutated PIK3CA genotypes had worse overall survival compared to patients with wild-type PIK3CA (HR 2.31; 95% CI: 1.51, 3.55; 95% PI: 0.54, 9.96; data from 3 studies) and the same was observed in the case of DFS rates (HR 1.82; 95% CI: 1.47, 2.25; 95% PI: 1.29, 2.56; data from 4 studies). CONCLUSION: Current evidence concerning the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer is inconclusive, although the majority of included studies support a potential negative effect, primarily among those with squamous cell carcinoma tumors.

Osteonectin as a screening marker for pancreatic cancer: A prospective study.

Objective Osteonectin plays a central role in various processes during the development of pancreatic adenocarcinoma. This prospective pilot study was performed to determine the feasibility of serum osteonectin as a screening tool for pancreatic cancer. Methods Blood samples were collected from 15 consecutive patients with newly diagnosed pancreatic cancer and 30 matched healthy controls. Serum osteonectin was measured using an osteonectin enzyme-linked immunosorbent assay kit. The primary outcomes were the diagnostic performance of serum osteonectin and the threshold value for differentiation of patients from controls. Results The median/quartile range of serum osteonectin in patients and controls were 306.8/288.5 ng/mL and 67.5/39.8 ng/mL, respectively. Osteonectin concentrations significantly differed among the study groups. A plasma osteonectin concentration of >100.18 ng/mL as selected by the receiver operating characteristic curves demonstrated an estimated area under the curve of 86% for prediction of pancreatic cancer. Tumour size was a significant predictor of serum osteonectin. A statistically significant difference in serum osteonectin between T1/T2 and T3/T4 tumours was found. Post-hoc comparisons revealed statistically significant differences in the serum osteonectin among the control, T1/T2, and T3/T4 groups. Conclusion Osteonectin may be used as a screening tool for pancreatic cancer, although this must be validated in prospective studies.

Potential Prediction of Acute Biliary Pancreatitis Outcome on Admission.

OBJECTIVES: This pilot study aimed to determine the feasibility of serum values of osteonectin, adiponectin, transforming growth factor beta 1, and neurotensin being used in clinical practice to predict the severity of acute pancreatitis. METHODS: Blood samples were collected from 45 consecutive newly diagnosed acute pancreatitis patients and 30 matched healthy controls. The 2 groups were matched according to age, sex, weight, height, diabetes, smoking, and alcohol consumption. The aforementioned markers were measured using enzyme-linked immunosorbent assay kits. RESULTS: Characteristics of acute pancreatitis patients and healthy controls were comparable. Osteonectin values differed significantly (P < 0.0001). Median/lower quartile/upper quartile of osteonectin levels for acute pancreatitis patients and healthy controls were 263.5/110.3/490.36 and 63.2/46.1/87.2 ng/mL, respectively. Two patients died, 1 patient underwent necrosectomy, and 4 patients had a prolonged intensive care unit/hospital stay. Acute Physiology and Chronic Health Evaluation II and Systemic Inflammatory Response Syndrome scores neither predicted serum values of any of the measured substances nor the clinical outcome (need for intervention, prolonged intensive care unit/hospital stay and mortality). Osteonectin was the only independent predictor for clinical outcome (P = 0.007). CONCLUSIONS: Serum osteonectin strongly discriminates healthy individuals from acute pancreatitis patients. Serum osteonectin shows promise in the prediction of the clinical outcome.

The influence of delayed cord clamping and cord milking on inflammatory cytokines in umbilical vein and neonatal circulation.

INTRODUCTION: The purpose of the present study was to compare the levels of tumor necrosis factor α (TNF-α), and interleukins (IL) 1, 6, 8 and 10 in the umbilical cord and neonatal circulation among neonates with early and late cord clamping. MATERIAL AND METHODS: A consecutive series of 76 cases of uncomplicated pregnancy and an uneventful parturition was evaluated. In 40 cases, delayed cord clamping was used and in the remaining 36, early cord clamping was practiced. Blood samples were collected from the umbilical vein immediately after cord clamping and at 24 h from the median cubital or basilic vein of the neonate. RESULTS: Significant differences were noted in the hematocrit and hemoglobin levels at 24 h that favored delayed clamping. None of the evaluated markers of inflammation differ between the two groups. Spearman's rho revealed a significant correlation between umbilical cord TNF-α and TNF-α neonatal values at 24 h (r = 0.551, p = 0.022) in the early clamped group. Significant correlations were also noted between umbilical cord TNF-α and TNF-α neonatal values at 24 h (r = 0.728, p = 0.001), umbilical cord IL-10 and neonatal IL-10 at 24 h (r = 0.487, p = 0.047) and umbilical cord IL-1b and neonatal IL-1b at 24 h (r = 0.516, p = 0.034). CONCLUSIONS: Delayed cord clamping or cord milking does not alter the levels of inflammatory cytokines in cord blood and neonatal serum. Future studies should evaluate the impact of delayed cord clamping in selected high-risk pregnancies.

Novel Inflammatory Markers in Hyperlipidemia: Clinical Implications.

Hyperlipidemia is characterized by abnormally increased plasma of any or all lipids and /or lipoproteins and is a confirmed risk factor for the formation of atherosclerosis. Inflammation plays a crucial role in the formation and progression of atherosclerosis and consequently on cardiovascular diseases. Nowadays, the effective role of the immune system and subsequently of systemic inflammation is well established. Multiple levels of evidence from experimental models and histopathologic assessment of tissues to systemic biomarkers and epidemiologic or clinical associations have revealed that inflammation is one of the basic mechanisms in the destabilization of the atherogenetic plaque which leads to clinical events. Several inflammatory markers are affiliated with lipids level and the process of atherosclerosis. The most known of them are interleukin 6 and interleukin 1ß, C-reactive protein, tumor necrosis factor-alpha, pentraxin3, serum amyloid A, sCD40, adhesion molecules, monocyte chemoattractant protein-1, sEndoglin, PAPP-A, chemokine 16, insulin like growth factor, lipoprotein-associated phospholipase A2 and galectin 3 but their role in atherogenesis is not well established for all of them. As atheromatosis is one of the main causes of death all over the world, in upcoming studies it will be useful to specify the exact role of these markers in this process in order to have a better prognosis, diagnosis and understanding of this disorder. The aim in this review is to study the literature on the novel inflammation markers of hyperlipidemia according to their clinical implications.

Comparison of inflammatory responses to a soccer match between elite male and female players.

The aim of this study was to compare the inflammatory responses between male and female soccer players for a period of 48 hours after an official match. Blood samples were taken from 83 subjects (22 elite male and 21 elite female soccer players and 20 male and 20 female inactive individuals) in the morning of the game day, immediately after the soccer game and 24 and 48 hours after the match. Average relative exercise intensity during the match was similar in male and female players, as indicated by mean heart rate that was 86.9 ± 4.3 and 85.6 ± 2.3% of maximal heart rate (p = 0.23), respectively. Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) increased 2- to 4-fold above resting values, peaking immediately after the match. C-reactive protein (CRP) and creatine kinase peaked 24 hours after the match. Interleukin 6, CRP, and creatine kinase responses were similar in male and female players, but the peak in TNF-α was 18% higher in male players. Interleukin 6, TNF-α, and CRP at rest were lower in male and female players compared with the control subjects, suggesting a protective effect of regular exercise training regarding the inflammatory profile. The results of this study show that a soccer match induces significant inflammatory responses in both male and female players, with only TNF-α peak values being lower in females. Because of the effects of inflammatory responses on performance and health of the players, it is suggested that coaches and trainers should adjust exercise training programs after a match to promote recovery and protect the athletes' health.

Invasive diagnostic procedures and risk of hypertensive disorders in pregnancy.

OBJECTIVE: To determine whether the risk of hypertensive complications differs among low-risk women who undergo prenatal diagnosis via chorionic villus sampling (CVS) and amniocentesis. METHODS: In a retrospective study, data were analyzed from women who underwent prenatal diagnosis by CVS or amniocentesis at Alexandra Maternity Hospital, Athens, Greece, between 1998 and 2011. All women had either transabdominal CVS at 10-13 weeks of pregnancy with a 20-gauge needle, or amniocentesis at 17-21 weeks with a 22-gauge needle, both under direct ultrasound guidance. Only women who had cytogenetically normal pregnancies and delivered at the study hospital were included. The main outcome measure was the development of hypertensive complications. RESULTS: Overall, 3243 women who underwent CVS and 6875 woman who underwent amniocentesis met the inclusion criteria, and their outcomes were analyzed. In total, 237 women (2.3%) developed hypertensive disorders during their pregnancy. The incidence of pre-eclampsia (2.4% vs. 0.8%) and total hypertensive disorders (3.8% vs. 1.7%) was significantly higher (P<0.001) in the CVS group than in the amniocentesis group. CONCLUSION: Women who underwent CVS had a significantly higher risk of developing hypertensive disorders in comparison to those who underwent amniocentesis. This finding warrants further investigation via a well-designed prospective randomized trial.

Amniotic fluid interleukin-6 and tumor necrosis factor-alpha at mid-trimester genetic amniocentesis: relationship to intra-amniotic microbial invasion and preterm delivery.

OBJECTIVE: To determine the value of amniotic fluid interleukin-6 (AF IL-6) and tumor necrosis factor-alpha (AF TNF-alpha) in the diagnosis of microbial invasion of the amniotic cavity and in the prediction of preterm delivery (PTD). STUDY DESIGN: Following amniocentesis, a sample of amniotic fluid was sent for aerobic and anaerobic bacterial cultures along with Ureaplasma urealyticum culture and it was also assessed for IL-6 and TNF-alpha. RESULTS: Forty-eight women who delivered preterm (<37 weeks) were matched with 96 controls. The AF IL-6 and TNF-alpha concentrations of women with spontaneous PTD were significantly higher than those who delivered at term (IL-6: 176.3 pg/ml [130.6-208.6] vs. 52.3 pg/ml [37.2-92.3]; TNF-alpha: 8.8 pg/ml [7.2-10.7] vs. 5.5 pg/ml [5.0-6.3]). AF IL-6 and TNF-alpha concentrations of >99.3 pg/ml and of >6.6 pg/ml respectively, had a sensitivity of 89.6% and 81.3% and a specificity of 80.3% and 79.2% for the prediction of spontaneous PTD. Moreover, AF IL-6 and TNF-alpha concentrations of >99.3 pg/ml and of 6.3 pg/ml respectively, had a sensitivity of 91.9% and 78.4% and a specificity of 73.8% and 70.1% for the prediction of a positive AF culture. CONCLUSIONS: Elevated mid-trimester concentrations of AF IL-6, or/and of TNF-alpha can identify women at risk for intra-amniotic infection and for spontaneous PTD.

Thrombomodulin: from haemostasis to inflammation and tumourigenesis.

Thrombomodulin (TM), a transmembrane endothelial receptor, participates in coagulation, in inflammation, in cancer and plays a role during embryogenesis. The nucleotide sequence of the TM cDNA allows the structure of this protein to be visualized. The protein starts with a signal peptide, followed by the N-terminal globular domain, six repeats of epidermal growth factor-like sequence, a serine/threonine-rich region, a transmembrane domain and a cytoplasmic domain. High-resolution nuclear magnetic resonance (NMR) spectroscopy was employed to define the exact thrombin-binding region. Residues Y(413)ILDD(417) and D(423)IDE(426) are crucial for binding to thrombin; the two critical amino acids for thrombin binding, Ile(414) and Ile(424), are brought into spatial proximity by beta-sheet structure. There also exist some residues for co-factor activity, namely Asp(349), Glu(357), Tyr(358), Phe(376) and Met(388). The complex transcriptional and post-transcriptional control of TM underline its importance in a wide variety of biological systems and pathophysiological processes.