The role of the PLGF in the prediction of the outcome in pregnancies with a small for gestational age fetus.

PURPOSE: To explore the value of measuring maternal serum PLGF in the prediction of the outcome of small for gestational age fetuses (SGA). METHODS: Singleton pregnancies referred with suspicion of SGA in the third trimester were included if they had: no indication for nor signs of imminent delivery, fetal abdominal circumference (AC) at or below the 10th centile and/or estimated fetal weight (EFW) at or below the 10th centile and/or umbilical artery pulsatility index (Umb-PI) at or above the 90th centile for gestation. Women with pre-eclampsia at presentation were excluded. Maternal blood was drawn at the first (index) visit and analyzed retrospectively. RESULTS: Fifty-one fetuses were examined. Multiple regression analysis showed that family history of microsomia, index EFW and PLGF were significant predictors of the birthweight centile; index femur length centile and PLGF were significant predictors of pre-eclampsia; PLGF and index systolic blood pressure were significant predictors of iatrogenic preterm delivery < 37 weeks, whereas PLGF and index EFW were significant predictors of birthweight ≤ 5th centile and admission to the neonatal intensive care unit. For all outcomes, the addition of maternal-fetal parameters did not improve the prediction compared to PLGF alone. Using a cutoff of 0.3 MoM for PLGF would identify 94.1% of the pregnancies with iatrogenic preterm delivery and/or intra-uterine death and all of the cases that developed pre-eclampsia, for a screen positive rate of 54.9%. Women with PLGF ≤ 0.3 MoM had a poor fetal/maternal outcome (iatrogenic preterm delivery, pre-eclampsia, intra-uterine death) in 61.5% of cases. CONCLUSION: In pregnancies complicated by SGA, PLGF identifies a very high-risk group that may benefit from intense surveillance.

sFLT1, PlGF, the sFLT1/PlGF Ratio and Their Association with Pre-Eclampsia in Twin Pregnancies-A Review of the Literature.

Twin pregnancies demonstrate a 2-3-fold higher chance of developing PE compared to singletons, and recent evidence has demonstrated that the sFLT1/PIGF ratio is strongly associated with PE, adverse pregnancy outcomes, as well as imminent deliveries due to PE complications. The primary objective of this systematic review was to summarise the available data on the levels of sFLT1, PlGF and their ratios in twin pregnancies and to investigate their association with the development of PE, adverse pregnancy outcomes and the timing of the delivery. A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. sFLT1 levels and the sFLT1/PIGF ratio appeared higher in twins compared to singleton pregnancies, especially in the third trimester, while PlGF levels appeared higher up until the third trimester, with their values showing no difference or being even lower than in singletons thereafter. The sFLT1/PIGF ratio has been reported to be an independent marker of adverse outcomes related to pre-eclampsia and is associated with the mean time until delivery in an inverse manner. Further research is required in order to establish the optimal sFLT1/PIGF cut-off values and to stratify the risk of adverse outcomes in twin pregnancies.

Development and Validation of Blood-Based Predictive Biomarkers for Response to PD-1/PD-L1 Checkpoint Inhibitors: Evidence of a Universal Systemic Core of 3D Immunogenetic Profiling across Multiple Oncological Indications.

BACKGROUND: Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICIs) remain limited to only a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetic and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveal a highly prevalent molecular profile predictive of response to PD-1/PD-L1 ICIs. A clinical blood test based on a set of eight (8) 3D genomic biomarkers has been developed and validated on the basis of an observational trial to predict response to ICI therapy. METHODS: The predictive eight biomarker set is derived from prospective observational clinical trials, representing 280 treatments with Pembrolizumab, Atezolizumab, Durvalumab, Nivolumab, and Avelumab in a broad range of indications: melanoma, lung, hepatocellular, renal, breast, bladder, colon, head and neck, bone, brain, lymphoma, prostate, vulvar, and cervical cancers. RESULTS: The 3D genomic eight biomarker panel for response to immune checkpoint therapy achieved a high accuracy of 85%, sensitivity of 93%, and specificity of 82%. CONCLUSIONS: This study demonstrates that a 3D genomic approach can be used to develop a predictive clinical assay for response to PD-1/PD-L1 checkpoint inhibition in cancer patients.

Association of human herpes, papilloma and polyoma virus families with bladder cancer.

The aim of the present study was to assess the possible etiologic role of human papillomavirus (HPV), human herpes virus (HHV) and the human polyoma virus families (BKV and JCV) in the tumourigenesis of bladder cancer. Thirty biopsy specimens from patients with different grades and stages of bladder cancer, who underwent transurethral bladder cancer resection, and 30 normal bladder mucosa specimens were analysed using polymerase chain reaction (PCR) for the detection of the above three virus family members. The presence of HPV was determined in all specimens with nested PCR and real-time quantitative PCR. All cancerous specimens, including the control group, were found to be negative both by PCR and real-time qPCR for the presence of HPV DNA, whilst all samples examined by PCR tested negative for the presence of HSV-1,2 Varicella zoster virus and HSV-7 DNA. Cytomegalovirus, HHV-6 and HHV-8 exhibited similar incidence in sample positivity in both cancerous and healthy tissues. EBV showed a higher prevalence in bladder cancer specimens compared to healthy tissue (p = 0.048), whilst BKV and JCV were detected only in tumour samples. The presence of EBV in a significant proportion of bladder tumours indicates the etiological role of this virus in cancer tumourigenesis.

Repair of an inguinoscrotal hernia containing the urinary bladder: a case report.

INTRODUCTION: Cases of patients with inguinoscrotal hernia containing the urinary bladder are very rare. These patients usually present with frequent episodes of urinary tract infection, difficulty in walking, pollakisuria and difficulty in initiating micturition because of incarceration of the urinary bladder into the scrotum. CASE PRESENTATION: We describe the case of an 80-year-old Caucasian man with an incarcerated urinary bladder into the scrotum who underwent surgical repair with mesh. CONCLUSIONS: Diagnosis of such cases often requires not only clinical examination but also specialized radiological examinations to show the ectopic position of the urinary bladder. Surgical repair in these patients is a real challenge for surgeons.

Implication of RAF and RKIP genes in urinary bladder cancer.

RKIP has been shown to regulate the RAS-RAF-MEK-ERK kinase cascade acting as modulator of apoptosis and metastasis in prostate cancer. Our goal was to examine the expression of the RAF (A-RAF, B-RAF and RAF-1) and RKIP genes in urinary bladder cancer. Microarray analysis and qPCR was employed to investigate the expression of RAF and RKIP, in 30 patients with transitional cell carcinoma (TCC) of the urinary bladder vs. the corresponding levels of adjacent normal tissue. Computational analysis was also performed on Gene Expression Omnibus (GEO) datasets, to unravel differences in the expression of RAF or RKIP between tumor and control samples, and between superficial and muscle invasive tumors. Microarray analysis revealed >2-fold expression of BRAF and RKIP in T2, T3, grade III tumors vs. controls. B-RAF over-expression was verified by qPCR in pT1, grade III tumors vs. their normal counterparts (p = 0.016). qPCR revealed a significant RKIP reduction in TCC vs. normal tissue (p = 0.002 and p < 0.001 for T1, grade II and Ta-T1, grade III, respectively); All RAF genes were positively correlated among each other (A-RAF/B-RAF, p = 0.003; A-RAF/RAF-1, p < 0.001; B-RAF/RAF-1, p = 0.050), whereas B-RAF was negatively correlated with RKIP in TCC (p = 0.050). Further computational analysis revealed different expression profiles for the genes of interest, among muscle invasive carcinomas, superficial TCCs, cystectomy specimens and normal tissue. The reduced RKIP mRNA levels in TCC and the elevated levels of B-RAF in pT1, grade III tumors vs. normal tissue, corroborate that these genes are involved in the pathogenesis of urinary bladder cancer.