Prediction of Caesarean Delivery

For expectant parents, a first birth is notable for its unpredictability, and the path to safe labour and delivery is commonly complicated by a requirement for unplanned caesarean delivery. The ability to anticipate an uncomplicated vaginal birth, or to predict the requirement for unplanned caesarean delivery, carries the potential to facilitate optimal birth choices. For example, elective caesarean delivery confers substantially less risk than unplanned caesarean delivery performed during the course of labour. Pre-delivery knowledge of a high predictive risk of requiring intrapartum caesarean delivery could lead to women opting to deliver by elective caesarean delivery, thereby lowering associated risks. Equally, pre-labour knowledge of a high prospect of achieving a successful and uncomplicated vaginal birth could result in enhanced motivation for women to deliver in a less medicalised environment. Predictive risk models have been utilised to good effect in other areas of medicine. The incorporation of a risk predictive tool for intrapartum caesarean delivery would enable women and their caregivers to choose the most appropriate management plan for each woman

Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer

Objective The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. Methods We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). Results We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43–0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22–1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51–1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. Conclusion We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation

First Trimester Prediction of Uteroplacental Disease- Results of the Prospective Handle Study

To assess the ability of non-invasive cardiac output monitoring (NICOM), a novel method of non-invasive maternal hemodynamic assessment using bioreactance, in combination with first trimester biomarkers to predict the evolution of gestational hypertension (GH), pre-eclampsia (PE) and normotensive fetal growth restriction (FGR)

Diagnostic evaluation, monitoring, and perioperative management of spinal cord compression in patients with Morquio syndrome.

Abstract Mucopolysaccharidosis IVA is an autosomal recessive condition caused by mutations in the GALNS gene, which encodes N-acetylgalactosamine-6-sulfatase, also called galactosamine-6-sulfatase (GALNS). A reduction in or absence of effective GALNS leads to faulty catabolism of keratan sulfate and chondroitin-6-sulfate within the lysosome; their accumulation causes cell, tissue, and organ dysfunction. The connective tissue, cartilage, ligaments, and bone of patients with Morquio A syndrome are particularly affected. Patients with Morquio A syndrome are at high risk of neurological complications because of their skeletal abnormalities; many patients are in danger of cervical myelopathy due to odontoid hypoplasia and ligamentous laxity leading to atlantoaxial subluxation. The multisystemic involvement of patients with Morquio A syndrome requires treatment by multidisciplinary teams; not all members of these teams may be aware of the potential for subluxation and quadriparesis. A multinational, multidisciplinary panel of 10 skeletal dysplasia or Morquio A syndrome specialists convened in Miami, FL on December 7 and 8, 2012 to develop consensus recommendations for early identification and effective management of spinal cord compression, for anesthesia and surgical best practices, and for effectual cardiac and respiratory management in patients with Morquio A syndrome. The target audience for these recommendations includes any physician who may encounter a patient with Morquio A syndrome, however doctors who do not have access to the full spectrum of specialists and resources needed to support patients with Morquio A syndrome should attempt to refer patients to a center that does. Physicians who manage Morquio A syndrome or comorbid conditions within specialty centers should review these expert panel recommendations and fully understand the implications of spinal cord instability for their own practices

Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1.

BACKGROUND: Influenza A viruses cause occasional pandemics and frequent epidemics. Licensed influenza vaccines that induce high antibody titers to the highly polymorphic viral surface antigen hemagglutinin must be re-formulated and readministered annually. A vaccine providing protective immunity to the highly conserved internal antigens could provide longer-lasting protection against multiple influenza subtypes. METHODS: We prepared a Modified Vaccinia virus Ankara (MVA) vector encoding nucleoprotein and matrix protein 1 (MVA-NP+M1) and conducted a phase I clinical trial in healthy adults. RESULTS: The vaccine was generally safe and well tolerated, with significantly fewer local side effects after intramuscular rather than intradermal administration. Systemic side effects increased at the higher dose in both frequency and severity, with 5 out of 8 volunteers experiencing severe nausea/vomiting, malaise, or rigors. Ex vivo T-cell responses to NP and M1 measured by IFN-γ ELISPOT assay were significantly increased after vaccination (prevaccination median of 123 spot-forming units/million peripheral blood mononuclear cells, postvaccination peak response median 339, 443, and 1443 in low-dose intradermal, low-dose intramuscular, and high-dose intramuscular groups, respectively), and the majority of the antigen-specific T cells were CD8(+). CONCLUSIONS: We conclude that the vaccine was both safe and remarkably immunogenic, leading to frequencies of responding T cells that appear to be much higher than those induced by any other influenza vaccination approach. Further studies will be required to find the optimum dose and to assess whether the increased T-cell response to conserved influenza proteins results in protection from influenza disease