Has the introduction of increased genetic prenatal testing affected rates of termination of pregnancy due to fetal abnormality?

Objective: Genetic high-resolution analyses and improved diagnostic imaging have impacted the ability to detect fetal disorders. It is unknown if this resulted in an alteration in the number of terminations of pregnancy due to fetal anomalies (TOPFA). The objective was to describe the incidence and indication of TOPFA.

Fibrinolytic and antibiotic treatment of prosthetic vascular graft infections in a novel rat model.

Objectives: We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy.

Materials And Methods: Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus.

Platelet aggregation in Klinefelter syndrome is not aggravated by testosterone replacement therapy: A longitudinal follow-up study.

Background: Men with Klinefelter syndrome (KS) are routinely offered testosterone replacement therapy (TRT) suggested to potentially promote platelet aggregation and increase cardiovascular risk.

Objective: We investigated platelet aggregation in men with KS before and during TRT.

Materials And Methods: Forty-one adult men with KS participated, of which 20 had no history of TRT at baseline, with 15 completing follow-up after 18 months TRT.

Genetic Variants in the Protein S ( ) Gene and Protein S Deficiency in a Danish Population.

Protein S (PS) deficiency is a risk factor for venous thromboembolism (VTE) and can be caused by variants of the gene encoding PS ( ). This study aimed to evaluate the clinical value of molecular analysis of the gene in PS-deficient participants. We performed Sanger sequencing of the coding region of the gene and multiplex ligation-dependent probe amplification to exclude large structural rearrangements.

Streptococcus agalactiae do not penetrate human chorioamniotic membranes in vitro but alter their biomechanical properties.

Introduction: Vaginal colonization with Streptococcus agalactiae (group B streptococci) is hypothesized to constitute a risk factor for preterm prelabor rupture of membranes. In vitro studies have shown that S. agalactiae strains isolated from infants with neonatal sepsis adhere to chorion cells of the human chorioamniotic membrane.

Systemic versus free antibiotic delivery in preventing acute exogenous implant related infection in a rat model.

We studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat model representing a generic acute exogenous joint infection. We hypothesized that evidence of infection (quantitative colony forming units [CFU], qualitative scanning electron microscopy [SEM], histopathology) (1a) would be reduced with local versus systemic antibiotic, (1b) any antibiotic would be superior to control, (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Study groups included infected and noninfected (1) control (no treatment), (2) systemic ceftriaxone (daily), (3) local tobramycin, and (4) local doxycycline (10 rats/group; power = 0.

Age-stratified reference intervals unlock the clinical potential of circulating cell-free DNA as a biomarker of poor outcome for healthy individuals and patients with colorectal cancer.

Circulating cell-free DNA (cfDNA) has spurred much interest as a biomarker in oncology. However, inter- and intra-individual cfDNA levels vary greatly. Consequently, in order to base clinical decisions on cfDNA measurements, normal reference intervals are essential to avoid that ordinary variation is confused with clinically relevant change.

Optimized tool for evaluation of platelet function measured by impedance aggregometry.

Platelet aggregation measured by impedance aggregometry is highly dependent on platelet count. We previously developed a tool to interpret impedance aggregometry based on the strong linear correlation between platelet counts and platelet aggregation at reduced platelet counts. The present study aimed to optimize the tool by expanding the model to include normal platelet counts.

Deleterious mis-splicing of STK11 caused by a novel single-nucleotide substitution in the 3' polypyrimidine tract of intron five.

Background: Pathogenic variants in STK11, also designated as LKB1, cause Peutz-Jeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation changes, polyposis, and a high risk of cancer.

Methods: A male meeting the clinical diagnostic criteria for Peutz-Jeghers syndrome underwent next-generation sequencing. To validate the predicted splicing impact of a detected STK11 variant, we performed RNA-Seq on mRNA extracted from patient-derived Epstein-Barr virus-transformed lymphocytes treated with cycloheximide to inhibit nonsense-mediated decay ex vivo.

Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential.

Novel and minimally-invasive prostate cancer (PCa)-specific biomarkers are needed to improve diagnosis and risk stratification. Here, we investigated the biomarker potential in localized and metastatic PCa (mPCa) of methylated circulating tumor DNA (ctDNA) in plasma. Using the Marmal-aid database and in-house datasets, we identified three top candidates specifically hypermethylated in PCa tissue: and (specificity/sensitivity: 80%-100%/75-94%).

Local Vancomycin Concentrations after Intra-articular Injection into the Knee Joint: An Experimental Porcine Study.

Intra-articular injection of vancomycin may be an important antimicrobial prophylactic supplement to systemic administration in the prevention of prosthetic joint infections. In eight female pigs, 500 mg of diluted vancomycin was given by intra-articular injection into the knee joint. Microdialysis was used for dense sampling of vancomycin concentrations over 12 hours in the synovial fluid of the knee joint, and in the adjacent femoral and tibial cancellous bone and subcutaneous tissue.

Protein C deficiency; PROC gene variants in a Danish population.

Introduction: Protein C deficiency is a heritable thrombophilia caused by numerous different genetic alterations in the protein C (PROC) gene. We aimed to identify variants causing protein C deficiency in a Danish population.

Material And Methods: Sanger sequencing of the PROC gene was performed in 20 probands and 26 relatives.

SERPINC1 variants causing hereditary antithrombin deficiency in a Danish population.

Introduction: Antithrombin deficiency is associated with increased risk of venous thromboembolism (VTE). We aimed to identify variants causing antithrombin deficiency in a Danish population.

Materials And Methods: We performed Sanger sequencing and, in relevant cases, multiplex ligation-dependent probe amplification analyses, in 46 individuals (23 index cases) with and 9 relatives without antithrombin deficiency.

Evaluation of a standardized protocol for thrombin generation using the calibrated automated thrombogram: A Nordic study.

Introduction: The thrombin generation assay-calibrated automated thrombogram (TGA-CAT) method is used to measure the overall coagulation capacity in plasma. However, the method is still considered to be a research tool, mainly because of its' lack of standardization.

Aim: Our study aimed to further raise the standardization level for the TGA-CAT method by evaluating a detailed standardization protocol and three reference plasmas' (RP)s ability to normalize results.

Semen Quality and Sperm DNA Integrity in Patients With Severe Active Inflammatory Bowel Disease and Effects of Tumour Necrosis Factor-alpha Inhibitors.

Background And Aims: The impact of severe inflammation on semen quality, including sperm DNA integrity, in men with inflammatory bowel disease [IBD] is unknown, as are the potential effects of anti-tumour necrosis factor-alpha [TNF-alpha] therapy. We investigated the influence of severe active IBD and anti-TNF-alpha treatment on semen quality.

Methods: We prospectively included 20 patients admitted with severe active IBD.

Evaluation of platelet function in thrombocytopenia.

Whole blood aggregometry is a functional assay for determination of platelet function. Until now, whole blood aggregometry has not been considered feasible at low platelet counts. Hence, the objectives of the present study were to explore platelet function in thrombocytopenia using a novel index of impedance aggregometry adjusted for platelet count and evaluate the association to platelet function assessed by flow cytometry.

Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus.

Biofilms formed by Staphylococcus aureus is a serious complication to the use of medical implants. A central part of the pathogenesis relies on S. aureus' ability to adhere to host extracellular matrix proteins, which adsorb to medical implants and stimulate biofilm formation.

The Role of Platelets in Venous Thromboembolism.

Multiple factors contribute to the risk of venous thromboembolism (VTE). Platelets have attracted much interest in arterial cardiovascular disease, whereas their role in VTE has received much less attention. Recent evidence suggests that platelets may play a more important role in VTE than previously anticipated.

Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome--a case control study.

Bernard-Soulier syndrome (BSS) is a rare severe autosomal recessive bleeding disorder. To date heterozygous carriers of BSS mutations have not been shown to have bleeding symptoms. We assessed bleeding using a semi-quantitative questionnaire, platelet parameters, PFA-100 closure times, ristocetin response, GP Ib/IX expression and VWF antigen in 14 BSS patients, 30 heterozygote carriers for related mutations and 29 controls.

Complementary effect of fibrinogen and rFVIIa on clotting ex vivo in Bernard-Soulier syndrome and combined use during three deliveries.

Women with Bernard-Soulier syndrome (BSS) are considered to be at high risk of serious bleeding during childbirth. Due to the frequently occurring platelet transfusion refractoriness, alternative prophylactic therapy is required. Using rotational thromboelastometry, we evaluated the whole blood coagulation profile of a pregnant woman with BSS before and after spiking ex vivo with different concentrations of recombinant activated factor VII (rFVIIa) and fibrinogen.

Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts.

Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole blood (WB) clot formation in ITP. Blood from ITP patients (n = 12) was drawn into tubes containing 3·2% citrate and corn trypsin inhibitor 18·3 μg/ml.

Fibrinogen as a hemostatic agent.

Coagulation factor I (fibrinogen) plays an essential role in the hemostatic system by bridging activated platelets and being the key substrate for thrombin in establishing a consolidating fibrin network. Fibrinogen is synthesized in the liver and the plasma concentration is 1 to 5-4.0 g/L.

The role of fibrinogen: a new paradigm in the treatment of coagulopathic bleeding.

Fibrinogen is involved in both primary and secondary hemostasis, playing an important role in platelet aggregation and the establishment of a fibrin network. Recent evidence suggests that very high levels of fibrinogen act as antithrombin and can reduce endogenous thrombin potential and compromise clot stability, particularly following a low tissue factor stimulus. Several laboratory methods for measuring plasma fibrinogen concentrations are available, but results vary depending on the type of method and the use of artificial colloid plasma expanders.