Outcome of antenatal invasive diagnostic tests in a fetal medicine unit with low case load in North Wales, United Kingdom.

The aim of this retrospective cohort study was to review rate of miscarriage following antenatal invasive diagnostic procedures from a unit where relatively low annual numbers of procedures are undertaken. Data were analysed for 201 chorionic villous samplings (CVSs) performed between January 2007 and June 2019 and 511 amniocenteses performed between January 2008 and June 2019, in singleton pregnancies. The miscarriage rates after CVS was 0% at 48 hours, 0.6% at 2 weeks and 2.5% up to 24 weeks of gestation. All four miscarriages following CVS had significant inherent high-risk features, therefore, it would be inappropriate to attribute these losses solely to the procedure itself. None of the women who had an amniocentesis had a miscarriage during the study period. We did not find a causal association between number of invasive procedures performed by an operator and miscarriage rate in our setting even with low annual numbers of invasive procedures.Impact StatementWhat is already known on this subject? Royal College of Obstetricians and Gynaecologists (RCOG) of UK recommends a minimum of at least 30 CVSs or amniocenteses procedures per year for a practitioner in order to maintain skills. A centre performing more fetal invasive procedures has lower miscarriage rates due to more experience of practitioners.What the results of this study add? This study is the first long-term audit data from a smaller fetal medicine unit with relatively low annual case load, suggesting that miscarriage risk may actually be lower than the current understanding. No additional risk of miscarriage or pregnancy loss following fetal invasive procedures even with relatively low annual numbers than that recommended by the RCOG.What the implications are of these findings for clinical practice and/or further research? The findings of this study are important in the era of non-invasive prenatal testing which will see the overall number of fetal invasive procedures decline with time. Competence in safely undertaking antenatal invasive procedure can possibly be maintained with lower annual procedure numbers. Units undertaking low number of antenatal invasive procedure must continuously audit their practice to ensure satisfactory standards and outcomes. More research is needed from smaller units to corroborate or refute the findings of this study.

Prospective cohort study of induction of labor: Indications, outcome and postpartum hemorrhage.

INTRODUCTION: This study was undertaken because of the increasing rate of induction of labor (IOL) in our hospital and its associated higher caesarean section (CS) rates. The objective was to ascertain the incidence, indications, methods, outcome, and complications of IOL, in particular postpartum hemorrhage. METHODS: This was a prospective observational cohort study of women who underwent IOL in a medium-sized district general hospital. Blood loss was measured by the gravimetric method and correlated to postpartum hemoglobin level within 48 hours of birth. RESULTS: A total of 445 women needed IOL (incidence 33%). Common indications were: small for gestational age (SGA) or fetal growth restriction (FGR) (18%), spontaneous rupture of membrane (17%), reduced fetal movement (16%), prolonged pregnancy (15%), and diabetes (13%). In all, 67% women achieved spontaneous vaginal delivery and 18% underwent caesarean section. With regard to blood loss, 62 women (14%) had postpartum hemorrhage (PPH) of >1000 mL and 22 women (4.9%) had a blood loss >1500 mL. The caesarean section rate was higher than the overall emergency caesarean section rate in that year. Incidence of PPH in this cohort was higher than the normal incidence. CONCLUSIONS: Increasing trend of induction of labor (IOL) is due to the changing clinical policy on management of small for gestational age babies, spontaneous rupture of membrane, reduced fetal movement and other complications of pregnancy. There is conflicting evidence on the effect of IOL on caesarean section rates. IOL is a risk factor for PPH. Accurate measurement of blood loss is essential in detecting a fall in hemoglobin which in turn helps in the appropriate management of PPH.

Challenges to professionalism and ethics in perioperative clinical practice.

Perioperative medicine can pose myriad challenges to professionalism and ethical practice. Medicine is a science, but definite end points, and predictable results and outcomes do not consistently occur. There is the potential for error during all steps of a patient's assessment and treatment. Examination findings, laboratory investigations, diagnosis, plans for and outcomes of surgery and long-term outcomes can all be uncertain and/or not meet expectations. Factors including pressures in the workplace, conflicts, ego, prescribed guidelines and pathways, the need to achieve healthcare targets, desire for autonomy and need to maintain multidisciplinary involvement in patient care can lead to an environment in which it is challenging for professionalism and ethics to thrive.

Targeting STAT3 by HO3867 induces apoptosis in ovarian clear cell carcinoma.

Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. Signal transducer and activator of transcription 3(STAT3) expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6). Therefore, this work was planned to investigate the role of STAT3 and examine the efficacy of a novel anti-cancer compound -HO-3867, which is an inhibitor of STAT3, using known OCCC cell lines. Results demonstrate that treatment with HO-3867 decreased expression of pSTAT3 Tyr705 as well pSTAT3 Ser727, while total STAT3 remained constant. STAT3 overexpression increased the migration capability in OVTOKO cells in vitro and led to an increased tumor size when injected in vivo. The inhibitory effect of HO-3867 on cell proliferation and cell survival was accompanied by increased apoptosis, within 24 h post treatment. Treatment with HO-3867 resulted in a decrease in Bcl-2 and increase of cleavage of caspase 3, caspase 7, and PARP, confirming induction of apoptosis after treatment with HO-3867. In addition, HO-3867 significantly inhibited formation of human umbilical vein endothelial cells capillary-like structures and invasion at both 5 and 10 µM concentrations. STAT3 expression plays an important role in the spread of OCCC in vitro as well as in vivo. Thus, we can exploit the STAT3 pathway for targeted drug therapy. Inhibition of pSTAT3 using HO-3867in OCCC cell lines appears to be a promising therapy. This is of utmost importance given the poor response of OCCC to standard chemotherapy regimens.