Development of a single-visit protocol for the management of pregnancy of unknown location following in vitro fertilization: a retrospective study.

STUDY QUESTION: Can women with pregnancy of unknown location (PUL) following in vitro fertilization (IVF) be risk-stratified regarding the subsequent need for medical intervention, based on their demographic characteristics and the results of serum biochemistry at the initial visit? SUMMARY ANSWER: The ratio of serum hCG to number of days from conception (hCG/C) or the initial serum hCG level at ≥5 weeks' gestation could be used to estimate the risk of women presenting with PUL following IVF and needing medical intervention during their follow-up. WHAT IS KNOWN ALREADY: In women with uncertain conception dates presenting with PUL, a single serum hCG measurement cannot be used to predict the final pregnancy outcomes, thus, serial levels are mandatory to establish a correct diagnosis. Serum progesterone levels can help to risk-stratify women at their initial visit but are not accurate in those taking progesterone supplementation, such as women pregnant following IVF. STUDY DESIGN, SIZE, DURATION: This was a retrospective study carried out at two specialist early pregnancy assessment units between May 2008 and January 2021. A total of 224 women met the criteria for inclusion, but 14 women did not complete the follow-up and were excluded from the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We selected women who had an IVF pregnancy and presented with PUL at ≥5 weeks' gestation. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 30/210 (14.0%, 95% CI 9.9-19.8) women initially diagnosed with PUL required surgical intervention. The hCG/C was significantly higher in the group of women requiring an intervention compared to those who did not (P = 0.003), with an odds ratio of 3.65 (95% CI 1.49-8.89, P = 0.004). A hCG/C <4.0 was associated with a 1.9% risk of intervention, which accounted for 25.7% of the study population. A similar result was obtained by substituting hCG/C <4.0 with an initial hCG level <100 IU/l, which was associated with 2.0% risk of intervention, and accounted for 23.8% of the study population (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is that it is retrospective in nature, and as such, we were reliant on existing data. WIDER IMPLICATIONS OF THE FINDINGS: A previous study in women with PUL after spontaneous conception found that a 2% intervention rate was considered low enough to eliminate the need for close follow-up and serial blood tests. Using the same 2% cut-off, a quarter of women with PUL after IVF could also avoid attending for further visits and investigations. STUDY FUNDING/COMPETING INTEREST(S): No external funding was required for this study. No conflicts of interest are required to be declared. TRIAL REGISTRATION NUMBER: N/A.

Myonuclear alterations associated with exercise are independent of age in humans.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with the nuclear lamina protein lamin A regulating nuclear shape, nuclear mechanics and ultimately gene expression. Defective lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than those from untrained individuals. Complementary to this, exercise resulted in increased levels of lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.

On the survival of the quantum depletion of a condensate after release from a magnetic trap.

We present observations of the high momentum tail in expanding Bose-Einstein condensates of metastable Helium atoms released from a harmonic trap. The far-field density profile exhibits features that support identification of the tails of the momentum distribution as originating in the in-situ quantum depletion prior to release. Thus, we corroborate recent observations of slowly-decaying tails in the far-field beyond the thermal component. This observation is in conflict with the hydrodynamic theory, which predicts that the in-situ depletion does not survive when atoms are released from a trap. Indeed, the depleted tails even appear stronger in the far-field than expected before release, and we discuss the challenges of interpreting this in terms of the Tan contact in the trapped gas. In complement to these observations, full quantum simulations of the experiment show that, under the right conditions, the depletion can persist into the far field after expansion. Moreover, the simulations provide mechanisms for survival and for the the large-momentum tails to appear stronger after expansion due to an acceleration of the depleted atoms by the mean-field potential. However, while in qualitative agreement, the final depletion observed in the experiment is much larger than in the simulation.

Measurement of a helium tune-out frequency: an independent test of quantum electrodynamics.

Despite quantum electrodynamics (QED) being one of the most stringently tested theories underpinning modern physics, recent precision atomic spectroscopy measurements have uncovered several small discrepancies between experiment and theory. One particularly powerful experimental observable that tests QED independently of traditional energy level measurements is the "tune-out" frequency, where the dynamic polarizability vanishes and the atom does not interact with applied laser light. In this work, we measure the tune-out frequency for the 23S1 state of helium between transitions to the 23P and 33P manifolds and compare it with new theoretical QED calculations. The experimentally determined value of 725,736,700(260) megahertz differs from theory [725,736,252(9) megahertz] by 1.7 times the measurement uncertainty and resolves both the QED contributions and retardation corrections.

Trap frequency measurement with a pulsed atom laser.

We describe a novel method of single-shot trap frequency measurement for a confined Bose-Einstein Condensate, which uses an atom laser to repeatedly sample the mean velocity of trap oscillations as a function of time. The method is able to determine the trap frequency to an accuracy of 39 ppm (16 mHz) in a single experimental realization, improving on the literature by a factor of three. Further, we show that by employing a reconstructive aliasing approach our method can be applied to trap frequencies more than a factor of 3 greater than the sampling frequency.

The significance of low first trimester serum progesterone in ongoing early pregnancies presenting as pregnancies of unknown location.

OBJECTIVES: The primary objective of this study was to ascertain whether there is association between low initial serum progesterone, sonographic parameters and clinical outcomes in women presenting with pregnancies of unknown location (PUL), which are found to be ongoing at their follow up scans in the first trimester. STUDY DESIGN: This was a non-interventional retrospective cohort study of 1056 patients spanning a 14-year period, conducted in the Early Pregnancy Unit (EPU) of an inner-city teaching hospital. Patients who had an ongoing singleton first trimester pregnancy after presenting with PUL were identified and categorised as having low progesterone if it was 32 nmol/l or lower. The crown-rump length (CRL), mean gestational sac diameter (MGSD) and gestational sac volume (GSV) were measured when the embryo was first seen, and the pregnancy outcome recorded. RESULTS: Pregnancies with low progesterone tended to have smaller gestational sacs (GS) on follow up scan (p = 0.001) and the sac was smaller than expected for a given CRL (p = 0.000). There was no ultrasound parameter that was characteristic of low progesterone. The observation of a smaller than expected MGSD for a given CRL remained even when only pregnancies with normal outcomes were analysed. Clinical outcome data were available for 854 (80.9 %) women. Overall, 81.4 % (n = 34/43) of pregnancies with low progesterone resulted in livebirth, compared to 91.7 % (n = 744/811) livebirths in pregnancies with higher levels (p = 0.0454). CONCLUSION: Pregnancies with low progesterone tend to have a smaller GS compared to those with a higher progesterone, and the GSs are smaller than expected for a given CRL. The current study shows that women with low progesterone at the start of pregnancy remain at higher risk of miscarriage, even when the pregnancy is initially found to be viable in the first trimester. These pregnancies also tend to be associated with the sonographic finding of a smaller GS than expected for a given gestational age, regardless of eventual outcome.

Direct Measurement of the Forbidden 2

We present the detection of the highly forbidden 2^{3}S_{1}→3^{3}S_{1} atomic transition in helium, the weakest transition observed in any neutral atom. Our measurements of the transition frequency, upper state lifetime, and transition strength agree well with published theoretical values and can lead to tests of both QED contributions and different QED frameworks. To measure such a weak transition, we develop two methods using ultracold metastable (2^{3}S_{1}) helium atoms: low background direct detection of excited then decayed atoms for sensitive measurement of the transition frequency and lifetime, and a pulsed atom laser heating measurement for determining the transition strength. These methods could possibly be applied to other atoms, providing new tools in the search for ultraweak transitions and precision metrology.

Ultrasound features of immature ovarian teratomas: Case series and review of literature.

INTRODUCTION: Immature ovarian teratomas are rare but account for 10-20% of ovarian cancers in women under the age of 20 years. This study aimed to characterise immature ovarian teratomas using grey-scale and Doppler ultrasonography and review the literature to refine the diagnosis of immature ovarian teratomas. METHODS: Patients with a confirmed histological diagnosis of immature ovarian teratoma from years 2006-2018, who had undergone a transvaginal ultrasound at two large teaching hospitals, were identified. The imaging was retrieved from the centres clinical databases. Ultrasound scans were performed by experienced ultrasound examiners and described according to International Ovarian Tumour Analysis criteria. RESULTS: Eight patients were identified in total with a mean age of 26 years (range 13-35). Half of the patients had a past history of a mature ovarian teratoma (3 ipsilateral, 1 contralateral). The cysts were generally large (median 115 mm), fast growing unilateral lesions with a single, peripheral predominantly solid component arising from the cyst wall. The solid component was hyperechoic with multiple foci of fibrosis and numerous small cysts. The cystic component typically formed less than 75% of the lesion and the cyst fluid was of low-level echogenicity. Subjective assessment of vascularity of the solid part of the tumours varied between scores of 1 and 2. Tumour markers showed a raised serum a-fetoprotein level in 42% of these patients. CONCLUSION: Although there were no ultrasound features that were pathognomonic of immature teratoma, the diagnosis should be suspected in a young woman with a large ovarian cyst with a fibrotic, microcystic solid component, particularly if she has a past history of a dermoid cyst.

Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex.

Brain endocannabinoids (eCB), acting primarily via the cannabinoid type 1 receptor (CB1r), are involved in the regulation of many physiological processes, including behavioral responses to stress. A significant neural target of eCB action is the stress-responsive norepinephrine (NE) system, whose dysregulation is implicated in myriad psychiatric and neurodegenerative disorders. Using Western blot analysis, the protein expression levels of a key enzyme in the biosynthesis of the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol lipase-α (DGL-α), and two eCB degrading enzymes monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) were examined in a mouse model that lacks the NE-synthesizing enzyme, dopamine ß-hydroxylase (DßH-knockout, KO) and in rats treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4). In the prefrontal cortex (PFC), DGL-α protein expression was significantly increased in male and female DßH-KO mice (P < 0.05) compared to wild-type (WT) mice. DßH-KO male mice showed significant decreases in FAAH protein expression compared to WT male mice. Consistent with the DßH-KO results, DGL-α protein expression was significantly increased in male DSP-4-treated rats (P < 0.05) when compared to saline-treated controls. MGL and FAAH protein expression levels were significantly increased in male DSP-4 treated rats compared to male saline controls. Finally, we investigated the anatomical distribution of MGL and FAAH in the NE containing axon terminals of the PFC using immunoelectron microscopy. MGL was predominantly within presynaptic terminals while FAAH was localized to postsynaptic sites. These results suggest that the eCB system may be more responsive in males than females under conditions of NE perturbation, thus having potential implications for sex-specific treatment strategies of stress-related psychiatric disorders.

Applications and limitations of regulatory RNA elements in synthetic biology and biotechnology.

Synthetic biology requires the design and implementation of novel enzymes, genetic circuits or even entire cells, which can be controlled by the user. RNA-based regulatory elements have many important functional properties in this regard, such as their modular nature and their ability to respond to specific external stimuli. These properties have led to the widespread exploration of their use as gene regulation devices in synthetic biology. In this review, we focus on two major types of RNA elements: riboswitches and RNA thermometers (RNATs). We describe their general structure and function, before discussing their potential uses in synthetic biology (e.g. in the production of biofuels and biodegradable plastics). We also discuss their limitations, and novel strategies to implement RNA-based regulatory devices in biotechnological applications. We close with a description of some common model organisms used in synthetic biology, with a focus on the current applications and limitations of RNA-based regulation.

High resolution approaches for the identification of amyloid fragments in brain.

BACKGROUND: It is now widely recognized that endogenous, picomolar concentrations of the 42 amino acid long peptide, amyloid-ß (Aß42) is secreted under normal physiological conditions and exerts important functional activity throughout neuronal intracellular compartments. Transgenic animal models that overexpress Aß42 and its precursor, amyloid precursor protein (APP), have not provided predictive value in testing new treatments for Alzheimer's disease (AD), resulting in failed clinical trials. While these results are discouraging, they underscore the need to understand the physiological roles of Aß42 and APP under normal conditions as well as at early pre- symptomatic stages of AD. New method: We describe the use of acrolein-perfusion in immunoelectron microscopy in combination with novel antibodies directed against endogenous murine Aß42 and APP fragments to study abnormalities in the endolysosomal system at early stages of disease. The specific requirements, limitations and advantages of novel antibodies directed against human and murine Aß42, APP and APP fragments are discussed as well as parameters for ultrastructural analysis of endolysosomal compartments. RESULTS: Novel antibodies and a detailed protocol for immunoelectron microscopy using acrolein as a fixative are described. Acrolein is shown to preserve intraneuronal Aß42 species, as opposed to paraformaldehyde fixed tissue, which primarily preserves membrane bound species. Comparison with existing method(s): Technology sensitive enough to detect endogenous Aß42 under physiological conditions has not been widely available. We describe a number of novel and highly sensitive antibodies have recently been developed that may facilitate the analysis of endogenous Aß42. CONCLUSIONS: Using novel and highly specific antibodies in combination with electron microscopy may reveal important information about the timing of aberrant protein accumulation, as well as the progression of abnormalities in the endolysosomal systems that sort and clear these peptides.

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study.

Background: Venetoclax is a selective, potent inhibitor of the anti-apoptotic B-cell leukemia/lymphoma-2 protein approved for treatment of chronic lymphocytic leukemia. We conducted a dose-finding study of venetoclax in combination with bendamustine-rituximab (BR) in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL). Patients and methods: BR was given for six cycles at standard doses. Intermittent and continuous oral venetoclax administration was explored at 50-1200 mg daily doses. Co-primary objectives included safety, pharmacokinetics (PKs), maximum-tolerated dose (MTD), and recommended phase II dose (RP2D); secondary objective was preliminary efficacy. Results: Sixty patients were enrolled: 32 with follicular lymphoma, 22 with diffuse large B-cell lymphoma, and 6 with marginal zone lymphoma. Nausea (70%), neutropenia (68%), diarrhea (55%), and thrombocytopenia (52%) were the most frequent adverse events (AEs). Most common grade 3/4 AEs were neutropenia (60%) and lymphopenia (38%). Serious AEs were reported in 24 patients; the most frequent were febrile neutropenia and disease progression (8% each). Five patients died from either disease progression (n = 4) or respiratory failure (n = 1). MTD was not reached; RP2D for venetoclax-BR combination was established as 800 mg daily continuously. Venetoclax PK exposure with and without BR was comparable. For all patients, overall response rate was 65%. Median duration of overall response, overall survival, and progression-free survival was 38.3 months [95% confidence interval (CI) 10.4-NR], not yet reached, and 10.7 months (95% CI 4.3-21.0), respectively. Conclusions: This study established the safety profile of venetoclax in combination with BR, and results demonstrated tolerability and preliminary efficacy of the combination. Additional follow-up is needed to better determine the future role of BR plus venetoclax in the treatment of relapsed/refractory B-cell NHL. Trial registered: Clinicaltrials.gov, NCT01594229.

Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial.

OBJECTIVE: Methotrexate is used routinely worldwide for the medical treatment of clinically stable women with a tubal ectopic pregnancy. This is despite the lack of robust evidence to show its superior effectiveness over expectant management. The aim of our multicenter randomized controlled trial was to compare success rates of methotrexate against placebo for the conservative treatment of tubal ectopic pregnancy. METHODS: This study took place in two early-pregnancy units in the UK between August 2005 and June 2014. Inclusion criteria were clinically stable women with a conclusive ultrasound diagnosis of a tubal ectopic pregnancy, presenting with a low serum beta human chorionic gonadotropin (ß-hCG) level of < 1500 IU/L. Women were assigned randomly to a single systemic injection of either 50 mg/m2 methotrexate or placebo. The primary outcome was a binary indicator for success of conservative management, defined as resolution of clinical symptoms and decline of serum ß-hCG to < 20 IU/L or a negative urine pregnancy test without the need for any additional medical intervention. An intention-to-treat analysis was followed. RESULTS: We recruited a total of 80 women, 42 of whom were assigned to methotrexate and 38 to placebo. The arms of the study were matched in terms of age, ethnicity, obstetric history, pregnancy characteristics and serum levels of ß-hCG and progesterone. The rates of success were similar for the two study arms: 83% with methotrexate and 76% with placebo. On univariate analysis, this difference was not statistically significant (χ2 (1 degree of freedom) = 0.53; P = 0.47). On multivariate logistic regression, the serum level of ß-hCG was the only covariate found to be significantly associated with outcome. The odds of failure increased by 0.15% for each unit increase in ß-hCG (odds ratio, 1.0015 (95% CI, 1.0002-1.003); P = 0.02). In 14 women presenting with serum ß-hCG of 1000-1500 IU/L, the success rate was 33% in those managed expectantly compared with 62% in those receiving methotrexate. This difference was not statistically significant and a larger sample size would be needed to give sufficient power to detect a difference in the subgroup of women with higher ß-hCG. In women with successful conservative treatment, there was no significant difference in median ß-hCG resolution times between study arms (17.5 (interquartile range (IQR), 14-28.0) days (n = 30) in the methotrexate group vs 14 (IQR, 7-29.5) days (n = 25) in the placebo group; P = 0.73). CONCLUSIONS: The results of our study do not support the routine use of methotrexate for the treatment of clinically stable women diagnosed with tubal ectopic pregnancy presenting with low serum ß-hCG (< 1500 IU/L). Further work is required to identify a subgroup of women with tubal ectopic pregnancy and ß-hCG ≥ 1500 IU/L in whom methotrexate may offer a safe and cost-effective alternative to surgery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Comparación entre una sola dosis de metotrexate sistémico y la conducta expectante en el tratamiento de casos de embarazo ectópico tubárico: un ensayo aleatorio controlado con placebo RESUMEN OBJETIVO: El metotrexate se utiliza de modo rutinario en todo el mundo para el tratamiento de las mujeres clínicamente estables con un embarazo ectópico tubárico. Esto sucede a pesar de la falta de evidencia rigurosa que demuestre que su eficacia es superior a la conducta expectante. El objetivo de este ensayo controlado aleatorio multicéntrico fue comparar las tasas de éxito del metotrexate con las de un placebo para el tratamiento cauteloso del embarazo ectópico tubárico. MÉTODOS: Este estudio se llevó a cabo en dos clínicas de control de gestación temprana en el Reino Unido entre agosto de 2005 y junio de 2014. Los criterios de inclusión fueron mujeres clínicamente estables con un diagnóstico ecográfico concluyente de embarazo ectópico tubárico, las cuáles presentaban una concentración sérica baja de la ß hormona coriónica gonadotrópica (ß-hCG) inferior a 1500 UI/L. Las mujeres fueron asignadas aleatoriamente a una sola inyección sistémica de 50 mg/m2 de metotrexate o a placebo. El resultado primario fue un indicador binario del éxito del tratamiento conservador, definido como la resolución de los síntomas clínicos y la disminución en el suero de la ß-hCG a <20 UI/L o una prueba de embarazo negativa en orina sin la necesidad de ninguna intervención médica adicional. Se hizo un análisis por intención de tratar. RESULTADOS: Se reclutó un total de 80 mujeres; a 42 de ellas se les asignó el metotrexate y a 38 el placebo. Los grupos del estudio se realizaron en función de la edad, el origen étnico, los antecedentes obstétricos, las características del embarazo y los niveles séricos de la ß-hCG y la progesterona. Las tasas de éxito fueron similares para los dos grupos de estudio: 83% con metotrexate y 76% con placebo. En el análisis univariante, esta diferencia no fue estadísticamente significativa (χ2 (1 grado de libertad) = 0,53; P = 0,47). En la regresión logística multivariante, el nivel sérico de la ß-hCG fue la única covariable que se encontró significativamente asociada con el resultado. Las probabilidades de fracaso aumentaron en un 0,15% por cada unidad de aumento de la ß-hCG (cociente de probabilidad 1,0015 (IC 95%, 1,0002-1,003); P = 0,02). La tasa de éxito en las 14 mujeres con un nivel sérico de la ß-hCG de 1000-1500 UI/L fue del 33% en las tratadas con conducta expectante frente al 62% en las que recibieron metotrexate. Esta diferencia no fue estadísticamente significativa, por lo que se necesitaría un tamaño de muestra mayor, lo suficiente como para poder detectar diferencias en el subgrupo de mujeres con una ß-hCG más elevada. En las mujeres en las que el tratamiento conservador tuvo éxito, no hubo una diferencia significativa en la mediana de los tiempos de resolución de la ß-hCG entre los grupos del estudio (17,5 (amplitud intercuartílica (IQR), 14-28,0) días (n = 30) en el grupo de metotrexate frente a 14 (IQR, 7-29.5) días (n = 25) en el grupo de placebo; P = 0,73). CONCLUSIONES: Los resultados de este estudio no apoyan el uso rutinario de metotrexate para el tratamiento de las mujeres clínicamente estables diagnosticadas con un embarazo ectópico tubárico que presenta un nivel sérico bajo la ß-hCG (<1500 UI/L). Serán necesarios estudios adicionales para identificar un subgrupo de mujeres con embarazo ectópico tubárico y ß-hCG ≥1500 UI/L para quienes el metotrexate puede ofrecer una alternativa segura y rentable en comparación con la cirugía. : : ,,。。 : 2005820146,2。,,ß(beta human chorionic gonadotropin,ß-hCG)<1500 IU/L。,(50 mg/m2 )。,ß-hCG<20 IU/L,。。 : 80,42,38。2、、、ß-hCG。2:83%,76%。,[χ2 (1)=0.53;P=0.47]。logistic,ß-hCG。ß-hCG,0.15%[,1.0015(95% CI,1.0002~1.003);P=0.02]。14ß-hCG1000~1500 IU/L,33%,62%。,ß-hCG。,2ß-hCG(P=0.73),17.5[(interquartile range,IQR),14~28.0](n=30),14 (IQR,7~29.5)(n=25)。 : 、、ß-hCG(<1500 IU/L)。,ß-hCG>1500 IU/L、。.

OC-13 - Safe and effective use of direct oral anticoagulants (DOAC) versus conventional anticoagulation for the treatment of cancer-related venous thromboembolism.

INTRODUCTION: Cancer is a risk factor for the development of venous thromboembolism (VTE). The standard of care for the treatment of cancer-related VTE is a low molecular weight heparin (LMWH) formulation. The treatment for these events can be painful, lengthy, and expensive. The development of DOAC has created new options for the treatment of VTE. Data from a recent systematic review suggested that the safety and effectiveness of DOAC in patients with cancer is equivalent to that of traditional therapies. If equivalent to LMWH, the use of DOAC in the treatment of cancer-related VTE would reduce the risk of VTE recurrence while giving patients freedom from subcutaneous injections. AIM: Our primary aim was to determine the rate of VTE recurrence in patients on anticoagulation. Secondary aims were determination of the rate of anticoagulant-associated clinically relevant bleeding and VTE recurrence-free survival. MATERIALS AND METHODS: We performed retrospective analysis (2014-2015) of the electronic medical records (EMR) of adult patients with cancer-related VTE treated with anticoagulation. We selected 122 patients for our final analysis according to the inclusion criteria. Demographic, laboratory, cancer diagnosis, and VTE diagnosis data were collected. We documented VTE recurrence as well as clinically relevant bleeding. Non-parametric statistical procedures were used to determine differences in variables associated with this study among the anticoagulant class groups, with a test significance level of 0.05. RESULTS: Among 122 patients, 89 (73%) were treated with LMWH, 26 (21%) were treated with DOAC, and 7 (6%) were treated with warfarin. The majority of VTE occurred in patients with advanced disease. The most common index event was pulmonary embolism (49%) followed by catheter-associated deep venous thrombosis (DVT) (24%). Recurrence of VTE occurred in 7.7% of patients receiving DOAC and 7.9% of patients receiving LMWH (P=NS). Major bleeding occurred more often with the use of DOAC (11.5%) than with LMWH (10.1%), but non-major bleeding was more common in patients receiving LMWH (9.0% versus 7.7%). These differences were not statistically significant. There was no mortality attributed to bleeding complications. The VTE recurrence-free survival rates were not statistically different among LMWH versus DOAC (Figure 1). CONCLUSIONS: Recurrence of cancer-associated VTE is not uncommon, and the treatment of VTE has significant hemorrhagic risks. Our analysis suggests that there is no significant difference in the rate of VTE recurrence and anticoagulant-related bleeding when using oral DOACs versus LMWH. Further studies are needed to compare the safety and effectiveness of these methods of anticoagulation.

Surgical treatment of Cesarean scar ectopic pregnancy: efficacy and safety of ultrasound-guided suction curettage.

OBJECTIVES: To assess the efficacy of ultrasound-guided suction curettage for management of pregnancies implanted into the lower uterine segment Cesarean section scar. METHODS: This was a retrospective study including women diagnosed with Cesarean section scar pregnancy at two large tertiary referral early pregnancy units between 1997 and 2014. Surgical evacuation was offered to selected women presenting in the first trimester ≤ 14 weeks' gestation. All procedures were performed transcervically under ultrasound guidance using suction curettage. A modified Shirodkar cervical suture was used in women who required additional measures to secure hemostasis. RESULTS: A total of 232 women with Cesarean section scar pregnancy were seen at the referral units; 191/232 (82.3%) women were treated surgically. The median intraoperative blood loss was 100 mL (range, 10-3000 mL); 9/191 (4.7% (95% CI, 1.7-7.7%)) women required blood transfusion and, in one (0.5% (95% CI, 0-1.5%)), life-saving hysterectomy had to be performed because of uncontrollable intraoperative bleeding. Of the women who attended for follow-up, 7/116 (6.0% (95% CI, 1.7-10.3%)) required a repeat surgical procedure because of retained products of conception. Multivariable analysis showed that the gestational sac diameter (odds ratio (OR), 1.10 (95% CI, 1.03-1.17)) and pregnancy vascularity on Doppler examination (OR, 3.41 (95% CI, 1.39-8.33)) were significant predictors of heavy intraoperative blood loss (> 1000 mL). CONCLUSIONS: Ultrasound-guided suction curettage is an effective method for the treatment of pregnancies implanted into a lower uterine segment Cesarean section scar and is associated with a low risk of blood transfusion and hysterectomy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cost-effectiveness of salpingotomy and salpingectomy in women with tubal pregnancy (a randomized controlled trial).

STUDY QUESTION: Is salpingotomy cost effective compared with salpingectomy in women with tubal pregnancy and a healthy contralateral tube? SUMMARY ANSWER: Salpingotomy is not cost effective over salpingectomy as a surgical procedure for tubal pregnancy, as its costs are higher without a better ongoing pregnancy rate while risks of persistent trophoblast are higher. WHAT IS KNOWN ALREADY: Women with a tubal pregnancy treated by salpingotomy or salpingectomy in the presence of a healthy contralateral tube have comparable ongoing pregnancy rates by natural conception. Salpingotomy bears the risk of persistent trophoblast necessitating additional medical or surgical treatment. Repeat ectopic pregnancy occurs slightly more often after salpingotomy compared with salpingectomy. Both consequences imply potentially higher costs after salpingotomy. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation of salpingotomy compared with salpingectomy in an international multicentre randomized controlled trial in women with a tubal pregnancy and a healthy contralateral tube. Between 24 September 2004 and 29 November 2011, women were allocated to salpingotomy (n = 215) or salpingectomy (n = 231). Fertility follow-up was done up to 36 months post-operatively. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We performed a cost-effectiveness analysis from a hospital perspective. We compared the direct medical costs of salpingotomy and salpingectomy until an ongoing pregnancy occurred by natural conception within a time horizon of 36 months. Direct medical costs included the surgical treatment of the initial tubal pregnancy, readmissions including reinterventions, treatment for persistent trophoblast and interventions for repeat ectopic pregnancy. The analysis was performed according to the intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Mean direct medical costs per woman in the salpingotomy group and in the salpingectomy group were €3319 versus €2958, respectively, with a mean difference of €361 (95% confidence interval €217 to €515). Salpingotomy resulted in a marginally higher ongoing pregnancy rate by natural conception compared with salpingectomy leading to an incremental cost-effectiveness ratio €40 982 (95% confidence interval -€130 319 to €145 491) per ongoing pregnancy. Since salpingotomy resulted in more additional treatments for persistent trophoblast and interventions for repeat ectopic pregnancy, the incremental cost-effectiveness ratio was not informative. LIMITATIONS, REASONS FOR CAUTION: Costs of any subsequent IVF cycles were not included in this analysis. The analysis was limited to the perspective of the hospital. WIDER IMPLICATIONS OF THE FINDINGS: However, a small treatment benefit of salpingotomy might be enough to cover the costs of subsequent IVF. This uncertainty should be incorporated in shared decision-making. Whether salpingotomy should be offered depends on society's willingness to pay for an additional child. STUDY FUNDING/COMPETING INTERESTS: Netherlands Organisation for Health Research and Development, Region Västra Götaland Health & Medical Care Committee. TRIAL REGISTRATION NUMBER: ISRCTN37002267.

Natural history of early first-trimester pregnancies implanted in Cesarean scars.

OBJECTIVE: To describe the ultrasound findings and natural history of pregnancies implanted within or on Cesarean section scars in the first trimester of pregnancy. METHODS: This was a prospective observational study of 10 women diagnosed with a pregnancy implanted in or on a Cesarean section scar in the first trimester, who declined medical intervention because of their desire to continue the pregnancy. The study population comprised women at < 12 weeks' gestation who were seen in our early pregnancy unit between January 2011 and September 2013. Nine women were followed up by serial ultrasound examinations and had detailed care plans for delivery at King's College Hospital (KCH). One woman was followed up and delivered at another teaching hospital. The first-trimester ultrasound findings were compared with the clinical outcome of the pregnancy. RESULTS: The nine patients who were followed up at KCH developed ultrasound findings of morbidly adherent placenta (MAP) in the second and third trimesters. All 10 patients were diagnosed with MAP at the time of delivery by Cesarean section. The gestational age at delivery ranged from 26 to 38 weeks. The uterus was conserved in five patients, and Cesarean hysterectomy was performed in the remaining five. All three women with complete implantation of the gestational sac within the scar and two of three cases with placental lakes in the first trimester had hysterectomies. The two cases with bulging of the gestational sac out of the uterine contour had a preterm emergency hysterectomy due to placenta percreta. Histology confirmed placenta accreta in the five hysterectomy specimens. There were no fetal or neonatal complications. CONCLUSIONS: Implantation of a pregnancy on or in a Cesarean section scar is a precursor of MAP; however, the degree of morbidity associated with this implantation is variable and difficult to predict based on first-trimester ultrasound findings only. The assessment of ongoing pregnancies implanted in Cesarean scars is most beneficial when performed between 7 and 9 weeks' gestation. Complete implantation within the myometrial defect, bulging of the trophoblast from the uterine contour and large placental lakes in the first trimester are ultrasound findings that may predict severe placenta accreta or percreta and consequently a poor outcome.

The psychological effects and patient acceptability of a test to predict viability in early pregnancy: a prospective randomised study.

OBJECTIVE: To establish if women obtain any measurable short term psychological benefit or perceived benefit from having a test to determine the probability of their pregnancy being on-going when this is uncertain on ultrasound examination. STUDY DESIGN: This was a prospective randomised controlled study conducted January 2012-June 2012 at the EPU of King's College Hospital. The study population was women who conceived spontaneously and had a single intrauterine gestational sac of <20mm mean diameter, with no visible embryo on their first ultrasound scan. Eligible women were randomised to have a test to calculate the probability of viability (cases) or not (controls). Depression and anxiety levels were calculated using the Hospital Anxiety and Depression Score (HADS) and were performed prior to randomisation and seven days later. A repeat scan for pregnancy outcome was performed after one to two weeks as clinically indicated. A sample size of 69 in each group was calculated to have 80% power to detect a probability of 0.362 that an observation in the cases was less than an observation in controls using a Wilcoxon Mann-Whitney rank-sum test with a 0.05 two-sided significance. RESULTS: At recruitment there was no significant difference in anxiety levels between cases and controls. After seven days anxiety levels were significantly lower in cases than controls (p=0.04). Of those who received the probability score, 55/70 (78.6% 95% CI 67.5-86.7%) found it useful and 58/70 (82.9% 95% CI 72.2-90.1) would choose to have the test in a future pregnancy if indicated. CONCLUSIONS: This study has demonstrated that there is evidence of psychological benefit from a simple blood test that gives women the likelihood that their pregnancy will be on-going at the next scan.