Effects of strict public health measures on seroprevalence of anti-SARS-CoV-2 antibodies during pregnancy.

INTRODUCTION: A substantial number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic throughout the course of infection. Nearly half of pregnant women with coronavirus disease 2019 (COVID-19) are asymptomatic upon diagnosis; these cases are not without risk of maternal morbidity. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in an unselected sample of pregnant women in Hong Kong. METHODS: This prospective cohort study included pregnant women who presented for routine Down syndrome screening (DSS) between November 2019 and October 2020; all women subsequently delivered at the booking hospitals. Serum antibodies against SARS-CoV-2 were analysed using a qualitative serological assay in paired serum samples taken at DSS and delivery for all participants. RESULTS: In total, 1830 women were recruited. Six women (0.33%) were seropositive at the DSS visit; this seropositivity persisted until delivery. Of the six women, none reported relevant symptoms during pregnancy; one reported a travel history before DSS and one reported relevant contact history. The interval between sample collections was 177 days (range, 161-195). Among women with epidemiological risk factors, 1.79% with travel history, 50% with relevant contact history, and 0.77% with community SARS-CoV-2 testing history, were seropositive. CONCLUSION: The low seroprevalence in this study suggests that strict public health measures are effective for preventing SARS-CoV-2 transmission. However, these measures cannot be maintained indefinitely. Until a highly effective therapeutic drug targeting SARS-CoV-2 becomes available, vaccination remains the best method to control the COVID-19 pandemic.

Outcome of radiofrequency ablation for selective fetal reduction before vs at or after 16 gestational weeks in complicated monochorionic pregnancy.

OBJECTIVE: To investigate whether gestational age at intervention (< or ≥ 16 weeks) and other factors affect the risk of loss of the cotwin after selective fetal reduction using radiofrequency ablation (RFA) in monochorionic (MC) pregnancy. METHODS: This was a single-center retrospective analysis of 63 consecutive RFA procedures performed at our institution from January 2011 to October 2019 for selective fetal reduction in complicated MC pregnancies. Indications for RFA were twin reversed arterial perfusion sequence (13 cases), twin-to-twin transfusion syndrome (12 cases), twin anemia-polycythemia sequence (two cases), selective fetal growth restriction (10 cases), discordant anomalies (17 cases) and multifetal pregnancy reduction in triplets or quadruplets with a MC pair (nine cases). Twenty-six (41.3%) of these procedures were performed before and 37 (58.7%) after 16 weeks. Potential factors that could affect the risk of loss of the cotwin, including gestational age at RFA, order of multiple pregnancy, amnionicity, indication for RFA and number of ablation cycles, were assessed first by univariate analysis and then by multivariate analysis. RESULTS: There were 17 (27.0%) cotwin losses. Ablation cycles numbering four or more was the only factor among those investigated to be associated with loss of the cotwin after RFA (P = 0.035; odds ratio, 5.21), while the indication for RFA, order of multiple pregnancy, amnionicity and gestational age at RFA had no effect. Comparing RFA performed at < 16 vs ≥ 16 weeks, there was no difference in the rate of cotwin loss (23.1% vs 29.7%; P = 0.558) or preterm prelabor rupture of the membranes before 34 weeks (7.7% vs 5.4%; P = 0.853), or in the median gestational age at delivery (36.2 vs 37.3 weeks; P = 0.706). CONCLUSIONS: RFA is a promising tool for early selective fetal reduction in MC pregnancy before 16 weeks. Four or more ablation cycles is a major risk factor for cotwin loss. Careful assessment pre- and post-RFA, together with proficient operative skills to minimize the number of ablation cycles, are the mainstay to ensure that this procedure is effective and safe. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Do specific ultrasonography features identified at the time of early pregnancy loss predict fetal chromosomal abnormality? - A systematic review and meta-analysis.

To investigate the association of specific ultrasonography features identified during the diagnosis of early pregnancy loss (EPL) and abnormal karyotype. This was a systematic review and meta-analysis conducted in accordance with PRISMA criteria. We searched PubMed, Cochrane and Ovid MEDLINE from 1977 to Jan 2017 to identify the articles that described EPL with karyotype and ultrasonography features. Risk differences were pooled to estimate the chromosomal abnormality rates in ultrasonography features, including pre-embryonic, enlarged yolk sac (YS), short crown rump length (CRL), small gestational sac (GS), symmetrical arrested growth embryo, or gestational sac with only a YS. Quality assessment of included studies was performed using Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklists for Observational Studies (2007 version). Thirteen studies were included in the meta-analysis. Chromosomal abnormality was more likely to occur in embryonic EPL and enlarged YS. On the other hand, short CRL, small GS, symmetrical arrested growth embryo, or gestational sac with only a YS, were not associated with an increased risk of fetal chromosomal abnormality. Ultrasonography features at the time of diagnosis of EPL have limited predictive value of fetal chromosomal abnormality.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

ASPRE trial: performance of screening for preterm pre-eclampsia.

OBJECTIVE: To examine the performance of screening for preterm and term pre-eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial. METHODS: This was a prospective first-trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks' gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg per day) vs placebo from 11-14 until 36 weeks' gestation, which showed that, in the aspirin group, the incidence of preterm PE was reduced by 62%. In the screened population, the detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%) pregnancies because of loss to follow-up or study withdrawal (n = 716), miscarriage (n = 243) or termination (n = 185). RESULTS: The study population of 25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE and 25 167 (97.6%) without PE. In combined first-trimester screening for preterm PE with a risk cut-off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and 43.1% (194/450) for term PE, at screen-positive rate of 10.5% (2707/25 797) and FPR of 9.2% (2375/25 797). CONCLUSION: The performance of screening in the ASPRE study was comparable with that of a study of approximately 60 000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of 10%. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Protocol for the prospective validation study: 'Screening programme for pre-eclampsia' (SPREE).

Pre-eclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. Early detection of PE can improve pregnancy outcome by providing timely intervention and closer monitoring. The current guideline from the UK National Institute for Health and Care Excellence (NICE) recommends that, at the booking visit, women identified with one major risk factor or more than one moderate risk factor for PE should be advised to take low-dose aspirin daily from 12 weeks until delivery. However, performance of the current method of screening is poor and identifies only about 35% of PE. Extensive studies in the last decade have established that the best performance for early prediction of PE can be achieved by using a novel Bayes' theorem-based method that combines maternal characteristics and medical history together with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation. This forms the 'combined test', which could be simplified to the 'mini combined test' when only maternal factors, MAP and PAPP-A are taken into consideration. We present the protocol (version 3.1, 14 November 2016) for the 'Screening programme for pre-eclampsia' (SPREE) study, a prospective multicenter cohort study that will be carried out in seven National Health Service maternity hospitals in England. Eligible pregnant women attending their routine scan at 11-13 weeks' gestation will be invited to participate in this study. Maternal characteristics and history and measurements of MAP, UtA-PI, serum PAPP-A and PlGF will be recorded according to standardized protocols. The patient-specific risk for PE will be calculated and data on pregnancy outcomes collected. We hypothesize that the first-trimester mini combined test and combined test for PE screening, using the Bayes' theorem-based method, are likely to be superior to the current method recommended by NICE that is based on maternal demographics and history alone. Enrollment for the study commenced in April 2016. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Birth weight in live births and stillbirths.

OBJECTIVE: To establish a normal range of birth weights for gestational age at delivery and to compare the proportion of live births and stillbirths that are classified as small-for-gestational age (SGA) according to our normal range vs that of the INTERGROWTH-21st standard. METHODS: The study population comprised 113 019 live births and 437 (0.4%) stillbirths. The inclusion criterion for establishing a normal range of birth weights for gestational age was the live birth of a phenotypically normal neonate ≥ 24 weeks' gestation and the exclusion criteria were smoking and prepregnancy hypertension, diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome, pre-eclampsia, gestational hypertension, gestational diabetes mellitus or iatrogenic preterm birth for fetal growth restriction in the current pregnancy. Inclusion criteria were met by 92 018 live births. The proportions of live births and stillbirths with birth weights < 5th and < 10th percentiles of our normal range and those according to the INTERGROWTH-21st standard were determined and compared by the chi-square test and McNemar test. RESULTS: The proportions of live births and stillbirths with a birth weight < 5th percentile according to our standard were significantly higher than and discordant with the proportion according to the INTERGROWTH-21st standard (live birth: 5.6% vs 3.4%; stillbirth: 37.2% vs 22.7%). Similarly, the proportion of live births and stillbirths with a birth weight < 10th percentile according to our standard were significantly higher than and discordant with those according to the INTERGROWTH-21st standard (live birth: 11.2% vs 6.9%; stillbirth: 44.3% vs 32.6%). CONCLUSION: The INTERGROWTH-21st standard underestimates the proportion of SGA live births and stillbirths in our population. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cervical cerclage for preterm birth prevention in twin gestation with short cervix: a retrospective cohort study.

OBJECTIVE: To determine if cervical cerclage reduces the rate of spontaneous early preterm birth in cases of dichorionic-diamniotic (DCDA) twin gestation with an ultrasound-detected short cervix. METHODS: This was a retrospective cohort study of 40 consecutive DCDA twin gestations at Saint Peter's University Hospital from November 2006 to November 2014 in which cervical cerclage was performed for an ultrasound-determined cervical length of 1-24 mm at 16-24 weeks' gestation. The cases were matched with 40 controls without cerclage for cervical length and gestational age at cervical assessment. The primary outcome measure was spontaneous birth < 32 weeks. RESULTS: There was no difference between the two groups in maternal age, body mass index (BMI), cigarette smoking, use of in-vitro fertilization (IVF), parity and prior spontaneous preterm birth. There were more Caucasian women among the controls compared with cases. In the cases, compared with controls, spontaneous delivery < 32 weeks was significantly less frequent (20.0% vs 50.0%; relative risk, 0.40 (95% CI, 0.20-0.80)). In the prediction of spontaneous delivery < 32 weeks, logistic regression analysis demonstrated that the risk was reduced with the insertion of cervical cerclage (odds ratio, 0.22 (95% CI, 0.058-0.835); P = 0.026), corrected for maternal age, BMI, racial origin, cigarette smoking, IVF, parity and previous preterm birth. CONCLUSION: In DCDA twin gestation with a short cervix, treatment with cervical cerclage may reduce the rate of early preterm birth. The findings suggest the need for adequate randomized controlled trials on cerclage in twin gestations with a short cervix. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Expression of Magnaporthe oryzae genes encoding cysteine-rich proteins secreted during nitrogen starvation and interaction with its host, Oryza sativa.

Previous studies have shown that the blast fungus, Magnaporthe oryzae, may experience nitrogen starvation during infection of its plant host (rice,Oryza sativa). Here, we studied the expression of seven genes encoding cysteine-rich proteins with N-terminal signal peptides during nitrogen limitation and throughout the infection process. Some genes were upregulated to a greater extent in weak pathogenic strains than in strong pathogenic strains when they were cultured in complete media, and the expression of some genes was higher in both weak and strong pathogenic strains cultured in 1/10-N and nitrogen starvation media. Furthermore, the expression of these genes was upregulated to different extents in the early stages of M. oryzae infection. These data demonstrate that the genes of interest are highly expressed in weak and strong pathogenic strains cultured under nitrogen limitation and at the early stage of the infection process. This indicates that cysteine-rich secreted proteins in the blast fungus might be involved in establishing disease in the host and that they are sensitive to nitrogen levels. Thus, their role in sensing nitrogen availability within the host is implied, which provides a basis for further functional identification of these genes and their products during plant infection.

Automated preoperative assessment of endothelial dysfunction and risk stratification for perioperative myocardial injury in patients undergoing non-cardiac surgery.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common complication with associated serious morbidity and mortality. Endothelial dysfunction might play an important role in MINS, and its rapid assessment could provide a novel method of risk stratification before surgery. METHODS: We studied 238 subjects scheduled to undergo intermediate or high-risk surgery in a two-centre prospective study to determine whether preoperative endothelial dysfunction identified by a reactive hyperaemia-peripheral arterial tonometry (RH-PAT) index could provide effective risk stratification for MINS, defined as serum troponin ≥0.04 µg litre(-1), within 3 postoperative days. RESULTS: The primary outcome occurred in 35 subjects (14.7%). Endothelial dysfunction was defined as an RH-PAT index of ≤1.22. Adjusted for age, Lee index and a composite measure of the extent of surgery, endothelial dysfunction was associated with MINS [odds ratio 10.1, 95% confidence interval (CI) 3.3-30.9, P=0.001] and increased time to discharge from hospital after surgery (hazard ratio 0.39, 95% CI 0.23-0.65, P=0.001). Endothelial dysfunction identified MINS with a sensitivity of 31%, a specificity of 96%, and a positive diagnostic likelihood ratio of 8.0. Risk classification for MINS was improved by the addition of RH-PAT-defined endothelial dysfunction to the Lee index (c-statistic increased from 0.69 to 0.77; integrated discrimination improvement 0.11, P=0.003). However, prognostic utility varied widely between sites. CONCLUSIONS: For patients undergoing non-cardiac surgery, non-invasive assessment of endothelial function might enhance preoperative risk stratification for perioperative myocardial injury. However, unexplained large inter-site variation in prognostic utility could limit widespread application and needs to be further understood.

How feasible is expectant management of interstitial ectopic pregnancy?

OBJECTIVE: To review the success rate of expectant management in a series of interstitial pregnancies. METHODS: We identified all women with an ultrasound diagnosis of interstitial pregnancy seen within a 9-year period (January 2004 to April 2013). The clinical history, ultrasound findings and biochemical results were reviewed. The outcome of all interstitial pregnancies managed conservatively was recorded. Treatment was considered as successful when the serum ß-human chorionic gonadotropin (ß-hCG) level declined below 20 IU/L without the need for further intervention. RESULTS: A total of 48 interstitial pregnancies were diagnosed during the study period. Surgery was the first-line treatment in nine (18.8%) cases. Thirty-eight (79.2%) women were offered non-surgical management: 19 (39.6%) had methotrexate (MTX) and 19 (39.6%) were managed expectantly. One (2.1%) woman returned to her local hospital following diagnosis and we were unable to obtain any follow-up information regarding her care. The median initial serum ß-hCG level and ectopic size were not significantly different between any of the groups according to initial treatment. The overall success rate of expectant management was 89.5%. There were no cases of ectopic rupture in this group. Length of follow-up ranged from 7 to 141 days with a median duration of follow-up of 50.6 days. CONCLUSION: Our data show that expectant management is an option for selected women with non-viable interstitial pregnancies and declining serum ß-hCG levels, irrespective of ectopic mass size and initial serum ß-hCG levels.

Maternal plasma cell-free fetal and maternal DNA at 11-13 weeks' gestation: relation to fetal and maternal characteristics and pregnancy outcomes.

OBJECTIVE: To examine the possible relationship between maternal and fetal characteristics and pregnancy outcomes on fetal and maternal cell-free (cf) DNA in maternal plasma at 11-13 weeks' gestation. METHODS: cfDNA was extracted from maternal plasma of 1,949 singleton pregnancies and chromosome-selective sequencing was used to determine the proportion of cfDNA and total cfDNA counts which was of fetal and maternal origin. Multivariate regression analysis was used to determine whether specific maternal and fetal characteristics and pregnancy complications, such as preeclampsia (PE), early spontaneous preterm birth (SPB) and delivery of small for gestational age (SGA) neonates, were significant predictors of fetal and maternal cfDNA in maternal plasma. RESULTS: The fetal and maternal cfDNA plasma concentration increased with serum pregnancy-associated plasma protein-A and free ß-human chorionic gonadotropin level, was higher in women of Afro-Caribbean and East-Asian racial origin than in Caucasians, and lower in smokers, but it was not significantly altered in pregnancies complicated by PE, SPB or SGA. The fetal cfDNA level was inversely related to maternal weight and uterine artery pulsatility index, and maternal cfDNA increased with maternal weight. CONCLUSIONS: The fetal and maternal cfDNA level in maternal plasma is affected by maternal and fetal characteristics, but it is not altered in pregnancy complications.

Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks' gestation: relation to maternal and fetal characteristics.

OBJECTIVE: To examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free (cf) DNA at 11-13 weeks' gestation and estimate the proportion of pregnancies at high risk of non-invasive prenatal testing (NIPT) failure because the fetal fraction is less than 4%. METHODS: In 1949 singleton pregnancies at 11-13 weeks' gestation cf-DNA was extracted from maternal plasma. Chromosome-selective sequencing of non-polymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of cf-DNA that was of fetal origin. Multivariable regression analysis was used to determine significant predictors of the fetal fraction among maternal and fetal characteristics. RESULTS: The fetal fraction decreased with increased maternal weight, it was lower in women of Afro-Caribbean origin than in Caucasians and increased with fetal crown-rump length, serum pregnancy-associated plasma protein-A, serum free ß-human chorionic gonadotropin, smoking and trisomy 21 karyotype. The median fetal fraction was 10.0% (interquartile range, 7.8-13.0%) and this decreased with maternal weight from 11.7% at 60 kg to 3.9% at 160 kg. The estimated proportion with fetal fraction below 4% increased with maternal weight from 0.7% at 60 kg to 7.1% at 100 kg and 51.1% at 160 kg. CONCLUSIONS: Fetal fraction in maternal plasma cf-DNA is affected by maternal and fetal characteristics.

Meta-analysis of second-trimester markers for trisomy 21.

OBJECTIVE: To summarize by meta-analysis the accumulated data on the screening performance of second-trimester sonographic markers for fetal trisomy 21. METHODS: We conducted a literature search to identify studies between 1995 and September 2012 that provided data on the incidence of sonographic markers in trisomy 21 and euploid fetuses at 14-24 weeks' gestation. Weighted independent estimates of detection rate, false-positive rate and positive and negative likelihood ratios (LR) of markers were calculated. RESULTS: A total of 48 studies was included in the analysis. The pooled estimates of positive and negative LR were, respectively: 5.83 (95% CI, 5.02-6.77) and 0.80 (95% CI, 0.75-0.86) for intracardiac echogenic focus; 27.52 (95% CI, 13.61-55.68) and 0.94 (95% CI, 0.91-0.98) for ventriculomegaly; 23.30 (95% CI, 14.35-37.83) and 0.80 (95% CI, 0.74-0.85) for increased nuchal fold; 11.44 (95% CI, 9.05-14.47) and 0.90 (95% CI, 0.86-0.94) for hyperechogenic bowel; 7.63 (95% CI, 6.11-9.51) and 0.92 (95% CI, 0.89-0.96) for mild hydronephrosis; 3.72 (95% CI, 2.79-4.97) and 0.80 (95% CI, 0.73-0.88) for short femur; 4.81 (95% CI, 3.49-6.62) and 0.74 (95% CI, 0.63-0.88) for short humerus; 21.48 (95% CI, 11.48-40.19) and 0.71 (95% CI, 0.57-0.88) for aberrant right subclavian artery (ARSA); and 23.27 (95% CI, 14.23-38.06) and 0.46 (95% CI, 0.36-0.58) for absent or hypoplastic nasal bone. The combined negative LR, obtained by multiplying the values of individual markers, was 0.13 (95% CI, 0.05-0.29) when short femur but not short humerus was included and 0.12 (95% CI, 0.06-0.29) when short humerus but not short femur was included. CONCLUSION: The presence of sonographic markers increases, and absence of such markers decreases, the risk for trisomy 21. In the case of most isolated markers there is only a small effect on modifying the pre-test odds for trisomy 21, but with ventriculomegaly, nuchal fold thickness and ARSA there is a 3-4-fold increase in risk and with hypoplastic nasal bone a 6-7-fold increase.

ATRA and the specific RARα agonist, NRX195183, have opposing effects on the clonogenicity of pre-leukemic murine AML1-ETO bone marrow cells.

All-trans retinoic acid (ATRA) is used successfully in the treatment of acute promyelocytic leukemia (APL). ATRA enhances hematopoietic stem cell self-renewal through retinoic acid receptor (RAR)γ activation while promoting differentiation of committed myeloid progenitors through RARα activation. Its lack of success in the treatment of non-APL acute myeloid leukemia (AML) may be related to ATRA's non-selectivity for the RARα and RARγ isotypes, and specific RARα activation may be more beneficial in promoting myeloid differentiation. To investigate this hypothesis, the effects of ATRA and the specific RARα agonist NRX195183 was assessed in AML1-ETO (AE)-expressing murine bone marrow (BM) progenitors. ATRA potentiated the in vitro clonogenicity of these cells while NRX195183 had the opposite effect. Morphological and flow cytometric analysis confirmed a predominantly immature myeloid population in the ATRA-treated AE cells while the NRX195183-treated cells demonstrated an increase in the mature myeloid population. Similarly, NRX195183 treatment promoted myeloid differentiation in an AE9a in vivo murine model. In the ATRA-treated AE cells, gene expression analyses revealed functional networks involving SERPINE1 and bone morphogenetic protein 2; AKT phosphorylation was upregulated. Collectively, these findings confirm the contrasting roles of specific RARα and RARγ activation in the clonogenicity and differentiation of AE cells with potential significant implications in the treatment of non-APL AML using a specific RARα agonist.

The impact of transcutaneous electrical stimulation therapy on appendicostomy operation rates for children with chronic constipation--a single-institution experience.

PURPOSE: Appendicostomy for antegrade continence enema is a minimally invasive surgical intervention that has helped many children with chronic constipation. At our institution, since 2006, transcutaneous electrical stimulation (TES) has been trialed to treat slow-transit constipation (STC) in children. This retrospective audit aimed to determine if TES use affected appendicostomy-formation rates and to monitor changes in practice. We hypothesized that appendicostomy rates have decreased for STC but not for other indications. METHODS: Appendicostomy-formation rate was determined for the 5 years before and after 2006. Children were identified as STC or non-STC from nuclear transit scintigraphy and patient records. RESULTS: Since 1999, 317 children were diagnosed with STC using nuclear transit scintigraphy with 121 during 2001 to 2005 (24.2/year) and 147 during 2006 to 2010 (29.4/year). Seventy-four children had appendicostomy formation. For 2001 to 2005, appendicostomy-formation rates for STC and non-STC children were similar: 5.4 per year (n = 27) and 4.8 per year (n = 24), respectively. For 2006 to 2010, appendicostomy-formation rates were 1.2 per year (n = 6) for STC and 3.2 per year (n = 16) for non-STC (χ(2), P = .04). CONCLUSION: Since 2006, appendicostomy-formation rates have significantly reduced in STC but not in non-STC children at our institute, coinciding with the introduction of TES as an alternative treatment for STC. Transcutaneous electrical stimulation has not been tested on non-STC children in this period.

Large loop excision of transformation zone and cervical length in the prediction of spontaneous preterm delivery.

OBJECTIVES: To investigate the association between previous large loop excision of transformation zone (LLETZ) and risk for subsequent spontaneous preterm delivery (sPD) and whether this effect is reflected in the measurement of cervical length at mid-gestation. DESIGN AND SETTING: A secondary analysis of data from women recruited for clinical trials of interventions to prevent preterm labour. POPULATION: A total of 26,867 women with singleton pregnancies attending for routine antenatal care. METHODS: Transvaginal sonographic measurement of cervical length was carried out at 20(+0) to 24(+6) weeks. Logistic regression analysis was used to determine the significant predictors of sPD among maternal characteristics, obstetric history, previous history of LLETZ and cervical length. MAIN OUTCOME MEASURES: Spontaneous preterm delivery. RESULTS: In the 473 women who had undergone LLETZ, compared with the 25,772 without a history of LLETZ, the rate of sPD before 34 weeks of gestation was higher (3.4 versus 1.3%, P = 0.0002) and the median cervical length was shorter (32 mm versus 34 mm, P < 0.0001). Regression analysis demonstrated that in the prediction of sPD there were significant contributions from racial origin, cigarette smoking, previous preterm delivery and LLETZ and the detection rate of sPD was 29.8%, at a false-positive rate of 10%. However, after addition of cervical length, LLETZ did not remain a significant predictor in the model, which detected 52.6% of sPD, at a false-positive rate of 10%. CONCLUSIONS: LLETZ increases the risk of sPD, even after adjustment for maternal risk factors. The effect of a previous LLETZ on sPD in a subsequent pregnancy is reflected in the measurement of cervical length at mid-gestation.