Taking Another Look at the Pornography Problems Due to Moral Incongruence Model: Does Gender Play a Role?

The pornography problems due to moral incongruence (PPMI) model is a premier framework for understanding problematic pornography use (PPU). However, past studies have generally examined men or entered gender as a covariate in primary analyses. Such approaches mask between-gender differences. Additionally, dysregulation constructs are also thought to be relevant to PPU, yet it is unclear the degree to which they incrementally predict PPU beyond moral incongruence constructs in non-pathological populations. We addressed these gaps by gathering a large sample of college students (n = 295 men, n = 838 women). Analyses with pornography users (n = 251 men, n = 407 women) were consistent with the PPMI model, adjusted for pornography use frequency. Findings did not change when dysregulation constructs of impulsivity and emotional resilience were added to the model. No paths significantly differed between genders. Altogether, among college student pornography users, religiosity was strongly positively correlated with moral disapproval (ß = .65 men, ß = .62 women), moral disapproval was moderately positively correlated with PPU (ß = .41 men, ß = .29 women), religiosity was initially moderately positively correlated with PPU (r = .21 men, r = .22 women), but became non-significant in the full model (ß = - .21 men, ß = - .04 women), and indirect effects of religiosity to PPU through moral disapproval were significant (indirect ß = .27 men, ß = .18 women). None of the dysregulation constructs significantly predicted PPU. The full model accounted for 23-22% of the PPU variance in men and women, respectively. Implications, future directions, and limitations are discussed.

Assessment of longitudinal brain development using super-resolution magnetic resonance imaging following fetal surgery for open spina bifida.

OBJECTIVES: Prenatal surgery is offered for selected fetuses with open spina bifida (OSB) to improve long-term outcome. We studied the effect of fetal OSB surgery on brain development using advanced magnetic resonance imaging (MRI) techniques to quantify the volume, surface area and shape of cerebral structures and to analyze surface curvature by means of parameters that correspond to gyrification. METHODS: We compared MRI data from 29 fetuses with OSB before fetal surgery (mean gestational age (GA), 23 + 3 weeks) and at 1 and 6 weeks after surgery, with that of 36 GA-matched control fetuses (GA range, 21 + 2 to 36 + 2 weeks). Automated super-resolution reconstruction provided three-dimensional isotropic volumetric brain images. Unmyelinated white matter, cerebellum and ventricles were segmented automatically and refined manually, after which volume, surface area and shape parameter (volume/surface area) were quantified. Mathematical markers (shape index (SI) and curvedness) were used to measure gyrification. Parameters were assessed according to lesion type (myelomeningocele vs myeloschisis (MS)), postoperative persistence of hindbrain herniation (HH) and the presence of supratentorial anomalies, namely partial agenesis of the corpus callosum (pACC) and heterotopia (HT). RESULTS: Growth in ventricular volume per week and change in shape parameter per week were higher at 6 weeks after surgery in fetuses with OSB compared with controls (median, 2500.94 (interquartile range (IQR), 1689.70-3580.80) mm3 /week vs 708.21 (IQR, 474.50-925.00) mm3 /week; P < 0.001 and 0.075 (IQR, 0.047-0.112) mm/week vs 0.022 (IQR, 0.009-0.042) mm/week; P = 0.046, respectively). Ventricular volume growth increased 6 weeks after surgery in cases with pACC (P < 0.001) and those with persistent HH (P = 0.002). During that time period, the change in unmyelinated white-matter shape parameter per week was decreased in OSB fetuses compared with controls (0.056 (IQR, 0.044-0.092) mm/week vs 0.159 (IQR, 0.100-0.247) mm/week; P = 0.002), particularly in cases with persistent HH (P = 0.011), MS (P = 0.015), HT (P = 0.022), HT with corpus callosum anomaly (P = 0.017) and persistent HH with corpus callosum anomaly (P = 0.007). At 6 weeks postoperatively, despite OSB fetuses having a lower rate of change in curvedness compared with controls (0.061 (IQR, 0.040-0.093) mm-1 /week vs 0.094 (IQR, 0.070-0.146) mm-1 /week; P < 0.001), reversing the trend seen at 1 week after surgery (0.144 (IQR, 0.099-0.236) mm-1 /week vs 0.072 (IQR, 0.059-0.081) mm-1 /week; P < 0.001), gyrification, as determined using SI, appeared to be increased in OSB fetuses overall compared with controls. This observation was more prominent in fetuses with pACC and those with severe ventriculomegaly (P-value range, < 0.001 to 0.006). CONCLUSIONS: Following fetal OSB repair, volume, shape and curvedness of ventricles and unmyelinated white matter differed significantly compared with those of normal fetuses. Morphological brain changes after fetal surgery were not limited to effects on the circulation of cerebrospinal fluid. These observations may have implications for postnatal neurocognitive outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Management of late-onset fetal growth restriction: pragmatic approach.

OBJECTIVES: There is limited prospective evidence to guide the management of late-onset fetal growth restriction (FGR) and its differentiation from small-for-gestational age. The aim of this study was to assess prospectively a novel protocol in which ultrasound criteria were used to classify women with suspected late FGR into two groups: those at low risk, who were managed expectantly until the anticipated date of delivery, and those at high risk, who were delivered soon after 37 weeks of gestation. We also compared the outcome of this prospective cohort with that of a historical cohort of women presenting similarly with suspected late FGR, in order to evaluate the impact of the new protocol. METHODS: This was a prospective study of women with a non-anomalous singleton pregnancy at ≥ 32 weeks' gestation attending a tertiary hospital in London, UK, between February 2018 and September 2019, with estimated fetal weight (EFW) ≤ 10th centile, or EFW > 10th centile in addition to a decrease in fetal abdominal circumference of ≥ 50 centiles compared with a previous scan, umbilical artery Doppler pulsatility index > 95th centile or cerebroplacental ratio < 5th centile. Women were classified as low or high risk based on ultrasound and Doppler criteria. Women in the low-risk group were delivered by 41 weeks of gestation, unless they subsequently met high-risk criteria, whereas women in the high-risk group (EFW < 3rd centile, umbilical artery Doppler pulsatility index > 95th centile or EFW between 3rd and 10th centiles (inclusive) with abdominal circumference drop or abnormal Dopplers) were delivered at or soon after 37 weeks. The primary outcome was adverse neonatal outcome and included hypothermia, hypoglycemia, neonatal unit admission, jaundice requiring treatment, suspected infection, feeding difficulties, 1-min Apgar score < 7, hospital readmission and any severe adverse neonatal outcome (perinatal death, resuscitation using inotropes or mechanical ventilation, 5-min Apgar score < 7, metabolic acidosis, sepsis, and cerebral, cardiac or respiratory morbidity). Secondary outcomes were adverse maternal outcome (operative delivery for abnormal fetal heart rate) and severe adverse neonatal outcome. Women managed according to the new protocol were compared with a historical cohort of 323 women delivered prior to the implementation of the new protocol, for whom management was guided by individual clinician expertise. RESULTS: Over 18 months, 321 women were recruited to the prospective cohort, of whom 156 were classified as low risk and 165 were high risk. Adverse neonatal outcome was significantly less common in the low-risk compared with the high-risk group (45% vs 58%; adjusted odds ratio (aOR), 0.6 (95% CI, 0.4-0.9); P = 0.022). There was no significant difference in the rate of adverse maternal outcome (18% vs 24%; aOR, 0.7 (95% CI, 0.4-1.2); P = 0.142) or severe adverse neonatal outcome (3.8% vs 8.5%; aOR, 0.5 (95% CI, 0.2-1.3); P = 0.153) between the low- and high-risk groups. Compared with women in the historical cohort classified retrospectively as low risk, low-risk women managed under the new protocol had a lower rate of adverse neonatal outcome (45% vs 58%; aOR, 0.6 (95% CI, 0.4-0.9); P = 0.026). CONCLUSIONS: Appropriate risk stratification to guide management of late FGR was associated with a reduced rate of adverse neonatal outcome in low-risk pregnancies. In clinical practice, a policy of expectantly managing women with a low-risk late-onset FGR pregnancy at term could improve neonatal and long-term development. Randomized controlled trials are needed to assess the effect of an evidence-based conservative management protocol for late FGR on perinatal morbidity and mortality and long-term neurodevelopment. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The incidence of physeal fractures in the lower limb and the frequency of premature physeal closure: a cohort study of 236 patients.

BACKGROUND AND PURPOSE: Physeal fractures represent 15-20% of all pediatric fractures and may lead to premature physeal closure (PPC). The aim of our study was to determine the incidence rates of physeal fractures in the lower limb and the proportion of PPC that lead to limb length discrepancy (LLD), and/or angular deformity (AD). PATIENTS AND METHODS: This retrospective study included 236 consecutive children with physeal fracture in the tibia, distal femur, or distal fibula. We estimated incidence rates and reviewed medical records and radiographs to obtain information regarding the development of PPC leading to LLD and AD. Of the 236 children, 100 had planned growth control or were referred for growth control due to symptoms of PPC. RESULTS: The total incidence rate was 35 (95% CI 30-39) per 100,000 person-years, with 1.2 (CI 0.5-23) for distal femur, 5.7 (CI 3.1-7.8) for proximal tibia, 14 (CI 11-17) for distal tibia, and 14 (CI 11-17) for distal fibula. The overall prevalence of PPC was 9.7% (CI 6.3-14), while the prevalence was 38% (CI 8.5-76) for distal femur, 15% (CI 5.9-31) for proximal tibia, 14% (CI 7.4--22) for distal tibia, and 1.1% (CI 0.3--59) for distal fibula. We found a significant higher hazard of PPC in fractures with ≥ 3 mm displacement (hazard ratio: 12, CI 1.5-97). CONCLUSION: 10% of children with physeal fractures developed PPC that led to LLD or AD. The highest hazard ratio was in children who had an initial fracture displacement. This study highlights the importance of routine and uniform growth evaluation after a physeal fracture.

COVID-19 and vertical transmission: assessing the expression of ACE2/TMPRSS2 in the human fetus and placenta to assess the risk of SARS-CoV-2 infection.

BACKGROUND: Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. METHODS: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. FINDINGS: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co-express the two proteins across the second trimester or at term. INTERPRETATION: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. TWEETABLE ABSTRACT: This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.

Reproducibility of assessment of full-dilatation Cesarean section scar in women undergoing second-trimester screening for preterm birth.

OBJECTIVE: To assess the reproducibility of a standardized method of measuring the Cesarean section (CS) scar, CS scar niche and their position relative to the internal os of the uterine cervix by transvaginal ultrasound in pregnant women with a previous full-dilatation CS. METHODS: This was a prospective, single-center reproducibility study on women with a singleton pregnancy and a previous full-dilatation CS who underwent transvaginal ultrasound assessment of cervical length and CS scar characteristics at 14-24 weeks' gestation. The CS scar was identified as a hypoechogenic linear discontinuity of the myometrium at the anterior wall of the lower uterine segment or cervix. The CS scar niche was identified as an indentation at the site of the scar with a depth of at least 2 mm. The CS scar position was evaluated by measuring the distance to the internal cervical os. CS scar niche parameters, including its length, depth, width, and residual and adjacent myometrial thickness, were assessed in the sagittal and transverse planes. Qualitative reproducibility was assessed by agreement regarding visibility of the CS scar and niche. Quantitative reproducibility of CS scar measurements was assessed using three sets of images: (1) real-time two-dimensional (2D) images (real-time acquisition and caliper placement on 2D images by two operators), (2) offline 2D still images (offline caliper placement by two operators on stored 2D images acquired by one operator) and (3) three-dimensional (3D) volume images (volume manipulation and caliper placement on 2D images extracted by two operators). Agreement on CS scar visibility and the presence of a niche was analyzed using kappa coefficients. Intraobserver and interobserver reproducibility of quantitative measurements was assessed using Bland-Altman plots. RESULTS: To achieve the desired statistical power, 72 women were recruited. The CS scar was visualized in > 80% of images. Interobserver agreement for scar visualization and presence of a niche in real-time 2D images was excellent (kappa coefficients of 0.84 and 0.85, respectively). Overall, reproducibility was higher for real-time 2D and offline 2D still images than for 3D volume images. The 95% limits of agreement (LOA) for intraobserver reproducibility were between ± 1.1 and ± 3.6 mm for all sets of images; the 95% LOA for interobserver reproducibility were between ± 2.0 and ± 6.3 mm. Measurement of the distance from the CS scar to the internal cervical os was the most reproducible 2D measurement (intraobserver and interobserver 95% LOA within ± 1.6 and ± 2.7 mm, respectively). Overall, niche measurements were the least reproducible measurements (intraobserver 95% LOA between ± 1.6 and ± 3.6 mm; interobserver 95% LOA between ± 3.1 and ± 6.3 mm). There was no consistent difference between measurements obtained by reacquisition of 2D images (planes obtained twice and caliper placed), caliper placement on 2D stored images or volume manipulation (planes obtained twice and caliper placed). CONCLUSIONS: The CS scar position and scar niche in pregnant women with a previous full-dilatation CS can be assessed in the second trimester of a subsequent pregnancy using either 2D or 3D volume ultrasound imaging with a high level of reproducibility. Overall, the most reproducible CS scar parameter is the distance from the CS scar to the internal cervical os. The method proposed in this study should enable clinicians to assess the CS scar reliably and may help predict pregnancy outcome. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cranial findings detected by second-trimester ultrasound in fetuses with myelomeningocele: a systematic review.

BACKGROUND: Abnormal intracranial findings are often detected at mid-trimester ultrasound (US) in fetuses with myelomeningocele (MMC). It is unclear whether these findings constitute a spectrum of the disease or are an independent finding, which should contraindicate fetal surgery. OBJECTIVE: To ascertain the spectrum and frequency of US-detected cranial findings in fetuses with MMC. SEARCH STRATEGY: MEDLINE, Embase, Web of Science and CENTRAL were searched from January 2000 to June 2020. SELECTION CRITERIA: Study reporting incidence of cranial US findings in consecutive cases of second-trimester fetuses with MMC. DATA COLLECTION AND ANALYSIS: Publication quality was assessed by Newcastle-Ottawa Scale (NOS) and modified NOS. Meta-analysis could not be performed as a result of high clinical diversity and study heterogeneity. MAIN RESULTS: Fourteen cranial US findings were reported in 15 studies. Findings in classic Chiari II malformation (CIIM) spectrum included posterior fossa funnelling (96%), small transcerebellar diameter (82-96%), 'banana' sign (50-100%), beaked tectum (65%) and 'lemon' sign (53-100%). Additional cranial findings were small biparietal diameter (BPD) and head circumference (HC) (<5th centile; 53 and 71%, respectively), ventriculomegaly (45-89%), abnormal pointed shape of the occipital horn (77-78%), thinning of the posterior cerebrum, perinodular heterotopia (11%), abnormal gyration (3%), corpus callosum disorders (60%) and midline interhemispheric cyst (42%). CONCLUSIONS: We identified 14 cranial findings by second-trimester US in fetuses with MMC. The relatively high incidence of these findings and their unclear prognostic significance might not contraindicate fetal surgery in the case of normal fetal genetic testing. Some cranial findings may independently affect postnatal outcome, however. Long-term detailed follow-up is required to investigate this. TWEETABLE ABSTRACT: A high rate of cranial abnormalities found on second-trimester ultrasound in fetuses with myelomeningocele.

Magnetic resonance imaging measurement of placental perfusion and oxygen saturation in early-onset fetal growth restriction.

OBJECTIVE: We hypothesised that a multi-compartment magnetic resonance imaging (MRI) technique that is sensitive to fetal blood oxygenation would identify changes in placental blood volume and fetal blood oxygenation in pregnancies complicated by early-onset fetal growth restriction (FGR). DESIGN: Case-control study. SETTING: London, UK. POPULATION: Women with uncomplicated pregnancies (estimated fetal weight [EFW] >10th centile for gestational age [GA] and normal maternal and fetal Doppler ultrasound, n = 12) or early-onset FGR (EFW <3rd centile with or without abnormal Doppler ultrasound <32 weeks GA, n = 12) were studied. METHODS: All women underwent MRI examination. Using a multi-compartment MRI technique, we quantified fetal and maternal blood volume and feto-placental blood oxygenation. MAIN OUTCOME MEASURES: Disease severity was stratified according to Doppler pulsatility index and the relationship to the MRI parameters was investigated, including the influence of GA at scan. RESULTS: The FGR group (mean GA 27+5  weeks, range 24+2 to 33+6  weeks) had a significantly lower EFW compared with the control group (mean GA 29+1  weeks; -705 g, 95% CI -353 to -1057 g). MRI-derived feto-placental oxygen saturation was higher in controls compared with FGR (75 ± 9.6% versus 56 ± 16.2%, P = 0.02, 95% CI 7.8-30.3%). Feto-placental oxygen saturation estimation correlated strongly with GA at scan in controls (r = -0.83). CONCLUSION: Using a novel multimodal MRI protocol we demonstrated reduced feto-placental blood oxygen saturation in pregnancies complicated by early-onset FGR. The degree of abnormality correlated with disease severity defined by ultrasound Doppler findings. Gestational age-dependent changes in oxygen saturation were also present in normal pregnancies. TWEETABLE ABSTRACT: MRI reveals differences in feto-placental oxygen saturation between normal and FGR pregnancy that is associated with disease severity.

Development and validation of predictive models for QUiPP App v.2: tool for predicting preterm birth in women with symptoms of threatened preterm labor.

OBJECTIVE: To develop enhanced prediction models to update the QUiPP App prototype, a tool providing individualized risk of spontaneous preterm birth (sPTB), for use in women with symptoms of threatened preterm labor (TPTL), incorporating risk factors, transvaginal ultrasound assessment of cervical length (CL) and cervicovaginal fluid quantitative fetal fibronectin (qfFN) test results. METHODS: Participants were pregnant women between 23 + 0 and 34 + 6 weeks' gestation with symptoms of TPTL, recruited as part of four prospective cohort studies carried out at 16 UK hospitals between October 2010 and October 2017. The training set comprised all women whose outcomes were known in May 2017 (n = 1032). The validation set comprised women whose outcomes were gathered between June 2017 and March 2018 (n = 506). Parametric survival models were developed for three combinations of predictors: risk factors plus qfFN test results alone, risk factors plus CL alone, and risk factors plus both qfFN and CL. The best models were selected using the Akaike and Bayesian information criteria. The estimated probability of sPTB < 30, < 34 or < 37 weeks' gestation and within 1 or 2 weeks of testing was calculated and receiver-operating-characteristics (ROC) curves were created to demonstrate the diagnostic ability of the prediction models. RESULTS: Predictive statistics were similar between the training and the validation sets at most outcome time points and for each combination of predictors. Areas under the ROC curves (AUC) demonstrated that all three algorithms had good accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1 and 2 weeks' post-testing in the validation set, particularly the model combining risk factors plus qfFN alone (AUC: 0.96 at < 30 weeks; 0.85 at < 34 weeks; 0.77 at < 37 weeks; 0.91 at < 1 week from testing; and 0.92 at < 2 weeks from testing). CONCLUSIONS: Validation of the new prediction models suggests that the QUiPP App v.2 can reliably calculate risk of sPTB in women with TPTL. Use of the QUiPP App in practice could lead to better targeting of intervention, while providing reassurance and avoiding unnecessary intervention in women at low risk. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Desarrollo y validación de modelos predictivos para la Aplicación QUiPP v.2: herramienta para predecir el parto pretérmino en mujeres con síntomas de amenaza de parto prematuro OBJETIVO: Desarrollar modelos de predicción mejorados para actualizar el prototipo de la Aplicación QUiPP, una herramienta que proporciona el riesgo individualizado de parto pretérmino espontáneo (PPTE), para su uso en mujeres con síntomas de amenaza de parto pretérmino (APPT), mediante la incorporación de los factores de riesgo, la evaluación de la longitud cervical (LC) mediante ecografía transvaginal y los resultados de la prueba de fibronectina fetal cuantitativa (qfFN, por sus siglas en inglés) del líquido cérvico-vaginal. MÉTODOS: Las participantes fueron mujeres embarazadas entre 23 + 0 y 34 + 6 semanas de gestación con síntomas de APPT, reclutadas como parte de cuatro estudios de cohorte prospectivos llevados a cabo en 16 hospitales del Reino Unido entre octubre de 2010 y octubre de 2017. El grupo de entrenamiento comprendía a todas las mujeres cuyos resultados se conocían en mayo de 2017 (n = 1032). El grupo de validación estaba compuesto por mujeres cuyos resultados se recogieron entre junio de 2017 y marzo de 2018 (n = 506). Se desarrollaron modelos paramétricos de supervivencia para tres combinaciones de predictores: factores de riesgo más resultados de pruebas de qfFN solamente, factores de riesgo más LC solamente, y factores de riesgo más tanto qfFN como LC. Los mejores modelos fueron seleccionados utilizando los criterios de información de Akaike y Bayesiano. Se calculó la probabilidad estimada de PPTE a <30, <34 o <37 semanas de gestación y dentro de 1 o 2 semanas de la prueba y se crearon curvas de la característica operativa del receptor (ROC, por sus siglas en inglés) para demostrar la capacidad de diagnóstico de los modelos de predicción. RESULTADOS: Las estadísticas de predicción fueron similares entre los grupos de entrenamiento y de validación en la mayoría de los puntos de tiempo de los resultados y para cada combinación de predictores. Las áreas bajo las curvas (ABC) ROC demostraron que los tres algoritmos tuvieron una buena precisión para la predicción del PPTE a <30, <34 y <37 semanas de gestación y dentro de 1 a 2 semanas después de la prueba en el grupo de validación, en particular el modelo que combina los factores de riesgo más qfFN por si solo (ABC: 0,96 a <30 semanas; 0,85 at <34 semanas; 0,77 at <37 semanas; 0,91 at <1 semana de la prueba; y 0,92 a <2 semanas de la prueba CONCLUSIONES: La validación de los nuevos modelos de predicción sugiere que la Aplicación QUiPP v.2 puede calcular de manera fiable el riesgo de PPTE en mujeres con APPT. El uso de la Aplicación QUiPP en la práctica podría llevar a un mejor cribado para la intervención, a la vez que daría seguridad y evitaría intervenciones innecesarias en mujeres con bajo riesgo.

A comparison of robotic and manual surgery for internal limiting membrane peeling.

PURPOSE: To compare the Preceyes Surgical Robotic System (Eindhoven, Netherlands) to manual internal limiting membrane (ILM) peeling using the Eyesi surgical simulator (VRmagic, Mannheim, Germany) as the operative platform. METHODS: A comparative study was carried out with surgeons initially performing ILM peeling manually and then with the robot. Twenty-three vitreoretinal surgeons agreed to participate and all consented to the use of their surgical data from the Eyesi surgical simulator. Surgeons were given a 5-min demonstration of the devices and were allowed to practice for 10 min before attempting the membrane peel. Initially, the peel was performed manually and afterwards, this was repeated using the robot-controlled forceps. Surgical simulator outcome measures were compared between approaches. RESULTS: The average time required for the procedure was 5 min for the manual approach and 9 min with the robot (paired t test, p = 0.002). Intraocular instrument movement was reduced by half with the robot. On average 344 mm was required to complete the ILM peeling with the robot compared with 600 mm using the manual approach (paired t test, p = 0.002). There were fewer macular retinal hemorrhages with the robot: 53 with manual surgery, 32 with the robot (Mann-Whitney U test, p = 0.035). Retinal injuries were eliminated with the robot. CONCLUSIONS: Intraocular robotic surgery is still in its infancy and validation work is needed to understand the potential benefits and limitations of emerging technologies. Safety enhancements over current techniques may be possible and could lead to the broader adoption of robotic intraocular surgery in the future.

Dynamic physiological temperature and pressure sensing with phase-resolved low-coherence interferometry.

We report the development and characterisation of highly miniaturised fibre-optic sensors for simultaneous pressure and temperature measurement, and a compact interrogation system with a high sampling rate. The sensors, which have a maximum diameter of 250 µm, are based on multiple low-finesse optical cavities formed from polydimethylsiloxane (PDMS), positioned at the distal ends of optical fibres, and interrogated using phase-resolved low-coherence interferometry. At acquisition rates of 250 Hz, temperature and pressure changes of 0.0021 °C and 0.22 mmHg are detectable. An in vivo experiment demonstrated that the sensors had sufficient speed and sensitivity for monitoring dynamic physiological pressure waveforms. These sensors are ideally suited to various applications in minimally invasive surgery, where diminutive lateral dimensions, high sensitivity and low manufacturing complexities are particularly valuable.

Achieving orphan designation for placental insufficiency: annual incidence estimations in Europe.

OBJECTIVE: To determine whether a novel therapy for placental insufficiency could achieve orphan drug status by estimating the annual incidence of placental insufficiency, defined as an estimated fetal weight below the 10th centile in the presence of abnormal umbilical artery Doppler velocimetry, per 10 000 European Union (EU) population as part of an application for European Medicines Agency (EMA) orphan designation. DESIGN: Incidence estimation based on literature review and published national and EU statistics. SETTING AND POPULATION: European Union. METHODS: Data were drawn from published literature, including national and international guidelines, international consensus statements, cohort studies and randomised controlled trials, and published national and EU statistics, including birth rates and stillbirth rates. Rare disease databases were also searched. RESULTS: The proportion of affected pregnancies was estimated as 3.17% (95% CI 2.93-3.43%), using a weighted average of the results from two cohort studies. Using birth rates from 2012 and adjusting for a pregnancy loss rate of 1/100 gave an estimated annual incidence of 3.33 per 10 000 EU population (95% CI 3.07-3.60 per 10 000 EU population). This fell below the EMA threshold of 5 per 10 000 EU population. CONCLUSIONS: Maternal vascular endothelial growth factor gene therapy for placental insufficiency was granted EMA orphan status in 2015 after we demonstrated that it is a rare, life-threatening or chronically debilitating and currently untreatable disease. Developers of other potential obstetric therapies should consider applying for orphan designation, which provides financial and regulatory benefits. TWEETABLE ABSTRACT: Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation.

Crash sign: new first-trimester sonographic marker of spina bifida.

OBJECTIVES: To describe a new first-trimester sonographic sign, the 'crash sign', associated with fetal open spina bifida, and to evaluate its clinical usefulness in the first-trimester diagnosis of spina bifida. METHODS: This was a retrospective review of patients referred to three fetal medicine centers in the first trimester (11 + 0 to 13 + 6 weeks) with suspected spina bifida. Spina bifida was confirmed by direct visualization of the spinal defect on ultrasound by two experts and, when possible, by fetal postmortem examination. Ultrasound images were reviewed for the presence of the crash sign, which is the posterior displacement of the mesencephalon and deformation against the occipital bone in the axial view. The first-trimester ultrasound images of a mixed group of 10 cases and 40 control fetuses without spina bifida were assessed for the presence of the crash sign by two assessors blinded to the diagnosis. RESULTS: The crash sign was present in 48 out of 53 confirmed cases of spina bifida. Of these, 27 had isolated spina bifida and 21 had an associated anomaly. Of the five cases without the crash sign, one had isolated spina bifida and four had an associated anomaly. The crash sign was not reported in any of the control fetuses. CONCLUSIONS: We have described a new first-trimester sonographic marker for the diagnosis of spina bifida. Our results suggest that the crash sign may be a useful tool in the first-trimester detection of spina bifida. Prospective evaluation of the crash sign would be beneficial, ideally in a routine clinical screening ultrasound setting. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Role of leucocyte caspase-1 activity in epidural-related maternal fever: a single-centre, observational, mechanistic cohort study.

BACKGROUND: Epidural-related maternal fever (ERMF) has been reported in ∼26% of labouring women. The underlying mechanisms remain unclear. We hypothesised that ERMF is promoted by bupivacaine disrupting cytokine production/release from mononuclear leucocytes [mononuclear fraction (MNF)]. We examined whether bupivacaine (i) reduces caspase-1 activity and release of the anti-pyrogenic cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), and (ii) is pro-inflammatory through mitochondrial injury/IL-1ß. METHODS: In labouring women, blood samples were obtained before/after epidural analgesia was implemented. Maternal temperature was recorded hourly for the first 4 h of epidural analgesia. Time-matched samples/temperatures were obtained from labouring women without epidural analgesia, pregnant non-labouring, and non-pregnant women. The primary clinical outcome was change in maternal temperature over 4 h after the onset of siting epidural catheter/enrolment. The secondary clinical outcome was development of ERMF (temperature ≥ 38°C). The effect of bupivacaine/saline on apoptosis, caspase-1 activity, intracellular IL-1ra, and plasma IL-1ra/IL-1ß ratio was quantified in MNF from labouring women or THP-1 monocytes (using flow cytometry, respirometry, or enzyme-linked immunosorbent assay). RESULTS: Maternal temperature increased by 0.06°C h-1 [95% confidence interval (CI): 0.03-0.09; P=0.003; n=38] after labour epidural placement. ERMF only occurred in women receiving epidural analgesia (five of 38; 13.2%). Bupivacaine did not alter MNF or THP-1 apoptosis compared with saline control, but reduced caspase-1 activity by 11% (95% CI: 5-17; n=10) in MNF from women in established labour. Bupivacaine increased intracellular MNF IL-1ra by 25% (95% CI: 10-41; P<0.001; n=10) compared with saline-control. Epidural analgesia reduced plasma IL-1ra/IL-1ß ratio (mean reduction: 14; 95% CI: 7-30; n=30) compared with women without epidural analgesia. CONCLUSIONS: Impaired release of anti-pyrogenic IL-1ra might explain ERMF mechanistically. Immunomodulation by bupivacaine during labour could promote ERMF.

Perinatal and long-term effects of maternal uterine artery adenoviral VEGF-A165 gene therapy in the growth-restricted guinea pig fetus.

Uterine artery application of adenoviral vascular endothelial growth factor A165 (Ad.VEGF-A165) gene therapy increases uterine blood flow and fetal growth in experimental animals with fetal growth restriction (FGR). Whether Ad.VEGF-A165 reduces lifelong cardiovascular disease risk imposed by FGR remains unknown. Here, pregnant guinea pigs fed 70% normal food intake to induce FGR received Ad.VEGF-A165 (1×1010 viral particles, n = 15) or vehicle ( n = 10), delivered to the external surface of the uterine arteries, in midpregnancy. Ad libitum-fed controls received vehicle only ( n = 14). Litter size, gestation length, and perinatal mortality were similar in control, untreated FGR, and FGR+Ad.VEGF-A165 animals. When compared with controls, birth weight was lower in male but higher in female pups following maternal nutrient restriction, whereas both male and female FGR+Ad.VEGF-A165 pups were heavier than untreated FGR pups ( P < 0.05, ANOVA). Postnatal weight gain was 10-20% greater in female FGR+Ad.VEGF-A165 than in untreated FGR pups, depending on age, although neither group differed from controls. Maternal nutrient restriction reduced heart weight in adult female offspring irrespective of Ad.VEGF-A165 treatment but did not alter ventricular wall thickness. In males, postnatal weight gain and heart morphology were not affected by maternal treatment. Neither systolic, diastolic, mean arterial pressure, adrenal weight, nor basal or challenged plasma cortisol were affected by maternal undernutrition or Ad.VEGF-A165 in either sex. Therefore, increased fetal growth conferred by maternal uterine artery Ad.VEGF-A165 is sustained postnatally in FGR female guinea pigs. In this study, we did not find evidence for an effect of maternal nutrient restriction or Ad.VEGF-A165 therapy on adult offspring blood pressure.

A randomised controlled trial of a brief intervention for illicit drug use linked to ASSIST screening in a primary healthcare setting: results from the Australian component of the World Health Organization Phase III ASSIST studies.

This report presents the findings from the Australian component of the Phase III World Health Organization (WHO) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) randomised controlled trial investigating the effectiveness of a 5-10-min brief intervention (BI) for illicit drug use delivered in primary healthcare (PHC) settings. Participants (n=171) recruited from a South Australian PHC setting (sexual health clinic) who scored in the 'moderate risk' range on the ASSIST were randomly allocated to an intervention group or wait-list control group at baseline and were followed up 3 months later. The ASSIST was administered to both groups at baseline and follow up as a measure of relative risk. Those in the intervention group received a prescribed 10-step BI at baseline. The majority (n=63) of participants received the BI for amphetamine-type stimulants (ATS) or cannabis (n=17). There was a significant reduction in total illicit substance (P<0.001) and ATS Involvement (P<0.01) for those receiving the ASSIST-linked BI, compared with control participants. There was no significant effect on cannabis involvement. The results of this study demonstrate that the ASSIST-linked BI may be a reasonably easy and effective way of reducing illicit substance use by Australian PHC clients.

Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins?

The introduction of mammographic screening has resulted in a rise in the detection rate of ductal carcinoma in situ (DCIS), currently accounting for one-fifth of screen-detected breast cancers. Although 60-70% of DCIS are treated with breast-conserving surgery (BCS) with or without radiotherapy, the frequency of subsequent surgery to re-excise positive margins in order to reduce the probability of recurrences remains high. DCIS recurrence is associated not only with financial, health and psychological implications; approximately half these recurrences are invasive disease. An appropriate margin width for patients undergoing BCS for invasive breast cancer has been largely agreed. Although there is a perception that such recommendations may be applicable to DCIS, major differences exist which may affect this application. Importantly, DCIS patients often do not receive systemic adjuvant (endocrine) therapy and not all receive radiotherapy in routine practice. There is evidence that wide margins (i.e. >10 mm) confer better protection against recurrence than positive (i.e. 0 mm) margins; however, there remains a debate concerning the optimum margin width between 0 and 10 mm. Previous studies have demonstrated that radiation therapy may not compensate for lack of re-excision in those patients with positive or close margins, while wide margins will inevitably compromise cosmesis and patients' body image perception. This review aims to address the clinical question of the minimal margin width in DCIS treated with BCS that is associated with the lowest recurrence rate and when, therefore, further surgical intervention for re-excision can be safely avoided. A range of clinical circumstances that might affect this are considered.

Total uterine artery blood volume flow rate in nulliparous women is associated with birth weight and gestational age at delivery.

OBJECTIVES: To investigate the relationship between total uterine artery blood volume flow rate (TVFR) and birth weight and gestational age at delivery, and to establish normal ranges of TVFR throughout pregnancy. METHODS: This was a prospective cohort study of 334 nulliparous women booking antenatal care at University College London Hospital between August 2008 and September 2009. Women underwent a transabdominal ultrasound examination of uterine arteries for measurement of TVFR at 12, 20 and 24 weeks' gestation. Pregnancy outcomes were recorded and linear regression was used to study the relationship between TVFR and gestational age at delivery and birth weight. RESULTS: A total of 551 ultrasound scans were performed. There was a significant, positive correlation between TVFR at 11-13 weeks (TVFR1) and at 22-26 weeks (TVFR3) and birth weight. For every 100-mL/min increase in TVFR1 and TVFR3, there was an increase in birth weight of 45 g and 27 g, respectively. There was also a positive association between TVFR1 and gestational age at delivery, with a 1.4-day increase in gestational age for every 100-mL/min increase of TVFR1. CONCLUSION: Ultrasound measurement of TVFR in the first trimester is significantly associated with both birth weight and gestational age at delivery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Urothelial cells may indicate underlying bacteriuria in pregnancy at term: a comparative study.

BACKGROUND: Urinary tract infection is common in pregnancy. Urine is sampled from by mid-stream collection (MSU). If epithelial cells are detected, contamination by vulvo-vagial skin and skin bacteria is assumed. Outside pregnancy, catheter specimen urine (CSU) is considered less susceptible to contamination. We compared MSU and CSU methods in term pregnancy to test these assumptions. METHODS: Healthy pregnant women at term gestation (n = 32, median gestation 38 + 6 weeks, IQR 37 + 6-39 + 2) undergoing elective caesarean section provided a MSU and CSU for paired comparison that were each analysed for bacterial growth and bladder distress by fresh microscopy, sediment culture and immunofluorescent staining. Participants completed a detailed questionnaire on lower urinary tract symptoms. Epithelial cells found in urine were tested for urothelial origin by immunofluorescent staining of Uroplakin III (UP3), a urothelial cell surface glycoprotein. Urothelial cells with closely associated bacteria, or "clue cells", were also counted. Wilcoxons signed rank test was used for paired analysis. RESULTS: Women reported multiple lower urinary tract symptoms (median 3, IQR 0-8). MSU had higher white blood cell counts (median 67 vs 46, z = 2.75, p = 0.005) and epithelial cell counts (median 41 vs 22, z = 2.57, p = 0.009) on fresh microscopy. The proportion of UP3+ cells was not different (0.920 vs 0.935, z = 0.08, p = 0.95), however MSU had a higher proportion of clue cells (0.978 vs 0.772, z = 3.17, p = 0.001). MSU had more bacterial growth on sediment culture compared to CSU specimens (median 8088 total cfu/ml vs 0, z = 4.86, p = 0.001). Despite this, routine laboratory cultures reported a negative screening culture for 40.6% of MSU specimens. CONCLUSION: Our findings have implications for the correct interpretation of MSU findings in term pregnancy. We observed that MSU samples had greater bacterial growth and variety when compared to CSU samples. The majority of epithelial cells in both MSU and CSU samples were urothelial in origin, implying no difference in contamination. MSU samples had a higher proportion of clue cells to UP3+ cells, indicating a greater sensitivity to bacterial invasion. Urinary epithelial cells should not be disregarded as contamination, instead alerting us to underlying bacterial activity.

The Acceptability and Feasibility of Screening for Alcohol and Drug Misuse in a Hospital Emergency Department.

OBJECTIVES: Screening and brief intervention (SBI) is an evidence-based technique for reducing harmful consumption of alcohol and other drugs, which has been shown to be effective in Emergency Departments (EDs). The feasibility of SBI in the ED, however, remains contentious and no studies have been conducted on this topic in a New Zealand ED. MATERIALS AND METHODS: This study recruited 8 experienced ED nurses who attempted to provide SBI, using the ASSIST-Lite tool, to as many of their patients as possible over one calendar month. All nurses participated in a comprehensive 1-day training workshop on the administration and interpretation of the ASSIST-Lite and linked brief intervention. RESULTS: Only 46 (11.79%) of the 390 eligible patients were given the opportunity to participate over the data collection period. Analysis of the data showed there was a significant, negative correlation between the number of patients in the ED and the average number of screens that were performed by the nurses, and that the number of screens waned immediately after SBI training. Following the data collection period, the nurse participants were interviewed about their experience. These interviews revealed 3 main themes that contextualized the willingness to, but inherent difficulty of, administering the SBI within the ED environment. CONCLUSIONS: High patient-to-nurse ratios in the ED currently preclude nurses from providing consistent SBI to all eligible patients; however, there are several practical considerations highlighted here that might help nurses increase the participation rate.