The fetal profile line:a proposal for a sonographic reference line to classify forehead and mandible anomalies in the second and third trimester

Objectives To test the fetal profile (FP) line, defined as the line that passes through the anterior border of the mandible and the nasion, as a reference line for forehead and mandible anomalies. Methods Volumes of 248 normal and 24 pathological fetuses (1636 and 1937?weeks gestation, respectively) were analysed retrospectively. When the FP line passes anteriorly, across or posteriorly to the frontal bone, this was defined as negative, zero or positive, respectively. When the FP line was positive the distance (F distance) between the FP line and the frontal bone was measured. Results No cases with a negative FP line were found in the normal fetuses. Before 27?weeks gestation the FP line was always zero except in one case. After 27?weeks gestation the FP line was positive in up to 25% (F distance (mean, range): 2.8, 2.13.6?mm). The FP line correctly identified 13 cases with retrognathia, 5 cases with frontal bossing and 3 cases with a sloping forehead. Conclusion Although large prospective studies are needed, the FP line may be a useful tool to detect second trimester profile anomalies such as retrognathia, sloping forehead and frontal bossing with the possibility of quantifying the latter. (c) 2012 John Wiley & Sons, Ltd

International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) - the propagation of knowledge in ultrasound for the improvement of OB/GYN care worldwide: experience of basic ultrasound training in Oman.

BACKGROUND: The aim of this study is to evaluate effectiveness of a new ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) Outreach Teaching and Training Program delivered in Muscat, Oman. METHODS: Quantitative assessments to evaluate knowledge and practical skills were administered before and after an ultrasound course for sonologists attending the ISUOG Outreach Course, which took place in November, 2017, in Oman. Trainees were selected from each region of the country following a national vetting process conducted by the Oman Ministry of Health. Twenty-eight of the participants were included in the analysis. Pre- and post-training practical and theoretical scores were evaluated and compared. RESULTS: Participants achieved statistically significant improvements, on average by 47% (p < 0.001), in both theoretical knowledge and practical skills. Specifically, the mean score in the theoretical knowledge test significantly increased from 55.6% (± 14.0%) to 81.6% (± 8.2%), while in the practical test, the mean score increased from 44.6% (± 19.5%) to 65.7% (± 23.0%) (p < 0.001). Performance was improved post-course among 27/28 participants (96.4%) in the theoretical test (range: 14 to 200%) and among 24/28 (85.7%) trainees in the practical skills test (range: 5 to 217%). CONCLUSION: Application of the ISUOG Basic Training Curriculum and Outreach Teaching and Training Course improved the theoretical knowledge and practical skills of local health personnel. Long-term re-evaluation is, however, considered imperative to ascertain and ensure knowledge retention

Influence of surface chemistry and morphology of nanoparticles on protein corona formation

Nanomaterials offer promising solutions as drug delivery systems and imaging agents in response to the demand for better therapeutics and diagnostics. However, the limited understanding of the interaction between nanoparticles and biological entities is currently hampering the development of new systems and their applications in clinical settings. Proteins and lipids in biological fluids are known to complex with nanoparticles to form a “biomolecular corona”. This has been shown to affect particles' morphology and behavior in biological systems and their interactions with cells. Hence, understanding how nanomaterials' physicochemical properties affect the formation and composition of this biocorona is a crucial step. This work evaluates existing literature on how morphology (size and shape), and surface chemistry (charge and hydrophobicity) of nanoparticles influence the formation of protein corona. The latest evidence suggest that although surface charge promotes the interaction with proteins and lipids, surface chemistry plays a leading role in determining the affinity of the nanoparticle for biomolecules and, ultimately, the composition of the corona. More recently the study of additional nanoparticles' properties like shape and surface chirality have demonstrated a significant effect on protein corona architecture, providing new tools to tailor biomolecular corona formation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies. Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial

BACKGROUND: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses. OBJECTIVE: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome. STUDY DESIGN: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European “TRUFFLE” trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome. RESULTS: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19–1.0]; delta short-term variation, 0.54 [confidence interval, 0.13–0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52–0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40–0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85). CONCLUSIONS: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses

Tuberculous Meningitis: an Endemic Cause of Intracranial Hypertension

Tuberculous meningitis (TBM) presents a complex clinical scenario, often marked by delayed recognition and high mortality. Our case involves a 27-year-old woman from Nepal with no significant medical history, presented with a two-week history of fatigue, altered consciousness, dizziness, vomiting, fever, holocranial headache, and photophobia. Initial examination revealed signs consistent with meningitis, including fever, hypertensive state, prostration, bilateral exophthalmos, sixth cranial nerve paresis, and positive Kernig/Brudzinski signs. Cerebrospinal fluid (CSF) exhibited characteristics typical of TBM: turbidity, lymphocytic-predominant pleocytosis, low glucose, and elevated protein. The patient was promptly started on meningeal doses of vancomycin, ceftriaxone, and acyclovir. However, persistent fever, neurological deterioration, and signs of increased intracranial pressure led to the decision to initiate conventional empiric treatment of tuberculosis (TB) with isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) and dexamethasone 1 week before cultural positivity for Mycobacterium tuberculosis of CSF. The case underscores the importance of considering TBM in patients from endemic regions, interpreting CSF findings, and initiating empirical treatment in critical scenarios, contributing to a positive patient outcome despite the diagnostic challenges.info:eu-repo/semantics/publishedVersio

The TRUFFLE study; fetal monitoring indications for delivery in 310 IUGR infants with 2 year's outcome delivered before 32 weeks of gestation.

OBJECTIVE: In the TRUFFLE study on outcome of early fetal growth restriction women were allocated to three timing of delivery plans according to antenatal monitoring strategies based on reduced computerized cardiotocographic heart rate short term variation (c-CTG STV) , early Ductus Venosus (DV p95) or late DV (DV noA) changes. However, many infants were per protocol delivered because of 'safety net' criteria, or for maternal indications, or 'other fetal indications' or after 32 weeks of gestation when the protocol was not applied anymore. It was the objective of the present post-hoc sub-analysis to investigate the indications for delivery in relation to outcome at 2 years in infants delivered before 32 weeks, to come to a further refinement of management proposals. METHODS: we included all 310 cases of the TRUFFLE study with known outcome at 2 years corrected age and 7 perinatal and infant deaths, apart from 7 cases with an inevitable death. Data were analyzed according to the randomization allocation and specified for the intervention indication. RESULTS: overall only 32% of fetuses born alive were delivered according to the specified monitoring parameter for indication for delivery. 38% were delivered because of safety net criteria, 15% because of other fetal reasons and 15% because of maternal reasons. In the c-CTG arm 51% of infants were delivered because of reduced STV. In the DV p95 arm 34% were delivered because of an abnormal DV and in the DV no A wave arm only 10% of cases were delivered accordingly. The majority of fetuses in the DV arms delivered for safety net criteria were delivered because of spontaneous decelerations. Two year's intact survival was highest in the combined DV arms as compared to the c-CTG arm (p = 0.05 when life born, p = 0.21 including fetal death), with no difference between the DV arms. Poorer outcome in the c-CTG arm was restricted to fetuses delivered because of decelerations in the safety net subgroup. Infants delivered because of maternal reasons had the highest birth weight and a non-significant higher intact survival. CONCLUSIONS: In this sub-analysis of fetuses delivered before 32 weeks the majority of infants were delivered for other reasons than according to the allocated CTG or DV monitoring strategy. Since in the DV arms CTG criteria were used as safety net criteria, but in the c-CTG arms no DV safety net criteria were applied, we speculate that the slightly poorer outcome in the CTG arm might be explained by absence of DV data. Optimal timing of delivery of the early IUGR fetus may therefore best be achieved by monitoring them longitudinally with DV and CTG monitoring

A generalized invariant imbedding equation II

Research into fetal development and medicin

Longitudinal study of computerised cardiotocography in early fetal growth restriction.

OBJECTIVES: To explore if in early fetal growth restriction (FGR) the longitudinal pattern of short-term fetal heart rate (FHR) variation (STV) can be used for identifying imminent fetal distress and if abnormalities of FHR registration associate with two-year infant outcome. METHODS: The original TRUFFLE study assessed if in early FGR the use of ductus venosus Doppler pulsatility index (DVPI), in combination with a safety-net of very low STV and / or recurrent decelerations, could improve two-year infant survival without neurological impairment in comparison to computerised cardiotocography (cCTG) with STV calculation only. For this secondary analysis we selected women, who delivered before 32 weeks, and who had consecutive STV data for more than 3 days before delivery, and known infant two-year outcome data. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values except the last one were calculated. Life table analysis and Cox regression analysis were used to calculate the day by day risk for a low STV or very low STV and / or FHR decelerations (DVPI group safety-net) and to assess which parameters were associated to this risk. Furthermore, it was assessed if STV pattern, lowest STV value or recurrent FHR decelerations were associated with two-year infant outcome. RESULTS: One hundred and fourty-nine women matched the inclusion criteria. Using the individual STV regression lines prediction of a last STV below the cCTG-group cut-off had a sensitivity of 0.42 and specificity of 0.91. For each day after inclusion the median risk for a low STV(cCTG criteria) was 4% (Interquartile range (IQR) 2% to 7%) and for a very low STV and / or recurrent decelerations (DVPI safety-net criteria) 5% (IQR 4 to 7%). Measures of STV pattern, fetal Doppler (arterial or venous), birthweight MoM or gestational age did not improve daily risk prediction usefully. There was no association of STV regression coefficients, a last low STV or /and recurrent decelerations with short or long term infant outcomes. CONCLUSION: The TRUFFLE study showed that a strategy of DVPI monitoring with a safety-net delivery indication of very low STV and / or recurrent decelerations could increase infant survival without neurological impairment at two years. This post-hoc analysis demonstrates that in early FGR the day by day risk of an abnormal cCTG as defined by the DVPI protocol safety-net criteria is 5%, and that prediction of this is not possible. This supports the rationale for cCTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DVPI is in the normal range

Right-heart dysfunction in women with congenital heart disease and pre-eclampsia

We read with interest the systematic review and meta-analysis on perinatal complications among pregnant women with congenital heart disease (CHD), by Martinez-Portilla et al. 1. The authors conclude that, apart from in a subpopulation of women with aortic steno-sis, the incidence of pre-eclampsia is not increased in women with CHD. It is surprising that, in this systematic review, not one report is included of the important ZAHARA (Zwangerschap bij Aangeboren HARtAf-wijkingen, translated as Pregnancy in Congenital Heart Disease) publications by the Dutch consortium of the University Hospitals of Groningen, Amsterdam, Rot-terdam, Utrecht, Nijmegen and their affiliated hospitals. It is even more surprising that one of the most important findings from this consortium is not evaluated in the meta-analysis: the association between right-heart dysfunction and pregnancy/perinatal outcome. This association was identified in women with corrected tetralogy of Fallot 2 or aortic coarctation 3 , in whom abnormal right-heart function was demonstrable before conception on both cardiosonography 4 and cardiac magnetic resonance imaging 5. Right-heart dysfunction is an intrinsic feature of pre-eclampsia 6,7 , as is venous hemody-namic dysfunction 8,9. It is well known that pre-eclampsia is a risk factor for cardiovascular disease later in life 10. Heart failure presents more commonly with preserved ejection fraction in women than in men 11 , and this is associated with right atrial remodeling and subsequent tri-cuspid regurgitation 12. In the evaluation of the association between cardiac (dys)function and pregnancy outcome, we believe that functional assessment of the right heart is mandatory. We invite the authors to add this assessment to their meta-analysis to see whether their conclusion regarding the lack of an association between CHD and adverse maternal/perinatal outcome persists

Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I—clinical impact

Objective: To evaluate the clinical impact of nationwide implementation of genome-wide non-invasive prenatal testing (NIPT) in pregnancies at increased risk for fetal trisomies 21, 18 and 13 (TRIDENT study). Method: Women with elevated risk based on first trimester combined testing (FCT ≥ 1:200) or medical history, not advanced maternal age alone, were offered NIPT as contingent screening test, performed by Dutch University Medical laboratories. We analyzed uptake, test performance, redraw/failure rate, turn-around time and pregnancy outcome. Results: Between 1 April and 1 September 2014, 1413/23 232 (6%) women received a high-risk FCT result. Of these, 1211 (85.7%) chose NIPT. One hundred seventy-nine women had NIPT based on medical history. In total, 1386/1390 (99.7%) women received a result, 6 (0.4%) after redraw. Mean turn-around time was 14 days. Follow-up was available in 1376 (99.0%) pregnancies. NIPT correctly predicted 37/38 (97.4%) trisomies 21, 18 or 13 (29/30, 4/4 and 4/4 respectively); 5/1376 (0.4%) cases proved to be false positives: trisomies 21 (n = 2), 18 (n = 1) and 13 (n = 2). Estimated reduction in invasive testing was 62%. Conclusion: Introduction of NIPT in the Dutch National healthcare-funded Prenatal Screening Program resulted in high uptake and a vast reduction of invasive testing. Our study supports offering NIPT to pregnant women at increased risk for fetal trisomy. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd