Cosmetic retinoid use in photoaged skin: A review of the compounds, their use and mechanisms of action.

The inevitable attrition of skin due to ultraviolet radiation, termed photoaging, can be partially restored by treatment with retinoid compounds. Photoaged skin in lightly pigmented individuals, clinically presents with the appearance of wrinkles, increased laxity, and hyper- and hypopigmentation. Underlying these visible signs of ageing are histological features such as epidermal thinning, dermal-epidermal junction flattening, solar elastosis and loss of the dermal fibrillin microfibrillar network, fibrillar collagen and glycosaminoglycans. Retinoid compounds are comprised of three main generations with the first generation (all-trans retinoic acid, retinol, retinaldehyde and retinyl esters) primarily used for the clinical and cosmetic treatment of photoaging, with varying degrees of efficacy, tolerance and stability. All-trans retinoic acid is considered the 'gold standard' for skin rejuvenation; however, it is a prescription-only product largely confined to clinical use. Therefore, retinoid derivatives are readily incorporated into cosmeceutical formulations. The literature reported in this review suggests that retinol, retinyl esters and retinaldehyde that are used in many cosmeceutical products, are efficacious, safe and well-tolerated. Once in the skin, retinoids utilize a complex signalling pathway that promotes remodelling of photoaged epidermis and dermis and leads to the improvement of the cutaneous signs of photoaging.

L'altération inévitable de la peau due aux rayons ultraviolets, appelée photovieillissement, peut être partiellement restaurée par un traitement à base de composés rétinoïdes. Chez les personnes à la pigmentation claire, le photovieillissement de la peau se manifeste au plan clinique par l'apparition de rides, un relâchement accru et une hyperpigmentation ou hypopigmentation. Ces signes visibles du vieillissement sont sous­tendus par des caractéristiques histologiques telles que l'amincissement de l'épiderme, l'aplatissement de la jonction dermo­épidermique, l'élastose solaire et la perte du réseau microfibrillaire de fibrilline dermique, du collagène fibrillaire et des glycosaminoglycanes. Les composés rétinoïdes sont constitués de trois générations principales, la première génération (acide tout­trans rétinoïque, rétinol, rétinaldéhyde et esters de rétinyle) étant principalement utilisée pour le traitement clinique et cosmétique du photovieillissement, avec des degrés variables d'efficacité, de tolérance et de stabilité. L'acide tout­trans rétinoïque est considéré comme la référence en matière de rajeunissement de la peau; il s'agit toutefois d'un produit délivré uniquement sur ordonnance, dont l'utilisation est largement limitée au domaine clinique. Les dérivés rétinoïdes sont donc volontiers incorporés ds formulations cosméceutiques. La littérature citée dans cette synthèse bibliographique laisse penser que le rétinol, les esters de rétinyle et le rétinaldéhyde, utilisés dans de nombreux produits cosmétiques, sont efficaces, sûrs et bien tolérés. Une fois dans la peau, les rétinoïdes utilisent une voie de signalisation complexe qui favorise le remodelage de l'épiderme et du derme photovieillis, et conduit à l'amélioration des signes cutanés du photovieillissement.

Visible light and human skin pigmentation: The importance of skin phototype.

Melanin is synthesised within melanocytes and transferred to keratinocytes in human skin, thereby regulating skin colour and protecting skin cells against UVR-induced damage. We commonly divide human skin into six phototypes (SPT)-I to -VI (Fitzpatrick scale) according to the skin's tanning response to UVR. In this pilot study, we investigated the impact of UVR (maximum 311nm), blue (peak 450nm) and green visible light (peak 530nm) on melanin production and type in healthy human skin histocultures (SPT-I, -II and -III). UVR, blue and green light stimulated a surface tanning response in SPT-II and -III, but not SPT-I. Using the Warthin-Starry stain for sensitive melanin detection, all three light treatments induced melanogenesis in SPT-II and -III skin. Surprisingly, blue and green light (but not UVR) stimulated melanin synthesis in SPT-I skin. Moreover, melanin synthesis induced by blue and green visible light in SPT-I, SPT-II, and SPT-III skin was not associated with a detectable increase in DNA damage or cell apoptosis. By contrast, both responses were detected after UVR. These data suggest that blue and green visible light can stimulate melanin production in fair-skinned individuals without, at least some of, the harmful consequences of UVR-induced pigmentation. We are currently examining the molecular basis of UVR-independent melanogenesis in fair skin.

The Natural History of Trisomy 21: Outcome Data from a Large Tertiary Referral Centre.

OBJECTIVE: The aim of the study was to prospectively gather data on pregnancy outcomes of prenatally diagnosed trisomy 21 (T21) in a large tertiary referral centre. METHODS: Data were gathered prospectively in a large tertiary referral centre over 5 years from 2013 to 2017 inclusively. Baseline demographic and pregnancy outcome data were recorded on an anonymized computerized database. RESULTS: There were 1,836 congenital anomalies diagnosed in the study period including 8.9% (n = 165) cases of T21. 79% (n = 131) were age 35 or older at diagnosis. 79/113 (69.9%) women chose a termination of pregnancy (TOP) following a diagnosis of T21. Amongst pregnancies that continued, there were 4 second-trimester miscarriages (4/34, 11.7%), 9 stillbirths (9/34, 26.4%), and 1 neonatal death, giving an overall pregnancy and neonatal loss rate of 14/34 (41.1%). CONCLUSION: The risk of foetal loss in prenatally diagnosed T21 is high at 38% with an overall pregnancy loss rate of 41.1%. This information may be of benefit when counselling couples who are faced with a diagnosis of T21 particularly in the context of limited access to TOP.

Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes.

Melanin granules cluster within supra-nuclear caps in basal keratinocytes (KCs) of the human epidermis, where they protect KC genomic DNA against ultraviolet radiation (UVR) damage. While much is known about melanogenesis in melanocytes (MCs) and a moderate amount about melanin transfer from MC to KC, we know little about the fate of melanin once inside KCs. We recently reported that melanin fate in progenitor KCs is regulated by rare asymmetric organelle movement during mitosis. Here, we explore the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. Short-term cultures of human skin explants were treated with cytochalasin-B and nocodazole to target actin filaments and microtubules, respectively. Treatment effects on melanin distribution were assessed by the Warthin-Starry stain, on centrosome-associated proteins by immunofluorescence microscopy, and on co-localisation with melanin granules by brightfield microscopy. Cytochalasin-B treatment disassembled supra-nuclear melanin caps, while nocodazole treatment moved melanin from the apical to basal KC domain. Centrosome and centriolar satellite-associated proteins showed a high degree of co-localisation with melanin. Thus, once melanin granules are transferred to KCs, their preferred apical distribution appears to be facilitated by coordinated movement of centrosomes and centriolar satellites. This mechanism may control melanin's strategic position within UVR-exposed KCs.

Evolution of a prenatal genetic clinic-A 10-year cohort study.

OBJECTIVE: To (a) evaluate the proportion of women where a unifying genetic diagnosis was obtained following assessment of an observed pattern of fetal anomalies and (b) assess trends in genetic testing in a joint fetal-medicine genetic clinic. METHOD: Retrospective cohort study of all women attending the clinic. Outcomes included (a) indication for referral, (b) genetic test performed and (c) diagnoses obtained. RESULTS: From 2008 to 2019, 256 patients were referred and reviewed, of which 23% (n = 59) were consanguineous. The main indication for referral was the observed pattern of fetal anomalies. Over 10 years, the number of patients reviewed increased from 11 to 35 per annum. A unifying genetic diagnosis was obtained in 43.2% (n = 79/183), the majority of which were diagnosed prenatally (50.6% [n = 40/79]). The main investigation(s) that was the ultimate diagnostic test was targeted gene panel sequencing 34.2% (n = 27/79), with this and exome sequencing becoming the dominant genetic test by 2019. Pregnancies reviewed due to an abnormal karyotype or microarray decreased as an indication for referral during the study period (21.6% [n = 16/74] 2008-2012 vs 16.5% [n = 30/182] in 2012-2019). CONCLUSION: A prenatal genetic clinic with a structured multi-disciplinary team approach may be successful in obtaining a unifying prenatal genetic diagnosis.

Is birth weight the major confounding factor in the study of gestational weight gain?: an observational cohort study.

BACKGROUND: Much interest has been focussed on both maternal obesity and gestational weight gain (GWG), particularly on their role in influencing birth weight (BW). Several large reviews have reported that excessive GWG is associated with an increase in BW. However recent large, well-designed, randomized controlled trials studying interventions aimed at reducing GWG have all consistently failed to show a reduction in BW despite achieving a reduction in GWG. The aim of this longitudinal prospective study was to examine the relationship between GWG and birth weight in women where GWG and Body Mass Index (BMI) were measured accurately in a strictly standardized way. METHODS: Women were enrolled at their convenience before 18 weeks gestation. Height and weight were measured accurately at the first antenatal visit and BMI calculated. Maternal weight was measured again after 37 weeks gestation. The weight of the baby was measured at birth. Relationships were tested using linear regression analysis, chi-squared tests and t-tests as appropriate. RESULTS: Of the 522 women studied, the mean BMI was 25.3 kg/m2 and 15.7% were obese. The mean BW at term was 3576 g (2160-5120) and 2.7% (n = 14) weighed ≥4500 g. The mean GWG overall was 12.3 kg (4.6 to 28.4) and GWG decreased as BMI increased. The mean GWG was less in obese women, at 8.7 kg (- 4.6 to 23.4), compared to non-obese,13.0 kg (0.6-28.4) (p < 0.001). Mean BW in obese women was 3630 g vs 3565 g in non-obese (p = 0.27). The total GWG correlated positively with BW (p < 0.001). When BW was subtracted from total GWG, GWG no longer correlated with BW (p = 0.12). CONCLUSIONS: The positive correlation between GWG in pregnancy and BW can be accounted for by the contribution of fetal weight to GWG antenatally without a contribution from increased maternal adiposity. There was a wide range of BW irrespective of the degree of GWG and obese women had a lower GWG than non-obese women. These findings help explain why Randomized Controlled Trials (RCTs) designed to reduce GWG have failed to decrease BW and suggest there is no causative link between excessive GWG and increased BW.

Do universal school-based mental health promotion programmes improve the mental health and emotional wellbeing of young people? A literature review.

AIMS AND OBJECTIVES: To examine evidence-using a range of outcomes-for the effectiveness of school-based mental health and emotional well-being programmes. BACKGROUND: It is estimated that 20% of young people experience mental health difficulties every year. Schools have been identified as an appropriate setting for providing mental health and emotional well-being promotion prompting the need to determine whether current school-based programmes are effective in improving the mental health and emotional well-being of young people. METHODS: A systematic search was conducted using the health and education databases, which identified 29 studies that measured the effectiveness of school-based universal interventions. Prisma guidelines were used during the literature review process. RESULTS: Thematic analysis generated three key themes: (i) help seeking and coping; (ii) social and emotional well-being; and (iii) psycho-educational effectiveness. CONCLUSION: It is concluded that whilst these studies show promising results, there is a need for further robust evaluative studies to guide future practice. RELEVANCE TO CLINICAL PRACTICE: All available opportunities should be taken to provide mental health promotion interventions to young people in the school environment, with a requirement for educational professionals to be provided the necessary skills and knowledge to ensure that the school setting continues to be a beneficial environment for conducting mental health promotion.

The relationship between maternal body composition in early pregnancy and foetal mid-thigh soft-tissue thickness in the third trimester in a high-risk obstetric population.

Maternal obesity is an emerging challenge in contemporary obstetrics. To date there has been no study analysing the relationship between specific maternal body composition measurements and foetal soft-tissue measurements. The aim of this study was to determine whether measurement of maternal body composition at booking predicts foetal soft-tissue trajectories in the third trimester. We analysed the relationship between foetal thigh in the third trimester and both maternal BMI and body composition using the Tanita digital scales in the first trimester. Foetal subcutaneous thigh tissue measurements were obtained at intervals of 28, 32 and 36 weeks of gestation. A total of 160 women were identified. There was a direct correlation between MTST at 36 weeks and BMI (p = .002). There was a positive correlation between MTST at 36 weeks and leg fat mass (p = .13) and leg fat free mass (p = .013). There was a positive correlation between arm fat free mass and MTST at 36 weeks. We showed there is an association between maternal fat distribution and foetal subcutaneous thigh tissue measurements. MTST may be more useful in determining if a child is at risk of macrosomia. Impact statement Previous studies have suggested that maternal obesity programmes intrauterine foetal adiposity and growth. The aim of this study was to examine the relationship in a high-risk obstetric population between measurements of maternal body composition in early pregnancy and the assessment of foetal adiposity in the third trimester using serial ultrasound measurements of mid-thigh soft-tissue thickness. BMI is only a surrogate measurement of fat and does not measure fat distribution. Our study shows the distribution of both maternal fat and fat-free mass in early pregnancy may be positively associated with foetal soft-tissue measurements in the third trimester. Maternal arthropometric measurements other than BMI may help predict babies at risk of macrosomia and neonatal adiposity.

Maternal arterial elasticity in the first trimester as a predictor of birthweight.

The early detection of foetal growth restriction and macrosomia is an important goal of modern obstetric care. Aberrant foetal growth is an important cause of perinatal morbidity and mortality. Current modalities for detecting the abnormal foetal growth are often inadequate. Pulse wave analysis using applanation tonometry is a simple and non-invasive test that provides information about the cardiovascular system. Arterial elasticity has previously been implicated in the pathophysiology of pre-eclampsia and cardiovascular disease. Our study examined the relationship between maternal arterial elasticity and birthweight by using pulse wave analysis. We discovered that increased large artery elasticity predicted a larger baby at birth. Large artery elasticity therefore has the potential to act as a useful screening tool which may help in the prediction of women who are at risk of aberrant foetal growth.

Frequency of nonthromboembolic imaging abnormalities in pregnant women referred for computed tomography pulmonary arteriography.

PURPOSE: The study sought to determine the frequency of nonthromboembolic imaging abnormalities in pregnant women referred for computed tomography pulmonary arteriography (CTPA). MATERIALS AND METHODS: CTPA studies on 100 consecutive pregnant women performed over a 5-year period were reviewed independently by 2 radiologists, with conflicts resolved by consensus. Age range was 18-43 years (mean 28 years). The presence or absence of pulmonary embolism and of nonthromboembolic imaging abnormalities was recorded. These were graded as A if the abnormalities were thought to provide potential alternative explanations for acute symptoms, B if findings were incidental that required clinical or radiologic follow-up, and C if the findings did not require further action. RESULTS: Pulmonary embolism was seen in 5 women. In 2 of these additional findings of consolidation and infarction were seen. Ninety-five women did not have pulmonary embolism. Eleven women (12%) had grade A abnormalities; 6 cases of consolidation, 2 cases of lobar collapse, and 3 cases of heart failure with pleural effusions. One woman had a grade B abnormality due to the presence of pulmonary nodules. Ten women had incidental grade C abnormalities. CONCLUSION: Pulmonary embolism occurs in 5% of pregnant women referred for CTPA. In pregnant women without embolism on CTPA, potential alternative causes for patient symptoms are seen on CT in 12% of cases.

Fetal subcutaneous tissue measurements in pregnancy as a predictor of neonatal total body composition.

OBJECTIVE: The purpose of this study was to examine the relationship between prenatal measures of subcutaneous tissue as surrogate markers of fetal nutritional status and correlate them with neonatal total body composition. METHODS: This prospective longitudinal study of 62 singleton pregnancies obtained serial biometry and subcutaneous tissue measurements at 28, 33 and 38 weeks gestation. These measurements were then correlated with neonatal body composition, which was analysed using the PEAPOD™ Infant Body Composition System (Cosmed USA, Concord, CA, USA). RESULTS: At 38 weeks gestation, fetal abdominal subcutaneous tissue (FAST) in millimetres was significantly associated with infant fat mass at delivery (+64 g per mm of FAST, p < 0.001). Thigh fat (TF) at 28 weeks gestation was associated with infant fat mass at delivery (+79 g/mm TF, p = 0.023). TF at 38 weeks gestation was associated with infant fat mass (+63/mm TF, p = 0.004). TF and FAST at 38 weeks were also predictive of both birth weight and increased abdominal circumference (AC) (p = 0.001) with FAST measurement predicting an additional 5.7 mm in AC per millimetre of FAST (p = 0.002) and TF predicting an additional 6.9 mm per mm of TF (p = 0.002). CONCLUSION: We believe that this study further validates the use of prenatal measures of subcutaneous tissue and may help to highlight fetuses at risk of newborn adiposity and metabolic syndrome.

Birth weight and neonatal adiposity prediction using fractional limb volume obtained with 3D ultrasound.

INTRODUCTION: The objective of this investigation was to study fetal thigh volume throughout gestation and explore its correlation with birth weight and neonatal body composition. This novel technique may improve birth weight prediction and lead to improved detection rates for fetal growth restriction. MATERIALS AND METHODS: Fractional thigh volume (TVol) using 3D ultrasound, fetal biometry and soft tissue thickness were studied longitudinally in 42 mother-infant pairs. The percentages of neonatal body fat, fat mass and fat-free mass were determined using air displacement plethysmography. Correlation and linear regression analyses were performed. RESULTS: Linear regression analysis showed an association between TVol and birth weight. TVol at 33 weeks was also associated with neonatal fat-free mass. There was no correlation between TVol and neonatal fat mass. Abdominal circumference, estimated fetal weight (EFW) and EFW centile showed consistent correlations with birth weight. Thigh volume demonstrated an additional independent contribution to birth weight prediction when added to the EFW centile from the 38-week scan (p = 0.03). CONCLUSION: Fractional TVol performed at 33 weeks gestation is correlated with birth weight and neonatal lean body mass. This screening test may highlight those at risk of fetal growth restriction or macrosomia.

Estimating fetal weight in gastroschisis: A 10 year audit of outcomes at the National Maternity Hospital.

OBJECTIVE: To identify whether conventional methods of estimating fetal growth (Hadlock's formula), which relies heavily on abdominal circumference measurements, are accurate in fetuses with gastroschisis. METHODS: A retrospective cohort study was performed between the period January 1, 2011 and December 31, 2021 in a tertiary referral maternity hospital identifying all pregnancies with a diagnosis of gastroschisis. Projected fetal weight was obtained using the formula (EFW [Hadlock's formula] + 185 g × [X/7]) where X was the number of days to delivery. RESULTS: During the study period 41 cases were identified. The median maternal age was 25. The median BMI was 25 and 63% were primiparous women (n = 26). Median gestation at diagnosis was 21 weeks. Median gestation at delivery was 36 weeks. A total of 4.8% of mothers had a history of drug use (n = 2). The rate of maternal tobacco use was 21.9% (n = 9). A total of 4.8% of fetuses had additional congenital anomalies including amniotic band syndrome and myelomeningocele (n = 2). Estimated fetal weight (EFW) and birth weight data were available for 34 cases. A Wilcoxon signed-rank test showed projected EFW using Hadlock's formula did not result in a statistically significant different birth weight (Z = -1.3, P = 0.169). Median projected weight and actual birth weight were 2241.35 and 2415 g respectively. Median difference was 0.64 g (95% CI: -148 to -28.5). CONCLUSION: Our data showed accuracy using standard formulae for EFW in fetuses with gastroschisis.

GridlockED as an Intervention for Nurses (GAAIN) Study.

BACKGROUND: GridlockED (The Game Crafter, LLC) is a serious game that was developed to teach challenges that face nursing and medical professionals in the emergency department (ED). However, few studies have explored nurses' perceptions of the utility, fidelity, acceptability, and applicability of the serious game modality. This study examined how ED nurses view GridlockED as a continuing education platform. METHOD: This single-center observational study explored how nurses engage with and respond to Grid-lockED. The convenience sample included participants recruited from a local continuing nursing education day. Participants completed a presurvey, engaged in a full game play session with the GridlockED game for approximately 45 minutes, and immediately completed a post-game play survey. RESULTS: Of the 48 participants (11 male, 37 female; 44 of 48 were RNs), most (91%) agreed that the workflow reflected in the game was equivalent to the flow in a typical ED. Almost all (96%) found the cases in the game reflective of real ED patients, and most (92%) found the game a useful educational tool to prepare new nurses to transition into the ED environment. CONCLUSION: The GridlockED game shows potential as a serious game to support nursing education, particularly for new ED nurse orientation and transition to ED practice. [J Contin Educ Nurs. 2024;55(5):231-238.].

Longitudinal measurement of fetal thigh soft tissue parameters and its role in the prediction of birth weight.

OBJECTIVE: The aim of this study was to profile longitudinal changes in thigh muscle and fat with gestation and to determine whether thigh measurements can improve the prediction of birth weight (BW). METHODS: A prospective longitudinal study of subcutaneous soft tissue measurements was conducted in 328 singleton fetuses at 28 and 37 weeks gestation. Estimated fetal weight (EFW) was calculated using abdominal circumference, femur length, biparietal diameter, and head circumference. RESULTS: The fetal abdominal subcutaneous tissue (FAST) and thigh muscle and fat show an increase with gestation. At 28 weeks gestation, the abdominal circumference, thigh fat, FAST, and EFW percentile were found to be significant predictors of BW. A combination of EFW percentile and thigh fat were found to be the optimal multivariate model at 28 weeks for predicting BW. At 37 weeks, BW prediction using EFW percentile, FAST, and thigh fat was the most accurate. The results revealed acceptable reproducibility for fetal thigh muscle and fat. CONCLUSION: This study provides reference ranges for thigh fat and muscle at 28 and 37 weeks gestation. The inclusion of fetal thigh fat in the algorithm improves the predictive power for birth weight. This information is important to explore the role of fetal thigh in the detection of aberrant growth.

Behaviour and sun exposure in holidaymakers alters skin microbiota composition and diversity.

Introduction: The skin microbiota plays a crucial role in maintaining epidermal homeostasis. Ultraviolet radiation (UVR) and other environmental challenges can impact the skin microbiota through direct and indirect mechanisms. This study aimed to investigate the effects of sun exposure on the skin microbiota and its relationship with individual skin phototypes. Methods: Healthy volunteers (n = 21 [4M, 17 F], mean age 33.2 years) holidayed in a sunny destination for a minimum of 7 days with swabs taken pre-holiday and up to 84 days post-holiday. Participant group was categorised by individual typology angle (ITA) classification and the composition of the skin microbiota was examined using 16S rRNA gene sequencing. Results: In the entire cohort and at all time points, the major bacterial phyla were Actinobacteria, Proteobacteria and Firmicutes. There was a significant change in microbial beta diversity at day 28 post-holiday, compared to baseline, for all participants. However, when participants were segregated into three cohorts dependent on the degree of skin tanning response between baseline (pre-holiday) and immediately one-day post-holiday, there was a reduction in Proteobacteria in the sun-seeking participants 1 day after the holiday, which recovered over time. Discussion: These findings suggest that sun exposure can affect the diversity and composition of the skin microbiota, which may have downstream effects on skin health.

Placenta accreta spectrum ultrasound stage and fetal growth.

OBJECTIVE: to evaluate fetal growth in pregnancies complicated by placenta accreta spectrum (PAS) and to compare fetal growth between cases stratified by ultrasound stage of PAS. METHODS: This was a prospective multicenter cohort study of women diagnosed with PAS between January 2018 and December 2021. We grouped participants into cases by ultrasound stage (PAS stage 1-3) and controls (PAS0). Fetal growth centiles at three timepoints with median gestational ages of 21 ± 1 weeks (interquartile range [IQR], 20 ± 1-22 ± 0 weeks), 28 ± 0 weeks (IQR, 27 ± 0-28 ± 5 weeks), and 33 ± 0 weeks (IQR, 32 ± 1-34 ± 0 weeks) and birth weight centiles were compared between cases and controls and between those with PAS stratified by ultrasound stage. RESULTS: A total of 53 women met inclusion criteria, with a mean age of 37 years (standard deviation, ±4.0 years) and body mass index of 27 kg/m2 (standard deviation, ±5.8 kg/m2 ). Median (IQR) fetal weight centiles were around the 50th centile at each timepoint, with no difference between groups. The incidence of small for gestational age (birth weight ≤ 10th percentile) and large for gestational age (birth weight ≥ 90th percentile) was 11.3% (n = 6) and 15.1% (n = 8), respectively, with no differences by ultrasound stage. The median birth weight centile was 64 (IQR, 26-85), with no differences between cases and controls or by ultrasound stage. CONCLUSIONS: In our cohort, a diagnosis of PAS was not associated with fetal growth restriction.

A multidisciplinary fetal neurosurgical service-5 years of fetal outcomes from a national referral centre.

BACKGROUND: A specialist fetal neurosurgical clinic was set up in order to improve patient care in a tertiary referral fetal medicine centre. The clinic provides a targeted clinical service for women diagnosed with fetal neurological abnormalities. The service consists of fetal MRI, fetal ultrasound and joint assessment and counselling from neurosurgery and fetal medicine teams. AIMS: We aimed to review this service that provides MDT expertise directly to parents and record the cases and pregnancy outcomes involved. METHODS: This is a prospective study of clinic data from Jan 2013 to Dec 2017. Information includes ultrasound scan findings, MRI results, karyotype results and pregnancy outcome data including post mortem results and data from the paediatric neurosurgery service at the affiliated children's hospital. RESULTS: From 2013 to 2017, there were 1852 major fetal anomalies diagnosed antenatally at the tertiary referral fetal medicine service and n = 306/1852 [16%] were primarily neurological in origin. The neurosurgical clinic reviewed 125 patients since 2013. The most common reasons for referral were spina bifida, n = 60 [48%] and isolated ventriculomegaly n = 43 [34%]. Other reasons for referral include agenesis of the corpus callosum n = 4 [3%], encephalocoele n = 5 [4%] and intracranial mass lesions n = 3 [2.4%]. Cases with borderline ventriculomegaly and cases with known chromosomal or genetic abnormalities were not typically referred to the clinic. Full outcome data were available on 110 of 125 women seen. Thirty-two women [29%] underwent invasive testing and 14 women [12.7%] had a termination of pregnancy. CONCLUSION: Multidisciplinary antenatal counselling supported with in utero MRI provides families with optimum information to inform them of likely neonatal outcome.

The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study.

BACKGROUND: Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility. METHODS: We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre. RESULTS: Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1. CONCLUSIONS: These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.

Definition of a critical bleed in patients with immune thrombocytopenia: Communication from the ISTH SSC Subcommittee on Platelet Immunology.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. In preparation for an upcoming guideline, the ITP Emergency Management Guideline Panel, including clinical experts in hematology, emergency medicine, research methodology, and patient representatives, identified the need for a standardized definition of a critical ITP bleed. The goal of the definition was to distinguish critical bleeds from bleeds that may not require urgent treatment, typically in the context of severe thrombocytopenia. METHODS: The panel met in person and virtually to achieve consensus on the criteria for critical bleeding events among patients with ITP. Existing ITP bleeding scores and published definitions of major bleeds in patients receiving anticoagulation informed the definition of a critical ITP bleed. The Platelet Immunology Scientific Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis endorsed the definition. RESULTS: A critical ITP bleed was defined as: (a) a bleed in a critical anatomical site including intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular with compartment syndrome; or (2) an ongoing bleed that results in hemodynamic instability or respiratory compromise. CONCLUSION: The definition of a critical ITP bleed was developed by the ITP Emergency Management Guideline Panel and endorsed by the Platelet Immunology SSC. It incorporates both anatomic and physiologic risk and pertains to patients with confirmed or suspected ITP who typically have severe thrombocytopenia (platelet count below 20 × 109 /L).