Prenatal diagnosis and outcome of fetuses with isolated agenesis of septum pellucidum: cohort study and meta-analysis

Objective: To evaluate the postnatal outcome of children with a prenatal diagnosis of apparently isolated agenesis of the septum pellucidum (ASP). Methods: A retrospective cohort study of cases of prenatally diagnosed ASP followed in two tertiary centers and a meta-analysis combining data from the cohort study with data from published studies identified in a systematic review were carried out. Only cases with apparently isolated ASP on antenatal ultrasound and/or magnetic resonance imaging and with available postnatal follow-up data were considered eligible for inclusion. The following outcomes were analyzed: incidence of chromosomal anomalies, agreement between antenatal and postnatal findings, overall incidence of septo-optic dysplasia (SOD) and incidence of major neurological disability (motor, language, coordination or behavioral disorder or epilepsy) in non-SOD children. The incidence of SOD in infants with apparently normal optic pathways on antenatal imaging was also evaluated. Results: Fifteen cases of isolated ASP, with median postnatal follow-up of 36 months (range, 12-60 months), were selected from the two centers. Six previously published studies met the inclusion criteria for the systematic review and a total of 78 cases were eligible for the analysis, including the 15 cases from our series. Genetic tests were carried out antenatally in 30 fetuses, of which two had an abnormal result (pooled proportion, 9.0% (95% CI, 1.8-20.7%); I2  = 0%). Additional or discordant imaging findings were noted postnatally in 9/70 (pooled proportion, 13.7% (95% CI, 3.5-29.0%); I2  = 63.9%) cases. Of all 78 neonates with available follow-up, SOD was diagnosed postnatally in 14 (pooled proportion, 19.4% (95% CI, 8.6-33.2%); I2  = 51.2%). In 60 cases, the optic pathways were considered to be normal on antenatal imaging, and six of these (pooled proportion, 9.1% (95% CI, 1.1-24.0%); I2  = 62.0%) were diagnosed postnatally with SOD. Of the 46 infants with available neurological follow-up who were not affected by SOD, a major neurological disability was diagnosed in three (pooled proportion, 6.5% (95% CI, 0.5-18.6%); I2  = 40.1%). Conclusions: In the vast majority of cases with a prenatal diagnosis of apparently isolated ASP, the prognosis is favorable. However, an additional anomaly is detected after birth in about 14% of cases and has a negative impact on clinical outcome. Detailed antenatal assessment of the brain and optic pathways is strongly recommended in order to identify the presence of associated anomalies. Antenatal visualization of apparently normal optic pathways does not rule out SOD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology

Lipoprotein Lipase Links Dietary Fat to Solid Tumor Cell Proliferation

Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain pre-formed, diet-derived fatty acids by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further demonstrate that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or fatty acid uptake will be necessary to target the requirement of cancer cells for FA

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals

Uterine artery Doppler in early labor and perinatal outcome of low-risk term pregnancies: prospective multicenter study

Objective: The prediction of adverse perinatal outcomes in low-risk pregnancies is poor, mainly due to the lack of reliable biomarkers. Uterine artery Doppler is closely associated with placental function and could assist in the peripartum detection of subclinical placental insufficiency. The objective of this study was to evaluate the relationship between mean uterine artery pulsatility index (PI) measured in early labor with obstetric intervention for suspected intrapartum fetal compromise and adverse perinatal outcomes in uncomplicated singleton term pregnancies. Methods: This was a prospective multicenter observational study conducted across four tertiary Maternity Units. Low-risk term pregnancies with spontaneous onset of labor were included. The mean uterine artery PI was recorded in between uterine contractions in women admitted for early labor and converted into multiples of the median (MoM). The primary outcome of the study was the occurrence of obstetric intervention - i.e., cesarean section or instrumental delivery - due to suspected intrapartum fetal compromise. The secondary outcome was represented by the occurrence of composite adverse perinatal outcome, defined as one of the following: acidemia (umbilical artery pH<7.10 and/or base excess >12) at birth and/or 5-min Apgar score < 7 and/or neonatal intensive care unit (NICU) admission. Results: Overall, 804 women were included, of whom 40 (5%) had a mean uterine artery PI MoM ≥95th percentile. Women who had an obstetric intervention for suspected intrapartum fetal compromise were more frequently nulliparous (72.2% vs 53.6%, P=0.008), had a higher frequency of mean uterine artery PI MoM ≥95th percentile (13.0% vs 4.4%, P=0.005), and had a longer duration of labor (456±221 vs 371±192 minutes, p=0.01). Logistic regression only retained as independently associated with obstetric intervention for suspected intrapartum fetal compromise mean uterine artery PI MoM ≥95th percentile (adjusted odds ratio (aOR), 3.48 (95% CI, 1.43-8.47), P=0.006) and multiparity (aOR, 0.45 (95% CI, 0.24-0.86), P=0.015). Mean uterine artery PI MoM ≥95th percentile was associated with a 0.13 (95% CI, 0.05-0.25) sensitivity, 0.96 (95% CI, 0.94-0.97) specificity, 0.18 (95% CI, 0.07-0.33) positive predictive value, 0.94 (95% CI, 0.92-0.95) negative predictive value, 2.95 (95% CI, 1.37-6.35) positive likelihood ratio and 1.10 (95% CI, 0.99-1.22) negative likelihood ratio for obstetric intervention for suspected intrapartum fetal compromise. Pregnancies with mean uterine artery PI MoM ≥ 95th percentile also showed a higher incidence of birthweight <10th percentile (20% vs 6.7%, P=0.002), NICU admission (7.5% vs 1.2%, P=0.001) and composite adverse perinatal outcome (15.0% vs 5.1%, P=0.008). Conclusion: Our study conducted on a cohort of low-risk term pregnancies enrolled in early spontaneous labor shows an independent association between increased mean uterine artery PI and obstetric intervention for suspected intrapartum fetal compromise, albeit with moderate capacity to rule in and poor capacity to rule out this condition. This article is protected by copyright. All rights reserved

VP54.04: Cerebral-placental uterine ratio assessment in early labour in low-risk term pregnancy and prediction of adverse outcome: prospective multicentre study

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The sonographic measurement of the ratio between the fetal head circumference and the obstetrical conjugate is accurate in predicting the risk of labor arrest: results from a multicenter prospective study

Labor arrest is estimated to account for approximately one-third of all primary cesarean deliveries, and is associated with an increased risk of adverse maternal and perinatal outcomes. One of the main causes is the mismatch between the size of the birth canal and that of the fetus, a condition usually referred to as cephalopelvic disproportion