Angiogenic imbalance in maternal and cord blood is associated with neonatal birth weight and head circumference in pregnancies with major fetal congenital heart defect.

OBJECTIVES: To ascertain whether abnormalities in neonatal head circumference and/or body weight are associated with levels of angiogenic/antiangiogenic factors in the maternal and cord blood of pregnancies with a congenital heart defect (CHD) and to assess whether the specific type of CHD influences this association. METHODS: This was a multicenter case-control study of women carrying a fetus with major CHD. Recruitment was carried out between June 2010 and July 2018 at four tertiary care hospitals in Spain. Maternal venous blood was drawn at study inclusion and at delivery. Cord blood samples were obtained at birth when possible. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in maternal and cord blood. Biomarker concentrations in the maternal blood were expressed as multiples of the median (MoM). RESULTS: PlGF, sFlt-1 and sEng levels were measured in the maternal blood in 237 cases with CHD and 260 healthy controls, and in the cord blood in 150 cases and 56 controls. Compared with controls, median PlGF MoM in maternal blood was significantly lower in the CHD group (0.959 vs 1.022; P < 0.0001), while median sFlt-1/PlGF ratio MoM was significantly higher (1.032 vs 0.974; P = 0.0085) and no difference was observed in sEng MoM (0.981 vs 1.011; P = 0.4673). Levels of sFlt-1 and sEng were significantly higher in cord blood obtained from fetuses with CHD compared to controls (mean ± standard error of the mean, 447 ± 51 vs 264 ± 20 pg/mL; P = 0.0470 and 8.30 ± 0.92 vs 5.69 ± 0.34 ng/mL; P = 0.0430, respectively). Concentrations of sFlt-1 and the sFlt-1/PlGF ratio in the maternal blood at study inclusion were associated negatively with birth weight and head circumference in the CHD group. The type of CHD anomaly (valvular, conotruncal or left ventricular outflow tract obstruction) did not appear to alter these findings. CONCLUSIONS: Pregnancies with fetal CHD have an antiangiogenic profile in maternal and cord blood. This imbalance is adversely associated with neonatal head circumference and birth weight. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Presurgery motor level assessment for prediction of motor level at birth in fetuses undergoing prenatal repair of open spina bifida: time to abandon anatomical level in counseling.

OBJECTIVES: First, to investigate the correlation between prenatal presurgery anatomical and motor levels of the lesion with motor level at birth in cases undergoing prenatal repair of open spina bifida and, second, to identify factors leading to a loss of two or more motor levels between the presurgery and postnatal assessments. METHODS: This was an observational study of singleton pregnancies undergoing prenatal repair of open spina bifida, conducted between March 2011 and May 2022. All fetuses underwent an ultrasound assessment at 20-24 weeks of gestation to determine the motor and anatomical levels of the lesion before surgery. The anatomical level of the lesion was defined as the highest open posterior vertebral arch. The motor level was determined by systematic observation of the lower limb movements and was defined as the most distal active muscle present. Prenatal repair was performed at 23-26 weeks. At birth, motor level was assessed by a rehabilitation specialist by physical examination. Cases of intrauterine death or termination of pregnancy and those delivered at other sites were excluded from the neonatal assessment. The agreement between presurgery motor level and motor level at birth, and between presurgery anatomical level and motor level at birth, was assessed using the weighted kappa index (wκ). Logistic regression analysis was used to assess factors leading to a loss of two or more motor levels between the presurgery and postnatal assessments. RESULTS: Presurgery motor and anatomical levels were assessed in 61 fetuses at a median gestational age of 22.7 (interquartile range (IQR), 21.6-24.4) weeks. Prenatal repair was performed at a median gestational age of 24.6 (IQR, 23.7-25.7) weeks. Motor level at birth was assessed in 52 neonates after exclusion of nine fetuses due to loss to follow-up or fetal loss. There was moderate agreement between presurgery motor level and motor level at birth (wκ = 0.42; 95% CI, 0.21-0.63), with a median difference of 0 (IQR, -2 to 9) levels. Factors leading to a loss of two or more motor levels between the presurgery ultrasound assessment and postnatal examination were higher presurgery anatomical level (odds ratio (OR), 0.59 (95% CI, 0.35-0.98); P = 0.04) and larger difference between the anatomical and motor levels before surgery (OR, 1.85 (95% CI, 1.12-3.06); P = 0.017). None of the other ultrasound, surgery-related or neonatal variables assessed was associated significantly with a loss of two or more motor levels. There was slight agreement between the presurgery anatomical level of the lesion and motor level at birth (wκ = 0.07; 95% CI, -0.02 to 0.15). CONCLUSIONS: There is moderate agreement between fetal motor level of the lesion before prenatal repair of open spina bifida and motor level at birth, as opposed to only slight agreement between presurgery anatomical level and motor level at birth. A loss of two or more motor levels between the presurgery and postnatal assessments is associated with a higher presurgery anatomical level and with a larger difference between the presurgery anatomical and motor levels. Consequently, motor level, rather than the anatomical level, should be used for prenatal counseling. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic accuracy of first-trimester combined screening for early-onset and preterm pre-eclampsia at 8-10 compared with 11-13 weeks' gestation.

OBJECTIVES: To compare the ability of first-trimester combined screening for pre-eclampsia (PE) to predict early-onset and preterm PE when pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation. METHODS: This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first-trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP-A and PlGF were assessed from the routine first-trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early-onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian-distribution model and The Fetal Medicine Foundation (FMF) competing-risks model. Receiver-operating-characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false-positive rates were computed to compare the performance of these algorithms when PAPP-A and PlGF were assessed before vs after 11 weeks. RESULTS: Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early-onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early-onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early-onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early-onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP-A and PlGF were measured before or after 11 weeks. In the prediction of early-onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP-A and MAP, which showed a greater AUC for the prediction of early-onset PE when PAPP-A was measured at or after 11 weeks. CONCLUSIONS: The prediction of early-onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two-step approach for PE risk assessment that permits immediate risk calculation at the time of the first-trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Treatment and outcome of 370 cases with spontaneous or post-laser twin anemia-polycythemia sequence managed in 17 fetal therapy centers.

OBJECTIVE: To investigate the antenatal management and outcome in a large international cohort of monochorionic twin pregnancies with spontaneous or post-laser twin anemia-polycythemia sequence (TAPS). METHODS: This study analyzed data of monochorionic twin pregnancies diagnosed antenatally with spontaneous or post-laser TAPS in 17 fetal therapy centers, recorded in the TAPS Registry between 2014 and 2019. Antenatal diagnosis of TAPS was based on fetal middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) in the TAPS donor and < 1.0 MoM in the TAPS recipient. The following antenatal management groups were defined: expectant management, delivery within 7 days after diagnosis, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)), laser surgery and selective feticide. Cases were assigned to the management groups based on the first treatment that was received after diagnosis of TAPS. The primary outcomes were perinatal mortality and severe neonatal morbidity. The secondary outcome was diagnosis-to-birth interval. RESULTS: In total, 370 monochorionic twin pregnancies were diagnosed antenatally with TAPS during the study period and included in the study. Of these, 31% (n = 113) were managed expectantly, 30% (n = 110) with laser surgery, 19% (n = 70) with IUT (± PET), 12% (n = 43) with delivery, 8% (n = 30) with selective feticide and 1% (n = 4) underwent termination of pregnancy. Perinatal mortality occurred in 17% (39/225) of pregnancies in the expectant-management group, 18% (38/215) in the laser group, 18% (25/140) in the IUT (± PET) group, 10% (9/86) in the delivery group and in 7% (2/30) of the cotwins in the selective-feticide group. The incidence of severe neonatal morbidity was 49% (41/84) in the delivery group, 46% (56/122) in the IUT (± PET) group, 31% (60/193) in the expectant-management group, 31% (57/182) in the laser-surgery group and 25% (7/28) in the selective-feticide group. Median diagnosis-to-birth interval was longest after selective feticide (10.5 (interquartile range (IQR), 4.2-14.9) weeks), followed by laser surgery (9.7 (IQR, 6.6-12.7) weeks), expectant management (7.8 (IQR, 3.8-14.4) weeks), IUT (± PET) (4.0 (IQR, 2.0-6.9) weeks) and delivery (0.3 (IQR, 0.0-0.5) weeks). Treatment choice for TAPS varied greatly within and between the 17 fetal therapy centers. CONCLUSIONS: Antenatal treatment for TAPS differs considerably amongst fetal therapy centers. Perinatal mortality and morbidity were high in all management groups. Prolongation of pregnancy was best achieved by expectant management, treatment by laser surgery or selective feticide. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).

Fetoscopic two-layer closure of open neural tube defects.

OBJECTIVE: Fetoscopy for closure of open neural tube defects (NTD) remains controversial, as the use of patches or single-layer closure is not considered to meet the standards of good neurosurgical reconstruction. In this study, we describe a fetoscopic two-layer (myofascial and skin) closure technique for the treatment of NTD in five patients and report the preliminary anatomical outcome at birth. METHODS: From February to September 2017, five pregnant women with a fetus with a NTD, including three cases of myelomeningocele and two cases of myelocele, were operated on using a fetoscopic two-layer closure technique. In this technique, with the uterus exteriorized and using three 10-Fr ports, the placode is dissected from the surrounding tissue and detethered, removing the cystic tissue. The skin is undermined by blunt dissection and the defect is sutured to the midline in two layers (myofascial and skin) using a running 4/0 resorbable barbed suture. RESULTS: Median gestational age at the procedure was 24 + 3 (range, 23 + 5 to 27 + 3) weeks. Surgery was successful in all cases, without any intraoperative complications. Median time in surgery was 180 (range, 140-180) min and median time for fetoscopy was 105 (range, 65-120) min. In terms of obstetric complications, three cases of premature rupture of membranes and one case of chorioamnionitis were recorded. Median gestational age at delivery was 34 + 1 (range, 25 + 4 to 37 + 2) weeks and two patients delivered vaginally. The closed defect was watertight with good quality tissue in all cases. CONCLUSION: Fetoscopic two-layer closure of NTD may improve the quality of the tissue covering the defect, diminishing the need for postnatal surgical revision, and preserving the well-documented beneficial effects of prenatal closure on the neural tissue and hindbrain herniation. However, this technique may not be appropriate for those cases with wide diastasis of the myofascial layer or with a low quantity of available tissue. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Brain angiogenic gene expression in fetuses with congenital heart disease.

OBJECTIVE: To assess potential differences in the expression of antiangiogenic and angiogenic factors and of genes associated with chronic hypoxia in cerebral tissue of euploid fetuses with congenital heart disease (CHD) vs those without. METHODS: Cerebral tissue was obtained from 15 fetuses with CHD and 12 control fetuses that had undergone termination of pregnancy. Expression profiles of the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF), and of genes associated with chronic hypoxia were determined by real-time polymerase chain reaction in tissue from the frontal cortex and the basal ganglia of the fetuses. RESULTS: Expression of sFlt-1 was 48% higher in the frontal cortex (P = 0.0431) and 72% higher in the basal ganglia (P = 0.0369) of CHD fetuses compared with controls. The expression of VEGF-A was 60% higher (P = 0.0432) and that of hypoxia-inducible factor 2-alpha was 98% higher (P = 0.0456) in the basal ganglia of CHD fetuses compared with controls. No significant differences were observed between the two groups in the expression of PlGF and hypoxia-inducible factor 1-alpha. CONCLUSION: An overall dysregulation of angiogenesis with a net balance towards an antiangiogenic environment was observed in the cerebral tissue of fetuses with CHD, suggesting that these fetuses may have an intrinsic angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal changes in fetal biometry and cerebroplacental hemodynamics in fetuses with congenital heart disease.

OBJECTIVES: To determine the longitudinal behavior of fetal biometric measures and cerebroplacental hemodynamics throughout gestation in fetuses with congenital heart disease (CHD). METHODS: Fetal biometry and Doppler hemodynamics (uterine artery (UtA), umbilical artery (UA) and fetal middle cerebral artery (MCA)) were measured serially in a cohort of consecutive fetuses diagnosed with CHD. Evaluations were made at various time points, from diagnosis (20-25 weeks) to delivery, with at least two measurements per fetus that were at least 2 weeks apart. Fetuses were classified into three groups according to the pattern of blood supply to the brain (placental vs systemic) that would be expected on the basis of the type of CHD. All parameters were transformed into Z-scores. A linear mixed model to analyze repeated measurements was constructed for each parameter to assess its behavior throughout gestation. RESULTS: Four hundred and forty-four ultrasound examinations were performed in 119 CHD fetuses, with a median of two measurements per fetus. The fetuses presented a small head at diagnosis (biparietal diameter (BPD) Z-score, -1.32 ± 0.99; head circumference (HC) Z-score, -0.79 ± 1.02), which remained small throughout gestation. UtA and UA pulsatility indices (PI) showed a significant increase towards the end of pregnancy, whereas no significant changes were observed in MCA-PI or cerebroplacental ratio (CPR) with gestational age. Both MCA and CPR presented significant differences in longitudinal behavior between CHD groups, while BPD and HC did not. CONCLUSIONS: CHD fetuses have a relatively small head from the second trimester of pregnancy, regardless of the type of CHD anomaly, and increasing resistance in the UtA and UA as pregnancy progresses, suggestive of increasing degree of placental impairment. Our findings indicate the early onset of mechanisms that could lead to poorer neurodevelopment later in life. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal ultrasound evaluation of segmental level of neurological lesion in fetuses with myelomeningocele: development of a new technique.

OBJECTIVES: To report our preliminary experience in the use of prenatal ultrasound examination to assess lower-limb movements in fetuses with myelomeningocele. We aimed to determine the accuracy of this method to establish the segmental level of neurological lesion, as this is the best known predictor of the future ability to walk. METHODS: This was a preliminary, observational study including fetuses with myelomeningocele operated on prenatally. The patterns of movements present and absent in the affected fetuses' lower limbs were evaluated systematically by ultrasound examination. According to the known nerve function associated with each muscle group, the segmental level of neurological lesion was established before birth. The agreement for the segmental levels assigned, between the prenatal ultrasound technique and the classical neurological clinical examination after birth (gold standard), was tested using the weighed kappa (wκ) index. RESULTS: Seventy-one fetuses with myelomeningocele were evaluated at the Hospital Universitari Vall d'Hebron. After counseling, the parents opted for prenatal surgery (26 cases), termination of pregnancy (43 cases) or postnatal repair (two cases). Five patients did not fulfil the inclusion criteria for prenatal surgery and three were excluded after birth. In the 18 fetuses that underwent surgery and were analyzed, the agreement between prenatal and postnatal segmental levels assigned was 91.7% for the right limb (wκ = 0.80) and 88.9% for the left limb (wκ = 0.73). CONCLUSIONS: The agreement found between prenatal and postnatal assignment of level of lesion in this preliminary study suggests that neurological sonographic evaluation is feasible before birth. This may provide accurate individualized information about the motor function and future ambulation prognosis of fetuses with myelomeningocele.

Fetal heart rate monitoring during fetoscopic repair of open spinal neural tube defects: a single-centre observational cohort study.

BACKGROUND: During fetal surgery, the haemodynamic stability of the fetus depends on the haemodynamic stability of the mother. The primary objective of this study was to assess changes in fetal heart rate (FHR) throughout the different stages of surgery. The secondary objective was to assess potential changes in maternal physiological parameters and their association with FHR. METHODS: This was a single-center observational cohort study conducted between 2015 and 2019 in 26 women undergoing intra-uterine fetoscopic repair of open spina bifida. The primary outcome was FHR. Maternal physiologic parameters were measured at the beginning, during and after surgery. The linear mixed-effects model fitted by maximum likelihood was used to assess changes in each variable at specific times throughout the surgery, and the repeated measures correlation coefficient was used to study the association between FHR and maternal physiological parameters. RESULTS: One (3.8%) case of fetal bradycardia (FHR <110 beats per minute) required the administration of intramuscular atropine. No other significant FHR changes were observed during surgery. Maternal oesophageal temperature (P <0.001), lactate levels (P=0.002), and mean arterial pressure (P=0.016) changed significantly during surgery, although none of these changes was clinically relevant. The FHR showed a significant association with maternal carbon dioxide tension (r=0.285, 95% CI 0.001 to 0.526) and maternal heart rate (r=0.302, 95% CI 0.025 to 0.535). CONCLUSION: The FHR remained stable during intra-uterine fetoscopic repair of open spina bifida. Maternal carbon dioxide tension and heart rate may have a mild influence on FHR.

Relative permittivity estimation of wheat starch: A critical property for understanding electrostatic hazards.

Wheat starch is a widely used material in the food, pharmaceutical and entertainment industry not considered hazard but recently associated to dust explosions during processing and handling. How an insulating starch grain is charged and how its ability to be polarized is affected by environmental conditions such as temperature, humidity and frequency? are fundamental questions that must be explored in order to understand the dust explosion phenomena. Here we investigate the dependence of temperature, humidity and low-frequency on the relative permittivity of wheat starch. We characterized starch at the micro and macro scales using atomic force microscopy-based techniques and capacitive planar sensor-based measurements respectively. The results show high values of permittivity (˜80) at the microscale (single starch grains) compared to the low values (10-20) at the macroscale (20 mg of wheat starch). The differences are attributed to the Maxwell-Wagner-Sillars interfacial polarization process on individual grains and potential charge exchange between grains. Permittivity is a critical property to investigate starch electrostatic hazards.

Pregnancy outcomes after maternal Zika virus infection in a non-endemic region: prospective cohort study.

OBJECTIVES: The aim was to describe pregnancy outcomes after Zika virus (ZIKV) infection in a non-endemic region. METHODS: According to the Spanish protocol issued after the ZIKV outbreak in Brazil in 2015, all pregnant women who had travelled to high-burden countries were screened for ZIKV. Serological and molecular tests were used to identify ZIKV-infected pregnant women. They were classified as confirmed ZIKV infection when reverse transcription (RT) PCR tested positive, or probable ZIKV infection when ZIKV immunoglobulin M and/or immunoglobulin G and ZIKV plaque reduction neutralization tests were positive. Women found positive using molecular or serological tests were prospectively followed-up with ultrasound scans and neurosonograms on a monthly basis until delivery; magnetic resonance imaging and amniotic fluid testing were performed after signed informed consent. Samples of placenta, and fetal and neonatal tissues were obtained. RESULTS: Seventy-two pregnant women tested positive for ZIKV infection: ten were confirmed by RT-PCR, and 62 were probable cases based on serological tests. The prevalence of adverse perinatal outcomes was 33.3% (three out of nine, 95% CI 12.1-64.6%): two cases of congenital ZIKV syndrome (CZS) and one miscarriage, all born to women infected in the first trimester of gestation. All ZIKV-confirmed women had persistent viraemias beyond 2 weeks (median 61.50 days; IQR 35.50-80.75). Amniotic fluid testing was only positive in the two fetuses with anomalies. CONCLUSION: The prevalence of perinatal adverse outcomes for women with ZIKV-confirmed infection was 33.3%. Amniocentesis for ZIKV RT-PCR is recommended when fetal abnormalities are found. Intensive prenatal and postnatal follow-up of ZIKV-infected pregnancies is advised in confirmed cases.

Management of unresectable, locally advanced pancreatic adenocarcinoma.

The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

In utero negativization of Zika virus in a foetus with serious central nervous system abnormalities.

We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract).

Ultrasound functional evaluation of fetuses with myelomeningocele: study of the interpretation of results.

OBJECTIVE: To assess the reliability of the interpretation of a new technique for the ultrasound evaluation of the level of neurological lesion in fetuses with myelomeningocele. METHODS: Observational study including myelomeningocele fetuses, referred to our center for the sonographic assessment of the fetal lower-limb movements, made and recorded by an expert in Maternal-fetal medicine and a specialist in Rehabilitation. Two observers, with different levels of expertise and blinded to each other's results, interpreted each recorded scan two different times. The agreement for the segmental levels assigned between the observers and the gold standard, the inter-observer and intra-observer reproducibility were tested using the weighed Kappa (wκ) index. RESULTS: Twenty-eight scans were recorded and evaluated. The agreement between the observers and the gold standard remained constant for the expert observer (wκ = 0.82) and increased (wκ = 0.66-wκ = 0.72) for the other one. The inter-observer and the intra-observer variability for the expert observer were wκ = 0.72 and wκ = 0.94, respectively. DISCUSSION: The agreement for the prenatal evaluation of the segmental neurological level was excellent, after a short training period, for observers with different degrees of expertise. The interpretation of this technique is reproducible enough and this supports its value for the prediction of postnatal motor function in myelomeningocele fetuses.

Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic cancer in Spain.

The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended.

Not So Giants: Mice Lacking Both Somatostatin and Cortistatin Have High GH Levels but Show No Changes in Growth Rate or IGF-1 Levels.

Somatostatin (SST) and cortistatin (CORT) are two highly related neuropeptides involved in the regulation of various endocrine secretions. In particular, SST and CORT are two primary negative regulators of GH secretion. Consequently, single SST or CORT knockout mice exhibit elevated GH levels; however, this does not lead to increased IGF-1 levels or somatic growth. This apparent lack of correspondence has been suggested to result from compensatory mechanisms between both peptides. To test this hypothesis, in this study we explored, for the first time, the consequences of simultaneously deleting endogenous SST and CORT by generating a double SST/CORT knockout mouse model and exploring its endocrine and metabolic phenotype. Our results demonstrate that simultaneous deletion of SST and CORT induced a drastic elevation of endogenous GH levels, which, surprisingly, did not lead to changes in growth rate or IGF-1 levels, suggesting the existence of additional factors/systems that, in the absence of endogenous SST and CORT, could counteract GH actions. Notably, elevation in circulating GH levels were not accompanied by changes in pituitary GH expression or by alterations in the expression of its main regulators (GHRH and ghrelin) or their receptors (GHRH receptor, GHS receptor, or SST/CORT receptors) at the hypothalamic or pituitary level. However, although double-SST/CORT knockout male mice exhibited normal glucose and insulin levels, they had improved insulin sensitivity compared with the control mice. Therefore, these results suggest the existence of an intricate interplay among the known (SST/CORT), and likely unknown, inhibitory components of the GH/IGF-1 axis to regulate somatic growth and glucose/insulin homeostasis.