Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study.

OBJECTIVE: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. METHODS: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. RESULTS: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta. CONCLUSIONS: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

How many roads lead to stillbirth rate reduction? A 30-year analysis of risk factors in a Northern Italy University care center.

BACKGROUND: Stillbirths affect more than 2.5 million pregnancies worldwide every year and the progress in reducing stillbirth rates is slower than that required by World Health Organization. The aim of the present study was to investigate which factors were associated with stillbirths in a University Hospital in the North of Italy, over a time span of 30 years. The goal was to identify which factors are potentially modifiable to reduce stillbirth rate. METHODS: Retrospective case-control study (358 stillbirths, 716 livebirths) subdivided into two study periods (1987-2006 and 2007-2017). RESULTS: The prevalence of conception obtained by assisted reproductive technologies, pregnancy at advanced maternal age, and complications of pregnancy such as preeclampsia, fetal growth restriction (FGR), and other fetal diseases (abnormal fetal conditions including fetal anemia, fetal hydrops, TORCH infections) increased through the years of the study. Despite a rising prevalence, the last 10 years showed a significant reduction in stillbirths associated with preeclampsia and FGR. Similarly, the risk of stillbirth related to abnormal fetal conditions decreased in the second study period and a history of previous stillbirth becomes a nonsignificant risk factor. CONCLUSIONS: Altogether these results suggest that in pregnancies perceived as "high risk" (i.e. previous stillbirth, preeclampsia, FGR, abnormal fetal conditions) appropriate care and follow-up can indeed lower stillbirth rates. In conclusion, the road to stillbirth prevention passes inevitably through awareness and recognition of risk factors.

Effects of gestational diabetes on fetal oxygen and glucose levels in vivo.

OBJECTIVE: Fetal hypoxia and acidemia have been reported in pregestational diabetic pregnancies in relation to poor glycaemic control, but it is still uncertain whether this is the case in apparently well-controlled gestational diabetes. POPULATION AND METHODS: Maternal arterial and umbilical venous and arterial blood samples were collected from 37 normal (N) and 38 pregnancies complicated by gestational diabetes (GDM) at the time of caesarean section. MAIN OUTCOME MEASURES: Respiratory gases, acid-base balance, lactate and glucose concentrations were measured. RESULTS: Both fetal and placental weights were significantly increased in GDM compared to N pregnancies, despite similar gestational age. Maternal biochemical parameters were similar in N and GDM but GDM fetuses were significantly more hypoxic (O2 saturation: N 63.2+/-13.9; GDM 53.8+/-14.6%, P<0.01; O2 content: N 5.5+/-1.4; GDM 4.8+/-1.2 mmol/l, P<0.05). Glucose (N 3.4+/-0.5, GDM 3.9+/-1.2 mmol/l, P<0.05) and lactate (N 1.32+/-0.49; GDM 1.64+/-0.75 mmol/l, P<0.05) concentrations were significantly increased in the umbilical vein in GDM compared to N fetuses. Placental histology was consistent with altered villous morphology. CONCLUSIONS: Our data indicate that fetuses from gestational diabetic mothers have increased umbilical glucose concentrations despite normal maternal glucose levels and a reduction in oxygen saturation and O2 content together with increased lactate concentration, reflecting altered fetal metabolism. These data suggest that 'good maternal metabolic control' achieved by currently used methods of monitoring glucose control is not sufficient to ensure a normal oxygenation status and metabolic milieu for the fetus in GDM pregnancies.

Neurosurgical aspects of dialysis-related spinal amyloidosis: Report of three cases and a review of the literature.

BACKGROUND AND PURPOSE: Osteoarticular manifestations of beta-2 microglobulin amyloidosis are often diagnosed in long-term dialyzed patients. However, spinal involvement is rare (10-25% of patients), and generally not associated with neurological deterioration. Compression of the spinal cord or roots is extremely rare, and probably under-recognized. METHODS: The authors describe three cases of spinal stenosis presenting with neurological signs in long-term dialyzed patients, prospectively collected over 2 years in two different institutions and treated by surgical decompression. In all three cases, the main cause of neural compression was amyloid deposition in the spine, either extradurally in the ligamentum flavum or intradurally. RESULTS: All patients improved after surgery and did not present any postoperative complications. However, two out of three patients with amyloid in the cervical spine required surgical revision to obtain a satisfactory decompression of the spinal cord. DISCUSSION: The authors discuss spinal amyloidosis which is a well-known complication of long-term dialysis. However, neurological complications such as spinal cord or radicular symptoms have been rarely reported and, when present in dialyzed patients, are symptoms that are often attributed to other causes. To our knowledge, this is the first case series that demonstrates the relationship between neurological deterioration and amyloid depositions in the spinal canal that occur in long-term dialyzed patients. The prevalence of spinal stenosis related to the presence of amyloid in this specific subgroup of patients is probably underestimated.

Tumour-associated fibroblasts contribute to neoangiogenesis in human parathyroid neoplasia.

Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) showed an abundant periacinar distribution of α-SMA(+) cells in normal parathyroid glands (n=3). This pattern was progressively lost in parathyroid adenomas (PAds; n=6) where α-SMA(+)cells were found to surround new microvessels, as observed in foetal parathyroid glands (n=2). Moreover, in atypical adenomas (n=5) and carcinomas (n=4), α-SMA(+) cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (n=37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation.

A rare case of transmural endometriosis in primary adenocarcinoma of the rectum.

Intestinal endometriosis of the rectum and sigmoid colon, occurring in up to 34% of pelvic endometriosis, mimics a wide number of conditions that are difficult to differentiate from inflammatory or malignant diseases. Herein we report the first case of transmural endometriosis concomitant with advanced primary rectal adenocarcinoma, presenting with obstructive symptoms. Correct diagnosis based on morphological identification and immunohistochemical characterization of the two entities is crucial for treatment.

Autophagy in placentas from acidotic newborns: an immunohistochemical study of LC3 expression.

Autophagy is an inducible catabolic process activated during compromised conditions, such as hypoxia. Neonatal encephalopathy (NE) is a syndrome of disturbed neurological function. No absolute prognostic indicators are available at birth to identify neonates at high risk to develop NE. Immunohistochemical staining with LC3 antibody was performed on 40 placentas from uneventful term singleton pregnancies with umbilical artery pH ≤ 7.00 at birth; semi-quantitative analysis was carried-out to estimate autophagy level. 6/40 (15%) neonates developed NE. Placentas from newborns with NE exhibited a higher LC3 expression. Autophagy protein expression in placentas with severe acidosis is a potential marker for poor outcome.

Autophagy in term normal human placentas.

Autophagy is an inducible catabolic process that responds to environment and is essential for cell survival during stress, starvation and hypoxia. Its function in the human placenta it is not yet understood. We collected 14 placentas: 7 at vaginal delivery and 7 at elective caesarean section after uneventful term pregnancies. The presence of autophagy was assessed in different placental areas by immunoblotting, immunohistochemistry and electron microscopy. We found that autophagy is significantly higher in placentas obtained from cesarean section than in those from vaginal delivery. Moreover there is a significant inverse relationship between autophagy and umbilical arterial glucose concentration.

Unusual osteoblastoma of the skull.

Benign osteoblastoma is a rare primary bone tumor, the location in the frontal bone being particularly rare (only a few cases described). The youngest age of occurrence reported is 3 years. We present a case of osteoblastoma occurred in a 4 1/2-month-old boy, located in the frontal bone.