Pregnancy and umbilical cord pathology: structural and functional parameters of the umbilical cord.

Scientific research in the field of physiology and pathology of the umbilical cord is quite limited and imperfect. The purpose of the study was to evaluate the histological architecture of the pathological umbilical cord and investigate the relationship between the main parameters and placental postnatal macromorphometric characteristics, which serve as a reflection of placental dysfunction. Four groups of patients were included, each undergoing a postnatal histological and topographic examination of the umbilical cord: Wharton's jelly edema (10 samples), velamentous cord insertion (10 samples), single umbilical artery (10 samples), and physiological pregnancy (10 samples). Compared to the control group, all newborn groups exhibited changes in umbilical vessel morphology, characterized by an increased Wagenworth index and a decreased Kernohan index. The functional indices of the umbilical vessels were found to be most severely affected in cases of Wharton's jelly edema. In cases of single umbilical artery, the changes in vascular functional parameters indicated their compensatory remodeling with the highest Wagenworth and Kernohan indices of the umbilical vein. Deviation from the normal average placental weight was observed in cases of Wharton's jelly volume pathology or velamentous cord insertion. However, in the case of a single umbilical artery, there were no significant deviations in the macromorphometry of the placenta.

The Placenta in Congenital Langerhans Cell Histiocytosis: A Case Report of Unusual Involvement of Chorionic Plate and Umbilical Vein.

The congenital presentation of Langerhans cell histiocytosis (LCH) is a rare presentation of an uncommon neoplastic process. Concurrent placental parenchymal involvement is even more rare, with just 2 cases of congenital multisystem LCH with placental involvement reported in English medical literature thus far. Here, we present a case of a liveborn male born at 37-weeks, 6-day gestation with congenital LCH focally involving the placenta. Langerhans cells were identified in an area of the placenta showing an unusual mononuclear cell infiltrate in the wall of the umbilical vein. Langerhans cells were also focally identified in areas of chronic villitis, as well as normal-appearing chorionic plate. The examination of the placenta in cases of clinical suspicion of LCH can be of paramount importance since it may provide the early diagnostic evidence of LCH. In this context, placental involvement by LCH should be considered even in the absence of abnormal histology.

A Recanalized Umbilical Vein Hypermetabolic Thrombosis Mimicked an Hepatocellular Carcinoma Recurrence: A New Pitfall?

ABSTRACT: A transarterial left hepatic artery radioembolization involving 90Y microspheres was performed on a cirrhotic man with hypermetabolic 18F-FDG segment III hepatocellular carcinoma. During the 18F-FDG PET/CT follow-up, the disappearance of the hypermetabolic lesion was initially observed. Then, a focal segment III hypermetabolism reappeared mimicking a recurrence before disappearing without any treatment. Finally, the hepatic MRI demonstrated that the transitory segment III hypermetabolism matched a thrombus of the dilated recanalized umbilical vein.

Fetal disseminated intravascular coagulopathy, hydrops and massive umbilical vein thrombosis consequence of a rare placental condition: multifocal chorangiomatosis.

Purpose: Villous capillary lesions are rare abnormal placental developmental conditions which include chorangiosis, chorangiomatosis, chorangioma and a rare variant of the latter called multiple chorangioma syndrome. The causes of villous capillary lesion are not completely clear but appear to involve excessive angiogenesis. MATERIALS AND METHODS: In this paper we start illustrating our experience of multifocal chorangiomatosis with the newborn affected by massive umbilical vein thrombosis, disseminated intravascular coagulopathy and hydrops, going to a literature review of cases available.Results: Two other similar cases have been previously published in literature. Comparing clinical characteristics and fetal outcomes, we confirm the association with unfavorable neonatal outcome mentioned in literature. Our case is the first characterized by severe hemolytic anemia, thrombocytopenia, heart congestion with the overlap of disseminated intravascular coagulopathy and massive umbilical vein thrombosis and congenital anomalies. CONCLUSIONS: Our clinical case and the review of literature highlight how multifocal chorangiomatosis, within the three subgroups identified, is the rarer form with distinct placental features and the worst outcomes for neonates. No cases of multifocal chorangiomatosis have never been described prenatally and, for further studies, could be reasonable investigate the involvement of some growth factors like vascular endothelial growth factor and placental growth factor that could lead to a detection of a subgroup of patient at higher risk to manifest placental vascular lesions and the follow fetal and maternal complications.

Necrotizing funisitis and calcification of umbilical vein: case report and review.

BACKGROUND: Necrotising funisitis (NF) is a rare, chronic stage of funisitis, a severe inflammation of the umbilical cord and an important risk factor for fetal adverse outcomes. NF is characterized by yellow-white bands running parallel to the umbilical blood vessels. These bands consist of inflammatory cells, necrotic debris, and calcium deposits. Calcification is visible in ultrasonography, which makes it possible to suspect NF when umbilical vascular wall calcification is detected by prenatal ultrasonography. CASE PRESENTATION: Ultrasonography revealed calcification of the umbilical venous wall in an expectant 31-year-old woman who was gravida 1, para 0. The woman required emergency cesarean section because of fetal distress and suspected umbilical cord torsion at 31 weeks gestation. The root of the umbilical cord was quite fragile and broke during the operation. The pathological results on the placenta showed histologic chorioamnionitis and NF. The infant was diagnosed to have neonatal sepsis and acidosis after delivery but was discharged without severe complications after a one-month hospitalization that included antibiotic and supportive therapy. CONCLUSION: NF is a rare and severe inflammation of the umbilical cord. Umbilical vascular wall calcification discovered in prenatal ultrasonography is diagnostically helpful.

Severe fetal anemia as a consequence of extra-abdominal umbilical vein varix: A case report and review of the literature.

Umbilical vein varix is associated with a high incidence of fetal anomalies and perinatal complications. There are two types of umbilical vein varix: fetal intra-abdominal and extra-abdominal. Herein, a case is reported of severe fetal anemia with extra-abdominal umbilical vein varix. A 33-year-old primigravida was referred to our hospital for fetal growth restriction, fetal cardiomegaly, and decreased fetal movements at 26 weeks' gestation. A Doppler assessment showed an elevated middle cerebral artery peak systolic velocity at 2.2 MoM, suggesting fetal anemia. Umbilical vein varix had caused intermittent turbulent flow, provoking hemolytic anemia. Intrauterine transfusion improved fetal circulatory failure and anemia and prolonged gestational period. At 33 weeks' gestation, the patient underwent cesarean delivery due to nonreassuring fetal status. Pathological analysis revealed focal loss of vascular smooth muscle of the umbilical vein. Extra-abdominal umbilical vein varix has been reported in 14 cases including this case. The antenatal diagnosis rate is reported to be 79%; fetal heartbeat abnormalities and fetal deaths were reported as 50% and 14%, respectively. Eighty-six percent of patients had intra-umbilical cord thrombosis, but currently this is the only case of hemolytic anemia. Furthermore, extra-abdominal umbilical vein varix may present as fetal hydrops with anemia. During ultrasound examination of fetal anemia, umbilical cord screening should be performed with caution.

Role and effect of vein-transplanted human umbilical cord mesenchymal stem cells in the repair of diabetic foot ulcers in rats.

Diabetic foot ulcer (DFU) is one of diabetic complications, which is frequently present and tormented in diabetes mellitus. Most multipotent mesenchymal stromal cells (MSCs) are capable of immune evasion, providing an allogeneic, ready-to-use, cell product option for therapeutic applications. The beneficial effect of MSCs for the treatment of a variety of traumatic injuries, such as open wounds, has been extensively explored. In this study, a rat DFU model was used to simulate the pathophysiology of clinical patients and to investigate the localization of human umbilical cord mesenchymal stem cells (hUC-MSCs) after intravenous transplantation and its role in DFU healing, so as to evaluate the potential of hUC-MSCs in the treatment of DFU. The diabetic rat model was established by streptozotocin injection, which was used to create full-thickness foot dorsal skin wounds to mimic DFU by a 6-mm skin biopsy punch and a Westcott scissor. The hUC-MSCs were transplanted through femoral vein, and the ulcer cicatrization situation and the fate of hUC-MSCs were evaluated. Our data suggest that intravenously transplantated hUC-MSCs have the ability to migrate and locate to the wound tissue and are helpful to wound healing in DFU rats, partly by regulating inflammation, trans-differentiation and providing growth factors that promote angiogenesis, cell proliferation and collagen deposition. Herein, we demonstrate that hUC-MSC transplantation is able to accelerate DFU healing in rats and transplantation of exogenous stem cells may be a potential strategy for clinical application in DFUs.

Intrauterine growth restriction is associated with sex-specific alterations in the nitric oxide/cyclic GMP relaxing pathway in the human umbilical vein.

INTRODUCTION: Intrauterine growth restriction (IUGR) is a leading cause of perinatal mortality and morbidity, and is linked to an increased risk to develop chronic diseases in adulthood. We previously demonstrated that IUGR is associated, in female neonates, with a decreased nitric oxide (NO)-induced relaxation of the umbilical vein (UV). The present study aimed to investigate the contribution of the smooth muscle components of the NO/cyclic GMP (cGMP) pathway to this alteration. METHODS: UVs were collected in growth-restricted or appropriate for gestational age (AGA) human term newborns. Soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinase (PKG) were studied by Western blot, cGMP production by ELISA and cyclic nucleotide phosphodiesterases (PDEs) activity using a colorimetric assay. Contribution of PDEs was evaluated using the non-specific PDEs inhibitor 3-isobutyl-1-methylxanthine (IBMX) in isolated vessel tension studies. RESULTS: NO-induced relaxation was reduced in IUGR females despite increased sGC protein and activity, and some increase in PKG protein compared to AGA. In males, no significant difference was observed between both groups. In the presence of IBMX, NO-stimulated cGMP production was significantly higher in IUGR than AGA females. Pre-incubation with IBMX significantly improved NO-induced relaxation in all groups and abolished the difference between IUGR and AGA females. CONCLUSION: IUGR is associated with sex-specific alterations in the UV's smooth muscle. The impaired NO-induced relaxation observed in growth-restricted females is linked to an imbalance in the NO/cGMP pathway. The beneficial effects of IBMX suggest that PDEs are implicated in such alteration and they could represent promising targets for therapeutic intervention.

ERK1/2-PPARγ pathway is involved in Chlamydia pneumonia-induced human umbilical vein endothelial cell apoptosis through increased LOX-1 expression.

Chlamydia pneumonia (C.pn) is a common respiratory pathogen that is involved in human cardiovascular diseases and promotes the development of atherosclerosis in hyperlipidemic animal models. C.pn reportedly up-regulated lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells. Recently, the anti-atherosclerotic activity of peroxisome proliferator-activated receptor γ (PPARγ) has been documented. In the present study, we investigated the effect of C.pn on LOX-1 expression in human umbilical vein endothelial cells (HUVECs) and identified the involvement of the PPARγ signaling pathway therein. The results showed that C.pn increased the expression of LOX-1 in HUVECs in a dose- and time-dependent manner. C.pn-induced up-regulation of LOX-1 was mediated by ERK1/2, whereas p38 MAPK and JNK had no effect on this process. C.pn induced apoptosis, inhibited cell proliferation, and decreased the expression PPARγ in HUVECs. Additionally, LOX-1 activity and cell injury caused by C.pn through activation of ERK1/2 was completely inhibited by rosiglitazone, a PPARγ agonist. In conclusion, we inferred that activation of PPARγ in HUVECs suppressed C.pn-induced LOX-1 expression and cell damage by inhibiting ERK1/2 signaling.

Is umbilical vein varix associated with changes in cerebroplacental ratio?

Objective: We aimed to review a single-center experience in follow-up and management of fetuses with umbilical vein varix (UVV) and to assess the effect of UVV on fetal Doppler parameters.Methods: We reviewed retrospectively maternal antenatal records, delivery records, and newborn records to identify cases of UVV. Further, we retrospectively compared 25 fetuses with isolated UVV and available cerebroplacental ratio (CPR) analysis with 75 matched controls.Results: We identified 67 cases of UVV. The median gestational age (GA) at diagnosis was 34 weeks (range: 26-41 weeks). The average diameter of UVV at diagnosis was 10.1 mm (range: 9-14 mm). The median GA at delivery was 36 + 6 (range: 33-41 weeks), with an average birth weight of 2918 g (range: 1278-4140 g). There was a single case of intrauterine death at 35 weeks. CPR was 2.13 ± 0.62 in isolated UVV group compared with 1.84 ± 0.61 in the control group (p < .05). Other Doppler parameters did not differ between fetuses with UVV compared with controls.Conclusions: CPR was significantly increased in the UVV group compared with control fetuses. This finding suggests that UVV is not associated with chronic fetal oxygen deprivation; it, therefore, may contribute to our understanding of the pathophysiology explaining abnormal pregnancy outcome in cases with UVV.

Thrombosis after umbilical venous catheterisation: prospective study with serial ultrasound.

BACKGROUND: Umbilical venous catheters (UVCs) are associated with thrombus formation. Most studies on thrombosis in infants with UVCs focus on only one part of the route, and none assessed a control group of infants without UVCs. OBJECTIVE: To determine the incidence and location of thrombi in infants after umbilical catheterisation and compare this with a control group of infants without umbilical catheters. DESIGN: Prospective observational study with serial ultrasonography of the UVC route from the umbilico-portal confluence to the heart. Ultrasonography was performed until day 14 after catheterisation in cases and day 14 after birth in controls. RESULTS: Thrombi in the UVC route were detected in 75% (30/40) of infants with UVCs in the study group, whereas no thrombi were detected in the control group of infants without UVCs (0/20) (p<0.001). Six thrombi (20%) were located in the right atrium. Most of these were also partly present in the ductus venosus. Six thrombi (20%) were located in the ductus venosus only, and in 12 infants (40%), the thrombus was at least partly located in the umbilico-portal confluence. Thrombi persisted after UVC removal in 25/30 cases. Two infants with thrombotic events were treated with low-molecular-weight heparin and resolution was found. In the other 23 infants managed expectantly, 2 died due to necrotising enterocolitis, 1 was lost to follow-up and in 20 spontaneous regression was seen. CONCLUSIONS: Thrombotic events occur frequently in infants after umbilical catheterisation. Most thrombi were asymptomatic and regressed spontaneously with expectant management. Routine screening for thrombi in UVCs is therefore not advised.

Severe fetal cardiomegaly caused by multiple non-giant placental chorioangiomas.

A pregnant woman was referred to our hospital due to fetal cardiomegaly. We recognised a dilated umbilical vein, which raised a suspicion of placental chorioangioma. A male neonate was delivered at 37 weeks of gestation. The cardiomegaly was gradually improved. Pathological examination identified five non-giant placental chorioangiomas. Multiple non-giant chorioangiomas may cause fetal complications despite the difficulty of prenatal diagnosis.

Effect of gestational diabetes mellitus and pregnancy-induced hypertension on human umbilical vein smooth muscle KATP channels.

Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) can jeopardize mother and/or fetus. Vascular ATP-sensitive potassium (KATP) channels most likely participate in the processes of diabetes and hypertension. The aim of this research was to examine whether GDM and PIH cause changes in the expression and function of KATP channels in vascular smooth muscle of human umbilical vein (HUV). Western blot and immunohistochemistry detected significantly decreased expression of Kir6.1 subunit of KATP channels in GDM and PIH, while the expression of SUR2B was unchanged. In GDM, a K+ channel opener, pinacidil caused reduced relaxation of the endothelium-denuded HUVs compared to normal pregnancy. However, its effects in HUVs from PIH subjects were similar to normal pregnancy. In all groups KATP channel blocker glibenclamide antagonized the relaxation of HUV induced by pinacidil without change in the maximal relaxations indicating additional KATP channel-independent mechanisms of pinacidil action. Iberiotoxin, a selective antagonist of large-conductance calcium-activated potassium channels, inhibited the relaxant effect of pinacidil in PIH, but not in normal pregnancy and GDM. Experiments performed in K+-rich solution confirmed the existence of K+-independent effects of pinacidil, which also appear to be impaired in GDM and PIH. Thus, the expression of KATP channels is decreased in GDM and PIH. In GDM, vasorelaxant response of HUV to pinacidil is reduced, while in PIH it remains unchanged. It is very likely that KATP channels modulation and more detailed insight in KATP channel-independent actions of pinacidil may be precious in the therapy of pathological pregnancies.

Long non-coding RNA GAPLINC promotes angiogenesis by regulating miR-211 under hypoxia in human umbilical vein endothelial cells.

In this study, we investigated the role of a long non-coding RNA GAPLINC in angiogenesis using human umbilical vein endothelial cells (HUVEC). We found that hypoxia and hypoxia-inducible factor 1α (HIF-1α) increased the expression of GAPLINC in HUVEC cells. Moreover, GAPLINC overexpression down-regulated miR-211 and up-regulated Bcl2 protein expression. Further rescue experiments confirmed that hypoxia directly increased GAPLINC expression. GAPLINC overexpression also increased cell migration and vessel formation which promoted angiogenesis, and these changes were attributed to the increased expression of vascular endothelial growth factor receptors (VEGFR) and delta-like canonical notch ligand 4 (DLL4) receptors. Finally, we demonstrated that GAPLINC promotes vessel formation and migration by regulating MAPK and NF-kB signalling pathways. Taken together, these findings comprehensively demonstrate that overexpression of GAPLINC increases HUVEC cells angiogenesis under hypoxia condition suggesting that GAPLINC can be a potential target for critical limb ischaemia (CLI) treatment.

Persistent right umbilical vein in isomerism.

OBJECTIVE: Our objective was to evaluate the incidence of a persistent right umbilical vein in isomerism versus situs solitus. METHODS: For this retrospective, observational, nonrandomized report, we identified fetuses with confirmed right umbilical veins from all patients referred for fetal echocardiography in Southern Nevada between January 2006 and January 2019. RESULTS: For the period January 2006 to January 2019, we identified 89 fetuses with situs solitus and a right umbilical vein from 16 320 women undergoing prenatal cardiac evaluation, resulting in a right umbilical vein incidence of 0.5% in situs solitus. For the same period, we identified 36 fetuses with isomerism and confirmatory umbilical vein imaging. Of the 36, 15 (42%) had right umbilical veins. Of the 15, four of 11 (19%) had left isomerism, and 11 of 15 (73%) had right isomerism (P = .006). CONCLUSIONS: A right umbilical vein is rare with situs solitus and common with isomerism. A right umbilical vein is more common in right isomerism than left isomerism and should alert the clinician to check for isomeric situs, especially right isomerism.

Antenatal sonographic features of persistent extrahepatic vitelline vein aneurysm confused with umbilical vein varix.

Background: The persistent vitelline vein is a portal venous system malformation arising during the embryonic period. These abnormal blood vessels frequently thrombose and can lead superior mesenteric vein obstruction or portal hypertension. Case report: We visualized a fetal intra-abdominal cystic mass with turbulent flow on prenatal ultrasound at 28 weeks' gestation. Initially diagnosed as an umbilical vein varix, it was later determined to be an extrahepatic persistent vitelline vein with an internal thrombus by postnatal ultrasound. It was successfully surgically excised. Conclusion: When an abnormal abdominal vascular structure near the umbilicus is found during prenatal ultrasonography, the persistent vitelline vein should be included in the differential diagnosis to allow prompt evaluation and treatment after birth.

Flavivirus NS1 Triggers Tissue-Specific Vascular Endothelial Dysfunction Reflecting Disease Tropism.

Flaviviruses cause systemic or neurotropic-encephalitic pathology in humans. The flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein involved in viral replication, immune evasion, and vascular leakage during dengue virus infection. However, the contribution of secreted NS1 from related flaviviruses to viral pathogenesis remains unknown. Here, we demonstrate that NS1 from dengue, Zika, West Nile, Japanese encephalitis, and yellow fever viruses selectively binds to and alters permeability of human endothelial cells from lung, dermis, umbilical vein, brain, and liver in vitro and causes tissue-specific vascular leakage in mice, reflecting the pathophysiology of each flavivirus. Mechanistically, each flavivirus NS1 leads to differential disruption of endothelial glycocalyx components, resulting in endothelial hyperpermeability. Our findings reveal the capacity of a secreted viral protein to modulate endothelial barrier function in a tissue-specific manner both in vitro and in vivo, potentially influencing virus dissemination and pathogenesis and providing targets for antiviral therapies and vaccine development.