Nuno Clode

The role of fibrin E on the modulation of endothelial progenitors adhesion, differentiation and angiogenic growth factor production and the promotion of wound healing.

Severe skin loss constitutes a major unsolved clinical problem worldwide. For this reason, in the last decades there has been a major push towards the development of novel therapeutic approaches to enhance skin wound healing. Neo-vessel formation through angiogenesis is a critical step during the wound healing process. Besides the contribution of pre-existing endothelial cells (EC), endothelial progenitor cells (EPCs) have also been implicated in wound healing acting either by differentiating into EC that incorporate the neo-vessels, or via the production of paracrine factors that improve angiogenesis. Here we tested the importance of different extracellular matrices (ECM) in regulating the angiogenic and wound healing potential of cord blood-derived EPC (CB-EPC). We compared the properties of several ECM and particularly of fibrin fragment E (FbnE) in regulating EPC adhesion, proliferation, differentiation and healing-promotion in vitro and in vivo. Our results show that CB-EPCs have increased adhesion and endothelial differentiation when plated on FbnE compared to collagens, fibronectin or fibrin. Using integrin neutralizing antibodies, we show that CB-EPC adhesion to FbnE is mediated by integrin α5β1. Gene expression analysis of CB-EPCs plated on different substrates revealed that CB-EPC grown on FbnE shows increased expression of paracrine factors such as VEGF-A, TGF-β1, SDF-1, IL-8 and MIP-1α. Accordingly, conditioned media from CB-EPC grown on FbnE induced EC tube formation and monocyte migration in vitro. To test the wound healing effects of FbnE in vivo we used an FbnE enriched scaffold in a cutaneous wound healing mouse model. In accordance with our in vitro data, co-administration of the FbnE enriched scaffold with CB-EPC significantly accelerated wound closure and wound vascularization, compared FbnE enriched scaffold alone or to using collagen-based scaffolds. Our results show that FbnE modulates several CB-EPC properties in vivo and in vitro, and as such promotes wound healing. We suggest the use of FbnE-based scaffolds represents a promising approach to resolve wound healing complications arising from different pathologies.

Acute effects of maternal cigarette smoking on fetal heart rate and fetal body movements felt by the mother

Acute effects of maternal cigarette smoking on fetal heart rate (FHR) and fetal body movements felt by the mother (FM) were studied in 51 pregnant volunteers. Thirty four were chronic smokers (6 or more cigarettes per day, with an average of 14 cigarettes/day) and 17 were sporadic smokers (1 to 5 cigarettes per day, with an averaged of 3 cigarettes/day). In both groups the number of FM, fetal reactivity and short-term FHR variability decreased significantly in the 20 minutes following cigarette smoking; a sustained FHR rise of 10 or more beats/min was also found after the cigarette in more than 50% of the cases in the 2 groups. No statistically significant differences were found among the 2 groups when the post-cigarette data were compared. We conclude that maternal cigarette smoking produces important acute effects upon FM and FHR regardless the average daily number of cigarettes smoked by the mother.

Vesicouterine fistula after manual removal of placenta in a woman with previous cesarean section

Vesicouterine fistula is one of the less common acquired urogenital fistula and a rare event in obstetrics. We report a case which occurred after a vaginal delivery followed by manual removal of placenta in a woman who had a previous cesarean section. The fistula was successfully repaired 5 weeks after delivery.

Near term twin pregnancy: clinical relevance of weight discordance at birth.

Abstract Objective: The aim of our study is to evaluate the clinical importance of near term weight discordance in twin pregnancies with both appropriate or with one small for gestational age newborn (AGA and SGA, respectively). Methods: We retrospectively studied 230 twin pregnancies that ended at ≥34 weeks′ gestation. Discordance was defined as an intertwin birth weight difference ≥20% calculated from the heavier newborn. The following data were compared between discordant and concordant pairs: maternal age, parity, mode of conception, placentation, hypertensive disorders of pregnancy, gestational age at birth, route of delivery, reason for termination of pregnancy, Apgar scores, birth weights, admission to neonatal intensive care unit, significant morbidity, malformations found at birth, and perinatal mortality. The discordant pairs were subdivided into two groups: (1) Both twins were AGA; (2) One of the twins was SGA. The two groups were compared to each other, and to the control group of concordant pairs. Results: One hundred and seventy-six twin pairs were concordant (control group) and 54 were discordant. The comparison between the concordant and the discordant groups did not show statistically significant differences in any of the examined parameters. However, the discordant group had a greater incidence of neonatal morbidity. When the discordant subgroups (AGA, n=24 vs. SGA n=30) were compared to the concordant group, these differences persist, particularly in the SGA group. Conclusion: In near term twin pregnancies, birth weight discordance does not seem to predict adverse perinatal outcome except when one of the newborns is SGA.

Prenatal diagnosis of thrombosis of the dural sinuses

Thrombosis of the cerebral venous vessels is a rare event in the neonatal period, and prenatal detection of dural sinus thrombosis is even rarer. A 19year-old woman with an uncomplicated pregnancy was referred at 22 weeks for a routine midtrimester ultrasonographic scan. The transabdominal scan revealed a triangular sonolucent area in the occipital region containing a round echogenic mass (Fig. 1). The scan also showed that the posterior segment of the superior sagittal sinus was dilated, with interruption of the venous flow— presumably at the level of the torcula herophili— caused by a homogeneous, 15-mm mass with a welldefined contour and no identifiable vascular flow. This structure was compatible with a blood clot

Prenatal ultrasonographic diagnosis of vein of Galen aneurysms – report of two cases

Aneurysms of the vein of Galen (AVG) represent less than 1% of all intracranial arteriovenous malformations. Two cases of prenatal diagnosis made by color Doppler ultrasonography at 32 weeks of gestation are reported. Both cases presented with antenatal mild cardiomegaly and both developed severe cardiac failure in the neonatal period. Embolization was unsuccessful and both infants died. These cases highlight the need for a careful evaluation of the time and mode of delivery; embolization must be performed after a fully informed decision.

VEGF signaling on hematopoietic precursors restricts B-lymphoid commitment in vitro and in vivo

Vascular endothelial growth factor (VEGF) signals on vascular and hematopoietic cells via its receptors, VEGFR-2 (KDR) and VEGFR-1 (FLT-1). Elevated levels of VEGF, such as during tumor growth or inflammation, have been suggested to suppress hematopoiesis; most studies refer to KDR as the main receptor involved in this inhibitory effect. In the present study, having detected expression of FLT-1 in B-lymphoid precursors, we exploited the possibility that VEGF signaling via FLT-1 might affect early B-cell commitment. Using a well-established in vitro B-cell differentiation assay, we demonstrate that FLT-1 blockade promotes B-cell commitment and subsequent differentiation, while KDR blockade has no effect on B-cell commitment. In agreement, in vivo transplantation of human (CD34+) or murine (Sca1+l/Lin-) FLT-1-negative hematopoietic precursors into irradiated severe combined immune-deficient mice restored the bone marrow lymphoid compartment, while transplanting the FLT-1-positive counterpart failed to repopulate the lymphoid compartment, and unexpectedly resulted in early death of the irradiated recipients due to hematopoietic suppression. Taken together, we suggest that VEGF signaling via FLT-1 on hematopoietic precursors may restrict lymphopoiesis.

Acute myocardial infarction in pregnancy recurring in the puerperium

Adnexal torsion is a surgical emergency. Approximately 15% of the ovarian torsions occur during pregnancy, usually in the first trimester and more frequently affects the right tube (Born et al. 2004). Adnexal torsion is frequently associated with ovarian enlargement and may follow hyperstimulation of the ovaries (Minutoli et al. 2001). Indeed our patient had received treatment with clomiphene citrate and hMG/hCG and enlargement of the ovaries was found. The diagnosis of the disease is difficult, especially during pregnancy and occasionally remains a diagnostic dilemma. The ultrasound findings, such as the appearance of a solid or cystic mass, with or without fluid collections in the pouch of Douglas, are non-specific findings. Colour Doppler sonography performed with a transvaginal probe may provide an early diagnosis of ovarian torsion. Furthermore, colour Doppler flow assessment can be used not only for the diagnosis but even for the post-treatment evaluation of the affected ovary’s recovery. In our case, the transvaginal ultrasonography visualised enlarged ovaries and a moderate amount of fluid in the pouch of Douglas, whereas the colour power Doppler sonography indicated absence of ovarian blood flow in the right ovary and a normal flow pattern in the left ovary. Cases of adnexal torsion occurring during the first trimester of pregnancy preferably undergo laparoscopy, which is well suited for diagnosis, evaluation and treatment. Laparotomy, however, is still considered to be a gold standard method of treatment. Usually, conservative treatment is warranted to preserve fertility, even in cases where the adnexa initially appear non-viable, and purple or black in colouration. In our case, the salpinx was totally necrotic, due to a delay in diagnosis and to intervene. Thus, an excision of the adnexum was performed.

Outpatient versus inpatient cervix priming with Foley catheter: A randomized trial

OBJECTIVE To compare clinical efficacy between outpatient and inpatient cervix priming with Foley catheter. STUDY DESIGN We conducted a randomized trial including term pregnancies with a single fetus in cephalic presentation, Bishop score<6, gestational age>41 weeks or medical indication for induction of labor. Patients were randomized to outpatient (n=65) or inpatient (n=65) priming with Foley catheter. Primary outcome was Bishop score change between outpatient and inpatient groups. Secondary comparisons included: delivery route and catheter application-to-delivery time. Statistical analysis was performed using Student́s t-test and χ2 test. We assessed the contribution of each demographic variable and setting of Foley priming to the variation in induction-to-delivery-time and inpatient time by using multivariate linear regression and the contribution of each demographic variable and setting of Foley to cesarean delivery rate for failed induction by using multivariate logistic regression. p<0.05 was considered statistically significant. RESULTS Average Bishop score change was not statistically different between the inpatient and outpatient groups (3.4 vs 2.9, p=0.37). Outpatient group had a shorter average catheter application-to-delivery time than the inpatient (38.2 vs 44.9. hrs, p=0.01) and an average of less 10h of hospital stay than inpatient group. Vaginal birth rate(72% outpatient vs 62% inpatient) was similar between groups. Outpatient group had a statistically significant lower rate of cesarean deliveries for failed induction of labor [2/65 (3%) vs 11/65 (17%), p=0.02]. There were three cases of chorioamnionitis for each group with no significant maternal or neonatal morbidity. CONCLUSIONS Outpatient priming with Foley catheter is as safe and effective as in the inpatient setting with shorter hospital stay and less cesarean deliveries for failed induction. ClinicalTrials.gov - NCT02842879.

Route of delivery following successful external cephalic version

To evaluate the delivery route and the indications for cesarean delivery after successful external cephalic version (ECV).