Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, COSA): study protocol for a multicentre, non-blinded, randomised controlled trial.

INTRODUCTION: Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation. METHODS AND ANALYSIS: This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78. ETHICS AND DISSEMINATION: The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal. TRIAL REGISTRATION: NCT05268640.

sFlt-1/PlGF Ratio Is Not a Good Predictor of Severe COVID-19 nor of Adverse Outcome in Pregnant Women with SARS-CoV-2 Infection-A Case-Control Study.

BACKGROUND: Elevated serum levels of sFlt-1 were found in non-pregnant severe COVID-19 patients. The aim was to investigate sFlt-1/PlGF ratio as a predictor of severe disease and adverse outcome in pregnant women with COVID-19. METHODS: A single-center case-control study was conducted in pregnant women with SARS-CoV-2 infection. SARS-CoV-2-negative pregnant women served as controls. Serum sFlt-1/PlGF ratio was assessed. The primary outcome was severe COVID-19 and the secondary outcome comprised adverse outcomes including severe COVID-19, intensive care unit admission, maternal multiple organ failure, preterm delivery, fetal demise, preeclampsia or hypertension diagnosed after COVID-19, maternal death. RESULTS: 138 women with SARS-CoV-2 infection and 140 controls were included. sFlt-1/PlGF ratio was higher in infected patients (11.2 vs. 24; p < 0.01) and in women with severe disease (50.8 vs. 16.2; p < 0.01). However, it was similar in women with adverse and non-adverse outcome (29.8 vs. 20; p = 0.2). The AUC of sFlt-1/PlGF ratio was 0.66 (95% CI 0.56-0.76) for the prediction of severe COVID-19, and 0.72 (95% CI 0.63-0.79) for the prediction of adverse outcome. CONCLUSIONS: sFlt-1 and sFlt-1/PlGF ratio are related to SARS-CoV-2 infection and the severity of COVID-19 during pregnancy. However, sFlt-1/PlGF ratio is not a good predictor of severe COVID-19 or adverse outcome.

Experience of 300 cases of prenatal fetoscopic open spina bifida repair: report of the International Fetoscopic Neural Tube Defect Repair Consortium.

BACKGROUND: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child. OBJECTIVE: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair. STUDY DESIGN: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry. RESULTS: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study. CONCLUSION: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks.

Contemporary management of prenatally diagnosed spina bifida aperta - an update.

Spina bifida aperta is a relatively common congenital defect that occurs in the general population. Once the disorder has been diagnosed, a discussion, that can be emotionally-charged, ensues about whether to treat it prenatally or to only offer surgery postnatally. Given that there are good arguments for and against both options, it is of paramount importance to gain a good understanding of the major advantages and disadvantages of the various surgical approaches. The aim of our paper is to summarize current knowledge about spina bifida and the potential benefits of prenatal surgery.

Sudden Fetal Hematologic Changes as a Complication of Amnioreduction in Twin-Twin Transfusion Syndrome.

We present the first case of a monochorionic twin pregnancy in which sudden hematologic changes occurred as a complication of the amnioreduction procedure for twin-twin transfusion syndrome (TTTS). At 33 weeks of gestation, 4 days after the amnioreduction, the recipient developed severe anemia while the donor developed severe polycythemia. Postnatal placental examination revealed several arteriovenous and venoarterial anastomoses, a pale placental mass of the recipient and a congested and plethoric placental mass of the donor. We speculate on the pathophysiologic changes and potential deleterious effects provoked by the decompressive amnioreduction. Decompression of the placenta and anastomoses after the amnioreduction may have led to an acute blood shift from recipient to donor (thus also a reversal of feto-fetal transfusion), resulting in anemia in the recipient and polycythemia in the donor twin. In the past 15 years, 13 TTTS cases with late presentation were treated with amnioreduction. This is the first time we encountered this severe complication, yielding an incidence of 8%. Although the optimal treatment in TTTS with late presentation is not known, perinatologists should be aware that treatment with amnioreduction can lead to sudden hematologic changes.

The chorionic bump associated with acrania--case report.

The chorionic bump is a rare abnormality of the gestational sac, presenting as a convex bulge from the choriodecidual surface into the sac, correlated with poor prognosis for the pregnancy We report a case of a 36-year-old pregnant woman, with a history of spontaneous abortion, who presented for an early scan a 6 weeks and 4 days of gestation. The pregnancy was spontaneous and unplanned. The patient conceived in less than 3 months after discontinuing oral contraceptives. No folic acid was taken before or in the pregnancy An ultrasound scan revealed a chorionic bump with a hypoechoic center and echogenic border, measuring 18.3 x 14.7 x 21.9 mm. No motion within the chorionic bump was detected upon color and power Doppler examination. The second scan was performed a week later at 7+4 wks. The chorionic bump had not changed in terms of size and sonographic appearance. An acranial fetus of CRL 45.5 mm was diagnosed at 11 + 2 wks. The concentration of free beta-hCG was 17.2 IU/L, corresponding to 0.37 MoM and PAPP-A levels were 1.31 IU/L, corresponding to 0.82 MoM. After counseling the patient opted for termination of pregnancy Very few cases of chorionic bumps have been described so far and, to the best of our knowledge, its coexistence with neural tube defects has been reported for the first time. We postulate a possibility of an underlying pathological mechanism for such coexistence. The chorionic bump is a focal convex bulge with irregular borders, protruding from the choriodecidual surface into the gestational sac and with different degrees of echogenicity usually a hypoechoic middle and echogenic border The chorionic bump might represent the following: a hematoma, an area of hemorrhage, a non-embryonic gestation, or a demise of an embryo in a twin pregnancy The presence of the bump is associated with a four-fold increase in the spontaneous abortion rate as compared with the general population. Decreased folate levels increase the incidence of neural tube defects. Oxidative stress resulting from folic acid deficiency may be responsible for neural tube defects through impairment of factors inhibiting apoptosis in the neuroepithelium. Fetuses with neural tube defects are at an increased risk of being aborted spontaneously Furthermore, women who deliver children with neural tube defects frequently have a history of miscarriage. Our patient did not take any folic acid and also had a history of spontaneous miscarriage. In the case we herein presented, the coexistence of acrania and placental pathology could be attributed to folate deficiency Such coexistence is described for the first time and could be accidental, but there is possible theoretical association between these two pathologies.

The calcium-sensing receptor and vitamin D receptor expression in tertiary hyperparathyroidism.

The parathormone (PTH) production is controlled by calcium and vitamin D, which interact with the calcium-sensing receptor (CaSR) and vitamin D receptor (VDR), respectively. All of these elements control calcium homeostasis, which is crucial for many physiological processes. Thus, impairment of the upstream component of this system, e.g. a decrease of CaSR and/or VDR, could result in hyperparathyroidism (HPTH). Therefore, the aim of this study was to assess the expression of CaSR and VDR in a tertiary form of HPTH (T-HPTH). The study involved 19 T-HPTH patients qualified for parathyroidectomy and 21 control parathyroids harvested from multi-organ cadaver donors. The small fragments of harvested glands were homogenized and used for Western blot analysis, whereas the remaining tissues underwent routine hematoxylin-eosin staining or immunostaining for CaSR and VDR. Among 64 T-HPTH parathyroids, 58 revealed the morphology of benign hyperplasia, 2 were identified as adenoma and 4 were classified as normal; some glands displayed a mixed histological phenotype. Western blot analysis revealed a decrease of CaSR and VDR in hyperplasia and adenoma-derived samples. However, no correlation between the types of hyperplasia and receptor expression was observed. On the other hand, microscopic analysis of CaSR- and VDR-immunostained sections revealed a highly differentiated and significantly decreased mean expression of both receptors, which correlated with parathyroid histology. The reason behind the impaired expression of CaSR and VDR in T-HPTH is unclear. It presumably results from constant parathyroid stimulation at the stage of S-HPTH, followed by further development of polyclonal autonomy. However, the verification of this thesis requires further study.

Impaired apoptosis of lymphocytes derived from patient with decreased expression of caspase-8 results in Alps-like phenotype.

Human autoimmune lymphoproliferative syndrome has been described as a result of various mutations concerning genes encoding receptor CD95 and/or its ligand - CD178. However, recently, several cases with identical clinical manifestation, despite a normal structure of CD95 or CD178 have also been reported. In this study we analyzed PBMC obtained from patient with clinically overt lymphoproliferative disorder. Using in vitro assays as well as molecular methods we tested expression and biological activity of CD95 and CD178 molecules. We found that analyzed patient's lymphocytes displayed normal cytotoxic activity against CD95-bearing targets. However, CD95-dependent induction of apoptosis in analyzed lymphocytes was diminished, as compared to healthy control. Surprisingly, the molecular studies did not reveal any abnormalities in structure of patient-derived CD95 receptor molecule. Therefore, expression of other factors involved in CD95-mediated signaling pathway was estimated using RNase protection assay. The expression of FADD was comparable to that of healthy control. However, it has been found that patient-derived lymphocytes expressed reduced amount of caspase-8 mRNA, as compared to control subject cells. This report confirms previous observations that lymphoproliferative disorder could be associated not only with CD95 and/or CD178 mutations, but also with dysfunction of other components of apoptosis induction pathway. However, the detailed molecular mechanism of observed abnormalities in caspase-8 expression remains to be elucidated.