Maternal COVID-19 infection and intrauterine fetal death: Impact on the placenta and fetus.

BACKGROUND: Placental damage due to viral infections increases risk of adverse perinatal outcomes. Histopathologic examination of placenta can provide information regarding association between infection and outcome. There is paucity of data describing placental pathology with respect to intrauterine fetal death (IUFD) in pregnant mothers affected with COVID-19. METHODS: 4 fetuses and 10 placentas, including one twin placenta from 9 women with history of IUFD and SARS-CoV-2 infection underwent evaluation. These findings were contrasted with 3 fetuses and 21 gestational age matched placentas from non-infected women with history of IUFD. RESULTS: Extensive gross placental lesions, mixture of histologic features (maternal/ fetal vascular malperfusion) and isolated cases of massive perivillous fibrin depositon and chronic intervillositis were observed in COVID-IUFD group. There were no distinguishing histologic findings when compared to control. Three fetuses showed signs of intraventricular/intraparenchymal hemorrhage in autopsy. CONCLUSION: These findings demonstrate that IUFD does not correspond with maternal symptoms and lacks distinctive lesion. However, there was significant placental damage which developed rapidly. These results show that SARS-CoV-2 infection results in rapid placental deterioration and fetal death. This information can be used to educate infected mothers and remind medical professionals, value of monitoring placental function especially following diagnosis of infection.

Mentoring a surgical team towards procedural competence in the early learning curve for selective fetoscopic laser photocoagulation.

INTRODUCTION: Selective fetoscopic laser photocoagulation (SFLP) for twin-to-twin transfusion syndrome (TTTS) is challenging for new surgeons at the start of their learning curve. We described an approach utilising telementoring and team-based training to facilitate rapid attainment of the skills required for safe and efficient practice with a limited caseload. METHODS: We conducted a prospective observational study of SFLP performed by the novice primary surgical team in three stages: under direct on-site supervision from an expert mentor (Group 1), with remote tele-guidance from that mentor (Group 2) and independently (Group 3), at an academic tertiary hospital in Singapore. The primary team undertook regular training on high-fidelity tissue models to accelerate skills acquisition and complement the surgical performance. RESULTS: 9 patients diagnosed with Stage 2 TTTS were assessed for procedural characteristics, surgical outcomes and perinatal survival following SFLP. There were no significant differences in operative duration, anastomoses ablated, gestational age or birth weight at delivery. The complications observed were: recurrent TTTS (22.2% of pregnancies), twin anaemia polycythaemia sequence (33.3%), preterm prelabour membrane rupture (22.2%) and delivery at < 32 weeks (44.4%). ≥ 1 twin was live-born in 88.9% of cases, while postnatal survival to six months of ≥ 1 twin occurred in 77.8% of cases. CONCLUSION: Systematic mentoring and specialised skills training are useful in aiding new surgeons to negotiate the steep learning curve and achieve good outcomes at the start of a new practice, particularly in the setting of low patient numbers. This is best paired with dedicated model training to achieve and maintain surgical dexterity for this complex procedure.

Hyperreactio luteinalis following frozen embryo transfer managed by fetal reduction.

We report a rare case of hyperreactio luteinalis (HL) which developed in association with triplet pregnancy in a 27-year-old woman who underwent assisted reproductive technology treatment for primary infertility. She had undergone frozen embryo transfer 2 months after ovarian retrieval. She presented in the first trimester with abdominal pain and distension associated with ovarian enlargement and did not respond to conservative management. Fetal reduction was done from triplets to twins which resulted in good symptomatic relief for the patient. Fetal reduction may be an effective approach in such situations when conservative strategies fail in HL.

Supraventricular tachycardia in one of the twins: The ethical dilemmas involved in treatment.

The pediatric cardiologist now has an important role to play in fetal medicine. They are often called upon to manage fetal cardiac problems such as arrhythmias or perform fetal cardiac interventions such as balloon valvuloplasty or atrial septostomy. In these scenarios, it becomes very important for the pediatric cardiologist to understand the concepts of "fetus as a patient," "viability," etc., and their implications in management. We try to shed light on these principles through our case scenario of managing supraventricular tachycardia in one of the fetuses of a twin pregnancy.

Phosphorylation of the SSBP2 and ABL proteins by the ZNF198-FGFR1 fusion kinase seen in atypical myeloproliferative disorders as revealed by phosphopeptide-specific MS.

The ZNF198-fibroblast growth factor receptor-1 (FGFR1) fusion kinase is a constitutively activated tyrosine kinase associated with a specific atypical myeloproliferative disease. The chimeric protein localizes to the cytoplasm, unlike the wild type FGFR1 receptor kinase, and presumably inappropriately phosphorylates specific targets as part of the oncogenic signaling cascade. Other than known targets of the FGFR1 kinase itself, few specific targets of ZNF198-FGFR1 have been identified. Using a genetically engineered HEK 293 cell system, we have identified proteins that are specifically phosphorylated in the presence of the fusion kinase using anti-phosphotyrosine immunoprecipitation and MS. Compared with 293 cells expressing exongenous wild type FGFR1, ZNF198-FGFR1 is associated with phosphorylation of several proteins including SSBP2, ABL, FLJ14235, CALM and TRIM4 proteins. The specificity of the phosphorylation events in the SSBP2 and ABL proteins, which have previously been implicated in leukemogenesis, was further confirmed independently using immunoprecipitation with protein-specific antibodies and Western blotting. The MS analysis also identified the phosphorylation events in the ZNF198 moiety in the chimeric protein that might be related to its function. These studies identify the intersection of several different leukemia-related pathways in the development of this myeloproliferative disorder and provide new insights into the substrates of FGFR1 under defined conditions.