The cancer genome atlas - TCGA molecular classification: A changing paradigm in the management of endometrial cancers

Conventionally, endometrial cancers have been risk-stratified as per the clinco-pathological factors. The Cancer Genome Atlas project identified four distinct molecular subtypes within endometrial cancers which further lead to the clinical validation of molecular classification by various research groups. The molecular classification has influenced the risk stratification, thereby impacting adjuvant treatment decisions and prognostication. Molecular classification has paved the precision oncology in gynaecological cancers further strengthening the ongoing advances in targeted therapies and immunotherapy. This review elaborately presents the development of a new molecular classification of endometrial cancers; its evidence-based clinical utility with a brief overview of future perspectives

Pregnancy outcomes, Newborn complications and Maternal-Fetal Transmission of SARS-CoV-2 in women with COVID-19: A systematic review of 441 cases

ABSTRACTObjectiveThe aim of this systematic review was to examine the maternal and fetal outcomes in pregnant women with COVID-19 and also assess the incidence of maternal-fetal transmission of SARS CO-V-2 infection.Data sourcesWe searched PUMBED. Medline, Embase, MedRxiv and bioRxiv databases upto 3rdMay 2020 utilizing combinations of word variants for “coronavirus” or “COVID-19” or “severe acute respiratory syndrome” or “SARS-COV-2” and “pregnancy”. We also included data from preprint articles.Study eligibility criteriaOriginal case reports and case series on pregnant women with diagnosis of SARS-CoV-2 infection.Study appraisal and synthesis methodsWe included 50 studies reporting the information on 441 pregnant women and 391 neonates. The primary outcome measures were maternal health characteristics and adverse pregnancy outcomes, neonatal outcomes and SARS-CoV-2 infection in neonates was extracted. Treatments given to pregnant women with COVID-19 were also recorded.ResultsOut of 441 women affected by COVID-19 in pregnancy, 387 women have delivered. There are nine maternal deaths reported. In pregnant women with COVID-19, the most common symptoms were fever (56%), cough (43%), myalgia (19%), dyspnea (18%) and diarrhea (6%). Pneumonia was diagnosed by CT scan imaging in 96 % of COVID-19 pregnant women. Pregnancy complications included delivery by cesarean section (80%), preterm labor (26%), fetal distress (8%) and premature rupture of membranes (9%). Six still births (2%) are reported. The most common co-morbidities associated with pregnant women with COVID-19 were hypertensive disorders (10%), diabetes (9%), placental disorders (2%), co-infections (3%), scarred uterus (3%) and hypothyroidism (3%). Amongst the neonates of COVID-19 mothers, preterm birth (25%), respiratory distress syndrome (8%), pneumonia (8%) were reported. There were four neonatal deaths reported. Vertical transmission rate of SARS-CoV-2 is estimated to be 8%.ConclusionIn pregnant women with COVID-19, hypertensive disorders and diabetes are common comorbidities and there is a risk of preterm delivery and maternal death. Amongst the neonates born to mothers with COVID-19, respiratory distress syndrome and pneumonia are common occurrence. There are reports of still births and neonatal deaths. There is an evidence of vertical transmission of SARS-CoV-2 infection in women with COVID-19.</jats:sec

A systematic review on Multisystem Inflammatory Syndrome in Children (MIS-C) with COVID-19: Development of a scoring system for clinical diagnosis

AbstractBackgroundThere is growing evidence of Multisystem Inflammatory Syndrome in Children (MIS-C) resembling Kawasaki disease in children infected with SARS-CoV-2. The review was undertaken to evaluate the case definition, the spectrum of clinical presentations and current management practices in children with COVID-19 presenting with or without MIS-C.MethodsThe individual patient data from 119 studies accounting for 333 children were analyzed. We devised a scoring system as per WHO criteria to classify the patients as MIS-C or without MIS-C. A score of 3 was given for the presence of fever (&gt;24h) and a score of 1 for lab-confirmed diagnosis of SARS-CoV-2. Additionally, a score of 1 was given for a) rash or conjunctivitis or muco-cutaneous inflammation signs, b) hypotension or shock, c) diarrhea, vomiting or abdominal pain, d) features of myocardial dysfunction as determined by abnormal eco-cardiography or elevated Troponin or N-terminal pro B-type Natriuretic Peptide (NT-proBNP), e) evidence of coagulopathy as evidenced by elevated levels of prothrombin time PT, partial thromboplastin time PTT or D-dimer, f) laboratory evidence of inflammation as determined by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) or procalcitonin. A negative score of (−3) was given when there was a diagnosis of sepsis, staphylococcal or streptococcal shock syndrome. Based on these criteria, a minimum score of 6 was essential to classify the child as MIS-C.ResultsBased on this score, 18% (52/289) of cases were identified to be MIS-C. A greater proportion of children with MIS-C had cardiac involvement (MIS-C 80% vs Non-MIS-C 20%) and gastrointestinal involvement (MIS-C 71% vs Non-MIS-C 12%). Lymphopenia was commonly reported in MIS-C (MIS-C 54.2% vs Non-MIS-C 29.7%). In addition to routine inflammatory markers, significantly greater proportion of children with MIS-C had elevated Ferritin, LDH, Fibrinogen and IL-6. Children with MIS-C were less likely to have respiratory symptoms like cough (MIS-C 25% vs Non-MIS-C 75%) and rhinorrhea (MIS-C 4% vs Non-MIS-C 22.8%). A greater proportion of children with MIS-C required intensive care and aggressive treatment; and mortality rates were also higher in MIS-C group (MIS-C 10% vs Non-MIS-C 1%).ConclusionThe children with COVID-19 having cardiac and/or gastrointestinal involvement are more likely to develop MIS-C. The children with MIS-C have higher mortality rates. The scoring system developed herein will aid clinicians in patient diagnosis and timely management.</jats:sec

Persistence of SARS-CoV-2 in the first trimester placenta leading to transplacental transmission and fetal demise from an asymptomatic mother

Abstract Coronavirus disease 2019 (COVID-19) is caused by infection of the respiratory tract by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which survives in the tissues during the clinical course of infection but there is limited evidence on placental infection and vertical transmission of SARS-CoV-2. The impact of COVID-19 in first trimester pregnancy remains poorly understood. Moreover, how long SARS-CoV-2 can survive in placenta is unknown. Herein, we report a case of a pregnant woman in the first trimester who tested positive for SARS-CoV-2 at 8 weeks of gestation, although her clinical course was asymptomatic. At 13 weeks of gestation, her throat swab tested negative for SARS-CoV-2 but viral RNA was detected in the placenta, and the Spike (S) proteins (S1 and S2) were immunolocalized in cytotrophoblast and syncytiotrophoblast cells of the placental villi. Histologically, the villi were generally avascular with peri-villus fibrin deposition and in some areas the syncytiotrophoblast layer appeared lysed. The decidua also had fibrin deposition with extensive leukocyte infiltration suggestive of inflammation. The SARS-CoV-2 crossed the placental barrier, as the viral RNA was detected in the amniotic fluid and the S proteins were detected in the fetal membrane. Ultrasonography revealed extensively subcutaneous edema with pleural effusion suggestive of hydrops fetalis and the absence of cardiac activity indicated fetal demise. This is the first study to provide concrete evidence of persistent placental infection of SARS-CoV-2 and its congenital transmission is associated with hydrops fetalis and intrauterine fetal demise in early pregnancy.</jats:p

Protocol for a prospective, hospital-based registry of pregnant women with SARS-CoV-2 infection in India: PregCovid Registry study

IntroductionPregnant women are at increased risk of contracting COVID-19 due to several factors and therefore require special attention. However, the consequences of the COVID-19 pandemic on pregnant women and their newborns remain uncharted. The PregCovid registry aims to document the impact of SARS-CoV-2 infection on pregnant, postpartum women and their newborns. The aim of the registry is also to determine mother-to-child transmission of SARS-CoV-2 infection in India.Methods and analysisPregCovid is a hospital-based registry for capturing information of pregnant, postpartum women with COVID-19 and their newborns in India. Medical case records of pregnant and postpartum women with a laboratory-confirmed diagnosis of COVID-19 will be captured in real-time using an online electronic patient record software. The data analysis will be carried out for symptoms, the severity of COVID-19, pregnancy complications, maternal morbidity and mortality, neonatal complications, mother-to-child transmission, etc. Data analysis will be carried out for different waves of the COVID-19 pandemic for rapid response and developing strategies well in advance to manage pregnant women infected with SARS-CoV-2. The evidence generated from the registry will be regularly shared with the appropriate authorities for policy decisions. Thus, the registry data may be useful for planning the strategies for better management of pregnant women with COVID-19.Ethics and disseminationThe study has been approved by the Institutional Ethics Committees of all the participating study sites under the Medical Education and Drugs Department, Government of Maharashtra, Topiwala National Medical College &amp; BYL Nair Charitable Hospital, Mumbai and ICMR-National Institute for Research in Reproductive and Child Health, Mumbai, India. The results from this study will be disseminated with local, state, and national health authorities, collaborators and the general population on the study website (https://pregcovid.com) as well as dissemination through scientific meetings and publications.Trial registration numberCTRI/2020/05/025423.</jats:sec

Protocol for a prospective, hospital-based registry of pregnant women with SARS-CoV-2 infection in India: PregCovid Registry study

ABSTRACTIntroductionPregnant women are at increased risk of contracting coronavirus disease 2019 (COVID-19) due to several factors and therefore require special attention. However, the consequences of the COVID-19 pandemic on pregnant women and their newborns remain uncharted. The PregCovid registry aims to document the impact of SARS-CoV-2 infection on pregnant, post-partum women and their newborns. The aim of the registry is also to determine mother-to-child transmission of SARS-CoV-2 infection in India.Methods and analysisPregCovid is a hospital-based registry for capturing information of pregnant, post-partum women with COVID-19 and their newborns in India. Medical case records of pregnant and post-partum women with laboratory-confirmed diagnoses of COVID-19 will be captured in real-time using an online electronic patient record (EPR) software. The frequency of each symptom will be calculated. The laboratory data will be analyzed for calculating the frequency of laboratory parameters consistently higher in women with COVID- The adverse pregnancy and neonatal outcomes will be analyzed and their frequency will be calculated. Response to treatment will be analyzed for frequency calculation (number of women treated with different treatment regimens). The mother-to-child transmission data will be analyzed from the RT-PCR and/ antibody data of neonatal and maternal samples tested wherever the information is available. The registry data will be crucial for developing strategies for reducing the adverse impact of COVID-19 on pregnant women and their new-born.Ethics and disseminationThe study is approved by the Institutional Ethics Committee of ICMR-National Institute for Research in Reproductive Health (#55/2020), BYL Nair Hospital, Mumbai, India (# 63/2020); and all the 18 participating study sites under Medical Education and Drugs Department of Government of Maharashtra. The Institutional Ethics Committees granted a waiver of consent as the data is collected from the medical case records.Trial registration numberCTRI/2020/05/025423Article summaryStrengths and limitations of this studyThe PregCovid registry is a hospital-based registry at dedicated COVID-19 hospitals in India. The registry will help to identify new epidemiological, clinical characteristics, obstetrics outcomes associated with pregnant women and/post-partum women with COVID-19 in India. The study will also generate information on clinical presentations and outcomes of neonatal born to mothers with COVID-19 in India.PregCovid registry will provide evidence of mother to child transmission of SARS-CoV-2 infection in Indian womenThe evidence on unusual presentations of COVID-19 in pregnant and post-partum women will be generated.The follow-up of participants is only till the discharge from the hospital. Long-term follow-up is not included in the study.</jats:sec

Persistence of SARS-CoV-2 in the first trimester placenta leading to vertical transmission and fetal demise from an asymptomatic mother

SummaryCoronaviruses infect the respiratory tract and are known to survive in these tissues during the clinical course of infection. However, how long can SARS-CoV-2 survive in the tissues is hitherto unknown. Herein, we report a case where the virus is detected in the first trimester placental cytotrophoblast and syncytiotrophoblasts five weeks after the asymptomatic mother cleared the virus from the respiratory tract. This first trimester placental infection was vertically transmitted as the virus was detected in the amniotic fluid and fetal membranes. This congenitally acquired SARS-CoV-2 infection was associated with hydrops and fetal demise. This is the first study providing concrete evidences towards persistent tissue infection of SARS-CoV-2, its congenital transmission in early pregnancy leading to intrauterine fetal death.</jats:p