With the emergence of SARS-CoV-2 and its rapid spread, concerns regarding its effects on pregnancy outcomes have been growing. We reviewed 245 pregnancies complicated by maternal SARS-CoV-2 infection across 48 studies listed on PubMed and MedRxiv. The most common clinical presentations were fever (55.9%), cough (36.3%), fatigue (11.4%), and dyspnea (12.7%). Only 4.1% of patients developed respiratory distress. Of all patients, 89.0% delivered via cesarean section ( n = 201 ), with a 33.3% rate of gestational complications, a 35.3% rate of preterm delivery, and a concerning 2.5% rate of stillbirth delivery or neonatal death. Among those tested, 6.45% of newborns were reported positive for SARS-CoV-2 infection. Relative to known viral infections, the prognosis for pregnant women with SARS-CoV-2 is good, even in the absence of specific antiviral treatment. However, neonates and acute patients, especially those with gestational or preexisting comorbidities, must be actively managed to prevent the severe outcomes being increasingly reported in the literature.
With the emergence of SARS-CoV-2 and its rapid spread, concerns regarding its effects on pregnancy outcomes have been growing. We reviewed 164 pregnancies complicated by maternal SARS-CoV-2 infection across 20 studies. The most common clinical presentations were fever (57.9%), cough (35.4%), fatigue (15.2%), and dyspnea (12.2%). Only 2.4% of patients developed respiratory distress. Of all patients, 84.5% delivered via Cesarean section, with a 23.9% rate of maternal gestational complications, 20.3% rate of preterm delivery, and a concerning 2.3% rate of stillbirth delivery. Relative to known viral infections, the prognosis for pregnant women with SARS-CoV-2 is good, even in the absence of specific antiviral treatment. However, neonates and acute patients, especially those with gestational or pre-existing co-morbidities, must be actively managed to prevent severe outcomes.
Background: Family history is one of the strongest predisposing factors for male breast cancer (MBC). Several MBC susceptibility genes have been identified, but the risk of MBC for individuals with a pathogenic variant in these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes. Methods: A search query was developed to identify MBC-related abstracts indexed in PubMed, with the followings structure: "Breast Neoplasms, Male"[Mesh] OR (((“Men”[MESH]) OR (male*[TIAB]) OR (man[TIAB]) OR (men[TIAB])) AND ((“Breast Neoplasms”[MESH]) OR (Breast Cancer*[TIAB]) OR (Breast neoplasm*[TIAB]))). A validated natural language processing (NLP) method was applied to retrieve and classify abstracts reporting penetrance estimates. Abstracts labeled as relevant were manually reviewed. The full-text papers of identified penetrance studies were then annotated to extract MBC risk data. These penetrance studies’ bibliographies were also reviewed to ensure comprehensiveness. Results: We identified 17 penetrance studies from 11,799 abstracts, covering five MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2 (Table 1). 53% of these studies were case-control studies, while the rest were cohort studies. Odds ratio (OR), cumulative risk (CR), and relative risk (RR) were three commonly reported risk measures. For BRCA2, eight out of nine studies reported significantly increased risk of MBC or a lifetime CR of over 6%; only one study reported an increased but not statistically significant risk. For BRCA1, one out of six studies reported an elevated lifetime CR of 5.8%, while a second reported a minor increase (OR=1.49) that was statistically significant. The risks reported in the remaining four studies showed no statistically significant increase in risk. Seven studies reported the penetrance of CHEK2, but the risks diverge between the variants tested (Table 2). All three PALB2 studies reported significantly increased risk, while only one ATM study reported an increased risk of MBC, which did not reach statistical significance. Conclusion: To our knowledge, this review provides the first complete set of reported penetrance data for five MBC susceptibility genes. Contradictory MBC risks (significantly increased risk vs. risks that were not statistically significant) were common, which may be due to the studies’ different ascertainment criteria resulting in risk estimates for differing populations. Risk across these studies cannot be directly compared unless studies adjust for ascertainment, though this cataloging of risk defines our current understanding. Table 1: MBC penetrance studiesGeneNumber of StudiesStudy TypeRisk Estimate ReportedMBC RiskBRCA296 Cohort, 3 Case-controlOR, RR, CRStatistically significant increased risk (or lifetime CR > 6%) in 8/9 studiesCHEK277 Case-controlOR, RRVarying risk by variantBRCA163 Cohort, 3 Case-controlOR, RR, CR, HRStatistically significant increased risk in 1/6 studies, one study report lifetime CR = 5.8%PALB231 Cohort, 2 Case-controlOR, RRStatistically significant increased risk in 3/3 studiesATM11 Case-controlORStatistically significant increased risk in 0/1 studyOR: odds ratio; RR: relative risk; CR: cumulative risk; HR: hazard ratio Table 2: As an example: Reported penetrance of CHEK2 for male breast cancer in studies with varying ascertainment criteriaFirst Author, Year of Publication, Patient Population*Pathogenic VariantNumber of CarriersRisk TypeRisk Estimate (95% CI)Statistical SignificanceMeijers-Heijboer H, 2002, Multiple Countries1100delC57RR10.28 (3.54-29.87)YesSyrjakoski K, 2004, Finland1100delC28OR1.27 (0.04-7.92)NoWasielewski M, 2009, Netherlands1100delC21OR4.1 (1.2-14.3)YesPritzlaff M, 2017, USAAll441OR2.4 (1.4-3.9)Yes1100delC135OR3.8 (1.7-7.8)YesI157T238OR1.3 (0.5-3.0)NoHallamies S, 2017, Finland1100delC30OR4.47 (1.51-13.18)YesI157T104OR1.12 (0.4-3.13)NoLu HM, 2019, USANot specifiedNot specifiedOR1.66 (0.04-10.34)NoKleiblova P, 2019, Czech RepublicTruncations3OR20.21 (3.5-80.0)YesDeleterious missense1OR11.87 (0.25-100.83)NoIntermediate missense2OR1.3 (0.15-5.07)NoNeutral missense2OR9.07 (0.98-40.41)NoOR: odds ratio; RR: relative risk* All studies in Table 2 are case-control studies Citation Format: Reem S Chamseddine, Jin Wang, Kanhua Yin, Preeti Singh, Jingan Zhou, Danielle Braun, Mark E Robson, Kevin S Hughes. Penetrance of male breast cancer susceptibility genes: A systematic review [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-40.
Background SARS-CoV-2 is a novel virus that appeared in China in November 2019 and spread rapidly. With no vaccine or effective treatment, countries have adopted different mitigation measures to reduce SARS-COV-2 spread with different efficacy.MethodsWe mapped the impact of mitigation measures across different countries. We compared regional SARS-COV-2 population burden via Kruskal-Wallis statistical testing. We analyzed time of adoption of mitigation measures and the impact of PCR testing on mitigation impact. We analyzed the association of climate, health, demographic and economic indicators with mitigation impact via non-parametric correlation tests. We performed mechanistic modelling of to predict short-term SARS-COV-2 case numbers in selected countries. ResultsMany countries showed a reduction of infection rates within one month of implementing mitigation measures. However, we identified a geographic cluster of countries centered on the Arabian Peninsula (AP) that show a high SARS-COV-2 population burden despite early adoption of mitigation measures. We find that higher air pollution levels (p=0.01), higher CO2 emissions (p=0.03) and younger population (p=0.02) were associated with reduced mitigation impact in AP countries. We also show that mechanistic modelling can closely predict confirmed case numbers in the short term.ConclusionsThe impact of mitigation measures varies greatly between countries. Countries with similar profiles as AP countries should adopt more stringent mitigation measures to more rapidly reduce SARS-CoV-2 spread. Specific interventions targeting young people may also be effective in reducing SARS-COV-2 spread.
Background SARS-CoV-2 is a novel virus that appeared in China in November 2019 and spread rapidly. With no vaccine or effective treatment, countries have adopted different mitigation measures to reduce SARS-COV-2 spread with different efficacy. Methods We mapped the impact of mitigation measures across different countries. We compared regional SARS-COV-2 population burden via Kruskal-Wallis statistical testing. We analyzed time of adoption of mitigation measures and the impact of PCR testing on mitigation impact. We analyzed the association of climate, health, demographic and economic indicators with mitigation impact via non-parametric correlation tests. We performed mechanistic modelling of to predict short-term SARS-COV-2 case numbers in selected countries. Results Many countries showed a reduction of infection rates within one month of implementing mitigation measures. However, we identified a geographic cluster of countries centered on the Arabian Peninsula (AP) that show a high SARS-COV-2 population burden despite early adoption of mitigation measures. We find that higher air pollution levels (p=0.01), higher CO2 emissions (p=0.03) and younger population (p=0.02) were associated with reduced mitigation impact in AP countries. We also show that mechanistic modelling can closely predict confirmed case numbers in the short term.
Gestational diabetes mellitus (GDM) is a well-established risk factor for fetal macrosomia. A significant number of patients with GDM also suffer from obesity, a factor associated with fetal macrosomia. An important question is whether GDM is independently associated with fetal macrosomia, or whether this relationship is merely the result of maternal obesity acting as a confounder. In this review of the literature, we attempt to further elucidate the relationship between GDM, maternal obesity, and fetal macrosomia.
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