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SARS-CoV-2 has had a significant impact on pregnancy outcomes due to the effects of the virus and the altered healthcare environment. Stillbirth has been relatively hidden during the COVID-19 pandemic, but a clear link between SARS-CoV-2 and poor fetal outcome emerged in the Alpha and Delta waves. A small minority of women/birthing people who contracted COVID-19 developed SARS-CoV-2 placentitis. In many reported cases this was linked to intrauterine fetal death, although there are cases of delivery just before imminent fetal demise and we shall discuss how some cases are sub-clinical. What is surprising, is that SARS-CoV-2 placentitis is often not associated with severe maternal COVID-19 infection and this makes it difficult to predict. The worst outcomes seem to be with diffuse placental disease which occurs within 21 days of COVID-19 diagnosis. Poor outcomes are often pre-dated by reduced fetal movements but are not associated with ultrasound changes. In some cases, there has also been maternal thrombocytopenia, or coagulation abnormalities, which may provide a clue as to which pregnancies are at risk of fetal demise if a further variant of concern is to emerge. In future, multidisciplinary collaboration and cross-boundary working must be prioritised, to identify quickly such a phenomenon and provide clinicians with clear guidance for reducing fetal death and associated poor outcomes. While we wait to see if COVID-19 brings a future variant of concern, we must focus on appropriate future management of women who have had SARS-CoV-2 placentitis. As a placental condition with an infectious aetiology, SARS-CoV-placentitis is unlikely to recur in a subsequent pregnancy and thus a measured approach to subsequent pregnancy management is needed.
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COVID-19 , Corioamnionite , Complicações Infecciosas na Gravidez , Gravidez , Feminino , Humanos , Natimorto/epidemiologia , SARS-CoV-2 , Placenta , Teste para COVID-19 , Pandemias , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Transmissão Vertical de Doenças InfecciosasRESUMO
The loops of modular polyketide synthases (PKSs) serve diverse functions but are largely uncharacterized. They frequently contain amino acid repeats resulting from genetic events such as slipped-strand mispairing. Determining the tolerance of loops to amino acid changes would aid in understanding and engineering these multidomain molecule factories. Here, tandem repeats in the DNA encoding 949 modules within 129 cis-acyltransferase PKSs were cataloged, and the locations of the corresponding amino acids within the module were identified. The most frequently inserted interdomain loop corresponds with the updated module boundary immediately downstream of the ketosynthase (KS), while the loops bordering the dehydratase are nearly intolerant to such insertions. From the 949 modules, no repetitive sequence loop insertions are located within ACP, and only 2 reside within KS, indicating the sensitivity of these domains to alteration.
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Proteína de Transporte de Acila/química , Aciltransferases/química , Bactérias/enzimologia , Proteínas de Bactérias/química , Policetídeo Sintases/química , Policetídeos/metabolismo , Proteína de Transporte de Acila/classificação , Proteína de Transporte de Acila/genética , Proteína de Transporte de Acila/metabolismo , Aciltransferases/classificação , Aciltransferases/genética , Aciltransferases/metabolismo , Sequência de Aminoácidos , Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Clonagem Molecular , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Cinética , Modelos Moleculares , Policetídeo Sintases/classificação , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Policetídeos/química , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , TermodinâmicaRESUMO
Follicular variant papillary thyroid carcinoma (FVPTC) may pose a diagnostic challenge due to higher likelihood of lower risk cytology compared to conventional papillary thyroid carcinoma (CPTC). Recent guidelines have recommended the use of sonographic features to guide decisions to biopsy thyroid nodules. The purpose of this study was to evaluate the sonographic features of CPTC and FVPTC. This is a retrospective study design done in an Academic teaching hospital setting. Preoperative ultrasounds of 79 patients with conventional CPTC (48) and FVPTC (31) were reviewed by a radiologist blinded to histological diagnosis. Sonographic features of nodules were classified according to the British Thyroid Association (BTA) U-classification system as normal (U1), benign (U2), indeterminate (U3), suspicious (U4), and malignant (U5). Pathology slides of patients with FVPTC were reviewed by two pathologists and subclassified into encapsulated, well circumscribed/partly encapsulated, and infiltrative subtypes. FVPTC had a significantly lower incidence of any calcifications (p = 0.0005), microcalcifications (p = 0.002), and irregular or lobulated margins (p = 0.03) than CPTC. Differences in hypoechogenicity (p = 0.06), taller > wide shape (p = 0.17) and presence of halo (p = 0.07) were not significant. FVPTC was significantly less likely to be classified sonographically as malignant (U5) (p = 0.006) or suspicious/malignant (U4/5) (p = 0.009) than conventional PTC. Among FVPTC cases, infiltrative FVPTC were more likely to be sonographically classified as suspicious/malignant (U4/5) than non-infiltrative FVPTC. FVPTC nodules are less likely to show sonographic features of malignancy than conventional PTC. Reliance solely on sonographic features for thyroid nodule evaluation may not be sufficient to exclude FVPTC.
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Adenocarcinoma Folicular , Carcinoma Papilar , Cuidados Pré-Operatórios , Neoplasias da Glândula Tireoide , Ultrassonografia/métodos , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/patologia , Adulto , Idoso , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/estatística & dados numéricosRESUMO
Purpose: To investigate the influence of lateral meniscal and cartilage pathology on the outcome after anterior cruciate ligament (ACL) reconstruction in patients who participate in pivoting sports. Methods: Using a single-surgeon patient registry, patients undergoing an anterior cruciate ligament reconstruction (ACLR) using bone-patellar tendon-bone autograft were evaluated with minimum 2-year patient reported outcomes evaluated using Marx, Tegner, Lysholm, and International Knee Documentation Committee scales. Patients were divided into 3 groups: isolated ACL surgery, ACLR with a partial lateral meniscectomy, or a ACLR with partial lateral meniscectomy and lateral compartment chondroplasty. Results: A total of 98 patients met inclusion criteria. Using the isolated ACL reconstruction group as a control, we found that Marx scores were greater in patients who additionally underwent a partial lateral meniscectomy at 1 year (P = .016). There were no significant differences between the ACL-only group and the ACL with partial lateral meniscectomy and chondroplasty group. Within the partial meniscectomy cohort comparing the patients with red-white zone tears with the patients with white-white zone tear, we found there were no significant differences when compared with the ACL-only control. There were no significant differences appreciated between groups using the International Knee Documentation Committee, Lysholm, and Tegner scales. Conclusions: ACL reconstruction using bone-patellar tendon-bone autograft with anteromedial portal drilling technique does not have any significant short-term (2-year outcome) differences in return to activity and patient-reported outcomes compared with if patients additionally have a partial lateral meniscectomy and/or lateral compartment chondroplasty. Additional partial lateral meniscectomy showed significantly greater Marx scores at 1 and 2 years' postoperatively. Level of Evidence: Level III, retrospective cohort study.
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Purpose: To investigate the relation between body mass index (BMI) and outcomes after anterior cruciate ligament reconstruction (ACLR) using 10-mm-diameter bone-patellar tendon-bone grafts. Methods: In this retrospective study, the Surgical Outcome System was used to measure patient-reported outcomes before and after ACLR between 2015 and 2019. The inclusion criteria consisted on patients undergoing primary ACLR performed by the senior surgeon, with recorded age of 15 years or older and BMI of 15.0 to 30. The exclusion criteria included revisions, concomitant procedures, age younger than 15 years, and unknown BMI. Patients were divided into cohorts to evaluate the Marx Activity Rating Scale (MARS), Tegner, International Knee Documentation Committee (IKDC), and Lysholm scores at various time points from injury to 2 years postoperatively. Results: A total of 137 patients (100 male and 37 female patients) with an average age of 33 years (95% confidence interval, 30.6-35.4 years) and average BMI of 23.58 (95% confidence interval, 23.1-24.0) were divided into those with a BMI of 15 to 23.4 (group A, n = 69) and those with a BMI of 23.5 to 30 (group B, n = 68). A significant difference in MARS scores was found between the BMI groups before treatment, with mean scores of 11.55 (group A) and 9.41 (group B) (P = .011), and Tegner scores showed significance at 2 years, with scores of 6.45 and 5.41 for groups A and B, respectively (P = .009). Daily function scores were all insignificant. Female patients exhibited no significant differences across any patient-reported outcome measures or time points. Contrarily, male patients showed a significant difference in pretreatment MARS scores (14.30 in group A vs 9.96 in group B, P = .011). Additionally, scores at 2 years depicted Tegner values of 7.40 in group A versus 5.30 in group B (P = .012) and IKDC values of 96.92 in group A versus 90.47 in group B (P = .048). All results for female and male patients aged 30 years or younger indicated no significance. Conclusions: Regardless of patient age or sex, BMI is not significantly associated with patient-reported outcomes after ACLR using 10-mm-diameter bone-patellar tendon-bone grafts. Level of Evidence: Level III, retrospective cohort study.
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AIMS: Diagnosis of hydatidiform mole or molar pregnancy based on morphology alone can be challenging, particularly in early gestation, necessitating the use of ancillary techniques for accurate diagnosis. We sought to adapt the VENTANA HER2 dual-colour dual-hapten in-situ hybridisation (D-DISH) assay by using the internal chromosome 17 enumeration probe to determine ploidy status. METHODS: We selected 25 products of conception, consisting of molar and non-molar cases, to validate the HER2 D-DISH assay. These cases had prior morphological assessment by a perinatal pathologist and ploidy analysis using molecular cytogenetics. Three independent observers, blinded to the original histopathological and genetic diagnosis, scored 10 representative areas on each slide. Interobserver variability was assessed by comparing the total scores of each observer using analysis of variance (ANOVA) and the kappa statistic. RESULTS: Our ploidy scoring system accurately determined the correct number of diploid and triploid conceptuses, demonstrating complete concordance with pre-existing ploidy status and the initial diagnosis. Interobserver agreement between three independent scorers was robust: ANOVA (p=0.36) and kappa statistic (0.812, p<0.001). We achieved clear separation of average nuclear signals for diploid and triploid conceptuses, which was statistically significant (p<0.05). Employing our innovative scoring system, known as the 'rule of 5', we established ploidy decision thresholds for all 25 cases. CONCLUSIONS: Our modified HER2 D-DISH ploidy assay simplifies the process of ploidy determination and improves the accuracy of morphological diagnosis of molar pregnancy. The HER2 D-DISH assay was selected for ploidy analysis due to the widespread availability of in-situ hybridisation in pathology laboratories.
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AIMS: A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM diagnosis. This study sought to evaluate the clinical accuracy of PHM diagnosis using morphological assessment supported by HER2 dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination. METHODS: Over a 2-year period, our unit examined 1265 products of conception (POCs) from which 103 atypical POCs were diagnosed as PHM or non-molar conceptuses with the assistance of HER2 D-DISH ploidy analysis. We retrospectively audited a sample of 40 of these atypical POCs using short tandem repeat genotyping. DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped using 24 polymorphic loci. Parental alleles in placental villi were identified by comparison to those in maternal decidua. To identify triploid PHM cases, we sought three alleles of equal peak height or two alleles with one allele peak twice the height of the other at each locus. RESULTS: Thirty-six of the 40 cases (19 PHM and 17 non-molar) were successfully genotyped and demonstrated complete concordance with the original diagnosis. All PHMs were diandric triploid of dispermic origin. In two non-molar diploid cases, we identified suspected trisomies (13 and 18), which potentially explains the pregnancy loss in these cases. CONCLUSIONS: This study validates the use of HER2 D-DISH ploidy analysis to support the diagnosis of a morphologically suspected PHM in our practice.
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AIMS: This study aimed to re-evaluate the incidence of hydatidiform mole (HM) and determine gestational trophoblastic disease (GTD) registration rates in Ireland following the establishment of the National GTD Registry in 2017. METHODS: We performed a 3-year retrospective audit of HM cases (January 2017 to December 2019) reported in our centre. In 2019, we surveyed Irish pathology laboratories to determine the number of HMs diagnosed nationally and compared this data to that recorded in the National GTD Registry. Additionally, we compared both local and national HM incidence rates to those reported internationally. RESULTS: In the 3-year local audit, we identified 87 HMs among 1856 products of conception (POCs) providing a local HM incidence rate of 3.92 per 1000 births. The 1-year pathology survey recorded 170 HMs in 6008 POCs, yielding a national incidence rate of 2.86 per 1000 births. Importantly, the local HM incidence rate exceeded the national incidence rate by 37% and the local partial HM incidence (1 in 296 births) was 64% higher than the nationally incidence rate (1 in 484 births). Notably, 42% of the HM and atypical POCs diagnosed nationally were not reported to the National GTD Registry. CONCLUSIONS: Our study reveals increased HM incidence rates both locally and nationally compared with previous Irish studies. The higher local PHM incidence may reflect more limited access to ploidy analysis in other pathology laboratories nationally. Significantly, almost half of the women with diagnosed or suspected HM were not registered with the National GTD Centre.
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Appendage shape is formed during development (and re-formed during regeneration) according to spatial and temporal cues that orchestrate local cellular morphogenesis. The caudal fin is the primary appendage used for propulsion in most fish species, and exhibits a range of distinct morphologies adapted for different swimming strategies, however the molecular mechanisms responsible for generating these diverse shapes remain mostly unknown. In zebrafish, caudal fins display a forked shape, with longer supportive bony rays at the periphery and shortest rays at the center. Here, we show that a premature, transient pulse of sonic hedgehog a (shha) overexpression during late embryonic development results in excess proliferation and growth of the central rays, causing the adult caudal fin to grow into a triangular, truncate shape. Both global and regional ectopic shha overexpression are sufficient to alter fin shape, and forked shape may be rescued by subsequent treatment with an antagonist of the canonical Shh pathway. The induced truncate fins show a decreased fin ray number and fail to form the hypural diastema that normally separates the dorsal and ventral fin lobes. While forked fins regenerate their original forked morphology, truncate fins regenerate truncate, suggesting that positional memory of the fin rays can be permanently altered by a transient treatment during embryogenesis. Ray finned fish have evolved a wide spectrum of caudal fin morphologies, ranging from truncate to forked, and the current work offers insights into the developmental mechanisms that may underlie this shape diversity.
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Hydatidiform moles are rare and thus most pathologists and geneticists have little experience with their diagnosis. It is important to promptly and correctly identify hydatidiform moles given that they are premalignant disorders associated with a risk of persistent gestational trophoblastic disease and gestational trophoblastic neoplasia. Improvement in diagnosis can be achieved with uniformization of diagnostic criteria and establishment of algorithms. To this aim, the Pathology and Genetics Working Party of the European Organisation for Treatment of Trophoblastic Diseases has developed guidelines that describe the pathological criteria and ancillary techniques that can be used in the differential diagnosis of hydatidiform moles. These guidelines are based on the best available evidence in the literature, professional experience and consensus of the experts' group involved in its development.
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Doença Trofoblástica Gestacional , Mola Hidatiforme , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/genética , Doença Trofoblástica Gestacional/diagnóstico , Doença Trofoblástica Gestacional/genética , Diagnóstico Diferencial , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologiaRESUMO
The aim of this study was to provide the first systematic description of human placental cytology appearances and to investigate syncytiotrophoblast nuclear organisation patterns using cytology techniques. Term placentas from normal pregnancies were sampled using fine-needle aspiration (FNA) and direct scrapes. Standard histological examination was also performed to exclude pathological changes in the placentas being studied. Both Papanicolaou-stained cytospin preparations and air-dried Giemsa slides from FNA provided high-quality material for cytological assessment with good cellularity. Among the key features of the cytology preparations were villous "microbiopsies" that allowed for the three-dimensional appreciation of villous branching patterns. Cytological appearances, including nuclear characteristics of villous cytotrophoblast and syncytiotrophoblast, were also well demonstrated. In microbiopsies and detached villous trophoblast sheets, complex patterns of syncytiotrophoblast nuclear organisation, not previously described cytologically, were observed, including irregular spacing of nuclei, syncytioplasm windows and linear nuclear arrangements. This study showed that placental cytology (a) provides technically excellent material for cytological evaluation, (b) confirms the presence of complex nuclear organisational patterns in the syncytiotrophoblast by eliminating the possibility of tangential sectioning artefact, (c) provides superior nuclear detail over standard histological sections and (d) may be an untapped research resource for the investigation of normal and pathological processes because of its ability to look at the placenta in a novel way and through its potential for both ex vivo and in vivo placental sampling.
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Gestational trophoblastic disease describes a group of rare pregnancy related disorders that span a spectrum of premalignant and malignant conditions. Hydatidiform mole (also termed molar pregnancy) is the most common form of this disease. Hydatidiform mole describes an abnormal conceptus containing two copies of the paternal genome, which is classified as partial when the maternal genome is present or complete when the maternal genome is absent. Hydatidiform mole typically presents in the first trimester with irregular vaginal bleeding and can be suspected on ultrasound but confirmation requires histopathological evaluation of the products of conception. Most molar pregnancies resolve without treatment after uterine evacuation, but occasionally the disease persists and develops into gestational trophoblastic neoplasia. Close monitoring of women after molar pregnancy, with regular measurement of human chorionic gonadotrophin concentrations, allows for early detection of malignancy. Given the rarity of the disease, clinical management and treatment is best provided in specialist centres where very high cure rates are achievable. This review looks at advances in the diagnosis and early management of gestational trophoblastic disease and highlights updates to disease classification and clinical guidelines. Use of molecular genotyping for improved diagnostic accuracy and risk stratification is reviewed and future biomarkers for the earlier detection of malignancy are considered.
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CONTEXT.: A severe third wave of COVID-19 disease affected Ireland in the first 3 months of 2021. In this wave, 1 second-trimester miscarriage and 6 stillbirths were observed in the Irish population because of placental insufficiency as a result of SARS-CoV-2 placentitis. This observation was at odds with the country's previous experience with COVID-19 disease in pregnant mothers. OBJECTIVE.: To describe the clinical and pathologic features of these pregnancy losses. DESIGN.: Retrospective review of clinical and pathologic data of cases of second-trimester miscarriage, stillbirth, or neonatal death identified by perinatal pathologists as being due to SARS-CoV-2 placentitis during the third wave of COVID-19 in Ireland. RESULTS.: Clinical and pathologic data were available for review in 6 pregnancies. Sequencing or genotyping of the virus identified SARS-CoV-2 alpha (B.1.1.7) in all cases. Three of the 6 cases had maternal thrombocytopenia, and fetal growth restriction was not prominent, suggesting a rapidly progressive placental disease. CONCLUSIONS.: The identification of SARS-CoV-2 alpha in all these cases suggests that the emergence of the variant was associated with an increased risk of fetal death due to SARS-CoV-2 placentitis when compared with the original virus. Maternal thrombocytopenia may have potential as a clinical marker of placentitis, but other inflammatory markers need investigation. Three of the 6 women had been assessed for reduced fetal movements in hospital some days before the fetal deaths actually occurred; this could suggest that there may be a window for intervention in some cases.
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Aborto Espontâneo , COVID-19 , Complicações Infecciosas na Gravidez , Trombocitopenia , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/patologia , Feminino , Morte Fetal/etiologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Irlanda/epidemiologia , Masculino , Placenta/patologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , SARS-CoV-2 , Natimorto/epidemiologiaRESUMO
CONTEXT.: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. OBJECTIVE.: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN.: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. RESULTS.: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. CONCLUSIONS.: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
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COVID-19 , Morte Perinatal , Placenta , Complicações Infecciosas na Gravidez , COVID-19/complicações , Feminino , Fibrina , Humanos , Hipóxia/patologia , Hipóxia/virologia , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Morte Perinatal/etiologia , Placenta/patologia , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , SARS-CoV-2 , NatimortoRESUMO
With the redefinition of polyketide synthase (PKS) modules, a new appreciation of their most downstream domain, the ketosynthase (KS), is emerging. In addition to performing its well-established role of generating a carbon-carbon bond between an acyl-CoA building block and a growing polyketide, it may gatekeep against incompletely processed intermediates. Here, we investigate 739 KSs from 92 primarily actinomycete, cis-acyltransferase assembly lines. When KSs were separated into 16 families based on the chemistries at the α- and ß-carbons of their polyketide substrates, a comparison of 32 substrate tunnel residues revealed unique sequence fingerprints. Surprisingly, additional fingerprints were detected when the chemistry at the γ-carbon was considered. Representative KSs were modeled bound to their natural polyketide substrates to better understand observed patterns, such as the substitution of a tryptophan by a smaller residue to accommodate an l-α-methyl group or the substitution of four smaller residues by larger ones to make better contact with a primer unit or diketide. Mutagenesis of a conserved glutamine in a KS within a model triketide synthase indicates that the substrate tunnel is sensitive to alteration and that engineering this KS to accept unnatural substrates may require several mutations.
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Aciltransferases/química , Ligases/química , Policetídeos/química , Domínio CatalíticoRESUMO
Using the updated module boundary of polyketide assembly lines, modules from the pikromycin synthase were recombined into engineered synthases that furnish an enantiomeric pair of 2-stereocenter triketide lactones at >99% ee with yields up to 0.39 g per liter of E. coli K207-3 in shake flasks.
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We present a case of third trimester pregnancy complicated by SARS-CoV-2 infection and subsequent reduced fetal movements, resulting in emergency Caesarean delivery with demonstrable placental SARS-CoV-2 placentitis. We show through illustration of this case and literature review that SARS-Co-V-2 placentitis is an uncommon but readily recognisable complication of maternal SARS-CoV-2 infection that may be a marker of potential vertical transmission and that may have the capacity to cause fetal compromise through a direct injurious effect on the placenta.
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COVID-19/complicações , Doenças Placentárias/virologia , Placenta/patologia , Complicações Infecciosas na Gravidez/virologia , Adulto , COVID-19/patologia , Feminino , Humanos , Doenças Placentárias/patologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Terceiro Trimestre da Gravidez , SARS-CoV-2RESUMO
CONTEXT.: SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown. OBJECTIVE.: To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants. DESIGN.: Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells. RESULTS.: Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. CONCLUSIONS.: SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.
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COVID-19/transmissão , COVID-19/virologia , Transmissão Vertical de Doenças Infecciosas , Macrófagos/virologia , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/patogenicidade , Adulto , COVID-19/imunologia , COVID-19/patologia , Proliferação de Células , Endotélio/patologia , Endotélio/virologia , Feminino , Humanos , Hiperplasia/patologia , Hiperplasia/virologia , Recém-Nascido , Macrófagos/patologia , Macrófagos/fisiologia , Masculino , Placenta/patologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/patologia , Estudos Retrospectivos , SARS-CoV-2/imunologia , Natimorto , Trofoblastos/patologia , Trofoblastos/virologiaRESUMO
Introduction: Individual placental and umbilical cord morphometry have been previously identified to have an association with fetal growth. This study aims to identify which of the morphometric measurements in combination are associated with pregnancies with small for gestational age (SGA) infants using digital imaging of the delivered placenta.Material and methods: This study examined 1005 placentas from consecutively delivered singleton pregnancies in a tertiary center. Standardized images of each placenta were taken. Placental weight and thickness; umbilical cord length and diameter were measured on gross examination. Distance from the placental cord insertion site to placental margin, length and breadth of the placenta and placental chorionic surface area were measured digitally using ImageJ software. Logistic regression models and area under the curve (AUC) were used to identify the best subset of morphometric measurements to classify infants as SGA (<10th centile).Results: Overall, 141 (14%) infants were SGA. The morphometric measurements at delivery most strongly associated with the classification of infants as SGA were placental weight (AUC = 0.806) and placental surface area (AUC = 0.749). Of the potential antenatal morphometric measurements, umbilical cord diameters, both placental (AUC = 0.644) and fetal end (AUC = 0.629) were most strongly associated with SGA. A logistic regression model with maternal age, smoking status, current history of preeclampsia, umbilical cord length, placental weight, birthweight-to-placental weight ratio and umbilical cord diameter (placental end) had a sensitivity of 53% and a false-positive rate of 2% (AUC = 0.945) for the classification of infants as SGA.Conclusion: Placental and umbilical cord morphometry measured at delivery are different between SGA and non-SGA infants. Further studies are warranted to investigate the feasibility and accuracy of ultrasound to measure placental and umbilical cord morphometry during pregnancy.
Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Placenta , Feminino , Desenvolvimento Fetal , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Placenta/diagnóstico por imagem , Gravidez , Cordão Umbilical/diagnóstico por imagemRESUMO
BACKGROUND: A rounded intraplacental hematoma (RIH) is a recently delineated placental lesion. Following the observation of two cases of RIH in placentas associated with stillbirth in 2012, we postulated that RIHs were associated with a higher risk obstetric phenotype when compared to other lesions characteristic of maternal vascular malperfusion (MVM). We aimed to investigate this further by reviewing the associated maternal and fetal characteristics in a series of prospectively identified cases. METHODS: Pregnancies where a RIH was identified on placental examination were prospectively collected from February 2014-July 2016. Comparison was made with pregnancies with placental evidence of MVM but without RIH. RESULTS: 26 placentas with a RIH were identified and 26 placentas with MVM were selected for comparison. There was a statistically significantly increased incidence of stillbirth in the RIH group as compared with the MVM-only group (pâ¯=â¯0.022). Also, pregnancies with RIHs had a lower maternal age (pâ¯=â¯0.041), decreased incidence of antenatally diagnosed growth restriction (pâ¯=â¯0.023), a trend to increased incidence of clinical abruption (pâ¯=â¯0.051) and heavier mean infant birthweight (pâ¯=â¯0.034). Both groups had a high incidence of pre-eclampsia, Caesarean section and preterm delivery when compared with the general population. DISCUSSION: This is the first study to prospectively identify and collect RIHs using standardised pathological criteria and more than doubles the number of reported cases to date. We present 2 comparable, high-risk cohorts but with a significantly increased incidence of stillbirth in those in which RIHs were seen. Further study of these lesions is justified with an emphasis on the potential for antenatal detection using ultrasound evaluation of placental texture.