RESUMEN
VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10-8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.
Asunto(s)
Diabetes Mellitus , Preeclampsia , Femenino , Humanos , Recién Nacido , Embarazo , Número de Embarazos , Oxitocina/metabolismo , Placenta/metabolismo , Preeclampsia/metabolismo , Proteómica , Receptores de Oxitocina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: The objective of this study is to examine risk factors for neonatal abstinence syndrome (NAS) among infants born to mothers with sickle cell hemoglobinopathies (SCH). STUDY DESIGN: Retrospective cohort study of nonanomalous, singleton infants born to mothers with laboratory confirmed SCH. Infants were included if they were diagnosed with NAS prior to hospital discharge. The outcome of interest was the association of maternal variables with NAS. RESULTS: Of 131 infants born to mothers with SCH, 4% (n = 5) were diagnosed with NAS. Mothers of infants with NAS were more likely to have SC disease (80%) compared with other SCH (20%), p = 0.001. Fifteen women had antepartum (AP) admissions for pain and/or sickle crisis. Of these patients, four infants (29%) were diagnosed with NAS. The median (5th and 95th percentile) maternal AP length of stay for women with infants diagnosed with NAS to mothers with sickle cell disease was 132 (5, 180) days (p = 0.02). CONCLUSION: Incidence of NAS among mothers with SCH is low; severe disease characterized by AP sickle cell crisis requiring prolonged AP admission for pain control significantly increases the risk of NAS. Further studies are needed to investigate the association of maternal opioid dose and NAS.
Asunto(s)
Anemia de Células Falciformes , Síndrome de Abstinencia Neonatal/etiología , Complicaciones Hematológicas del Embarazo , Analgésicos Opioides/uso terapéutico , Anemia de Células Falciformes/tratamiento farmacológico , Femenino , Humanos , Recién Nacido , Madres , Síndrome de Abstinencia Neonatal/epidemiología , Embarazo , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Estudios RetrospectivosAsunto(s)
Metaplasia , Humanos , Esófago/patología , Niño , Masculino , Enfermedades del Esófago/patología , FemeninoRESUMEN
Congenital coronary artery anomalies are rare. Pathologists are exposed to those in mainly two settings; in association with sudden death and usually extreme exercise in young adults, and in association with complex congenital heart disease in the pediatric and perinatal population. Pediatric pathologists, other pathologists and pathologists' assistants performing pediatric or forensic autopsies therefore need to be familiar with coronary artery anomalies.
Asunto(s)
Anomalías de los Vasos Coronarios/patología , Anomalías de los Vasos Coronarios/clasificación , HumanosRESUMEN
We report on a case of a prenatally diagnosed non-immune hydrops fetalis and cystic hygroma associated with the balanced translocation t(5;9)(q11.2;p22), an association that to our knowledge has not been reported previously. Both parents had normal karyotypes. The infant was born prematurely at 33 and 3/7 weeks gestation and expired 12 h after delivery.
Asunto(s)
Cromosomas Humanos Par 5/genética , Cromosomas Humanos Par 9/genética , Hidropesía Fetal/genética , Linfangioma Quístico/genética , Complicaciones del Embarazo/genética , Adulto , Femenino , Humanos , Hidropesía Fetal/patología , Recién Nacido , Linfangioma Quístico/patología , Embarazo , Complicaciones del Embarazo/patología , Diagnóstico Prenatal , Translocación GenéticaRESUMEN
SARS-CoV-2 infects cells via binding to ACE2 and TMPRSS2, which allows the virus to fuse with host cells. The viral RNA is detected in the placenta of SARS-CoV-2-infected pregnant women and infection is associated with adverse pregnancy complications. Therefore, we hypothesize that SARS-CoV-2 infection of placental cells induces pro-inflammatory cytokine release to contribute to placental dysfunction and impaired pregnancy outcomes. First, expression of ACE2 and TMPRSS2 was measured by qPCR in human primary cultured term cytotrophoblasts (CTBs), syncytiotrophoblast (STBs), term and first trimester decidual cells (TDCs and FTDCs, respectively), endometrial stromal cells (HESCs) as well as trophoblast cell lines HTR8, JEG3, placental microvascular endothelial cells (PMVECs) and endometrial endothelial cells (HEECs). Later, cultured HTR8, JEG3, PMVECs and HEECs were treated with 10, 100, 1000 ng/ml of recombinant (rh-) SARS-CoV-2 S-protein ± 10 ng/ml rh-IFNγ. Pro-inflammatory cytokines IL-1ß, 6 and 8, chemokines CCL2, CCL5, CXCL9 and CXCL10 as well as tissue factor (F3), the primary initiator of the extrinsic coagulation cascade, were measured by qPCR as well as secreted IL-6 and IL-8 levels were measured by ELISA. Immunohistochemical staining for SARS-CoV-2 spike protein was performed in placental specimens from SARS-CoV-2-positive and normal pregnancies. ACE2 levels were significantly higher in CTBs and STBs vs. TDCs, FTDCs and HESCs, while TMPRSS2 levels were not detected in TDCs, FTDCs and HESCs. HTR8 and JEG3 express ACE2 and TMPRSS2, while PMVECs and HEECs express only ACE2, but not TMPRSS2. rh-S-protein increased proinflammatory cytokines and chemokines levels in both trophoblast and endothelial cells, whereas rh-S-protein only elevated F3 levels in endothelial cells. rh-IFNγ ± rh-S-protein augments expression of cytokines and chemokines in trophoblast and endothelial cells. Elevated F3 expression by rh-IFNγ ± S-protein was observed only in PMVECs. In placental specimens from SARS-CoV-2-infected mothers, endothelial cells displayed higher immunoreactivity against spike protein. These findings indicated that SARS-CoV-2 infection in placental cells: 1) induces pro-inflammatory cytokine and chemokine release, which may contribute to the cytokine storm observed in severely infected pregnant women and related placental dysfunction; and 2) elevates F3 expression that may trigger systemic or placental thrombosis.
Asunto(s)
COVID-19 , Enfermedades Placentarias , Complicaciones Infecciosas del Embarazo , Enzima Convertidora de Angiotensina 2 , Línea Celular Tumoral , Citocinas/metabolismo , Células Endoteliales/patología , Femenino , Humanos , Placenta/metabolismo , Enfermedades Placentarias/patología , Embarazo , Mujeres Embarazadas , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/metabolismo , Tromboplastina/metabolismoRESUMEN
A case of a premature infant with lactic acidosis and hepatic iron accumulation, born to a mother with multiple fetal demises, is presented and discussed by both clinician and pathologist, in this traditional clinico-pathologic conference. The discussion includes the differential diagnoses of lactic acidosis and hepatic iron accumulation in infants.
Asunto(s)
Acidosis Láctica/fisiopatología , Muerte Fetal , Feto/fisiopatología , Hierro/metabolismo , Hígado/patología , Acidosis Láctica/patología , Adulto , Resultado Fatal , Femenino , Feto/patología , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Embarazo , SíndromeRESUMEN
CONTEXT.: This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. OBJECTIVE.: To accurately reflect the preexisting diseases and pathologic conditions of decedents with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection through autopsy. DESIGN.: Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple-choice and open-ended survey responses. RESULTS.: Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than 1 preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. CONCLUSIONS.: Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of comorbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.
Asunto(s)
COVID-19/patología , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Brasil/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , Causas de Muerte , Enfermedad Crónica , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
We report a case of spondyloepiphyseal dysplasia congenita (SED congenita), diagnosed at autopsy of a term infant. Prenatal ultrasound at 20 weeks of gestation had shown shortening of all the fetal long bones, with bowing of the femora and humeri, clubfeet, and small thoracic cage. We discuss the diagnostic features of SED and the main differential diagnoses.
Asunto(s)
Osteocondrodisplasias/congénito , Osteocondrodisplasias/patología , Adulto , Diagnóstico Diferencial , Femenino , Humanos , EmbarazoRESUMEN
Common arterial trunk is a rare anomaly on its own, but with an intact ventricular septum it is extremely rare. An unexpected finding at autopsy prompted a review of the literature and a review of the developmental considerations associated with the outflow tracts. The case presented was an intrauterine fetal death at 37 weeks gestation. At autopsy, the only anatomic abnormalities were pulmonary dominant common arterial trunk with an intact ventricular septum, ventriculo-arterial septal defect, coarctation and widely patent arterial duct. A review of the literature and the developmental concepts related to the outflow tracts of the developing heart demonstrate the rare nature of this particular variation of common arterial trunk.
RESUMEN
The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex was first described by Carey et al. in 1978. It constitutes a specific combination of malformations. There are very few case reports of discordant OEIS in monozygotic twins and very few reports of OEIS in association with both hypoplastic left heart and ventricular septal defect. Our case represents the fifth reported case of cardiac malformations in a fetus with OEIS complex.
Asunto(s)
Anomalías Múltiples/diagnóstico por imagen , Síndrome del Corazón Izquierdo Hipoplásico/diagnóstico por imagen , Gemelos Monocigóticos , Ano Imperforado/diagnóstico , Cloaca/anomalías , Resultado Fatal , Femenino , Hernia Umbilical/diagnóstico , Humanos , Masculino , Embarazo , Segundo Trimestre del Embarazo , Diagnóstico Prenatal , Radiografía , Escoliosis/diagnóstico , Escoliosis/diagnóstico por imagen , Ultrasonografía PrenatalRESUMEN
Perineal hernias are very rare and mostly reported in adults, with only 7 cases reported in children. We report a female fetus, terminated at 18 weeks of gestation due to trisomy 18. In addition to multiple typical findings of trisomy 18, this fetus had perineal hernia with defect of the perineal skin and prolapse of multiple bowel loops. To our knowledge there are no reported cases of perineal hernia presenting antenatally nor are there reported cases of perineal hernia associated with trisomy 18.
Asunto(s)
Cromosomas Humanos Par 18 , Feto/anomalías , Hernia/congénito , Perineo/anomalías , Trisomía , Anomalías Múltiples , Adulto , Resultado Fatal , Femenino , Humanos , Embarazo , Ultrasonografía PrenatalRESUMEN
Teratoma is the leading neoplasm diagnosed in neonates and infants. Although over 99% of teratomas found in the fetus and newborn are histologically benign, those tumors may cause death if vital structures are involved or if the airway is compromised. We review the literature on antenatal intrapericardial teratomas and report a case of intrapericardial teratoma, with massive pericardial effusion and fetal hydrops, diagnosed on antenatal ultrasound at 21 weeks of gestation. Pericardioamniotic shunt was placed at 22 weeks and 6 days gestational age. In spite of successful drainage of the pericardial effusion, fetal demise was documented 8 days later, likely due to tumor compression of the heart.
Asunto(s)
Corazón Fetal , Derrame Pericárdico/cirugía , Diagnóstico Prenatal , Teratoma , Ultrasonografía Prenatal , Femenino , Muerte Fetal , Corazón Fetal/diagnóstico por imagen , Corazón Fetal/cirugía , Feto/cirugía , Edad Gestacional , Humanos , Hidropesía Fetal/diagnóstico , Hidropesía Fetal/diagnóstico por imagen , Hidropesía Fetal/cirugía , Embarazo , Teratoma/diagnóstico , Teratoma/diagnóstico por imagen , Teratoma/cirugíaRESUMEN
The pathophysiology of juvenile nasopharyngeal angiofibroma (JNA) has yet to be fully elucidated, but the influence of steroid hormones in their growth has been suggested. This neoplasm is known to afflict adolescent males. However, only a minority of the neoplastic cells express androgen receptors. The expression of estrogen receptor beta by the tumor cells recently has been demonstrated. Aromatase (P450) is an enzyme which is responsible for converting androgens to estrogens. However, the rule of aromatase in the pathogenesis of JNA is unknown. In this study we attempt to explain the hormone-induced growth theory by characterizing the aromatase (P450) in JNA. We examined five sinonasal JNA from adolescent males, all of which stained positive for aromatase. We propose that this enzyme is responsible for the local conversion of androgens into estrogens, which subsequently bind to the estrogen receptors leading to the growth of these tumors.
Asunto(s)
Angiofibroma/patología , Aromatasa/metabolismo , Neoplasias Nasofaríngeas/patología , Adolescente , Andrógenos/genética , Niño , Técnica del Anticuerpo Fluorescente Directa , Humanos , Inmunohistoquímica , Masculino , Receptores Androgénicos/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
A case of pleuropulmonary blastoma in a 13-year-old child, exposed to the Chernobyl disaster while in-utero, is presented and discussed by both clinician and pathologist, in this traditional clinical-pathologic conference. The discussion includes the differential diagnoses of chest mass in children.
Asunto(s)
Neoplasias Pulmonares/diagnóstico , Blastoma Pulmonar/diagnóstico , Neoplasias Torácicas/diagnóstico , Adolescente , Quimioterapia Adyuvante , Terapia Combinada , Diagnóstico Diferencial , Resultado Fatal , Humanos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/terapia , Masculino , Neumonectomía , Blastoma Pulmonar/cirugía , Blastoma Pulmonar/terapia , Radioterapia Adyuvante , Neoplasias Torácicas/cirugía , Neoplasias Torácicas/terapia , Tomografía Computarizada por Rayos XRESUMEN
The Aicardi syndrome is characterized by infantile spasms, corpus callosum agenesis, and chorioretinal lacunae and almost exclusively affects females (very rarely, 47, XXY males). The crucial genetic mishap likely occurs in the postzygotic stage, but the variable clinical phenotype among the approximately 450 known cases has not been explained. No consistent mutations or deletions exist among patients. We encountered a baby girl with early onset infantile spasms. She had left-sided cleft lip/palate, costovertebral defects, scoliosis, callosal agenesis, and microphthalmia. She expired at the age of 3 months of respiratory infection. On autopsy she had thoracic hemivertebrae with rib defects, bilateral microphthalmia, microcornea, posterior colobomata, abnormalities of the retinal pigment epithelium, absence of normal ganglion cells in the retina, gross asymmetry of the brain with cerebral polymicrogyria, total callosal agenesis, cerebral subcortical and subependymal nodular heterotopias, cerebellar nodular heterotopias, and tegmental/basal unilateral brainstem hypoplasia. Cerebellar and retinal migration defects have not been described before in Aicardi syndrome and may have had a bearing on this patient's eventual outcome.
Asunto(s)
Encefalopatías/congénito , Encefalopatías/patología , Cerebelo/anomalías , Malformaciones del Desarrollo Cortical/patología , Neuronas/patología , Anomalías Múltiples/patología , Encefalopatías/complicaciones , Movimiento Celular , Femenino , Humanos , Recién Nacido , Espasmos Infantiles/congénito , SíndromeRESUMEN
Heteromorphisms of chromosome 9 are among the most common variations in the human karyotype. The pericentromeric polymorphisms of chromosome 9 include variations in the size of q-arm heterochromatin, pericentric inversions, and rarely, additional C-band-negative, G-band-positive material. The finding of a polymorphic variant, either in prenatal screening or in chromosomal analysis for phenotypic abnormalities, may cause parental anxiety and initiate genetic counselling. We report a case of a 39-year-old primigravida with unremarkable pregnancy, who had amniocentesis due to advanced maternal age. Chromosomal analysis demonstrated a long arm (q) variant of chromosome 9 with an enlarged heteromorphic area, approximately three times longer than known reported variants. Prenatal analysis demonstated an identical variant in the probands phenotypically normal father, uncle, and paternal grandmother, confirming an apparently "normal" variant.
Asunto(s)
Cromosomas Humanos Par 9/genética , Variación Genética , Heterocromatina/genética , Amniocentesis , Niño , Bandeo Cromosómico , Familia , Femenino , Estudios de Seguimiento , Crecimiento y Desarrollo/fisiología , Humanos , Cariotipificación , Masculino , Linaje , Polimorfismo Genético , Embarazo , Resultado del Embarazo , Diagnóstico Prenatal , Factores de Tiempo , Ultrasonografía PrenatalRESUMEN
Twin reversed arterial perfusion sequence (TRAP) resulting in an acardiac twin is a rare occurrence. Acardia requires the presence of arterial-arterial anastomosis, with retrograde perfusion of poorly oxygenated blood from the normal twin to the acardiac twin, venous-venous anastomosis carrying blood back from the acardiac to the normal twin, and circulatory failure of the acardiac twin. Although vascular anastomoses in cases of TRAP have been well described, there is little published literature on the microscopic changes in the placenta in TRAP sequence. We report a case of monochorionic monozygotic twins with an acardiac twin, large arterial-arterial anastomosis, and direct continuity of the umbilical cord veins. The placenta showed villous immaturity, striking villous calcifications, and extensive fetal thrombotic vasculopathy of the umbilical vein of the donor twin and the chorionic plate vessels. Thrombi in the umbilical vessels of the acardiac twin have been reported, and trombi in donor twin organs have been seen after fetal demise in utero. But to our knowledge there is no previously reported thrombi in the donor twin umbilical vessels or the chorionic plate veins. This may have implications not only as a possible factor in the etiology of TRAP, but also and more important as a possible risk factor for thrombotic events in the donor twin. Further studies with clinico-pathological correlation are needed to explore this issue.
Asunto(s)
Enfermedades en Gemelos , Corazón Fetal/anomalías , Cardiopatías Congénitas/patología , Placenta/patología , Gemelos Monocigóticos , Trombosis de la Vena/patología , Adulto , Vellosidades Coriónicas/patología , Femenino , Muerte Fetal , Cardiopatías Congénitas/embriología , Humanos , Circulación Placentaria , Embarazo , Ultrasonografía Prenatal , Venas Umbilicales/patología , Trombosis de la Vena/genéticaRESUMEN
Intestinal malrotation has an incidence of 1 per 6000 live births. The most serious consequence of malrotation is volvulus. Midgut volvulus is a rare condition in which the small bowel and proximal colon twist around the superior mesenteric artery, leading to a high-grade proximal bowel obstruction and vascular compromise of the intestine, thereby leading to infarction of the involved intestine. Midgut volvulus rarely occurs antenatally and is usually not lethal in utero. There are only 7 cases of intrauterine fetal demise caused by midgut volvulus reported in the literature. We report a case of intrauterine fetal demise at 38 weeks of gestation, due to cardiovascular failure and shock from midgut volvulus. Non-specific abnormalities, including ascites and dilated bowel, had been seen on the antenatal ultrasound from the 15th week of gestation. In addition to the volvulus, the fetus had intestinal atresia and arthrogryposis.
Asunto(s)
Obstrucción Intestinal/diagnóstico por imagen , Vólvulo Intestinal/diagnóstico por imagen , Anomalía Torsional/diagnóstico por imagen , Ultrasonografía Prenatal/métodos , Útero/diagnóstico por imagen , Adolescente , Resultado Fatal , Femenino , Feto , Edad Gestacional , Humanos , Obstrucción Intestinal/etiología , Vólvulo Intestinal/complicaciones , Masculino , Embarazo , Anomalía Torsional/complicacionesRESUMEN
Bartter syndrome, a group of disorders that encompasses multiple genetic defects with similar clinical presentation, has been divided into six different genotypes, according to different genetic defects, and into three main clinical variants (or phenotypes). Classic laboratory findings in all variants include hypochloremia, hypokalemia, and metabolic alkalosis with excessive excretion of chloride and potassium. Classic Bartter syndrome, neonatal Bartter syndrome, and Gitelman syndrome are the three main clinical variants. Classic Bartter syndrome and neonatal Bartter syndrome have defects in genes that affect transport channels in the ascending loop of Henle, where as in Gitleman syndrome the defect occurs in the transport channels of the distal convoluted tubule. Classic Bartter syndrome and neonatal Bartter syndrome have similar presenting symptoms, potential outcomes, and treatment, but different ages at presentation. Gitelman syndrome, a more benign condition than the other clinical variants, has the classic hallmark finding of hypomagnesemia and low to normal excretion of calcium. This differentiates it from the classic and neonatal variants of the disease. With early diagnosis and proper treatment, Bartter syndrome has a good prognosis. But failure to identify it can lead to tubulointerstitial nephritis and renal failure. We present a case of a 6-month-old boy with Bartter syndrome who presented with poor weight gain and an abdominal mass.