Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report.

BACKGROUND: Intrauterine fetal demise is a recognized complication of coronavirus disease 2019 in pregnant women and is associated with histopathological placental lesions. The pathological mechanism and virus-induced immune response in the placenta are not fully understood. A detailed description of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced inflammation in the placenta during fetal demise is crucial for improved clinical management. CASE PRESENTATION: We report the case of a 27-week gestation SARS-CoV-2-asymptomatic unvaccinated pregnant woman without comorbidities or other risk factors for negative pregnancy outcomes with a diagnosis of intrauterine fetal demise. Histopathological findings corresponded to patterns of subacute inflammation throughout the anatomic compartments of the placenta, showing severe chorioamnionitis, chronic villitis and deciduitis, accompanied by maternal and fetal vascular malperfusion. Our immunohistochemistry results revealed infiltration of CD68+ macrophages, CD56+ Natural Killer cells and scarce CD8+ T cytotoxic lymphocytes at the site of placental inflammation, with the SARS-CoV-2 nucleocapsid located in stromal cells of the chorion and chorionic villi, and in decidual cells. CONCLUSION: This case describes novel histopathological lesions of inflammation with infiltration of plasma cells, neutrophils, macrophages, and natural killer cells associated with malperfusion in the placenta of a SARS-CoV-2-infected asymptomatic woman with intrauterine fetal demise. A better understanding of the inflammatory effects exerted by SARS-CoV-2 in the placenta will enable strategies for better clinical management of pregnant women unvaccinated for SARS-CoV-2 to avoid fatal fetal outcomes during future transmission waves.

Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence.

BACKGROUND: The great obstetrical syndromes of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether 1 or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. OBJECTIVE: This study aimed to determine how the quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent or reversed umbilical artery Doppler indices and hypertensive disorders of pregnancy or the 2 conditions combined among subjects with disease severity that warrant early preterm delivery. We hypothesized that the trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulated that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction with no additional effect when hypertension is concomitantly present. STUDY DESIGN: In this retrospective cohort study, paraffin-embedded placental tissue was obtained from 4 groups, namely (1) patients with severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, (2) patients with severe fetal growth restriction with absent or reversed umbilical artery Doppler indices and no hypertension, (3) gestational age-matched, appropriately grown pregnancies with hypertensive disease, and (4) gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed, followed by artificial intelligence-driven morphometric analyses. The number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled using linear regression. RESULTS: Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi; 95% confidence interval, -467 to -98; P<.01), a smaller stem villous area (-4.3 mm2; 95% confidence interval, -7.3 to -1.2; P<.01), and fewer stem villous vessels (-4967 stem villous vessels; 95% confidence interval, -8501 to -1433; P<.01) with no difference in the total vascular area. In contrast, placental abnormalities in cases with severe growth restriction were limited to terminal villi with global decreases in the number of villi (-873 terminal villi; 95% confidence interval, -1501 to -246; P<.01), the villous area (-1.5 mm2; 95% confidence interval, -2.7 to -0.4; P<.01), the number of blood vessels (-5165 terminal villous vessels; 95% confidence interval, -8201 to -2128; P<.01), and the vascular area (-0.6 mm2; 95% confidence interval, -1.1 to -0.1; P=.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. CONCLUSION: Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent or reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions in the combination of growth restriction and hypertension, suggesting that distinct pathophysiological pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to lead to more severe pathologic consequences. Delineating mechanisms that underly the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Lower-extremity malperfusion syndrome in patients undergoing proximal aortic surgery for acute type A aortic dissection.

Objective: Data regarding management of lower-extremity malperfusion in the setting of type A aortic dissection are limited. This study aimed to compare acute type A aortic dissection with lower-extremity malperfusion outcomes in patients undergoing lower-extremity revascularization with no revascularization. Methods: Consecutive patients undergoing acute type A aortic dissection surgery were identified from a prospectively maintained database. Perioperative variables were compared between patients with and without lower-extremity malperfusion. Factors associated with lower-extremity malperfusion, revascularization, and mortality were determined using univariable Cox regression and Firth's penalized likelihood modeling. Results: From January 2007 to December 2021, 601 patients underwent proximal aortic repair for acute type A aortic dissection at a quaternary care center. Of these, 85 of 601 patients (14%) presented with lower-extremity malperfusion and were more often male (P = .02), had concomitant moderate or greater aortic insufficiency (P = .05), had lower ejection fraction (P = .004), had preoperative dialysis dependence (P = .01), and had additional cerebral, visceral, and renal malperfusion syndromes (P < .001). Kaplan-Meier estimated survival fared worse with lower-extremity malperfusion compared with no lower-extremity malperfusion at 1, 5, and 10 years (84% vs 77%, 74% vs 71%, 65% vs 52%, respectively, P = .03). In the lower-extremity malperfusion group, 15 of 85 patients (18%) underwent lower-extremity revascularization without significant differences in postoperative morbidity and mortality compared with patients not undergoing revascularization. Need for peripheral revascularization was associated with peripheral vascular disease (hazard ratio, 3.7 [1.0-14.0], P = .05) and pulse deficit (hazard ratio, 5.6 [1.3-24.0], P = .02) at presentation. Conclusions: Patients presenting with type A aortic dissection and lower-extremity malperfusion have worse overall survival compared with those without lower-extremity malperfusion. However, not all patients with type A aortic dissection and lower-extremity malperfusion require revascularization.

Morphological placental findings in women infected with SARS-CoV-2 according to trimester of pregnancy and severity of disease.

INTRODUCTION: Placental morphology findings in SARS-CoV-2 infection are considered nonspecific, although the role of trimester and severity of infection are underreported. Therefore, we aimed to investigate abnormal placental morphology, according to these two criteria. METHODS: This is an ancillary analysis of a prospective cohort study of pregnant women with suspected SARS-CoV-2 infection, managed in one maternity, from March 2020 to October 2021. Charting of clinical/obstetric history, trimester and severity of COVID-19 infection, and maternal/perinatal outcomes were done. Placental morphological findings were classified into maternal and fetal circulatory injury and acute/chronic inflammation. We further compared findings with women with suspected disease which tested negative for COVID-19. Diseases' trimester of infection and clinical severity guided the analysis of confirmed COVID-19 cases. RESULTS: Ninety-one placental discs from 85 women were eligible as a COVID-19 group, and 42 discs from 41 women in negative COVID-19 group. SARS-CoV-2 infection occurred in 68.2% during third trimester, and 6.6% during first; 16.5% were asymptomatic, 61.5% non-severe and 22.0% severe symptomatic (two maternal deaths). Preterm birth occurred in 33.0% (one fetal death). Global maternal vascular malperfusion (MVM) were significant in COVID-19 group whether compared with negative COVID-19 tests group; however, fetal vascular malperfusion lesions and low-grade chronic villitis were not. Three placentas had COVID-19 placentitis. Decidual arteriopathy was associated with infection in first/mid trimester, and chorangiosis in asymptomatic infections. DISCUSSION: Placental abnormalities after an infection by COVID-19 were more frequent after first/mid-trimester infections. Extensive placental lesions are rare, although they may be more common upon underlying medical conditions.

Postoperative acute kidney injury after thoracic endovascular aortic repair for acute type B aortic dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has evolved as the standard for treating complicated acute type B aortic dissection (ATBAD). Acute kidney injury (AKI) is a common complication in critically ill patients and is commonly observed in patients with ATBAD. The purpose of the study was to characterize AKI after TEVAR. METHODS: All patients who underwent TEVAR for ATBAD from 2011 through 2021 were identified using the International Registry of Acute Aortic Dissection. The primary end point was AKI. A generalized linear model analysis was performed to identify a factor associated with postoperative AKI. RESULTS: A total of 630 patients presented with ATBAD and underwent TEVAR. The indication for TEVAR was complicated ATBAD in 64.3%, high-risk uncomplicated ATBAD in 27.6%, and uncomplicated ATBAD in 8.1%. Of 630 patients, 102 (16.2%) developed postoperative AKI (AKI group) and 528 patients (83.8%) did not (non-AKI group). The most common indication for TEVAR was malperfusion (37.5%). In-hospital mortality was significantly higher in the AKI group (18.6% vs 4%; P < .001). Postoperatively, cerebrovascular accident, spinal cord ischemia, limb ischemia, and prolonged ventilation were more commonly observed in the AKI group. The expected mortality was similar at 2 years between the two groups (P = .51). Overall, the preoperative AKI was observed in 95 (15.7%) in the entire cohort consisting of 60 (64.5%) in the AKI group and 35 (6.8%) in the non-AKI group. A history of CKD (odds ratio, 4.6; 95% confidence interval, 1.5-14.1; P = .01) and preoperative AKI (odds ratio, 24.1; 95% confidence interval, 10.6-55.0; P < .001) were independently associated with postoperative AKI. CONCLUSIONS: The incidence of postoperative AKI was 16.2% in patients undergoing TEVAR for ATBAD. Patients with postoperative AKI had a higher rate of in-hospital morbidities and mortality than those without. A history of CKD and preoperative AKI were independently associated with postoperative AKI.

Case report: Multi-site perfusion strategy for type A acute aortic dissection complicated with cerebral malperfusion.

Acute type A dissection presenting with cerebral malperfusion has high morbidity and mortality. Given the complexity of underlying vascular involvement, it is a challenging clinical scenario. Many of these patients are not deemed surgical candidates. If surgery is considered, it often requires complex aortic arch and neck vessel reconstruction. We present a 48-year-old male with an acute type A aortic dissection that presented with paraplegia and decreased level of consciousness. A Computed Tomography showed occlusion of both common carotid arteries. He was successfully treated with a multi-site perfusion strategy and a Hybrid Frozen Elephant Trunk graft to achieve fast restoration of the cerebral circulation and minimize brain ischemia and permanent neurological damage. From this case, we learn that aggressive arch and neck vessel reconstruction supported by multi-site perfusion could help improve mortality and neurological outcomes in selected patients.

Outcomes of emergency surgery for acute type A aortic dissection complicated by malperfusion syndrome.

OBJECTIVE: The study objective was to determine the impact of malperfusion syndrome on in-hospital mortality and midterm survival after emergency aortic arch reconstruction for acute type A aortic dissection. METHODS: This was an observational study of aortic surgeries from 2010 to 2018. All patients with acute type A aortic dissection undergoing open aortic arch reconstruction were included. Patients were dichotomized by the presence or absence of malperfusion syndrome and were analyzed for differences in short-term postoperative outcomes, including morbidity and in-hospital mortality. Kaplan-Meier survival estimation and multivariable Cox analysis were performed to identify variables associated with survival. RESULTS: A total of 467 patients undergoing aortic arch reconstruction for acute type A aortic dissection were identified, of whom 332 (71.1%) presented without malperfusion syndrome and 135 (28.9%) presented with malperfusion syndrome. Patients with malperfusion syndrome had higher in-hospital mortality (21.5% vs 5.7%) than patients without malperfusion syndrome. After multivariable adjustment, malperfusion syndrome was associated with worse survival (hazard ratio, 2.43, 95% confidence interval, 1.61-3.66, P < .001) compared with patients without malperfusion syndrome. The predicted risk of mortality increased as the number of malperfused vascular beds increased. Patients with coronary malperfusion syndrome and neuro-malperfusion syndrome had reduced survival compared with the rest of the cohort (P < .05). CONCLUSIONS: Malperfusion syndrome is associated with higher in-hospital mortality and reduced survival for patients with acute type A aortic dissection, with the risk of mortality increasing as the number of malperfused vascular beds increases. Coronary malperfusion syndrome and neuro-malperfusion syndrome may represent a high-risk subgroup of patients presenting with acute type A aortic dissection complicated by malperfusion syndrome. Finally, malperfusion syndrome may benefit from immediate surgical intervention to restore true lumen perfusion, as opposed to operative delay.

Case Report: Placental Maternal Vascular Malperfusion Affecting Late Fetal Development and Multiorgan Infection Caused by SARS-CoV-2 in Patient With PAI-1 4G/5G Polymorphism.

Background: Pregnant women are susceptible to the novel coronavirus (SARS-CoV-2), and the consequences for the fetus are still uncertain. Here, we present a case of a pregnant woman with subclinical hypothyroidism and a plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism who was infected with SARS-CoV-2 at the end of the third trimester of pregnancy, with unexpected evolution of death of the newborn 4 days postpartum. Methods: Nested PCR was performed to detect the virus, followed by ssDNA sequencing. Results: Transplacental transmission of SARS-CoV-2 can cause placental inflammation, ischemia, and neonatal viremia, with complications such as preterm labor and damage to the placental barrier in patients with PAI-1 4G/5G polymorphism. Conclusion: We showed a newborn with several damages potentially caused due to the PAI-1 polymorphisms carried by the mother infected with SARS-CoV-2 during pregnancy.

Arc of Buhler: A lifesaving anatomic variation. A case report.

The presence of malperfusion syndrome in cases of complicated acute type B aortic dissection is a negative predictive factor and urgent intervention is indicated. Anatomic variations, such as the Arc of Buhler, contribute anastomotic channels and can preserve the visceral blood supply. In this case report, we describe the overall management of a 54-year-old man who presented with a type B aortic dissection. Initially, conservative management was chosen, as indicated for an uncomplicated type B dissection, but the dissection deteriorated. Despite the fact that severe occlusion of the celiac artery was detected on Computed Tomography (CT) angiography, the Arc of Buhler anatomical variation was present, contributing adequate visceral blood supply. After considering this finding, the patient was treated effectively with thoracic endovascular aortic repair (TEVAR).

A presença da síndrome de má perfusão em casos de dissecção aórtica aguda do tipo B complicada é um fator preditor negativo, e uma intervenção urgente é indicada. As variações anatômicas, tais como o arco de Buhler, contribuem como canais anastomóticos e podem preservar o suprimento sanguíneo visceral. Neste relato de caso, descrevemos o manejo geral de um paciente do sexo masculino, de 54 anos, que apresentou uma dissecção aórtica do tipo B. Inicialmente, o manejo conservador foi escolhido, conforme indicado para dissecção do tipo B não complicada, mas a dissecção sofreu deterioração. Apesar de uma oclusão grave da artéria celíaca ter sido detectada na angiotomografia computadorizada, a variação anatômica do arco de Buhler estava presente, contribuindo para o suprimento sanguíneo visceral adequado. Após levar em consideração esse achado, o paciente foi tratado de forma efetiva com reparação endovascular da aorta torácica.

Arc of Buhler: A lifesaving anatomic variation. A case report / Arco de Buhler: uma variação anatômica que salva vidas - relato de caso

Abstract The presence of malperfusion syndrome in cases of complicated acute type B aortic dissection is a negative predictive factor and urgent intervention is indicated. Anatomic variations, such as the Arc of Buhler, contribute anastomotic channels and can preserve the visceral blood supply. In this case report, we describe the overall management of a 54-year-old man who presented with a type B aortic dissection. Initially, conservative management was chosen, as indicated for an uncomplicated type B dissection, but the dissection deteriorated. Despite the fact that severe occlusion of the celiac artery was detected on Computed Tomography (CT) angiography, the Arc of Buhler anatomical variation was present, contributing adequate visceral blood supply. After considering this finding, the patient was treated effectively with thoracic endovascular aortic repair (TEVAR).

Resumo A presença da síndrome de má perfusão em casos de dissecção aórtica aguda do tipo B complicada é um fator preditor negativo, e uma intervenção urgente é indicada. As variações anatômicas, tais como o arco de Buhler, contribuem como canais anastomóticos e podem preservar o suprimento sanguíneo visceral. Neste relato de caso, descrevemos o manejo geral de um paciente do sexo masculino, de 54 anos, que apresentou uma dissecção aórtica do tipo B. Inicialmente, o manejo conservador foi escolhido, conforme indicado para dissecção do tipo B não complicada, mas a dissecção sofreu deterioração. Apesar de uma oclusão grave da artéria celíaca ter sido detectada na angiotomografia computadorizada, a variação anatômica do arco de Buhler estava presente, contribuindo para o suprimento sanguíneo visceral adequado. Após levar em consideração esse achado, o paciente foi tratado de forma efetiva com reparação endovascular da aorta torácica.

Distal Extent of Surgery for Acute Type A Aortic Dissection.

Acute type A aortic dissection (TAAD) is a complex disease associated with extremely high morbidity and mortality for which we advocate a coordinated, protocol-driven system of care delivery that begins at patient diagnosis and continues throughout and beyond aortic reconstruction. Essential components of TAAD repair include prompt restoration of true lumen blood flow with obliteration of the false lumen flow, resection of the primary tear sites, restoration of valvular competency, and elimination of any organ malperfusion. This article focuses specifically on extent of repair of the aortic arch and explains our protocols regarding cannulation location and technique, cerebral and distal organ protection strategy, management of the brachiocephalic vessels, and extent of distal aortic reconstruction. We describe an operative strategy for TAAD repair that includes (1) continuous neurocerebral monitoring in all cases, (2) uninterrupted antegrade and/or retrograde cerebral perfusion (depending upon extent of arch repair) during open arch reconstruction, (3) aortic arch replacement technique with or without brachiocephalic vessel replacement using a custom trifurcate graft, and (4) descending aortic stabilization with or without the use of an elephant or frozen elephant trunk (distal stent graft). Our protocol for extent of aortic arch and brachiocephalic reconstruction has been standardized and is predicated on distinct pathoanatomic findings and/or cerebral malperfusion that are outlined.

The Placenta in Neonatal Encephalopathy: A Case-Control Study.

OBJECTIVE: We assessed whether specific histologic placental lesions were associated with risk for neonatal encephalopathy, a strong predictor of death or cerebral palsy. STUDY DESIGN: Case-control study of singletons with gestational ages ≥35 weeks. Data were abstracted from a prospectively collected database of consecutive births at a hospital in which placental samples from specified sites are collected and stored for all inborn infants. Placentas of infants with neonatal encephalopathy were compared with randomly selected control infants (ratio of 1:3). Placental histologic slides were read by a single experienced perinatal pathologist unaware of case status, using internationally recommended definitions and terminology. Findings were grouped into inflammatory, maternal, or fetal vascular malperfusion (FVM) and other lesions. RESULTS: Placental samples were available for 73 of 87 (84%) cases and 253 of 261 (97%) controls. Delivery complications and gross placental abnormalities were more common in cases, of whom 4 died. Inflammation and maternal vascular malperfusion did not differ, and findings consistent with global FVM were more frequent in case (20%) than control (7%) placentas (P = .001). There was a trend toward more segmental FVM and high-grade FVM (fetal thrombotic vasculopathy) among cases. Some type of FVM was observed in 24% of placentas with neonatal encephalopathy. In infants with both neonatal encephalopathy and placental FVM, more often than in infants with neonatal encephalopathy without FVM, electronic fetal monitoring tracings were considered possibly or definitely abnormal (P = .028). CONCLUSIONS: Vascular malperfusion of subacute or chronic origin on the fetal side of the placenta was associated with increased risk of neonatal encephalopathy.

Tratamiento en la disección aórtica torácica con prótesis endovascular / Treatment of the thoracic aortic dissection with stents

El tratamiento de endoprótesis endovascular para la disección aórtica aparece con buenos resultados a mediano tiempo. Las posteriores indicaciones, por ejemplo, tanto la disección del arco aórtico como las disecciones aórticas agudas no complicadas se encuentran bajo estudio.

O tratamento de endoprótese endovascular para a dissecção aórtica aparece com bons resultados a médio prazo. As posteriores indicações, por exemplo, tanto a dissecção do arco aórtico quanto as dissecções aórticas agudas não complicadas se encontram sob estudo.

Endovascular stent-graft therapy for aortic dissection is emerging with good midterm results. Further indications, i.e. aortic arch dissection and uncomplicated acute aortic dissections, are under evaluation.