The current clinical guidelines for the management of aortic abdominal aneurysms (AAAs) overlook the structural and mechanical heterogeneity of the aortic tissue and its role in the regional weakening that drives disease progression. This study is a comprehensive investigation of the structural and biomechanical heterogeneity of AAA tissue along the length and circumference of the aorta, by means of regional ex vivo and in vivo properties. Biaxial testing and histological analysis were performed on ex vivo human aortic specimens systematically collected during open repair surgery. Wall-shear stress and three-dimensional principal strain analysis were performed to allow for in vivo regional characterization of individual aortas. A marked effect of position along the aortic length was observed in both ex vivo and in vivo properties, with the central regions corresponding to the aneurysmal sac being significantly different from the adjacent regions. The heterogeneity along the circumference of the aorta was reflected in the ex vivo biaxial response at low strains and histological properties. Present findings uniquely show the importance of regional characterization for aortic assessment and the need to correlate heterogeneity at the tissue level with non-invasive measurements aimed at improving clinical outcomes.
Several studies have demonstrated a potential interaction between mesenchymal stem cells (MSCs) and saccular aneurysms. In this study, we sought to determine whether allogenic bone marrow-derived MSCs had the ability to prevent aneurysm formation in a known rabbit elastase aneurysm model. MSCs were injected intravenously in experimental rabbits at the time of surgical creation and two weeks postcreation and compared with control rabbits receiving vehicle injection. Angiography was used to compare aneurysm measurements four weeks postcreation, and aneurysms were harvested for histological properties. Serum was collected longitudinally to evaluate cytokine alterations. Serum from control animals was also utilized to perform in vitro tests with MSCs to compare the effect of the serologic environment in animals with and without aneurysms on MSC proliferation and cytokine production. While aneurysm morphometric comparisons revealed no differences, significant cytokine alterations were observed in vitro and in vivo , suggesting both anti-inflammatory and proinflammatory processes were occurring in the presence of MSCs. Histological analyses suggested that tunica intima hyperplasia was inhibited in the presence of MSCs.
This study correlates low strain tangential modulus (LTM) and transition zone onset (TZo) stress, biomechanical parameters that occur within the physiological range of stress seen in vivo, with tissue strength and histopathologic changes in aneurysmal ascending aortic tissue.Ascending aortic aneurysm tissue samples were collected from 41 patients undergoing elective resection. Samples were subjected to planar biaxial testing to quantify LTM and TZo. These were then correlated with strength assessed from uniaxial testing and with histopathologic quantification of pathologic derangements in elastin, collagen, and proteoglycan (PG).Decreased LTM and TZo were correlated with reduced strength (P < .05), PG content (P < .05), and elastin content (P < .05). Reduced TZo also was correlated with increased elastin fragmentation (P < .05).LTM and TZo are correlated with common biomechanical and histopathologic alterations in ascending aortic aneurysm tissue that are thought to relate to the risk of acute aortic syndromes. LTM and TZo are measured under conditions approximating in vivo physiology and have the potential to be obtained noninvasively using medical imaging techniques. Therefore, they represent parameters that warrant future study as potential contributors to our growing knowledge of pathophysiology, disease progression, and risk stratification of aortic disease.
We describe the architectural patterns of advanced ovarian/pelvic high-grade serous carcinomas that have been treated with upfront surgery, followed by adjuvant chemotherapy or neoadjuvant chemotherapy, followed by interval debulking to explore the association with the chemotherapeutic response. For 70 cases of advanced (i.e. stage III/IV) high-grade serous carcinomas (33 platinum resistant/intermediate, 37 platinum sensitive; 24 neoadjuvantly treated, 44 primary surgery), all tumor-containing histologic slides were reviewed by 1 of 3 pathologists. Histologic type was confirmed and the following features were assessed: major architectural pattern and the presence of any of 8 predefined minor architectural patterns (papillary, transitional cell carcinoma-like, micropapillary, microcystic, nested papillary, slit-like, glandular, solid). A semiquantitative assessment of psammoma bodies, histiocytic response, necrosis, nuclear atypia, and single-cell invasion was performed. Mitotic count was performed in 10 HPF and 1 HPF was counted for intraepithelial lymphocytes. The morphologic features were tested for an association with previous neoadjuvant chemotherapy and response to chemotherapy (resistant/intermediate versus chemotherapy-sensitive cases stratified by neoadjuvant chemotherapy), which was carried out using χ tests for categorical variables and analysis of variance for continuous data. Combinations of features were analyzed using unsupervised clustering (Wald). Although 8 of 18 features were significantly different when samples from neoadjuvantly treated patients were compared with those not previously treated, no individual histomorphologic feature or a combination of features was associated with response to chemotherapy. Further subtyping of high-grade serous carcinomas will likely need ancillary molecular markers that may have a greater potential to identify cases that will not respond to platinum-based chemotherapy.
Fibromuscular dysplasia is a rare, non-atherosclerotic non-inflammatory vascular disease that most commonly involves the renal arteries and carotid arteries, but has been described in nearly every vascular bed in the body. Complications of fibromuscular dysplasia include aneurysms and vascular dissection. We present a rare case of fibromuscular dysplasia involving the aorta, complicated by type A aortic dissection.
BackgroundMyocarditis is generally a self-limited illness with a benign course. Certain pathogens—such as cytomegalovirus (CMV)—can cause severe/fulminant forms of myocarditis leading to congestive heart failure or sudden cardiac death (SCD). Case PresentationA 54-year-old female was diagnosed with systemic lupus erythematosus (SLE) in hospital and received inpatient immunosuppression due to significant multi-organ involvement. After a prolonged admission, she later died of an in-hospital cardiac arrest. Autopsy revealed CMV myocarditis involving the anterior wall of the left ventricle and cardiac conduction system. We postulated that both CMV and complications of SLE caused the patient’s SCD. DiscussionMyocarditis can vary in its presentation, severity, and diagnostic workup. Immunocompromised hosts are at risk of opportunistic infections such as CMV and are therefore prone to developing more severe forms of myocarditis. When caring for this patient population, it becomes necessary for clinicians to consider atypical manifestations of opportunistic pathogens in their diagnostic approach. RESUME Contexte La myocardite est généralement une maladie autolimitée dont l’évolution est bénigne. Certains agents pathogènes, tels que le cytomégalovirus (CMV), peuvent provoquer des formes graves/ fulminantes de myocardite entraînant une insuffisance cardiaque congestive ou une mort cardiaque subite (MCS). Présentation de casUne femme de 54 ans a reçu un diagnostic de lupus érythémateux disséminé (LED) à l’hôpital et a été hospitalisée pour une immunosuppression due à une importante atteinte de plusieurs organes. Après une longue hospitalisation, elle est décédée d’un arrêt cardiaque à l’hôpital. L’autopsie a révélé une myocardite à CMV impliquant la paroi antérieure du ventricule gauche et le système de conduction cardiaque. Nous avons émis l’hypothèse que le CMV et les complications du LED étaient tous deux à l’origine de l’arrêt cardiaque de la patiente. DiscussionLa myocardite peut varier dans sa présentation, sa gravité et son diagnostic. Les hôtes immunodéprimés sont exposés au risque d’infections opportunistes telles que le CMV et sont donc susceptibles de développer des formes plus graves de myocardite. Lorsqu’ils s’occupent de cette population de patients, les cliniciens doivent tenir compte des manifestations atypiques des agents pathogènes opportunistes dans leur approche diagnostique.
Abstract Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN active neutrophils, downregulated interferon-stimulated genes and activated IL-1R2 + neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFN active neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see ‘Data availability’ section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
Solid organ transplant (SOT) recipients are vulnerable to severe infection during induction therapy. We report a case of a 67-year-old male who died unexpectedly 10 days after receiving a kidney transplant (KTx) on February 10, 2020. There was no clear cause of death, but COVID-19 was considered, retrospectively, as the death occurred shortly after the first confirmed case of COVID-19 in Canada. We confirmed the presence of SARS-CoV-2 components in the allograft and patient lung tissue using immunohistochemistry (IHC) for SARS-CoV-2 spike (S) protein and RNA scope in situ hybridization for SARS-CoV-2 RNA.
