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Placental SARS-CoV-2 viral replication is associated with placental coagulopathy and neonatal complications [Letter]

Tiozzo, Caterina; Manzano, Claudia; Lin, Xinhua; Bowler, Selina; Gurzenda, Ellen; Botros, Bishoy; Thomas, Kristen; Chavez, Martin; Hanna, Iman; Hanna, Nazeeh
PMID: 37952868
ISSN: 1097-6868
CID: 5610842

Histopathology of the Mitral Valve Residual Leaflet in Obstructive Hypertrophic Cardiomyopathy

Troy, Aaron L; Narula, Navneet; Massera, Daniele; Adlestein, Elizabeth; Alvarez, Isabel Castro; Janssen, Paul M L; Moreira, Andre L; Olivotto, Iacopo; Stepanovic, Alexandra; Thomas, Kristen; Zeck, Briana; Chiriboga, Luis; Swistel, Daniel G; Sherrid, Mark V
BACKGROUND:Mitral valve (MV) elongation is a primary hypertrophic cardiomyopathy (HCM) phenotype and contributes to obstruction. The residual MV leaflet that protrudes past the coaptation point is especially susceptible to flow-drag and systolic anterior motion. Histopathological features of MVs in obstructive hypertrophic cardiomyopathy (OHCM), and of residual leaflets specifically, are unknown. OBJECTIVES/OBJECTIVE:The purpose of this study was to characterize gross, structural, and cellular histopathologic features of MV residual leaflets in OHCM. On a cellular-level, we assessed for developmental dysregulation of epicardium-derived cell (EPDC) differentiation, adaptive endocardial-to-mesenchymal transition and valvular interstitial cell proliferation, and genetically-driven persistence of cardiomyocytes in the valve. METHODS:Structural and immunohistochemical staining were performed on 22 residual leaflets excised as ancillary procedures during myectomy, and compared with 11 control leaflets from deceased patients with normal hearts. Structural components were assessed with hematoxylin and eosin, trichrome, and elastic stains. We stained for EPDCs, EPDC paracrine signaling, valvular interstitial cells, endocardial-to-mesenchymal transition, and cardiomyocytes. RESULTS:= 0.08). No markers of primary cellular processes were identified. CONCLUSIONS:MV residual leaflets in HCM were characterized by histologic findings that were likely secondary to chronic hemodynamic stress and may further increase susceptibility to systolic anterior motion.
PMID: 37383048
ISSN: 2772-963x
CID: 5540432

Extensive fibrosis in mediastinal seminoma is a diagnostic pitfall in small biopsies: two case reports

Liccardi, Anthony R.; Thomas, Kristen; Narula, Navneet; Azour, Lea; Moreira, Andre L.; Zhou, Fang
Background: In mediastinal biopsies that show fibrosis, the differential diagnosis includes fibrosing mediastinitis, immunoglobulin G subclass 4-related disease, Hodgkin lymphoma, as well as reactive fibrotic and inflammatory changes adjacent to other processes including neoplasms. Cases Description: We report two cases of incidentally detected mediastinal seminoma that contained extensive areas of paucicellular fibrosis, which precluded accurate preoperative biopsy diagnosis. The fibrosis consisted of mildly inflamed, densely scarred tissue with thin dilated vessels, and was present to a significant extent that is suggestive of spontaneous regression. These features are not currently described in the World Health Organization Classification of Thoracic Tumors. In both patients, needle and open biopsies sampled only the fibrotic areas of the tumors, and the final diagnosis was not achieved until surgical excision was performed. After surgery, both patients received chemotherapy, and were alive without evidence of disease at 3.4 years and 1 year post-operatively, respectively. Tumor fibrosis composed approximately 95% and 50% of each patient"™s tumor, respectively. In one of the patients, correlation of the needle biopsy position with the positron emission tomography (PET) scan revealed that the biopsy needle had sampled a non-metabolically active portion of the tumor. Conclusions: While pathologic spontaneous regression is well-described in gonadal germ cell tumors, it is not well-reported in extragonadal locations. Prospective knowledge of this diagnostic pitfall and targeting PET-avid regions of the tumor may increase the diagnostic yield and help to avoid non-indicated surgical interventions.
ISSN: 2522-6711
CID: 5499892

A Systematic Review of Telehealth-Based Pediatric Cancer Rehabilitation Interventions on Disability

Skiba, Meghan B.; Wells, Stephanie J.; Brick, Rachelle; Tanner, Lynn; Rock, Kelly; Marchese, Victoria; Khalil, Nashwa; Raches, Darcy; Thomas, Kristin; Krause, Kate J.; Swartz, Maria C.
Background: Telehealth is an emerging method which may overcome barriers to rehabilitation access for pediatric cancer survivors (aged ≤19 years). This systematic review aimed to examine telehealth-based rehabilitation interventions aimed at preventing, maintaining, or improving disability in pediatric cancer survivors. Methods: We performed systematic searches in Ovid MEDLINE, Ovid EMBASE, Cochrane Library, SCOPUS, Web of Science, and CINAHL Plus between 1994 and 2022. Eligible studies included telehealth-based interventions assessing disability outcomes in pediatric cancers. Results: Database searches identified 4,040 records. Nine unique interventions met the eligibility criteria. Telehealth delivery methods included telephone (n = 6), email (n = 3), mobile health applications (n = 3), social media (n = 3), videoconferencing (n = 2), text messaging (n = 2), active video gaming (n = 2), and websites (n = 2). Interventions focused on physical activity (n = 8) or self-management (n = 1). Outcomes assessing disability varied (n = 6). Three studies reported statistically and clinically significant results. Narrative synthesis of findings was constructed based on the Picker's principles for patient-centered care: (1) values, preferences, and needs; (2) involve family and friends; (3) coordination of care; (4) provide social support; (5) holistic well-being; and (6) information and communication. Conclusions: Telehealth-based rehabilitation interventions for pediatric cancer survivors is an emerging research area with potential to improve disability outcomes. Adequately powered trials with consistency in disability outcome measures are warranted. Additional research is needed to determine the effectiveness and best practices for telehealth-based pediatric cancer rehabilitation.
ISSN: 1530-5627
CID: 5622412

Placental Tissue Destruction and Insufficiency from COVID-19 Causes Stillbirth and Neonatal Death from Hypoxic-Ischemic Injury: A Study of 68 Cases with SARS-CoV-2 Placentitis from 12 Countries

Schwartz, David A; Avvad-Portari, Elyzabeth; Babál, Pavel; Baldewijns, Marcella; Blomberg, Marie; Bouachba, Amine; Camacho, Jessica; Collardeau-Frachon, Sophie; Colson, Arthur; Dehaene, Isabelle; Ferreres, Joan Carles; Fitzgerald, Brendan; Garrido-Pontnou, Marta; Gerges, Hazem; Hargitai, Beata; Helguera-Repetto, A Cecilia; Holmström, Sandra; Irles, Claudine Liliane; Leijonhfvud, Ã…sa; Libbrecht, Sasha; Marton, Tamás; McEntagart, Noel; Molina, James T; Morotti, Raffaella; Nadal, Alfons; Navarro, Alexandra; Nelander, Maria; Oviedo, Angelica; Oyamada Otani, Andre Ricardo; Papadogiannakis, Nikos; Petersen, Astrid C; Roberts, Drucilla J; Saad, Ali G; Sand, Anna; Schoenmakers, Sam; Sehn, Jennifer K; Simpson, Preston R; Thomas, Kristen; Valdespino-Vázquez, M Yolotzin; van der Meeren, Lotte E; Van Dorpe, Jo; Verdijk, Robert M; Watkins, Jaclyn C; Zaigham, Mehreen
CONTEXT.—/UNASSIGNED:Perinatal death is an increasingly important problem as the COVID-19 pandemic continues, but the mechanism of death has been unclear. OBJECTIVE.—/UNASSIGNED:To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for SARS-CoV-2. DESIGN.—/UNASSIGNED:Case-based retrospective clinico-pathological 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.—/UNASSIGNED:All 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis, the three findings constituting SARS-CoV-2 placentitis. 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%; 25/68) and chronic villitis (32%; 22/68). 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.—/UNASSIGNED: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.
PMID: 35142798
ISSN: 1543-2165
CID: 5156852

COVID-19 Patients with GI Manifestations May be Associated with Extensive Microthrombosis in the Small Intestine, a Study from 13 Autopsy Cases [Meeting Abstract]

Saberi, Shahram; Lin, Lawrence; Thomas, Kristen; Chiriboga, Luis; Sarkar, Suparna; Cao, Wenqing (Wendy)
ISSN: 0023-6837
CID: 5243132

COVID-19 Patients with GI Manifestations May be Associated with Extensive Microthrombosis in the Small Intestine, a Study from 13 Autopsy Cases [Meeting Abstract]

Saberi, Shahram; Lin, Lawrence; Thomas, Kristen; Chiriboga, Luis; Sarkar, Suparna; (Wendy) Cao, Wenqing
ISSN: 0893-3952
CID: 5243262

COVID-19 Patients with GI Manifestations May be Associated with Extensive Microthrombosis in the Small Intestine, a Study from 13 Autopsy Cases [Meeting Abstract]

Saberi, Shahram; Lin, Lawrence; Thomas, Kristen; Chiriboga, Luis; Sarkar, Suparna; Cao, Wenqing (Wendy)
ISSN: 0893-3952
CID: 5525682

Hofbauer Cells and COVID-19 in Pregnancy

Schwartz, David A; Baldewijns, Marcella; Benachi, Alexandra; Bugatti, Mattia; Bulfamante, Gaetano; Cheng, Ke; Collins, Rebecca R J; Debelenko, Larisa; De Luca, Danièle; Facchetti, Fabio; Fitzgerald, Brendan; Levitan, Daniel; Linn, Rebecca L; Marcelis, Lukas; Morotti, Denise; Morotti, Raffaella; Patanè, Luisa; Prevot, Sophie; Pulinx, Bianca; Saad, Ali G; Schoenmakers, Sam; Strybol, David; Thomas, Kristen; Tosi, Delfina; Toto, Valentina; van der Meeren, Lotte E; Verdijk, Robert M; Vivanti, Alexandre J; Zaigham, Mehreen
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.
PMID: 34297794
ISSN: 1543-2165
CID: 5037572

Underestimation of SARS-CoV-2 infection in placental samples [Letter]

Hanna, Nazeeh; Lin, Xinhua; Thomas, Kristen; Vintzileos, Anthony; Chavez, Martin; Palaia, Thomas; Ragolia, Louis; Verma, Sourabh; Khullar, Poonam; Hanna, Iman
PMID: 34297970
ISSN: 1097-6868
CID: 4954872