Testing of tissue specimens obtained from SARS-CoV-2 nasopharyngeal swab-positive donors.

Risk for transmission of SARS-CoV-2 through allogeneic human tissue transplantation is unknown. To further evaluate the risk of virus transmission, tissues were obtained from deceased donors who had tested positive for SARS-CoV-2 RNA via nasopharyngeal swab. This study evaluated an array of human tissues recovered for transplantation, including bone, tendon, skin, fascia lata, vascular tissues, and heart valves. Tissue samples and plasma or serum samples, if available, were tested for viral RNA (vRNA) using a real time PCR system for the presence of virus RNA. All samples were tested in quadruplicate for both subgenomic (sgRNA) and genomic (gRNA) RNA encoding the SARS-CoV-2 nucleocapsid gene. Amplification of a cellular housekeeping gene served as the positive control for every sample. A total of 47 tissue samples from 17 donors were tested for SARS-CoV-2 RNA. Four donors had plasma or serum available for paired testing. SARS-CoV-2 RNA was not detected from any tissue or plasma/serum sample tested. Based on these findings, risk of transmission through the transplantation of tissue types studied from SARS-CoV-2 infected donors is likely to be low.

Aortic tissue pathology in reoperative post-dissection repair following prior use of BioGlue.

AIM: The benefits of BioGlue as a surgical adjunct in aortic procedures have been demonstrated in several studies, but limited information is available regarding the associated histopathological findings of aortic tissue at the time of reoperation. The objective of this study was to assess, at reoperation, the histopathological characteristics of aortic tissue which has had BioGlue applied during a previous surgery. METHODS: This prospective, single-center, single-arm study enrolled patients who were undergoing aortic reoperation and who had BioGlue used during previous aortic surgery. Histopathological assessment of aortic specimens obtained intraoperatively was performed on tissue that would have been removed independent of subject participation in the study. RESULTS: A total of 11 patients were enrolled and based on gross assessment, excessive amounts of BioGlue had been applied during the initial surgery in 36.4% of cases. The samples with the greatest amount of residual BioGlue demonstrated moderate to marked inflammatory responses, while the remaining samples demonstrated minimal to moderate inflammatory responses. Calcification of residual BioGlue was noted in 4 cases. Substantial medial degeneration was associated with suture line dehiscence in 4 cases, some of which had a large quantity of residual BioGlue. No evidence of suture degradation was observed. CONCLUSIONS: Cases with surgical anastomosis dehiscence were associated with substantial medial degeneration. While no histologic findings directly linked BioGlue to these degenerative changes, a contributory role cannot be excluded. Following the manufacturer's instructions for appropriate application of BioGlue is crucial to prevent potential complications.

Prevalence, determinants, and correlates of coagulation necrosis and contraction band necrosis in donor hearts.

BACKGROUND: Exploration of pathologic changes in donor hearts and finding the association of pathologic findings with potentially reversible cardiac condition may result in allowing such hearts to recover and be used for transplantation. METHODS: We enrolled consecutive donors from one federally designated Organ Procurement Organization for one calendar year. Hearts rejected for transplantation underwent pathological examination. We studied the association of pathologic findings with the mechanism of death. RESULTS: A total of 81 hearts were rejected for transplantation. The most common pathologic findings were coagulation necrosis (CN) in 17.3% and contraction band necrosis (CBN) in 34.6%. Anoxic brain injury was present in 78.6% of the donors who had CN, and only in 29.9% of those without CN (P = 0.002). CBN was more commonly associated with subarachnoid hemorrhage (17.9% vs 1.9% of donors with and without CBN, P = 0.017). Only hearts with CBN had significantly lower LVEF (P = 0.017). CONCLUSION: Coagulation necrosis and CBN are the most common pathologic findings in the hearts rejected for transplantation. While CN is more prevalent in anoxic brain injury, CBN is more often present in subarachnoid hemorrhage. This may be clinically important because CBN is a pathologic hallmark of catecholamine-induced cardiomyopathy which is potentially reversible.

Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis.

Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues.

A bifunctional molecule that displays context-dependent cellular activity.

The cell-permeable dihydrofolate reductase inhibitor methotrexate was covalently linked to a ligand for the protein FKBP to create a bifunctional molecule called MTXSLF. The covalent tether between the two ligands was designed to be prohibitively short, so that unfavorable protein-protein interactions between DHFR and FKBP preclude formation of a trimeric complex. In vitro and in vivo experiments demonstrate that MTXSLF is an effective inhibitor of human DHFR, but that efficacy is decreased in the presence of human FKBP due to the high concentration of FKBP and its tight affinity for MTXSLF. MTXSLF also inhibits Plasmodium falciparum DHFR in vitro, but a low concentration of the weaker binding Plasmodium FKBP has no effect on the inhibitory potency of MTXSLF in vivo. These studies illustrate a potentially general strategy for modulating the biological activity of synthetic molecules that depends on the ligand-binding properties of a nontarget protein.