Mitral Annular Calcification as a Possible Nidus for Endocarditis: A Descriptive Series with Bacteriological Differences Noted.

BACKGROUND: Mitral annular calcification (MAC) is a chronic inflammatory process with similarities to atherosclerosis. It is common in elderly patients and those with renal dysfunction. Although MAC is associated with cardiovascular morbidity, its relationship to infective endocarditis is unclear. The aim of this study was to test the hypothesis that MAC would be prevalent in patients with mitral valve vegetations and that vegetations would frequently occur on calcific nodules. A secondary aim was to look for possible bacteriological differences between vegetations attached to the calcified annulus versus leaflet vegetations. METHODS: We retrospectively reviewed all echocardiographic studies of patients with native mitral valve vegetations from January 2007 to August 2015 (N = 56). We searched for (1) presence of MAC, (2) location of MAC, and (3) vegetation location (on calcium deposits or distant). MAC was defined as focal echo brightness in a nodular or band-like pattern. The modified Duke criteria were used to confirm the diagnosis of infective endocarditis. Transthoracic, transesophageal, and three-dimensional echocardiograms (when available) at the time of infection were evaluated by a single reader. RESULTS: Twenty-eight subjects were infected with Staphylococcus aureus, 17 with a streptococcal species, and five with other organisms; blood cultures were sterile in 6. Thirty-four (61%) subjects had some degree of MAC, while 22 (39%) had none. Among those with MAC, the vegetation was located on the calcium deposits in 22 (65%), versus in 12 (35%) where it was not. Among all 56 subjects, when S. aureus was the infecting organism it was present on MAC in 16/28 (57%) versus 6/28 (21%; P = .01) for other bacterial species. By contrast, streptococcal infections more frequently involved the leaflets (16/17 [94%]) versus nonstreptococcal infections (18/39 [46%]; P = .0008). CONCLUSIONS: MAC may act as a nidus for infection especially with S. aureus. Differences in mechanism of attachment between S. aureus and streptococci may account for the observed difference in frequency of attachment of vegetations to MAC.

Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer.

OBJECTIVE: Despite an 80% response rate to chemotherapy, epithelial ovarian cancer has the highest case fatality rate of all gynecologic malignancies. Several studies have shown the efficiency of anticancer peptides PNC-27 and PNC-28 in killing a variety of cancer cells selectively in vitro and in vivo. The purpose of this study was to evaluate the efficacy of PNC-27 against human primary epithelial ovarian cancer. METHODS: We established primary cultures of freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas. Two cell lines were obtained, one from mucinous cystadenocarcinoma, and the other from high-grade papillary serous carcinoma. The cancerous properties of these cells were characterized in vitro morphologically, by their growth requirements and serum independence. Treatment effects with PNC-27 were followed qualitatively by light microscopy, and quantitatively by measuring inhibition of cell growth using the MTT cell proliferation assay and direct cytotoxicity by measuring lactate dehydrogenase (LDH). RESULTS: PNC-27 inhibits in a dose-dependent manner the growth of and is cytotoxic to human primary cancer cells that had been freshly isolated from two ovarian epithelial cancers. The results further show that the control peptide PNC-29 has no effect on the primary cancer cells. Our results also show that PNC-27 is cytotoxic to cells from long-established and chemotherapy-resistant human ovarian cancer cell lines. CONCLUSION: These findings show, for the first time, the efficacy of PNC-27 on freshly isolated, primary human cancer cells. Our results indicate the potential of PNC-27 peptide as an efficient alternative treatment of previously untreated ovarian cancer as well as for ovarian cancers that have become resistant to present chemotherapies.