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51. Candida infective endocarditis: An observational cohort study with a focus on therapy.

Author

Campagnac C., Llopis J., Marco F., Mestres C.A., Moreno A., Ninot S., Pare C., Pericas J.M., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Leoni M.E.G., Robles J.A.G., Ramallo V.G., Cruz A.F., Kestler M., Marin M., Selles M.M., Abella H.R., Roda J.R., Lopez R.A., Pinilla B., Pinto A., Valerio M., Vazquez P., Verde E., Almirante B., De Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Wang A., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., DiPersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Levine D., Riddle J., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Park L.P., Sanderford B., Stafford J., Anstrom K., Karchmer A.W., Sexton D.J., Durack D.T., Eykyn S., Moreillon P., Sexton. D.J., Arnold C.J., Johnson M., Bayer A.S., Bradley S., Giannitsioti E., Miro J.M., Tornos P., Tattevin P., Strahilevitz J., Spelman D., Athan E., Nacinovich F., Lamas C., Barsic B., Fernandez-Hidalgo N., Munoz P., Chu V.H., Clara L., Sanchez M., Casabe J., Cortes C., Oses P.F., Ronderos R., Sucari A., Thierer J., Altclas J., Kogan S., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., De Oliveira Ramos A., Weksler C., Ferraiuoli G., Golebiovski W., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Fernandez R., Franco L., Gonzalez J., Jaramillo A.N., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Vincelj J., Freiberger T., Pol J., Zaloudikova B., Ashour Z., Kholy A.E., Mishaal M., Osama D., Rizk H., Aissa N., Alauzet C., Alla F., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Flecher E., Michelet C., Revest M., Chevalier F., Jeu A., Remadi J.P., Rusinaru D., Tribouilloy C., Bernard Y., Chirouze C., Hoen B., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Helen G., Sofia A., Ioannis D., Thomas T., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Sharma G., Francis J., Nair L., Thomas V., Venugopal K., Hannan M.M., Hurley J.P., Cahan A., Gilon D., Israel S., Korem M., Durante-Mangoni E., Mattucci I., Pinto D., Agrusta F., Senese A., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Kanafani Z., Kanj S.S., Sharif-Yakan A., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Murdoch D.R., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Liew Y.-Y., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Falces C., Garcia-De-La-Maria C., Fita G., Gatell J.M., Heras M., Campagnac C., Llopis J., Marco F., Mestres C.A., Moreno A., Ninot S., Pare C., Pericas J.M., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Leoni M.E.G., Robles J.A.G., Ramallo V.G., Cruz A.F., Kestler M., Marin M., Selles M.M., Abella H.R., Roda J.R., Lopez R.A., Pinilla B., Pinto A., Valerio M., Vazquez P., Verde E., Almirante B., De Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Wang A., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., DiPersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Levine D., Riddle J., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Park L.P., Sanderford B., Stafford J., Anstrom K., Karchmer A.W., Sexton D.J., Durack D.T., Eykyn S., Moreillon P., Sexton. D.J., Arnold C.J., Johnson M., Bayer A.S., Bradley S., Giannitsioti E., Miro J.M., Tornos P., Tattevin P., Strahilevitz J., Spelman D., Athan E., Nacinovich F., Lamas C., Barsic B., Fernandez-Hidalgo N., Munoz P., Chu V.H., Clara L., Sanchez M., Casabe J., Cortes C., Oses P.F., Ronderos R., Sucari A., Thierer J., Altclas J., Kogan S., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., De Oliveira Ramos A., Weksler C., Ferraiuoli G., Golebiovski W., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Fernandez R., Franco L., Gonzalez J., Jaramillo A.N., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Vincelj J., Freiberger T., Pol J., Zaloudikova B., Ashour Z., Kholy A.E., Mishaal M., Osama D., Rizk H., Aissa N., Alauzet C., Alla F., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Flecher E., Michelet C., Revest M., Chevalier F., Jeu A., Remadi J.P., Rusinaru D., Tribouilloy C., Bernard Y., Chirouze C., Hoen B., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Helen G., Sofia A., Ioannis D., Thomas T., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Sharma G., Francis J., Nair L., Thomas V., Venugopal K., Hannan M.M., Hurley J.P., Cahan A., Gilon D., Israel S., Korem M., Durante-Mangoni E., Mattucci I., Pinto D., Agrusta F., Senese A., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Kanafani Z., Kanj S.S., Sharif-Yakan A., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Murdoch D.R., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Liew Y.-Y., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Falces C., Garcia-De-La-Maria C., Fita G., Gatell J.M., and Heras M.

Abstract

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.Copyright © 2015, American Society for Microbiology.

Published
2015

52. Immunohistochemical study of PTEN and phosphorylated mTOR proteins in familial and sporadic invasive breast carcinomas

Author

Bakarakos, P. Theohari, I. Nomikos, A. Mylona, E. Papadimitriou, C. Dimopoulos, A.-M. Nakopoulou, L.

Abstract

Aims: Loss of phosphatase and tensin homologue (PTEN) leads to activation of several kinases, including mammalian target of rapamycin (mTOR), which promotes cell cycle progression. The aim was to study the expression of PTEN and phosphorylated (p)-mTOR in familial and sporadic invasive breast carcinomas and their relation to clinicopathological features, molecular indices (Wnt1) and patients' survival. Methods and results: PTEN and p-mTOR were detected immunohistochemically in 215 sections of invasive breast carcinomas (112 with a familial history of breast cancer). Image analysis was used and univariate and multivariate analyses employed for statistical evaluation of results. PTEN was detecte5d in the nucleus (73.5%) and p-mTOR in the cytoplasm (44.2%) of cancer cells. Loss of PTEN protein was more frequently detected in women with a familial history of breast cancer (72%) (P < 0.0001), while its expression was negatively correlated with Wnt1, in total (P = 0.049). p-mTOR showed a positive association with lymph node status (P = 0.010) and was found to have a negative impact on patients' overall survival (P = 0.016). Conclusions: Loss of PTEN protein expression appears to occur more frequently in women with a family history of breast cancer, whereas activation of mTOR protein seems to be related to a more aggressive phenotype. © 2010 Blackwell Publishing Limited.

Published
2010

53. Engagement of fatty acids with toll-like receptor 2 drives interleukin-1β production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis

Author

Joosten, L.A.B. Netea, M.G. Mylona, E. Koenders, M.I. Malireddi, R.K.S. Oosting, M. Stienstra, R. Van De Veerdonk, F.L. Stalenhoef, A.F. Giamarellos-Bourboulis, E.J. Kanneganti, T.-D. Van Der Meer, J.W.M.

Abstract

Objective The concept that intraarticular crystals of uric acid by themselves trigger episodes of painful gouty arthritis is inconsistent with the clinical reality. Patients with large deposits of monosodium urate monohydrate (MSU) crystals (tophi) do not necessarily experience gouty attacks. In fact, it is the excessive consumption of food or alcohol that elicits the inflammation of the acute gout attack. The aim of this study was to identify the precise mechanism that initiates flares of gouty arthritis. Methods Human peripheral blood mononuclear cells (PBMCs) and murine macrophages were stimulated in vitro with MSU, free fatty acids (FFAs), or both in combination. Thereafter, production of interleukin-1β (IL-1β) and activation of caspase 1 were determined. Gouty arthritis was induced in mice with deficiencies in the genes for caspase 1, ASC, NALP3, or IL-1β, and the lack of inflammasome activity during joint swelling or other joint pathologic features was investigated in these mice. Results MSU crystals had no biologic effects on PBMCs from healthy subjects, whereas the FFA C18:0 in the presence of MSU crystals induced the release of large amounts of IL-1β following engagement of Toll-like receptor 2 (TLR-2). Interaction of FFAs, but not alcohol, with TLR-2 synergized with MSU crystals to induce an inflammatory reaction. An important event of MSU/FFA-induced acute joint inflammation is the activation of the inflammasome. MSU/FFA-induced release of IL-1β was dependent on activation of caspase 1 and ASC, but surprisingly, not NALP3. Conclusion The synergistic effect between FFAs and MSU crystals leads to ASC/caspase 1-driven IL-1β release. This mechanism could explain how constitutionally derived metabolic events initiate attacks of gout via the induction of IL-1β-mediated joint inflammation. © 2010 by the American College of Rheumatology.

Published
2010

54. Peroxisome proliferator-activated receptor gamma expression in urothelial carcinomas of the bladder: Association with differentiation, proliferation and clinical outcome

Author

Mylona, E. Giannopoulou, I. Diamantopoulou, K. Bakarakos, P. Nomikos, A. Zervas, A. Nakopoulou, L.

Abstract

Aims: Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcriptional factor that regulates the transcription of various target genes. Our purpose is to investigate the clinicopathologic and prognostic significance of PPARγ expression in human urothelial bladder cancer (BUC). Methods: Immunohistochemistry was applied in 117 paraffin-embedded specimens of human BUC to detect the proteins PPARγ and Ki67. The image analysis method was used for the evaluation of the immunohistochemical staining. Results: PPARγ protein was localized in the nuclei of the malignant cells. Its expression was inversely associated with the stage of BUCs (p < 0.001), tumor grade (p = 0.007) and the expression of the proliferation marker Ki67 (p = 0.015) while it was found to exert a favorable effect on patients' overall survival (p = 0.001). Conclusion: The findings of the present study suggest that in BUC, PPARγ expression can identify patients with a better prognosis who suffer from more differentiated, non-invasive tumors, of a low proliferative potential. © 2008 Elsevier Ltd. All rights reserved.

Published
2009

55. The clinicopathologic and prognostic significance of CD44+/CD24-/low and CD44-/CD24+ tumor cells in invasive breast carcinomas

Author

Mylona, E. Giannopoulou, I. Fasomytakis, E. Nomikos, A. Magkou, C. Bakarakos, P. Nakopoulou, L.

Subjects
skin and connective tissue diseases
Abstract

Cells with distinct phenotypes and stem cell-like properties have been reported to exist in breast cancer. The aim of the present study was to investigate the clinicopathologic and prognostic significance of the CD44+/CD24-/low and CD44-/CD24+ tumor phenotypes' prevalence. Double immunohistochemistry was applied on a series of 155 paraffin-embedded breast tissue specimens to detect CD44 and CD24. Evaluation of the phenotypes was performed by image analysis. The prevalence of CD44+/CD24-/low and CD44-/CD24+ tumor cells was 58.7% and 82.6%, respectively. The dominance of the CD44+/CD24-/low tumor cells was inversely associated with lymph node metastasis (P = .019) and tended to inversely associate with the stage of the disease (P = .068). Moreover, the prevalence of CD44+/CD24-/low was found to exert no significant impact on patients' prognosis although it displayed a tendency toward an increase in disease-free survival (P = .074). On the other hand, the prevalence of CD44-/CD24+ tumor cells was found to have no clinicopathologic significance. However, it was found to exert an unfavorable impact on both relapse-free (P = .009) and overall survival (P = .046) of the patients with breast carcinomas of intermediate differentiation (grade 2). In breast tissue, CD44+/CD24-/low tumor cells seem to be associated with lack of lymph node metastasis and a tendency toward an increase of the relapse-free survival of the patients. On the contrary, tumor cells with the phenotype CD44-/CD24+ seem to identify patients with worse disease-free and overall survival within the group of intermediate-grade differentiation patients whose prognosis is difficult to assess. © 2008.

Published
2008

56. Prognostic value of microsatellite instability determined by immunohistochemical staining of hMSH2 and hMSH6 in urothelial carcinoma of the bladder

Author

Mylona, E. Zarogiannos, A. Nomikos, A. Giannopoulou, I. Nikolaou, I. Zervas, A. Nakopoulou, L.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, digestive system diseases
Abstract

Mismatch repair (MMR) genes are involved in the recognition and repair of acquired DNA damage, which arises during cell division, thus playing an essential role in preserving genetic stability. Immunohistochemistry was applied to 130 specimens from urothelial carcinoma (UC) of the bladder to detect expression of MMR gene products hMSH2 and hMSH6, and to investigate its clinicopathological and prognostic value. hMSH2 and hMSH6 protein expression was exclusively detected in the nuclei of malignant cells. Of the 112 cases evaluable for hMSH2, 29 (25.9%) were negative and of the 130 UCs evaluable for hMSH6, 64 (49.2%) were negative, and were thus considered to depict MSI. Nuclear hMSH2 values were statistically lower in non-invasive UCs (Ta-T1) (p=0.013) and in carcinomas with decreased p53 staining (p=0.04). Lower hMSH6 values were more often met in well-differentiated tumors (p

Published
2008

57. Lymphatic and blood vessel morphometry in invasive breast carcinomas: relation with proliferation and VEGF-C and -D proteins expression

Author

Mylona, E. Nomikos, A. Alexandrou, P. Giannopoulou, I. Keramopoulos, A. Nakopoulou, L.

Abstract

INTRODUCTION: The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size related parameters as well as their correlation with the proliferative potential of the tumor and VEGF-C and -D expression. METHODS: Both single and double immunohistochemistry were applied on a series of 146 paraffin-embedded breast tissue specimens to detect VEGF-C and -D as well as lymphatics and blood microvessels, respectively. Computer-assisted morphometry was performed to evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as well as various vascular size related parameters. RESULTS: Lymphatics were detected within the stroma at the tumor border, while blood vessels were located in both the interior of the tumor mass and peritumor stroma. BV major axis, minor axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and p=0.008 respectively), while LV major axis, minor axis and the perimeter inversely correlated with tumor nuclear grade (p=0.045, p=0.037 and p=0.032 respectively) and topoisomerase IIalpha (p=0.015, p=0.024 and p=0.045 respectively). The same LV parameters were found to positively correlate with cancerous VEGF-C (p

Published
2007

58. Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma

Author

Mylona, E. Alexandrou, P. Mpakali, A. Giannopoulou, I. and Liapis, G. Markaki, S. Keramopoulos, A. Nakopoulou, L.

Abstract

Aims: Vascular endothelial growth factors C and D (VEGF-C and VEGF-D) play a major role in lymphangiogenesis and activate VEGF receptor 3 (VEGFR-3). Our purpose was to study the clinicopathologic and clinical value of VEGF-C, VEGF-D and VEGFR-3 in invasive breast carcinoma. Material and methods: Immunohistochemistry was performed in paraffin-embedded tissue specimens from 177 invasive breast carcinomas to detect the proteins VEGF-C, VEGF-D, VEGFR-3, p53, Ki67, c-erbB-2, topoII alpha and ER/PR. The results were statistically processed. Results: VEGF-C, VEGF-D and VEGFR-3 were found to be predominantly expressed in the cytoplasm of the malignant cells. VEGF-C occasionally showed a submembranous intensification. VEGF-D and VEGFR-3 were also immunodetected in the nuclei of the malignant cells. Nuclear VEGF-D was positively correlated to p53, Ki67 and topoII alpha proteins’ expression (p = 0.003, p = 0.009 and p = 0.017 respectively) and nuclear VEGFR-3 to topoII alpha (p = 0.034). Cytoplasmic expression of VEGF-C and its submembranous intensification were found to be independent indicators of patients’ overall and disease-free survival, respectively (p = 0.003 and p = 0.044 respectively). The group with high expression of both cytoplasmic VEGF-C and stromal VEGFR-3 showed poor overall survival (p = 0.024) and the group with both submembranous VEGF-C and stromal VEGFR-3 immunostaining showed poor both disease-free and overall survival (p = 0.012 and p = 0.038 respectively). Conclusion: VEGF-D and VEGFR-3 seem to exert proliferative activity in invasive breast carcinomas. VEGF-C was found to be an independent indicator of patient’s poor prognosis and the simultaneous expression of tumor VEGF-C and stromal VEGFR-3 yielded additional prognostic information. (c) 2006 Elsevier Ltd. All rights reserved.

Published
2007

59. The clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 according to their localization in invasive breast carcinoma

Author

Mylona, E. Nomikos, A. Magkou, C. Kamberou, M. and Papassideri, I. Keramopoulos, A. Nakopoulou, L.

Abstract

Aims: To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c-erbB2 and peroxisome proliferator-activated receptor (PPAR) gamma. Methods and results: Immunohistochemistry was carried out on 175 paraffin-embedded breast tissue specimens to detect MT1-MMP, MMP-9, oestrogen receptor (ER), progesterone receptor, c-erbB-2, Ki67, topoisomerase II alpha (topo II alpha) and PPAR gamma protein expression. Results: Both MT1-MMP and MMP-9 were expressed in the cytoplasm of the malignant cells and the peritumoral stroma. Cytoplasmic MT1-MMP was more often observed in ER+ tumours (P = 0.022), of a lower nuclear grade (P = 0.020) and with reduced expression of Ki67 and topo II alpha (P = 0.027 and P = 0.006, respectively). Moreover, cytoplasmic MT1-MMP was positively associated with MMP-9 (P = 0.010) and PPAR gamma (P < 0.0001). Cytoplasmic MMP-9 was inversely associated with Ki67 (P = 0.034) and topo II alpha (P = 0.004), whereas its relationship with MT1-MMP (P = 0.034) and PPAR gamma (P = 0.024) was found to be positive. Stromal MMP-9 was more often observed in c-erbB2+ tumours (P = 0.043) and had an unfavourable impact on overall and relapse-free survival in both univariate (P = 0.0157 and P = 0.0274, respectively) and multivariate analyses (P = 0.007 and P = 0.024, respectively). Conclusions: Cytoplasmic MT1-MMP and MMP-9 seem to be related to well-differentiated tumours, with a low proliferation potential, while stromal MMP-9 is associated with an aggressive tumour phenotype and is recognized as an independent poor prognostic indicator.

Published
2007

60. Extra copies of chromosomes 16 and X in invasive breast carcinomas are related to aggressive phenotype and poor prognosis

Author

Nakopoulou, L. Panayotopoulou, E.G. Giannopoulou, I. Tsirmpa, I. Katsarou, S. Mylona, E. Alexandrou, P. Keramopoulos, A.

Abstract

Background: Breast cancer is a genetically complex disease, which involves the accumulation of various structural and numerical chromosomal aberrations. Aim: To assess the numerical status of chromosomes 16 and X by interphase cytogenetics, in 114 women with primary invasive breast carcinomas, in relation to clinicopathological parameters, patients' overall survival and indices of cell growth (c-erbB-2, topoisomerase IIα (topoIIα)) and cell survival (caspase-3, bcl-2). Experimental design: Chromogenic in situ hybridisation with pericentromeric probes was performed for molecular analysis, while oestrogen and progesterone receptors, cerbB-2, topoIIα, caspase-3 and bcl-2 expression was immunohistochemically detected (ABC/HRP). The results were statistically assessed by univariate and multivariate analyses. Results: Polysomy of chromosomes 16 and X was detected as the predominant aberration (73.7% and 57.9%, respectively). Gain of chromosome 16 copies was associated with high nuclear grade (p = 0.009), increased tumour size (p = 0.041), advanced stage (p = 0.002), the expression of topoIIα (p = 0.005) and worse overall survival by multivariate analysis (p = 0.032). Chromosome X polysomy was increased in ductal carcinomas of high histological grade (p = 0.008), in high nuclear grade tumours (p = 0.001), and was associated with the expression of topoIIα (p = 0.005), loss of caspase-3 (p = 0.036) and impaired prognosis of ductal carcinomas (p = 0.041). Conclusions: Polysomy of chromosomes 16 and X was reported as the predominant alteration in phenotypically aggressive breast tumours, characterised by poor differentiation, increased growth potential and impaired prognosis, whereas gain of chromosome X in particular is probably implicated in cell survival.

Published
2007

61. The prognostic value of the topographic distribution of uPAR expression in invasive breast carcinomas

Author

Giannopoulou, I. Mylona, E. Kapranou, A. Mavrommatis, J. Markaki, S. Zoumbouli, Ch. Keramopoulos, A. Nakopoulou, L.

Subjects
skin and connective tissue diseases, neoplasms, biological factors
Abstract

uPA system plays an important role in cancer invasion and metastasis. The binding of uPA to its receptor, uPAR, is necessary for the activation of uPA system. We studied by immunohistochemistry the distribution pattern of uPAR on 173 paraffin-embedded samples of invasive breast carcinomas in relation to clinicopathologic data and patients' survival. uPAR was detected in both the malignant and stromal cells in the 68.8 and 74.6% of the cases, respectively. uPAR of cancerous cells was more often observed in lobular carcinomas (P=0.012). Stromal expression of uPAR was inversely associated with ER of the tumor (P=0.044) and was found to be an independent prognosticator of patients' shortened relapse-free survival (P=0.018). These results suggest that stromal uPAR influences more directly tumor behaviour, being related to an aggressive tumor phenotype and patients' poor relapse-free survival. © 2006 Elsevier Ireland Ltd. All rights reserved.

Published
2007

62. Lymphatic and blood vessel morphometry in invasive breast carcinomas: Relation with proliferation and VEGF-C and -D proteins expression

Author

Mylona, E., Nomikos, A., Alexandrou, P., Giannopoulou, I., Keramopoulos, A., and Nakopoulou, Lydia

Subjects
616 - Patología. Medicina clínica. Oncología, Breast cancer, Angiogenesis
Abstract

Introduction: The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size related parameters as well as their correlation with the proliferative potential of the tumor and VEGF-C and -D expression. Methods: Both single and double immunohistochemistry were applied on a series of 146 paraffin-embedded breast tissue specimens to detect VEGF-C and -D as well as lymphatics and blood microvessels, respectively. Computer-assisted morphometry was performed to evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as well as various vascular size related parameters. Results: Lymphatics were detected within the stroma at the tumor border, while blood vessels were located in both the interior of the tumor mass and peritumor stroma. BV major axis, minor axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and p=0.008 respectively), while LV major axis, minor axis and the perimeter inversely correlated with tumor nuclear grade (p=0.045, p=0.037 and p=0.032 respectively) and topoisomerase IIa (p=0.015, p=0.024 and p=0.045 respectively). The same LV parameters were found to positively correlate with cancerous VEGF-C (p

Published
2007

63. Knowledge of students training to be health care professionals about AIDS transmission

Author

Roupa, Zoi, Mylona, E., and Raftopoulos, Vasilios

Subjects
Aids trasmittion, HIV, Medical and Health Sciences
Abstract

Knowledge of how the HIV virus is transmitted and how we can protect ourselves against it will lead individuals to adopt appropriate sexual behavior, thus preventing transmission of HIV. An evaluation of this knowledge in a young population of reproductive age is fundamental when drawing up and assessing health education programs.

Published
2007

64. Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome

Author

Mylona, E. Magkou, C. Giannopoulou, I. Agrogiannis, G. Markaki, S. Keramopoulos, A. Nakopoulou, L.

Abstract

Introduction: Our aim was to study the expression pattern of tissue inhibitor of metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its clinicopathological and prognostic value as well as its relation to markers indicative of the tumor phenotype. Methods: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 173 invasive breast carcinomas to detect the proteins TIMP-3, estrogen receptor (ER), progesterone receptor, p53, c-erbB-2, topoisomerase IIα and Bcl-2. Results: TIMP-3 protein was immunodetected in the cytoplasm of the malignant cells and the peritumoral stroma, as well as in in situ carcinoma and normal epithelium. Reduced expression of TIMP-3 protein within cancer cells was correlated with carcinomas of high nuclear and histological grade (p = 0.032 and p = 0.015, respectively), and low ER expression (p = 0.053). Moreover, TIMP-3 immunopositivity was inversely correlated with the expression of p53 and topoIIα proteins (p = 0.002 and p = 0.008, respectively), whereas it was positively associated with Bcl-2 expression (p = 0.020). Reduced expression of TIMP-3 protein within cancer cells was found to have an unfavorable impact on disease-free survival (p = 0.052) in the entirety of the patient population, as well as in both subgroups of lymph-node-positive and mutant-p53-negative patients (p = 0.007 and p = 0.037, respectively). Stromal localization of TIMP-3 protein was found to have no clinicopathological or prognostic value. Conclusion: This is the first immunohistochemical study to show that TIMP-3 protein within cancer cells is associated with tumor phenotype. Reduced expression of TIMP-3 protein within cancer cells was found to correlate with an aggressive tumor phenotype, negatively affecting the disease-free survival of both subgroups of lymph node-positive and mutant-p53-negative patients. © 2006 Mylona et al.; licensee BioMed Central Ltd.

Published
2006

65. Study of phospho-beta-catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome

Author

Nakopoulou, L Mylona, E Papadaki, I Kavantzas, N and Giannopoulou, I Markaki, S Keramopoulos, A

Abstract

beta-Catenin has a crucial role in cell-cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated beta-catenin, as well as its relation to the tumors’ phenotype, in breast cancer. Immunohistochemistry was applied on 141 paraffin-embedded breast tissue specimens for the detection of phospho-beta-catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and TIMP-1. For each case, a phospho-beta-catenin index was determined by image analysis. Phospho-beta-catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho-beta-catenin was statistically higher in carcinomas of smaller tumor size (P = 0.030), lower stage (P = 0.026), decreased Ki-67 and high c-erbB-2 immunoreactivity (P = 0.052 and P = 0.037, respectively). Nuclear phospho-beta-catenin showed a parallel correlation with ER and ER beta (P = 0.022 and P = 0.043, respectively), bcl-2 (P = 0.042), uPAR in cancer cells (P = 0.041) and TIMP-1, although the correlation was borderline (P = 0.066). Cytoplasmic phospho-beta-catenin was found to be independently correlated with prolonged disease-free and overall survival (P = 0.046 and P = 0.002, respectively), whereas nuclear localization was correlated with a shortened overall survival (P = 0.046). In conclusion, phospho-beta-catenin may have a different involvement in invasive breast carcinomas, according to its subcellular distribution. Nuclear localization seems to be related to an aggressive tumor phenotype, negatively affecting patients’ overall survival, whereas cytoplasmic localization is associated with a favorable tumor phenotype and a longer disease-free and overall survival.

Published
2006

66. The multifunctional role of the immunohistochemical expression of MMP-7 in invasive breast cancer

Author

Mylona, E Kapranou, A Mavrommatis, J Markaki, S and Keramopoulos, A Nakopoulou, L

Abstract

Mylona E, Kapranou E, Mavrommatis J, Markaki S, Keramopoulos A, Nakopoulou L. The multifunctional role of the immunohistochemical expression of MMP-7 in invasive breast cancer. APMIS 2005; 113:246-55. The secretion of matrix metalloproteinases (MMPs) is crucial in the metastasis of cancer cells, since MMPs are responsible for the degradation of extracellular matrix (ECM). Among them, matrix metalloproteinase-7 (MMP-7) or matrilysin 1 is a stromelysin which degrades type-IV collagen, fibronectin and laminin. Immunohistochernistry was performed to detect MMP-7 protein in infiltrative breast carcinomas. MMP-7 was studied along with clinicopathological parameters, disease-free and overall survival, and p53, c-erbB-2, topoIIa, MMP-2, uPAR and P-catenin. MMP-7 immunoreactivity was detected in the cytoplasm of cancer cells in 54.2% (96/177) and tumor stromal cells in 47.5%, (84/177), as well as in normal epithelium adjacent to malignant epithelium. MMP-7 reactivity in cancer cells displayed an inverse association with nuclear grade (p = 0.049) and topoIIa (p=0.03). A parallel association was observed between the expression of MMP-7 in both malignant and stromal cells with uPAR in cancer cells (p=0.033 and p=0.027, respectively). MMP-7 of tumor stromal cells depicted a parallel correlation with MMP-2 of the same cell type (p=0.044), while abnormal P-catenin expression was inversely associated with MMP-7 of cancer cells (p=0.047). Our results show the multifunctional role of MMP-7 in the mammary gland, since it seems to be associated with a less aggressive phenotype, while, at the same time, being involved in invasion, through its collaboration with indicators of invasion.

Published
2005

67. Effect of different ERK2 protein localizations on prognosis of patients with invasive breast carcinoma

Author

Nakopoulou, L Mylona, E Rafailidis, P Alexandrou, P and Giannopoulou, I Keramopoulos, A

Subjects
environment and public health
Abstract

Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK1/2, which have been implicated in the pathogenesis of cancer. We examined 151 cases of invasive breast carcinoma by immunohistochemistry and compared the ERK2 expression with clinicopathological parameters, MMP-11 immunoexpression and patients’ survival. ERK2 immunoexpression was detected in the cytoplasm and nucleus of cancer cells in 37.7% and 19.2% of cases, respectively. Nuclear ERK2 was inversely correlated with ER (p=0.039), whereas cytoplasmic ERK2 was positively correlated with MMP-11 in fibroblasts (p=0.032) and more often expressed in lobular than ductal carcinomas (p=0.026). Nuclear ERK2 expression was found to be an independent prognostic factor of shortened overall survival of patients (p=0.040), while cytoplasmic ERK2 had an independent, favorable effect on both disease-free and overall survival (p < 0.0001 and p=0.002, respectively). These findings suggest that the different subcellular localizations of ERK2 seem to be related to different, possibly contradictory, effects on patient survival.

Published
2005

68. PPAR gamma expression in breast cancer: clinical value and correlation with ER beta

Author

Papadaki, I Mylona, E Giannopoulou, I Markaki, S and Keramopoulos, A Nakopoulou, L

Abstract

Aims: To examine the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in invasive breast carcinoma in relation to known clinicopathological features, ERbeta, and relapse-free and overall patient survival. PPARgamma is a ligand-activated transcriptional factor that regulates the transcription of various target genes and has been implicated in human breast cancer. Methods and results: We performed immunohistochemistry to detect PPARgamma, ERalpha, PR and ERbeta in 170 infiltrative breast carcinomas. The results were subjected to statistical analysis. PPARgamma was detected in the cytoplasm of 58% of breast carcinoma samples. PPARgamma did not differ with regard to any of the clinicopathological parameters except for histological grade, to which it was found to be inversely correlated (P = 0.019), and ERbeta, to which it was positively related (P = 0.016). As regards relapse-free survival, in univariate statistical analysis PPARgamma was found to exert a marginally favourable impact on all the patients (P = 0.076), but a strong one on patients with ductal carcinoma (P = 0.027), whereas Cox’s regression analysis depicted PPARgamma to be an independent prognosticator for patients with ductal carcinoma (P = 0.039). No association was found between PPARgamma expression and overall survival. Conclusion: These results indicate the favourable impact of PPARgamma expression on disease-free survival of patients with ductal breast carcinoma and its possible cooperation with ERbeta in exerting that favourable effect.

Published
2005

69. One-year outcome following biological or mechanical valve replacement for infective endocarditis.

Author

Pangercic A., Munoz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., de Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D.J., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Dipersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Levine D., Riddle J., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Park L.P., Sanderford B., Stafford J., Anstrom K., Bayer A.S., Karchmer A.W., Durack D.T., Eykyn S., Moreillon P., Delahaye F., Chu V.H., Altclas J., Barsic B., Delahaye A., Freiberger T., Gordon D.L., Hannan M.M., Hoen B., Kanj S.S., Lejko-Zupanc T., Mestres C.A., Pachirat O., Pappas P., Lamas C., Selton-Suty C., Tan R., Tattevin P., Wang A., Clara L., Sanchez M., Casabe J., Cortes C., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., de Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., Tranchesi R.A.M., Paiva M.G., Fortes C.Q., Ramos A.O., Ferraiuoli G., Golebiovski W., Weksler C., Santos M., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Fernandez R., Franco L., Gonzalez J., Jaramillo A.N., Bukovski S., Krajinovic V., Sharma G., Rudez I., Vincelj J., Pol J., Zaloudikova B., Ashour Z., El Kholy A., Mishaal M., Osama D., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Goehringer F., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Vandenesch F., Donal E., Donnio P.Y., Flecher E., Michelet C., Revest M., Chevalier F., Jeu A., Remadi J.P., Rusinaru D., Tribouilloy C., Bernard Y., Chirouze C., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Thomas T., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Papanikolaou K., Francis J., Nair L., Thomas V., Venugopal K., Hannan M., Hurley J., Cahan A., Gilon D., Israel S., Korem M., Strahilevitz J., Durante-Mangoni E., Mattucci I., Pinto D., Agrusta F., Senese A., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Anouti K., Chahoud J., Kanafani Z., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., van der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Murdoch D.R., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Liew Y.-Y., Tan R.-S., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., Falces C., Garcia-De-la-maria C., Fita G., Gatell J.M., Heras M., Llopis J., Marco F., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J.M., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Pangercic A., Munoz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., de Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D.J., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Dipersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Levine D., Riddle J., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Park L.P., Sanderford B., Stafford J., Anstrom K., Bayer A.S., Karchmer A.W., Durack D.T., Eykyn S., Moreillon P., Delahaye F., Chu V.H., Altclas J., Barsic B., Delahaye A., Freiberger T., Gordon D.L., Hannan M.M., Hoen B., Kanj S.S., Lejko-Zupanc T., Mestres C.A., Pachirat O., Pappas P., Lamas C., Selton-Suty C., Tan R., Tattevin P., Wang A., Clara L., Sanchez M., Casabe J., Cortes C., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., de Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., Tranchesi R.A.M., Paiva M.G., Fortes C.Q., Ramos A.O., Ferraiuoli G., Golebiovski W., Weksler C., Santos M., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Fernandez R., Franco L., Gonzalez J., Jaramillo A.N., Bukovski S., Krajinovic V., Sharma G., Rudez I., Vincelj J., Pol J., Zaloudikova B., Ashour Z., El Kholy A., Mishaal M., Osama D., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Goehringer F., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Vandenesch F., Donal E., Donnio P.Y., Flecher E., Michelet C., Revest M., Chevalier F., Jeu A., Remadi J.P., Rusinaru D., Tribouilloy C., Bernard Y., Chirouze C., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Thomas T., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Papanikolaou K., Francis J., Nair L., Thomas V., Venugopal K., Hannan M., Hurley J., Cahan A., Gilon D., Israel S., Korem M., Strahilevitz J., Durante-Mangoni E., Mattucci I., Pinto D., Agrusta F., Senese A., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Anouti K., Chahoud J., Kanafani Z., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., van der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Murdoch D.R., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Liew Y.-Y., Tan R.-S., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., Falces C., Garcia-De-la-maria C., Fita G., Gatell J.M., Heras M., Llopis J., Marco F., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J.M., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., and Marin M.

Abstract

Methods and results Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54 years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p = 0.0009) and 25.3% vs 16.6% (p <.0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10 years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). Conclusions Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction. Background Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Published
2014

73. Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

Author

Zaloudikova B., Garcia-De-La-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Munoz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., De Alarcon A., Parra R., Alestig E., Johansson M., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Di Persio J., Salstrom S.-J., Baddley J., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Cabell C.H., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Barsic B., Dickerman S., Krajinovic V., Pappas P., Altclas J., Carosi G., Casabe J.H., Chu V.H., Delahaye F., Edathodu J., Fortes C.Q., Olaison L., Pangercic A., Patel M., Rudez I., Tamin S.S., Vincelj J., Bayer A.S., Wang A., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., De Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Cereceda M., Fica A., Mella R.M., Bukovski S., Freiberger T., Pol J., Sharma G., Ashour Z., Kholy A.E., Mishaal M., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Revest M., Tattevin P., Violette J., Chevalier F., Jeu A., Rusinaru D., Sorel C., Tribouilloy C., Bernard Y., Chirouze C., Hoen B., Leroy J., Plesiat P., Naber G.C., Neuerburg C., Mazaheri B., Naber C., Athanasia S., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Francis J., Nair L., Thomas D.M.V., Venugopal K., Hannan M., Hurley J., Cahan A., Gilon D., Israel S., Korem M., Strahilevitz J., Tripodi M.F., Casillo R., Cuccurullo S., Dialetto G., Durante-Mangoni E., Irene M., Ragone E., Utili R., Cecchi E., Rosa F.D., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Sfeir J., Yasmine M., Abidin I., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Murdoch D.R., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Halim M., Lum L.-N., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., Falces C., Zaloudikova B., Garcia-De-La-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Munoz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., De Alarcon A., Parra R., Alestig E., Johansson M., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Di Persio J., Salstrom S.-J., Baddley J., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Cabell C.H., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Barsic B., Dickerman S., Krajinovic V., Pappas P., Altclas J., Carosi G., Casabe J.H., Chu V.H., Delahaye F., Edathodu J., Fortes C.Q., Olaison L., Pangercic A., Patel M., Rudez I., Tamin S.S., Vincelj J., Bayer A.S., Wang A., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., De Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Cereceda M., Fica A., Mella R.M., Bukovski S., Freiberger T., Pol J., Sharma G., Ashour Z., Kholy A.E., Mishaal M., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Revest M., Tattevin P., Violette J., Chevalier F., Jeu A., Rusinaru D., Sorel C., Tribouilloy C., Bernard Y., Chirouze C., Hoen B., Leroy J., Plesiat P., Naber G.C., Neuerburg C., Mazaheri B., Naber C., Athanasia S., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Francis J., Nair L., Thomas D.M.V., Venugopal K., Hannan M., Hurley J., Cahan A., Gilon D., Israel S., Korem M., Strahilevitz J., Tripodi M.F., Casillo R., Cuccurullo S., Dialetto G., Durante-Mangoni E., Irene M., Ragone E., Utili R., Cecchi E., Rosa F.D., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Sfeir J., Yasmine M., Abidin I., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Murdoch D.R., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Halim M., Lum L.-N., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., and Falces C.

Abstract

Background. The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Methods. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Results. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval[CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). Conclusions. There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.Copyright © The Author 2012.

Published
2013

74. HACEK Infective Endocarditis: Characteristics and Outcomes from a Large, Multi-National Cohort.

Author

Revest M., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Lum L.-N., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castan~eda X., Cervera C., Rio A., Falces C., Garcia-de-la-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Mun~oz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., de Alarcon A., Parra R., Alestig E., Johansson M., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., DiPersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Baloch K., Corey G.R., Dixon C.C., Fowler Jr. V.G., Harding T., Jones-Richmond M., Pappas P., Park L.P., Redick T., Stafford J., Anstrom K., Chu V.H., Karchmer A.W., Murdoch D.R., Sexton D.J., Wang A., Bayer A.S., Cabell C.H., Chu V., Durack D.T., Eykyn S., Hoen B., Moreillon P., Olaison L., Raoult D., Rubinstein E., Chambers S.T., Murdoch D., Bouza E., Hannan M.M., Kanafani Z.A., Lang S., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Altclas J., Silvia Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Konecny P., Lawrence R., Rees D., Feneley M.P., Harkness J., Jones P., Post J., Reinbott P., Ryan S., Gattringer R., Wiesbauer F., Andrade A.R., de Brito A.C.P., Guimara~es A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., de Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., de Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Morris A.M., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Barsic B., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Vincelj J., Freiberger T., Pol J., Zaloudikova B., Ashour Z., Kholy A.E., Mishaal M., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Sharma G., Tattevin P., Violette J., Chevalier F., Jeu A., Rusinaru D.M.D., Sorel C., Tribouilloy C., Bernard Y., Chirouze C., Leroy J., Plesiat P., Naber C., Mazaheri B., Neuerburg C., Athanasia S., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Francis J., Nair L., Thomas V., Venugopal K., Hannan M., Hurley J., Gilon D., Israel S., Korem M., Strahilevitz J., Tripodi M.F., Casillo R., Cuccurullo S., Dialetto G., Durante-Mangoni E., Irene M., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Sfeir J., Yasmine M., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., van der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Revest M., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Lum L.-N., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castan~eda X., Cervera C., Rio A., Falces C., Garcia-de-la-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Mun~oz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., de Alarcon A., Parra R., Alestig E., Johansson M., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., DiPersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Baloch K., Corey G.R., Dixon C.C., Fowler Jr. V.G., Harding T., Jones-Richmond M., Pappas P., Park L.P., Redick T., Stafford J., Anstrom K., Chu V.H., Karchmer A.W., Murdoch D.R., Sexton D.J., Wang A., Bayer A.S., Cabell C.H., Chu V., Durack D.T., Eykyn S., Hoen B., Moreillon P., Olaison L., Raoult D., Rubinstein E., Chambers S.T., Murdoch D., Bouza E., Hannan M.M., Kanafani Z.A., Lang S., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Altclas J., Silvia Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Konecny P., Lawrence R., Rees D., Feneley M.P., Harkness J., Jones P., Post J., Reinbott P., Ryan S., Gattringer R., Wiesbauer F., Andrade A.R., de Brito A.C.P., Guimara~es A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., de Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., de Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Morris A.M., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Barsic B., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Vincelj J., Freiberger T., Pol J., Zaloudikova B., Ashour Z., Kholy A.E., Mishaal M., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Sharma G., Tattevin P., Violette J., Chevalier F., Jeu A., Rusinaru D.M.D., Sorel C., Tribouilloy C., Bernard Y., Chirouze C., Leroy J., Plesiat P., Naber C., Mazaheri B., Neuerburg C., Athanasia S., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Francis J., Nair L., Thomas V., Venugopal K., Hannan M., Hurley J., Gilon D., Israel S., Korem M., Strahilevitz J., Tripodi M.F., Casillo R., Cuccurullo S., Dialetto G., Durante-Mangoni E., Irene M., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Sfeir J., Yasmine M., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., van der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., and Chipigina N.

Abstract

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p<0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p<0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p<0.01) and younger age (OR 0.62; CI 0.49-0.90; p<0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p<0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences. © 2013 Chambers et al.

Published
2013

75. HACEK Infective Endocarditis: Characteristics and Outcomes from a Large, Multi-National Cohort

Author

Abbate, A, Chambers, ST, Murdoch, D, Morris, A, Holland, D, Pappas, P, Almela, M, Fernandez-Hidalgo, N, Almirante, B, Bouza, E, Forno, D, del Rio, A, Hannan, MM, Harkness, J, Kanafani, ZA, Lalani, T, Lang, S, Raymond, N, Read, K, Vinogradova, T, Woods, CW, Wray, D, Corey, GR, Chu, VH, Clara, L, Sanchez, M, Nacinovich, F, Fernandez Oses, P, Ronderos, R, Sucari, A, Thierer, J, Casabe, J, Cortes, C, Altclas, J, Kogan, S, Spelman, D, Athan, E, Harris, O, Kennedy, K, Tan, R, Gordon, D, Papanicolas, L, Eisen, D, Grigg, L, Street, A, Korman, T, Kotsanas, D, Dever, R, Jones, P, Konecny, P, Lawrence, R, Rees, D, Ryan, S, Feneley, MP, Post, J, Reinbott, P, Gattringer, R, Wiesbauer, F, Andrade, AR, Passos de Brito, AC, Guimaraes, AC, Grinberg, M, Mansur, AJ, Siciliano, RF, Varejao Strabelli, TM, Campos Vieira, ML, de Medeiros Tranchesi, RA, Paiva, MG, Fortes, CQ, Ramos, ADO, Ferraiuoli, G, Golebiovski, W, Lamas, C, Santos, M, Weksler, C, Karlowsky, JA, Keynan, Y, Morris, AM, Rubinstein, E, Jones, SB, Garcia, P, Cereceda, M, Fica, A, Mella, RM, Barsic, B, Bukovski, S, Krajinovic, V, Pangercic, A, Rudez, I, Vincelj, J, Freiberger, T, Pol, J, Zaloudikova, B, Ashour, Z, El Kholy, A, Mishaal, M, Rizk, H, Aissa, N, Alauzet, C, Alla, F, Campagnac, C, Doco-Lecompte, T, Selton-Suty, C, Casalta, J-P, Fournier, P-E, Habib, G, Raoult, D, Thuny, F, Delahaye, F, Delahaye, A, Vandenesch, F, Donal, E, Donnio, PY, Michelet, C, Revest, M, Tattevin, P, Violette, J, Chevalier, F, Jeu, A, Dan, Rusinaru, Sorel, C, Tribouilloy, C, Bernard, Y, Chirouze, C, Hoen, B, Leroy, J, Plesiat, P, Naber, C, Neuerburg, C, Mazaheri, B, Athanasia, S, Giannitsioti, E, Mylona, E, Paniara, O, Papanicolaou, K, Pyros, J, Skoutelis, A, Sharma, G, Francis, J, Nair, L, Thomas, V, Venugopal, K, Hannan, M, Hurley, J, Gilon, D, Israel, S, Korem, M, Strahilevitz, J, Tripodi, MF, Casillo, R, Cuccurullo, S, Dialetto, G, Durante-Mangoni, E, Irene, M, Ragone, E, Utili, R, Cecchi, E, De Rosa, F, Imazio, M, Trinchero, R, Tebini, A, Grossi, P, Lattanzio, M, Toniolo, A, Goglio, A, Raglio, A, Ravasio, V, Rizzi, M, Suter, F, Carosi, G, Magri, S, Signorini, L, Baban, T, Kanafani, Z, Kanj, SS, Sfeir, J, Yasmine, M, Abidin, I, Tamin, SS, Martinez, ER, Nieto, GIS, van der Meer, JTM, Chambers, S, Murdoch, DR, Dragulescu, S, Ionac, A, Mornos, C, Butkevich, OM, Chipigina, N, Kirill, O, Vadim, K, Edathodu, J, Halim, M, Lum, L-N, Tan, R-S, Lejko-Zupanc, T, Logar, M, Mueller-Premru, M, Commerford, P, Commerford, A, Deetlefs, E, Hansa, C, Ntsekhe, M, Armero, Y, Azqueta, M, Castaneda, X, Cervera, C, Falces, C, Garcia-de-la-Maria, C, Fita, G, Gatell, JM, Marco, F, Mestres, CA, Miro, JM, Moreno, A, Ninot, S, Pare, C, Pericas, J, Ramirez, J, Rovira, I, Sitges, M, Anguera, I, Font, B, Guma, JR, Bermejo, J, Garcia Fernandez, MA, Gonzalez-Ramallo, V, Marin, M, Munoz, P, Pedromingo, M, Roda, J, Rodriguez-Creixems, M, Solis, J, Tornos, P, de Alarcon, A, Parra, R, Alestig, E, Johansson, M, Olaison, L, Snygg-Martin, U, Pachirat, O, Pachirat, P, Pussadhamma, B, Senthong, V, Casey, A, Elliott, T, Lambert, P, Watkin, R, Eyton, C, Klein, JL, Bradley, S, Kauffman, C, Bedimo, R, Crowley, AL, Douglas, P, Drew, L, Fowler, VG, Holland, T, Mudrick, D, Samad, Z, Sexton, D, Stryjewski, M, Wang, A, Lerakis, S, Cantey, R, Steed, L, Dickerman, SA, Bonilla, H, DiPersio, J, Salstrom, S-J, Baddley, J, Patel, M, Peterson, G, Stancoven, A, Afonso, L, Kulman, T, Levine, D, Rybak, M, Cabell, CH, Baloch, K, Dixon, CC, Harding, T, Jones-Richmond, M, Park, LP, Redick, T, Stafford, J, Anstrom, K, Bayer, AS, Karchmer, AW, Sexton, DJ, Chu, V, Durack, DT, Phil, D, Eykyn, S, Moreillon, P, Abbate, A, Chambers, ST, Murdoch, D, Morris, A, Holland, D, Pappas, P, Almela, M, Fernandez-Hidalgo, N, Almirante, B, Bouza, E, Forno, D, del Rio, A, Hannan, MM, Harkness, J, Kanafani, ZA, Lalani, T, Lang, S, Raymond, N, Read, K, Vinogradova, T, Woods, CW, Wray, D, Corey, GR, Chu, VH, Clara, L, Sanchez, M, Nacinovich, F, Fernandez Oses, P, Ronderos, R, Sucari, A, Thierer, J, Casabe, J, Cortes, C, Altclas, J, Kogan, S, Spelman, D, Athan, E, Harris, O, Kennedy, K, Tan, R, Gordon, D, Papanicolas, L, Eisen, D, Grigg, L, Street, A, Korman, T, Kotsanas, D, Dever, R, Jones, P, Konecny, P, Lawrence, R, Rees, D, Ryan, S, Feneley, MP, Post, J, Reinbott, P, Gattringer, R, Wiesbauer, F, Andrade, AR, Passos de Brito, AC, Guimaraes, AC, Grinberg, M, Mansur, AJ, Siciliano, RF, Varejao Strabelli, TM, Campos Vieira, ML, de Medeiros Tranchesi, RA, Paiva, MG, Fortes, CQ, Ramos, ADO, Ferraiuoli, G, Golebiovski, W, Lamas, C, Santos, M, Weksler, C, Karlowsky, JA, Keynan, Y, Morris, AM, Rubinstein, E, Jones, SB, Garcia, P, Cereceda, M, Fica, A, Mella, RM, Barsic, B, Bukovski, S, Krajinovic, V, Pangercic, A, Rudez, I, Vincelj, J, Freiberger, T, Pol, J, Zaloudikova, B, Ashour, Z, El Kholy, A, Mishaal, M, Rizk, H, Aissa, N, Alauzet, C, Alla, F, Campagnac, C, Doco-Lecompte, T, Selton-Suty, C, Casalta, J-P, Fournier, P-E, Habib, G, Raoult, D, Thuny, F, Delahaye, F, Delahaye, A, Vandenesch, F, Donal, E, Donnio, PY, Michelet, C, Revest, M, Tattevin, P, Violette, J, Chevalier, F, Jeu, A, Dan, Rusinaru, Sorel, C, Tribouilloy, C, Bernard, Y, Chirouze, C, Hoen, B, Leroy, J, Plesiat, P, Naber, C, Neuerburg, C, Mazaheri, B, Athanasia, S, Giannitsioti, E, Mylona, E, Paniara, O, Papanicolaou, K, Pyros, J, Skoutelis, A, Sharma, G, Francis, J, Nair, L, Thomas, V, Venugopal, K, Hannan, M, Hurley, J, Gilon, D, Israel, S, Korem, M, Strahilevitz, J, Tripodi, MF, Casillo, R, Cuccurullo, S, Dialetto, G, Durante-Mangoni, E, Irene, M, Ragone, E, Utili, R, Cecchi, E, De Rosa, F, Imazio, M, Trinchero, R, Tebini, A, Grossi, P, Lattanzio, M, Toniolo, A, Goglio, A, Raglio, A, Ravasio, V, Rizzi, M, Suter, F, Carosi, G, Magri, S, Signorini, L, Baban, T, Kanafani, Z, Kanj, SS, Sfeir, J, Yasmine, M, Abidin, I, Tamin, SS, Martinez, ER, Nieto, GIS, van der Meer, JTM, Chambers, S, Murdoch, DR, Dragulescu, S, Ionac, A, Mornos, C, Butkevich, OM, Chipigina, N, Kirill, O, Vadim, K, Edathodu, J, Halim, M, Lum, L-N, Tan, R-S, Lejko-Zupanc, T, Logar, M, Mueller-Premru, M, Commerford, P, Commerford, A, Deetlefs, E, Hansa, C, Ntsekhe, M, Armero, Y, Azqueta, M, Castaneda, X, Cervera, C, Falces, C, Garcia-de-la-Maria, C, Fita, G, Gatell, JM, Marco, F, Mestres, CA, Miro, JM, Moreno, A, Ninot, S, Pare, C, Pericas, J, Ramirez, J, Rovira, I, Sitges, M, Anguera, I, Font, B, Guma, JR, Bermejo, J, Garcia Fernandez, MA, Gonzalez-Ramallo, V, Marin, M, Munoz, P, Pedromingo, M, Roda, J, Rodriguez-Creixems, M, Solis, J, Tornos, P, de Alarcon, A, Parra, R, Alestig, E, Johansson, M, Olaison, L, Snygg-Martin, U, Pachirat, O, Pachirat, P, Pussadhamma, B, Senthong, V, Casey, A, Elliott, T, Lambert, P, Watkin, R, Eyton, C, Klein, JL, Bradley, S, Kauffman, C, Bedimo, R, Crowley, AL, Douglas, P, Drew, L, Fowler, VG, Holland, T, Mudrick, D, Samad, Z, Sexton, D, Stryjewski, M, Wang, A, Lerakis, S, Cantey, R, Steed, L, Dickerman, SA, Bonilla, H, DiPersio, J, Salstrom, S-J, Baddley, J, Patel, M, Peterson, G, Stancoven, A, Afonso, L, Kulman, T, Levine, D, Rybak, M, Cabell, CH, Baloch, K, Dixon, CC, Harding, T, Jones-Richmond, M, Park, LP, Redick, T, Stafford, J, Anstrom, K, Bayer, AS, Karchmer, AW, Sexton, DJ, Chu, V, Durack, DT, Phil, D, Eykyn, S, and Moreillon, P

Abstract

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p<0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p<0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p<0.01) and younger age (OR 0.62; CI 0.49-0.90; p<0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p<0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences.

Published
2013

76. Engagement of fatty acids with Toll-like receptor 2 drives interleukin-1beta production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis.

Author

Joosten, L.A.B., Netea, M.G., Mylona, E., Koenders, M.I., Malireddi, R.K., Oosting, M., Stienstra, R., Veerdonk, F.L. van de, Stalenhoef, A.F.H., Giamarellos-Bourboulis, E.J., Kanneganti, T.D., Meer, J.W.M. van der, Joosten, L.A.B., Netea, M.G., Mylona, E., Koenders, M.I., Malireddi, R.K., Oosting, M., Stienstra, R., Veerdonk, F.L. van de, Stalenhoef, A.F.H., Giamarellos-Bourboulis, E.J., Kanneganti, T.D., and Meer, J.W.M. van der

Abstract

01 november 2010, Contains fulltext : 88681.pdf (publisher's version ) (Closed access), OBJECTIVE: The concept that intraarticular crystals of uric acid by themselves trigger episodes of painful gouty arthritis is inconsistent with the clinical reality. Patients with large deposits of monosodium urate monohydrate (MSU) crystals (tophi) do not necessarily experience gouty attacks. In fact, it is the excessive consumption of food or alcohol that elicits the inflammation of the acute gout attack. The aim of this study was to identify the precise mechanism that initiates flares of gouty arthritis. METHODS: Human peripheral blood mononuclear cells (PBMCs) and murine macrophages were stimulated in vitro with MSU, free fatty acids (FFAs), or both in combination. Thereafter, production of interleukin-1beta (IL-1beta) and activation of caspase 1 were determined. Gouty arthritis was induced in mice with deficiencies in the genes for caspase 1, ASC, NALP3, or IL-1beta, and the lack of inflammasome activity during joint swelling or other joint pathologic features was investigated in these mice. RESULTS: MSU crystals had no biologic effects on PBMCs from healthy subjects, whereas the FFA C18:0 in the presence of MSU crystals induced the release of large amounts of IL-1beta following engagement of Toll-like receptor 2 (TLR-2). Interaction of FFAs, but not alcohol, with TLR-2 synergized with MSU crystals to induce an inflammatory reaction. An important event of MSU/FFA-induced acute joint inflammation is the activation of the inflammasome. MSU/FFA-induced release of IL-1beta was dependent on activation of caspase 1 and ASC, but surprisingly, not NALP3. CONCLUSION: The synergistic effect between FFAs and MSU crystals leads to ASC/caspase 1-driven IL-1beta release. This mechanism could explain how constitutionally derived metabolic events initiate attacks of gout via the induction of IL-1beta-mediated joint inflammation.

Published
2010

78. Non-Hodgkin's lymphoma and tuberculosis coexistence in the same organs: a report of two cases.

Author

Fanourgiakis, Panagiotis, Mylona, E, Androulakis, I I, Eftychiou, C, Vryonis, E, Georgala, Aspasia, Skoutelis, Athanasios, Aoun, Michel, Fanourgiakis, Panagiotis, Mylona, E, Androulakis, I I, Eftychiou, C, Vryonis, E, Georgala, Aspasia, Skoutelis, Athanasios, and Aoun, Michel

Abstract

Non-Hodgkin's lymphoma (NHL) may be preceded by chronic inflammatory diseases and furthermore has been related to immune deficiency. Tuberculosis (TB), on the other hand, is a chronic infectious disease whose presentation and reactivation is known to be promoted by cell mediated immunodeficiency. The coexistence of NHL and TB in the same organ is rare. We report two cases of NHL and TB coexistence in two different organs: cervical lymph nodes and kidney. The cases illustrate how misleading the concurrence of NHL and TB infection can be, delaying the diagnosis and treatment of either disease., Case Reports, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2008

83. Field performance of dry covers and limestone addition for acid generation control of Lavrion sulphide tailings, Greece.

Author

Mylona E., 6th ICARD International conference on acid rock drainage Cairns, Queensland 14-Jul-0314-Jul-03, Papassiopi N., Paspaliaris I., Xenidis A., Mylona E., 6th ICARD International conference on acid rock drainage Cairns, Queensland 14-Jul-0314-Jul-03, Papassiopi N., Paspaliaris I., and Xenidis A.

Abstract

The tailings have been deposited over an area of about ten hectares and the performance of three acid- generation control techniques was assessed under field conditions. These involved the application of two types of dry cover, a synthetic high-density polyethylene (HDPE) liner and a compacted clay layer with capillary barriers, and a low permeability hardpan layer formed at the tailings surface by limestone addition. A control test pad was also used and lysimeters were installed beneath the four plot areas. Monitoring over a period of 6 years showed that, due to the dry climate, a small amount of water percolates through the pyrites in the control area, corresponding to 20-25 mm/year. The water is highly acidic, pH 1.2, and contains a heavy load of contaminants such as 40 g/l Fe, 15 g/l Zn and 1.5 g/l As. The HDPE cover eliminated percolation of water into the material for a period of five years, after which the volume of leachates increased to values similar to those in the control plot. The amount of water collected in the clay cover was minimal, corresponding to approximately 5% of the drainage volume in the control area. In the plot involving limestone addition, the volume of drainage initially collected was almost double that of the control area. After three years, significant reduction in the amount of percolated water was observed, attributed to the formation of a hardpan layer at a depth of 40-80 cm from the surface., The tailings have been deposited over an area of about ten hectares and the performance of three acid- generation control techniques was assessed under field conditions. These involved the application of two types of dry cover, a synthetic high-density polyethylene (HDPE) liner and a compacted clay layer with capillary barriers, and a low permeability hardpan layer formed at the tailings surface by limestone addition. A control test pad was also used and lysimeters were installed beneath the four plot areas. Monitoring over a period of 6 years showed that, due to the dry climate, a small amount of water percolates through the pyrites in the control area, corresponding to 20-25 mm/year. The water is highly acidic, pH 1.2, and contains a heavy load of contaminants such as 40 g/l Fe, 15 g/l Zn and 1.5 g/l As. The HDPE cover eliminated percolation of water into the material for a period of five years, after which the volume of leachates increased to values similar to those in the control plot. The amount of water collected in the clay cover was minimal, corresponding to approximately 5% of the drainage volume in the control area. In the plot involving limestone addition, the volume of drainage initially collected was almost double that of the control area. After three years, significant reduction in the amount of percolated water was observed, attributed to the formation of a hardpan layer at a depth of 40-80 cm from the surface.

Published
2003

98. Rehabilitation of the flotation tailings dam in Lavrion. Part I: environmental characterisation and development studies. Part II: field application.

Author

Kontopoulos A., Clean technology for the mining industry Santiago, Chile 15-May-9617-May-96, Adam K., Komnitsas K., Mylona E., Xenidis A., Kontopoulos A., Clean technology for the mining industry Santiago, Chile 15-May-9617-May-96, Adam K., Komnitsas K., Mylona E., and Xenidis A.

Abstract

The tailings in the closed Greek dam are toxic and hazardous, with acid generation potential, EPA TCLP test toxicity, a high bioavailable fraction of heavy metals and poor quality of pore water. A cost-effective solution would be partial neutralisation of the top zone and the addition of a light earth cover. The neutralising action of limestone on pyrite was studied in a series of laboratory lysimeter tests. Acid generation and heavy metal release was significantly reduced by complete mixing, even when limestone was added at a rate much lower than stoichiometric. The top 0.8 m of tailings was mixed by repeated cross-ploughing with 200 kg/t of limestone sand, trucked from quarries 30-45 km away. A further 0.1 m compressed limestone layer was spread on top to add alkalinity, reduce slippage and impede root penetration. A 30 cm protective soil layer and 40 cm of topsoil were added. Total costs were Gr Dr3.2/m2., The tailings in the closed Greek dam are toxic and hazardous, with acid generation potential, EPA TCLP test toxicity, a high bioavailable fraction of heavy metals and poor quality of pore water. A cost-effective solution would be partial neutralisation of the top zone and the addition of a light earth cover. The neutralising action of limestone on pyrite was studied in a series of laboratory lysimeter tests. Acid generation and heavy metal release was significantly reduced by complete mixing, even when limestone was added at a rate much lower than stoichiometric. The top 0.8 m of tailings was mixed by repeated cross-ploughing with 200 kg/t of limestone sand, trucked from quarries 30-45 km away. A further 0.1 m compressed limestone layer was spread on top to add alkalinity, reduce slippage and impede root penetration. A 30 cm protective soil layer and 40 cm of topsoil were added. Total costs were Gr Dr3.2/m2.

Published
1996

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