Ramponi F, Puranik R, Wilson MK, Bannon PG
Eur J Cardiothorac Surg 2012 Nov;42(5):904
PMID: 22723616
Serum biomarkers of neurologic injury in cardiac operations
Seco M, Edelman JJ, Wilson MK, Bannon PG, Vallely MP
Ann. Thorac. Surg. 2012 Sep;94(3):1026-33
PMID: 22857981
Abstract
Assessment of subtle neurocognitive decline after surgical procedures has been hampered by heterogeneous testing techniques and a lack of reproducibility. This review summarizes the sensitivity and specificity of biomarkers of neurologic injury to determine whether they can be applied in the postoperative period to accurately predict neurocognitive decline. Creatine kinase-brain type, neuron-specific enolase, and S100B can be released into serum during operations by extracranial sources. Glial fibrillary acidic protein is a sensitive marker, and there are extracranial sources that are antigenically different from the brain-derived form. Serum levels of tau protein after acute neurologic injury do not reliability correlate with incidence.
Rare non-synonymous variations in the transcriptional activation domains of GATA5 in bicuspid aortic valve disease
Padang R, Bagnall RD, Richmond DR, Bannon PG, Semsarian C
J. Mol. Cell. Cardiol. 2012 Aug;53(2):277-81
PMID: 22641149
Abstract
Bicuspid aortic valve (BAV) is the commonest congenital heart disease and a highly heritable trait; however, only the NOTCH1 gene has been linked to limited cases of BAV in humans. Recently, the transcription factor GATA5 has been shown to have an essential role in aortic valve development, and targeted deletion of Gata5 in mice is associated with partially penetrant BAV formation. Here, we investigated the relationship between GATA5 gene variants and BAV with its associated aortopathy. One hundred unrelated individuals with confirmed BAV were prospectively recruited. Following collection of clinical information and DNA extraction, the coding regions and splice signal sequences of the GATA5 gene were screened for sequence variations. The clinical characteristics of the cohort included a male predominance (77%), mean age of diagnosis 29 ± 22 years, associated aortopathy in 59% and positive family history for BAV in 13%. Genetic analysis identified the presence of 4 rare non-synonymous variations within the GATA5 transcriptional activation domains, namely Gln3Arg, Ser19Trp, Tyr142His and Gly166Ser, occurring in one patient each. Gln3Arg and Tyr142His substitutions affect highly conserved and functionally relevant residues, and are likely to impact on the transcriptional activation of GATA5 target regions. A novel Ser19Trp variation was identified at a highly conserved amino acid residue in one patient, while the Gly166Ser variant was found in a familial case of BAV and associated aortopathy. Rare non-synonymous variations in the functionally important GATA5 transcriptional activation domains may be important in the pathogenesis of BAV disease in humans.
Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma
Kirschner MB, Cheng YY, Badrian B, Kao SC, Creaney J, Edelman JJ, Armstrong NJ, Vallely MP, Musk AW, Robinson BW, McCaughan BC, Klebe S, Mutsaers SE, van Zandwijk N, Reid G
J Thorac Oncol 2012 Jul;7(7):1184-91
PMID: 22617246
Abstract
INTRODUCTION: We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a biomarker for malignant mesothelioma (MM).
METHODS: Using miRNA microarrays, we profiled plasma samples from MM patients and healthy controls. miRNAs with significantly different abundance between cases and controls were validated in a larger series of MM patients and in an independent series of MM patients using quantitative real-time polymerase chain reaction. Levels of candidate miRNAs were also quantified in MM tumor samples.
RESULTS: We compared cell-free miRNA profiles in plasma from MM patients with healthy controls. Reviewing 90 miRNAs previously reported to be associated with MM, we found that the levels of two miRNAs, miR-29c* and miR-92a, were elevated in plasma samples from MM patients. In addition, we identified 15 novel miRNAs present at significantly higher levels in the plasma of MM patients. Further analysis of candidate miRNAs by real time-quantitative polymerase chain reaction confirmed that one of them, miR-625-3p, was present in significantly higher concentration in plasma/serum from MM patients and was able to discriminate between cases and controls, in both the original and the independent series of patients. MiR-625-3p was also found to be up-regulated in tumor specimens from a group of 18 MM patients, who underwent extrapleural pneumonectomy.
CONCLUSION: Our data confirm the potential of miR-29c* and miR-92a as candidate tumor markers and reveal that miR-625-3p is a promising novel diagnostic marker for MM.
Importance of gender in diffuse malignant peritoneal mesothelioma
Cao C, Yan TD, Deraco M, Elias D, Glehen O, Levine EA, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH,
Ann. Oncol. 2012 Jun;23(6):1494-8
PMID: 22056853
Abstract
BACKGROUND: Combined therapy involving cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has been shown to improve survival outcomes for patients with diffuse malignant peritoneal mesothelioma (DMPM). The present study aims to investigate gender as a potential prognostic factor on overall survival.
PATIENTS AND METHODS: Over a period of two decades, 294 patients who underwent CRS and perioperative intraperitoneal chemotherapy were selected from a large multi-institutional registry to assess the prognostic significance of gender on overall survival.
RESULTS: Female patients were shown to have a significantly improved survival outcome than male patients (P < 0.001). Staging according to a recently proposed tumor-node-metastasis categorization system was significant in both genders. Older female patients had significantly worse survival than younger female patients (P = 0.019), a finding that was absent in male patients. Female patients with low-stage disease were found to have a very favorable long-term outcome after combined treatment.
CONCLUSIONS: Gender has demonstrated a significant impact on overall survival for patients with DMPM after CRS and perioperative intraperitoneal chemotherapy. An improved understanding of the role of estrogen in the pathogenesis of DMPM may improve the prognostication of patients and determine the role of adjuvant hormonal treatment in the future.
Letter by Edelman et al regarding article, “Second internal thoracic artery versus radial artery in coronary artery bypass grafting: a long-term, propensity score-matched follow-up study”
Edelman JJ, Bannon PG, Vallely MP
Circulation 2012 May;125(17):e630; author reply e631
PMID: 22547761
Abstract
Prospective Registry On Mesothelioma Peritonei Treatment (PROMPT): study design and rationale
Cao C, Yan TD, Morris DL, van der Speeten K, Laurberg S, Glehen O, Link K, Piso P, Tentes AA, Deraco M, Larsen SG, Kecmanovic D, Bayón LG, Melero JT, González-Moreno S, Mahteme H, Gertsch P, Moran B, Esquivel J, Alexander R, Levine EA, Sugarbaker PH
Tumori 2012 Jan-Feb;98(1):166-71
PMID: 22495719
