Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling

BACKGROUND: Conventional cytogenetic and comparative genomic hybridization (CGH) studies in brain malignancies have shown that glioblastoma multiforme (GBM) is characterized by complex structural and numerical alterations. However, the limited resolution of these techniques has precluded the precise identification of detailed specific gene copy number alterations. RESULTS: We performed a genome-wide survey of gene copy number changes in 20 primary GBMs by CGH on cDNA microarrays. A novel amplicon at 4p15, and previously uncharacterized amplicons at 13q32-34 and 1q32 were detected and are analyzed here. These amplicons contained amplified genes not previously reported. Other amplified regions containg well-known oncogenes in GBMs were also detected at 7p12 (EGFR), 7q21 (CDK6), 4q12 (PDGFRA), and 12q13-15 (MDM2 and CDK4). In order to identify the putative target genes of the amplifications, and to determine the changes in gene expression levels associated with copy number change events, we carried out parallel gene expression profiling analyses using the same cDNA microarrays. We detected overexpression of the novel amplified genes SLA/LP and STIM2 (4p15), and TNFSF13B and COL4A2 (13q32-34). Some of the candidate target genes of amplification (EGFR, CDK6, MDM2, CDK4, and TNFSF13B) were tested in an independent set of 111 primary GBMs by using FISH and immunohistological assays. The novel candidate 13q-amplification target TNFSF13B was amplified in 8% of the tumors, and showed protein expression in 20% of the GBMs. CONCLUSION: This high-resolution analysis allowed us to propose novel candidate target genes such as STIM2 at 4p15, and TNFSF13B or COL4A2 at 13q32-34 that could potentially contribute to the pathogenesis of these tumors and which would require futher investigations. We showed that overexpression of the amplified genes could be attributable to gene dosage and speculate that deregulation of those genes could be important in the development and progression of GBM. Our findings highlight the important influence in GBM of signaling pathways such as the PI3K/AKT, consistent with the invasive features of this tumor

Diagnostic accuracy of 18F-FDG PET/CT in infective endocarditis and implantable cardiac electronic device infection: A cross-sectional study.

Early diagnosis of infective endocarditis (IE) is based on the yielding of blood cultures and echocardiographic findings. However, they have limitations and sometimes the diagnosis is inconclusive, particularly in patients with prosthetic valves (PV) and implantable cardiac electronic devices (ICED). The primary aim of this study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with suspected IE an ICED infection. METHODS: A prospective study with 80 consecutive patients with suspected IE and ICED infection (65 men and 15 women with a mean age of 68±13 years old) between June 2013 and May 2015 was performed in our hospital. The inclusion criteria was clinically suspected IE and ICED infection at the following locations: native valve (NV) (n = 21), PV (n = 29) or ICED (n = 30) [(automatic implantable defibrillator (n = 11) or pacemaker (n = 19)]. Whole-body 18F-FDG PET/CT with a myocardial uptake suppression protocol with unfractionated heparin was performed in all patients. The final diagnosis of infection was established by the IE study Group according to the clinical, echocardiographic and microbiological findings. RESULTS: A final diagnosis of infection was confirmed in 31 patients: NV (n = 6), PV (n = 12) and ICED (n = 13). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for 18F-FDG PET/CT was 82%, 96%, 94% and 87%, respectively. 18F-FDG PET/CT was false negative in all cases with infected NV. 18F-FDG PET/CT was able to reclassify 63/70 (90%) patients initially classified as possible IE by modified Duke criteria. In 18/70 cases 18F-FDG PET/CT changed possible to definite IE (26%) and in 45/70 cases changed possible to rejected IE (64%). Additionally, 18F-FDG PET/CT identified 8 cases of septic embolism and 3 colorectal cancer in patients with final diagnosis of IE. CONCLUSION: 18F-FDG PET/CT proved to be a useful diagnostic tool in suspected IE and ICED infection and should be included in the diagnostic algorithm for early diagnosis. 18F-FDG PET/CT is not useful in the diagnosis of IE in NV, but should be also considered in the initial assessment of this complex scenario to rule out extracardiac complications and possible neoplasms

Experience of parents who have suffered a perinatal death in two Spanish hospitals: a qualitative study

Background: Perinatal grief is a process that affects families in biological, psychological, social and spiritual terms. It is estimated that every year there are 2.7 million perinatal deaths worldwide and 4.43 deaths for every 1000 births in Spain. The aim of this study is to describe and understand the experiences and perceptions of parents who have suffered a perinatal death. Methods: A qualitative study based on Gadamer’s hermeneutic phenomenology. The study was conducted in two hospitals in the South of Spain. Thirteen mothers and eight fathers who had suffered a perinatal death in the 5 years prior to the study participated in this study. In-depth interviews were carried out for data collection. Inductive analysis was used to find themes based on the data. Results: Eight sub-themes emerged, and they were grouped into three main themes: ‘Perceiving the threat and anticipating the baby’s death: “Something is going wrong in my pregnancy”’; ‘Emotional outpouring: the shock of losing a baby and the pain of giving birth to a stillborn baby’; “We have had a baby”: The need to give an identity to the baby and legitimise grief’. Conclusion: The grief suffered after a perinatal death begins with the anticipation of the death, which relates to the mother’s medical history, symptoms and premonitions. The confirmation of the death leads to emotional shock, characterised by pain and suffering. The chance to take part in mourning rituals and give the baby the identity of a deceased baby may help in the grieving and bereavement process. Having empathy for the parents and notifying them of the death straightaway can help ease the pain. Midwives can help in the grieving process by facilitating the farewell rituals, accompanying the family, helping in honouring the memory of the baby, and supporting parents in giving the deceased infant an identity that makes them a family member

Diagnostic accuracy of 18F-FDG PET/CT in infective endocarditis and implantable cardiac electronic device infection: A cross-sectional study.

Early diagnosis of infective endocarditis (IE) is based on the yielding of blood cultures and echocardiographic findings. However, they have limitations and sometimes the diagnosis is inconclusive, particularly in patients with prosthetic valves (PV) and implantable cardiac electronic devices (ICED). The primary aim of this study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with suspected IE an ICED infection. METHODS: A prospective study with 80 consecutive patients with suspected IE and ICED infection (65 men and 15 women with a mean age of 68±13 years old) between June 2013 and May 2015 was performed in our hospital. The inclusion criteria was clinically suspected IE and ICED infection at the following locations: native valve (NV) (n = 21), PV (n = 29) or ICED (n = 30) [(automatic implantable defibrillator (n = 11) or pacemaker (n = 19)]. Whole-body 18F-FDG PET/CT with a myocardial uptake suppression protocol with unfractionated heparin was performed in all patients. The final diagnosis of infection was established by the IE study Group according to the clinical, echocardiographic and microbiological findings. RESULTS: A final diagnosis of infection was confirmed in 31 patients: NV (n = 6), PV (n = 12) and ICED (n = 13). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for 18F-FDG PET/CT was 82%, 96%, 94% and 87%, respectively. 18F-FDG PET/CT was false negative in all cases with infected NV. 18F-FDG PET/CT was able to reclassify 63/70 (90%) patients initially classified as possible IE by modified Duke criteria. In 18/70 cases 18F-FDG PET/CT changed possible to definite IE (26%) and in 45/70 cases changed possible to rejected IE (64%). Additionally, 18F-FDG PET/CT identified 8 cases of septic embolism and 3 colorectal cancer in patients with final diagnosis of IE. CONCLUSION: 18F-FDG PET/CT proved to be a useful diagnostic tool in suspected IE and ICED infection and should be included in the diagnostic algorithm for early diagnosis. 18F-FDG PET/CT is not useful in the diagnosis of IE in NV, but should be also considered in the initial assessment of this complex scenario to rule out extracardiac complications and possible neoplasms

Diagnostic accuracy of 18F-FDG PET/CT in infective endocarditis and implantable cardiac electronic device infection: A cross-sectional study.

Early diagnosis of infective endocarditis (IE) is based on the yielding of blood cultures and echocardiographic findings. However, they have limitations and sometimes the diagnosis is inconclusive, particularly in patients with prosthetic valves (PV) and implantable cardiac electronic devices (ICED). The primary aim of this study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with suspected IE an ICED infection. METHODS: A prospective study with 80 consecutive patients with suspected IE and ICED infection (65 men and 15 women with a mean age of 68±13 years old) between June 2013 and May 2015 was performed in our hospital. The inclusion criteria was clinically suspected IE and ICED infection at the following locations: native valve (NV) (n = 21), PV (n = 29) or ICED (n = 30) [(automatic implantable defibrillator (n = 11) or pacemaker (n = 19)]. Whole-body 18F-FDG PET/CT with a myocardial uptake suppression protocol with unfractionated heparin was performed in all patients. The final diagnosis of infection was established by the IE study Group according to the clinical, echocardiographic and microbiological findings. RESULTS: A final diagnosis of infection was confirmed in 31 patients: NV (n = 6), PV (n = 12) and ICED (n = 13). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for 18F-FDG PET/CT was 82%, 96%, 94% and 87%, respectively. 18F-FDG PET/CT was false negative in all cases with infected NV. 18F-FDG PET/CT was able to reclassify 63/70 (90%) patients initially classified as possible IE by modified Duke criteria. In 18/70 cases 18F-FDG PET/CT changed possible to definite IE (26%) and in 45/70 cases changed possible to rejected IE (64%). Additionally, 18F-FDG PET/CT identified 8 cases of septic embolism and 3 colorectal cancer in patients with final diagnosis of IE. CONCLUSION: 18F-FDG PET/CT proved to be a useful diagnostic tool in suspected IE and ICED infection and should be included in the diagnostic algorithm for early diagnosis. 18F-FDG PET/CT is not useful in the diagnosis of IE in NV, but should be also considered in the initial assessment of this complex scenario to rule out extracardiac complications and possible neoplasms