Lower Patient Survival Research Articles

Imaging findings of recurrent pancreatic cancer following resection.

Pancreatic cancer is a challenging malignancy to treat, largely due to aggressive regional involvement, early systemic dissemination, high recurrence rate, and subsequent low patient survival. Generally, 15-20% of newly diagnosed pancreatic cancers are candidates for possible curative resection. Eighty percent of these patients, however, will experience locoregional or distant recurrence in first 2years. Although there is no strong evidence-based guideline for optimal surveillance after pancreatic cancer resection, careful comparison of surveillance follow-up multi-detector CT (MDCT) studies with a postoperative baseline MDCT examination aids detection of early recurrent pancreatic cancer. In this review article, we describe imaging findings suggestive of recurrent pancreatic cancer and review routine and alternative imaging options.

Hypermethylation of MEG3 promoter correlates with inactivation of MEG3 and poor prognosis in patients with retinoblastoma

BackgroundIn our previous study, we revealed that MEG3 was a tumor suppressor gene in retinoblastoma and inhibited proliferation of retinoblastoma cells by regulating the activity of the Wnt/β-catenin pathway. Here, we further explored the mechanism of MEG3 inactivation in retinoblastoma.MethodsMSP and qRT-PCR were performed to detect the methylation status of MEG3 promoter and levels of MEG3 expression, respective. To further explore relationship between MEG3 expression and epigenetic modifications, 5-Aza-CdR was used to interfere with DNA methylation. In addition, we evaluated proliferation, apoptosis and the expression of β-catenin via CCK-8, flow cytometric analysis and western blot analysis, respective.ResultsHypermethylation of MEG3 promoter was observed more frequently in retinoblastoma tissues and was highly associated with low MEG3 expression and poor survival of retinoblastoma patients. We also provided evidence demonstrating that hypermethylation of MEG3 promoter depressed MEG3 expression, promoted proliferation, inhibited apoptosis and increased β-catenin expression of retinoblastoma cells in vitro.ConclusionsOur present study indicates that promoter silencing by hypermethylation may account for the loss of MEG3 expression and predict poor prognosis.

Endothelial-derived interleukin-6 induces cancer stem cell motility by generating a chemotactic gradient towards blood vessels.

Recent evidence suggests that the metastatic spread of head and neck squamous cell carcinomas (HNSCC) requires the function of cancer stem cells endowed with multipotency, self-renewal, and high tumorigenic potential. We demonstrated that cancer stem cells reside in perivascular niches and are characterized by high aldehyde dehydrogenase (ALDH) activity and high CD44 expression (ALDHhighCD44high) in HNSCC. Here, we hypothesize that endothelial cell-secreted interleukin-6 (IL-6) contributes to tumor progression by enhancing the migratory phenotype and survival of cancer stem cells. Analysis of tissue microarrays generated from the invasive fronts of 77 HNSCC patients followed-up for up to 11 years revealed that high expression of IL-6 receptor (IL-6R) (p=0.0217) or co-receptor gp130 (p=0.0422) correlates with low HNSCC patient survival. We observed that endothelial cell-secreted factors induce epithelial to mesenchymal transition (EMT) and enhance invasive capacity of HNSCC cancer stem cells. Conditioned medium from CRISPR/Cas9-mediated IL-6 knockout primary human endothelial cells is less chemotactic for cancer stem cells in a microfluidics-based system than medium from control endothelial cells (p<0.05). Blockade of the IL-6 pathway with a humanized anti-IL-6R antibody (tocilizumab) inhibited endothelial cell-induced motility in vitro and decreased the fraction of cancer stem cells in vivo. Notably, xenograft HNSCC tumors vascularized with IL-6-knockout endothelial cells exhibited slower tumor growth and smaller cancer stem cell fraction. These findings demonstrate that endothelial cell-secreted IL-6 enhances the motility and survival of highly tumorigenic cancer stem cells, suggesting that endothelial cells can create a chemotactic gradient that enables the movement of carcinoma cells towards blood vessels.

The biology and mathematical modelling of glioma invasion: a review.

Adult gliomas are aggressive brain tumours associated with low patient survival rates and limited life expectancy. The most important hallmark of this type of tumour is its invasive behaviour, characterized by a markedly phenotypic plasticity, infiltrative tumour morphologies and the ability of malignant progression from low- to high-grade tumour types. Indeed, the widespread infiltration of healthy brain tissue by glioma cells is largely responsible for poor prognosis and the difficulty of finding curative therapies. Meanwhile, mathematical models have been established to analyse potential mechanisms of glioma invasion. In this review, we start with a brief introduction to current biological knowledge about glioma invasion, and then critically review and highlight future challenges for mathematical models of glioma invasion.

LncRNA H19 is a major mediator of doxorubicin chemoresistance in breast cancer cells through a cullin4A-MDR1 pathway.

Development of chemoresistance is a persistent problem during cancer treatment. Long non-coding RNAs (LncRNAs) are currently emerging as an integral functional component of the human genome and as critical regulators of cancer development and progression. In the present study, we investigated the role and molecular mechanism of H19 lncRNA in chemoresistance development by using doxorubicin (Dox) resistance in breast cancer cells as a model system. H19 lncRNA expression was significantly increased in anthracycline-treated and Dox-resistant MCF-7 breast cancer cells. This H19 overexpression was contributed to cancer cell resistance to anthracyclines and paclitaxel as knockdown of H19 lncRNA by a specific H19 shRNA in Dox-resistant cells significantly improved the cell sensitivity to anthracyclines and paclitaxel. Furthermore, gene expression profiling analysis revealed that a total of 192 genes were associated with H19-mediated Dox resistance. These genes were enriched in multiple KEGG pathways that are related to chemoresistance. Using genetic and pharmacological approaches, we demonstrated that MDR1 and MRP4 were major effectors of H19-regulated Dox resistance in breast cancer cells as MDR1 and MRP4 expression was markedly elevated in Dox-resistant cells while dramatically reduced when H19 was knocked down. Moreover, we found that CUL4A, an ubiquitin ligase component, was a critical factor bridging H19 lncRNA to MDR1 expression, and a high tumor CUL4A expression was associated with low survival in breast cancer patients treated with chemotherapy. These data suggest that H19 lncRNA plays a leading role in breast cancer chemoresistance, mediated mainly through a H19-CUL4A-ABCB1/MDR1 pathway.

Clinicopathological pattern and outcome of pediatric malignant ovarian germ cell tumors: South Egypt Cancer Institute experience.

Malignant ovarian germ cell tumors (MOGCTs) are rare and represent 1-1.5% of all cancers in children and adolescents. The aim of this study is to analyze the clinicopathological pattern at presentation and management and outcome of MOGCTs in children and adolescents. Retrospective study included all girls diagnosed with MOGCTs between January 2005 and January 2015 in Pediatric and Surgical Oncology Departments at South Egypt Cancer Institute, Assiut University. Data were collected from patients' records including initial presentation, diagnosis (tumor markers and imaging), surgical staging and pathologic types. Management (surgical and chemotherapy details) and outcomes were also analyzed. Forty girls aged between 4 to 17years (mean age of 9.5years) with diagnosis of MOGCTs during study period were included. The most common presenting symptoms and signs were abdominal swelling, abdominal pain, and pelvic mass. Precocious puberty was noted in two patients. Surgical interventions in most patients were unilateral salpingo-oophorectomy (n=20). Early stages I and II were reported in 15 and 12 patients respectively, while 10 patients had stage-III disease and 3 patients had stage IV. Yolk sac tumors were reported in 27.5% of patients. All patients were treated with platinum based chemotherapy. The 7-year overall survival was higher for patients with early stages (I and II) compared with advanced stages (III and IV) (100% versus 30.8% respectively. Early presentation with appropriate management using fertility sparing surgery and platinum-based chemotherapy provides excellent survival with fertility preservation in children and adolescents. Based on the lower survival of patients with advanced disease, efforts should focus on increasing the awareness in the community of the importance of early diagnosis of ovarian tumors. II (retrospective study).

Prognostic relevance of NG2/CSPG4, CD44 and Ki-67 in patients with glioblastoma.

Neuron-glial antigen 2 (NG2, also known as CSPG4) and hyaluronic acid receptor CD44 are chondroitin sulphate proteoglycans actively involved in brain development and its malignant transformation. Here, we aimed to compare prognostic significances of NG2, CD44 and Ki-67 expression in glioblastoma multiforme patients. Totally, 45 tissue samples and 83 paraffin-embedded tissues for 75 patients were analysed. The prognostic values of the genes were analysed using Kaplan-Meier survival curves. Grade III gliomas showed 2-fold difference in NG2 expression between anaplastic astrocytoma and oligoastrocytoma (10.1 ± 3.5 and 25.5 ± 14.5, respectively). For grade IV gliomas, upregulated NG2 expression (21.0 ± 6.8) was associated with poor glioblastoma multiforme prognosis (overall survival < 12 months) compared with glioblastoma multiforme patients with good prognosis (4.4 ± 3.2; overall survival > 12 months). Multivariate survival analysis using Cox proportional hazards model confirmed that high NG2 expression was associated with low survival of the patients (hazard ratio: 3.43; 95% confidence interval: 1.18-9.93; p = 0.02), whereas age (hazard ratio: 1.02; 95% confidence interval: 0.96-1.09; p = 0.42), tumour resection (hazard ratio: 1.03; 95% confidence interval: 0.98-1.08; p = 0.25) and sex (hazard ratio: 0.62; 95% confidence interval: 0.21-1.86; p = 0.40) did not show significant association with prognosis. Although the positive correlation was shown for NG2 and CD44 expression in the glioblastomas (Pearson coefficient = 0.954), Kaplan-Meier and multivariate survival analyses did not revealed a significant association of the increased CD44 expression (hazard ratio: 2.18; 95% confidence interval: 0.50-9.43; p = 0.30) or high Ki-67 proliferation index (hazard ratio: 1.10; 95% confidence interval: 1.02-1.20; p = 0.02) with the disease prognosis. The results suggest that upregulation of NG2/CSPG4 rather than changes in CD44 or Ki-67 expression is associated with low overall survival in glioblastoma multiforme patients, supporting NG2/CSPG4 as a potential prognostic marker in glioblastoma.

Short-term and long-term results of endovascular and open repair of abdominal aortic aneurysms in Germany

BackgroundEndovascular aortic repair (EVAR) has emerged as a standard of care for abdominal aortic aneurysm (AAA) repair. However, real-world evidence to compare this technology to open aortic repair (OAR) is limited. Major gaps exist related to long-term outcomes of therapies worldwide. MethodsHealth insurance claims data of Germany's third largest insurance provider, DAK-Gesundheit, were used to determine outcomes after interventions for intact AAA (iAAA) and ruptured AAA (rAAA). The study included patients operated on between October 2008 and April 2015. ResultsIncluded were 5509 patients (3627 EVAR and 1859 OAR). Median follow-up was 2.44 years (range, 0-6.46 years). The in-hospital mortality was lower after EVAR compared with OAR for both iAAA (1.2% vs 5.4%) and rAAA (26.1% vs 42%; P < .001). Postoperative length of stay and occurrence of complications were also lower after EVAR. The in-hospital mortality benefits of EVAR were most prominent in octogenarians (iAAA: EVAR, 2.2%; OAR, 18.2%; rAAA: EVAR, 34.4%; OAR, 62.3%; P < .001). However, the early survival benefit after EVAR reversed at ∼1.5 years, and Cox proportional hazard models revealed no differences in overall survival between EVAR and OAR. Landmark analysis focusing on patients surviving the procedure has shown lower survival in patients with EVAR. ConclusionsIn this largest European investigation to date using health insurance claims data, we found that in-hospital outcomes in Germany favor EVAR, which is comparable to findings reported in the United States and the United Kingdom. Trends toward lower long-term survival after EVAR after discharge are important and require future research and reflection.

Abstract 5906: TIMP-1 expression is inversely correlated with miRNA125a-5p and let-7e in non-small-cell lung carcinoma

Abstract Epigenetic alterations are emerging as significant elements in our understanding the biology of lung cancer which remains the leading cause of cancer deaths worldwide. In earlier studies we have shown that tissue inhibitor of metalloproteinase 1 (TIMP-1) overexpression in NSCLC cells results in aggressive tumors in mice. We have also demonstrated TIMP-1’s anti-apoptotic activity in these cells. It is well documented that miRNAs are involved in many physiological and neoplastic processes, including apoptosis. We have previously shown that knocking down TIMP-1 in A549 NSCLC cells alters the miRNA profile in these cells with upregulation of miR-125a-5p. Subsequently, we have identified that miR let-7e is also upregulated in TIMP-1 KD clones. The present study is focused on confirming the involvement of miR-125a-5p with TIMP-1 by using mimics and antagomirs of 125a-5p. Furthermore, we have sought to validate this relationship in vivo by examining these patterns in clinical samples. We added mimics of miR-125a-5p into the parental A549 cells, which resulted in down regulation of TIMP-1 levels. We were then able to rescue TIMP-1 downregulation by adding antagomirs of miR-125a-5p to the same cells. MiR-125a-5p binding sites were identified in TIMP-1 3’ UTR and using luciferase assay, we have confirmed that TIMP-1 is indeed a bona fide target of miR-125a-5p. Translational studies were carried out using archived NSCLC adenocarcinoma tissues from the Surgical Pathology archives at AU Medical Center. We first measured expression level of TIMP-1 by RT-PCR in 20 tumors and paired normal adjacent tissues and divided the samples into 2 groups, those with low and high TIMP-1 expression levels. Tissues were then interrogated for TIMP-1 and miR-125a-5p and let- 7e miRNA expression using chromogenic in situ hybridization. We identified negative correlation pattern between tumor and paired normal adjacent tissue samples. Generally, TIMP-1 was highly expressed in the tumor region, while miRNA expression was relatively decreased when compared with adjacent normal tissues. miRNA 125a-5p and let- 7e are known tumor suppressors in NSCLC. Analyzing secondary data (adenocarcinoma) by KM plotter we found that high TIMP1 correlated with lower patient survival with a hazard ratio of 3.17 (2.3-4.37) and a log rank p value of 8.1e-14. These studies provide additional clarity and further extend our understanding of the relationship between these miRNA families and TIMP-1 expression. Citation Format: Ammar Kutiyanawalla, Sampa Ghoshal-Gupta, Byung R. Lee, Ashis Mondal, Ravindra Kolhe, Amyn M. Rojiani, Mumtaz V. Rojiani. TIMP-1 expression is inversely correlated with miRNA125a-5p and let-7e in non-small-cell lung carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5906. doi:10.1158/1538-7445.AM2017-5906

Abstract 1913: SOX9 regulates cancer stem-like cells in non-small cell lung cancer

Abstract Lung cancer is the leading cause of cancer death worldwide in both men and women, every year killing more people than breast, prostate and colon cancers combined. Drug/radiation resistance and tumor relapse contribute to low patient survival, which has largely been attributed to the acquisition of stem-like cells (CSCs), or tumor initiating cells. Moreover, conventional therapies are not effective against CSCs. This signifies the need to identify mechanisms of CSC regulation which could lead to the discovery of CSC-specific drug targets and the development of more effective drug therapies. An embryonic transcription factor SOX9 has been implicated in CSC regulation in a number of cancer types, but little is known about its role in non-small cell lung cancer (NSCLC). We demonstrated that high SOX9 expression correlates with poor survival in lung cancer patients by analyzing The Cancer Genome Atlas (TCGA) data. We hypothesized that SOX9 plays a key role in tumor progression and chemoresistance by upregulating CSCs in NSCLC. To test this hypothesis, SOX9 expression was stably or transiently knocked down in NSCLC cells, and their effects on CSC formation and biomarkers, and on drug resistance were investigated. Our results showed that SOX9 knockdown decreased the number of tumor spheres in NSCLC cell lines. Furthermore, SOX9 knockdown downregulated the expression and activity of stem cell marker ALDH1A1 as determined by Western blot and flow cytometric assays. Consistent with this finding, overexpression of SOX9 in non-cancer lung epithelial Beas-2B cells elevated tumor sphere formation, supporting the role of SOX9 in CSC regulation. Analysis of the soft agar colony formation assay further showed that SOX9 knockdown inhibited anchorage-independent growth in NSCLC cells. More importantly, SOX9 knockdown resulted in an increased sensitivity of the cells to a chemotherapeutic drug cisplatin, whereas SOX9 overexpression decreased it. Together, our results indicate an important role of SOX9 in the regulation of CSCs in NSCLC and suggest its potential utility as a drug target for chemoresistant lung cancer. Citation Format: Maria Voronkova, Sudjit Luanpitpong, Heimo Riedel, Yon Rojanasakul. SOX9 regulates cancer stem-like cells in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1913. doi:10.1158/1538-7445.AM2017-1913

Validating a Lower Urine Output Criteria in Predicting Death in Critically Ill Patients

Introduction: Urine output provides a rapid estimate for kidney function, and its use has been incorporated in the diagnosis of acute kidney injury. However, not many studies had validated its use compared to the plasma creatinine. It has been showed that the ideal urine output threshold for prediction of death or the need for dialysis was 0.3 ml/kg/h. We aim to assess this threshold in our local ICU population. Methods: This was a secondary analysis of an observational study done in critically ill patients. Hourly urine output data was collected, and a moving average of 6-hourly urine output was calculated over the first 48 hours of ICU admission. AKIuo was defined if urine output ≤ 0.5 ml/kg/h, and UO0.3 was defined as urine output ≤ 0.3 ml/kg/h. Results: 143 patients were recruited into the study, of these, 87 (61%) had AKIuo, and 52 (36%) had UO0.3. The AUC of AKIuo in predicting death was 0.62 (0.51 to 0.72), and UO0.3 was 0.66 (0.55 to 0.77). There was lower survival in patients with AKIuo and UO0.3 compared to those without (p=0.01, and 0.001, respectively). However, only UO0.3 but not AKIuo independently predicted death (HR 2.44 (1.15 to 5.18). Conclusions: A threshold of 6 hourly urine output of 0.3 ml/kg/h but not 0.5 ml/kg/h independently predictive of death. This support previous finding of a lower threshold of urine output criteria for optimal prediction.

Subclinical Antibody-Mediated Rejection

Subclinical Antibody-Mediated Rejection

High Total 68Ga-DOTATATE-Avid Tumor Volume (TV) is associated with low progression-free survival and high disease-specific mortality rate in patients with neuroendocrine tumors

High Total 68Ga-DOTATATE-Avid Tumor Volume (TV) is associated with low progression-free survival and high disease-specific mortality rate in patients with neuroendocrine tumors

Specific microRNA–mRNA Regulatory Network of Colon Cancer Invasion Mediated by Tissue Kallikrein–Related Peptidase 6

Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer. KLK6 suppression resulted in decreased cells invasion in vitro with a minimal effect on the cell growth and viability. In vivo, animals with orthotopic colon tumors deficient in KLK6 expression had the statistically significant increase in survival rates (P=.005) and decrease in incidence of distant metastases. We further performed the integrated miRNA and messenger RNA (mRNA) expression profiling to identify functional miRNA-mRNA interactions associated with KLK6-mediated invasiveness of colon cancer.Through bioinformatics analysis we identified and functionally validated the top two up-regulated miRNAs, miR-182 and miR-203, and one down-regulated miRNA, miRNA-181d, and their seven mRNA effectors. The established miRNA-mRNA interactions modulate cellular proliferation, differentiation and epithelial–mesenchymal transition (EMT) in KLK6-expressing colon cancer cells via the TGF-β signaling pathway and RAS-related GTP-binding proteins. We confirmed the potential tumor suppressive properties of miR-181d and miR-203 in KLK6-expressing HCT116 cells using Matrigel invasion assay. Our data provide experimental evidence that KLK6 controls metastasis formation in colon cancer via specific downstream network of miRNA-mRNA effectors.

Overexpression of p53 protein is a marker of poor prognosis in Mexican women with breast cancer.

Breast cancer (BC) is a disease with different clinical, histological and molecular characteristics, frequently presenting mutated tumour-suppressing genes and oncogenes. P53 is a known tumour suppressor that is often mutated in BC; several mutations in p53 inhibit its role as a transcriptional repressor of several oncogenes. Topoisomerase2α (TOP2α) is a gene target of p53, and it is also a known target for anthracyclines. The aim of the present study, was to analyse the genetic alterations of p53 and TOP2α genes and their levels of protein expression, as well as their association with survival in Mexican women with BC. A total of 102biopsies were collected (tumour and adjacent tissues) from patients with BC. To identify point mutations and deletions in the p53 gene, the Sanger sequencing method was carried out. Deletions or amplifications for TOP2α gene were determined using quantitative polymerase chain reaction (qPCR). In addition, the expression of the TOP2α and p53 proteins was evaluated by western blotting. Furthermore, p53 protein expression was analysed by proximity ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-negative breast cancer (TNBC); the average age at the time of diagnosis of these patients was 50years, and Scarff-Bloom-Richardson (SBR) histological gradeIII (p=0.0089). No differences in point mutations or deletions in p53, and deletions or amplifications as well as protein expression level of TOP2α were observed between patients with TNBC and non-TNBC patients. However, patients with TNBC showed p53 protein overexpression as determined by PLA-qPCR and western blotting (p<0.0001). Furthermore, we found an association between TOP2α amplification and overexpression of its protein in patients with TNBC (p<0.0001). Concerning p53, overexpression resulted in a lower survival in patients with BC.

Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: Review of 58 cases

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.

Combined Use of Neutrophil to Lymphocyte Ratio and C-Reactive Protein Level to Predict Clinical Outcomes in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.

Background and ObjectivesBoth neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) are biomarkers associated with poor prognosis of patients with acute myocardial infarction (AMI). However, the combined usefulness of NLR and CRP in predicting adverse outcomes has not been investigated.Subjects and MethodsWe analyzed 381 consecutive AMI patients who underwent percutaneous coronary intervention (PCI) from January 2012 to January 2014. The endpoints were all-cause mortality, recurrent myocardial infarction (MI), stent thrombosis, repeat revascularization, stroke, and major adverse cardiac and cerebrovascular events (MACCE) at 2-year follow-up. Included patients were divided into 4 groups according to the optimal cut-off values for NLR and CRP on receiver operating characteristic analysis predicting mortality.ResultsPatients with both high NLR (>6.30) and high CRP (>0.76) had significantly greater risk of all-cause death and MACCE at 24 months, with no significant increase in the risk of recurrent MI, stent thrombosis, or stroke compared with patients with either low NLR or low CRP, as well as those with low NLR and low CRP. Kaplan-Meier analysis revealed significantly lower survival in patients with high NLR-CRP. On Cox multivariate analysis, high NLR-CRP (hazard ratio 23.172, 95% confidence interval 6.575 to 81.671, p<0.001) was an independent predictor of all-cause death.ConclusionElevated levels of both NLR and CRP are associated with increased risk of long-term mortality in AMI patients who have undergone PCI.

Gastric Adenocarcinoma Treatment in Africa: Surgery Alone or Perioperative Chemotherapy?

Aim: Evaluate the impact of MAGIC trial on gastric adenocarcinoma’s management in Africa. Method and methodology: It was about a review of literature on therapeutic aspects of gastric adenocarcinoma in the African area. We have taken a census of 21 articles including 2792 patients published between 1980 and 2013. We have distinguished articles published before 2006 (group 1) from those published after 2006 (group 2) to better understand therapeutic changes after that perioperative chemotherapy has become a standard in gastric adenocarcinoma’s management. Results: Surgery remains in Africa the first and practically the only treatment weapon in gastric adenocarcinoma: 46% to 92% people in the 1st group and 65% to 100% people in the 2nd group underwent surgical procedures. Perioperative chemotherapy takes longer to be part of therapeutic habits (0.18%). Factors related to patients such alteration of general state with a WHO performance status superior to 2 in 72% of cases, the lack of financial accessibility to anticancerous drugs explains partly the non-use of perioperative chemotherapy. This is also due to factors peculiar to our sanitation structures which don’t have enough cancer specialists. So we noticed that MAGIC trial is simply ignored in certain studies. The lack of adoption of perioperative chemotherapy explains with delayed diagnosis the low survival of patients in the African area. Conclusion: MAGIC trial practically has no effect on therapeutic behavior yet comparatively to gastric adenocarcinoma in Africa. The insurance particularly relies on surgery only until now. However, it might enable us to improve gastric adenocarcinoma’s survival rates.

Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: Review of 58 cases.

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.

CBIO-05. FATTY ACID OXIDATION IS REQUIRED FOR THE RESPIRATION AND PROLIFERATION OF MALIGNANT GLIOMA CELLS

Glioma is the most common form of primary malignant brain tumour, with approximately 4 cases per 100,000 people per year. Gliomas, like many tumours, are thought to rely primarily upon aerobic glycolysis for energy production. However, high levels of glycolysis have been identified in brain tumours through the study of cells that have adapted to culture conditions (Michelakis et al. Sci Trans Med 2010); cells that have been cultured in the absence of serum have been shown to retain their original characteristics and are more suitable for chemical and genetic screening (Pollard et al. Cell Stem Cell 2008). Our findings demonstrate that primary-cultured human glioma cells grown under serum-free conditions require fatty acid oxidation to maintain respiratory and proliferative activity. Specifically, enzymes required for fatty acid oxidation are observed in cells within human glioblastoma tissue, fatty acid oxidation is the primary contributor to respiratory activity in cells isolated from human glioma, and this metabolic pathway is a limiting factor in the proliferation of human and mouse glioma cells cultured in the absence of serum. Moreover, pharmacological inhibition of fatty acid oxidation, using etomoxir, prolongs survival in a syngeneic mouse model of malignant glioma. Finally, we find that transcriptional upregulation of genes whose products play a role in fatty acid oxidation is significantly associated with lower survival in patients with low-grade glioma. Since fatty acid oxidation enzymes are present and functional in glioma tissues, this metabolic pathway could potentially be targeted to reduce energy production and cellular proliferation to provide therapeutic benefit to patients with malignant glioma. While there are currently several dozen under active clinical investigation for the treatment of glioma, there is a clear unmet need in this patient group and our data provide an entirely new pathway to target for the treatment of this cancer.