Acute myocardial infarction: profile and management at a tertiary care hospital in Karachi

Objective: Acute Myocardial Infarction (AMI) is a rising epidemic in developing countries. While studies in the West have established the characteristics and management of AMI patients, comprehensive data reflecting these issues in the Pakistani subjects is scarce. This study examined the profile and management of AMI in patients hospitalized at a tertiary care hospital in Karachi, Pakistan.Methods: Three hundred forty four patients admitted in 1998 with the diagnosis of AMI met our inclusion criteria. Data on presentation, investigations, monitoring and therapy was obtained. Chi-square and t tests were used to analyze the data.Results: Out of 344 patients with AMI, 71% were males; 58% had a Q wave MI. Majority of the patients who presented within 2 hours of symptom onset (36%), had chest pain. Patients with dyspnea and no chest pain were more likely to present after 12 hours of the onset of symptoms. In-house mortality was found to be 10.8%. Low HDL and diabetes was associated with in-hospital complications. Twenty nine percent of patients were given thrombolytic therapy with a mean door-to-needle time of 1 hour 36 minutes; 33% of patients who were eligible of Streptokinase did not receive it. Cardiac catheterization was performed in 28% patients. Echocardiography and Exercise Tolerance Test, both under utilized, were performed in 67% and 16% of patients, respectively. Two hundred sixteen (70%) patients discharged from hospital were contacted via telephone and the 1-year mortality rate among them was 28%.CONCLUSION: The profile and management of AMI was in coherence with earlier, Western studies. Chest pain units need to be established in the Emergency Room. Patients should be risk stratified prior to discharge. Public awareness regarding primary and secondary prevention and symptoms of AMI needs to be increased

Properties of metabolic graphs: biological organization or representation artifacts?

<p>Abstract</p> <p>Background</p> <p>Standard graphs, where each edge links two nodes, have been extensively used to represent the connectivity of metabolic networks. It is based on this representation that properties of metabolic networks, such as hierarchical and small-world structures, have been elucidated and null models have been proposed to derive biological organization hypotheses. However, these graphs provide a simplistic model of a metabolic network's connectivity map, since metabolic reactions often involve more than two reactants. In other words, this map is better represented as a hypergraph. Consequently, a question that naturally arises in this context is whether these properties truly reflect biological organization or are merely an artifact of the representation.</p> <p>Results</p> <p>In this paper, we address this question by reanalyzing topological properties of the metabolic network of <it>Escherichia coli </it>under a hypergraph representation, as well as standard graph abstractions. We find that when clustering is properly defined for hypergraphs and subsequently used to analyze metabolic networks, the scaling of clustering, and thus the hierarchical structure hypothesis in metabolic networks, become unsupported. Moreover, we find that incorporating the distribution of reaction sizes into the null model further weakens the support for the scaling patterns.</p> <p>Conclusions</p> <p>These results combined suggest that the reported scaling of the clustering coefficients in the metabolic graphs and its specific power coefficient may be an artifact of the graph representation, and may not be supported when biochemical reactions are atomically treated as hyperedges. This study highlights the implications of the way a biological system is represented and the null model employed on the elucidated properties, along with their support, of the system.</p

RUNX3 Mediates Suppression of Tumor Growth and Metastasis of Human CCRCC by Regulating Cyclin Related Proteins and TIMP-1

Here we presented that the expression of RUNX3 was significantly decreased in 75 cases of clear cell renal cell carcinoma (CCRCC) tissues (p<0.05). Enforced RUNX3 expression mediated 786-O cells to exhibit inhibition of growth, G1 cell-cycle arrest and metastasis in vitro, and to lost tumorigenicity in nude mouse model in vivo. RUNX3-induced growth suppression was found partially to regulate various proteins, including inhibition of cyclinD1, cyclinE, cdk2, cdk4 and p-Rb, but increase of p27Kip1, Rb and TIMP-1. Therefore, RUNX3 had the function of inhibiting the proliferative and metastatic abilities of CCRCC cells by regulating cyclins and TIMP1

Coordinated Activation of Candidate Proto-Oncogenes and Cancer Testes Antigens via Promoter Demethylation in Head and Neck Cancer and Lung Cancer

Background: Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC) and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC. Methodology/Principal Findings: We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells. Conclusions/Significance: Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs i

Disease Gene Interaction Pathways: A Potential Framework for How Disease Genes Associate by Disease-Risk Modules

BACKGROUND: Disease genes that interact cooperatively play crucial roles in the process of complex diseases, yet how to analyze and represent their associations is still an open problem. Traditional methods have failed to represent direct biological evidences that disease genes associate with each other in the pathogenesis of complex diseases. Molecular networks, assumed as 'a form of biological systems', consist of a set of interacting biological modules (functional modules or pathways) and this notion could provide a promising insight into deciphering this topic. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we hypothesized that disease genes might associate by virtue of the associations between biological modules in molecular networks. Then we introduced a novel disease gene interaction pathway representation and analysis paradigm, and managed to identify the disease gene interaction pathway for 61 known disease genes of coronary artery disease (CAD), which contained 46 disease-risk modules and 182 interaction relationships. As demonstrated, disease genes associate through prescribed communication protocols of common biological functions and pathways. CONCLUSIONS/SIGNIFICANCE: Our analysis was proved to be coincident with our primary hypothesis that disease genes of complex diseases interact with their neighbors in a cooperative manner, associate with each other through shared biological functions and pathways of disease-risk modules, and finally cause dysfunctions of a series of biological processes in molecular networks. We hope our paradigm could be a promising method to identify disease gene interaction pathways for other types of complex diseases, affording additional clues in the pathogenesis of complex diseases

Acute kidney injury in patients treated with immune checkpoint inhibitors

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

Liquid biopsies come of age: towards implementation of circulating tumour DNA

Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a ‘liquid biopsy’ for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.We would like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A11906, A20240, A15601) (to N.R., J.D.B.), the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 337905 (to N.R.), the Cambridge Experimental Cancer Medicine Centre, and Hutchison Whampoa Limited (to N.R.), AstraZeneca (to R.B., S.P.), the Cambridge Experimental Cancer Medicine Centre (ECMC) (to R.B., S.P.), and NIHR Biomedical Research Centre (BRC) (to R.B., S.P.). J.G.C. acknowledges clinical fellowship support from SEOM