225 research outputs found
Trends in hospitalizations among medicare survivors of aortic valve replacement in the United States from 1999 to 2010
No full textAbstract not availableKarthik Murugiah, Yun Wang, John A. Dodson, Sudhakar V. Nuti, Kumar Dharmarajan, Isuru Ranasinghe, Zack Cooper, Harlan M. Krumhol
Most important outcomes research papers on device therapies for cardiomyopathies
No full textAakriti Gupta, Kumar Dharmarajan, Rachel Dreyer, Behnood Bikdeli, Ruijun Chen, Vivek T. Kulkarni, Ruizhi Shi, Abbas Shojaee, Isuru Ranasinghe for The Edito
Most important outcomes research papers on hypertension
No full textThe following are highlights from the new series, Circulation: Cardiovascular Quality and Outcomes Topic Review. This series will summarize the most important manuscripts, as selected by the Editor, which have published in the Circulation portfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes, as well as general cardiology audience. The studies included in this article represent the most significant research related to hypertension.Ruijun Chen, Kumar Dharmarajan, Vivek T. Kulkarni, Natdanai Punnanithinont, Aakriti Gupta,Behnood Bikdeli, Purav S. Mody, and Isuru Ranasinghe for the Edito
Most important outcomes research papers on stroke and transient ischemic attack
No full textThe following are highlights from the new series, Circulation: Cardiovascular Quality and Outcomes Topic Review. This series will summarize the most important manuscripts, as selected by the Editor, that have published in the Circulation portfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes, and general cardiology audience. The studies included in this article represent the most significant research related to stroke and transient ischemic attack. (Circ Cardiovasc Quality and Outcomes. 2014; 7:191-204.) © 2014 American Heart Association, Inc.Rachel Dreyer, Karthik Murugiah, Sudhakar V. Nuti, Kumar Dharmarajan, Serene I. Chen, Ruijun Chen, Brian Wayda, Isuru Ranasinghe, for the Edito
Regional variation in hospitalisation and mortality in heart failure: comparison of England and Lombardy using multistate modelling
No full textHeart failure (HF) is a common, serious chronic condition with high morbidity, hospitalisation and mortality. The healthcare systems of England and the northern Italian region of Lombardy share important similarities and have comprehensive hospital administrative databases linked to the death register. We used them to compare admission for HF and mortality for patients between 2006 and 2012 (n = 37,185 for Lombardy, 234,719 for England) with multistate models. Despite close similarities in age, sex and common comorbidities of the two sets of patients, in Lombardy, HF admissions were longer and more frequent per patient than in England, but short- and medium-term mortality was much lower. English patients had more very short stays, but their very elderly also had longer stays than their Lombardy counterparts. Using a three-state model, the predicted total time spent in hospital showed large differences between the countries: women in England spent an average of 24 days if aged 65 at first admission and 19 days if aged 85; in Lombardy these figures were 68 and 27 days respectively. Eight-state models suggested disease progression that appeared similar in each country. Differences by region within England were modest, with London patients spending more time in hospital and having lower mortality than the rest of England. Whilst clinical practice differences plausibly explain these patterns, we cannot confidently disentangle the impact of alternatives such as coding, casemix, and the availability and use of non-hospital settings. We need to better understand the links between rehospitalisation frequency and mortality
Sex differences in trajectories of risk after rehospitalization for heart failure, acute myocardial infarction, or pneumonia
No full textBackground: Women have an increased risk of rehospitalization in the immediate postdischarge period; however, few studies have determined how readmission risk dynamically changes on a day-to-day basis over the full year after hospitalization by sex and how these differences compare with the risk for mortality. Methods and Results: We identified >3 000 000 hospitalizations of patients with a principal discharge diagnosis of heart failure, acute myocardial infarction, or pneumonia and estimated sex differences in the daily risk of rehospitalization/death 1 year after discharge from a population of Medicare fee-for-service beneficiaries aged 65 years and older. We calculated the (1) time required for adjusted rehospitalization/mortality risks to decline 50% from maximum values after discharge, (2) time required for the adjusted readmission risk to approach plateau periods of minimal day-to-day change, and (3) extent to which adjusted risks are greater among recently hospitalized patients versus Medicare patients. We identified 1 392 289, 530 771, and 1 125 231 hospitalizations for heart failure, acute myocardial infarction, and pneumonia, respectively. The adjusted daily risk of rehospitalization varied by admitting condition (hazard rate ratio for women versus men, 1.10 for acute myocardial infarction; hazard rate ratio, 1.04 for heart failure; and hazard rate ratio, 0.98 for pneumonia). However, for all conditions, the adjusted daily risk of death was higher among men versus women (hazard rate ratio women versus with men, <1). For both sexes, there was a similar timing of peak daily risk, half daily risk, and reaching plateau. Conclusions: Although the association of sex with daily risk of rehospitalization varies across conditions, women are at highest risk after discharge for acute myocardial infarction. Future studies should focus on understanding the determinants of sex differences in rehospitalization risk among conditions.Rachel P. Dreyer, Kumar Dharmarajan, Angela F. Hsieh, John Welsh, Li Qin, Harlan M. Krumhol
Wnt antagonist, secreted frizzled-related protein 4 (SFRP4) and peptides from its associated domains, increases chemotherapeutic response of cancer stem cells of malignant mesothelioma cell lines
No full textAbstract
Malignant mesothelioma (MM) is a highly aggressive cancer associated with past asbestos exposure that is characterized by rapid progression, late metastases and poor prognosis. There is a need for much improved and novel therapies for this cancer through improved biological understanding of the disease.Previous studies have shown that SFRPs in general and SFRP4 in particular are down regulated in mesothelioma tissue and cell lines 1-4. Based on our own study and previously demonstrated a role for sFRP4 in making chemoresistant tumours amenable to chemotherapeutics 5-16. We have now progressed our work into the effects of peptides derived from the cysteine-rich domain and the netrin-like domain of sFRP4 on tumour initiating cells derived from MM cell lines.We examined the effect of secreted frizzled-related protein 4 (sFRP4), a Wnt signaling antagonist and its associated peptides, in chemosensitizing the MM cell line ONE 58 and JU77 and MM cancer stem cells (CSCs) enriched from these two cell lines to chemotherapeutics.We found tumorspheres exposed to sFRP4 and peptides alone and in combination with cisplatin induced cell death and decreased CD133 and ALDH1 expression.We thus identified for the first time that sFRP4 and associated peptides could help to sensitise to chemotherapeutics and destroy cancer stem cells of MM cell line, which would lead to effective treatment regimen to combat malignant mesothelioma. Our initial in vitro data exemplify the ability of these peptides in diminishing the numbers of therapy-resistant Tumor initiating cells (TICs).
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Citation Format: Vanathi Perumal, Senthil Kumar, Frank Arfuso, Simon Fox, Arunasalam Dharmarajan. Wnt antagonist, secreted frizzled-related protein 4 (SFRP4) and peptides from its associated domains, increases chemotherapeutic response of cancer stem cells of malignant mesothelioma cell lines [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 932. doi:10.1158/1538-7445.AM2017-932</jats:p
Human face shaped microstrip patch antennas for ultra-wideband applications.
No full textMasters Degree. University of KwaZulu-Natal, Durban.Abstract available in pdf
Readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia among young and middle-aged adults: a retrospective observational cohort study
No full textBACKGROUND: Patients aged ≥ 65 years are vulnerable to readmissions due to a transient period of generalized risk after hospitalization. However, whether young and middle-aged adults share a similar risk pattern is uncertain. We compared the rate, timing, and readmission diagnoses following hospitalization for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among patients aged 18-64 years with patients aged ≥ 65 years. METHODS AND FINDINGS: We used an all-payer administrative dataset from California consisting of all hospitalizations for HF (n=206,141), AMI (n=107,256), and pneumonia (n=199,620) from 2007-2009. The primary outcomes were unplanned 30-day readmission rate, timing of readmission, and readmission diagnoses. Our findings show that the readmission rate among patients aged 18-64 years exceeded the readmission rate in patients aged ≥ 65 years in the HF cohort (23.4% vs. 22.0%, p<0.001), but was lower in the AMI (11.2% vs. 17.5%, p<0.001) and pneumonia (14.4% vs. 17.3%, p<0.001) cohorts. When adjusted for sex, race, comorbidities, and payer status, the 30-day readmission risk in patients aged 18-64 years was similar to patients ≥ 65 years in the HF (HR 0.99; 95%CI 0.97-1.02) and pneumonia (HR 0.97; 95%CI 0.94-1.01) cohorts and was marginally lower in the AMI cohort (HR 0.92; 95%CI 0.87-0.96). For all cohorts, the timing of readmission was similar; readmission risks were highest between days 2 and 5 and declined thereafter across all age groups. Diagnoses other than the index admission diagnosis accounted for a substantial proportion of readmissions among age groups <65 years; a non-cardiac diagnosis represented 39-44% of readmissions in the HF cohort and 37-45% of readmissions in the AMI cohort, while a non-pulmonary diagnosis represented 61-64% of patients in the pneumonia cohort. CONCLUSION: When adjusted for differences in patient characteristics, young and middle-aged adults have 30-day readmission rates that are similar to elderly patients for HF, AMI, and pneumonia. A generalized risk after hospitalization is present regardless of age.Isuru Ranasinghe, Yongfei Wang, Kumar Dharmarajan, Angela F. Hsieh, Susannah M. Bernheim, Harlan M. Krumhol
Breast cancer stem-like cells are inhibited by diosgenin, a steroidal saponin, by the attenuation of the Wnt β-catenin signaling via the Wnt antagonist secreted frizzled related protein-4
No full textBackground: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone in approaching anticancer therapies. Targeting this minor subpopulation of chemo- and radio-resistant stem-like cells, termed as the cancer stem cells (CSCs) and their eradication could significantly enhance clinical outcomes. Most of the presently administered chemotherapeutics target the tumor bulk but are ineffective against the CSCs. We report here that diosgenin (DG), a naturally occurring steroidal saponin, could effectively inhibit CSCs from three breast cancer cell lines, MCF7, T47D and MDA-MB-231, by inducing apoptosis and inhibiting the CSC associated phenotypes. Methods: CSCs were enriched in these cells lines, characterized for CSC traits by immunocytochemistry and flow cytometry. Proliferation and apoptosis assays were performed in these breast CSCs in the presence of DG to obtain the inhibitory concentration. Apoptosis was confirmed with gene expression analysis, Western blotting and propidium iodide staining. TCF-LEF reporter assay, sFRP overexpression and RNAi silencing studies were performed to study regulation of the Wnt pathway. Statistical significance was evaluated by a two-sided Student's t-test. Results: Using the TCF-LEF reporter system, we show the effect of DG on CSCs is predominantly through the network regulating CSC self renewal, the Wnt β-catenin pathway. Specifically, the Wnt antagonist, the secreted frizzled related protein 4, (sFRP4), had a defining role in the action of DG. Gain-of-function of sFRP4 in CSCs could improve the response to DG wherein CSC mediators were inhibited, β-catenin was down regulated and the effectors of epithelial to mesenchymal transition and pro-invasive markers were repressed. Conversely, the loss-of-function of sFRP4 had a reverse effect on the CSC population which therein became enriched, their response to DG treatment was modest, β-catenin levels increased, GSK3β expression decreased and the expression of epithelial markers of CSC was completely abrogated. Conclusion: These findings demonstrate the effect of DG on inhibiting the resilient breast CSCs which could provide a benchmark for the development of DG-based therapies in breast cancer treatment. © 2017 Bhuvanalakshmi, Basappa, Rangappa, Dharmarajan, Sethi, Kumar and Warrier
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