Showing papers by "Atlantic Health System published in 2014"
TL;DR: In insight into the relationship between tumor dissemination and metabolic attributes of human cancer stem cells, spheroid cells were found to be enriched for cells with cancer stem cell-like characteristics and contributed to tumor generation, progression and chemotherapy resistance.
Abstract: Cells with sphere forming capacity, spheroid cells, are present in the malignant ascites of patients with epithelial ovarian cancer (EOC) and represent a significant impediment to efficacious treatment due to their putative role in progression, metastasis and chemotherapy resistance. The exact mechanisms that underlie EOC metastasis and drug resistance are not clear. Understanding the biology of sphere forming cells may contribute to the identification of novel therapeutic opportunities for metastatic EOC. Here we generated spheroid cells from human ovarian cancer cell lines and primary ovarian cancer. Xenoengraftment of as few as 2000 dissociated spheroid cells into immune-deficient mice allowed full recapitulation of the original tumor, whereas >105 parent tumor cells remained non-tumorigenic. The spheroid cells were found to be enriched for cells with cancer stem cell-like characteristics such as upregulation of stem cell genes, self-renewal, high proliferative and differentiation potential, and high aldehyde dehydrogenase (ALDH) activity. Furthermore, spheroid cells were more aggressive in growth, migration, invasion, scratch recovery, clonogenic survival, anchorage-independent growth, and more resistant to chemotherapy in vitro. 13C-glucose metabolic studies revealed that spheroid cells route glucose predominantly to anaerobic glycolysis and pentose cycle to the detriment of re-routing glucose for anabolic purposes. These metabolic properties of sphere forming cells appear to confer increased resistance to apoptosis and contribute to more aggressive tumor growth. Collectively, we demonstrated that spheroid cells with cancer stem cell-like characteristics contributed to tumor generation, progression and chemotherapy resistance. This study provides insight into the relationship between tumor dissemination and metabolic attributes of human cancer stem cells and has clinical implications for cancer therapy.
305 citations
TL;DR: In this paper, the authors examined the levels of various forms of amyloid β peptides (Aβ) in the brain, plasma and lymph nodes in a transgenic model of Alzheimer's disease (AD) at different ages.
44 citations
TL;DR: Performance on the 6 MWT is independently associated with all-cause mortality and is of prognostic utility in community-dwelling older adults.
Abstract: Objective: To examine the association between 6-min walk test (6 MWT) performance and all-cause mortality, coronary heart disease mortality, and incident coronary heart disease in older adults. Method: We conducted a time-to-event analysis of 1,665 Cardiovascular Health Study participants without prevalent cardiovascular disease with a 6 MWT. Results: During a mean follow-up of 8 years, there were 305 incident coronary heart disease events, and 504 deaths of which 100 were coronary heart disease–related deaths. The 6 MWT performance in the shortest two distance quintiles was associated with increased risk of all-cause mortality (290-338 m: hazard ratio [HR] = 1.7; 95% confidence interval [CI] = [1.2, 2.5]; <290 m: HR = 2.1; 95% CI = [1.4, 3.0]). The adjusted risk of coronary heart disease mortality incident events among those with a 6 MWT < 290 m was not significant. Discussion: Performance on the 6 MWT is independently associated with all-cause mortality and is of prognostic utility in community-dwelling...
40 citations
TL;DR: Differences in mitral valve geometry are observed between asymmetric and symmetric tethering patterns in IMR, and an asymmetric pattern is associated with increased MR severity.
Abstract: Background Ischemic mitral regurgitation (IMR) results from mitral leaflet tethering from left ventricular remodeling. Heterogeneity in local or global left ventricular remodeling can result in differential tethering patterns and affect mitral valve function and the degree of mitral regurgitation. The aims of this study were to compare mitral valve geometry in asymmetric and symmetric tethering patterns using three-dimensional transesophageal echocardiography and to examine the impact of tethering pattern on IMR severity. Methods Sixty-two patients with moderate or greater IMR underwent three-dimensional transesophageal echocardiography for the assessment of mitral valve geometry. Symmetric and asymmetric tethering patterns were determined by mitral regurgitation jet direction and coaptation of the mitral leaflets. The ratio of posterior to anterior leaflet tethering angle was a measure of tethering pattern (the higher the ratio, the more asymmetric the pattern). Overall tethering degree was assessed by tenting volume (TV). Results Compared with the symmetric group, the asymmetric group had less annular dilatation, greater annular heights (10.3 ± 1.9 vs 8.5 ± 1.9 mm, P P P P P = .001) were predictors of IMR severity. Conclusions Differences in mitral valve geometry are observed between asymmetric and symmetric tethering patterns in IMR. IMR degree is affected by both the pattern of tethering and the total degree of tethering. For the same degree of tethering, an asymmetric pattern is associated with increased MR severity. The pattern of mitral leaflet tethering may be considered in therapeutic decision making.
39 citations
TL;DR: Pediatric Early Warning Score is associated with the level of care at ED disposition but does not provide adequate sensitivity and specificity to be used in isolation, and performance characteristics are better for patients with respiratory complaints.
Abstract: ObjectiveThe objective of this study was to determine the association between the Pediatric Early Warning Score (PEWS) at time of emergency department (ED) disposition and level of care.MethodsWe conducted a prospective observational study with a convenience sample of patients aged 0 to 21 years in
34 citations
Cincinnati Children's Hospital Medical Center1, Children's Hospital of Philadelphia2, Mayo Clinic3, Atlantic Health System4, Nationwide Children's Hospital5, University of California, San Francisco6, Children's Hospital of Eastern Ontario7, University of Toronto8, University at Buffalo9, Emory University10
TL;DR: An elevated PMN CD64 index is associated with both mucosal inflammation and an increased risk for clinical relapse in pediatric CD and is a reliable marker for sustained remission in patients with CD receiving maintenance therapy.
Abstract: Background
Neutrophil expression of the Fcγ receptor I (CD64) is upregulated in adult patients with clinically active inflammatory bowel disease (IBD). We tested the relationship of CD64 with mucosal inflammation and clinical relapse in pediatric Crohn's disease (CD).
29 citations
01 Nov 2014
TL;DR: Aβ concentration was low to undetectable in splenic lymphoid tissue and several other control tissues including heart, lung, liver, kidneys and intestine of the same animals, strongly suggesting that Aβ peptides in lymph nodes are derived from the brain.
Abstract: Evidence has shown that lymphatic drainage contributes to removal of debris from the brain but its role in the accumulation of amyloid β peptides (Aβ) has not been demonstrated. We examined the levels of various forms of Aβ in the brain, plasma and lymph nodes in a transgenic model of Alzheimer's disease (AD) at different ages. Herein, we report on the novel finding that Aβ is present in the cervical and axillary lymph nodes of AD transgenic mice and that Aβ levels in lymph nodes increase over time, mirroring the increase of Aβ levels observed in the brain. Aβ levels in lymph nodes were significantly higher than in plasma. At age 15.5months, there was a significant increase of monomeric soluble Aβ40 (p=0.003) and Aβ42 (p=0.05) in the lymph nodes over the baseline values measured at 6months of age. In contrast, plasma levels of Aβ40 showed no significant changes (p=0.68) and plasma levels Aβ42 significantly dropped (p=0.02) at the same age. Aβ concentration was low to undetectable in splenic lymphoid tissue and several other control tissues including heart, lung, liver, kidneys and intestine of the same animals, strongly suggesting that Aβ peptides in lymph nodes are derived from the brain.
28 citations
01 Jul 2014
TL;DR: This study demonstrates significant racial differences in surgical delay in a group of breast cancer patients treated in the New York region, which may reflect tacit attitudes of medical providers or processes insensitive to patient educational needs.
Abstract: ObjectiveTo evaluate surgical treatment delay disparities by race/ethnic group in a group of breast cancer patients treated in the New York region.DesignCohort study.SettingTwo affiliated hospitals in the New York region.ParticipantsPatients admitted at two affiliated hospitals in the New York region for breast cancer treatment during 2007–2011.Main outcome measureTime to receiving first surgery for breast cancer, defined as the time in days between initial diagnosis (biopsy) and definitive surgical treatment (lumpectomy or mastectomy). Predicted time to first surgery by race group was also analysed using a multivariate linear regression model with adjustments made for several demographic and clinical factors.ResultsTotally, 3071 patients who were first treated with surgery were identified. Racial background was classified as White, African American or Asian/other. Overall median time to surgery was 28 days: 28 days in whites, and 34 and 29 days in African Americans and Asian/others, respectively (p = 0.0...
25 citations
TL;DR: RSLND using methylene blue cervical injection can identify SLN in most patients with EC, and IHC ultrastaging improves the detection of node positive disease when compared to traditional pathological evaluation.
24 citations
TL;DR: It is concluded that impairment of γ-secretase can paradoxically increase Aβ by transiently skirting Aβ degradation in the endosome and adds to the growing body of literature suggesting that preservingγ- secretase activity, rather than inhibiting it, is important for prevention of neurodegeneration.
Abstract: BACE1 (β-secretase) and α-secretase cleave the Alzheimer's amyloid β protein (Aβ) precursor (APP) to C-terminal fragments of 99 aa (CTFβ) and 83 aa (CTFα), respectively, which are further cleaved by γ-secretase to eventually secrete Aβ and Aα (a.k.a. P3) that terminate predominantly at residues 40 and 42. A number of γ-secretase inhibitors (GSIs), such as N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), have been developed with the goal of reducing Aβ to treat Alzheimer's disease (AD). Although most studies show that DAPT inhibits Aβ in a dose-dependent manner several studies have also detected a biphasic effect with an unexpected increase at low doses of DAPT in cell cultures, animal models and clinical trials. In this article, we confirm the increase in Aβ40 and Aβ42 in SH-SY5Y human neuroblastoma cells treated with low doses of DAPT and identify one of the mechanisms for this paradox. We studied the pathway by first demonstrating that stimulation of Aβ, a product of γ-secretase, was accompanied by a parallel increase of its substrate CTFβ, thereby demonstrating that the inhibitor was not anomalously stimulating enzyme activity at low levels. Secondly, we have demonstrated that inhibition of an Aβ degrading activity, endothelin converting enzyme (ECE), yielded more Aβ, but abolished the DAPT-induced stimulation. Finally, we have demonstrated that Aα, which is generated in the secretory pathway before endocytosis, is not subject to the DAPT-mediated stimulation. We therefore conclude that impairment of γ-secretase can paradoxically increase Aβ by transiently skirting Aβ degradation in the endosome. This study adds to the growing body of literature suggesting that preserving γ-secretase activity, rather than inhibiting it, is important for prevention of neurodegeneration.
17 citations
TL;DR: Laroscopic sacrocolpopexy had a positive impact on sexual function at 1 year regardless of whether a porcine dermis or a polypropylene mesh material was used.
Abstract: Objective: This study aimed to compare sexual function before and 1 year after laparoscopic sacrocolpopexy using a porcine dermis or a polypropylene mesh material. Methods: This was a secondary analysis of sexual function measured before and 1 year after laparoscopic sacrocolpopexy in a group of 81 sexually active women participating in a randomized controlled trial comparing porcine dermis and polypropylene mesh. Sexual function was assessed using the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Responses to individual questions from the physical domain of the PISQ-12 were also analyzed. Additional information included the type of mesh material used and whether a concomitant suburethral sling or perineorrhaphy was performed. Results: There was a significant postoperative improvement in total PISQ-12 scores for the entire cohort (33.2 vs 38.3, P G 0.01). Similarly, PISQ-12 scores were significantly improved in both groups (33.2 preoperative vs 37.4 one year postoperative in the porcine dermis, P G 0.01 and 33.2 vs 39.2 in the polypropylene mesh, P G 0.01). There were no differences between the 2 graft material groups. Preoperatively, 63.0% (48/76) of women reported avoiding sexual intercourse because of bulging in vagina (PISQ12-question #8), at 1 year postoperatively only 4% (3/76) had a positive response (P G 0.01). We observed a significant decrease in the number of women who reported pain during intercourse at 12 months as evidenced by the responses to the PISQ12-question #5, 47.4% (36/76) versus 26.3% (20/76) (P G 0.01). The addition of a suburethral sling or a perineorrhaphy did not negatively impact sexual function at 1 year. Conclusions: Laparoscopic sacrocolpopexy had a positive impact on sexual function at 1 year regardless of whether a porcine dermis or a polypropylene mesh material was used.
TL;DR: Findings showed that gas-forming soft tissue infections of the lower extremity, commonly diagnosed as gas gangrene, are rarely caused by Clostridium species.
Abstract: The Infectious Disease Society of America has defined gas gangrene as an infection caused by Clostridium species. However, in many clinical settings, soft tissue infections that produce subcutaneous gas have been diagnosed as gas gangrene without identification of the presence of Clostridium species. Instead, the diagnosis was based on clinical and radiographic findings. A chart review was performed of 25 consecutive patients treated at the Atlantic Health System for infections of the lower extremity that were diagnosed as gas gangrene. Wound cultures from the 25 patients grew 31 different species of bacteria. The most prevalent organism was Staphylococcus aureus, which accounted for 17 of 31 (54.84%) different organisms identified and 19.77% of 86 separate aerobic or anaerobic cultures. The most prevalent genus was Streptococcus, which accounted for 20 (64.52%) of the organisms identified and 23.26% of the cultures. The most prevalent anaerobic genus was Peptostreptococcus, which accounted for 8 (25.81%) of the organisms identified and 9.3% of the cultures. None of the cultures grew Clostridium species. These findings showed that gas-forming soft tissue infections of the lower extremity, commonly diagnosed as gas gangrene, are rarely caused by Clostridium species.
TL;DR: This case demonstrates the state-of-the-art approach to the clinical challenge of prenatal microcephaly and defines unique findings associated with compound heterozygous STIL gene mutations c.2354_2355dupGA and c.3835C>T.
TL;DR: The addition of a single-incision suburethral sling at the time of robotic sacrocolpopexy in women with SUI resulted in an 87 % cure rate at 1 year.
Abstract: Introduction and hypothesis
The objective of this study was to evaluate the efficacy and safety of the Miniarc Precise® single-incision sling (American Medical Systems, Minnetonka, MN, USA) placed at the time of a robotic sacrocolpopexy.
TL;DR: Equilibrium and kinetics data show that colesevelam is equivalent in its tablet and oral suspension formulation, and having 2 effective oral routes enhances convenience and improves compliance, both of which contribute to maximal therapeutic outcomes.
Abstract: Introduction: Colesevelam HCl (colesevelam) is a bile acid sequestrant initially approved by the US Food and Drug Administration (FDA) in 2000 as an adjunct to diet and exercise to lower elevated low-density lipoprotein cholesterol (LDL-C) levels in adults with primary lipidemia, as monotherapy, or in combination with a statin. More recently, the drug was approved for use in adults with type 2 diabetes mellitus (T2DM) to improve glycemic control. Thus, colesevelam is currently the only single-agent monotherapy approved by the FDA to lower both LDL-C and glycated hemoglobin (A1c) levels in adults with T2DM and elevated LDL-C. Moreover, the formulation options for colesevelam have also expanded since its original approval. Materials and Methods: A Medline search was conducted to provide evidence to support the efficacy and safety for the use of colesevelam tablets or oral suspension preparations when treating patients with lipidemia, T2DM, or both. No limitations were placed on publication date or a...
TL;DR: Identifying risk factors may assist the surgeon in mitigation of risk with preoperative optimization, intraoperative decision-making for diversion, and heightened postoperative vigilance for anastomotic leak.
25 Nov 2014
TL;DR: Important needs and potential solutions to be considered in providing long-term support to patients with PD and their caregivers are identified.
Abstract: Background: We desired relevant information from patients with Parkinson’s disease (PD) and their caregivers for help in planning a long-term support program. Methods: We compared 3 ap-proaches: 1) a standard needs assessment questionnaire, the Camberwell assessment of need in the elderly, 2) an open-ended listing of needs, and 3) participation in a narrative medicine program in which health care professionals were involved. Results: On the questionnaire, patients reported physical needs as the most important while their caregivers were more concerned about psychological needs. The open-ended listings revealed additional needs, particularly access to re-liable information about PD and to opportunities to participate in clinical research. The narrative medicine process yielded a number of new insights and proposed solutions, particularly related to the heterogeneity of needs across individuals, the importance of providing hope, and the fact that caregivers expressed that their needs had been largely neglected. Participation in the narrative medicine sessions led to an increase in measured empathy by health care professionals, an im-provement in measured depression among PD patients, but a worsening of measured depression among the caregivers. Conclusions: We have identified important needs and potential solutions to be considered in providing long-term support to patients with PD and their caregivers.
01 Jan 2014
TL;DR: I began my career in 1994 as an interventional cardiologist, and I thought the world of medicine was totally mechanistic; my patient has a blocked artery; I have a stent and a statin in my toolbox; I fix the artery—end of story.
Abstract: I began my career in 1994 as an interventional cardiologist, and I thought the world of medicine was totally mechanistic. My patient has a blocked artery; I have a stent and a statin in my toolbox; I fix the artery—end of story. There is nothing wrong with this approach in acute care. This type of medicine, the backbone of conventional medical education, can save lives. We were trained not to prevent disease but to treat acute problems. This training assumes patients are acutely ill and that the answer lies in some sort of “magic bullet.” They are not coming to us for preventive care.
Patent•
09 Oct 2014TL;DR: In this article, a lockable storage container and delivery device is provided that exposes the access port of liquid medicinal vials (such as for insulin) while maintaining identification, security, organization and inventory data access, for easy and documented administration of such medicine.
Abstract: A lockable storage container and delivery device is provided that exposes the access port of liquid medicinal vials (such as for insulin) while maintaining identification, security, organization and inventory data access, for easy and documented administration of such medicine. The container has individual compartments for various types of medication, or variants of a similar medication (such as various types of insulin) in one convenient and secure container that provides optimal, efficient, cost-saving and safe delivery of medicine to patients.