Co-testing for detection of high-grade cervical intraepithelial neoplasia and cancer compared with cytology alone: a meta-analysis of randomized controlled trials.

BACKGROUND: Human papillomavirus (HPV) DNA testing combined with cytology has been recommended as a primary cervical cancer screening strategy. METHODS: PubMed/MEDLINE, Embase, the Cochrane Library and the NIH trial registry were searched for randomized controlled trials comparing co-testing with cytology alone for the detection of high-grade CIN lesions and cancers. Of 1156 articles identified, four met inclusion criteria. The performance of co-testing and cytology alone was compared at baseline screening, second round screening and overall. Cumulative meta-analysis, Begg's test, Egger's test and sensitivity analysis were performed. RESULTS: At baseline, co-testing was associated with a significantly higher detection rate of CIN 2+ [risk ratio (RR) = 1.41, 95% confidence interval (CI): 1.12, 1.76] and a non-significantly higher CIN 3+ detection rate (RR = 1.15, 95% CI: 0.99, 1.33). At second round screening, co-testing was associated with significantly lower detection rates of both CIN 2+ and CIN 3+ (RR = 0.77, 95% CI: 0.63, 0.93; RR = 0·68, 95% CI: 0.55, 0.85). The overall detection rate did not differ between co-testing and cytology alone for CIN 2+ (RR: 1·19, 95% CI: 0.99, 1.46) or CIN3+ (RR: 0.99, 95% CI: 0.87, 1.14). CONCLUSION: Co-testing increases the detection of CIN2+ lesions at baseline and significantly decreases the detection rates of CIN2+ or CIN3+ lesions at subsequent screening compared with cytology alone.

Survey of the clinical assessment and utility of near-infrared cerebral oximetry in cardiac surgery.

OBJECTIVES: Near-infrared cerebral oximetry increasingly is used for monitoring during cardiac surgery. Nonetheless, the scientific basis for incorporating this technology into clinical practice, the indications for when to do so, and standard diagnostic and treatment algorithms for defining abnormal values are yet to be rigorously defined. The authors hypothesized that there would be (1) variation in clinical use and practices for near-infrared spectroscopy (NIRS), and (2) variation in management of patients when clinicians are provided with NIRS information. In order to test this hypothesis, they sought to assess the nature and strength of response heterogeneity among anesthesiologists and cardiac perfusionists when provided with cardiac surgery patient scenarios and cerebral oximetry data. DESIGN: A prospectively collected survey. SETTING: A hospital-based, multi-institutional, multinational study. PARTICIPANTS: By e-mail, the authors surveyed the membership of the Society of Cardiovascular Anesthesiologists and the online Cardiovascular Perfusion Forum. INTERVENTIONS: This survey was focused on ascertaining what actions clinicians would take in each scenario, given case information and cerebral oximetry tracings. Questions were based on 11 patient scenarios selected to represent small, large, symmetric, or asymmetric decreases in measured regional cerebral oxygen saturation (rScO2) encountered during cardiac surgery. Information on the respondents' (n = 796; 73% anesthesiologists) clinical practice, demography, and cerebral oximetry utilization was collected. An index of dispersion was used to assess response heterogeneity overall and within demographic subgroups. MEASUREMENTS AND MAIN RESULTS: The majority of respondents indicated that cerebral oximetry monitoring was either useful or an essential monitor, especially perfusionists and clinicians who used cerebral oximetry most frequently. There were marked differences in responses between perfusionists and anesthesiologists for 4 of the 6 scenarios (p<0.005 for each of these 4 scenarios) occurring during cardiopulmonary bypass. Scenarios having greatest rScO2 reduction or asymmetry in rScO2 were associated with the highest dispersion, indicating least agreement in management. Scenarios with mild or moderate rScO2 reduction were associated with the lowest dispersion, indicating greater agreement in management. CONCLUSIONS: Although experimental data gradually are accumulating to support the role for cerebral oximetry monitoring during cardiac surgery, the results of the present survey support the view that its role remains poorly defined, and consensus for its appropriate use is lacking. Importantly, the authors observed marked variation in the use, perceived utility, and management of patients for 4 of the 6 CPB scenarios between perfusionists and anesthesiologists who share the management of CPB. These findings support the need for well-designed, adequately-powered clinical trials examining the value of this technology.

Impedance of novel therapeutic technologies: the case of stem cells.

Embryonic stem cell (ES) technology has advanced considerably within the past three decades and has gained prominent distinction within the emerging field of regenerative medicine. As it now enters the nascent stages of clinical application, many hopes and expectations arise along with questions as to where the technology will go. This paper evaluates the technical and practical obstacles that must be overcome before it can fully translate into the clinical context, the existence of strong opposition to the technology, political and legal barriers that have impeded its progression, and the role of healthcare reform in creating new social and economic priorities. In contrast to the technological imperative, a driving force seeking to implement the most recent scientific advances into medical practice, we refer to such translational obstacles as "technological impedance." Rather than expending inordinate effort to preserve existing systems that continue to possess major hurdles, we advocate fostering interdisciplinary approaches in the development of new generation platforms and embracing disruptive innovations that create solutions to technological impedance and move us forward in healthcare delivery. Clin Trans Sci 2012; Volume 5: 422-427.

Humanin, a cytoprotective peptide, is expressed in carotid atherosclerotic [corrected] plaques in humans.

OBJECTIVE: The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN) is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques. METHODS AND RESULTS: Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001). These data were further confirmed by immunoblot (density of HN/ß-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01). TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01). Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization), smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9. CONCLUSIONS: The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque.

The science and ethics of induced pluripotency: what will become of embryonic stem cells?

For over a decade, the field of stem cell research has advanced tremendously and gained new attention in light of novel insights and emerging developments for regenerative medicine. Invariably, multiple considerations come into play, and clinicians and researchers must weigh the benefits of certain stem cell platforms against the costs they incur. Notably, human embryonic stem (hES) cell research has been a source of continued debate, leading to differing policies and regulations worldwide. This article briefly reviews current stem cell platforms, looking specifically at the two existing pluripotent lines available for potential therapeutic applications: hES cells and induced pluripotent stem (iPS) cells. We submit iPS technology as a viable and possibly superior alternative for future medical and research endeavors as it obviates many ethical and resource-related concerns posed by hES cells while prospectively matching their potential for scientific use. However, while the clinical realities of iPS cells appear promising, we must recognize the current limitations of this technology, avoid hype, and articulate ethically acceptable medical and scientific goals.

Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice.

OBJECTIVE: Humanin (HN) is a cytoprotective peptide derived from endogenous mitochondria, expressed in the endothelial layer of human vessels, but its role in atherogenesis in vivo is not known. In vitro study, however, HN reduced oxidized low-density lipoprotein induced formation of reactive oxygen species and apoptosis. The present study tested the hypothesis that long term treatment with HN will have a protective role against endothelial dysfunction and progression of atherosclerosis in vivo. METHODS AND RESULTS: Daily intraperitonial injection of the HN analogue HNGF6A for 16 weeks prevented endothelial dysfunction and decreased atherosclerotic plaque size in the proximal aorta of ApoE-deficient mice fed on a high cholesterol diet, without showing direct vasoactive effects or cholesterol-reducing effects. HN was expressed in the endothelial layer on the aortic plaques. HNGF6A treatment reduced apoptosis and nitrotyrosine immunoreactivity in the aortic plaques without affecting the systemic cytokine profile. HNGF6A also preserved expression of endothelial nitric oxide synthase in aorta. CONCLUSIONS: HN may have a protective effect on endothelial function and progression of atherosclerosis by modulating oxidative stress and apoptosis in the developing plaque.

Long-term survival with metastatic carcinoid tumors: a case report and review of the literature.

Post hoc studies investigating patients with metastatic carcinoid tumors consistently have demonstrated outcomes that are not all too promising in terms of long-term survival, particularly for those with multiple metastases to the small bowel, mesentery, and liver. Here we present a patient with these clinical findings who, contrary to current expectations, has survived much longer than anticipated. This case is a sobering reminder for physicians not only to evaluate carefully and care for their patients but also to choose their words carefully in all communication with them.