160,472 research outputs found

    TRA-1-60-positive/CD45low cells found in the peripheral blood of prostate cancer patients with metastatic disease – A proof-of-concept study

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    Purpose Over 90% of all cancer related deaths are due to metastasis. However, current diagnostic tools can\u27t reliably discriminate between invasive and localized cancers. Patients and methods In this proof-of-concept study, we employed the embryonic stem cell marker TRA-1-60 (TRA+) to identify TRA + cells within the blood of prostate cancer patients and searched for TRA + cells in men with metastatic and localized cancers. We isolated whole peripheral blood mononuclear cells from 26 metastatic prostate cancer patients, from 13 patients with localized prostate cancer and from 17 healthy controls. Cells were stained for DAPI, CD45 and TRA + by immunofluorescence and imaged by epi-fluorescence microscopy. Imaged-based software was used both to identify TRA + cells, and to analyze CD45 levels in TRA+ and negative cells. Results We found high numbers of TRA + cells within the blood of metastatic cancer patients, whereas healthy individuals or men with localized prostate cancer showed none or very low numbers of TRA + cells. Further analysis of the CD45 levels of TRA + cells revealed a small population of TRA + cells with almost undetectable CD45 levels that were found frequently in metastatic prostate cancer patients. By excluding CD45 positive cells from the TRA + cell pool, we were able to refine the assay to be highly specific in identifying men with metastatic disease. In fact, the difference of CD45 levels between TRA+ and negative cells was a robust measure to distinguish between men with localized and metastatic prostate cancers in this small patient cohort. Conclusions The data suggest that metastatic prostate cancer patient have significant numbers of TRA+/CD45low cells which might represent a potential tool for diagnostic assessment in the future

    Risk Score, Causes, and Clinical Impact of Failure of Transradial Approach for Percutaneous Coronary Interventions

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    ObjectivesTo study the causes of and to develop a risk score for failure of transradial approach (TRA) for percutaneous coronary intervention (PCI).BackgroundTRA-PCI failure has been reported in 5% to 10% of cases.MethodsTRA-PCI failure was categorized as primary (clinical reasons) or crossover failure. Multivariate analysis was performed to determine independent predictors of TRA-PCI failure, and an integer risk score was developed.ResultsFrom January to June 2010, TRA-PCI was attempted in 1,609 (97.3%) consecutive patients, whereas 45 (2.7%) had primary TRA-PCI failure. Crossover TRA-PCI failure occurred in 30 (1.8%) patients. Causes of primary TRA-PCI failure included chronic radial artery occlusion (11%), previous coronary artery bypass graft (27%), and cardiogenic shock (20%). Causes for crossover TRA-PCI failure included: inadequate puncture in 17 patients (57%); radial artery spasm in 5 (17%); radial loop in 4 (13%); subclavian tortuosity in 2 (7%); and inadequate guide catheter support in 2 (7%) patients. Female sex (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.95 to 5.26, p < 0.0001), previous coronary artery bypass graft (OR: 6.1; 95% CI: 3.63 to 10.05, p < 0.0001), and cardiogenic shock (OR: 11.2; 95% CI: 2.78 to 41.2, p = 0.0011) were independent predictors of TRA-PCI failure. Risk score values from 0 to 7 predicted a TRA-PCI failure rate from 2% to 80%.ConclusionsIn a high-volume radial center, 2.7% of patients undergoing PCI are excluded from initial TRA on clinical grounds, whereas crossover to femoral approach is required in only 1.8% of the cases. A new simple clinical risk score is developed to predict TRA-PCI failure

    Ultrasound assessment of transversus abdominis muscle contraction ratio during abdominal hollowing: a useful tool to distinguish between patients with chronic low back pain and healthy controls?

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    Spine stabilisation exercises, in which patients are taught to preferentially activate the transversus abdominus (TrA) during "abdominal hollowing” (AH), are a popular treatment for chronic low back pain (cLBP). The present study investigated whether performance during AH differed between cLBP patients and controls to an extent that would render it useful diagnostic tool. 50patients with cLBP (46.3±12.5years) and 50healthy controls (43.6±12.7years) participated in this case-control study. They performed AH in hook-lying. Using M-mode ultrasound, thicknesses of TrA, and obliquus internus and externus were determined at rest and during 5s AH (5measures each body side). The TrA contraction-ratio (TrA-CR) (TrA contracted/rest) and the ability to sustain the contraction [standard deviation (SD) of TrA thickness during the stable phase of the hold] were investigated. There were no significant group differences for the absolute muscle thicknesses at rest or during AH, or for the SD of TrA thickness. There was a small but significant difference between the groups for TrA-CR: cLBP 1.35±0.14, controls 1.44±0.24 (p<0.05). However, Receiver Operator Characteristics (ROC) analysis revealed a poor and non-significant ability of TrA-CR to discriminate between cLBP patients and controls on an individual basis (ROC area under the curve, 0.60 [95% CI 0.495; 0.695], p=0.08). In the patient group, TrA-CR showed a low but significant correlation with Roland Morris score (Spearman Rho=0.328; p=0.02). In conclusion, the difference in group mean values for TrA-CR was small and of uncertain clinical relevance. Moreover, TrA-CR showed a poor ability to discriminate between control and cLBP subjects on an individual basis. We conclude that the TrA-CR during abdominal hollowing does not distinguish well between patients with chronic low back pain and healthy control

    Distal Versus Conventional Radial Access for Coronary Angiography and Intervention The DISCO RADIAL Trial

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    BACKGROUND Currently, transradial access (TRA) is the recommended access for coronary procedures because of increased safety, with radial artery occlusion (RAO) being its most frequent complication, which will increasingly affect patients undergoing multiple procedures during their lifetimes. Recently, distal radial access (DRA) has emerged as a promising alternative access to minimize RAO risk. A large-scale, international, randomized trial comparing RAO with TRA and DRA is lacking. OBJECTIVES The aim of this study was to assess the superiority of DRA compared with conventional TRA with respect to forearm RAO. METHODS DISCO RADIAL (Distal vs Conventional Radial Access) was an international, multicenter, randomized controlled trial in which patients with indications for percutaneous coronary procedure using a 6-F Slender sheath were randomized to DRA or TRA with systematic implementation of best practices to reduce RAO. The primary endpoint was the incidence of forearm RAO assessed by vascular ultrasound at discharge. Secondary endpoints include crossover, hemostasis time, and access site-related complications. RESULTS Overall, 657 patients underwent TRA, and 650 patients underwent DRA. Forearm RAO did not differ between groups (0.91% vs 0.31%; P = 0.29). Patent hemostasis was achieved in 94.4% of TRA patients. Crossover rates were higher with DRA (3.5% vs 7.4%; P = 0.002), and median hemostasis time was shorter (180 vs 153 minutes; P < 0.001). Radial artery spasm occurred more with DRA (2.7% vs 5.4%; P = 0.015). Overall bleeding events and vascular complications did not differ between groups. CONCLUSIONS With the implementation of a rigorous hemostasis protocol, DRA and TRA have equally low RAO rates. DRA is associated with a higher crossover rate but a shorter hemostasis time. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

    Cardiac Catheterizations in Patients With Prior Coronary Bypass Surgery:Impact of Access Strategy on Short-Term Safety and Long-Term Efficacy Outcomes

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    Little data are available on access strategy outcomes for cardiac catheterizations in patients with prior coronary artery bypass graft surgery (CABG). We investigated the effect of transradial access (TRA) and transfemoral access (TFA) on short-term major vascular complications (MVC) and long-term major adverse cardiovascular events (MACE). In this single-center, retrospective cohort study, 1084 patients met our inclusion criteria (TRA = 469; TFA = 615). The cumulative incidence for the primary safety endpoint MVC at 30 days (a composite of major bleeding, retroperitoneal hematoma, dissection, pseudoaneurysm, and arteriovenous fistula) was lower with TRA (0.7% vs 3.0%, P &lt;.01) and this difference remained significant after propensity score adjustment (odds ratio: 0.24; 95% CI, 0.07-0.83; P =.024). The cumulative incidence for the primary efficacy endpoint MACE at 36 months (a composite of all-cause mortality, myocardial infarction, stroke, and urgent target vessel revascularization) was 28.6% with TRA and 27.6% with TFA, respectively. Kaplan-Meier curves showed no difference for the primary efficacy endpoint (P =.65). Contrast use (mL) was significantly lower with TRA (130 [100-180] vs 150 [100-213], P &lt;.01). In conclusion, in patients with prior CABG, TRA was associated with significantly fewer short-term MVC and contrast use, but not with a difference in long-term MACE, compared with TFA.</p

    Therapeutic targeting of integrin αvβ6 in breast cancer

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    BACKGROUND: Integrin ?v?6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of ?v?6 has yet to be elucidated in breast cancer.METHODS: Protein expression of integrin subunit beta6 (?6) was measured in breast cancers by immunohistochemistry (n &gt; 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of ?6 in breast cell lines, the role of ?v?6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ? 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.RESULTS: High expression of either the mRNA or protein for the integrin subunit ?6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of ?6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P &lt; .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.CONCLUSIONS: Targeting ?v?6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.<br/

    La relazione che organizza il contesto sanitario: domanda dell’utenza e risposta dei servizi sanitari, nel territorio e nell’ospedale - The relationship which organizes the healthcare context: users’ demand and response of healthcare services, in the territory and the hospital

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    Our intent is to present citizens’ demand of health care services in Italy through a research structured in three studies. We used the Emotional Text Analysis (ETA) to lead the three s tudies: the first study regarded the citizens’expectations of the healthcare services, the second study regarded the point of view of the hospital personnel (medical doctors and nurses), the third regarded the point of view of the General Practitioners onthe health care services. These three studies are briefly presented. Data and outcome of an Assumed Similarity Test applied to all experimental subjects of the three studies in order to make a comparison among them, are also presented. The findings of the Emotional Text Analysis show that citizens, potential users of health services, center their requests on their individual subjectivity, and seek answers both to their suffering and to the feeling of alienation that characterizes the being sick feeling that makes them go to a medical doctor. For their part, general practitioners and hospital doctors immediately transform this subjective feeling in an objective medical diagnosis. Here a first gap emerges between patient’s demand and medical response, leavingthe possibility of an alliance on the diagnosis in order to jointly fight the disease. It has long been in place though a change that has expelled the patient also from sharing the diagnostic process, increasingly taken from self-centered dynamics within the healthcare system. This widens the gap between the request of the citizens and the response of the health services, that contributes to that conflictual growth to which defensive medicine gives a dysfunctional answer. The Assumed Similarity Test contributes to the interpretation of the health care dynamic identified in the Emotional Text Analysis; particularly in regard to the unfolding conflict, given by the hypothesis emerging from the data analysis, that a feeling of closeness for the hospital personnel goes along with an emotional stance of overpowering the othe

    La rappresentazione del rapporto tra utenti e sistema sanitario: I modelli culturali dei medici di medicina generale - The representation of the relationship between users and healthcare system: Cultural models of general practitioners

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    The present research study explores the emotional and symbolic representation of the Italian healthcare system and specifically of general medical services reported by a group of Italian general practitioners. General medicine is recently affected by a structural change which could be sustained also by a cultural revolution, however this revolution seems to be oriented to expected values without a clear methodology which promotes and accompanies this cultural change. The present study deals with the lack of practices due to these unrealized expected values and assumes that for intervening it is necessary knowing the existing culture before thinking to change it. Interviews to 36 general practitioners were analyzed by Emotional Text Analysis (AET). Results highlight a factorial space characterized by five clusters. According to respondents’ perspective, healthcare problems refer to two large issues characterized by powerlessness of general practitioners to intervene. On the one hand, there is health emergency, dealt with by first aid and emergency medicine. On the other hand, there is chronicity, especially affecting the elderly, which is dealt with by other workers (nurses, private family assistants, social workers) who care patients at home and replace physicians. The general practitioners’ work is difficult because of many different reasons; but the central theme is the lack of absolute power – based on morality and consciousness – which leads to the perception of catastrophic consequences for medical profession and the physician-patient relationship. Often, general practitioners are in their offices and are not able to go to patients’ home, therefore they cannot create care relationships based on trust and dependence which allow useful and trustworthy interventions. In sum, the core theme emerging from data refers to the general practitioners’ perceived lack of personal and trust-based relationships with patients
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