Myocardial scintigraphy and clinical stratification as predictors of events in renal transplant candidates

Background: We tested the hypothesis that the universal application of myocardial scanning with single-photon emission computed tomography (SPECT) would result in better risk stratification in renal transplant candidates (RTC) compared with SPECT being restricted to patients who, in addition to renal disease, had other clinical risk factors. Methods: RTCs (n=363) underwent SPECT and clinical risk stratification according to the American Society of Transplantation (AST) algorithm and were followed up until a major adverse cardiovascular event (MACE) or death. Results: Of the 363 patients, 79 patients (22%) had an abnormal SPECT scan and 270 (74%) were classified as high risk. Both methods correctly identified patients with increased probability of MACE. However, clinical stratification performed better (sensitivity and negative predictive value 99% and 99% vs. 25% and 87%, respectively). High-risk patients with an abnormal SPECT scan had a modest increased risk of events (log-rank = 0.03; hazard ratio [HR] = 1.37; 95% confidence interval [95% CI], 1.02-1.82). Eighty-six patients underwent coronary angiography, and coronary artery disease (CAD) was found in 60%. High-risk patients with CAD had an increased incidence of events (log-rank = 0.008; HR=3.85; 95% CI, 1.46-13.22), but in those with an abnormal SPECT scan, the incidence of events was not influenced by CAD (log-rank = 0.23). Forty-six patients died. Clinical stratification, but not SPECT, correlated with the probability of death (log-rank = 0.02; HR=3.25; 95% CI, 1.31-10.82). Conclusion: SPECT should be restricted to high-risk patients. Moreover, in contrast to SPECT, the AST algorithm was also useful for predicting death by any cause in RTCs and for selecting patients for invasive coronary testing.

The Absence of Coronary Calcification Does Not Exclude Obstructive Coronary Artery Disease or the Need for Revascularization in Patients Referred for Conventional Coronary Angiography

Objectives This study was designed to evaluate whether the absence of coronary calcium could rule out >= 50% coronary stenosis or the need for revascularization. Background The latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients. Methods A substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before. Results In all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 +/- 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of >= 50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 >= 50% stenosis. The overall sensitivity for CS = 0 to predict the absence of >= 50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with >= 50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium. Conclusions The absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification. (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors [CORE-64]; NCT00738218) (J Am Coll Cardiol 2010;55:627-34) (C) 2010 by the American College of Cardiology Foundation

Distribution of an asymmetrical copepod, Hatschekia plectropomi, on the gills of Plectropomus leopardus

Hatschekia plectropomi, an ectoparasitic copepod found on the gills, infected Plectropomus leopardus from Heron Island Reef with 100% prevalence (n = 32) and a mean +/- S.E. infection intensity of 131.9 +/- 22.1. The distribution of 4222 adult female parasites across 32 individual host fish was investigated at several organizational levels ranging from the level of holobranch pairs to that of individual filaments. Parasites demonstrated a site preference for the two central holobranchs (2 and 3). Along the lengths of hemibranchs, filaments near the dorsal and ventral ends and those in the proximity of the bend region were rarely occupied. The probability of coming into contact with a suitable attachment site and the ability to withstand ventilation forces at that site were proposed as the major factors affecting distribution. Two H. plectropomi morphotypes were identified based on the direction of body curvature. Regardless of morphotype, 99.9% of individuals were attached such that the convex side of the body was oriented towards the oncoming ventilating water currents. Further, 93.3% of individuals attached to the posterior faces of filaments, leading to a predictable pattern of attachment for this species. It is suggested that the direction of body curvature develops in response to the direction of the ventilating water currents. (c) 2006 The Fisheries Society of the British Isles.

The Use of Smell Identification Tests in the Diagnosis of Parkinson`s Disease in Brazil

Smell identification tests may be of routine clinical value in the differential diagnosis of PD but are subject to cultural variation and have not been systematically evaluated in the Brazilian population. We have applied culturally adapted translations of the University of Pennsylvania 40-item smell identification test (UPSIT-40) and the 16-item identification test from Sniffin` Sticks (SS-16) to nondemented Brazilian PD patients and controls. Pearson`s correlation coefficient between the test scores was 0.76 (95% CI 0.70-0.81, n = 204, P < 0.001). To calculate reliability measures for each test we used the diagnosis (either PD or control) as outcome variable for separate logistic regression analyses using the score in the UPSIT-40 or the SS-16 as a covariate. The SS-16 specificity was 89.0% with a sensitivity of 81.1% (106 PD and 118 controls). The UPSIT-40 specificity was 83.5% and its sensitivity 82.1% (95 PD and 109 controls). Regression curves were used to associate an individual`s smell test score with the probability of belonging to the PD, as opposed to the control group. Our data provide support for the use of the UPSIT-40 and SS-16 to help distinguish early PD from controls. (c) 2008 Movement Disorder Society

Use of methotrexate in older patients - A risk-benefit assessment

Methotrexate is eliminated almost entirely by the kidneys. The risk of methotrexate toxicity is therefore increased in patients with poor renal function, most likely as a result of drug accumulation. Declining renal function with age may thus be an important predictor of toxicity to methotrexate. Up to 60% of all patients who receive methotrexate for rheumatoid arthritis (RA) discontinue taking it because of adverse effects, most of which occur during the first year of therapy. Gastrointestinal complications are the most common adverse effects of methotrexate, but hepatotoxicity, haematological toxicity, pulmonary toxicity, lymphoproliferative disorders and exacerbation of rheumatic nodules have all been reported, Decreased renal function as a result of disease and/or aging appears to be an important determinant of hepatic, lymphoproli ferative and haematological toxicity, Concomitant use of low doses of folic acid has been recommended as an approach to limiting toxicity. Interactions between methotrexate and several nonsteroidal anti-inflammatory drugs have been reported, but they may not be clinically significant. However, caution is advised in the use of such combinations in patients with reduced renal function. More serious toxicities (e.g. pancytopenia) may result when other inhibitors of folate utilisation [e.g. cotrimoxazole (trimethoprim-sulfamethoxazole)] or inhibitors of renal tubular secretion (e.g. probenecid) are combined with methotrexate. Before starting low dose methotrexate therapy in patients with RA, a full blood count, liver function tests, renal function tests and chest radiography should be performed. Blood counts and liver function tests should be repeated at regular intervals. Therapeutic drug monitoring of methotrexate has also been suggested as a means of limiting toxicity. Patients with RA usually respond very favourably to low dose methotrexate therapy, and the probability of patients continuing their treatment beyond 5 years is greater than for other slow-acting antirheumatic drugs. Thus, given its sustained clinical utility and relatively predictable toxicity profile, low dose methotrexate is a useful addition to the therapy of RA.

An analysis of valve re-replacement after aortic valve replacement with biologic devices

Biologic valve re-replacement was examined in a series of 1343 patients who underwent aortic valve replacement at The Prince Charles Hospital, Brisbane, with a cryopreserved or 4 degrees C stored allograft valve or a xenograft valve, A parametric model approach was used to simultaneously model the competing risks of death without re-replacement and re-replacement before death, One hundred eleven patients underwent a first re-replacement for a variety of reasons (69 patients with xenograft valves, 28 patients with 4 degrees C stored allograft valves, and 14 patients with cryopreserved allograft valves), By multivariable analysis younger age at operation was associated with xenograft, 4 degrees C stored allograft, and cryopreserved allograft valve re-replacement, However, this effect was examined in the context of longer survival of younger patients, which increases their exposure to the risk of re-replacement as compared with that in older patients whose decreased survival reduced their probability of requiring valve re-replacement, In patients older than 60 years at the time of aortic valve replacement, the probability of re-replacement (for any reason) before death was similar for xenografts and cryopreserved allograft valves but higher for 4 degrees C stored valves, However, in patients younger than 60 years, the probability of re-replacement at any time during the remainder of the life of the patient was lower with the cryopreserved allograft valve compared with the xenograft valve and 4 degrees C stored allografts.

Validation of a strategy to diagnose coronary artery disease and predict cardiac events in high-risk renal transplant candidates

Background We validated a strategy for diagnosis of coronary artery disease ( CAD) and prediction of cardiac events in high-risk renal transplant candidates ( at least one of the following: age >= 50 years, diabetes, cardiovascular disease). Methods A diagnosis and risk assessment strategy was used in 228 renal transplant candidates to validate an algorithm. Patients underwent dipyridamole myocardial stress testing and coronary angiography and were followed up until death, renal transplantation, or cardiac events. Results The prevalence of CAD was 47%. Stress testing did not detect significant CAD in 1/3 of patients. The sensitivity, specificity, and positive and negative predictive values of the stress test for detecting CAD were 70, 74, 69, and 71%, respectively. CAD, defined by angiography, was associated with increased probability of cardiac events [log-rank: 0.001; hazard ratio: 1.90, 95% confidence interval (CI): 1.29-2.92]. Diabetes (P=0.03; hazard ratio: 1.58, 95% CI: 1.06-2.45) and angiographically defined CAD (P=0.03; hazard ratio: 1.69, 95% CI: 1.08-2.78) were the independent predictors of events. Conclusion The results validate our observations in a smaller number of high-risk transplant candidates and indicate that stress testing is not appropriate for the diagnosis of CAD or prediction of cardiac events in this group of patients. Coronary angiography was correlated with events but, because less than 50% of patients had significant disease, it seems premature to recommend the test to all high-risk renal transplant candidates. The results suggest that angiography is necessary in many high-risk renal transplant candidates and that better noninvasive methods are still lacking to identify with precision patients who will benefit from invasive procedures. Coron Artery Dis 21: 164-167 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Behavior Profile of Family Members of Donors and Nondonors of Organs

Organ transplant shortage is a global problem caused by several factors, most of which are related to members of the family, who play it major role in the donation process. Objective. We sought to determine the most determinant features in the donor profile that relate to positive decisions versus refusal of donation. Material and Methods. Fifty-six families who were approached by the Organ Procurement Organization (OPO) from November 2004 to April 2006 agreed to participate in this work. To assess donor profiles, we used it structured interview. Results. Parental involvement directly in decisions about donation lead to significantly less frequent consent (P = .005), young donor age was associated with a reduced probability of donation (P = .002), violent death negatively influenced donation consent, excluding suicide (P = .004). Conclusion. The present study showed violent death, young patient age, and parental donation consent to be the most important factors that make it harder to obtain consent organ donation. When a collateral relative (sibling/uncle) or children were responsible for the donation decision, there was more success of consent.

Endostatin- and interleukin-2-expressing retroviral bicistronic vector for gene therapy of metastatic renal cell carcinoma

Background Metastatic renal cell carcinoma (mRCC) is one of the most treatment-resistant malignancies. Despite all new therapeutic advances, almost all patients develop resistance to treatment and cure is rarely seen. In the present study, we evaluated the antitumor effect of a bicistronic retrovirus vector encoding both endostatin (ES) and interleukin (IL)-2 using an orthotopic metastatic RCC mouse model. Methods Balb/C-bearing Renca cells were treated with NIH/3T3-LendIRES-IL-2-SN cells. In the survival studies, mice were monitored daily until they died. At the end of the in vivo experiment, serum levels of IL-2 and ES were measured, the lung was weighed, and the number of metastatic nodules, nodule area, tumor vessels and proliferation of tumor-infiltrating Renca cells were determined. Results Inoculation of NIH/3T3-LendIRES-IL-2-SN cells resulted in an increase in ES and IL-2 levels in the treated group (p < 0.05). There was a significant decrease in lung wet weight, lung nodule area and tumor vessels in the treated group compared to the control group (p < 0.001). The proliferation of Renca cells in the bicistronic-treated group was significantly reduced compared to the control group (p < 0.05). Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice submitted to bicistronic therapy (log-rank test, p = 0.0016). Bicistronic therapy caused an increase in the infiltration of CD4, CD4 interferon (IFN)gamma-producing, CD8, CD8 IFN gamma-producing and natural killer (CD49b) cells. Conclusions Retroviral bicistronic gene transfer led to the secretion of functional ES and IL-2 that was sufficiently active to: (i) inhibit tumor angiogenesis and tumor cell proliferation and (ii) increase the infiltration of immune cells (C) Copyright. 2011 John Wiley & Sons, Ltd.

Endostatin gene therapy enhances the efficacy of IL-2 in suppressing metastatic renal cell carcinoma in mice

We investigated whether the administration of IL-2 combined with endostatin gene therapy was able to produce additive or even synergistic immunomodulatory activity in a mouse model of metastatic renal carcinoma. Renca cells were injected into the tail vein of BALB/c mice. After 24 h, the animals were randomly divided into four groups (5 mice/group). One group of mice was the control, the second group received treatment with 100,000 UI of Recombinant IL-2 (Proleukin, Chiron) twice a day, 1 day per week during 2 weeks (IL-2), the third group received treatment with a subcutaneous inoculation of 3.6 x 10(6) endostatin-producing cells, and the fourth group received both therapies (IL-2 + ES). Mice were treated for 2 weeks. In the survival studies, 10 mice/group daily, mice were monitored daily until they died. The presence of metastases led to a twofold increase in endostatin levels. Subcutaneous inoculation of NIH/3T3-LendSN cells resulted in a 2.75 and 2.78-fold increase in endostatin levels in the ES and IL-2 + ES group, respectively. At the end of the study, there was a significant decrease in lung wet weight, lung nodules area, and microvascular area (MVA) in all treated groups compared with the control group (P < 0.001). The significant difference in lung wet weight and lung nodules area between groups IL-2 and IL-2 + ES revealed a synergistic antitumor effect of the combined treatment (P < 0.05). The IL-2 + ES therapy Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice treated with the combined therapy (log-rank test, P = 0.0028). Conjugated therapy caused an increase in the infiltration of CD4, CD8 and CD49b lymphocytes. An increase in the amount of CD8 cells (P < 0.01) was observed when animals received both ES and IL-2, suggesting an additive effect of ES over IL-2 treatment. A synergistic effect of ES on the infiltration of CD4 (P < 0.001) and CD49b cells (P < 0.01) was also observed over the effect of IL-2. Here, we show that ES led to an increase in CD4 T helper cells as well as cytotoxic lymphocytes, such as NK cells and CD8 cells, within tumors of IL-2 treated mice. This means that ES plays a role in supporting the actions of T cells.

White matter microstructure underlying default mode network connectivity in the human brain

Resting state functional magnetic resonance imaging (fMRI) reveals a distinct network of correlated brain function representing a default mode state of the human brain The underlying structural basis of this functional connectivity pattern is still widely unexplored We combined fractional anisotropy measures of fiber tract integrity derived from diffusion tensor imaging (DTI) and resting state fMRI data obtained at 3 Tesla from 20 healthy elderly subjects (56 to 83 years of age) to determine white matter microstructure e 7 underlying default mode connectivity We hypothesized that the functional connectivity between the posterior cingulate and hippocampus from resting state fMRI data Would be associated with the white matter microstructure in the cingulate bundle and fiber tracts connecting posterior cingulate gyrus With lateral temporal lobes, medial temporal lobes, and precuneus This was demonstrated at the p<0001 level using a voxel-based multivariate analysis of covariance (MANCOVA) approach In addition, we used a data-driven technique of joint independent component analysis (ICA) that uncovers spatial pattern that are linked across modalities. It revealed a pattern of white matter tracts including cingulate bundle and associated fiber tracts resembling the findings from the hypothesis-driven analysis and was linked to the pattern of default mode network (DMN) connectivity in the resting state fMRI data Out findings support the notion that the functional connectivity between the posterior cingulate and hippocampus and the functional connectivity across the entire DMN is based oil distinct pattern of anatomical connectivity within the cerebral white matter (C) 2009 Elsevier Inc All rights reserved

Midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation

PURPOSE: To evaluate retrospectively the midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation. MATERIALS AND METHODS: During a 9-year period, 18 children with obstruction of a hepatic vein (HV) or inferior vena cava (IVC) anastomosis underwent percutaneous transluminal angioplasty (PTA) with balloon dilation or stent placement in case of PTA failure after liver transplantation. Patients` body weights ranged from 7.7 kg to 42.6 kg (mean, 18.8 kg +/- 9). Potential predictors of patency were compared between balloon dilation and stent placement groups. RESULTS: Forty-two procedures were performed (range, 1-11 per patient; mean, 2). Technical and initial clinical success were achieved in all cases. Major complications included one case of pulmonary artery stent embolization and one case of hemothorax. Three children (25%) with HV obstruction were treated with PTA and nine (75%) were treated with stent placement. Three children with IVC obstruction (75%) were treated with PTA and one (25%) was treated with a stent. There were two children with simultaneous obstruction at the HV and IVC; one was treated with PTA and the other with a stent. Cases of isolated HV stenosis have a higher probability of patency with balloon-expandable stent treatment compared with balloon dilation (P < .05). Follow-up time ranged from 7 days to 9 years (mean, 42 months +/- 31), and the primary assisted patency rate was 100% when stent placement was performed among the first three procedures. CONCLUSIONS: In cases of venous outflow obstruction resulting from HV and/or IVC lesions after pediatric liver transplantation, percutaneous endovascular treatment with balloon dilation or stent placement is a safe and effective alternative treatment that results in long-term patency.

Potential Effect of Using ABO-Compatible Living-Donor Liver Transplantation

Liver transplantation increased 1.84-fold from 1988 to 2004. However, the number of patients on the waiting list for a liver increased 2.71-fold, from 553 to 1500. We used a mathematical equation to analyze the potential effect of using ABO-compatible living-donor liver transplantation (LDLT) on both our liver transplantation program and the waiting list. We calculated the prevalence distribution of blood groups (O, A, B, and AB) in the population and the probability of having a compatible parent or sibling for LDLT. The incidence of ABO compatibility in the overall population was as follows: A, 0.31; B, 0.133; O, 0.512; and AB, 0.04. The ABO compatibility for parent donors was blood group A, 0.174; B, 0.06; O, 0.152; and AB, 0.03; and for sibling donors was A, 0.121; B, 0.05; O, 0.354; and AB, 0.03. Use of LDLT can reduce the pressure on our liver transplantation waiting list by decreasing its size by at least 16.5% at 20 years after its introduction. Such a program could save an estimated 3600 lives over the same period.

Late Gadolinium Enhancement Magnetic Resonance Imaging in the Diagnosis and Prognosis of Endomyocardial Fibrosis Patients

Background-Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiography is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of EMF has not been investigated. Methods and Results-Thirty-six patients (29 women; age, 54 +/- 12 years) with EMF diagnosis after clinical evaluation and comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes, ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole (mL/m(2)). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most prominent. There was a relation between increased FT/body surface area and worse New York Heart Association functional class and with increased probability of surgery (P<0.05). The histopathologic examination of resected FT showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area >19 mL/m(2) had an increased mortality rate, with a relative risk of 10.8. Conclusions-Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition. (Circ Cardiovasc Imaging. 2011;4:304-311.)

Adverse Drug Reactions and Drug Interactions as Causes of Hospital Admission in Oncology

Context. Although several studies have evaluated the frequency of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in general medicine, few studies have looked at the epidemiology of adverse drug events (ADEs) in oncology. Objectives. We sought to investigate how many hospital admissions in oncology are related to a DDI or an ADR. Methods. All cancer patients admitted to an oncology ward during an eight-month period had their charts retrospectively evaluated for reasons of hospitalization, using a 4-point scale (definitely, probably, possibly, or unlikely associated) to classify admissions by their probability of being associated with either a DDI or an ADR. Results. From September 2007 to May 2008, there were 550 hospital admissions and 458 were eligible. Among unplanned admissions (n = 298), 39 (13.0%, 95% confidence interval [CI] 9.4%-17.4%) were considered to be associated with an ADE, 33 (11.0%, 95% CI 7.7%-15.2%) with an ADR, and six (2.0%, 95% CI 0.7%-4.3%) with a DDI. The most common DDIs involved warfarin, captopril, and anti-inflammatory agents, and the most frequent ADR was neutropenic fever post-chemotherapy. Most patients were discharged completely recovered, but two patients died. Conclusion. Approximately one in 10 unplanned hospitalizations of cancer patients is associated with an ADE. Prospective and population-based studies are warranted to evaluate their magnitude in oncology. J Pain Symptom Manage 2011;42:342-353. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.