Ankle-Brachial Index: A Simple Way to Predict Mortality among Patients on Hemodialysis - A Prospective Study

Background: Ankle-brachial index (ABI) can access peripheral artery disease and predict mortality in prevalent patients on hemodialysis. However, ABI has not yet been tested in incident patients, who present significant mortality. Typically, ABI is measured by Doppler, which is not always available, limiting its use in most patients. We therefore hypothesized that ABI, evaluated by a simplified method, can predict mortality in an incident hemodialysis population. Methodology/Principal Findings: We studied 119 patients with ESRD who had started hemodialysis three times weekly. ABI was calculated by using two oscillometric blood pressure devices simultaneously. Patients were followed until death or the end of the study. ABI was categorized in two groups normal (0.9-1.3) or abnormal (<0.9 and >1.3). There were 33 deaths during a median follow-up of 12 months (from 3 to 24 months). Age (1 year) (hazard of ratio, 1.026; p = 0.014) and ABI abnormal (hazard ratio, 3.664; p = 0.001) were independently related to mortality in a multiple regression analysis. Conclusions: An easy and inexpensive technique to measure ABI was tested and showed to be significant in predicting mortality. Both low and high ABI were associated to mortality in incident patients on hemodialysis. This technique allows nephrologists to identify high-risk patients and gives the opportunity of early intervention that could alter the natural progression of this population.

Ventilatory threshold is related to walking tolerance in patients with intermittent claudication

Background: This study assessed the relationship between lower limb hemodynamics and metabolic parameters with walking tolerance in patients with intermittent claudication (IC). Patients and methods: Resting ankle-brachial index (ABI), baseline blood flow (BF), BF response to reactive hyperemia (BFRH), oxygen uptake (VO2), initial claudication distance (ICD) and total walking distance (TWD) were measured in 28 IC patients. Pearson and Spearman correlations were calculated. Results: ABI, baseline BF and BF response to RH did not correlate with ICD or TWD. VO2 at first ventilatory threshold and VO(2)peak were significantly and positively correlated with ICD (r = 0.41 and 0.54, respectively) and TWD (r = 0.65 and 0.71, respectively). Conclusions: VO(2)peak and VO2 at first ventilatory threshold, but not ABI, baseline BF and BFHR were associated with walking tolerance in IC patients. These results suggest that VO2 at first ventilatory threshold may be useful to evaluate walking tolerance and improvements in IC patients.

Pathogen levels and clinical response to periodontal treatment in patients with Interleukin 8 haplotypes

The aim of this study was to investigate the effect of non-surgical treatment of periodontitis on the levels of periodontopathogens and clinical parameters in patients with different genetic backgrounds produced by polymorphisms in the Interleukin (IL8) gene. Thirty patients grouped according to IL8 ATC/TTC or AGT/TTC haplotypes were submitted to non-surgical periodontal treatment. Levels of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were determined in 240 subgingival plaque samples by qPCR. The association between IL8 haplotypes and the levels of periodontopathogens and clinical parameters was investigated by multilevel analysis accounting for the clustering of diseased sites analyzed within patients. It was observed that neither levels of periodontopathogens nor non-surgical treatment was associated with the IL8 haplotype. The clinical parameters after periodontal treatment were similar in diseased and healthy sites, independently of the IL8 haplotype. Nonetheless, in the same period, diseased sites of AGT/TTC patients harbored higher levels of P. gingivalis, T. denticola, T. forsythia, and red complex than those of ATC/TTC patients. However, the non-surgical periodontal therapy decreased the levels of these periodontopathogens and of the tested clinical parameters of diseased sites in both groups. Non-surgical therapy is equally effective in improving clinical parameters and decreasing the levels of periodontopathogens, independent of the genotype groups produced by the IL8 haplotype.

Hausdorff Distance evaluation of orthodontic accessories' streaking artifacts in 3D model superimposition

The aim of this study was to determine whether image artifacts caused by orthodontic metal accessories interfere with the accuracy of 3D CBCT model superimposition. A human dry skull was subjected three times to a CBCT scan: at first without orthodontic brackets (T1), then with stainless steel brackets bonded without (T2) and with orthodontic arch wires (T3) inserted into the brackets' slots. The registration of image surfaces and the superimposition of 3D models were performed. Within-subject surface distances between T1-T2, T1-T3 and T2-T3 were computed and calculated for comparison among the three data sets. The minimum and maximum Hausdorff Distance units (HDu) computed between the corresponding data points of the T1 and T2 CBCT 3D surface images were 0.000000 and 0.049280 HDu, respectively, and the mean distance was 0.002497 HDu. The minimum and maximum Hausdorff Distances between T1 and T3 were 0.000000 and 0.047440 HDu, respectively, with a mean distance of 0.002585 HDu. In the comparison between T2 and T3, the minimum, maximum and mean Hausdorff Distances were 0.000000, 0.025616 and 0.000347 HDu, respectively. In the current study, the image artifacts caused by metal orthodontic accessories did not compromise the accuracy of the 3D model superimposition. Color-coded maps of overlaid structures complemented the computed Hausdorff Distances and demonstrated a precise fusion between the data sets.

Inflammation in cancer cachexia: To resolve or not to resolve (is that the question?)

Background & aims: Cachexia is associated with poor prognosis and shortened survival in cancer patients. Growing evidence points out to the importance of chronic systemic inflammation in the aetiology of this syndrome. In the recent past, chronic inflammation was considered to result from overexpression and release of pro-inflammatory factors. However, this conception is now the focus of debate, since the importance of a crescent number of pro-resolving agents in the dissolution of inflammation is now recognised - leading to the hypothesis that chronic inflammation occurs rather due to failure in the resolution process. We intend to put forward the possibility that this may also be occurring in cancer cachexia. Methods: Recent reviews on inflammation and cachexia, and on the factors involved in the resolution of inflammation are discussed. Results: The available information suggests that indeed, inflammation resolution failure may be present in cachexia and therefore we speculate on possible mechanisms. Conclusions: We emphasise the importance of studying resolution-related mechanisms in cancer cachexia and propose the opening of a new venue for cachexia treatment. (C) 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer

Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. Patients and Methods Patients were randomly assigned to first-or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand-foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

Toward the optimal dose metric in continuous renal replacement therapy

Purpose: There is no consensus on the optimal method to measure delivered dialysis dose in patients with acute kidney injury (AKI). The use of direct dialysate-side quantification of dose in preference to the use of formal blood-based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has been recommended for dose assessment in critically-ill patients with AKI. We evaluate six different blood-side and dialysate-side methods for dose quantification. Methods: We examined data from 52 critically-ill patients with AKI requiring dialysis. All patients were treated with pre-dilution CWHDF and regional citrate anticoagulation. Delivered dose was calculated using blood-side and dialysis-side kinetics. Filter function was assessed during the entire course of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12 hours. Results: Median daily treatment time was 1,413 min (1,260-1,440). The median observed effluent volume per treatment was 2,355 mL/h (2,060-2,863) (p<0.001). Urea mass removal rate was 13.0 +/- 7.6 mg/min. Both EKR (r(2)=0.250; p<0.001) and K-D (r(2)=0.409; p<0.001) showed a good correlation with actual solute removal. EKR and K-D presented a decline in their values that was related to the decrease in filter function assessed by the FUN/BUN ratio. Conclusions: Effluent rate (ml/kg/h) can only empirically provide an estimated of dose in CRRT. For clinical practice, we recommend that the delivered dose should be measured and expressed as K-D. EKR also constitutes a good method for dose comparisons over time and across modalities.

The negative binomial-beta Weibull regression model to predict the cure of prostate cancer

In this article, for the first time, we propose the negative binomial-beta Weibull (BW) regression model for studying the recurrence of prostate cancer and to predict the cure fraction for patients with clinically localized prostate cancer treated by open radical prostatectomy. The cure model considers that a fraction of the survivors are cured of the disease. The survival function for the population of patients can be modeled by a cure parametric model using the BW distribution. We derive an explicit expansion for the moments of the recurrence time distribution for the uncured individuals. The proposed distribution can be used to model survival data when the hazard rate function is increasing, decreasing, unimodal and bathtub shaped. Another advantage is that the proposed model includes as special sub-models some of the well-known cure rate models discussed in the literature. We derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes. We analyze a real data set for localized prostate cancer patients after open radical prostatectomy.

Toll-like receptor 3: implications for proinflammatory microenvironment in human breast cancer

Under many circumstances, the host constituents that are found in the tumor microenvironment support a malignancy network and provide the cancer cells with advantages in proliferation, invasiveness and metastasis establishment at remote organs. It is known that Toll like receptors (TLRs) are expressed not only on immune cells but also on cancer cells and it has suggested a deleterious role for TLR3 in inflammatory disease. Hypothesizing that altered IFN gamma signaling may be a key mechanism of immune dysfunction common to cancer as well CXCR4 is overexpressed among breast cancer patients, the mRNA expression of TLR3, CXCR4 and IFN gamma in breast cancer tumor tissues was investigated. No statistically significant differences in the expression of CXCR4 mRNA, IFN gamma and TLR3 between healthy and tumor tissues was observed, however, it was verified a positive correlation between mRNA relative expression of TLR3 and CXCR4 (p < 0.001), and mRNA relative expression of TLR3 was significantly increased in breast cancer tumor tissue when compared to healthy mammary gland tissue among patients expressing high IFN gamma (p = 0.001). Since the tumor microenvironment plays important roles in cancer initiation, growth, progression, invasion and metastasis, it is possible to propose that an overexpression of IFN gamma mRNA due to the pro-inflammatory microenvironment can lead to an up-regulation of CXCR4 mRNA and consequently to an increased TLR3 mRNA expression even among nodal negative patients. In the future, a comprehensive study of TLR3, CXCR4 and IFN gamma axis in primary breast tumors and corresponding healthy tissues will be crucial to further understanding of the cancer network.

Neurovascular anatomical variations in the anterior palate observed on CBCT images

Objective: This study aimed to assess the presence of additional foramina and canals in the anterior palate region, through cone beam computed tomography (CBCT) images, describing their location, direction, and diameter. Materials & Methods: CBCT exams of 178 subjects displaying the anterior maxilla were included and the following parameters were registered: gender; age group; presence of additional foramina in the anterior palate (AFP) with at least 1 mm in diameter; location and diameter of AFP; and direction of bony canals associated with AFP. Results: Twenty-eight patients (15.7%) presented AFP and in total 34 additional foramina were registered. No statistical differences between patients with or without AFP were found for gender or age. The average diameter of AFP was 1.4 mm (range from 1 to 1.9 mm). Their location was variable, with most of the cases occurring in the alveolar process near the incisors or canines (n = 27). In 18 cases, AFP was associated with bony canals with upward or oblique direction toward the anterior nasal cavity floor. In 14 cases, the canal presented as a direct extension of the canalis sinuosus, in an upward direction laterally to the nasal cavity aperture. In two cases, the canal was observed adjacent to the incisive and joined the nasopalatine canal superiorly. Discussion: CBCT images have a crucial role in the recognition of anatomical variations by allowing detailed tridimensional evaluations. Additional foramina and canals in the anterior region of the upper jaw are relatively frequent. Practitioners should be aware and trained to identify these variations. Conclusions: Over 15% of the population studied had additional foramina in the anterior palate, between 1 mm and 1.9 mm wide, with variable locations. In most cases the canals associated with these foramina either presented as a direct extension of the canalis sinuosus, or coursed towards the nasal cavity floor.

Subcutaneous Tissue Thickness is an Independent Predictor of Image Noise in Cardiac CT

Background: Few data on the definition of simple robust parameters to predict image noise in cardiac computed tomography (CT) exist. Objectives: To evaluate the value of a simple measure of subcutaneous tissue as a predictor of image noise in cardiac CT. Methods: 86 patients underwent prospective ECG-gated coronary computed tomographic angiography (CTA) and coronary calcium scoring (CAC) with 120 kV and 150 mA. The image quality was objectively measured by the image noise in the aorta in the cardiac CTA, and low noise was defined as noise < 30HU. The chest anteroposterior diameter and lateral width, the image noise in the aorta and the skin-sternum (SS) thickness were measured as predictors of cardiac CTA noise. The association of the predictors and image noise was performed by using Pearson correlation. Results: The mean radiation dose was 3.5 ± 1.5 mSv. The mean image noise in CT was 36.3 ± 8.5 HU, and the mean image noise in non-contrast scan was 17.7 ± 4.4 HU. All predictors were independently associated with cardiac CTA noise. The best predictors were SS thickness, with a correlation of 0.70 (p < 0.001), and noise in the non-contrast images, with a correlation of 0.73 (p < 0.001). When evaluating the ability to predict low image noise, the areas under the ROC curve for the non-contrast noise and for the SS thickness were 0.837 and 0.864, respectively. Conclusion: Both SS thickness and CAC noise are simple accurate predictors of cardiac CTA image noise. Those parameters can be incorporated in standard CT protocols to adequately adjust radiation exposure.