Group Median Values Research Articles

PP.16.15] THE RELATION BETWEEN PULSATILE (STIFFNESS RELATED) AND STEADY BLOOD PRESSURE COMPONENTS AND LEFT ATRIAL VOLUME IN THE CONTEXT OF LEFT VENTRICULAR MASS INDEX

Objective: To verify the relation between a range of blood pressure components (steady and pulsatile) and carotid-femoral pulse wave velocity and measures of left atrial volume. Design and method: In a group of inhabitants of suburban area of Krakow, we measured 24 hour (SBP24 h, DBP24 h, MAP24 h, PP24 h) and central (cSBP, cDBP, cMAP, cPP) blood pressures and carotid-femoral pulse wave velocity (PWV), parameters of left ventricular mass (LVM, LVMI) and left atrial volume (LAV, LAVI), and gathered anthropometric data, information on habits and relevant medical history. Further, with division according to sex-stratified dichotomised LVMI (95 g/m2 for women and 115 g/m2 for men) we performed correlation analysis to identify possibly significant relations between measures of left atrial volume and other studied parameters. We also fitted linear regression models in order to assess the respective value of steady and pulsatile BP components as factors related to measures of left atrial volume. Results: The mean (SD) age of 205 participants (66% women,50% hypertensives) was 53.6 years(±8.3). After group division we identified statistically significant correlations (p < 0.05) only in persons below the group-median value of LVMI. For LAV they were as follows: SBP24h(r = 0.26), MAP24h(r = 0.16), PP24h(r = 0.28), cSBP(r = 0.33), cDBP(r = 0.29), cMAP(0.34), cPP(r = 0.20), PWV(r = 0.25). For LAVI the values were the following: SBP24h(r = 0.24), PP24h(r = 0.28), cSBP(r = 0.34), cDBP(r = 0.30), cMAP(r = 0.32), cPP(r = 0.25), PWV(r = 0.28). In the regression analysis,MAP, and not PP, SBP and PWV, both from 24 h and pulse wave analysis, is related with left atrial volume, in persons below the group-median value of LVMI(p < 0,05). For LAV: beta = 0.35 for cMAP and beta = 0.35 for MAP24 h. For LAVI: beta = 0.13 for cMAP. In persons with significant increase in LVMI there was no relation between BPs and PWV and left atrial volume measures. Conclusions: Contrary to current knowledge underlying the role of stiffness related BPs in the hard and intermediate outcomes, we found that mean arterial pressure is associated with greater left atrial volumes. The fact that the relation is blunted in persons with greater LVMI, itself related more to MAP than PP, shows the importance of this particular form of target organ damage in relation to LAV.

Properties of the motor unit action potential shape in proximal and distal muscles of the upper limb in healthy and post-stroke individuals.

Spectral analysis of surface electromyograms (sEMG) is often used to estimate central and peripheral characteristics of a motor unit (MU) population, such as average conduction velocity, proportion of muscle fiber types, and pattern of MU recruitment. This estimation is based on the assumption that the sEMG adequately reflects the frequency characteristics of the underlying MU action potentials (MUAP). However, sEMG has limitations in this respect, based on physiological and non-physiological factors that influence its frequency content. We present a method to examine characteristics of a MU population more reliably by assessing the distributions of frequency content and amplitude for a collection of individual MUAPs, identified using high-density sEMG decomposition. We demonstrate the use of this approach to examine how MU characteristics differ across muscles and in the post-stroke state by presenting preliminary data from deltoid (DELT), biceps (BIC), and finger flexor (FF) MU populations from 12 post-stroke individuals and 8 able-bodied controls. The results show differences in the magnitude and range of MUAP median frequencies across muscles in both groups. The group median values were higher in the stroke group for the DELT and FF and lower in the stroke group for the BIC. The range of frequencies was larger in the stroke group for all muscles. The distribution of MUAP RMS amplitude in both stroke and control groups had a substantially larger range in FF than in DELT and BIC. The group median values for the FF were twice as large in the stroke group. In addition, there were differences in the frequency and amplitude results between MUAP and global sEMG analyses. The implications of these findings and possible applications of the approach are discussed.

Clinical significance of serum laminin levels in patients with lung cancer.

Cellular adhesion molecules are considered useful markers in the diagnosis and prognosis of several types of malignant tumors. Laminin, a major structural component of the basement membrane, is a strong promoter of cell adhesion, migration, differentiation and proliferation via integrins and other cell surface receptors. The present study aimed to evaluate the clinical significance of the serum level of laminin in lung cancer patients. A total of 80 patients with lung cancer were enrolled in the study. The serum laminin level was measured by the solid-phase sandwich enzyme-linked immunosorbent assay method. The median age was 58.5 years (range, 36-80 years). The majority of the patients had non-small cell lung carcinoma (85%) and stage IV disease (56%). The baseline serum laminin levels of patients were significantly higher compared to the control group (median values 1.17 vs. 0.78 ng/ml, P=0.033). However, the clinical variables, such as age, gender, histology, stage of disease and response to chemotherapy, were not correlated with serum laminin level (P>0.05). Similarly, serum laminin level was not associated with survival (P=0.68). In conclusion, the serum level of laminin may have a diagnostic value in lung cancer patients. However, its predictive and prognostic roles were not observed.

Levels of serum fibronectin as a biomarker in gastric cancer patients: Correlation with clinical diagnosis and outcome

Fibronectin is an important component of the extracellular matrix and serves a role in the pathogenesis of multiple malignancies. The expression of fibronectin also affects the outcome for patients with cancer. The objective of the present study was to determine the clinical significance of the serum fibronectin levels in patients with gastric cancer. A total of 63 patients with a pathologically confirmed diagnosis of gastric cancer were enrolled into the present study. Serum fibronectin concentrations were determined by the solid-phase sandwich enzyme-linked immunosorbent assay method. Age and sex matched healthy controls (n=30) were included in the analysis. The median age at diagnosis was 62 years (range 28-82 years). The baseline serum fibronectin levels of the patients with gastric cancer were significantly higher compared with those in the control group (median values, 606, vs. 193 ng/ml; P<0.001). The known clinical variables, including the age of the patient, gender, site of lesion, histology, histological grade, stage of disease and serum tumor markers, including lactate dehydrogenase, carcinoembryonic antigen and cancer antigen 19.9, were not found to be correlated with serum fibronectin concentrations (P>0.05). In addition, no correlation was observed in serum fibronectin level and response to chemotherapy (P=0.12). Serum fibronectin concentration demonstrated no prognostic role on survival (P=0.43). In conclusion, the serum levels of fibronectin may have a good diagnostic marker in patients with gastric cancer. However, its predictive and prognostic values remain to be elucidated.

(68)Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer.

We aim to investigate the pharmacokinetics and distribution of the recently clinically introduced radioligand (68)Ga-PSMA-11 in men with recurrent prostate cancer (PC) by means of dynamic and whole-body PET/CT. The correlation between PSA levels and (68)Ga-PSMA-11 PET parameters is also investigated. 31 patients with biochemical failure after primary PC treatment with curative intent (median age 71.0years) were enrolled in the analysis. The median PSA value was 2.0ng/mL (range = 0.1 - 130.0ng/mL) and the median Gleason score was 7 (range = 5 - 9). 8/31 (25.8%) of the included patients had a PSA value < 0.5ng/ml. All patients underwent dynamic PET/CT (dPET/CT) scanning (60min) of the pelvis and lower abdomen as well as whole-body PET/CT with (68)Ga-PSMA-11. dPET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). 22/31 patients (71.0%) were (68)Ga-PSMA-11-positive, while 9/31 (29.0%) patients were (68)Ga-PSMA-11-negative. The median PSA value in the (68)Ga-PSMA-11-positive group was significantly higher (median = 2.35ng/mL; range = 0.19 - 130.0ng/mL) than in the (68)Ga-PSMA-11-negative group (median value: 0.34ng/mL; range = 0.10 - 4.20ng/mL). A total of 76 lesions were semi-quantitatively evaluated. PC recurrence-associated lesions demonstrated a mean SUVaverage = 12.4 (median = 9.0; range = 2.2 - 84.5) and mean SUVmax = 18.8 (median = 14.1; range = 3.1 - 120.3). Dynamic PET/CT studies of the pelvis revealed the following mean values for the PC recurrence-suspicious lesions: K1 = 0.26, k3 = 0.30, influx = 0.14 and FD = 1.24. Time-activity curves derived from PC-recurrence indicative lesions revealed an increasing (68)Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate, but significant, correlation between PSA levels and the number of lesions detected on (68)Ga-PSMA-11 PET/CT (r = 0.54) and between PSA levels and SUVaverage (r = 0.48) or SUVmax (r = 0.44). Ga-PSMA-11 PET/CT demonstrated an overall detection rate of 71.0% 60min p.i. of the radiotracer in a mixed patient population with respect to PSA levels and including patients with very low PSA values. Higher PSA values were associated with a higher detection rate. The tracer uptake in PC-recurrence-indicative lesions is increasing during the 60minutes of dynamic PET acquisition.

Correlation between Colon Transit Time Test Value and Initial Maintenance Dose of Laxative in Children with Chronic Functional Constipation

PurposeTo evaluate the correlation between colon transit time (CTT) test value and initial maintenance dose of polyethylene glycol (PEG) 4000 or lactulose.MethodsOf 415 children with chronic functional constipation, 190 were enrolled based on exclusion criteria using the CTT test, defecation diary, and clinical chart. The CTT test was performed with prior disimpaction. The laxative dose for maintenance was determined on the basis of the defecation diary and clinical chart. The Shapiro-Wilk test and Pearson's and Spearman's correlations were used for statistical analysis.ResultsThe overall group median value and interquartile range of the CTT test was 43.8 (31.8) hours. The average PEG 4000 dose for maintenance in the overall group was 0.68±0.18 g/kg/d; according to age, the dose was 0.73±0.16 g/kg/d (<8 years), 0.53±0.12 g/kg/d (8 to <12 years), and 0.36±0.05 g/kg/d (12 to 15 years). The dose of lactulose was 1.99±0.43 mL/kg/d (<8 years) or 1.26±0.25 mL/kg/d (8 to <12 years). There was no significant correlation between CTT test value and initial dose of laxative, irrespective of the subgroup (encopresis, abnormal CTT test subtype) for either laxative. Even in the largest group (overall, n=109, younger than 8 years and on PEG 4000), the correlation was weak (Pearson's correlation coefficient [R]=0.268, p=0.005). Within the abnormal transit group, subgroup (n=73, younger than 8 years and on PEG 4000) correlation was weak (R=0.267, p=0.022).ConclusionCTT test value cannot predict the initial maintenance dose of PEG 4000 or lactulose with linear correlation.

Acoustic radiation force impulse with shear wave speed quantification of pancreatic masses: A prospective study.

Acoustic Radiation Force Impulse (ARFI) is a new ultrasound technique that evaluates mechanical properties of tissues. To evaluate the use of ARFI with shear waves speed quantification for pancreatic masses characterization during the ultrasound examination. 123 pancreatic lesions were prospectively evaluated. Median shear waves speeds were compared with Mann-Whitney U test. Two reading methods were applied for the characterization of adenocarcinoma: more than one measurement above the top shear waves speed (SWS) value. Two reading methods were applied to diagnose mucinous lesion: at least 2 (method 1) or 3 (method 2) numerical measurements. Sensitivity, specificity, positive and negative predictive values and accuracy of each reading method were calculated. Forty volunteers were included for normal ARFI values. In the adenocarcinoma group median SWS value was 2.74 m/s. In the volunteers group the median SWS value was 1.17 m/s. Significant difference between SWS median values of adenocarcinoma and normal pancreas was found (P < 0.05). For the diagnosis of pancreatic solid masses if more than one measurement is above the top SWS value of 4.00 m/s results in the study, the diagnosis of ductal adenocarcinoma is highly specific with specificity and PPV of 100%. Good sensitivity (73.3%) and specificity (83.3%) were obtained for the characterization of mucinous cystic lesions. Acoustic Radiation Force Impulse imaging could help in the non-invasive characterization of solid and cystic lesions of the pancreas during a conventional US examination.

Prediction of Rupture Sites in Abdominal Aortic Aneurysms After Finite Element Analysis

Purpose: To associate regions of highest local rupture risk from finite element analysis (FEA) to subsequent rupture sites in abdominal aortic aneurysms (AAA). Methods: This retrospective multicenter study analyzed computed tomography angiography (CTA) data from 13 asymptomatic AAA patients (mean age 76 years; 8 men) experiencing rupture at a later point in time between 2005 and 2011. All patients had CTA scans before and during the rupture event. FEA was performed to calculate peak wall stress (PWS), peak wall rupture risk (PWRR), rupture risk equivalent diameters (RRED), and the intraluminal thrombus volume (ILTV). PWS and PWRR locations in the prerupture state were compared with subsequent CTA rupture findings. Visible contrast extravasation was considered a definite (n=5) rupture sign, while a periaortic hematoma was an indefinite (n=8) sign. A statistical comparison was performed between the 13-patient asymptomatic AAA group before and during rupture and a 23-patient diameter-matched asymptomatic AAA control group that underwent elective surgery. Results: The asymptomatic AAAs before rupture showed significantly higher PWRR and RRED values compared to the matched asymptomatic AAA control group (median values 0.74 vs 0.52 and 77 vs 59 mm, respectively; p<0.0001 for both). No statistical differences could be found for PWS and ILTV. Ruptured AAAs showed the highest maximum diameters, PWRR, and RRED values. In 7 of the ruptured AAAs (2 definite and 5 indefinite rupture signs), CTA rupture sites correlated with prerupture PWRR locations. Conclusion: The location of the PWRR in unruptured AAAs predicted future rupture sites in several cases. Asymptomatic AAA patients with high PWRR and RRED values have an increased rupture risk.

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer.

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.

Proceso de validación de un instrumento para medir la lectura crítica de informes de investigación médica

IntroductionCritical appraisal is a learning tool that should be familiar to professors and students. Educational strategies should focus on the student's active learning. Valid and reliable tools should be constructed in order to measure progress in this field. ObjectiveTo construct, validate and determine the consistency of a tool for evaluating critical reading. MethodTool: a review was conducted on published articles on the construction of evaluation tools, surveys, cases and controls, diagnostic tests, randomised clinical trials, cohorts, follow-up and meta-analyses. Eight articles on each design were finally selected. They were summarised and statements and items were developed, by examining the document validity, consistency, design, statistics, results, and the discussion. The items were based on critical reading indicators: interpretation, judgment, and proposals. Validation was obtained using the Delphi technique in 2 rounds that included six Doctors or Masters in Science or Education, previously experienced in the use of these tools. It was balanced with 96 items, 16 per design and 32 per indicator, with 48 “true or false” answers. Grading was blind and using a software program to avoid capture errors. Medians were obtained for analysis. A pilot test was applied to two groups of student interns (neophytes G1 and intervened G2) and consistency was established with the Kuder-Richardson formula. Extremes were compared with the Mann-Whitney U test. The level of randomness was also determined. ResultsA consistency of 0.79 was obtained, although concurrent validity was inadequate (Spearman=0.31). There were overall differences in the group median values, G1 vs. G2 (11 vs. 29) as well as in random answers (70% vs.8%), and in comparison of extremes (P<.0019). ConclusionsIt is necessary to construct and update tools for measuring the development of this complex and transcendental ability required for the critical appraisal of published medical information.

Glycemia Lowering and Risk for Heart Failure: Recent Evidence from Studies of Dipeptidyl Peptidase Inhibition.

The global epidemic of type 2 diabetes mellitus (T2DM) has substantial implications for cardiovascular disease–related morbidity and mortality.1 The prevalence of T2DM in patients with heart failure (HF) is high, with strong and independent association between T2DM and incident HF observed in multiple prospective studies and in randomized-controlled clinical trials. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which enrolled subject’s ≥55 years of age with hypertension and ≥1 risk factor, patients with T2DM had a 2-fold risk for HF hospitalization or death after adjustment for other risk factors (RR, 1.95). The association with T2DM was independent of coronary artery disease and at least equivalent in magnitude and greater than that for electrocardiographic left ventricular (LV) hypertrophy.2 All measures of glycemia including fasting, postprandial, measures of insulin resistance, and hemoglobin A1c (HbA1c) have been associated with risk of developing HF, with the association extending to both HF with preserved ejection fraction and to HF with reduced ejection fraction.3,4 A substantial body of evidence from preclinical studies, endomyocardial biopsies in humans and more recently with cardiac MRI, support increased myocardial stiffness in T2DM related to alteration in extracellular matrix. There are multiple proximate mediators that have been hypothesized to play a role including advanced glycation end product deposition and reactive oxygen species that may increase myocardial stiffness during diastole, by cross-linking collagen or by enhancing collagen formation.5,6 Another pernicious proximal mediator is the elevation in postprandial lipids, such as remnant lipoproteins, characteristic of atherogenic dyslipidemia, a highly prevalent abnormality in T2DM, that may result in direct myocellular deposition of lipid, leading to microcirculatory dysfunction, alteration in substrate use and mitochondrial dysfunction.7,8 Indeed, positron emission tomography studies show reduced myocardial glucose uptake in favor of fatty acid …

Clinical significance of serum interleukin-18 (IL-18) levels in patients with gastric cancer

An inappropriate production of interleukin-18 (IL-18) contributes to the pathogenesis of malignancies and may influence the clinical outcome of patients. The objective of this study was to determine the clinical significance of the serum levels of IL-18 in patients with gastric cancer. A total of 63 patients with a pathologically confirmed diagnosis of gastric cancer were enrolled into this study. Serum IL-18 concentrations were determined by the solid-phase sandwich Elisa method. Age- and sex-matched 30 healthy controls were included in the analysis. The median age at diagnosis was 62years, range 28 to 82years. The baseline serum IL-18 levels of the gastric cancer patients were a significantly higher than those in the control group (median values 1436.4 vs. 638.4pg/mL, respectively, P<0.001). The known clinical variables including age of patient, gender, site of lesion, histology, histological grade, stage of disease, and serum tumor markers such as LDH, CEA, and CA 19.9 were not found to be correlated with serum IL-18 concentrations (P>0.05). Moreover, no correlation was found between serum IL-18 level and response to chemotherapy (P=0.34). Serum IL-18 concentration was also found no prognostic role on survival (P=0.21). In conclusion, serum levels of IL-18 may have a good diagnostic marker in patients with gastric cancer. However, its predictive and prognostic values were not determined.

Lubiprostone for Treatment of Opioid-induced Constipation: Analysis of Influencing Factors

Introduction: Opioid-induced constipation (OIC) frequently results from chronic opioid treatment. Lubiprostone (LUB) efficacy was evaluated in 3 similar phase 3, randomized, double-blind, placebocontrolled, 12-week studies in chronic, non-cancer pain patients with OIC (<3 spontaneous bowel movements [SBMs]/week) at baseline. Two studies enrolled methadone users: 1 met the primary endpoint of change from baseline (CFB) in SBM frequency at Week 8, the other did not. Despite similar design, mean morphine equivalent daily dose (MEDD) of methadone in LUB-treated subjects in the latter study was 32% higher than in the successful study. Unknown at the time of these studies, methadone dosedependently inhibits the ClC-2-mediated secretory effect of LUB (Cuppoletti et al., Cell Biochem Biophys 2013;66:53-63). Methods: Post-hoc sensitivity analyses were used to evaluate the impact of high-dose methadone on CFB in SBM frequency at Week 8 in the intent-to-treat (ITT) population excluding all subjects taking methadone, and separately, excluding subjects taking high-dose (≥200 mg MEDD) methadone. A final sensitivity analysis used a median group replacement simulation for this endpoint. In this analysis, group median values for non-methadone patients and patients taking <200 mg MEDD methadone replaced Week 8 CFB values of methadone and high-dose methadone patients, respectively. Results: Excluding methadone-treated subjects from analysis resulted in clearly improved observed treatment effects in favor of LUB in both studies (Table). Though the second study did not achieve statistical significance in this analysis, clinical effect size was similar across the studies and thus the results were corroborative. In the replacement simulation, highly statistically and clinically significant improvements were observed for both trials for all simulations (p≤0.001). Adverse events were generally mild to moderate, and primarily gastrointestinal. Conclusion: LUB appears effective and well-tolerated in OIC patients with chronic, non-cancer pain taking non-methadone-type opioids. Disclosure - Ms. Losch-Beridon - Employee and holder of stock options: Sucampo Pharma Americas, LLC; Dr. Lichtlen - Consultant to Sucampo; Mr. Wang - Employee of Sucampo Pharma Americas, LLC. This research was supported by an industry grant from Sucampo Pharma Americas, LLC; Takeda Pharmaceuticals International, Inc.Table 1: Methadone Sensitivity Analyses: Change From Baseline, SBM Frequency, Week 8

Calculating intraventricular pressure difference using a multi-beat spatiotemporal reconstruction of color m-mode echocardiography.

This work aims to provide a methodology to improve the analysis of color-M-Mode (CMM) echocardiograms, as used to assess cardiac function. Specifically, we presented a methodology for the combined analysis of multiple heartbeat cycles and improve the accuracy of intraventricular pressure difference (IVPD) calculation. CMM sweep speed and heartbeat variations impact the accuracy of IVPD calculation. Proper orthogonal decomposition (POD) is used to decompose and reconstruct a representative CMM scan from multiple heartbeats, with reduced noise and improved resolution. For three demonstration subjects, at least 9 beats were recorded at sweep speeds of 25, 50, 75, 100, and 150mm/s. For all subjects, the beats from the 25mm/s group resulted in low IVPD (median values: 1.93, 1.94 and 3.15mmHg) compared to the 150mm/s group (median values: 3.67, 3.98 and 5.18mmHg). Reconstructed heartbeats for these subjects returned IVPD of 4.74, 3.23, and 5.14mmHg. These results demonstrate the strong dependence of IVPD on the temporal resolution and that the proposed reconstruction method can return more accurate IVPDs for low resolution CMMs. This new method was applied to 5 clinical cohorts (3 normals, 1 restrictive, and 1 hypertrophied) and returned increased median IVPD from 2.93-4.41mmHg for Normal 1, 2.14-3.30mmHg for Normal 2, 1.84-3.64mmHg for Normal 3, 2.28-3.00mmHg for restrictive and 1.56-1.69mmHg for hypertrophied. Our results show that beat-to-beat variations and temporal resolution affect the IVPD. Our new method rectifies low resolutions and beat-to-beat variability of the CMM data and allows for more accurate IVPD measurement independent of scanner acquisition settings and beat variations.

Serum transforming growth factor-beta 1 (TGF-β1) levels have diagnostic, predictive, and possible prognostic roles in patients with melanoma.

Transforming growth factor-beta 1 (TGF-β1) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of TGF-β1 in melanoma patients. A total of 60 patients with a pathologically confirmed diagnosis of melanoma were enrolled into this study. Serum TGF-β1 concentrations were determined by the solid-phase sandwich ELISA method. Thirty age- and sex-matched healthy controls were included in the analysis. The median age at diagnosis was 53.5 years (range 16 to 88 years). The baseline serum TGF-β1 levels of the melanoma patients were significantly higher than those in the control group (median values 171.85 vs. 19.95 pg/mL, respectively; p < 0.001). The known clinical variables including age of patient, gender, site of lesion, histology, stage of disease, and serum LDH levels were not found to be correlated with serum TGF-β1 concentrations (p > 0.05). However, the chemotherapy-responsive patients had higher serum TGF-β1 levels compared with chemotherapy-unresponsive ones (p = 0.05). Additionally, serum TGF-β1 concentration was a trend to have a prognostic role on survival (p = 0.07). Patients with elevated serum TGF-β1 concentrations had close to significantly favorable overall survival compared to those with lower levels (median 30.1 vs. 20.9 months, respectively). In conclusion, serum levels of TGF-β1 have diagnostic, predictive, and possible prognostic roles in melanoma patients.

Abstract W P8: Role of Core Infarct Volume Affecting the Number Needed to Treat in Endovascular Therapy for Acute Ischemic Stroke From Large Vessel Occlusion

Purpose: The infarct core has been hypothesized to be highly predictive of treatment effect for endovascular intervention in acute ischemic stroke from large vessel proximal occlusion. The purpose of this study was to determine how it affects the number of patients needed to treat (NNT) by this therapy to improve long term functional status. Methods: Patients with acute stroke not eligible and/or refractory to IV rtPA, treated by the Penumbra System (N=463) were pooled from various studies: Pivotal (N=83), PICS (N=174), RetroSTART (N=96) and START (N=110). They were compared with 62 control patients who were eligible for but not treated by endovascular therapy. The NNT for both groups to achieve 90 day functional independence as defined by an mRS score of ≤2 were compared. The impact of the infarct core at presentation defined by ASPECTS trichotomized as small (8-10), medium (5-7) and large (0-4) was assessed. The distribution of the infarct core (N) for Penumbra:control patients were: 257:50, 155:7 and 51:3, respectively for small, medium and large. Two control patients did not have ASPECTS scores. Results: There were no differences in baseline characteristics between the two group median values (Control;Penumbra): Age (72;68), NIHSS (18;17), ASPECTS (ASP) (9;8). There were significant differences in rate of recanalization, all-cause mortality and good functional outcome (mRS ≤2) but not symptomatic ICH (Table). The NNT to improve functional status was 5.6 for the entire cohort of treated patients, 4.7 for those with small core, 4.1 for medium and 12.8 for large. Conclusion: These data indicate that endovascular treatment may not be effective in patients with a large infarct core and could contribute to the high NNT needed to achieve long term good functional status. Eliminating this group at time of triage may significantly lower the NNT and improve the treatment effect of this therapy.

Atazanavir and lopinavir profile in pregnant women with HIV: tolerability, activity and pregnancy outcomes in an observational national study

Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P < 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P < 0.001). In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options.

Influence of arterial hypertension on renal function in patients with obstructive sleep apnea hypopnea syndrome

Introduction Aim of the study has been an investigation of possible relationship between glomerular filtration rate (GFR) and arterial hypertension (AH) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Materials and methods Forty patients (35 male, 5 female, mean age 43.3±12.5year) with OSAHS (apnea–hypopnea index (AHI) >5episodes/h) have been included in the study. Investigated 40 patients have been divided into the two groups: patients having only OSAHS (group I) and patients having OSAHS and AH (group II). GFR has been estimated using the Cockcroft–Gault formula. Normal rates for GFR have been estimated as 100–130ml/m/1.73m 2 . For statistical analysis of GFR classified groups median values have been used as a dividing point. Relationship between GFR and AH has been estimated according to Pearson χ 2 and Fisher exact test. Results Increased values for GFR have been revealed in both groups. However, relatively lower rates from median values of GFR have been detected in 11 patients from group I (55%; CI 34.2–74.2%) and in 12 patients from group II (60%; CI 38.7–78.1%). Statistically significant differences have not been observed between two groups of patients; while tendency of higher GFR values from median ones have been revealed in the group I (169.0±52.5 vs. 157.5±36.8ml/m/1.73m 2 , p =0.427). Conclusion Hyperfiltration is common for patients with OSAHS. In the same time a presence of arterial hypertension is accompanied only by tendency for decrease of absolute values of glomerular filtration rate. Acknowledgement Anna Petrosyan laboratory technician.

P2.028 Evaluation of the Vaginal Microbiota Using Quantitative Real-Time PCR

BackgroundFor characterization of the vaginal microflora, it is often necessary to assess quantities of microorganisms. The study objective was to evaluate vaginal microflora in norm, bacterial vaginosis (BV) and vulvovaginitis...

Neither Cyclosporine nor Tacrolimus Deteriorate Endothelial Function in Renal Transplant Recipients Assessed With Reactive Hyperernia Index

BackgroundCardiovascular mortality in renal transplant recipients is nearer 10-fold higher than in general population. Immunosuppressive therapy is one possible cause, for these drugs can modify cardiovascular risk factors, which can induce endothelial dysfunction, the first step in the process of atherosclerosis. The aim of this study was to compare vasodilatatory function of endothelium in renal transplant recipients in relation to the immunosuppressive drug—cyclosporine or tacrolimus. Materials and methodsWe examined 40 patients at 48.9 ± 36 months post–renal transplantation: 22 taking tacrolimus (group 1) and 18 taking cyclosporine (group 2). The renal transplant recipients were compared with a control group of 18 healthy people. Endothelial function was assessed by peripheral arterial tonometry (PAT) using the EndoPAT 2000 device to measure RHI (reactive hyperemia index) and AI% (augmentation index%). ResultsThe overall median values of RHI were higher than the value accepted as a normal (1.67). The RHI median value in group 1 was 2.00 (quartile 1: 1.66; quartile 2: 2.72), not different from that in group 2 [1.90 (quartile 1: 1.56; quartile 2: 2.17)] or the controls [2.11 (quartile 1: 1.77; quartile 2: 2.50)]. Multivariate analysis revealed age to be the independent factor influencing RHI in all examined groups but treatment with calcium channel blockers appeared to be the only independent factor influencing RHI among renal transplant recipients. AI% values were not significantly different between the 2 groups of renal transplant recipients, but it was significantly higher among the controls than among subjects treated with tacrolimus. ConclusionsVasodilatatory function of endothelium assessed by PAT in renal transplant recipients was not worse than in healthy people. It was not different between cyclosporine or tacrolimus. Arterial stiffness measured as AI% depend on age but not the calcineurin inhibitor, which showed little effect.