The value of different resistance parameters in distinguishing biopsy-proved dysfunction of renal allografts

The data concerning the value of duplex sonography in diagnosing parenchymatous renal allograft dysfunction are controversial. Most early studies did not take into consideration the many factors influencing resistance parameters. We therefore performed a prospective, biopsy-controlled study with exclusion of all known sources of error regarding resistance parameters. Furthermore we investigated the value of a new resistance parameter, the systolic deceleration percentage. Forty-seven duplex sonographic studies were performed on 43 patients (30 male, 13 female, median age 47 years, range 7-70). Fourteen studies were done on normally functioning grafts (control group) an average of 33 days after transplantation. Thirty-three studies were performed on dysfunctional grafts immediately prior to biopsy. Grafts which had been transplanted more than a year previously or with vascular findings or any other clinical or sonographic pathology probably explaining function deterioration were excluded. In all patients, the resistive index (RI), pulsatility index (PI) and systolic deceleration percentage (DP) were calculated in the main renal artery and in the interlobar artery. Of the 33 grafts with dysfunction, nine had vascular rejection (VR), 11 interstitial rejection (IR), 11 cyclosporin A toxicity (CAT) and two other histologies (OR). The mean RI in normal grafts (NO) was 0.71±0.06 in the main artery and 0.68±0.06 in the interlobar artery, in VR 0.86±0.12 and 0.80±0.18, in IR 0.72±0.05 and 0.70±0.07, in CAT 0.67±0.06 and 0.65±0.07 and in OR 0.64±0.07 and 0.60±0.01. For PI, the values were 1.45±0.23 and 1.41±0.28 (NO), 3.5±2.13 and 2.92±2.16 (VR), 1.55±0.26 and 1.46±0.33 (IR), 1.32±0.25 and 1.27±0.26 (CAT) and 1.30±0.34 and 1.13±0.04 (OR). For DP we calculated 28±5% and 29±6% (NO), 43±14% and 36±6% (VR), 29±9% and 27±9% (IR), 31±8% and 32±7% (CAT ) and 32±4% and 28±3% (OR). The sensitivity/specificity for VR with a cutoff mean+2 SD was 0.44/1 for RI, 0.55/0.97 for PI and 0.33/0.89 for DP. It was concluded that:(1) despite the high selection of our patient group, diagnostic accuracy of duplex sonography for diagnosing parenchymatous function disorder in renal allograft remains insufficient; (2) in vascular rejection only, the resistance parameters differ significantly from the values of normal allografts; (3) the higher the cutoff of resistance parameters, the better the specificity and the worse the sensitivity for diagnosing vascular rejection; (4) of all investigated resistance parameters, the RI is the most practical due to a simple measurement techniqu

Early renal transplant dysfunction due to arterial kinking stenosis

The main differential diagnoses of early renal trans-plant dysfunction include ischaemic damage, cyclospo-rin toxicity, and rejection [1]. Rarer causes include bleeding, ureteral obstruction, urinary leak, venou

Analysis of BRAF and NRAS Mutation Status in Advanced Melanoma Patients Treated with Anti-CTLA-4 Antibodies: Association with Overall Survival?

Ipilimumab and tremelimumab are human monoclonal antibodies (Abs) against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival in advanced melanoma patients. Currently, there is no proven association between the BRAFV600 mutation and the disease control rate in response to ipilimumab. This analysis was carried out to assess if BRAFV600 and NRAS mutation status affects the clinical outcome of anti-CTLA-4-treated melanoma patients. This is a retrospective multi-center analysis of 101 patients, with confirmed BRAF and NRAS mutation status, treated with anti-CTLA-4 antibodies from December 2006 until August 2012. The median overall survival, defined from the treatment start date with the anti-CTLA-4. Abs-treatment to death or till last follow up, of BRAFV600 or NRAS mutant patients (n = 62) was 10.12 months (95% CI 6.78-13.2) compared to 8.26 months (95% CI 6.02-19.9) in BRAFV600/NRASwt subpopulation (n = 39) (p = 0.67). The median OS of NRAS mutated patients (n = 24) was 12.1 months and although was prolonged compared to the median OS of BRAF mutated patients (n = 38, mOS = 8.03 months) or BRAFV600/NRASwt patients (n = 39, mOS = 8.26 months) the difference didn't reach statistical significance (p = 0.56). 69 patients were able to complete 4 cycles of anti-CTLA-4 treatment. Of the 24 patients treated with selected BRAF- or MEK-inhibitors, 16 patients received anti-CTLA 4 Abs following either a BRAF or MEK inhibitor with only 8 of them being able to finish 4 cycles of treatment. Based on our results, there is no difference in the median OS in patients treated with anti-CTLA-4 Abs implying that the BRAF/NRAS mutation status alone is not sufficient to predict the outcome of patients treated with anti-CTLA-4 Abs

A combination of l-arabinose and chromium lowers circulating glucose and insulin levels after an acute oral sucrose challenge

<p>Abstract</p> <p>Background</p> <p>A growing body of research suggests that elevated circulating levels of glucose and insulin accelerate risk factors for a wide range of disorders. Low-risk interventions that could suppress glucose without raising insulin levels could offer significant long-term health benefits.</p> <p>Methods</p> <p>To address this issue, we conducted two sequential studies, the first with two phases. In the first phase of Study 1, baseline fasting blood glucose was measured in 20 subjects who consumed 70 grams of sucrose in water and subsequently completed capillary glucose measurements at 30, 45, 60 and 90 minutes (Control). On day-2 the same procedure was followed, but with subjects simultaneously consuming a novel formula containing l-arabinose and a trivalent patented food source of chromium (LA-Cr) (Treatment). The presence or absence of the LA-Cr was blinded to the subjects and testing technician. Comparisons of changes from baseline were made between Control and Treatment periods. In the second phase of Study 1, 10 subjects selected from the original 20 competed baseline measures of body composition (DXA), a 43-blood chemistry panel and a Quality of Life Inventory. These subjects subsequently took LA-Cr daily for 4 weeks completing daily tracking forms and repeating the baseline capillary tests at the end of each of the four weeks. In Study 2, the same procedures used in the first phase were repeated for 50 subjects, but with added circulating insulin measurements at 30 and 60 minutes from baseline.</p> <p>Results</p> <p>In both studies, as compared to Control, the Treatment group had significantly lower glucose responses for all four testing times (AUC = <it>P </it>< 0.0001). Additionally, the Treatment was significantly more effective in lowering circulating insulin after 60 minutes from baseline (AUC = <it>P </it>= < 0.01). No adverse effects were found after acute sucrose challenge or in those who consumed LA-Cr daily for four weeks.</p> <p>Conclusions</p> <p>As compared to a placebo control, consumption of a LA-Cr formula after a 70-gram sucrose challenge was effective in safely lowering both circulating glucose and insulin levels.</p> <p>Trial Registration</p> <p>Clinical Trials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT0110743">NCT0110743</a></p

Anticoagulation Management Practices and Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Clinical Research Study.

Whether anticoagulation management practices are associated with improved outcomes in elderly patients with acute venous thromboembolism (VTE) is uncertain. Thus, we aimed to examine whether practices recommended by the American College of Chest Physicians guidelines are associated with outcomes in elderly patients with VTE. We studied 991 patients aged ≥65 years with acute VTE in a Swiss prospective multicenter cohort study and assessed the adherence to four management practices: parenteral anticoagulation ≥5 days, INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulation, early start with vitamin K antagonists (VKA) ≤24 hours of VTE diagnosis, and the use of low-molecular-weight heparin (LMWH) or fondaparinux. The outcomes were all-cause mortality, VTE recurrence, and major bleeding at 6 months, and the length of hospital stay (LOS). We used Cox regression and lognormal survival models, adjusting for patient characteristics. Overall, 9% of patients died, 3% had VTE recurrence, and 7% major bleeding. Early start with VKA was associated with a lower risk of major bleeding (adjusted hazard ratio 0.37, 95% CI 0.20-0.71). Early start with VKA (adjusted time ratio [TR] 0.77, 95% CI 0.69-0.86) and use of LMWH/fondaparinux (adjusted TR 0.87, 95% CI 0.78-0.97) were associated with a shorter LOS. An INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulants was associated with a longer LOS (adjusted TR 1.2, 95% CI 1.08-1.33). In elderly patients with VTE, the adherence to recommended anticoagulation management practices showed mixed results. In conclusion, only early start with VKA and use of parenteral LMWH/fondaparinux were associated with better outcomes

Solvation and Protonation of Coumarin 102 in Aqueous Media - a Fluorescence Spectroscopic and Theoretical Study

The ground and excited state protonation of Coumarin 102 (C102), a fluorescent probe applied frequently in heterogeneous systems with an aqueous phase, has been studied in aqueous solutions by spectroscopic experiments and theoretical calculations. For the dissociation constant of the protonated form in the ground state, was obtained from the absorption spectra, for the excited state dissociation constant was obtained from the fluorescence spectra. These values were closely reproduced by theoretical calculations via a thermodynamic cycle – the value of also by calculations via the Förster cycle - using an implicit-explicit solvation model (polarized continuum model + addition of a solvent molecule). The theoretical calculations indicated that (i) in the ground state C102 occurs primarily as a hydrogen bonded water complex, with the oxo group as the binding site, (ii) this hydrogen bond becomes stronger upon excitation; (iii) in the ground state the amino nitrogen atom, in the excited state the carboxy oxygen atom is the protonation site. A comprehensive analysis of fluorescence decay data yielded the values kpr = 3.271010 M-1 s 1 for the rate constants of excited state protonation, and kdpr = 2.78108 s-1 for the rate constant of the reverse process (kpr and kdpr were treated as independent parameters). This, considering the relatively long fluorescence lifetimes of neutral C102 (6.02 ns) and its protonated form (3.06 ns) in aqueous media, means that a quasi-equilibrium state of excited state proton transfer is reached in strongly acidic solutions

A high Gas6 level in plasma predicts venous thromboembolism recurrence, major bleeding and mortality in the elderly: a prospective multicenter cohort study.

Essentials Predictive ability of pro-hemostatic Gas6 for recurrent venous thromboembolism (VTE) is unknown. We measured Gas6 levels in 864 patients with VTE over 3 years. High Gas6 (&gt; 157%) at diagnosis is associated with VTE recurrence, major bleeding and mortality. Gas6 plasma levels measured 12 months after the index VTE are discriminatory for VTE recurrence. SUMMARY: Background Growth arrest-specific gene 6 (Gas6) is a prohemostatic protein with an unknown predictive ability for recurrent venous thromboembolism (VTE). In the elderly, VTE results in higher mortality but does not have a higher rate of recurrence than in younger patients. Consequently, anticoagulation management in the elderly is challenging. Objective To prospectively investigate the performance of Gas6 in predicting VTE recurrence, major bleeding and mortality in the elderly. Methods Consecutive patients aged ≥ 65 years with acute VTE were followed for a period of 3 years. Primary outcomes were symptomatic VTE recurrence, major bleeding, and mortality. Plasma Gas6 was measured with ELISA. Results Gas6 levels were measured in 864 patients at the time of the index VTE (T1) and, in 70% of them, also 12 months later (T2). The Gas6 level at T1 was discriminatory for VTE recurrence (C-statistic, 0.56; 95% confidence interval [CI] 0.51-0.62), major bleeding (0.60, 95% CI 0.55-0.65) and mortality (0.69, 95% CI 0.65-0.73) up to 36 months. VTE recurrence up to 24 months after T2 was discriminated by the Gas6 level at T2 (0.62, 95% CI 0.54-0.71). High Gas6 levels (&gt; 157%) and continuous Gas6 levels at T1 were associated with VTE recurrence up to 6 months and 12 months, respectively. Conclusions In elderly patients, a high Gas6 level is associated with higher risks of VTE recurrence, major bleeding, and death. These findings support further studies to assess the performance of Gas6 in adjusting the length of anticoagulation

Upconversion-induced heat generation and thermal lensing in Nd:YLF and Nd:YAG

We investigate the influence of interionic upconversion between neighboring ions in the upper laser level of Nd:YLF and Nd:YAG on population dynamics, heat generation, and thermal lensing under lasing and non-lasing conditions. It is shown that cascaded multiphonon relaxations following each upconversion process generate significant extra heat dissipation in the crystal under non-lasing compared to lasing conditions. Owing to the unfavorable temperature dependence of thermal and thermo-optical parameters, this leads, firstly, to a significant temperature increase in the rod, secondly, to strong thermal lensing with pronounced spherical aberrations and, ultimately, to rod fracture in a high-power end-pumped system. In a three-dimensional finite-element calculation, excitation densities, upconversion rates, heat generation temperature profiles, and thermal lensing are calculated. Differences in thermal lens power between non-lasing and lasing conditions up to a factor of six in Nd:YLF and up to a factor of two in Nd:YAG are experimentally observed and explained by the calculation. This results in a strong deterioration in performance when operating these systems in a Q-switched regime, as an amplifier, or on a low-gain transition. Methods to decrease the influence of interionic upconversion are discussed. It is shown that tuning of the pump wavelength can significantly alter the rod temperature