Objective: There are some data regarding the role of cystatin C, a cysteine proteinase inhibitor, in determining the glomerular filtration rate (GFR) more accurately. We aimed to evaluate the ...correlation of serum cystatin C levels with the serum creatinine levels and GFR calculated by Cockcroft-Gault and modification of diet in renal disease (MDRD) formulations in the patients who received cisplatin-based chemotherapy. We also intended to demonstrate its potential use in the early prediction of the renal function changes in these patients. Materials and methods: In the study, 34 patients receiving cisplatin-based chemotherapy with various malignancies were included. The levels of cisplatin were determined prior to the chemotherapy and at the end of cisplatin infusion during the therapy. GFR was calculated by Cockcroft-Gault and MDRD formulations prior to the therapy and at the end of the third course. Results: A statistically significant linear correlation was found between the serum levels of cystatin C and creatinine prior to the chemotherapy (r = 0.42, p = 0.013). However, there was no correlation among the level of cystatin C subsequent to the cisplatin infusion and serum creatinine level following the third course and MDRD and creatinine clearance-Cockcroft-Gault formulations. Conclusion: Even though the serum cystatin C levels were correlated with the serum creatinine levels in our study, it was concluded that it was not an appropriate parameter to predict the potential impairments in the renal function during the chemotherapy.
Background
: The different influences of one of the PRL isoforms (PRL I) on the cardiovascular system have been described in the past.
Aim
: Our goal was to establish an appropriate iv dose of 2 PRL ...isoforms (PRL I and PRL II) in intact rats. After establishing this dose, PRL I (0.01 mg/kg) or PRL II (0.001 mg/kg) was administered in bolus 10 min before left anterior descending coronary artery occlusion (7 min) followed by re-perfusion (15 min). We then aimed to study and compare the effects of these isoforms on ischemia- and re-perfusion-induced arrhythmias in the ischemia and re-perfusion-induced arrhythmias model in rats.
Materials and methods
: Mortality index, ventricular fibrillation and tachycardia (VF, VT) incidence and duration, systolic, diastolic, and mean arterial blood pressure, heart rate and myocardial index of oxygen consumption pressure rate product (PRP) were measured and calculated.
Results
: Both PRL isoforms reduced animal mortality (from 50 to 18.75 and 25%, respectively). PRL II significantly reduced VF incidence (to 25%) as well as VT duration (18.21±3.09) and these effects were markedly different from PRL I and from the control group (
p
<0.05). Both PRL reduced PRP in the recovery phase (
p
<0.05).
Conclusions
: We proved that supra-physiological doses of PRL isoforms administered in bolus could protect against sudden cardiac death as well as severe arrhythmias episodes during re-perfusion. Because of PRL’s positive influence on the cardiovascular system and as an endogenous, well-tolerated substance, it might be of potential clinical use.
The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates ...were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.
The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible ...for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin.
We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors.
Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p>0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors of univariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level.
Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment.
The permeation of supercritical CO
2 and SF
6 across two different types of microporous membranes has been studied as a function of temperature and feed pressure. A general picture appears where for ...both species the permeance as a function of the feed pressure has a maximum. For both the polymeric and the silica membranes close to the temperature where the different species become supercritical the maximum in the permeance is observed at the critical pressure. In the supercritical regime the main mechanism for the mass transport is viscous flow, and there is almost no contribution from surface diffusion through the micropores. The permeance of the fluids obtained for different condition can be described by a single mobility constant, which is independent of temperature and pressure.
The trachea whole organ perfusion technique was used to study the effect of tumor necrosis factor (TNF) and interleukin-1 (IL-1) on the adherence of otitis media pathogen Streptococcus pneumoniae ...(Spn) type 6A. Tracheas were removed from chinchillas and divided equally. One-half trachea was activated by incubation with 1-10 ng/ml of either TNF or IL-1 prior to the addition of Spn 6A to the organ culture perfusion chamber. Colony forming units (cfu) of Spn/millimeter trachea were determined for activated tracheas and controls. Dose response and kinetics data were generated for each cytokine. The specificity of each reaction was determined by neutralization studies with specific anti-cytokine antibodies. The data indicate that both TNF and IL-1 increase the adherence of Spn to the respiratory epithelium of this tubal organ and suggest a mechanism which may facilitate enhanced adherence in vivo and thereby contribute to the pathogenesis of otitis media and other upper respiratory tract diseases. Language: English
Evidence is strengthening for the morphological evaluation of tumor infiltrating lymphocytes (TILs) in breast cancer. Herein, the concepts for TILs assessment are laid out by pathologists to ...facilitate their wider evaluation and consistent interpretation. The goal of this article is to promote the evaluation of TILs as a biomarker in research, clinical trial settings and day-to-day practice.
The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC.
A standardized methodology for evaluating TILs is now needed as a prerequisite for integrating this parameter in standard histopathological practice, in a research setting as well as in clinical trials. This article reviews current data on the clinical validity and utility of TILs in BC in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections, acknowledging the future potential of molecular/multiplexed approaches.
The methodology provided is sufficiently detailed to offer a uniformly applied, pragmatic starting point and improve consistency and reproducibility in the measurement of TILs for future studies.
For many cancers, adolescents and young adults (AYAs) have a poorer prognosis than pediatric patients. Our study evaluates survival outcomes of children (0‐17 years) and AYAs (18‐39 years) diagnosed ...with acute myeloid leukemia (AML) in the Netherlands between 1990 and 2015 (N = 2058) utilizing the population‐based Netherlands Cancer Registry, which includes information on therapy and site of primary treatment. Five‐ and 10‐year relative (disease‐specific) survival were estimated for all patients, children and AYAs. Multivariable analyses were performed using generalized linear models (excess mortality) and logistic regression (early mortality). AYAs with AML had a substantially lower 5‐ and 10‐year relative survival than children (5‐year: 43% vs 58%; 10‐year: 37% vs 51%). The gap in 5‐year relative survival was largest (nearly 20 percent‐points) in 2010 to 2015, despite survival improvements over time across all ages. The multivariable‐adjusted excess risk of dying was 60% higher in AYAs (95% CI: 37%‐86%). Early mortality (death within 30 days of diagnosis) declined over time, and did not differ between children and AYAs. In conclusion, AYAs diagnosed with AML in the Netherlands had a worse prognosis than pediatric patients. The survival gap seemed most pronounced in recent years, suggesting that improvements in care resulting in better outcome for children have not led to equal benefits for AYAs.
What's new?
For many cancers, children under 18 have better survival outcomes than adolescents and young adults, age 18‐39. Here, the authors evaluated long‐term survival of young people diagnosed with acute myeloid leukemia in the Netherlands. When they compared outcomes, they found that adolescents and young adults had a worse prognosis than children. Although survival has improved across all age groups, the disparity between children and adolescents and young adults has widened. Treatments that improved outcomes for children, therefore, do not appear to have benefited adolescents and young adults to the same degree.
Massive sets of stellar spectroscopic observations are rapidly becoming available and these can be used to determine the chemical composition and evolution of the Galaxy with unprecedented precision. ...One of the major challenges in this endeavour involves constructing realistic models of stellar spectra with which to reliably determine stellar abundances. At present, large stellar surveys commonly use simplified models that assume that the stellar atmospheres are approximately in local thermodynamic equilibrium (LTE). To test and ultimately relax this assumption, we have performed non-LTE calculations for 13 different elements (H, Li, C, N, O, Na, Mg, Al, Si, K, Ca, Mn, and Ba), using recent model atoms that have physically-motivated descriptions for the inelastic collisions with neutral hydrogen, across a grid of 3756 1D
MARCS
model atmospheres that spans 3000 ≤
T
eff
∕K ≤ 8000, − 0.5 ≤log
g
∕cm s
−2
≤ 5.5, and − 5 ≤ Fe/H ≤ 1. We present the grids of departure coefficients that have been implemented into the GALAH DR3 analysis pipeline in order to complement the extant non-LTE grid for iron. We also present a detailed line-by-line re-analysis of 50 126 stars from GALAH DR3. We found that relaxing LTE can change the abundances by between − 0.7 dex and + 0.2 dex for different lines and stars. Taking departures from LTE into account can reduce the dispersion in the A/Fe versus Fe/H plane by up to 0.1 dex, and it can remove spurious differences between the dwarfs and giants by up to 0.2 dex. The resulting abundance slopes can thus be qualitatively different in non-LTE, possibly with important implications for the chemical evolution of our Galaxy. The grids of departure coefficients are publicly available and can be implemented into LTE pipelines to make the most of observational data sets from large spectroscopic surveys.
Interactions between a single emitter and cavity provide the archetypical system for fundamental quantum electrodynamics. Here we show that a single molecule of Atto647 aligned using DNA origami ...interacts coherently with a sub-wavelength plasmonic nanocavity, approaching the cooperative regime even at room temperature. Power-dependent pulsed excitation reveals Rabi oscillations, arising from the coupling of the oscillating electric field between the ground and excited states. The observed single-molecule fluorescent emission is split into two modes resulting from anti-crossing with the plasmonic mode, indicating the molecule is strongly coupled to the cavity. The second-order correlation function of the photon emission statistics is found to be pump wavelength dependent, varying from g
(0) = 0.4 to 1.45, highlighting the influence of vibrational relaxation on the Jaynes-Cummings ladder. Our results show that cavity quantum electrodynamic effects can be observed in molecular systems at ambient conditions, opening significant potential for device applications.
PDF
