Predicting postoperative pancreatic fistula in pancreatic head resections: which score fits all?

PURPOSE: Postoperative pancreatic fistula (POPF) is a major complication of pancreatic surgery and can be fatal. Better stratification of patients into risk groups may help to select those who might benefit from strategies to prevent complications. The aim of this study was to validate ten prognostic scores in patients who underwent pancreatic head surgery. METHODS: A total of 364 patients were included in this study between September 2012 and August 2017. Ten risk scores were applied to this cohort. Univariate and multivariate analyses were performed considering all risk factors in the scores. Furthermore, the stratification of patients into risk categories was statistically tested. RESULTS: Nine of the scores (Ansorge et al., Braga et al., Callery et al., Graham et al., Kantor et al., Mungroop et al., Roberts et al., Yamamoto et al. and Wellner et al.) showed strong prognostic stratification for developing POPF (p < 0.001). There was no significant prognostic value for the Fujiwara et al. risk score. Histology, pancreatic duct diameter, intraabdominal fat thickness in computed tomography findings, body mass index, and C-reactive protein were independent prognostic factors on multivariate analysis. CONCLUSION: Most risk scores tend to stratify patients correctly according to risk for POPF. Nevertheless, except for the fistula risk score (Callery et al.) and its alternative version (Mungroop et al.), many of the published risk scores are obscure even for the dedicated pancreatic surgeon in terms of their clinical practicability. There is a need for future studies to provide strategies for preventing POPF and managing patients with high-risk stigmata.

Insights on the catalytic behaviour of sulfonic acid-functionalized ionic liquids (ILs) in transesterification reactions - voltammetric characterization of sulfonic task-specific ILs with bisulfate anions.

This work shows for the first time the link between the amount of free sulfuric acid (as detected by cyclic voltammetry) and the activity of sulfonic-acid-functionalized ionic liquids (ILs) as acid catalysts for a transesterification reaction, and demonstrates that sulfonic acid groups, while are not directly involved in the catalysis, release the free acid during the reaction. Two imidazolic ILs with bisulfate as the counterion and their corresponding task-specific ILs (TSILs) that resulted from the addition of a sulfonic acid group inside the imidazolic-base structure were studied. The outstanding catalytic activity at room temperature of the TSILs 1-(4-sulfonic acid)-butyl-3-methylimidazolium bisulfate ([bsmim]HSO4) and 1-(4-sulfonic acid)-butyl-imidazolium bisulfate ([bsHim]HSO4) for the transesterification of p-nitrophenyl acetate with methanol was associated to the significant amounts of free sulfuric acid in equilibria with the ionic pairs. It was concluded that these TSILs function as reservoirs for releasing the free acid, which is the actual acid catalyst. In contrast, the corresponding non-sulfonic ILs supply very little amounts of free acid and consequently present low catalytic activities at room temperature, which in fact can be improved by increasing the reaction temperature up to 100 °C.

A Polyclonal Immune Function Assay Allows Dose-Dependent Characterization of Immunosuppressive Drug Effects but Has Limited Clinical Utility for Predicting Infection on an Individual Basis.

Dosage of immunosuppressive drugs after transplantation critically determines rejection and infection episodes. In this study, a global immune function assay was characterized among controls, dialysis-patients, and transplant-recipients to evaluate its utility for pharmacodynamic monitoring of immunosuppressive drugs and for predicting infections. Whole-blood samples were stimulated with anti-CD3/toll-like-receptor (TLR7/8)-agonist in the presence or absence of drugs and IFN-γ secretion was measured by ELISA. Additional stimulation-induced cytokines were characterized among T-, B-, and NK-cells using flow-cytometry. Cytokine-secretion was dominated by IFN-γ, and mainly observed in CD4, CD8, and NK-cells. Intra-assay variability was low (CV = 10.4 ± 6.2%), whereas variability over time was high, even in the absence of clinical events (CV = 65.0 ± 35.7%). Cyclosporine A, tacrolimus and steroids dose-dependently inhibited IFN-γ secretion, and reactivity was further reduced when calcineurin inhibitors were combined with steroids. Moreover, IFN-γ levels significantly differed between controls, dialysis-patients, and transplant-recipients, with lowest IFN-γ levels early after transplantation (p < 0.001). However, a single test had limited ability to predict infectious episodes. In conclusion, the assay may have potential for basic pharmacodynamic characterization of immunosuppressive drugs and their combinations, and for assessing loss of global immunocompetence after transplantation, but its application to guide drug-dosing and to predict infectious on an individual basis is limited.

Assessment of in vitro cytotoxicity of imidazole ionic liquids and inclusion in targeted drug carriers containing violacein.

Violacein (Viol) is a pigment produced by several Gram-negative bacteria with many bioactivities, such as anticancer, virucide, and antiparasitic. However, violacein is insoluble under physiological conditions preventing its potential therapeutic uses. Surface-active ionic liquids (SAILs) based on the cation 1-alkylimidazolium ([C n Him]) with n = 10 to 16 alkyl carbon side chain lengths and acetate, bromide, methanesulfonate (S) or trifluoroacetate (F) as counterions were synthesized and screened to dissolve Viol in micellar aqueous media and for toxicological studies on the human lung carcinoma A549 cell line. Screening allowed the selection of 1.5 × 10-3% (w/v) [C16Him]-S because it combines low cytotoxicity with 71.5% cell viability and good interaction with 95.2% of the violacein kept in micellar solution for at least 48 h. [Viol-([C16Him]-S)] complex was used to develop an efficient hybrid solid lipid nanoparticle (SLN) carrier based on myristyl myristate and poloxamer 188 and tailored with folate to target cancer cells. Cellular SLN uptake was evaluated with fluorescent DiOC18 on A549, HCT-116, and HeLa cell lines expressing or not the folate receptor. The results showed fivefold incorporation of Viol nanoparticles in HCT-116 and HeLa cell cultures, displaying a high level of folate receptor. Biophysical characterization of the hybrid solid lipid carrier containing Viol was performed by dynamic light scattering, Fourier transform infrared, X-ray diffraction and X-ray photoelectron spectroscopies, and by transmission electron and cryo-transmission microscopies.

Understanding the Role of Protic Ionic Liquids (PILs) in Reactive Systems: Rational Selection of PILs for the Design of Green Synthesis Strategies for Allylic Amines and ß-Amino Esters.

The reactive behaviour of protic ionic liquids (PILs) has been shown to be governed not only by their chemical structures but also by their global compositions, which include the presence of free acids and bases at equilibrium with ionic pairs. Six PILs composed of primary, secondary, or tertiary alkyl ammonium cations with two couterions, nitrate or acetate, were tested in model reactions with unsaturated substrates. The free species that were naturally present in these liquids were identified by cyclic voltammetry. Only tributylammonium nitrate was found to be mostly composed just of the ionic pair; the other five PILs also contain variable amounts of free acid and amine. In reactive systems, these free species determine the products of the reaction. In particular, allylic amines and ß-amino esters were obtained in good yields (91 and 75 %, respectively) by reaction of conjugated dienes and acrylates in the presence of PILs. By taking into account the actual composition of each PIL, it was possible to direct the reaction path towards a specific product with good yields, to ensure acid catalysis, to avoid polymerization of the substrate, and to promote phase transfer of products. These results establish some useful guidelines for the rational design of new PIL-based one-step synthetic strategies.

Determination of glyphosate, AMPA and glufosinate in dairy farm water from Argentina using a simplified UHPLC-MS/MS method.

Argentina, together with the USA and Brazil, produces approximately 80% of the total worldwide glyphosate loadings. The development of a simplified ultra-high performance liquid chromatographic tandem mass spectrometric method (UHPLC-MS/MS) for the determination of glyphosate, aminomethylphosphonic acid (AMPA) and glufosinate in water is described, including studies of several alternatives of 9-fluorenylmethylchloroformate (FMOC-Cl) derivatization and pretreatment steps. The proposed method includes acidification and neutralization of a low sample volume (3 mL), 2 hours derivatization step, cleanup with dichloromethane, followed by reverse phase UHPLC-MS/MS determination of the analytes. Figures of merit were satisfactory in terms of linearity, selectivity, accuracy and intermediate precision (%REC 70-105% with RSD < 15%). Limits of quantification (LOQ) were suitable for monitoring purposes (0.6, 0.2, 0.1 µg/L for glyphosate, AMPA and glufosinate respectively). The validated methodology was applied for the analysis of livestock wells waters from 40 dairy farms located in the central region of Argentina. Glyphosate and AMPA were quantified in 15% and 53% of the analyzed samples with concentrations ranging from 0.6-11.3 µg/L and 0.2-6.5 µg/L respectively. Greater concentrations of glyphosate were also verified in waters from open-reservoir tanks, which are directly exposed to the farm environment. In these cases glyphosate and AMPA occurrence increased, being quantified in the 33% and 61% of the samples with values ranging 0.6-21.2 µg/L and 0.2-4.2 µg/L respectively. Also in this case glufosinate was found in 52% samples at

New solvents designed on the basis of the molecular-microscopic properties of binary mixtures of the type (protic molecular solvent + 1-butyl-3-methylimidazolium-based ionic liquid).

The main purpose of this work is to analyze the microscopic feature of solvent systems resulting from the basis of binary mixtures formed by a protic molecular solvent (methanol, ethanol, propan-1-ol, propan-2-ol, and 2-ethoxyethanol) and a 1-butyl-3-methylimidazolium (bmim)-based ionic liquid (IL) cosolvent composed of different anions (tetrafluoroborate, hexafluorophosphate, chloride, and bromide). At the same time, a complementary aim is to evaluate the incidence of anion type on the solvation pattern. The empirical solvatochromic parameters E(T)(N), π*, ß, and α were determined from the UV-vis solvatochromic shifts of adequate probes. The behavior of the solvent systems was analyzed according to their deviation from ideality. E(T)(N) polarity and π* dipolarity/polarizability exhibit positive deviation from ideal behavior in all binary mixtures at the explored compositions. Moreover, E(T)(N) and α parameters display synergetic effects in some binary mixtures composed of tetrafluoroborate and hexafluorophosphate anions. The influence of anion nature on the response patterns is clearly manifested in the basicity ß and acidity α of the media. This is connected with the degree and type of interaction between the anions and the 1-butyl-3-methylimidazolium cation. The ion-pair character of the ionic liquids affects their interactions with a solute or a molecular solvent. The application of an appropriate preferential solvation model allowed us to obtain valuable information about solute-solvent and solvent-solvent interactions of the selected ionic liquid mixtures. It is possible to identify relevant mixtures paying particular attention to the most remarkable microscopic properties, the acidity and the basicity, in order to propose "new solvents". Thus, the solvating feature can be tailored selecting the molecular and/or the ionic component at a particular composition. A simplified combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) equation is shown to satisfactorily predict the solvatochromic parameters within [protic molecular solvent + bmim-based IL].

Mantle flow drives the subsidence of oceanic plates.

The subsidence of the sea floor is generally considered a consequence of its passive cooling and densifying since its formation at the ridge and is therefore regarded as a function of lithospheric age only. However, the lithosphere is defined as the thermal boundary layer of mantle convection, which should thus determine its structure. We examined the evolution of the lithosphere structure and depth along trajectories representative of the underlying mantle flow. We show that along these flow lines, the sea-floor depth varies as the square root of the distance from the ridge (as given by the boundary-layer equation) along the entire plate, without any flattening. Contrary to previous models, no additional heat supply is required at the base of the lithosphere.

Nitroso group transfer in s-nitrosocysteine: evidence of a new decomposition pathway for nitrosothiols.

The rate of S-nitrosocysteine decomposition in a pH range between 0.7 < pH < 13 exhibits first- and second-order dependence on total cysteine concentration. The second-order term is only observed for pH values between 6.9 < pH < 12. Both first- and second-order terms show a complex dependence on the acidity of the medium. They increase with increasing pH, reaching a maximum value around pH = 8 and then decrease with further increase in pH. An analysis of the reaction products reveals the absence of nitrite ion and ammonia. No evidence of catalysis by copper ions is observed. These results suggest the existence of a new decomposition pathway for S-nitrosocysteine, which proceeds via an intramolecular nitroso group transfer producing a primary N-nitrosamine that decomposes rapidly to give the corresponding diazonium salt. The nitroso group transfer reaction occurs intermolecularly for the decomposition pathway exhibiting a quadratic dependence on cysteine concentration. Both nitroso group transfer pathways are subject to acid catalysis by cysteine. Kinetic results indicate that the extent of S...NO bond cleavage in the transition state is ahead of protonation of the AH...S sulfur atom. The results obtained show the existence of a new decomposition pathway for the S-nitrosocysteine where NO is not released, and hence, it has a significant biological impact due to the potential use of nitrosothiols as NO donors.