Decreased body mass index is associated with impaired survival in lung cancer patients with brain metastases: A retrospective analysis of 624 patients.

Body mass index (BMI) is a prognostic factor in several cancer types. We investigated the prognostic role of BMI in a large patient cohort with newly diagnosed lung cancer brain metastases (BM) between 1990 and 2013. BMI at diagnosis of BM and graded prognostic assessment (GPA) were calculated. Definitions were underweight (BMI <18.50), weight within normal range (BMI 18.50-24.99) and overweight (BMI ≥ 25.00). A total of 624 patients (men 401/624 [64.3%]; women 223/624 [35.7%]; median age of 61 [range 33-88]) were analysed. Histology was non-small cell lung cancer in 417/622 (66.8%), small cell lung cancer (SCLC) in 205/624 (32.9%) and not otherwise specified in 2/624 (0.3%) patients. About 313/624 (50.2%) had normal BMI, 272/624 (43.5%) were overweight and 39/624 (6.3%) were underweight. Underweight patients had shorter median overall survival (3 months) compared to patients with normal BMI (7 months) and overweight (8 months; p < .001; log rank test). At multivariate analysis, higher GPA class (HR 1.430; 95% cumulative incidence, CI 1.279-1.598; p < .001; Cox regression model), SCLC histology (HR 1.310; 95% CI 1.101-1.558) and presence of underweight (HR 1.845; 95% CI 1.317-2.585; p = .014; Cox regression model) were independent prognostic factors. Underweight at diagnosis of BM in lung cancer is associated with an unfavourable prognosis.

Hope as determinant for psychiatric morbidity in family caregivers of advanced cancer patients.

OBJECTIVE: Home care of advanced cancer patients often has adverse effects on physical and mental health of family caregivers. Little is known about the long-term effects of continuous caregiving on mental health as compared with the effects of bereavement. The objectives of this study were to describe the course of psychiatric morbidity in family caregivers over time, to identify the impact of the patients' death on caregivers, and to explore possible predictor variables for psychiatric morbidity. METHODS: This multi-institutional, prospective study included 80 family caregivers of 80 advanced cancer patients for baseline and 9 months follow-up assessment. Possible psychiatric disorders (ie, depression, anxiety, posttraumatic stress disorder, and alcohol abuse/dependence) as well as potentially predictive factors (ie, sociodemographic factors, burden, hope, and coping mechanisms) were assessed. RESULTS: Follow-up assessment was conducted on average 9.2 months (±2.9) after baseline assessment. Prevalence rates of anxiety and posttraumatic stress disorder decreased significantly over time, whereas depression and alcoholism remained stable. Bereavement was experienced by 53% of caregivers in the follow-up period. The patients' death had no influence on psychiatric morbidity at follow-up. Predictors for the development of a psychiatric disorder varied according to condition, with hope and emotion-oriented coping identified as important influences, especially for anxiety and depression. CONCLUSION: Family caregivers with certain psychiatric disorders might need targeted psychosocial support to ensure their mental well-being and prevent long-term disability. Supporting hope and functional coping strategies early after the patient's diagnosis might limit development and extent of psychiatric morbidity.

Informal caregivers of advanced-stage cancer patients: Every second is at risk for psychiatric morbidity.

PURPOSE: Informal caregivers of advanced cancer patients are known to suffer from high distress due to their caregiving responsibilities. Nevertheless, a comprehensive evaluation of psychiatric morbidity is often missing in clinical practice due to time resources, and mental health problems may be unnoticed in this population. A feasible approach is needed to identify caregivers at risk for psychiatric disorders to offer targeted interventions and enhance their well-being. METHODS: This cross-sectional, multi-institutional study screened 345 caregivers of advanced cancer patients for psychiatric disorders (i.e., depression, anxiety, posttraumatic stress disorder, and alcohol abuse/dependence) and assessed factors potentially associated with mental health diagnoses (including socio-demographic factors, burden, hope, caring-related quality of life, and coping preferences). RESULTS: Overall, almost 52 % of participants had one or more suspected psychiatric disorders, with anxiety being the most prevalent. Perceived hope, higher burden, and more emotion-oriented coping were associated with psychiatric morbidity in this sample. Spouses and parents showed significantly more symptoms of psychiatric disorders than other relatives. CONCLUSIONS: This study confirms the high risk of informal caregivers of advanced cancer patients to develop psychiatric disorders and suggests a practically feasible approach to identify at risk caregivers to offer support.

The PERS(2) ON score for systemic assessment of symptomatology in palliative care: a pilot study.

The comprehensive assessment of symptoms is the basis for effective, individualised palliative treatment. Established scoring systems provide in-depth information but are often lengthy and hence unsuitable. We introduce the PERS(2) ON score as a short and practically feasible score to evaluate symptom burden. Fifty patients admitted to a Palliative Care Unit rated seven items, i.e. pain, eating (loss of appetite/weight loss), rehabilitation (physical impairment), social situation (possibility for home care), suffering (anxiety/burden of disease/depression), O2 (dyspnoea) and nausea/emesis, on a scale ranging from 0 (absence) to 10 (worst imaginable), resulting in a score ranging from 0 to 70. Assessments were performed at admission, 7 days after admission and at the day of discharge. Symptom intensity scores were calculated, and change over time was evaluated. A significant improvement was observed from the PERS²ON score between admission and 7 days (P < 0.001; paired t-test). Significant improvement from baseline evaluation to evaluation on the day of discharge was observed (P = 0.001; paired t-test). This study provides initial evidence that the PERS²ON score is both feasible and sensitive to changes of the most prominent symptoms in palliative care. It may be useful in clinical practice to direct palliative treatment strategies and provide targeted symptom management.

Dabigatran in patients with atrial fibrillation: perioperative and periinterventional management.

In any type of invasive surgery, the patient's individual risk of thromboembolism has to be weighed against the risk of bleeding. Based on various everyday situations in clinical routine, the purpose of the present expert recommendations is to provide appropriate perioperative and periinterventional management for patients with atrial fibrillation undergoing long-term treatment with the thrombin inhibitor dabigatran. As we currently have no routine laboratory test to measure therapeutic levels of the substance or the risk of bleeding, general measures such as a standardized documentation of the patient's history, a sufficient time interval between the last preoperative dose and the procedure, and careful control of local hemostasis should be given special attention.

Interfacial mechanism of lipolysis as self-regulated process.

Obesity is a serious public health concern with an increasing prevalence worldwide. The diet contributes strongly to this problem and high-fat food leads to unhealthy conditions. Fat digestion is an energy intensive process as it requires hydrolysis to allow the body to profit from this nutrient. This additional energy expenditure is also present in a highly redundant hormonal regulation system for fat storage which is converted in not a readily accessible form (therefore, an upstream is required in order to tackle fat-related diseases). Due to the low water solubility of oils and fats, the lipase catalyzed reactions take place at a specific locus, the oil-water interface. Despite considerable efforts in the past the effects of the interfacial composition on lipase activity have been only qualitatively understood until recently. It has recently been undertaken a detailed study of the interfacial behavior of lipases, their substrates and products which have contributed to shed light into the mechanism of lipolysis [1-4]. In addition, there are strong evidences that lipase activity is a function of interfacial composition and changes concurrently with lipolytic conversion [1]. In these cases lipase "inhibition" should be attributed to substrate depletion and not to lipase desorption or denaturation as previously hypothesized [5]. This self-limiting effect through the feedback of interfacial composition to the reaction conditions of the enzyme opens a new avenue to control lipase catalysis through the interface. A set of experiments are proposed which can be performed to further characterize and gain a deeper insight into interfacial enzymology.

Lipase-catalyzed reactions at interfaces of two-phase systems and microemulsions.

This work describes the influence of two polar lipids, Sn-1/3 and Sn-2 monopalmitin, on the activity of lipase in biphasic systems and in microemulsions. In previous communications, we have shown that Sn-2 monoglycerides can replace Sn-1,3 regiospecific lipases at the oil-water interface, causing a drastically reduced rate of lipolysis. We here demonstrate that even if the lipase is expelled from the interface, it can catalyze esterification of the Sn-2 monoglyceride with fatty acids in both macroscopic oil-water systems and in microemulsions, leading to formation of di- and triglycerides.

Lipases at interfaces: a review.

Lipases are acyl hydrolases that play a key role in fat digestion by cleaving long-chain triglycerides into polar lipids. Due to an opposite polarity between the enzyme (hydrophilic) and their substrates (lipophilic), lipase reaction occurs at the interface between the aqueous and the oil phases. Hence, interfaces are the key spots for lipase biocatalysis and an appropriate site for modulating lipolysis. Surprisingly enough, knowledge about the effects of the interfacial composition on lipase catalysis is still limited and only described by the term "interfacial quality". Recent systematic studies based on a biophysical approach allowed for the first time to show the effects of the interfacial microenvironment on lipase catalysis. These studies demonstrate that lipase activity as a function of interfacial composition is more attributed to substrate inaccessibility rather than to enzyme denaturation or inactivation, as it is often hypothesized. A detailed analysis of the interfacial properties of all compounds involved in triglyceride digestion revealed that lipolysis is a self-regulated reaction. This feedback mechanism can be explored as a new avenue to control lipase catalysis. To substantiate this hypothesis, oil hydrolysis in a model gastro-intestinal system was performed, which can be seen as an interfacial engineering approach to enzyme reactivity control. The presented characterization of the interfacial composition and its consequences provide a new approach for the understanding of lipase reactions at interfaces with direct impact on biotechnological and health care applications.

Traveller's thrombosis: international consensus statement.

In 2001, consensus meetings on traveller's thrombosis were held in Vienna and Berlin. The results of these conferences were subsequently published in VASA 2002. In 2006 a follow-up conference was organized in Hall, Tirol, Austria, in order to review new and emerging data and to update the conclusions and recommendations of the 2001 meetings. Prior to the conference key papers from peer-reviewed journals were pre-circulated to all participants. The consensus group discussed the data and drafted an updated statement. Thereafter, the writing group summarised the results including the pre-circulated material and additional papers identified by a formal literature search up to December 2007. In this article current knowledge on the incidence, pathophysiology and prevention of traveller's thrombosis is summarised. The assessment of individual risk is described and recommendations for prevention of traveller's thrombosis are given, based upon the conclusions of the Hall Conference.

Lipases at interfaces: unique interfacial properties as globular proteins.

The adsorption behavior of two globular proteins, lipase from Rhizomucor miehei and beta-lactoglobulin, at inert oil/water and air/water interfaces was studied by the pendant drop technique. The kinetics and adsorption isotherms were interpreted for both proteins in different environments. It was found that the adopted mathematical models well describe the adsorption behavior of the proteins at the studied interfaces. One of the main findings is that unique interfacial properties were observed for lipase as compared to the reference beta-lactoglobulin. A folded drop with a "skinlike" film was formed for the two proteins after aging followed by compression. This behavior is normally associated with protein unfolding and covalent cross-linking at the interface. Despite this, the lipase activity was not suppressed. By highlighting the unique interfacial properties of lipases, we believe that the presented work contributes to a better understanding of lipase interfacial activation and the mechanisms regulating lipolysis. The results indicate that the understanding of the physical properties of lipases can lead to novel approaches to regulate their activity.

Adsorption of polar lipids at the water-oil interface.

Dietary fat has long been recognized as an essential component in nutrition. However, most of the lipids present in food need to be converted into more bioavailable compounds. Lipases have a crucial role in converting triglycerides into more polar lipids with increased water solubility and a tendency to form micelles. However, the surface active molecules generated by lipolysis may have a detrimental effect on the interfacial biocatalysis. In the present work we evaluate the interfacial properties of lipase-generated molecules during fat digestion. By using the pendant drop technique we assessed the amphiphilic character of fatty acid salts, monoglycerides, and diglycerides as individual surfactants and mixtures. The experimental results are fitted with a mathematical model, which assists in the determination of the interfacial properties of the surfactants. Our results show that monoglycerides have considerably higher interfacial activity than fatty acid salts and diglycerides. Therefore, the interface will soon be dominated by monoglycerides. The pH dependency of the interfacial activity of fatty acids is also explored in the current work. We believe that our results can contribute to a better understanding of the complex interfacial phenomena occurring during fat digestion.

Lipase-catalyzed reactions at different surfaces.

Starting from gold chips, we have tailor-made three surfaces by the self-assembly monolayer technique: one entirely hydrophobic, one hydrophobic with dispersed carboxyl groups, and one hydrophilic, containing hydroxyl groups. Rhizomucor miehei lipase has been adsorbed to the hydrophobic and the hydrophilic surfaces and covalently bound to the surface containing carboxyl groups. The adsorption of two substrates-capric acid (decanoic acid) and monocaprin-on the lipase-covered surfaces was monitored by the surface plasmon resonance (SPR) technique. Biocatalysis was also performed in the SPR instrument by circulating a solution of the substrate, dissolved in an 85:15 water-glycerol mixture at a(w) = 0.81, through the instrument, thus exposing the capric acid or the monocaprin to the lipase-covered surfaces. The product composition was found to depend on the type of surface used. Lipase adsorbed at the hydrophilic surface favored hydrolysis, and capric acid was the main product formed when monocaprin was used as substrate. Lipase adsorbed at a hydrophobic surface and, in particular, lipase covalently bound to a hydrophobic surface favored condensation. More dicaprin than capric acid was formed in experiments with monocaprin as the substrate. Reactions performed outside the SPR instrument showed that small amounts of triglyceride were also formed under these conditions. We believe that this work constitutes the first example of the SPR instrument being used for in-situ biotransformation.

Reversibility and irreversibility of adsorption of surfactants and proteins at liquid interfaces.

It is shown experimentally that the desorption of sodium decyl sulphate from the liquid/air interface is purely diffusion controlled, while the desorption of higher surface active surfactants such as the non-ionic surfactants Triton X-100 and tridecyl dimethyl phosphine oxide obeys a mixed mechanism. The desorption kinetics of beta-lactoglobulin (BLG) and beta-casein is, however, determined by a barrier mechanism. From the analysis of the BLG and beta-casein desorption kinetics at different temperatures the activation energy of desorption is calculated. The values obtained are rather close to the free energy of adsorption. The theoretical model of desorption kinetics predicts that these two energetic parameters are similar if the adsorption activation energy is low. This explains why substances with a higher adsorption activity have a lower desorption rate. Adsorption kinetics studies for beta-casein with and without forced convection show the same equilibrium surface tension values. This leads to the conclusion that the protein adsorption at liquid interfaces is thermodynamically reversible, although the slow desorption kinetics would allow to assume it to be an irreversible process.

Crystallography of dispersed liquid crystalline phases studied by cryo-transmission electron microscopy.

Low molecular weight surfactants, for example monoglycerides and phospholipids, form a multitude of self-assembled structures, such as inverted cubic or hexagonal mesophases, if brought into contact with water/oil. These mesophases can be dispersed in water using adequate surface-active materials such as low molecular weight surfactants or surface active polymers. In order to use such mesophase particles for incorporating drugs and aromas, it is essential to determine their internal crystallographic structure and to understand their mechanism of stabilization. Cryo-transmission electron microscopy was used to investigate the internal structure of different dispersed particles at various temperatures and oil contents. It is shown here that cryo-transmission electron microscopy, in combination with fast Fourier transform and tilting experiments, is effective in obtaining information on crystallographic structure, space group and morphology of particles with reversed bicontinuous cubic and hexagonal structures. In particular, using the presence or the absence of the {111} reflections and viewing the same particle under different axes of observation allows one to discriminate between the Im3m and Pn3m space groups. A major advantage of cryo-transmission electron microscopy is the ability to analyse single particles. This allows the identification of particles present at very low concentrations and the coexistence of particles with different internal self-assembly structures. With this technique we have obtained strong evidence for the presence of two cubic internal self-assembly structures with different space groups within the same dispersion. In addition, we found that cryo-transmission electron microscopy combined with tilting experiments enables the analysis of internal particle morphology, allowing the discussion of mechanisms for hexosome stabilization.

Personalizing Foods for Health and Delight.

Consumer goods have become increasingly individualized over the past 50 y, and the scientific knowledge of genetics, diet, and metabolism will bring similar personal values to foods and health.

The quality of oral anticoagulation before, during and after a period of patient self-management.

The study analyzes the quality of anticoagulation during a 3-year follow-up on patients who were treated by an anticoagulation clinic (ACS) for 1 year (Phase I), performed weekly self-management of anticoagulation (PSM) after a specific training for another year (Phase II) and finally returned to be treated by the anticoagulation clinic (ACS) for a third year (Phase III). The mean fraction of INR values within therapeutic target range was higher in Phase II (0.69 +/- 0, 11) compared to Phases I (0.40 +/- 0.20) and III (0.56 +/- 0.18; p < 0.05). Time spent in therapeutic target range was higher in Phase II (0.70 +/- 0.10) compared to Phases I (0.43 +/- 0.25) and III (0.60 +/- 0.17; p < 0.05). Mean square deviation from target value was lower in Phase II (0.39 +/- 0.17) compared to Phases I (0.81 +/- 0.44) and III (0.64 +/- 0.39, p = 0.05). Thus, the quality of anticoagulation during Phase II (PSM) was significantly better compared to Phases I (ACS) and III (ACS) in all endpoints tested. This shows that the quality of oral anticoagulation deteriorates again if patient self-management is stopped and patients return to conventional treatment. Furthermore, the quality of anticoagulation was better in Phase III (post-PSM) compared with Phase I (pre-PSM) although the type of treatment was identical in both phases (ACS). This suggests that the increased patient empowerment and enhanced compliance acquired during PSM (Phase II) might have a positive impact on the quality of anticoagulation, even when patients return to the conventional treatment (ACS).

Improved oil solubilization in oil/water food grade microemulsions in the presence of polyols and ethanol.

Microemulsions based on five-component mixtures for food applications and improved oil solubilization have been studied. The compositions included water, oil phase [such as R(+)-limonene and medium-chain triglycerides (MCT)], short-chain alcohols (such as ethanol), polyols (propylene glycol and glycerol), and several surfactants and their corresponding mixtures (nonionic, such as ethoxylated sorbitan esters, polyglycerol esters, sugar ester, and anionic, such as phosphatidylcholine). The phase behavior of these systems is discussed with respect to the influence of polyols and short-chain alcohols on the degree of solubilization of oils in the aqueous phase. The alcohol and polyols modify the interfacial spontaneous curvature and the flexibility of the surfactant film, enhancing the oil solubilization capacity of the microemulsions. The solubilization of R(+)-limonene was dramatically improved in the presence of the alcohol and polyols, whereas the improvement of solubilization for triglycerides containing MCT was less pronounced. In some systems high oil solubilization was achieved, and some of them can be easily diluted to infinity both with the aqueous phase and with the oil phase. Viscosity measurements along selected dilution lines [characterized by a single continuous microemulsion region starting from a pseudo binary solution (surfactant/oil phase) to the microemulsion (water/polyol corner)] indicate that at a certain composition the system inverts from a W/O to an O/W microemulsion.

Structured fluids as microreactors for flavor formation by the Maillard reaction.

Thermal reactions of cysteine/furfural and cysteine/ribose mixtures were studied in model systems to gain more insight into the influence of structured fluids such as L(2) microemulsions and cubic phases on the generation of aroma compounds. Formation of 2-furfurylthiol from cysteine/furfural was particularly efficient in L(2) microemulsions and cubic phases compared to aqueous systems. The reaction led to the formation of two new sulfur compounds, which were identified as 2-(2-furyl)thiazolidine and, tentatively, N-(2-mercaptovinyl)-2-(2-furyl)thiazolidine. Similarly, generation of 2-furfurylthiol and 2-methyl-3-furanthiol from cysteine/ribose mixtures was strongly enhanced in structured fluids. The cubic phase was shown to be even more efficient in flavor generation than the L(2) microemulsion. It was denoted "cubic catalyst" or "cubic selective microreactor". The obtained results are interpreted in terms of a surface and curvature control of the reactions defined by the structural properties of the formed surfactant associates.

The decanucleotide polymorphism in the factor VII promoter predicts factor VII plasma levels but not the risk of acute coronary syndromes.

It is known from large epidemiological studies that the elevation of coagulation factor VII in plasma is an independent risk factor for acute coronary syndromes. The level of factor VII is influenced by polymorphic sites in the factor VII gene. However, data on the association of such polymorphisms with the risk of acute coronary syndromes are conflicting. A decanucleotide insertion/deletion polymorphic site has been described in the promoter of the factor VII gene that leads to a dramatic change in the plasma factor VII levels. We therefore analyzed the association of this polymorphism with the risk of acute coronary syndromes in a case-control study. Included in the study were 111 patients with angiographically documented acute coronary syndromes and 108 age- and sex-matched individuals from the same geographic area without signs or symptoms of coronary heart disease. The presence or absence of the decanucleotide stretch at position -323 in the promoter of factor VII was monitored using a polymerase chain reaction (PCR)-based restriction technique. The prevalence of the genotype with the homozygous deletion was similar in the patients with acute coronary syndromes (79.2%) and in the control patients (79.6%). There was a non-significant trend toward a higher prevalence of the homozygote deletion in patients with premature acute coronary syndromes (77.4%) compared with an age-matched subgroup of the control patients (67. 5%) (odds ratio [OR] 1.6, confidence interval [CI] 0.95, 0.61-3.93). Thus, we could not find a significant association of the occurrence of acute coronary events with the insertion/deletion polymorphism in factor VII.