Cancer cachexia: a systematic literature review of items and domains associated with involuntary weight loss in cancer

Background

The concept of cancer-related anorexia/cachexia is evolving as its mechanisms are better understood. To support consensus processes towards an updated definition and classification system, we systematically reviewed the literature for items and domains associated with involuntary weight loss in cancer.

Methods

Two search strings (cachexia, cancer) explored five databases from 1976 to 2007. Citations, abstracts and papers were included if they were original work, in English/German language, and explored an item to distinguish advanced cancer patients with variable degrees of involuntary weight loss. The items were grouped into the 5 domains proposed by formal expert meetings.

Results

: Of 14,344 citations, 1275 abstracts and 585 papers reviewed, 71 papers were included (6325 patients; 40–50% gastrointestinal, 10–20% lung cancer). No single domain or item could consistently distinguish cancer patients with or without weight loss or having various degrees of weight loss. Anorexia and decreased nutritional intake were unexpectedly weakly related with weight loss. Explanations for this could be the imprecise measurement methods for nutritional intake, symptom interactions, and the importance of systemic inflammation as a catabolic drive. Data on muscle mass and strength is scarce and the impact of cachexia on physical and psychosocial function has not been widely assessed.

Conclusions

Current data support a modular concept of cancer cachexia with a variable combination of reduced nutritional intake and catabolic/hyper-metabolic changes. The heterogeneity in the literature revealed by this review underlines the importance of an agreed definition and classification of cancer cachexia.     

Psychological characteristics associated with the onset and course of asthma in children and adolescents: A systematic review of longitudinal effects

Objective

To systematically review all available studies that investigated the longitudinal relationships between the psychological characteristics of children and adolescents suffering from asthma and those of their caregivers, and the onset and course of the asthma.

Methods

Relevant studies were identified using Medline, PubMed, and PsychINFO between 1970 and September 2009.

Results

Twenty studies matching inclusion criteria were reviewed. Six studies focused on child-specific psychological characteristics in relation to the onset and course of asthma. No compelling evidence was found for an association with asthma onset, but there was some evidence that the child's psychological characteristics can contribute to the subsequent course of asthma. Fourteen studies considered the effects of the psychological characteristics of the caregivers. Eleven studies found significant relationships between the psychological problems of caregivers and the subsequent onset and unfavorable course of the asthma in the child.

Conclusion

In pediatric asthma both the psychological characteristics of the affected children and their caregivers appear to contribute to the course and possibly also to the onset of the condition.     

Similarities in Thromboelastometric (ROTEM®) Findings between Humans and Baboons

Introduction

Interest in visco-elastic testing in different clinical scenarios has increased but few data are available on thromboelastometric findings in primates.

Materials and Methods

Blood cell count (hemoglobin, hematocrit, platelet count), coagulation parameters (prothrombin time, International Normalized Ratio, fibrinogen), and ROTEM® (Tem International GmbH, Munich, Germany) variables were analyzed using blood from 25 anesthetized male baboons and 21 non-anesthetized healthy volunteers. The platelet component of the clot was calculated as the difference in maximum clot elasticity (MCE) between the whole blood clot (EXTEM test) and the fibrin-based clot (FIBTEM test). In subgroups of each species, 10 μg abciximab was added to the regular FIBTEM reagent (cytochalasin D) for additional platelet inhibition.

Results

Blood cell count was comparable between humans and primates. Both fibrinogen concentration (p < 0.0001) and maximum clot firmness (MCF) in FIBTEM assays were significantly lower in baboons (p > 0.0001, and p = 0.006, respectively). PT, INR, and clotting time in NATEM assays were significantly prolonged in humans compared with baboons. MCF in NATEM, EXTEM and INTEM assays was not different between baboons and humans. Clot lysis in NATEM, EXTEM and INTEM assays was significantly higher in humans (p < 0.0001). In contrast FIBTEM clot lysis was significantly higher in baboons (p = 0.01). Addition of abciximab into the FIBTEM assay resulted in a significant reduction in MCF and MCE (p < 0.001) and, consequently, the platelet component increased similar in both humans and baboons (p < 0.001).

Conclusion

Activated ROTEM® tests revealed broad similarities between humans and baboons. ROTEM® assays developed for use in humans can also be used in baboons.     

Toxicity of so-called edible hijiki seaweed (Sargassum fusiforme) containing inorganic arsenic

The UK Food Standards Agency and its counterparts in other countries have warned consumers not to eat hijiki (Sargassum fusiforme; synonym Hizikia fusiformis), a Sargasso seaweed, because it contains large amounts of inorganic arsenic. We investigated dietary exposure of hijiki in weaning male F344/N rats fed an AIN-93G diet supplemented with 3% (w/w) hijiki powder for 7 weeks, compared with those fed only an AIN-93G diet. Body weight, body temperature, blood and tissue arsenic concentrations, plasma biochemistry and hematological parameters were measured. We found that feeding rats a 3% hijiki diet led to a marked accumulation of arsenic in blood and tissues, and evoked a high body temperature and abnormal blood biochemistry including elevated plasma alkaline phosphatase activity and inorganic phosphorus, consistent with arsenic poisoning. These findings should prompt further investigations to identify the health hazards related to consumption of hijiki and related Sargassum species in humans.     

Depletion of melamine and cyanuric acid in serum from catfish Ictalurus punctatus and rainbow trout Onchorhynchus mykiss

Melamine and its triazine analogs, such as cyanuric acid, have been used to artificially inflate protein content both in animal feed ingredients, as well as in milk products produced for human consumption. We report here a LC–MS/MS method to quantify and confirm melamine and cyanuric acid in serum from channel catfish and rainbow trout with a limit of quantification of 0.8 μg/mL. The method was applied to serum samples from a residue depletion study in which fish were given a single oral dose of 20 mg/kg body weight melamine, cyanuric acid, or both compounds together. Samples were taken at 1, 3, 7, 14, and 28 days (an additional 42 day was added for trout). When given alone or in combination with cyanuric acid, melamine residues were highest on day 1 in both catfish and trout. Cyanuric acid was only quantifiable at day 1 in trout when given alone, and not at all in catfish. The serum half life of melamine in catfish was 1.50–1.62 days and 3.09–3.67 days in trout. This work highlights the differences of depletion kinetics in fish, which can be measured in days, as compared to the depletion in mammals, measured in hours.     

Long-term administration of fasudil improves cardiomyopathy in streptozotocin-induced diabetic rats

Inhibition of Rho kinase (ROCK) has been shown to improve diabetic-related disorders. In this study, the cardio-protective effects and potential mechanisms of fasudil, a selective ROCK inhibitor, on diabetic cardiomyopathy were investigated in a streptozotocin (STZ)-induced diabetic rat model. Eight weeks after diabetes was induced by a single tail vein injection of 60 mg/kg STZ, rats were administered long-term fasudil or captopril as a control over a four-week period. Similar to the effect of captopril, fasudil treatment significantly protected against STZ-induced hemodynamic, histopathologic changes and decreased serum lactate dehydrogenase and creatine phosphokinase. Moreover, fasudil significantly down-regulated ROCK I mRNA expression and ROCK activity, reduced cardiac collagen deposition, and decreased the incidence of apoptosis and ratio of Bax/Bcl-2 protein expression. Additionally, fasudil potently elevated superoxide dismutase activity and suppressed the extent of lipid peroxidation in sera and hearts of diabetic rats. Our findings indicated that long-term treatment with fasudil could improve cardiac dysfunction, attenuate myocardial injury and prevent pathological changes in a rat model of diabetic cardiomyopathy. These effects could be attributed to regulation of antioxidative activities, suppression of myocardial hypertrophy, apoptosis, fibrosis and subsequent cardiac remodeling. These results may help to expand the clinical application of fasudil for diabetic cardiomyopathy.     

Prediction of gross motor development and independent walking in infants born very preterm using the Test of Infant Motor Performance and the Alberta Infant Motor Scale

Background

One objective of a neonatal follow-up program is to examine and predict gross motor outcome of infants born preterm.

Aims

To assess the concurrent validity of the Test of Infant Motor Performance (TIMP) and the Alberta Infant Motor Scale (AIMS), the ability to predict gross motor outcome around 15 months corrected age (CA), and to explore factors associated with the age of independent walking.

Methods

95 infants, born at a gestational age < 30 weeks, were assessed around 3, 6 and 15 months CA. At 3 months CA, correlations of raw-scores, Z-scores, and diagnostic agreement between TIMP and AIMS were determined. AIMS-score at 15 months CA and parental-reported walking age were outcome measures for regression analyses.

Results

The correlation between TIMP and AIMS raw-scores was 0.82, and between Z-scores 0.71. A cut-off Z-score of − 1.0 on the TIMP had 92% diagnostic agreement (κ = 0.67) with an AIMS-score < P10. Neither TIMP- nor AIMS-scores at 3 months CA were associated with the gross motor outcome at 15 months CA. The AIMS-scores at 6 months CA predicted the AIMS-scores at 15 months CA with an explained variance of 19%. Median walking age was 15.7 months CA, with which only the hazard ratio of the AIMS at 6 months CA and ethnicity were significantly associated.

Conclusions

Prediction of gross motor development at 15 months CA and independent walking was not possible prior to 6 months CA using the AIMS, with restricted predictive value. Cultural and infant factors seem to influence the onset of independent walking.     

Visual search and attention in five-year-old very preterm/very low birth weight children

Introduction

This study aimed to establish visual search performance and attention functioning in very preterm/very low birth weight (VP/VLBW) children using novel and well established measures, and to study their contribution to intellectual functioning.

Methods

Visual search and attention network efficiency were assessed in 108 VP/VLBW children and 72 age matched term controls at 5.5 years corrected age. Visual search performance was investigated with a newly developed paradigm manipulating stimulus density and stimulus organization. Attention functioning was studied using the Attention Network Test (ANT). Intellectual functioning was measured by a short form of the Wechsler Preschool and Primary Scale of Intelligence. Data were analyzed using ANOVAs and multiple regression analyses.

Results

Visual search was less efficient in VP/VLBW children as compared to term controls, as indicated by increased search time (0.31 SD, p = .04) and increased error rate (0.36 SD, p = .02). In addition, VP/VLBW children demonstrated poorer executive attention as indicated by lower accuracy for the executive attention measure of the ANT (0.61 SD, p < .001). No differences were found for the alerting (0.06 SD, p = .68) and orienting attention measures (0.13 SD, p = .42). Visual search time and error rate, and executive attention, collectively, accounted for 14% explained variance in full scale IQ (R² = .14, p < .001).

Discussion

VP/VLBW children were characterized by less efficient visual search ability and reduced executive attention. Visual attention dysfunctions contributed to intelligence, suggesting the opportunity to improve intellectual functioning by using interventions programs that may enhance attention capacities.     

Cord blood 8-isoprostane in the preterm infant

Background

Cord blood 8-isoprostane (8-IP) is a marker of lipid peroxidation in the peripartum period. The independent association with degree of prematurity is not well-described.

Objective

To identify patterns of lipid peroxidation among early, moderate and late preterm infants, and to understand how cord blood 8-IP varies with gestational age (GA) and related covariates.

Study design

Mother–infant pairs from 237 preterm births were studied as part of a longitudinal birth cohort study. GA subgroups were defined as extremely (≤ 28w), moderately (29–33w), and late (34–36w) preterm. Cord blood 8-IP was measured using EIA. Elevated 8-IP (4th quartile) was the primary outcome for multivariate logistic regression models, which were adjusted for maternal age/race, multiple gestation and infant gender, as well as other relevant covariates.

Results

Elevated 8-IP was associated with extremely preterm birth (OR = 4.31; 95% CI = 1.90, 9.76), and was inversely associated with increasing GA (OR = 0.88; 95% CI = 0.80, 0.97). Elevated 8-IP was also associated with decreasing birth weight (BW), clinical chorioamnionitis, fetal inflammatory response of the placenta (FIR), and signs of perinatal depression. The GA on 8-IP association appeared to be modified by several maternal disease and fetal–infant factors. Lastly, the indirect associations between log-transformed 8-IP, GA and BW appeared to be most prominent for GA < 30w and for BW < 2000 g.

Conclusion

Lipid peroxidation in preterm birth, and the relative influence of accompanying peripartum factors, varies according to degree of prematurity. These findings have important implications for the developmental regulation of antioxidant defense and its impact on neonatal outcomes.