Cachexia, dietetic consultation, and survival in patients with pancreatic and periampullary cancer: A multicenter cohort study

It is unclear to what extent patients with pancreatic cancer have cachexia and had a dietetic consult for nutritional support. The aim was to assess the prevalence of cachexia, dietitian consultation, and overall survival in these patients. This prospective multicenter cohort study included patients with pancreatic cancer, who participated in the Dutch Pancreatic Cancer Project and completed patient reported outcome measures (2015–2018). Additional data were obtained from the Netherlands Cancer Registry. Cachexia was defined as self-reported >5% body weight loss, or >2% in patients with a BMI <20 kg/m2 over the past half year. The Kaplan–Meier method was used to analyze overall survival. In total, 202 patients were included from 18 centers. Cachexia was present in 144 patients (71%) and 81 of those patients (56%) had dietetic consultation. Cachexia was present in 63% of 94 patients who underwent surgery, 77% of 70 patients who received palliative chemotherapy and 82% of 38 patients who had best supportive care. Dietitian consultation was reported in 53%, 52%, and 71%, respectively. Median overall survival did not differ between patients with and without cachexia, but decreased in those with severe weight loss (12 months (IQR 7–20) vs. 16 months (IQR 8–31), p = 0.02), as compared to those with <10% weight loss during the past half year. Twothirds of patients with pancreatic cancer present with cachexia of which nearly half had no dietetic consultation. Survival was comparable in patients with and without cachexia, but decreased in patients with more severe weight loss

Coexistence via Resource Partitioning Fails to Generate an Increase in Community Function

Classic ecological theory suggests that resource partitioning facilitates the coexistence of species by reducing inter-specific competition. A byproduct of this process is an increase in overall community function, because a greater spectrum of resources can be used. In contrast, coexistence facilitated by neutral mechanisms is not expected to increase function. We studied coexistence in laboratory microcosms of the bactivorous ciliates Paramecium aurelia and Colpidium striatum to understand the relationship between function and coexistence mechanism. We quantified population and community-level function (biomass and oxygen consumption), competitive interactions, and resource partitioning. The two ciliates partitioned their bacterial resource along a size axis, with the larger ciliate consuming larger bacteria than the smaller ciliate. Despite this, there was no gain in function at the community level for either biomass or oxygen consumption, and competitive effects were symmetrical within and between species. Because other potential coexistence mechanisms can be ruled out, it is likely that inter-specific interference competition diminished the expected gain in function generated by resource partitioning, leading to a system that appeared competitively neutral even when structured by niche partitioning. We also analyzed several previous studies where two species of protists coexisted and found that the two-species communities showed a broad range of biomass levels relative to the single-species states

Beyond Genetic Factors in Familial Amyloidotic Polyneuropathy: Protein Glycation and the Loss of Fibrinogen's Chaperone Activity

Familial amyloidotic polyneuropathy (FAP) is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR). This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease

Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs

Optimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i) DC activation/maturation milieu (TNF-α +/- IFN-α) and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865), (ii) CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672)-pulsed DCs, prepared without IFN-α, (iii) association between circulating T regulatory cells (Tregs) and clinical responses

An update on vitamin B12-related gene polymorphisms and B12 status.

Vitamin B12 is an essential micronutrient in humans needed for health maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental and genetic factors. Evidence for the genetic basis of vitamin B12 status is poorly understood. However, advancements in genomic techniques have increased the knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene and genome-wide association (GWA) studies, associations between genetic loci in several genes involved in vitamin B12 metabolism have been identified. The objective of this literature review was to identify and discuss reports of associations between single-nucleotide polymorphisms (SNPs) in vitamin B12 pathway genes and their influence on the circulating levels of vitamin B12. Relevant articles were obtained through a literature search on PubMed through to May 2017. An article was included if it examined an association of a SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds ratios were used to describe the strength of an association, and a  < 0.05 was considered as statistically significant. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data. From 23 studies which fulfilled the selection criteria, 16 studies identified SNPs that showed statistically significant associations with vitamin B12 concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with vitamin B12 status were identified in total, from the following populations: African American, Brazilian, Canadian, Chinese, Danish, English, European ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and residents of the USA. Overall, the data analyzed suggests that ethnic-specific associations are involved in the genetic determination of vitamin B12 concentrations. However, despite recent success in genetic studies, the majority of identified genes that could explain variation in vitamin B12 concentrations were from Caucasian populations. Further research utilizing larger sample sizes of non-Caucasian populations is necessary in order to better understand these ethnic-specific associations

Conservatism and novelty in the genetic architecture of adaptation in Heliconius butterflies

10 pagesInternational audienceUnderstanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima

Prognostic factors for medium- and long-term survival of esophageal cancer patients in the Netherlands

Background and Objectives Medium- and long-term survival is low in esophageal cancer (EC) patients, which is thought to be due to tumor characteristics. Our aim was to determine both tumor- and non-tumor-related characteristics affecting survival in these patients. Methods Patients with primary EC between 1990 and 2008 in the southern part of the Netherlands were identified. Multivariable logistic regression was used to identify determinants of survival. Results In total, 703 patients with EC were included for the 1-year, 551 for the 3-year and 436 for the 5-year survival analysis. Poor 1-year survival was independently associated with chemoradiation (compared to surgery), positive lymph nodes (N1-stage) and 1 or >= 2 comorbidities. Adenocarcinoma (EAC) compared to squamous cell carcinoma was significantly associated with a better 1-year survival. Poor 3- and 5-year survival was associated with N1-stage and chemoradiation. Positive prognostic factors for 3- and 5-year survival were neoadjuvant therapy and female gender. Conclusion Both tumor-related (negative lymph nodes and EAC histology) and non-tumor-related factors (surgery, neoadjuvant therapy, and female gender) are associated with a better survival of EC. Although it is not clear how histology and gender affect EC survival, knowledge of these factors may be relevant for clinical decision making. J. Surg. Oncol. 2014 109:465-471. (c) 2013 Wiley Periodicals, Inc

The Effect of Socioeconomic Status on Staging and Treatment Decisions in Esophageal Cancer

Background: Optimal treatment choice for patients with esophageal cancer (EC) is complex and largely determined by tumor characteristics, comorbidity, and age. Goals: This study describes the role of patient characteristics, among which is socioeconomic status (SES), in EC treatment. Study: Patients diagnosed with primary EC between 1990 and 2008 in the southern part of the Netherlands were identified using the Eindhoven Cancer Registry. Multivariable logistic and proportional hazard regression analyses were used to identify determinants of treatment and survival. Results: We included 1914 patients, and 37% of them underwent intentionally curative treatment. Low-SES patients were diagnosed at older age (16% vs. 9%, age more than or equal to 80) and with more advanced tumor stages (13% vs. 10%, stage T4) than high-SES patients. Age less than 60 compared with 70 to 79 years [adjusted odds ratio, 4.51; 95% confidence interval (CI), 2.98-6.84] and high SES compared with low SES (adjusted odds ratio 1.59; 95% CI, 1.07-2.37) were independent predictors for cura Conclusions: SES is an important factor in treatment choice of EC. As health care is equally accessible to the whole population in the Netherlands, this suggests that both patient-related and physician-related factors are involved in this phenomenon