Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?

Background

Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate.

Aims

To give new insights into cachexia’s pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases.

Methods

A systematic review was performed in PubMed using the keywords (“cancer” OR “cardiac” cachexia AND “human” OR “patient” AND “plasma” or “serum”). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators.

Results

Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients.

Conclusion

The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes.

     

Paleoparasitology: perspectives with new techniques.

Paleoparasitology is the study of parasites found in archaeological material. The development of this field of research began with histological identification of helminth eggs in mummy tissues, analysis of coprolites, and recently through molecular biology. An approach to the history of paleoparasitology is reviewed in this paper, with special reference to the studies of ancient DNA identified in archaeological material.     

pfcrt Polymorphism and the spread of chloroquine resistance in Plasmodium falciparum populations across the Amazon Basin

The widespread occurrence of drug-resistant malaria parasites in South America presents a formidable obstacle to disease control in this region. To characterize parasite populations and the chloroquine-resistance profile of Plasmodium falciparum in the Amazon Basin, we analyzed a DNA segment of the pfcrt gene, spanning codons 72-76, and genotyped 15 microsatellite (MS) markers in 98 isolates from 6 areas of Brazil, Peru, and Colombia where malaria is endemic. The K76T mutation, which is critical for chloroquine resistance, was found in all isolates. Five pfcrt haplotypes (S[tct]MNT, S[agt]MNT, CMNT, CMET, and CIET) were observed, including 1 previously found in Asian/African isolates. MS genotyping showed relatively homogeneous genetic backgrounds among the isolates, with an average of 3.8 alleles per marker. Isolates with identical 15-loci MS haplotypes were found in different locations, suggesting relatively free gene flow across the Amazon Basin. Allopatric isolates carrying SMNT and CMNT haplotypes have similar genetic backgrounds, although parasites carrying the CIET haplotype have some exclusive MS alleles, suggesting that parasites with CIET alleles were likely to have been introduced into Brazil from Asia or Africa. This study provides the first evidence of the Asian pfcrt allele in Brazil and a detailed analysis of P. falciparum populations, with respect to pfcrt haplotypes, in the Amazon Basin.     

Impact of cardiac resynchronization therapy on inflammatory biomarkers and cardiac remodeling: The paradox of functional and echocardiographic response

Introduction

Response to cardiac resynchronization therapy (CRT) can currently be assessed by clinical or echocardiographic criteria, and there is no strong evidence supporting the use of one rather than the other. Reductions in B-type natriuretic peptide (BNP) and C-reactive protein (CRP) have been shown to be associated with CRT response. This study aims to assess variation in BNP and CRP six months after CRT and to correlate this variation with criteria of functional and echocardiographic response.

The impacts of abnormal color vision on people's life: an integrative review

Quality of Life Research - This article shows an integrative review on the impact that abnormal color vision may have on the daily routine of individuals. We followed the PRISMA guidelines for...     

Urinary albumin excretion: a predictor of glomerular findings in adults with microscopic haematuria

BACKGROUND: Microscopic haematuria without proteinuria is a common clinical finding. When urological causes are excluded, usual findings on renal biopsy are IgA nephropathy (which can progress to end-stage renal failure) or thin basement membrane nephropathy (which has an excellent prognosis). A non-invasive test to discriminate between the two would be useful. Aim: To examine the value of measurement of urinary albumin excretion in discriminating glomerular causes of microscopic haematuria in patients without proteinuria on urine dipstick tests. DESIGN: Single-centre retrospective cross-sectional observational study. METHODS: Adult patients who underwent renal biopsy for microscopic haematuria over a 6-year period from January 1994 were identified. Study entry required normal renal function, no proteinuria detected by dipstick, and urinary albumin excretion <300 mg/24 h. Patients with IgA nephropathy had follow-up for a mean of 58 months after biopsy. RESULTS: Of 169 patients fulfilling study criteria, 119 (70%) had normoalbuminuria (<30 mg/24 h); 52 (30%) had microalbuminuria (30-299 mg/24 h). Of those with normoalbuminuria, 106 (89%) had thin basement membrane nephropathy or no glomerular abnormality. Thirteen (11%) had IgA nephropathy, and of 12 of these followed-up for a mean 64 months, none developed overt, dipstick-positive proteinuria. In contrast, 24 (48%) of those with microalbuminuria had IgA nephropathy, and of 22 followed-up for a mean 55 months, five developed overt proteinuria. DISCUSSION: Urinary albumin excretion is an indicator of likely glomerular findings in microscopic haematuria, and may influence whether a renal biopsy is necessary.     

Numbers needed for treatment and their respective confidence intervals: useful tools to assess clinical significance and uncertainty associated with medical interventions]

This is a narrative review of a concept--number needed to treat (NNT). The proprieties of NNTs are described. Furthermore NNTs as important tools for medical decision are discussed. In particular, conditions that make calculus and the interpretation of NNTs somewhat more complex are commented. Namely, we consider situations where the results are not primarily binary or are expressed as "time to event" or come from a meta-analysis. The inconsistencies that might occur when NNTs are calculated from meta-analysis are discussed in some detail. Definitions for parameters derived from NNTs, as numbers needed to harm (NNH), unqualified success (NNTUS) and unmitigated failure (NNHUF) are given. Finally the usefulness of NNTs and absolute risk reductions to communicate risk to individual patients are considered. It is concluded that despite NNTs being powerful tools for medical decision, in the case of communicating risks to the individual patient absolute risks might be preferable.     

Scales to assess sleep impairment in Parkinson's disease: Critique and recommendations

There is a broad spectrum of sleep disturbances observed in Parkinson's disease (PD). A variety of scales have been applied to the evaluation of PD sleep and wakefulness, but only a small number have been assessed specifically for clinimetric properties in the PD population. The movement disorder society has commissioned this task force to examine these scales and to assess their use in PD. A systematic literature review was conducted to explore the use of sleep scales in PD and to determine which scales qualified for a detailed critique. The task force members, all of whom have extensive experience in assessing sleep in PD reviewed each of the scales using a structured proforma. Scales were categorized into recommended, suggested and listed according to predefined criteria. A total of 48 potential scales were identified from the search and reviewed. Twenty‐nine were excluded because they did not meet review criteria or were variations of scales already included, leaving 19 scales that were critiqued and rated by the task force based on the rating criteria. Only six were found to meet criteria for recommendation or suggestion by the task force: the PD sleep scale (PDSS) and the Pittsburgh sleep quality index (PSQI) are recommended for rating overall sleep problems to screen and to measure severity, the SCOPA‐sleep (SCOPA) is recommended for rating overall sleep problems both to screen and to measure severity, and for rating daytime sleepiness; the Epworth sleepiness scale (ESS) is recommended for rating daytime sleepiness to screen and to measure severity; the inappropriate sleep composite score (ISCS) is suggested for rating severe daytime sleepiness or sleep attacks to screen and to measure severity; and the Stanford sleepiness scale (SSS) is suggested for rating sleepiness and to measure severity at a specific moment. The task force does not recommend the development of new scales, but emphasizes the need for educational efforts to train physicians in sleep interview techniques and polysomnography. © 2010 Movement Disorder Society     

Association of genetic variants in the adiponectin encoding gene (ADIPOQ) with type 2 diabetes in Japanese Brazilians

AimThe objective of this study is to assess the contribution of ADIPOQ variants to type 2 diabetes in Japanese Brazilians.MethodsWe genotyped 200 patients with diabetes mellitus (100 male and 100 female, aged 55.0 years [47.5–64.0 years]) and 200 control subjects with normal glucose tolerant (NGT) (72 male and 128 female, aged 52.0 years [43.5–64.5 years]).ResultsWhereas each polymorphism studied (T45G, G276T, and A349G) was not significantly associated with type 2 diabetes mellitus, the haplotype GGA was overrepresented in our diabetic population (9.3% against 3.1% in NGT individuals, P=.0003). Also, this haplotype was associated with decreased levels of adiponectin. We also identified three mutations in exon 3: I164T, R221S, and H241P, but, owing to the low frequencies of them, associations with type 2 diabetes could not be evaluated. The subjects carrying the R221S mutation had plasma adiponectin levels lower than those without the mutation (2.10 μg/ml [1.35–2.55 μg/ml] vs. 6.68 μg/ml [3.90–11.23 μg/ml], P=.015). Similarly, the I164T mutation carriers had mean plasma adiponectin levels lower than those noncarriers (3.73 μg/ml [3.10–4.35 μg/ml] vs. 6.68 μg/ml [3.90–11.23 μg/ml]), but this difference was not significant (P=.17).ConclusionsWe identified in the ADIPOQ gene a risk haplotype for type 2 diabetes in the Japanese Brazilian population.