Prognostic significance of insulin-like growth factor-I serum levels in acute decompensation of cirrhosis

Context: IGF-I serum levels are suppressed in cirrhosis, but its prognostic significance is unknown.

Objectives: To investigate the prognostic value of IGF-I in patients admitted for acute decompensation of cirrhosis.

Materials and methods: Cohort study that included 103 patients. IGF-I was measured by enzyme-linked immunosorbent assay (ELISA).

Results: Ninety-day mortality was 26.2% and it was independently associated with MELD, age and IGF-I. The Kaplan–Meier survival probability at 90 days was 94.3% in patients with IGF-I?≥13?ng/mL and 63.2% for patients with IGF-I?<13?ng/mL (p?=?.001).

Discussion and conclusion: IGF-I levels are independently associated with mortality in acute decompensation of cirrhosis.     

Determination of natural moisturizing factors in the skin: Raman microspectroscopy versus HPLC

Background: Natural moisturizing factor (NMF) is used as genotypic and phenotypic biomarker in diagnostics. This study is a side-to-side comparison of two different methods to determine NMF in atopic dermatitis patients: Raman microspectroscopy and stratum corneum tape stripping followed by HPLC.

Results: Measured NMF values were significantly correlated (R²?=?.61; p?<?.0001), both methods demonstrated a concentration-depth dependence of NMF and reduced NMF levels in the carriers of filaggrin null mutations. Good agreement between measurements of left and right arms indicated robustness and good reproducibility of both methods.

Conclusions: Both methods showed comparable performance, choice of method will rather be influenced by practical consideration.     

Effect of shoulder stability exercises on hand grip strength in patients with shoulder impingement syndrome

Background: Shoulder impingement syndrome (SIS) is the second most common musculoskeletal condition that causes shoulder pain in the general population. Shoulder girdle muscle imbalance and posterior capsule tightness have been implicated as contributing factors.

Objective: The purpose of this study was to investigate the effect of shoulder stability exercises (SSEs) on hand grip strength in patients with unilateral SIS.

Methods: A total of 16 patients with a mean age of 32?±?9.3?years diagnosed with stage II unilateral SIS participated in this study. A standardized SSE programme was conducted in the clinic under the direct 1-to-1 supervision of a physical therapist thrice weekly for 4?weeks for a total of 12 sessions on the affected and non-affected shoulders. The effect of the SSE programme on isometric hand grip strength was analysed.

Results: A significant difference (p?=?.016) was observed in the hand grip strength of the affected shoulder side before and after the intervention, but no significant difference (p?=?1.0) was found in the hand grip strength of the non-affected shoulder side post-intervention.

Conclusion: The reduction in isometric hand grip strength of the affected shoulder side compared to that of the non-affected shoulder side in the same subject before the intervention shows that SIS significantly affects the hand grip strength of the affected side. SSEs significantly affect the isometric hand grip strength of SIS patients.     

Impact of CT-apelin and NT-proBNP on identifying non-responders to cardiac resynchronization therapy

Context: Assessment of response to cardiac resynchronization therapy (CRT) is essential.

Objective: To assess the predictive value of CT-apelin together with NT-proBNP in patients undergoing CRT.

Methods: Serum CT-apelin and NT-proBNP were measured by ELISA before, and six months after CRT. Primary endpoint was non-response (<4% increase in LVEF) after six months.

Results: From 81 patients, 15 proved to be non-responders. Six-month CT-apelin was superior compared to NT-proBNP in identifying non-responders by multivariate ROC (CT-apelin: p?=?0.01, NT-proBNP: p?=?0.13) and by logistic regression (CT-apelin: p?=?0.01, NT-proBNP: p?=?0.41) analyses.

Conclusion: Six-month CT-apelin might be a valuable novel biomarker in identifying non-responders to CRT that was superior to NT-proBNP.     

Low YKL-40 in chronic heart failure may predict beneficial effects of statins: analysis from the controlled rosuvastatin multinational trial in heart failure (CORONA)

Context and objective: To evaluate if YKL-40 can provide prognostic information in patients with ischemic heart failure (HF) and identify patients who may benefit from statin therapy.

Materials and methods: The association between serum YKL-40 and predefined outcome was evaluated in 1344 HF patients assigned to rosuvastatin or placebo.

Results: YKL-40 was not associated with outcome in adjusted analysis. In YKL-40 tertile 1, an effect on the primary outcome (HR 0.50, p?=?0.006) and CV death (HR 0.54, p?=?0.040) was seen by rosuvastatin in adjusted analysis.

Conclusions: A beneficial modification of outcome was observed with statin therapy in patients with low YKL-40 levels.     

Big endothelin-1 level is a useful marker for predicting the presence of isolated coronary artery ectasia

Context: Endothelin-1(ET-1) has been implicated in coronary artery disease (CAD) and may be associated with coronary artery ectasia (CAE).

Objective: To clarify the relationship between big ET-1 and isolated CAE.

Methods: We measured big ET-1 with ELISA in 216 patients (CAE, n?=?72; CAD, n?=?72; normal, n?=?72) and evaluated the link with isolated CAE.

Results: The level of plasma big ET-1 was significantly higher in patients with isolated CAE (p?<?0.001). Big ET-1 was strongly and independently associated with CAE by multivariate analysis (OR 95%CI: 1.026 (1.018–1.034), p?=?0.000).

Conclusions: Big ET-1 may be a useful predictor for the presence of isolated CAE.     

Dynamic variation of histone H3 trimethyl Lys4 (H3K4me3) and heterochromatin protein 1 (HP1) with employment length in nickel smelting workers

Objective: To investigate the dynamic variation in H3K4me3 and HP1 with employment length in nickel smelting workers.

Methods: Blood samples were collected from 140 nickel smelting workers and 140 age-matched office workers to test for H3K4me3, and HP1 levels.

Results: H3K4me3 was statistically significantly different (p?<?0.05) between the two groups and positively correlated with employment length (r_s?=_?0.267). HP1 was not correlated with employment length (p?=?0.066) but was significantly different between the two groups.

Conclusions: Chronic exposure to nickel can induce oxidative damage, and increase H3K4me3 expression and inhibit HP1 expression.     

CXCR4 as a prognostic biomarker in gastrointestinal cancer: a meta-analysis

Background: CXCR4 is a member of the C-X-C chemokine receptor family, which is associated with multiple types of cancer. Although it has been widely reported, the prognostic value of CXCR4 expression in gastrointestinal (GI) cancer remains controversial.

Methods: A meta-analysis was conducted to investigate the relationship between CXCR4 and prognosis of patients with GI cancer. Subgroup analysis was also performed according to tumour subtypes and heterogeneity test.

Results: A total of 24 studies including 3637 cases suggested that overexpression of CXCR4 is significantly associated with overall survival (OS) for patients with GI cancer (HR = 1.71, 95% CI = 1.45–2.03, p?=?0.000). Subgroup analysis also indicated that high CXCR4 expression in oesophagus, gastric and colorectal cancer all predicted a worse prognosis (HR = 1.52, 95% CI = 1.26–1.84, p?=?0.001 for oesophagus cancer; HR = 1.59, 95% CI = 1.10–2.30, p?=?0.015 for gastric cancer; HR = 2.21, 95% CI = 1.56–3.14, p?=?0.000 for colorectal cancer).

Conclusions: CXCR4 may serve as a prognostic indicator in GI cancer patients.     

Blood markers of inflammation and endothelial dysfunction in cardioembolic stroke: systematic review and meta-analysis

Context: Various processes including inflammation and endothelial dysfunction have been implicated in the pathogenesis of cardioembolic (CE) strokes.

Objective: To review the evidence and investigate the association between immune-inflammatory biomarkers and CE strokes versus other stroke subtypes.

Methods: We systematically reviewed the literature (sources: MEDLINE, web-based register http://stroke-biomarkers.com, reference lists) with quality assessment and meta-analysis of selected articles.

Results: The most consistent association was found between C-reactive protein (CRP) and CE strokes when compared to other stroke subtypes (standardized mean difference 0.223 (0.116, 0.343); p?<?0.001)

Conclusions: Our findings confirm a possible association between selected inflammatory biomarkers and CE stroke.     

Ankle kinematics and kinetics during gait in healthy and rheumatoid arthritis post-menopausal women

Objective: In the literature, it is not clear whether rheumatoid arthritis (RA) post-menopausal women have different ankle biomechanical parameters than healthy post-menopausal women. This study aimed to compare the ankle kinematics and kinetics during the gait stance phase of RA post-menopausal women with age-matched healthy post-menopausal women.

Materials and methods: A three-dimensional motion analysis system (9 cameras; 200?Hz) synchronised with a force plate (1000?Hz) was used to assess ankle kinematics and kinetics during barefoot walking at a natural and self-selected speed. A biomechanical model was used to model body segments and joint centres (combined anthropometric measurements and the placement of 39 reflective markers). Thirty-six women (18 RA post-menopausal women and 18 age-matched healthy post-menopausal women) performed 14 valid trials (comprising seven left and seven right footsteps on a force plate). Lower limb muscle mass was evaluated by an octopolar bioimpedance analyser.

Results: RA post-menopausal women yielded a longer stance phase and controlled dorsiflexion sub-phase (p?<?0.001), higher dorsiflexion at the final controlled dorsiflexion sub-phase and lower plantar flexion at toe off (p?<?0.05), lower angular displacements (p?<?0.05), and lower ankle moment of force peak and ankle power peak (p?<?0.001). No intergroup differences were found in lower limb muscle mass.

Conclusions: RA post-menopausal women yielded changes in ankle kinematic and kinetic parameters during the gait stance phase, resulting in a lower capacity to produce ankle moment of force and ankle power during the propulsive gait phase.     

Use of GPS tags to describe the home ranges,migration routes,stop-over locations and breeding area of Taiga Bean Geese Anser fabalis fabalis wintering in central Scotland

Capsule: Taiga Bean Geese Anser fabalis fabalis wintering near Falkirk, Scotland staged in Denmark, Norway and Sweden and summered in central Sweden.

Aims: To determine the migration routes, timing of movements, breeding area and home ranges of Taiga Bean Geese wintering near Falkirk, Scotland.

Methods: Ten Taiga Bean Geese, caught on the wintering grounds in Scotland, were marked with neck collars carrying global positioning system (GPS) tags. A further 21 geese were fitted with individually marked plastic neck collars. GPS location data were collected and field counts and searches for individually marked geese were undertaken to provide detailed information on their location throughout the year.

Results: Seven GPS tags provided information away from Scotland, indicating that two migration routes were used en route to the breeding grounds in Dalarna, Sweden. During the non-breeding season, the total home range of the geese was approximately 466?km², although the total area within agricultural fields used by the geese may have been as small as 13?km².

Conclusions: The timing of movements, migration routes, breeding area and identification of important stop-over sites for this wintering population are described for the first time.     

Differential expression of circulating vascular cell adhesion molecule-1 in subjects with coronary artery disease and cardiac syndrome X without known diabetes mellitus

Context: Inflammation is one of the mechanisms underlying cardiac syndrome X (CSX).

Objectives: Few studies have compared the expression of inflammatory or adhesion molecules between coronary artery disease (CAD) versus CSX.

Materials and methods: Ninety-two CSX and 145 CAD subjects without known diabetes mellitus underwent coronary angiogram for angina.

Results: Vascular cell adhesion molecule (VCAM)-1 (median, 507 versus 431?ng/ml, p?=?0.001) was significantly higher in the CAD group. In the binary regression, VCAM-1 was a significant differential factor for CAD versus CSX.

Discussion and conclusion: Adhesion molecules might be implicated in the differential expression of macro versus microvascular coronary disease.

Trial registration number: NCT01198730 at https://clinicaltrials.gov     

Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project

Purpose: Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population.

Materials and methods: The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n?=?30,193, age = 60.2?±?11.5?year).

Results: Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90–3.89, p?<?0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28–3.14, p?<?0.001).

Conclusions: Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.     

Sleep-disordered breathing is associated with higher carboxymethyllysine level in elderly women but not elderly men in the cardiovascular health study

Context: Carboxymethyl-lysine (CML) results from oxidative stress and has been linked to cardiovascular disease.

Objective: The objective of this study is to investigate the association between sleep-disordered breathing (SDB) – a source of oxidative stress – and CML.

Materials and methods: About 1002 participants in the Cardiovascular Health Study (CHS) were studied.

Results: Women with SDB had significantly higher CML concentration compared with those without SDB (OR?=?1.63, 95%CI?=?1.03–2.58, p?=?0.04). The association was not significant among men.

Discussion: SDB was associated with CML concentration among elderly women but not men in the Cardiovascular Health Study.

Conclusion: Accumulation of CML may be an adverse health consequence of SDB     

Base excision repair pathway: PARP1 genotypes as modulators of therapy response in cervical cancer patients

Context: Genetic polymorphisms in genes of the base excision repair (BER) pathway appear to modulate the therapy response of cancer patients. PARP1 protein recognizes the DNA strand damage and facilitates the subsequent recruitment of BER proteins. Few studies have reported an association between PARP1 Val762Ala polymorphism (rs1136410) and cancer therapy response.

Objective: The purpose of our study was to determine whether PARP1 Val762Ala polymorphism have prognostic value in patients with cervical cancer.

Materials and methods: Two hundred and sixty adult patients, with histologically confirmed cervical cancer, at FIGO-stages IB2-IVA, primarily treated with concurrent chemotherapy (cisplatin) and radiotherapy. Overall survival (OS) and disease-free survival (DFS) were the primary end points of the analysis. The PARP1 Val762Ala genetic variants were analyzed by allelic discrimination by real-time PCR.

Results: We observed that peri- and postmenopausal women carrying the C-allele present a statistically significant lower OS and DFS (log-rank test, p?=?0.008 and p?=?0.006, respectively) among those with early stage cervical cancer. Cox regression analysis confirmed these results, after adjustment for other prognostic factors (for OS: HR, 3.70; 95%CI, 1.32–10.38; p?=?0.013 and for DFS: HR, 3.97; 95%CI, 1.59–9.93; p?=?0.003).

Conclusions: This is the first study evaluating the effect of PARP1 Val762Ala polymorphism in treatment response in cervical cancer patients. PARP1 genotypes may contribute as an independent prognostic factor in cervical cancer, being useful in predicting the clinical outcome.     

Riboflavin as an independent and accurate biomarker for adherence in a randomized double-blind and placebo-controlled clinical trial

Background: Medication adherence is critical for success of clinical trials.

Objective: To assess oral riboflavin is an adherence marker.

Methods: Riboflavin was incorporated into active treatment and placebo pills for a clinical trial lasting for 2 years.

Results: The accuracy (area under the receiver operating curve) of urinary riboflavin was 0.91 as a binary classifier of adherence, and was similar or better than for two active study ingredients daidzein (0.92) and genistein (0.87) (all p?<?0.0001). Decreased adherence over time was similar in the two study groups.

Conclusion: Riboflavin is an accurate and useful biomarker for study pill ingestion.     

Micronucleus frequency and content in healthy relatives of cancer patients

Objective: To compare chromosomal damage in lymphocytes of individuals who did or did not report first-degree relatives with cancer.

Materials and methods: Cases and controls (68 each) were matched for sex, age and radon exposure. Chromosomal damage was quantified as frequency of micronucleus-containing cells and proportion of centromere-free micronuclei.

Results: Individuals not reporting cancer in their families showed lower values of both the frequency of micronucleus-containing cells (n.s.) and the proportion of centromere-free micronuclei (p?<?0.05) in some subgroups, but not in all.

Conclusion: The chromosomal damage observed may be due to inheritable genomic instability, but environmental influences cannot be excluded.     

Effect of pesticide exposure on the cholinesterase activity of the occupationally exposed tea garden workers of northern part of West Bengal,India

Context: Pesticide poisoning and related deaths are a global concern, but there is little information about its effect on the occupationally exposed tea garden workers of North Bengal.

Objective: This study investigates the level of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the blood of the tea garden workers at risk of exposure to a mixture of pesticides.

Materials and methods: The study sample consisted of pesticide exposed workers, non-exposed (control), smokers and alcoholics. AChE and BuChE activity was measured and tested for significance.

Results: Results showed that AChE activity was half in the pesticide exposed individuals than controls (p≤ 0.001). BuChE activity was also significantly decreased in the pesticide exposed individuals than controls (p≤ 0.001), while AChE and BuChE activity in smokers and alcoholics were not different from that of controls. However, significantly decreased AChE and BuChE activities were recorded in pesticide exposed workers compared to smokers and alcoholics.

Conclusions: The results indicated that the decrease in enzyme activities in tea garden workers was due to mixed pesticides (containing organophosphates) exposure. Age was not found to influence the enzyme activities. However, the gender had little effect on the enzyme activities but the effect was not so prominent.     

Associations of rs1883832 and rs4810485 polymorphisms of CD40 gene with myocardial infarction in the Tunisian population

Context: Cluster of differentiation 40 (CD40), and its ligand CD40L, are major co-stimulatory molecules whose interactions are important in both cellular and humoral immunity, and has been suggested to play a role in the pathogenesis of acute coronary syndrome.

Objective: The aim of this study was to examine the association of CD40 polymorphisms (-1?C>T (rs1883832) and 945G>T (rs4810485)) and myocardial infarction (MI), and to test the association of CD40 gene haplotypes with MI in Tunisians.

Materials and methods: Three hundred and fifty MI patients and 301 apparently healthy controls were included in the study. The polymorphisms of CD40 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: There were significant differences in the genotype and allele frequencies of CD40 gene -1?C>T (rs1883832) polymorphism between cases and controls. Stratifying according to gender, the association between the TT genotype and MI was statistically significant in males, only. Haplotype analysis revealed that the C-T and T-G haplotypes were associated with an increased risk of MI (p?=?0.012 and p?<?0.001, respectively).

Conclusions: Our work showed a significant association between the -1?C>T (rs1883832) polymorphism of the CD40 gene and MI in the Tunisians.     

Thrombin generation is increased in patients with Clostridium difficile colitis – a pilot study

Background: There are only limited data in the literature on the thrombotic risk of patients with Clostridium difficile (CD) colitis, although this disease is widespread throughout the world.

Objective: The aim of this study was to explore thrombin generation in these patients – the best way to evaluate their coagulation.

Methods: A prospective observational study was conducted during 15 months on hospitalized patients with CD colitis. Thrombin generation was performed in platelet-poor plasma using a Ceveron^® alpha analyzer and was compared with a group of volunteer control subjects.

Results: Thirty-three patients and 51 control subjects were enrolled in the study. Two biomarkers – mean velocity index and peak thrombin – were significantly higher in patient group, compared to the control subjects (p?=?0.010, respectively, p?=?0.0395). This pattern of thrombin generation suggests that patients with CD colitis without septic shock have a potential thrombotic risk. The mean velocity index significantly correlated with the estimated related risk of death according to the Charlson age-comorbidity index.

Conclusions: The higher values of thrombin generation suggest that CD colitis increases the thromboembolic risk. The pattern of thrombin generation could identify patients with particularly higher thromboembolic risk. They are potential candidates for thromboprophylaxis strategies and monitorization.