Risk Association Between the NF-κB1 -94ins/delATTG Promoter Polymorphism and Inflammatory Bowel Diseases: A Meta-Analysis

Background

Extensive investigation of the NF-κB1 -94ins/delATTG promoter polymorphism for risk association with ulcerative colitis (UC) and Crohn’s disease (CD) risk has yielded conflicting results.

Aims

The objective of this meta-analysis was to evaluate the risk association between the NF-κB1 -94ins/delATTG promoter polymorphism and UC and CD.

Methods

All eligible case–control studies of the association of NF-κB1 -94ins/delATTG promoter polymorphism with UC and CD were identified in the Pubmed and Embase databases. From these data, odds ratios (OR) with 95?% confidence intervals (CI) were calculated. Meta-analysis was performed for alleles (D vs. W) and genotypes (DD?+?WD vs. WW, DD vs. WW?+?WD, DD vs. WW, WD vs. WW) in a fixed/random effects model.

Results

Nine case–control studies that included 4,447 cases (2,631 UC and 1,816 CD) and 2,195 controls were identified. Results indicated increased risk association of D allele carriers with UC (D vs. W: OR?=?1.08, 95?% CI?=?1.01–1.17, P?=?0.03; DD vs. WW?+?WD: OR?=?1.16, 95?% CI?=?1.01–1.32, P?=?0.04 and DD vs. WW: OR?=?1.20, 95?% CI?=?1.03–1.39, P?=?0.02). No risk association was identified with CD.

Conclusion

This meta-analysis indicated that the NF-κB1 -94ins/delATTG promoter polymorphism is a risk factor for UC but not CD.     

Gamma glutamyl transferase activity

Objective

Increased serum gamma-glutamyl transferase (GGT) activity is known to be associated with atherosclerotic diseases. Thoracic aortic intima-media thickness (IMT) was reported as a marker of preclinical atherosclerosis. However, there is a lack of research directly examining the relationship between serum GGT activity and thoracic aortic IMT. Therefore, we aimed to investigate the association between serum GGT activity and thoracic aortic IMT.

Patients and methods

The study population consisted of 329 patients without coronary artery disease, who underwent transesophageal echocardiography (TEE) examination for various indications from January 2011 to April 2013. GGT, high-sensitivity C-reactive protein (hs-CRP) and other biochemical markers were measured in all patients. The patients were classified into tertiles according to their GGT activities (GGT_low mid ≥?19 U/l high ≥?29).

Results

The highest aortic IMT values were observed in the GGT_high group compared with the GGT_mid and GGT_low groups (p?mid group were higher than in the GGT_low group (p?Conclusion The higher serum GGT concentrations within the “normal” range were associated with a greater IMT of the thoracic aorta. GGT activity may be a predictor of the extent of subclinical aortic atherosclerosis assessed with thoracic aortic IMT.     

Interleukin-6 and E-selectin in acute coronary syndromes and stable angina pectoris

Objectives

The purpose of the study was to compare the serum levels of interleukin-6 (IL-6), E-selectin, and trans-fatty acids (TFA) between those with stable and unstable angina pectoris.

Methods

From September 2008 to March 2009, a case?Ccontrol study was performed at two university hospitals. We included 89 patients with acute coronary syndrome (ACS) including patients with myocardial infarction and those with unstable angina pectoris (case group) and 93 patients with stable angina pectoris (control group). The two groups were matched with respect to demographic characteristics and risk factors of cardiovascular diseases. Serum levels of IL-6 and E-selectin were measured using the enzyme linked immunosorbent assay, while TFA and lipoproteins were measured using gas chromatography and enzymatic methods, respectively.

Results

No significant differences between baseline characteristics of the two study groups were observed. Patients with stable angina had significantly higher serum levels of total cholesterol (187.0?±?3.7 vs. 171.6?±?4.2?mg/dl; p?=?0.009), low density lipoproteins (104.8?±?2.4 vs. 95.4?±?2.7; p?=?0.017), and TFA (1.41?±?0.47 vs. 1.24?±?0.69?mg/dl; p?=?0.047) compared to those with ACS. Serum levels of IL-6 were found to be significantly higher in those with stable angina compared to those with ACS (102.4?±?1.9 vs. 224.6?±?3.6; p?=?0.007). However, patients with ACS had higher levels of E-selectin (53.5?±?25.7 vs. 49.2?±?23.5???g/dl; p?=?0.52), but the difference did not reach statistical significance.

Conclusion

In the current study, inflammation as measured by IL-6 and E-selectin was not found to play an important role in progression of ischemic heart disease from stable angina to unstable angina or myocardial infarction, which is contrary to previous studies.     

Oxidative stress and antioxidant capacity in patients with chronic pancreatitis with and without diabetes mellitus

Aim

To determine oxidant stress and antioxidant capacity in chronic pancreatitis (CP) patients with and without diabetes mellitus.

Methods

This study is a secondary data analysis of our earlier study on 127 (male?=?86) patients with CP, grouped as those with diabetes (case; n?=?23) and those without diabetes (control). Markers of antioxidant status included vitamins A and E, total antioxidant capacity (TAC; measured as ferric-reducing ability of plasma [FRAP]), and total glutathione (T-GSH). Markers for oxidative stress included lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS) and serum superoxide dismutase (s-SOD).

Results

Patients with diabetes were older (mean [SD] age 36.4 [9.7] vs. 29.3 [10.0] years; p?=?0.032), had longer duration of CP [4 (0.3?C21) vs. 3 (0.3?C24) years; p?=?0.07), and had a lower TAC (269.8 [92.4] vs. 355.5 [128.6] ??moles Fe⁺² liberated; p?=?0.003) compared to those without diabetes. In multiple logistic regression analysis taking all exploratory variables, FRAP (<270 ??moles Fe⁺² liberated) was associated with diabetes independent of duration of CP, age of patients, and TBARS levels. However, oxidative stress levels were not different between diabetic and nondiabetic patients.

Conclusions

Diabetes was found to be associated with longer duration of CP and with low antioxidant capacity. Further studies will be needed to evaluate a causal association.     

Association of genetic variants in tachykinins pathway genes with colorectal cancer risk

Purpose

This study aims to explore the associations of polymorphisms in tachykinin, precursor 1 (TAC1), tachykinin receptor 1 (TACR1), and tachykinin receptor 2 (TACR2) genes and their interactions with the risk of colorectal cancer (CRC) among Chinese population.

Methods

A population-based case-control study which included 394 cases and 393 cancer-free controls was carried out. A total of 19 tagSNPs in the three genes were chosen based on HapMap and NCBI datasets and genotyped by SNPshot assay. Multiple logistic regression models were applied to evaluate the associations of SNPs with CRC after adjustment for potential covariates. Furthermore, generalized multifactor dimensionality reduction (GMDR) method was used to test the interactive effect among three genes on CRC.

Results

Compared with those carrying rs3755457 CC/CT or rs12477554 TT/CT genotype, individuals carrying homozygous variants had higher risk of colorectal cancer (adjusted OR?=?1.80, 95?% CI?=?1.03–3.13, P?=?0.039 for rs3755457; adjusted OR?=?1.73, 95?% CI?=?1.07–2.79, P?=?0.024 for rs12477554). As for rs10198644, GG genotype was associated with a 1.72-fold (95?% CI?=?0.37–0.88) decreased risk when compared with the common CC genotype. Moreover, the GMDR analysis indicated that the best interactive model included five polymorphisms: rs2072100 (TAC1), rs10198644 (TACR1), rs2193409 (TACR1), rs3771810 (TACR1), and rs4644560 (TACR2).

Conclusions

Our study suggests that tachykinins pathway genes may participate in the development of CRC and the potential interactions among the three genes on CRC may exist, which has to be confirmed in future larger studies.     

Predictors for diabetic retinopathy in normoalbuminuric people with type 2 diabetes mellitus

Background

Previous studies have reported that microalbuminuria is an independent risk factor for the prevalence of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). For this reason, the clinical significance of DR in normoalbuminuric type 2 DM patients may be overlooked. The aim of this study was to investigate the prevalence of DR and predictors for DR in normoalbuminuric patients with type 2 DM.

Methods

A total 310 patients with type 2 DM and normoalbuminuria, who were referred to the Department of Ophthalmology for screening of DR were included in this study. DR was clinically graded according to the International Clinical Diabetic Retinopathy guidelines. The urinary albumin excretion rate (UAER) was assessed via 24-hour urine collection and measured by immunoturbidimetric assay. Normoalbuminuria was defined as a UAER?Results DR of any grade was present in 64/310 (20.7?%) patients. Mild non-proliferative diabetic retinopathy (NPDR) was most prevalent in patients with DR of any grade (36/64, 56?%). The duration of diabetes (OR 1.01, 95?% CI, 1.01 ?C 1.02, p?Conclusions Our findings suggest that patients with normoalbuminuric type 2 DM also require close monitoring for the early detection of DR, especially if they have a higher UAER, longer duration of diabetes, or lower hemoglobin levels.     

Increased serum resistin levels in patients with coronary slow-flow phenomenon

Background

Slow coronary flow (SCF) is an angiographic finding characterized by delayed opacification of the epicardial coronary arteries without obstructive coronary disease. Resistin, an adipocytokine, plays a major role besides low-grade inflammation in atherosclerotic vascular processes and may be of importance in other coronary pathologies such as SCF.

Methods

The present study was cross-sectional and observational, consisting of 70 individuals who underwent coronary angiography and had angiographically normal coronary arteries of varying coronary flow rates. The study included 50 patients with isolated SCF and 20 control participants with normal coronary flow (NCF).

Results

There were no statistically significant differences between the SCF and NCF groups with respect to age, gender, presence of hypertension or diabetes mellitus, and smoking habit, except for increased creatinine levels (p?=?0.014). The serum resistin level was significantly higher in the SCF group than in the NCF group (8.4?±?7.2 vs. 5.4?±?2.6 ng/ml, p?=?0.014). Ln-transformed resistin levels correlated positively with left anterior descending (LAD) coronary artery TIMI frame count (TFC) (r?=?0.408, p?<?0.001) as well as with glucose (r?=?0.340, p?=?0.004), creatinine (r?=?0.248, p?=?0.044), and C-reactive protein (CRP; r?=?0.283, p?=?0.023) levels, and negatively with LAD coronary flow velocity (r?=???0.314, p?=?0.009). When multivariate analyses were performed, in linear regression analysis, ln-resistin was associated with a longer TFC [beta (standardized regression coefficient): 0.404, p?=?0.001] and lower coronary flow velocity (beta: ??0.280, p?=?0.035); in logistic regression analysis, ln-resistin was an independent predictor of the presence of SCF (OR: 6.692, 65?%CI: 1.117–40.1, p?=?0.037).

Conclusion

We demonstrated, for the first time, a significant increase in serum resistin levels in patients with SCF compared to subjects with NCF. We believe that further studies are needed to clarify the role of resistin in patients with SCF.     

Renal impairment and coronary collaterals in patients with acute coronary syndrome

Objective

We aimed to elucidate the relationship between mild-to-moderate renal impairment and the development of coronary collateral vessels (CCV) in patients with acute coronary syndrome (ACS).

Methods

We enrolled 461 patients with ACS who underwent coronary angiography for the first time. The development of CCV was assessed with the Rentrop score. Kidney function was classified according to the estimated glomerular filtration rate (eGFR). The Gensini score was used to show the extent of atherosclerosis.

Results

The mean eGFR value was 89.9?±?24.3 U/l for patients with no development of collaterals and 82.7?±?20.5 for patients who had CCV. The mean age was 59?±?11 years and 349 patients (75.7?%) were male. Rentrop classifications 1-2-3 (presence of CCV) were determined in 222 (48.1?%) patients. The presence of CCV was significantly associated with low levels of eGFR (p?=?0.001), increased serum creatinine levels (p?=?0.034), high levels of serum albumin (0.036), and the Gensini score (p?<?0.001). Multivariate analysis showed that the Gensini score was an independent predictor of the presence of CCV (OR?=?1.090, 95?% CI: 1.032–1.151, p?=?0.002).

Conclusion

We suggest that the association between mild-to-moderate renal impairment and the presence of CCV may be explained by increased myocardial ischemia and severe CAD.     

Prognostic significance of fragmented QRS in patients with non-ST elevation myocardial infarction

Objectives

The aim of this study was to evaluate the predictive value of fragmented QRS (fQRS) among non-ST elevation acute coronary syndrome (ACS) patients.

Design

The fQRS on standard 12-lead ECGs in 179?patients (63% males, mean age 60.9?±?12.3?years) were analyzed. Cardiac events and cardiac mortality were regarded as two outcomes to determine whether fQRS was a clinical prognostic factor; its prognostic value was then assessed adjusting for other covariates.

Results

Cardiac mortality (18 (17.0%) vs. 4 (5.5%)) and major cardiac event rate (46 (43.4%) vs. 22 (30.1%)) were higher in the fQRS group compared with the non-fQRS group during a mean follow-up of 12?months. A Kaplan–Meier survival analysis revealed significantly lower event-free survival for cardiac events (p?=?0.030) and cardiac mortality (p?=?0.020). Multivariate Cox regression analysis revealed that significant fQRS was an independent significant predictor for cardiac events and cardiac mortality.

Conclusion

These results indicate that the occurrence of fQRS in the ECG is a powerful predictor of decreased survival in NSTEMI. The prognostic importance of fQRS was incremental to clinical and conventional factors.     

Increased H-FABP concentrations in nonalcoholic fatty liver disease

Aim

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder which is reported as the hepatic manifestation of metabolic syndrome with an increased risk of cardiovascular events. Patients with NAFLD are also at risk of future cardiac events independently of metabolic syndrome. The aim of this study was to examine serum concentrations of heart type fatty acid binding protein (H-FABP) in NAFLD and to investigate its correlations with metabolic parameters and subclinical atherosclerosis.

Patients and methods

A total of 34 patients with NAFLD and 35 healthy subjects were enrolled in the study. NAFLD patients had elevated liver enzymes and steatosis graded on ultrasonography. Healthy subjects had normal liver enzymes and no steatosis on ultrasonography. H-FABP levels were measured using an enzyme linked immunosorbent assay (ELISA) method and correlations with metabolic parameters and subclinical atherosclerosis were examined. Subclinical atherosclerosis was determined with carotid artery intima–media thickness (CIMT) which was measured by high resolution B mode ultrasonography.

Results

H-FABP levels were elevated in patients with NAFLD (16.3?±?4.0 ng/ml) when compared with healthy controls (13.8?±?2.1 ng/ml; p??<?0.001). NAFLD patients had significantly higher CIMT than the controls had (0.64?±?0.17 mm vs. 0.43?±?0.14 mm, p?=?0.009). The H-FABP concentrations were significantly positively correlated with body mass index (r?=?0.255, p?=?0.042), fasting blood glucose level (r?=?0.300, p?=?0.013), CIMT (r?=?0.335, p?=?0.043), and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r?=?0.156, p?=?0.306). In multiple linear regression analysis, H-FABP levels were only independently associated with CIMT (p?=?0.04)

Conclusion

Serum H-FABP concentrations increase in patients with NAFLD. Our results may not only suggest that H-FABP is a marker of subclinical myocardial damage in patients with NAFLD but also of subclinical atherosclerosis, independent of metabolic syndrome and cardiac risk factors.     

Endothelial function in children and adolescents with mucopolysaccharidosis

Background

Although coronary artery pathology is a prominent feature of mucopolysaccharidosis (MPS), it may be underestimated by coronary angiography because of its diffuse nature. It is also generally assumed that cardiovascular risk is increased in MPS and reduced following hematopoietic stem cell transplantation (HSCT) or enzyme replacement therapy (ERT), but this has never been formally evaluated. Non-invasive methods of assessing vascular endothelial function may provide a measure of cardiovascular risk in MPS. We evaluated endothelial function, using digital reactive hyperemia, in youth with MPS and in healthy controls.

Methods

Digital reactive hyperemic index (RHI) was measured in 12 children and adolescents (age 10.3?±?3.9 years old; 11 boys) with treated MPS and nine age- and gender-matched (11.4?±?4.0; 8 boys) healthy controls. An independent t-test was used to compare RHI between individuals with MPS and controls.

Results

Children and adolescents with MPS (MPS type II: N?=?5; type I: N?=?4; type VI: N?=?3) whether treated by HSCT (N?=?4) or ERT (N?=?8) had significantly lower RHI compared to controls (MPS 1.22?±?0.19 vs. controls 1.46?±?0.32, p?<?0.05).

Conclusion

These preliminary findings suggest that children and adolescents with treated MPS have significantly poorer endothelial function when compared to healthy controls. Further investigation into the utility of endothelial function for risk stratification and the long term implications of reduced endothelial function in MPS is warranted.     

Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: a pilot study

Background

Physical inactivity is a risk factor for the development of non-alcoholic fatty liver disease (NAFLD). ??Hybrid training??, a training that involves both voluntary and electrical muscle contractions, causes beneficial alterations in muscles even after short durations of exercise. The aim of this study was to investigate the therapeutic efficacy of hybrid training in patients with NAFLD.

Methods

Thirty-five patients with NAFLD who were resistant to lifestyle counseling were assigned to a hybrid-training group (n?=?12) or a control group (n?=?23). In the hybrid-training group, quadriceps and hamstrings were contracted voluntarily or electrically for 19?min twice a week. In the control group, patients received lifestyle counseling. The therapeutic efficacy of the hybrid training was evaluated after 12?weeks of the intervention.

Results

Serum alanine aminotransferase (ALT) levels and hepatic steatosis grade were significantly decreased in the hybrid-training group compared to that of the control group (?14.1?±?5.8 vs. 3.5?±?5.4?IU/mL; P?<?0.05, ?0.67?±?0.19 vs. 0.09?±?0.06 grade; P?<?0.01, respectively). No significant changes were seen between the two groups in skeletal muscle mass. The decreases in homeostasis model assessment of insulin resistance (HOMA-IR) value and in serum IL-6 levels were significantly greater in the hybrid-training group than in the control group (?6.2?±?3.2 vs. 0.4?±?0.6; P?<?0.05, ?3.1?±?1.1 vs. 1.1?±?0.5?pg/mL; P?<?0.01, respectively).

Conclusion

Hybrid training of voluntary and electrical muscle contractions improved hepatic steatosis and reduced insulin resistance and serum IL-6 levels in NAFLD patients who are resistant to lifestyle counseling.     

Gut Bacterial Translocation Contributes to Microinflammation in Experimental Uremia

Background

Microinflammation frequently develops in chronic uremia with pathological intestinal changes. However, the relationship between gut bacterial translocation and microinflammation in uremia has not been widely investigated.

Aim

This study aimed to investigate whether gut microbiome dysbiosis and translocation occurred in experimental uremia, and whether they consequently contributed to microinflammation.

Methods

Forty rats underwent surgical renal mass 5/6 ablation. The surviving (uremic group, n?=?21) and healthy (sham group, n?=?20) rats were used in the experiment. Postoperative blood, livers, spleens, and mesenteric lymph nodes (MLNs) were subjected to bacterial 16S ribosomal DNA amplification to determine if bacteria were present. Bacterial genomic DNA samples from the MLNs and colon were amplified with specific primers designed by the 16S rRNA sequence of the species obtained from blood, livers, and spleens. Pyrosequencing was used to analyze the colonic microbiome of each subject. Intestinal permeability to ^99mTc-DTPA, plasma hs-CRP, and IL-6 were measured.

Results

Bacterial DNA in extraintestinal sites and altered colonic microbiomes were detected in some rats in the uremic group. Bacterial genomic DNA in MLNs and colon were obtained by primers specific for bacterial species observed from blood, livers, and spleens of identical individuals. Intestinal permeability, plasma hs-CRP, and IL-6 levels were statistically higher in the uremic group compared with the sham group. Plasma hs-CRP and IL-6 were significantly higher in uremic rats with bacterial DNA in their blood than in those without.

Conclusions

Gut microbiome dysbiosis occurs and bacteria translocate to the systemic and lymph circulation, thereby contributing to microinflammation in experimental uremia.     

Robotic-assisted rehabilitation of proximal humerus fractures in virtual environments

Background and objective

With the growing incidence of upper arm fractures among older people, innovative treatment strategies will be needed in geriatric rehabilitation. A pilot study was designed to test the feasibility of robotic-assisted rehabilitation after proximal humeral fractures.

Patients and methods

Within a sample of 8?older patients (79.5?±?6.12?years), functional ability, quality and range of movement, self-rated impairment, quality of life, and user satisfaction were measured in an observational pre-/postdesign. During rehabilitation robotic-assisted training was applied.

Results

Training motivation and acceptance were high in this sample, showing improvements in functional ability (p?=?0.03), quality of movement (p?=?0.02), range of motion, self-evaluation (p?=?0.01), and quality of life.

Conclusion

This pilot study highlights the possible implementation of robotic-assisted rehabilitation after proximal humeral fractures in geriatric rehabilitation. The measurement and training protocol was suitable to document progress in rehabilitation.     

Association of epicardial fat thickness with TIMI risk score in NSTEMI/USAP patients

Background

The association of epicardial adipose tissue (EAT) with coronary artery disease has been shown in previous studies. Furthermore, the relationship between EAT and acute coronary syndrome was studied recently. Herein, we investigated the relationship between EAT thickness and the thrombolysis in myocardial infarction (TIMI) risk score for non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (USAP).

Patients and methods

The study included 144 patients with NSTEMI/USAP. The study population was divided into two subgroups according to TIMI risk scores as group I (≤?4, n?=?86) and group II (>?4, n?=?58). Stepwise multivariable logistic regression analysis was used to assess the independent association of clinical parameters with TIMI risk score.

Results

EAT thickness was higher in group II than in group I (8.2?±?2.1 vs. 6.2?±?2.2, p?Conclusion In conclusion, EAT thickness is independently associated with TIMI risk score and may be an emerging risk factor for adverse events in NSTEMI/USAP patients.     

Cardiac hemodynamics and proinflammatory cytokines during biatrial and right atrial appendage pacing in patients with interatrial block

Purpose

Interatrial block (IAB) frequently coexists with sinus node disease and is considered a risk factor of left atrial dysfunction, atrial arrhythmias, and heart failure development. Conventional right atrial appendage (RAA) pacing impairs intra- and interatrial conductions and consequently prolongs P wave duration. Biatrial (BiA) pacing helps correct IAB, but its advantageous influence remains controversial. The aim of the study was to compare the effects of BiA and RAA pacing on cardiac hemodynamics and serum concentrations of inflammatory markers and neuropeptides.

Methods

Twenty-eight patients with IAB and preserved atrio-ventricular conduction treated with BiA pacing were studied. Standard invasive hemodynamic measurements were performed during BiA and RAA pacings. Furthermore, the influence of 1 week of BiA and RAA pacing on neuropeptides: atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and markers of inflammation: high sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and neopterin was examined.

Results

BiA pacing resulted in significant increase of cardiac output (CO) and reduction of pulmonary capillary wedge pressure. We demonstrated significantly lower concentrations of ANP, hs-CRP, IL-6, and neopterin after 1 week of BiA in comparison to RAA pacing. BNP levels remained unchanged.

Conclusions

BiA pacing in comparison to RAA pacing improves hemodynamic performance in patients with IAB and preserved atrio-ventricular conduction. BiA pacing is associated with reduction of ANP and markers of inflammation (hs-CRP, IL-6, and neopterin).     

Effects of 10?days of modest intermittent hypoxia on circulating measures of inflammation in healthy humans

Purpose

Obstructive sleep apnea (OSA) is a common disease which is associated with elevated inflammatory markers and adhesion molecules, possibly due to nightly intermittent hypoxia (IH). The purpose of this study was to test the hypothesis that IH would increase systemic inflammatory markers in healthy human males.

Methods

Healthy, young male subjects (n?=?9; 24?±?2?years) were exposed to a single daily isocapnic hypoxia exposure (oxyhemoglobin saturation?=?80%, 1?h/day) for 10 consecutive days. Serum granulocyte macrophage colony-stimulating factor, interferon-??, interleukin-1??, interleukin-6, interleukin-8, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 were measured before and following the 10?days of IH using Luminex.

Results

Nine subjects completed the study (24?±?2?years; 24?±?2?kg/m²). The mean oxyhemoglobin saturation was 80.8?±?1.6% during the hypoxia exposures. There was no significant change in any of the markers of inflammation (paired t test, P?>?0.2 all cytokines).

Conclusions

These findings suggest that (1) a more substantial or a different pattern of hypoxemia might be necessary to activate systemic inflammation, (2) the system may need to be primed before hypoxic exposure, or (3) increases in inflammatory markers in patients with OSA may be more related to other factors such as obesity or nocturnal arousal.     

Predictors of sustained ventricular arrhythmia episodes in patients with primary ICD indication

Aims

Implantable cardioverter?Cdefibrillators (ICD) reduce mortality in patients with severely impaired left ventricular function. In randomized studies, female patients are underrepresented and data on ICD therapy is limited. Atrial fibrillation (AF) is a determinant of poor prognosis but has not been consistently evaluated. We evaluated the risk factors for the occurrence of ventricular arrhythmia episodes in patients with primary ICD prophylaxis.

Methods

Consecutive patients after ICD implantation for primary prophylaxis were followed. During follow-up, detected sustained episodes of ventricular arrhythmia were documented. Multivariate analysis controlled for propensity score was used to evaluate the correlation between gender, history of AF, and the occurrence of ventricular arrhythmia episodes.

Results

A total of 400 patients (19.8% female; n?=?79) were included. During follow-up, 64 patients (16%) had appropriate ICD therapy episodes. Men (18%) had significantly more often episodes than women (8%; p?=?0.025). Patients with a history of AF (102, 25.5%) had significantly more often episodes (30%) compared to patients without a history of AF (11%; p?Conclusion Male gender and history of AF are independent predictors for the occurrence of sustained ventricular arrhythmia in primary ICD prophylaxis. Further studies need to evaluate whether history of AF in female patients might be an indicator for higher risk of sudden cardiac arrhythmic death.     

Substrate metabolism during basal and hyperinsulinemic conditions in adolescents and young-adults with Barth syndrome

Background

Barth syndrome (BTHS) is a rare X-linked disorder that is characterized by mitochondrial abnormalities, infantile or childhood onset of cardioskeletal myopathy, and high mortality rates. It is currently unknown if BTHS related mitochondrial dysfunction results in substrate metabolism abnormalities and thereby contributes to cardioskeletal myopathy in patients with BTHS.

Methods

Adolescents and young adults with BTHS (n?=?5, 20?±?4 yrs) and age and activity matched healthy controls (n?=?5, 18?±?4 yrs) underwent an hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracers for measurement of lipolysis, fatty acid oxidation, glucose disposal, and whole-body proteolysis rates; dual energy x-ray absorptiometry for measurement of body composition and 2-D and strain echocardiography for measurement of left ventricular function.

Results

Participants with BTHS had lower fat-free mass (FFM) (BTHS: 31.4?±?6.9 vs. Control: 46.7?±?5.3 kg, p?<?0.005), lower systolic function (strain, BTHS: -15.2?±?2.4 vs. Control: ?19.0?±?2.4 %, p?<?0.05), greater insulin-stimulated glucose disposal rate per kg FFM (BTHS: 96.5?±?16.3 vs. Control: 67.4?±?17.6 μmol/kgFFM/min, p?<?0.05), lower basal (BTHS: 4.6?±?2.7 vs. Control: 11.9?±?4.4 μmol/kgFM/min, p?<?0.05) and hyperinsulinemic (BTHS: 1.6?±?0.4 vs. Control: 3.6?±?1.6 μmol/kgFM/min, p?<?0.05) lipolytic rate per kg fat mass (FM), and a trend towards higher basal leucine rate of appearance per kg FFM (BTHS: 271.4?±?69.3 vs. Control: 193.1?±?28.7 μmol/kgFFM/hr, p?=?0.07) compared to controls. Higher basal leucine rate of appearance per kg FFM (i.e. whole-body proteolytic rate) tended to be associated with lower left ventricular systolic strain (r?=??0.57, p?=?0.09).

Conclusion

Whole-body fatty acid, glucose and amino acid metabolism kinetics when expressed per unit of body composition are altered and appear to be related to cardioskeletal myopathy in humans with BTHS. Further studies examining myocardial substrate metabolism and whole-body substrate metabolism during increased energy demands (e.g., exercise) and their relationships to skeletal and cardiac function are recommended.