Expression of Phosphofructokinase in Skeletal Muscle Is Influenced by Genetic Variation and Associated With Insulin Sensitivity

Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression quantitative trait loci [eQTLs]) as well as expression associated with measures of insulin sensitivity. We investigated associations of 3,799,401 genetic variants in expression of >7,000 genes from three cohorts (n = 104). We identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P < 1.96 × 10⁻⁵) and 49 expression–insulin sensitivity phenotype associations (i.e., fasting insulin, homeostasis model assessment–insulin resistance, and BMI) (FDR <5%; P = 1.34 × 10⁻⁴). One of these associations, fasting insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL (rs4547172; P = 7.69 × 10⁻⁶) was nominally associated with glucose uptake, glucose oxidation rate, intramuscular triglyceride content, and metabolic flexibility (P = 0.016–0.048; n = 178). We explored eQTL results using published data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for the PFKM eQTL (rs11168327; r² = 0.75) was nominally associated with T2D (DIAGRAM P = 2.7 × 10⁻³). Taken together, our analysis highlights PFKM as a potential regulator of skeletal muscle insulin sensitivity.     

Angiographic success and procedural complications in patients undergoing retrograde percutaneous coronary chronic total occlusion interventions: A weighted meta-analysis of 3482 patients from 26 studies

Background

The efficacy and safety profile of retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We sought to perform a weighted meta-analysis of the success and complication rates of retrograde CTO PCI.

Methods

We conducted a meta-analysis of 26 studies published between 2006 and April 2013 reporting in-hospital outcomes of retrograde CTO PCI. Data on procedural success, frequency of death, emergent coronary artery bypass graft surgery (CABG), stroke, myocardial infarction (MI), perforation, tamponade, stent thrombosis, major vascular or bleeding events, contrast nephropathy, and radiation skin injury were collected.

Results

A total of 26 studies with 3482 patients and 3493 target CTO lesions were included. Primary retrograde CTO PCI was attempted in 52.4%. Pooled estimates of outcomes were as follows: procedural success 83.3% [95% confidence interval (CI): 79.0% to 87.7%]; death 0.7% (95% CI: 0.5% to 1.2%); urgent CABG 0.7% (95% CI: 0.4% to 1.2%); tamponade 1.4% (95% CI: 1.0% to 2.2%); collateral perforation 6.9% (95% CI: 4.6% to 10.4%); coronary perforation 4.3% (95% CI: 1.2% to 15.4%); donor vessel dissection 2% (95% CI: 0.9% to 4.5%); stroke 0.5% (95% CI: 0.2% to 1.0%); MI 3.1% (95% CI: 0.2% to 5.0%); Q wave MI 0.6% (95% CI: 0.4% to 1.1%); vascular access complications 2% (95% CI: 0.9% to 4.5%); contrast nephropathy 1.8% (95% CI: 0.8% to 3.7%); and wire fracture and equipment entrapment 1.2% (95% CI: 0.6% to 2.5%).

Conclusions

Retrograde CTO PCI is associated with high procedural success rate and acceptable risk for procedural complications.     

Safety and Effectiveness of Drug-Eluting Versus Bare-Metal Stents in Saphenous Vein Bypass Graft Percutaneous Coronary Interventions : Insights From the Veterans Affairs CART Program

Background

Stenosis of saphenous vein grafts (SVGs) after coronary artery bypass grafting (CABG) is common and often requires percutaneous coronary interventions (PCI) for treatment. However, data for the effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) in SVG-PCI are unclear.

Objectives

This study sought to examine the association between DES versus BMS used during SVG PCI and clinical outcomes in the national Veterans Affairs integrated healthcare system.

Methods

We studied a national cohort of 2,471 post-CABG veterans undergoing SVG-PCI between 2008 and 2011 at all Veterans Affairs hospitals and compared clinical outcomes of between those receiving DES and BMS. Clinical outcomes included procedural complications, myocardial infarction (MI), and all-cause mortality. Comparisons were made in a propensity-matched cohort using Cox proportional hazards regression models.

Results

DES were used in 1,549 SVG-PCI patients (63%) and the use of DES increased progressively with each calendar year (50% in 2008 to 69% in 2011). Incidence of procedural complications was low and comparable in both groups (2.8% among BMS vs. 2.3% among DES patients; p = 0.54). During long-term (>2 years) follow-up, use of DES was associated with lower mortality than BMS (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.57 to 0.89) and similar rates of MI (HR: 0.94; 95% CI: 0.71 to 1.24) in the propensity-matched cohort.

Conclusions

In a national cohort of veterans, we observed widespread and increasing use of DES during SVG-PCI. In long-term follow-up, compared with BMS, DES use was safe and effective in SVG-PCI patients.     

Multiple behavioral risk factors for chronic diseases in adults aged 50+: regional differences across eleven European countries

Aim

The aim of this study was to estimate the differences in prevalence of multiple behavioral risk factors (MBRFs) for chronic diseases in European adults, from eleven North, Central and South European countries.

Subjects and methods

We used data from 26,656 adults, aged 50+ years, participating in the Survey of Health, Ageing and Retirement in Europe (2004/05). Physical inactivity, high body weight, smoking and risky alcohol consumption were assessed and estimated based on sampling weights, controlling for socioeconomic characteristics.

Results

53.4 % of adults had 2+ MBRFs. Prevalence in the total sample was highest for physical inactivity (71.2 %) and lowest for smoking (18.1 %). The cluster of high body weight and physical inactivity had the highest prevalence of MBRFs (35.4 %), with higher prevalence in Southern Europe (p?<?0.05). Smoking and alcohol consumption presented the greatest degree of clustering (observed to expected ratio?=?2.44). Spain and Greece had the highest prevalence of clustering 2+ MBRFs, whereas Southern European countries had a higher mean number of MBRFs, compared to North and Central European regions (p?<?0.05).

Conclusion

Prevalence of MBRFs varied between countries, with Southern European countries engaging in more risky behaviors. Primary prevention programmes should be developed to reduce MBRFs in this population.     

Bacterial Lymphadenitis at a Major Referral Hospital in France from 2008 to 2012

Lymph node enlargement is a common medical problem, and in a large number of patients, the causes of lymphadenopathy remain undiagnosed. We report a thorough microbiological analysis of 1,688 lymph node biopsy specimens collected in our bartonellosis reference center. We studied lymph node biopsy samples from patients with suspected regional infectious lymph node enlargement from January 2008 to December 2012. To evaluate a useful strategy for the diagnosis of infectious lymphadenitis, specimens were cultured and subjected to molecular assays. Histologic analysis was done when possible. A total of 642 (38%) biopsy specimens were infected with a bacterial agent, and quantitative PCR (qPCR) was significantly better than 16S rRNA gene PCR (rrs) for the detection of Bartonella henselae (P = 0.05), Mycobacterium tuberculosis (P = 0.05), and Mycobacterium avium (P = 0.007). Molecular assays were significantly better than bacterial cultures for the diagnosis of Francisella tularensis (P = 0.017) but were less effective for detecting M. tuberculosis (P = 0.004) and M. avium (P = 0.001). Histologic analysis was done for 412 lymph nodes, and 20% of these were compatible with an infectious lymphadenitis, whereas a neoplasm was found in 29% of these lymph nodes. M. tuberculosis was detected significantly more in female than in male patients (P = 0.01), and patients with cat scratch disease (CSD) were younger than patients with M. tuberculosis, Tropheryma whipplei, and F. tularensis. Negative rrs PCR does not exclude the diagnosis of infectious lymphadenitis. Histologic analysis of lymph node biopsy specimens is critical, as a diagnosis of infectious lymphadenitis does not preclude other concurrent diseases.     

Revascularization of the limbs using vein grafts after vascular injuries

We report on 32 patients with vascular injury of a limb undergoing a total of 41 revascularization procedures with interposition vein grafts. A combined arterial and venous injury was present in nine cases, an isolated venous injury in four, and an isolated arterial injury in 19 cases. Eighteen per cent of patients with arterial injuries had normal distal pulses on initial examination. Preoperative arteriography was performed in 12 cases, and intraoperative arteriography in four. All venous injuries were diagnosed at operation. In most cases, the contralateral greater saphenous vein was used for grafting. Four patients had postoperative thrombosis after arterial reconstruction resulting in below knee amputation in two cases. Two patients suffered from postoperative swelling caused by venous insufficiency, one after ligation of an injured axillary vein, and the other one following venous thrombosis of a superficial femoral vein repair. It is concluded that revascularization of arterial and venous injuries of the extremities with interposition vein grafts is successful in most cases resulting in low amputation rates, and should be attempted in all major vascular injuries in viable limbs.