Remote ischemic preconditioning has a neutral effect on the incidence of kidney injury after coronary artery bypass graft surgery.

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease (CKD). Remote ischemic preconditioning (RIPC) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI. We undertook a randomized controlled trial of RIPC to prevent AKI in 86 patients with CKD (estimated glomerular filtration rate under 60 ml/min per 1.73 m(2)) undergoing coronary artery bypass graft (CABG) surgery. Forty-three patients each were randomized to receive standard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion. The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery. Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C, neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18), and urinary biomarkers including NGAL, IL-18, and kidney injury molecule-1 measured at 6, 12, and 24 h after CABG, and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury. Clinical and operative characteristics were similar between the preconditioned and control groups. AKI developed in 12 patients in both groups within 48 h of CABG. There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG. Thus, RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD.

The impact of socioeconomic status and social deprivation on musculoskeletal limitations.

BACKGROUND: Objective (SES) and subjective socioeconomic status (SSS) affect symptom intensity and magnitude of limitations. Identification of potentially modifiable social risk factors might contribute to additional opportunities for optimizing musculoskeletal health. QUESTIONS/PURPOSES: (1) There are no correlations between magnitude of limitations (as measured with Patient-Reported Outcomes Measurement Information System Physical Function [PROMIS PF computer adaptive test]) and components of SES or SSS in people with musculoskeletal disease; (2) There are no factors (including level of social deprivation) independently associated with PROMIS PF. METHODS: One hundred and fifty-nine patients presenting to clinicians specializing in the treatment of a broad variety of musculoskeletal conditions were prospectively enrolled in the study. We recorded patient demographics and assessed patients' socioeconomic status using the MacArthur Sociodemographic questionnaire and physical disability rating using PROMIS PF. Patients deprivation index was retrieved using their 9-digit ZIP codes. We used bivariate analysis to determine correlations between magnitude of limitations and socioeconomic status. We created a stepwise backward multivariable linear regression model to assess factors independently associated with PROMIS PF. RESULTS: Weak correlations were found on bivariate analysis of PROMIS PF with SSS measured as "Place in community" (r 0.28; P < 0.001) and "Place in the United States of America" (r 0.25; P = 0.002). In the multivariable models, the area deprivation index was not independently associated with physical limitations. Male gender (beta regression coefficient [ß] 4.1; 95% CI 0.71 to 7.5; P = 0.018) and having net worth of $5000 - $19,999 (ß 6.3; 95% CI 0.35 to 12; P = 0.038) or $20,000 - $99,999 (ß 5.8; 95% CI 2.1 to 9.5; P = 0.003) when compared to having net worth of less than $4999 were independently associated with better physical function. Being unemployed or disabled and keeping house, being a student, or retired were independently associated with worse physical function (ß -12; 95% CI -18 to -7.0; P < 0.001; ß -5.6; 95% CI -9.9 to -1.4; P = 0.009, respectively), when compared to working full-time or part-time. CONCLUSIONS: Objective and subjective measures of socioeconomic status are associated with magnitude of physical limitations in patients with musculoskeletal illness. These factors should be considered when developing treatment plans for patients with musculoskeletal conditions. LEVEL OF EVIDENCE: Level II prognostic study.

Randomised trial of the comparison of drug-eluting stents in patients with diabetes: OCT DES trial.

Background: To date, there have been limited comparisons performed between everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in patients with diabetes mellitus (DM). The objectives of this study was to assess the use of second-generation drug-eluting stents in patients with DM, using optical coherence tomography (OCT) to compare the level of stent coverage of Boston Scientific Promus Element EES compared with Medtronic Resolute Integrity ZES.(Clinicaltrials.gov number NCT02060357). Methods: This is a single-centre randomised blinded trials assessing two commercially available stents in 60 patients with diabetes (ZES: n=30, EES: n=30). Patients underwent intracoronary assessment at 6 months with OCT assessing stent coverage, malapposition, neointimal thickness and percentage of in-stent restenosis (ISR). Results: Of the 60 patients randomised, 46 patients underwent OCT analysis. There was no difference in baseline characteristics between the two groups. Both Promus Element and Resolute Integrity had low rates of uncovered struts at 6 months with no significant difference between the two groups (2.44% vs 1.24%, respectively; P=0.17). Rates of malapposition struts (3.9% vs 2.5%, P=0.25) and percentage of luminal loss did not differ between stent types. In addition, there was no significant difference in major adverse cardiovascular events (P=0.24) between the stent types. Conclusions: This study is the first randomised trial to evaluate OCT at 6 months for ZES and EES in patients with diabetes. Both stents showed comparable strut coverage at 6 months, with no difference in ISR rates at 6 months.

Outcomes after chronic total occlusion percutaneous coronary interventions: an observational study of 5496 patients from the Pan-London CTO Cohort.

BACKGROUND: Chronic total occlusions (CTO) are commonly encountered in patients undergoing coronary angiography; however, percutaneous coronary intervention (PCI) is infrequently performed owing to technical difficulty, the perceived risk of complications and a lack of randomized data. The aim of this study was to analyse the frequency and outcomes of CTO-PCI procedures in a large contemporary cohort of successive patients. PATIENTS AND METHODS: We undertook an observational cohort study of 48 234 patients with stable angina of which 5496 (11.4%) procedures were performed for CTOs between 2005 and 2015 at nine tertiary cardiac centres across London, UK. Outcome was assessed by in-hospital major adverse cardiac events and all-cause mortality at a median follow-up of 4.8 years (interquartile range: 2.2-6.4 years). RESULTS: Over time, there was an increase in the proportion of elective PCI procedures performed for CTOs, but no increase in the absolute number. Overall success rates increased over time (74.3% in 2005 to 81.5% in 2015; P=0.0003) despite an increase in case complexity (previous myocardial infarction, diabetes, renal failure, previous coronary artery bypass grafting, peripheral vascular disease and left ventricular impairment) that correlated with procedural advancements. Successful CTO PCI was associated with lower mortality [9.5%, 95% confidence interval (CI): 8.1-11.6 vs. 15.3%, 95% CI: 13.7-20.6, P<0.0001] that persisted after multivariate cox analysis (hazard ratio: 0.37, 95% CI: 0.25-0.62) and propensity matching (hazard ratio=0.36, 95% CI: 0.18-0.73, P=0.0005). CONCLUSION: Successful procedures were associated with lower mortality suggesting that the greater uptake of CTO PCI may improve clinical outcomes in a wider population than are currently being offered therapy.

Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1.

Activation of group 1 metabotropic glutamate receptors (mGluRs) induces long-term depression (LTD) of synaptic transmission that relies on dendritic protein synthesis. We investigated the signal transduction pathways required for mGluR-LTD to identify candidate mechanisms for mGluR regulation of synaptic protein synthesis. Our results demonstrate a role for extracellular signal-regulated protein kinase (ERK), a subclass of the mitogen-activated protein kinases (MAPKs), in mGluR-LTD in area CA1 of the rat hippocampus. Inhibitors of the upstream kinase of ERK, MAP/ERK kinase significantly reduce mGluR-LTD induced by the group 1 agonist dihydroxyphenylglycine (DHPG) and synaptic stimulation but do not affect NMDA receptor-dependent LTD. In contrast, inhibitors of p38 MAPK were ineffective against DHPG-induced LTD. Consistent with the role of ERK in mGluR-LTD, we observed that DHPG treatment of hippocampal slices (isolated CA1), at concentrations that induce LTD, results in a robust phosphorylation of ERK but not of p38 MAPK. These results point to ERK as an important regulator of mGluR-LTD and a potential mechanism for mGluR regulation of synaptic protein synthesis.

Radial primary percutaneous coronary intervention is independently associated with decreased long-term mortality in high-risk ST-elevation myocardial infarction patients.

AIM: To compare long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) using radial and femoral arterial access. METHODS AND RESULTS: The present study was an observational cohort study of patients with STEMI treated consecutively with PPCI between 2004 and 2011 at a single centre. The primary end point was all-cause mortality at a median follow-up of 3 years.Among 2727 patients, 1600 (58.7%) underwent PPCI via the femoral route. The femoral group was older (64.7 vs. 61.7 years; P < 0.0001), and had higher rates of diabetes (18.6% vs. 16.0%; P < 0.0001), previous PCI (11.2 vs. 7.8%; P = 0.004), previous myocardial infarction (15.3 vs. 8.3%; P < 0.0001) and cardiogenic shock (9.8 vs. 1.3%; P < 0.0001). Bleeding complications were more frequent in the femoral group (4.7 vs. 1.2%; P < 0.0001). The 5-year death rate was significantly higher in the femoral group than in the radial group (10.4 vs. 3.0%; P < 0.0001). After adjustment for confounding variables, bleeding complications [heart rate 2.07 (95% confidence interval 1.05-4.08)] and femoral access [heart rate 1.60 (95% confidence interval 1.02-2.53)] were independent predictors of all-cause mortality. After stratification using the propensity score, excess long-term mortality in patients treated via the femoral approach was predominantly in patients with a high baseline risk of death. CONCLUSION: Patients undergoing PPCI via the femoral route are at a higher risk of adverse short-term and long-term outcomes than patients undergoing PPCI via the radial route. Patients with a high baseline risk may benefit most from radial access, and future outcome studies should focus on the most at-risk patients.

The impact of socio-economic status on all-cause mortality after percutaneous coronary intervention: an observational cohort study of 13,770 patients.

AIMS: The relation between socio-economic status (SES) and outcomes after percutaneous coronary intervention (PCI) has not been established. We sought to determine whether or not socio-economic status impacts on prognosis after PCI. METHODS AND RESULTS: This was an observational cohort study of 13,770 consecutive patients who underwent PCI at a single centre between 2005 and 2011. Patient socio-economic status was defined by the English Index of Multiple Deprivation (IMD) score, according to residential postcode. Patients were analysed by quintile of IMD score (Q1, least deprived; Q5, most deprived). Median follow-up was 3.7 (IQR: 2.0-5.1) years and the primary outcome was all-cause mortality. Patients in Q5 (most deprived) were younger, more commonly South Asian, and had higher rates of smoking, diabetes mellitus, renal impairment, previous MI, and previous PCI than patients in Q1. Rates of long-term mortality increased progressively across the five quintiles of IMD score in a linear fashion (p=0.0004), as did rates of recurrent MI, target vessel revascularisation, and CABG. The difference in mortality rates persisted after adjustment for other potential confounding factors after multivariate analysis (Q5 vs. Q1: HR 1.93, 95% CI: 1.38-2.69). CONCLUSIONS: In this large contemporary cohort of patients receiving PCI, socio-economic status was associated with prognosis in a linear fashion.

Prognostic impact of anaemia on patients with ST-elevation myocardial infarction treated by primary PCI.

AIM: The aim of this study was to investigate the effects of baseline anaemia on the outcome in patients treated by primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction. METHODS: This study was a retrospective cohort study of 2418 patients with ST-elevation myocardial infarction treated by PPCI between January 2004 and August 2010 at a single centre. We investigated the outcome in patients with anaemia compared with that in patients with a normal haemoglobin (Hb) level. Anaemia was defined according to the WHO definition as an Hb level less than 12 g/dl for female individuals and less than 13 g/dl for male individuals. We also calculated hazard ratios using a stratified model according to the Hb level. RESULTS: A total of 471 (19%) patients were anaemic at presentation. The anaemic cohort was older (72.2 vs. 62.4 years, P<0.0001) and had a higher incidence of diabetes (28 vs. 16%, P<0.0001), hypertension (57 vs. 43%, P=0.01), hypercholesterolaemia (48 vs. 40%, P=0.007), previous PCI (15 vs. 9%, P<0.0001), previous myocardial infarction (23 vs. 12%, P=0.002), and cardiogenic shock (12 vs. 5%, P<0.0001). Over a mean follow-up period of 3 years there was significantly higher all-cause mortality in the anaemic group compared with the normal Hb group (20.4 vs. 13.5%, P<0.0001). However, after adjustment for all variables using multivariate analysis, anaemia (on the basis of the WHO definitions) was found not to be an independent predictor of mortality or major adverse cardiac events over the follow-up period. Further, when we used a model stratified by g/dl, we found that there was an increased risk for adverse outcomes among men with low Hb levels. There appeared to be a threshold value of Hb (13 g/dl) associated with increased risk. Although a similar trend was observed among women, no significant difference was observed. CONCLUSION: Patients with anaemia undergoing PPCI are at a higher risk of an adverse outcome. Anaemia is a simple and powerful marker of poor prognosis. Although anaemia (based on the WHO definitions) does not appear to be an independent predictor of all-cause mortality or major adverse cardiac events after PPCI on multivariate analysis, there appears to be a threshold value of Hb among men, below which there is an associated increased risk for PPCI.

Anatomic predisposition to ligamentous Lisfranc injury: a matched case-control study.

BACKGROUND: Subtle, or ligamentous, Lisfranc injuries occur following low-energy trauma to the midfoot and can be debilitating. Since they are ligamentous, they may not heal, requiring arthrodesis in some cases. Certain mortise anatomic characteristics on radiographs have been shown to be associated with a predisposition to the ligamentous subtype of Lisfranc injuries. It is not known whether there are other morphometric characteristics, such as arch height or the relative length of the second metatarsal, that can similarly influence the predisposition to these injuries. METHODS: The present retrospective matched case-control study involved fifty-two control subjects and twenty-six patients with ligamentous Lisfranc injuries treated from 2006 to 2010 at two institutions. Clinical and radiographic data (second metatarsal length relative to foot length, first intermetatarsal angle, navicular-cuboid overlap relative to cuboid vertical height, first metatarsal-talus angle, and calcaneal pitch angle) were examined for the existence of significant differences between control and Lisfranc subjects. Logistic regression analysis was then performed to evaluate potential risk for injury on the basis of these anatomic variables. RESULTS: Compared with matched controls, patients with a ligamentous Lisfranc injury were found to have a significantly smaller ratio of second metatarsal length to foot length (p < 0.001) on weight-bearing radiographs. CONCLUSIONS: Occurrence of a ligamentous Lisfranc injury was shown to be associated with a smaller ratio of second metatarsal length to foot length; >50% of patients in the injury group had a ratio of <29%.

Influence of female sex on long-term mortality after acute coronary syndromes treated by percutaneous coronary intervention: a cohort study of 7304 patients.

AIM: Female sex has been associated with worse outcome after percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). We assessed the influence of female sex on the long-term outcome of patients undergoing PCI for ACS. This included an unadjusted analysis and a fully-adjusted multivariate analysis including a propensity score. METHODS: This was an observational cohort study involving 7304 patients who had PCI for ACS [ST-elevation myocardial infarction (STEMI), non-ST elevation (NSTE) ACS] between October 2003 and September 2010. We analysed the effect of female sex on outcome. RESULTS: The primary end point was all-cause mortality, which was obtained from the UK Office of National Statistics at a median follow-up of 3.2 years (IQR: 1.5-4.6). Women were significantly older and had higher rates of diabetes mellitus compared with men. Over long-term follow-up, mortality was significantly higher in women with ACS compared with men; as a whole [all ACS: odds ratio (OR) 1.351, P<0.001] or when analysed by ACS type (NSTE ACS: OR 1.260, P=0.009; STEMI: OR 1.625, P<0.001). However, after adjustment using multivariate analysis, female sex was not an independent predictor of mortality in any ACS group (all ACS: OR 0.978, P=0.772; NSTE ACS: OR 0.954, P=0.603; STEMI: OR 1.081, P=0.567). This observation remained after the incorporation of a propensity score into the multivariate analysis [OR 0.95, 95% confidence interval 0.82-1.10]. CONCLUSION: Women presenting with ACS were older and had more baseline comorbidities. Female sex, however, does not appear to be an independent risk factor for mortality in our cohort.

Out-of-hours primary percutaneous coronary intervention for ST-elevation myocardial infarction is not associated with excess mortality: a study of 3347 patients treated in an integrated cardiac network.

OBJECTIVES: Timely delivery of primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment elevation myocardial infarction (STEMI). Optimum delivery of PPCI requires an integrated network of hospitals, following a multidisciplinary, consultant-led, protocol-driven approach. We investigated whether such a strategy was effective in providing equally effective in-hospital and long-term outcomes for STEMI patients treated by PPCI within normal working hours compared with those treated out-of-hours (OOHs). DESIGN: Observational study. SETTING: Large PPCI centre in London. PARTICIPANTS: 3347 STEMI patients were treated with PPCI between 2004 and 2012. The follow-up median was 3.3 years (IQR: 1.2-4.6 years). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was long-term major adverse cardiac events (MACE) with all-cause mortality a secondary endpoint. RESULTS: Of the 3347 STEMI patients, 1299 patients (38.8%) underwent PPCI during a weekday between 08:00 and 18:00 (routine-hours group) and 2048 (61.2%) underwent PPCI on a weekday between 18:00 and 08:00 or a weekend (OOHs group). There were no differences in baseline characteristics between the two groups with comparable door-to-balloon times (in-hours (IHs) 67.8 min vs OOHs 69.6 min, p=0.709), call-to-balloon times (IHs 116.63 vs OOHs 127.15 min, p=0.60) and procedural success. In hospital mortality rates were comparable between the two groups (IHs 3.6% vs OOHs 3.2%) with timing of presentation not predictive of outcome (HR 1.25 (95% CI 0.74 to 2.11). Over the follow-up period there were no significant differences in rates of mortality (IHs 7.4% vs OFHs 7.2%, p=0.442) or MACE (IHs 15.4% vs OFHs 14.1%, p=0.192) between the two groups. After adjustment for confounding variables using multivariate analysis, timing of presentation was not an independent predictor of mortality (HR 1.04 95% CI 0.78 to 1.39). CONCLUSIONS: This large registry study demonstrates that the delivery of PPCI with a multidisciplinary, consultant-led, protocol-driven approach provides safe and effective treatment for patients regardless of the time of presentation.

Primary percutaneous coronary intervention for ST-elevation myocardial infarction in a patient with a single coronary artery arising from the right aortic sinus.

We report the first case of primary percutaneous coronary intervention (PPCI) in a patient with a single coronary artery arising from the right aortic sinus. With the increasing availability of PPCI, more patients with coronary artery anomalies will undergo this procedure. This report highlights both the feasibility and safety of PPCI in patients with even the rarest of coronary artery anomalies.

Altered synaptic plasticity in a mouse model of fragile X mental retardation.

Fragile X syndrome, the most common inherited form of human mental retardation, is caused by mutations of the Fmr1 gene that encodes the fragile X mental retardation protein (FMRP). Biochemical evidence indicates that FMRP binds a subset of mRNAs and acts as a regulator of translation. However, the consequences of FMRP loss on neuronal function in mammals remain unknown. Here we show that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP. This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome.