Red cell N5-methyltetrahydrofolate concentrations and C677T methylenetetrahydrofolate reductase genotype in patients with stroke

AIMS: To investigate the relation between total red cell folate, red cell N(5)-methyltetrahydrofolate (N(5)MTHF) concentrations, and N(5)N(10)-methylenetetrahydrofolate reductase (MTHFR) genotypes in stroke. METHODS: The study comprised 120 consecutive patients presenting to hospital with acute stroke. Multivitamin supplement use was recorded. Serum and red cell folate were measured by microbiological assays using Lactobacillus casei and Enterococcus faecalis, and by the DPC-BioMediq Immulite 2000 analyser. Total plasma homocysteine (tHcy), serum cobalamin, and serum vitamin B(6) were measured and the C677T MTHFR genotype determined. RESULTS: There were no significant differences in blood tHcy or vitamin concentrations according to MTHFR genotype in the overall patient cohort. However, when patients taking vitamins were excluded, total red cell folate and red cell N(5)MTHF were significantly lower in patients with the TT genotype compared with CT or CC genotypes. In the overall cohort, irrespective of genotype, red cell folate was significantly lower when assayed microbiologically than with the Immulite assay. This discrepancy remained after exclusion of patients taking vitamins. CONCLUSION: Total red cell folate and red cell N(5)MTHF are significantly lower in stroke patients with the TT compared with the CT and TT MTHFR genotypes, particularly those not taking vitamin supplements. Microbiological assays that measure biologically active folates provide substantially lower estimates of folate than the Immulite assay. Because folate is a key determinant of blood homocysteine values, these findings may impact on the interpretation of the strength and independence of the association between raised blood concentrations of homocysteine and atherothrombosis risk reported in most epidemiological studies.     

Assessment of borderzone ischemia with a combined MR imaging-MR angiography-MR spectroscopy protocol

We attempted to assess whether magnetic resonance imaging (MRI)-MR angiography (MRA)-MR spectroscopy (MRS) measurements can be used in the differentiation of patients in whom severe carotid lesions result in chronically hypoperfused regions and in whom the collateral capacity is sufficient to maintain a normal cerebral blood flow. Sixty-six patients with severe stenosis of the internal carotid artery (ICA) and 19 control subjects underwent MRI, 1H MRS, and MRA. Anaerobic metabolic changes in the middle cerebral artery (MCA) territory were studied by assessing N-acetyl-L-aspartate (NAA)/choline and lactate/ NAA ratios. Quantitative flow was measured in the ICA, in the basilar artery, and in the MCA. Thirty-four patients had borderzone infarcts, 16 patients had territory infarcts, and 16 patients had no infarcts on MRI. Patients with border-zone infarcts had significantly reduced flow in the ICA (P < 0.001) and in the MCA (P < 0.05) and decreased NAA/ choline ratios (P < 0.001) in non-infarcted regions compared with control subjects (P < 0.001) but also compared with patients with territory infarcts (P < 0.05) and patients without infarcts (P < 0.05). Flow measurements in the ICA and MCA and metabolic measurements in the MCA territory can be applied to select patients in whom cerebral perfusion pressure is insufficient to maintain normal cellular integrity.     

Patient's quality of life and hearing outcomes after stapes surgery

Objectives: To determine the quality of life (QOL) after stapes surgery and whether audiological parameters for hearing correlate with specific QOL factors. Design: A retrospective cross‐sectional study. Setting: A tertiary referral centre. Participants: A series of 35 patients who underwent stapes surgery of which three were excluded because they were <18 years of age, chronically or mentally ill, or in a dependant relationship. Response rate was 93% (30/32). Nine were further excluded because they had revision or bilateral surgery, or missing data. Twenty‐one patients were included in this study. Main outcome measures: The Glasgow Benefit Inventory (GBI) was used to evaluate general QOL and the Hearing Disability and Handicap Scale (HDHS) was used as a disease‐specific measure. The Belfast Rule of Thumb and Glasgow Benefit Plot assessed hearing outcomes. Results: Operative success was 86% using the Belfast Rule of Thumb and 95% had closure of the air–bone gap to within 20 dB. 81.8% of patients reported a better overall QOL as surgery. Glasgow Benefit Inventory Social and GBI Physical scores correlated positively with the HDHS speech component (P < 0.05). The duration of hearing loss correlated inversely with the average HDHS score (P < 0.05). Conclusion: The majority of patients report a better QOL as undergoing stapes surgery. Speech impacts on people's physical and social QOL of patients. Quality of life tools, in addition to objective audiologic measurements can provide clinicians with patients’ subjective perspective that helps guide clinical decision‐making and counselling.     

Efficacy and safety of low intensity vitamin K antagonists in Western and East-Asian patients with left-sided mechanical heart valves

Journal of Thrombosis and Thrombolysis - The optimal INR target in patients with mechanical heart valves is unclear. Higher INR targets are often used in Western compared with East Asian countries....     

Management of peripheral arterial disease in the elderly: focus on cilostazol

Symptomatic and asymptomatic peripheral arterial disease (PAD) is a common problem in the elderly. The management of PAD includes the prevention of cardiovascular events and relief of symptoms – most commonly intermittent claudication (IC). Both require treatment of the causes and consequences of atherothrombosis, but some strategies are more effective for prevention of cardiovascular events and others are more effective for the relief of symptoms. Priorities for the prevention of cardiovascular events include smoking cessation, exercise, antiplatelet therapy, and the treatment of dyslipidemia, hypertension, and diabetes. Walking time and ability are improved by exercise. The benefit of numerous drugs in the treatment of IC has been assessed. The results have generally been disappointing, but there is some evidence that statins and cilostazol (an inhibitor of phosphodiesterase 3) are of benefit. Meta-analyses suggest that cilostazol increases maximum walking distance by 40%–50% and improves other objective measures of walking. The safety profile of cilostazol in patients with PAD appears to be acceptable although the mechanism for its effect on IC is unclear. In addition to risk factor management, treatment with cilostazol should be considered in patients with disabling IC.     

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE‐LY trial

Background

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives

To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE‐LY trial.

Methods

HAS‐BLED, ORBIT, ATRIA and HEMORR₂HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results

There were 1182 (6.5%) major bleeding events during a median follow‐up of 2.0 years. For all the four schemes, high‐risk subgroups had higher risk of major bleeding (all P  < 0.001). The ORBIT score showed the best discrimination with c‐indices of 0.66, 0.66 and 0.62, respectively, for major, life‐threatening and intracranial bleeding, which were significantly better than for the HAS‐BLED score (difference in c‐indices: 0.050, 0.053 and 0.048, respectively, all P  < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P  = 0.0019), ATRIA (P  < 0.001) and HEMORR₂HAGES (P  < 0.001) scores. HAS‐BLED score showed a nonsignificant trend for interaction (P  = 0.0607).

Conclusions

Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

     

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a ≥50% or ≥0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.