Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue

AbstractObjectivesPrevious clinical trials suggest that coenzyme Q10 might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q10 therapy on coenzyme Q10 levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q10 on mitochondrial function; to test the effect of coenzyme Q10 in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q10 therapy improves recovery of the heart after cardiac surgery.MethodsPatients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q10 (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed.ResultsPatients receiving coenzyme Q10 (n = 62) had increased coenzyme Q10 levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q10 than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q10 exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% ± 4.3% vs 64.0% ± 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I.ConclusionsPreoperative oral coenzyme Q10 therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q10 levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress

Comparison of 1.5T and 3T 1H MR Spectroscopy for Human Brain Tumors

OBJECTIVE: We wanted to estimate the practical improvements of 3T proton MR spectroscopy ((1)H MRS) as compared with 1.5T (1)H MRS for the evaluation of human brain tumors. MATERIALS AND METHODS: Single voxel (1)H MRS was performed at both 1.5T and 3T in 13 patients suffering with brain tumors. Using the same data acquisition parameters at both field strengths, the (1)H MRS spectra were obtained with a short echo time (TE) (35 msec) and an intermediate TE (144 msec) with the voxel size ranging from 2.0 cm(3) to 8.7 cm(3). The signal to noise ratios (SNRs) of the metabolites (myoinositol [MI], choline compounds [Cho], creatine /phosphocreatine [Cr], N-acetyl-aspartate [NAA], lipid and lactate [LL]) and the metabolite ratios of MI/Cr, Cho/Cr, Cho/NAA and LL/Cr were compared at both TEs between the two field strengths in each brain tumor. The degrees of spectral resolution between the Cho and Cr peaks were qualitatively compared between the two field strengths in each brain tumor. RESULTS: The SNRs of the metabolites at 3T demonstrated 49-73% increase at a short TE (p 0.05) compared with those of 1.5T. The SNR of inverted lactate at an intermediate TE decreased down to 49% with poorer inversion at 3T (p < 0.05). There was no significant difference in the metabolite ratios between the two field strengths. The degrees of the spectral resolution at 3T were slightly superior to those of 1.5T at a short TE. CONCLUSION: As compared with 1.5T, 3T 1H MRS demonstrated 49-73% SNR increase in the cerebral metabolites and slightly superior spectral resolution only at a short TE, but little at an intermediate TE, in the brain tumors. There was no significant difference in the metabolite ratios between the two field strengths

Blood Pressure and Penumbral Sustenance in Stroke from Large Vessel Occlusion

The global burden of stroke remains high, and of the various subtypes of stroke, large vessel occlusions (LVOs) account for the largest proportion of stroke-related death and disability. Several randomized controlled trials in 2015 changed the landscape of stroke care worldwide, with endovascular thrombectomy (ET) now the standard of care for all eligible patients. With the proven success of this therapy, there is a renewed focus on penumbral sustenance. In this review, we describe the ischemic penumbra, collateral circulation, autoregulation, and imaging assessment of the penumbra. Blood pressure goals in acute stroke remain controversial, and we review the current data and suggest an approach for induced hypertension in the acute treatment of patients with LVOs. Finally, in addition to reperfusion and enhanced perfusion, efforts focused on developing therapeutic targets that afford neuroprotection and augment neural repair will gain increasing importance. ET has revolutionized stroke care, and future emphasis will be placed on promoting penumbral sustenance, which will increase patient eligibility for this highly effective therapy and reduce overall stroke-related death and disability

Protocols for Endovascular Stroke Treatment Diminish the Weekend Effect Through Improvements in Off-Hours Care

Introduction: The weekend effect is a well-recognized phenomenon in which patient outcomes worsen for acute strokes presenting outside routine business hours. This is attributed to non-uniform availability of services throughout the week and evenings and, though described for intravenous thrombolysis candidates, is poorly understood for endovascular stroke care. We evaluated the impact of institutional protocols on the weekend effect, and the speed and outcome of endovascular therapy as a function of time of presentation.Method: This study assesses a prospective observational cohort of 129 consecutive patients. Patients were grouped based on the time of presentation during regular work hours (Monday through Friday, 07:00–19:00 h) vs. off-hours (overnight 19:00–07:00 h and weekends) and assessed for treatment latency and outcome.Results: Treatment latencies did not depend on the time of presentation. The door to imaging interval was comparable during regular and off-hours (median time 21 vs. 19 min, respectively, p &lt; 0.50). Imaging to groin puncture was comparable (71 vs. 71 min, p &lt; 1.0), as were angiographic and functional outcomes. Additionally, treatment intervals decreased with increased protocol experience; door-to-puncture interval significantly decreased from the first to the fourth quarters of the study period (115 vs. 94 min, respectively, p &lt; 0.006), with the effect primarily seen during off-hours with a 28% reduction in median door-to-puncture times.Conclusions: Institutional protocols help diminish the weekend effect in endovascular stroke treatment. This is driven largely by improvement in off-hours performance, with protocol adherence leading to further decreases in treatment intervals over time

Tumour progression or pseudoprogression?:A review of post-treatment radiological appearances of glioblastoma

Glioblastoma (GBM) is a common brain tumour in adults, which, despite multimodality treatment, has a poor median survival. Efficacy of therapy is assessed by clinical examination and magnetic resonance imaging (MRI) features. There is now a recognised subset of treated patients with imaging features that indicate "progressive disease" according to Macdonald's criteria, but subsequently, show stabilisation or resolution without a change in treatment. In these cases of "pseudoprogression", it is believed that non-tumoural causes lead to increased contrast enhancement and conventional MRI is inadequate in distinguishing this from true tumour progression. Incorrect diagnosis is important, as failure to identify pseudoprogression could lead to an inappropriate change of effective therapy. The purpose of this review is to outline the current research into radiological assessment with MRI and molecular imaging of post-treatment GBMs, specifically the differentiation between pseudoprogression and tumour progression

Predictors of functional outcome vary by the hemisphere of involvement in major ischemic stroke treated with intra-arterial therapy: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Conflicting data exists regarding the effect of hemispheric lateralization on acute ischemic stroke outcome. Some of this variability may be related to heterogeneous study populations, particularly with respect to the level of arterial occlusion. Furthermore, little is known about the relationship between stroke lateralization and predictors of outcome. The purpose of this study was to characterize the impact of stroke lateralization on both functional outcome and its predictors in a well-defined population of anterior circulation proximal artery occlusions treated with IAT.</p> <p>Methods</p> <p>Thirty-five consecutive left- and 35 consecutive right-sided stroke patients with intracranial ICA and/or MCA occlusions who underwent IAT were retrospectively analyzed. Ischemic change on pre-treatment imaging was quantified. Reperfusion success was graded using the Mori scale. Good outcome at three months was defined as an mRS ≤ 2. Left- and right-sided strokes were compared for outcome and its predictors.</p> <p>Result</p> <p>Of 70 patients with median NIHSS score of 18 (IQR, 14-21), 19 (27.1%) had a good outcome. There were 21 terminal ICA and 49 MCA occlusions. There was no difference in the rate of good outcomes between left- (n = 9) and right-sided (n = 10) strokes (p = 0.99). There were no significant differences in occlusion level, age, ischemic change on initial imaging and degree of reperfusion between left- and right-sided strokes. Left-sided strokes had higher baseline NIHSS scores (p = 0.02) and lower admission SBP (p = 0.009). Independent predictors of outcome for left-sided strokes were NIHSS (p = 0.0002) and reperfusion (p = 0.006), and for right-sided strokes were age (p = 0.002) and reperfusion (p = 0.003). In univariate analysis, pre-treatment ischemic change on NCCT was associated with outcome only for left-sided strokes (p = 0.05).</p> <p>Conclusions</p> <p>In anterior circulation proximal artery occlusions treated with IAT, hemispheric lateralization influences the clinical and imaging predictors of outcome. Most notably, NIHSS predicts outcome only for the left-sided strokes in this population. This finding has important implications for outcome prediction in the acute setting and indicates a need for stroke severity scales more sensitive to right hemispheric deficits.</p

The Anticoagulation of Calf Thrombosis (ACT) project: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Half of all lower limb deep vein thrombi (DVT) in symptomatic ambulatory patients are located in the distal (calf) veins. While proximal disease warrants therapeutic anticoagulation to reduce the associated risks, distal DVT often goes untreated. However, a proportion of untreated distal disease will undoubtedly propagate or embolize. Concern also exists that untreated disease could lead to long-term post thrombotic changes. Currently, it is not possible to predict which distal thrombi will develop such complications. Whether these potential risks outweigh those associated with unrestricted anticoagulation remains unclear. The Anticoagulation of Calf Thrombosis (ACT) trial aims to compare therapeutic anticoagulation against conservative management for patients with acute symptomatic distal deep vein thrombosis.</p> <p>Methods</p> <p>ACT is a pragmatic, open-label, randomized controlled trial. Adult patients diagnosed with acute distal DVT will be allocated to either therapeutic anticoagulation or conservative management. All patients will undergo 3 months of clinical and assessor blinded sonographic follow-up, followed by 2-year final review. The project will commence initially as an external pilot study, recruiting over a 16-month period at a single center to assess feasibility measures and clinical event rates. Primary outcome measures will assess feasibility endpoints. Secondary clinical outcomes will be collected to gather accurate data for the design of a definitive clinical trial and will include: (1) a composite endpoint combining thrombus propagation to the popliteal vein or above, development of symptomatic pulmonary embolism or sudden death attributable to venous thromboembolic disease; (2) the incidence of major and minor bleeding episodes; (3) the incidence of post-thrombotic leg syndrome at 2 years using a validated screening tool; and (4) the incidence of venous thromboembolism (VTE) recurrence at 2 years.</p> <p>Discussion</p> <p>The ACT trial will explore the feasibility of comparing therapeutic anticoagulation to conservative management in acute distal DVT, within a modern cohort. We also aim to provide contemporary data on clot propagation, bleeding rates and long-term outcomes within both groups. These results will inform the conduct of a definitive study if feasibility is established.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN75175695">ISRCTN75175695</a></p