Markus Béchir

Anti–Tumor Necrosis Factor-α Treatment Improves Endothelial Function in Patients With Rheumatoid Arthritis

Background— Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-α in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-α antibody infliximab on disease activity and endothelial function in patients with active RA. Methods and Results— Eleven RA patients (mean age 46±5 years; disease duration 9±2 years) with high disease activity despite treatment with stable doses of methotrexate (≤25 mg/wk) and prednisone (≤10 mg/d) were investigated. Clinical status and endothelium-dependent and -independent vasodilation of the brachial artery as assessed by high-resolution ultrasoun...

Selective COX-2 Inhibition Improves Endothelial Function in Coronary Artery Disease

Background—There is an ongoing debate as to whether the gastrointestinal safety of COX-2 inhibition compared with nonsteroidal antiinflammatory drugs (NSAIDs) may come at the cost of increased cardiovascular events. In view of the large number of patients at cardiovascular risk requiring chronic analgesic therapy with COX-2 inhibitors for arthritic and other inflammatory conditions, the effects of selective COX-2 inhibition on clinically useful surrogates for cardiovascular disease, particularly endothelial function, need to be determined. Methods and Results—Fourteen male patients (mean age, 66±3 years) with severe coronary artery disease (average of 2.6 vessels with stenosis >75%) undergoing stable background therapy with aspirin and statins were included. The patients received celecoxib (200 mg BID) or placebo for a duration of 2 weeks in a double-blind, placebo-controlled, crossover fashion. After each treatment period, flow-mediated dilation of the brachial artery, high-sensitivity C-reactive protein, oxidized LDL, and prostaglandins were measured. Celecoxib significantly improved endothelium-dependent vasodilation compared with placebo (3.3±0.4% versus 2.0±0.5%, P =0.026), whereas endothelium-independent vasodilation, as assessed by nitroglycerin, remained unchanged (9.0±1.6% versus 9.5±1.3%, P =0.75). High-sensitivity C-reactive protein was significantly lower after celecoxib (1.3±0.4 mg/L) than after placebo (1.8±0.5 mg/L, P =0.019), as was oxidized LDL (43.6±2.4 versus 47.6±2.6 U/L, P =0.028), whereas prostaglandins did not change. Conclusions—This is the first study to demonstrate that selective COX-2 inhibition improves endothelium-dependent vasodilation and reduces low-grade chronic inflammation and oxidative stress in coronary artery disease. Thus, selective COX-2 inhibition holds the potential to beneficially impact outcome in patients with cardiovascular disease.

The model for end-stage liver disease allocation system for liver transplantation saves lives, but increases morbidity and cost: a prospective outcome analysis

We analyzed the first 100 patients who underwent liver transplantation by Model for End‐Stage Liver Disease (MELD) allocation, and compared the outcome of patients on the waiting list and after orthotopic liver transplantation with the last 100 patients who underwent transplantation prior to the introduction of the MELD system in July 2007. MELD allocation resulted in decreased waiting list mortality (386 versus 242 deaths per 1000 patient‐years, P < 0.0001) and the transplantation of sicker recipients (uncorrected median MELD score 13.5 versus 20, P = 0.003). Recipient posttransplant morbidity was significantly higher, mainly caused by increased percentage of renal failure requiring renal replacement therapy (13 versus 46%, P < 0.0001). However, kidney function recovered in most cases within 6 months after OLT. Hospital mortality remained similar in both groups (6% versus 9%). Patient 1‐year survival was 91% versus 83% (pre‐MELD versus MELD era, P = 0.2154), graft 1‐year survival was 88% versus 78% (P = 0.1013), respectively. Costs accumulated were significantly higher after introduction of the MELD policy (US

Noninvasive cardiac output and blood pressure monitoring cannot replace an invasive monitoring system in critically ill patients

81,967 versus US

Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury.

127,453, a 55% increase, P = 0.02) with a strong correlation with the individual MELD score (P < 0.0001). The MELD system addresses the goal of fairness well. However, the postoperative course appears more difficult in the MELD era with increased financial burden, but reasonable patient and graft survival. This is the inevitable price to balance justice and utility in liver graft allocation. Liver Transpl 17:674–684, 2011.

Dysfunctional Baroreflex Regulation of Sympathetic Nerve Activity in Patients With Vasovagal Syncope

BackgroundMonitoring of cardiac output and blood pressure are standard procedures in critical care medicine. Traditionally, invasive techniques like pulmonary artery catheter (PAC) and arterial catheters are widely used. Invasiveness bears many risks of deleterious complications. Therefore, a noninvasive reliable cardiac output (CO) and blood pressure monitoring system could improve the safety of cardiac monitoring. The aim of the present study was to compare a noninvasive versus a standard invasive cardiovascular monitoring system.MethodsNexfin HD is a continuous noninvasive blood pressure and cardiac output monitor system and is based on the development of the pulsatile unloading of the finger arterial walls using an inflatable finger cuff. During continuous BP measurement CO is calculated. We included 10 patients with standard invasive cardiac monitoring system (pulmonary artery catheter and arterial catheter) comparing invasively obtained data to the data collected noninvasively using the Nexfin HD.ResultsCorrelation between mean arterial pressure measured with the standard arterial monitoring system and the Nexfin HD was r2 = 0.67 with a bias of -2 mmHg and two standard deviations of ± 16 mmHg. Correlation between CO derived from PAC and the Nexfin HD was r2 = 0.83 with a bias of 0.23 l/min and two standard deviations of ± 2.1 l/min; the percentage error was 29%.ConclusionAlthough the noninvasive CO measurement appears promising, the noninvasive blood pressure assessment is clearly less reliable than the invasively measured blood pressure. Therefore, according to the present data application of the Nexfin HD monitoring system in the ICU cannot be recommended generally. Whether such a tool might be reliable in certain critically ill patients remains to be determined.

Effects of statins on endothelial function and lipid profile in HIV infected persons receiving protease inhibitor-containing anti-retroviral combination therapy: a randomised double blind crossover trial

IntroductionThe optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism.MethodsIn twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 μl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios.ResultsBrain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu.ConclusionsArterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury.

Model of end stage liver disease (MELD) score greater than 23 predicts length of stay in the ICU but not mortality in liver transplant recipients

Background—The interplay of resting muscle sympathetic nerve activity (MSA) and the baroreceptor reflex in patients with vasovagal syncope remains elusive. Hence, the aim of the present study was to investigate MSA, baroreceptor sensitivity, heart rate, and blood pressure under resting conditions and during orthostatic stress in patients with a history of vasovagal syncope. Methods and Results—MSA was measured using microneurography at rest and during lower body negative pressure (LBNP) to mimic orthostatic stress in patients with a history of vasovagal syncope (n=10) and in age-matched healthy controls (n=8). Heart rate and blood pressure were simultaneously recorded. Cardiac baroreceptor sensitivity was calculated with the spectral technique (&agr; coefficient). Resting MSA in the patients with syncope was significantly increased as compared with controls (42.4±2.3 versus 26.5±3.6 bursts/min, P =0.001), whereas activation of MSA during orthostatic stress in the patient group was significantly blunted (5.1±1.6 versus 15.2±2.1 bursts/min at LBNP −50 mm Hg, P =0.002). In the patients with syncope, cardiac baroreceptor sensitivity was significantly reduced under supine resting conditions (8.5±0.7 versus 13.0±1.1 ms/mm Hg, P =0.001), as well as under orthostatic stress (7.3±0.7 versus 13.4±1.5 ms/mm Hg, P =0.003). Conclusions—This study shows that in patients with vasovagal syncope, resting MSA is increased and baroreflex regulation during orthostatic stress is blunted, thus leading to impaired MSA adaptation. These results provide new insights into mechanisms of vasovagal syncope and suggest that pharmacological modulation of baroreceptor sensitivity may represent a promising treatment of neuromediated syncope.

Differential temporal profile of lowered blood glucose levels (3.5 to 6.5 mmol/l versus 5 to 8 mmol/l) in patients with severe traumatic brain injury

Introduction of anti-retroviral combination therapy has profoundly altered both the course and prognosis of the disease in HIV infected persons. Recent data, however, have raised concerns that anti-retroviral combination therapy is associated with premature manifestation of coronary artery disease.1 In particular, protease inhibitors have been linked to metabolic changes such as insulin resistance, abnormalities in lipid metabolism and lipodystrophy, and increased coronary artery calcification. While previous studies have reached conflicting conclusions about the incidence of myocardial infarction, the most substantial database recently provided by Friis-Moller and co-workers demonstrated an increased incidence in HIV infected persons receiving protease inhibitors or non-nucleoside reverse transcriptase inhibitor-containing therapy.2 One of the postulated mechanisms of pro-atherogenic effects of protease inhibitors is the promotion of atherosclerotic lesion formation by an increase in CD36-dependent cholesteryl ester accumulation in macrophages. Additionally, hypercholesterolaemia promotes a CD36-dependent and endothelial nitric oxide synthase mediated endothelial dysfunction. Endothelial dysfunction is associated with future risk of adverse cardiovascular events.3 Impaired endothelial function was previously shown in HIV infected persons receiving protease inhibitor therapy.4 The effect of statins (hydroxy-methyl-glutaryl coenzyme A reductase inhibitors) in anti-retroviral combination therapy associated dyslipidaemia remains to be determined. As most statins are metabolised by the cytochrome P450 3A4 isoform, and thus interfere with the metabolism of many anti-retroviral drugs, resulting in increased toxicity, cytochrome P450 independent statins, such as pravastatin, may be advantageous. Hence, the present study aimed to evaluate the effects of pravastatin on endothelial function and plasma lipid profile in …

Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury

IntroductionThe impact of model of end stage liver disease (MELD) score on postoperative morbidity and mortality is still elusive, especially for high MELD. There are reports of poorer patient outcome in transplant candidates with high MELD score, others though report no influence of MELD score on outcome and survival.MethodsWe retrospectively analyzed data of 144 consecutive liver transplant recipients over a 72-month period in our transplant unit, from January 2003 until December 2008 and performed uni- and multivariate analysis for morbidity and mortality, in particular to define the influence of MELD to these parameters.ResultsThis study identified MELD score greater than 23 as an independent risk factor of morbidity represented by intensive care unit (ICU) stay longer than 10 days (odds ratio 7.0) but in contrast had no negative impact on mortality. Furthermore, we identified transfusion of more than 7 units of red blood cells as independent risk factor for mortality (hazard ratio 7.6) and for prolonged ICU stay (odds ratio [OR] 7.8) together with transfusion of more than 10 units of fresh frozen plasma (OR 11.6). Postoperative renal failure is a strong predictor of morbidity (OR 7.9) and postoperative renal replacement therapy was highly associated with increased mortality (hazard ratio 6.8), as was hepato renal syndrome prior to transplantation (hazard ratio 13.2).ConclusionsThis study identified MELD score greater than 23 as an independent risk factor of morbidity represented by ICU stay longer than 10 days but in contrast had no negative impact on mortality. This finding supports the transplantation of patients with high MELD score but only with knowledge of increased morbidity.