Assessment of changes in blood glucose concentration with intravascular microdialysis.

Blood glucose and its variability of is a major prognostic factor associated with morbidity. We hypothesized that intravenous microdialysis incorporated in a central venous catheter (CVC) would be interchangeable with changes in blood glucose measured by the reference method using a blood gas analyzer. Microdialysis and central venous blood glucose measurements were simultaneously recorded in high-risk cardiac surgical patients. The correlation between absolute values was determined by linear regression and the Bland-Altman test for repeated measurements was used to compare bias, precision, and limits of agreement. Changes in blood glucose measurement were evaluated by four-quadrant plot and trend interchangeability methods (TIM). In the 23 patients analyzed, the CVC was used as part of standard care with no complications. The correlation coefficient for absolute values (N = 99) was R = 0.91 (P < 0.001). The bias, precision and limits of agreement were - 9.1, 17.4 and - 43.2 to 24.9 mg/dL, respectively. The concordance rate for changes in blood glucose measurements (N = 77) was 85% with the four-quadrant plot. The TIM showed that 14 (18%) changes of blood glucose measurements were uninterpretable. Among the remaining 63 (82%) interpretable changes, 23 (37%) were interchangeable, 13 (20%) were in the gray zone, and 27 (43%) were not interchangeable. Microdialysis using a CVC appears to provide imprecise absolute blood glucose values with risk of insulin misuse. Moreover, only one third of changes in blood glucose measurements were interchangeable with the reference method using the TIM.

Relative effect of APOE ε4 on neuroimaging biomarker changes across the lifespan.

OBJECTIVE: To provide a comprehensive understanding of APOE ε4 effects across the lifespan on the 3 main neuroimaging biomarkers. METHODS: Two hundred seven community-dwelling, cognitively normal APOE ε4 carriers and noncarriers aged 20-87 years were involved in this study. They underwent structural MRI, fluorodeoxyglucose-PET, and florbetapir-PET scans. The effects of APOE, age, and APOE × age interaction were assessed voxel-wise for each modality. RESULTS: There was no significant effect of APOE or APOE × age interaction on gray matter volume and glucose metabolism, although decreases with age tended to be stronger in noncarriers than in carriers. In contrast, ß-amyloid (Aß) deposition was significantly higher in carriers compared with noncarriers in a largely distributed network, and there was a significant APOE × age interaction such that Aß deposition increased nonlinearly with age in APOE ε4 carriers only. CONCLUSIONS: Our findings highlight a differential effect of APOE ε4 on amyloid vs neurodegeneration biomarkers. APOE ε4 mainly influences Aß deposition, while the effects on gray matter volume and glucose metabolism are at best subtle. CLINICALTRIALSGOV IDENTIFIER: NCT01638949.

Is it worth to report the presence of a single and additional band in the cerebrospinal fluid detected by isoelectrofocusing?

Despite the revisions of the Mac Donald criteria of multiple sclerosis (MS) in 2010, the cerebrospinal fluid (CSF) analysis by isoelectrofocusing (IEF) remains useful for atypical presentations of MS. The IEF is considered as positive when at least two or more additional bands are detected in the CSF by comparison with the patient's serum but sometimes, the IEF interpretation is more difficult. The goal of our study was to determine the significance when a single band in the CSF is detected by IEF. We conducted a retrospective study on 990 patients who underwent a lumbar puncture followed by a CSF analysis by IEF. Only 2% display such IEF profile (i.e. single and additional band in the CSF). A diagnosis of clinically isolated syndrome or MS was evidenced in 4 among those 21 patients. In conclusion, our data suggest that even if the presence of a single and additional band in the CSF is a rare situation, it should be mentioned to clinicians to not exclude the hypothesis of an inflammatory demyelinating disease of the central nervous system.

Accuracy of plasma neutrophil gelatinase-associated lipocalin in the early diagnosis of contrast-induced acute kidney injury in critical illness.

PURPOSE: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI). We evaluated the diagnostic and prognostic accuracies of plasma NGAL (pNGAL) for contrast-induced AKI (CI-AKI) in critically ill patients. METHODS: In a prospective observational study in two adult intensive care units in a university hospital, 100 consecutive critically ill patients with stable serum creatinine concentrations up to 48 h before contrast medium (CM) injection were enrolled. Serial blood sampling for pNGAL analysis was performed at enrolment, 2, 6, and 24 h after CM injection. The primary outcome was CI-AKI, defined by AKIN criteria, within the first 72 h following CM injection. Secondary outcomes were the need for renal replacement therapy (RRT) and mortality. RESULTS: Of the 98 patients analyzed, 30 developed CI-AKI. The pNGAL levels did not differ in patients with or without CI-AKI, and were higher in septic patients compared to nonseptic patients, and in patients with AKI preceding CM injection. The discriminative value of pNGAL to predict CI-AKI and mortality was poor; although, it did predict the need for RRT requirement after CM injection (area under receiver-operating characteristic curve, 0.85, 0.80, 0.83 and 0.86 at H0, H2, H6 and H24, respectively). CONCLUSION: CI-AKI was common in critically ill patients. pNGAL levels were higher in patients with sepsis or previous AKI, but did not help to diagnose CI-AKI any earlier than serum creatinine after CM injection. However, pNGAL could be of interest to detect patients at risk of subsequent RRT requirement.

Dynamics of procalcitonin and bacteremia in neutropenic adults with acute myeloid leukemia.

Sensitive markers of infection are rare or of limited validity in neutropenic patients. Procalcitonin (PCT), a precursor protein of calcitonin, is a specific and sensitive marker of severe bacterial infections during short-term neutropenia. Because the value of PCT measurements among patients undergoing long periods of neutropenia remains uncertain and because several mechanisms, such as bacterial or fungal infections, reactions to drugs or blood products or tumor-associated events, can cause fever, we described the dynamics of PCT in 29 acute myeloid leukemia (AML) patients with 39 instances of chemotherapy-induced neutropenia. Plasma levels of PCT were determined prospectively by an immunoluminometric assay every four days starting at the onset of chemotherapy and continuing until the resolution of fever. We found that bacteremia did increase PCT levels above 0.5ng/mL and these levels predicted bacteremia at day 15 of chemotherapy. This finding may be relevant in the decision to alter antibiotic regimens to decrease toxicity and cost when patients remain febrile at day 15.

Contribution of deletion in angiotensin-converting enzyme but not A1166C angiotensin II type-1 receptor gene polymorphisms to clinical outcomes in atherothrombotic disease.

BACKGROUND AND AIMS: Angiotensin-converting enzyme insertion/deletion (rs4340) and angiotensin II type 1 receptor A1166C (rs5186) gene polymorphisms may be involved in coronary heart disease (CHD). This study was designed to evaluate potential relationships between these polymorphisms and the risk of long-term all-cause mortality and major adverse cardiovascular events (MACE) in patients requiring revascularization for atherothrombotic disease (ATD) lesions. METHOD: This prospective observational study concerned patients referred for supra-aortic vessel disease (SVD), CHD, peripheral artery occlusive disease (PAOD) or visceral artery disease (VAD). Collected data included ATD referral site, ATD symptoms, personal and familial medical histories, ATD extent, vascular risk factors, biological values, medication use and rs4340 and rs5186 polymorphisms. The primary end point was all-cause mortality. The secondary end point, MACE, included cardiovascular death, clinical ischemic event related to SVD, CHD, PAOD or VAD. RESULTS: The cohort comprised 956 patients of whom 872 (91.2%) were genotyped and followed for 21.1 ± 9.9 months. Patients were referred for SVD (25.9%), CHD (42.3%), PAOD (35.2%) or VAD (1.6%). All-cause mortality and MACE rates were 7.6 and 27.2%, respectively. When comparing I/D + D/D vs. I/I genotypes, rs4340 polymorphism was associated with higher all-cause mortality rates according to uni- and multivariate analyses (p=0.008 and 0.011, respectively). Other differences were not significant (rs4340 polymorphism and MACE, rs5186 polymorphism and all-cause mortality and MACE). No interaction was found between the polymorphisms. Other independent predictors of all-cause mortality included PAOD history, SVD history, body mass index <25 kg/m(2), HbA(1c) ≥6.5%, absence of dyslipidemia and no use of aspirin. CONCLUSION: rs4340 polymorphism is associated with long-term all-cause mortality in advanced ATD patients requiring revascularization, whereas rs5186 polymorphism does not.

Procalcitonin levels and bacterial aetiology among COPD patients admitted to the ICU with severe pneumonia: a prospective cohort study.

BACKGROUND: Serum procalcitonin (PCT) is considered useful in predicting the likeliness of developing bacterial infections in emergency setting. In this study, we describe PCT levels overtime and their relationship with bacterial infection in chronic obstructive pulmonary disease (COPD) critically ill patients with pneumonia. METHODS: We conducted a prospective cohort study in an ICU of a University Hospital. All consecutive COPD patients admitted for pneumonia between September 2005 and September 2006 were included. Respiratory samples were tested for the presence of bacteria and viruses. Procalcitonin was sequentially assessed and patients classified according to the probability of the presence of a bacterial infection. RESULTS: Thirty four patients were included. The PCT levels were assessed in 32/34 patients, median values were: 0.493 microg/L [IQR, 0.131 to 1.471] at the time of admission, 0.724 microg/L [IQR, 0.167 to 2.646] at six hours, and 0.557 microg/L [IQR, 0.123 to 3.4] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 microg/L in 3/32 (9%) patients and greater than 0.25 microg/L in 22/32 (69%) patients, suggesting low and high probability of bacterial infection, respectively. Fifteen bacteria and five viruses were detected in 15/34 (44%) patients. Bacteria were not detected in patients with PCTmax levels < 0.1 microg/L. In contrast, bacteria were detected in 4/7 (57%) patients estimated unlikely to have a bacterial infection by PCT levels (PCTmax > 0.1 and < 0.25 microg/L). CONCLUSION: Based on these results we suggest that a PCT level cut off > 0.1 microg/L may be more appropriate than 0.25 microg/L (previously proposed for non severe lower respiratory tract infection) to predict the probability of a bacterial infection in severe COPD patients with pneumonia. Further studies testing procalcitonin-based antibiotic strategies are needed in COPD patients with severe pneumonia.

Angiotensin converting enzyme insertion/deletion genetic polymorphism: its impact on renal function in critically ill patients.

OBJECTIVE: Previous clinical studies have suggested an association between the insertion/deletion (I/D) genetic polymorphism of angiotensin converting enzyme and acute or chronic diseases. We aimed to test the prognostic value of the I-allele, which is associated with lower angiotensin converting enzyme activity, on acute kidney injury. DESIGN: Prospective 6-month noninterventional study. SETTING: Intensive care unit of a University Hospital. PATIENTS AND METHODS: One hundred eighty consecutive admitted white patients for an expected intensive care unit stay >48 hr. Angiotensin converting enzyme genetic polymorphism was screened for genotype (I/D polymorphism analysis by polymerase chain reaction amplification) and phenotype (measurement of the circulating rate of angiotensin converting enzyme by spectrophotometry). Acute kidney injury was assessed according to Risk, Injury, Failure, Loss, and End-stage Kidney classification. INTERVENTION: None. RESULTS: II, ID, and DD genotype frequencies were 25%, 48%, and 27%, respectively. II and ID genotypes were associated with lower baseline circulating rates of angiotensin converting enzyme (20 +/- 14 and 22 +/- 18 U/L, respectively, vs. 30 +/- 23 U/L for DD genotype; p = 0.04). Repartition of angiotensin converting enzyme genotypes were different in patients with and without acute kidney injury (p < 0.0001), with greater II genotype proportion in acute kidney injury patients (42% vs. 13% for those without acute kidney injury). After adjustment on the identified prognostic factors, II genotype was independently associated with increased risk of acute kidney injury (adjusted odds ratio, 6.5; 95% confidence interval, 2.4-17.7; p = 0.0002), then death among patients with acute kidney injury (adjusted odds ratio, 1.7; 95% confidence ratio, 1.1-2.6; p = 0.02). CONCLUSION: These data confirm the key role of the renin-angiotensin system to maintain glomerular filtration rate, and highlight an association between a genetic factor and susceptibility to and prognosis of acute kidney disease.

Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study.

BACKGROUND: Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population. METHODS: We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay. RESULTS: Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%-75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 microg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 microg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 microg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 microg/L in 14/35 (40%) patients and more than 0.25 microg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 microg/L and three had a PCTmax less than 0.1 microg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 microg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 microg/L respectively, P = 0.80). CONCLUSION: The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 microg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.

Risk of acute brain injury related to cerebral microembolism during cardiac catheterization performed by right upper limb arterial access.

BACKGROUND AND PURPOSE: The primary objective of this study was to assess the incidence of new cerebral infarcts related to cardiac catheterization in patients explored through the right transradial approach. METHODS: This prospective study involved 41 consecutive patients with severe aortic valve stenosis. To assess the incidence of cerebral infarction, all patients underwent cerebral diffusion-weighted MRI before and after cardiac catheterization through the right transradial approach. RESULTS: We detected only two patients (4.9%) with new, small, isolated acute cerebral diffusion abnormalities postcatheterization. All patients remained asymptomatic. CONCLUSIONS: New cerebral lesions on diffusion-weighted MRI are infrequent in patients explored through the right transradial approach. Randomized studies are warranted to confirm for potential advantages of transradial approach versus the femoral approach in cardiac catheterization.

Relation between the A1166C angiotensin II type 1 receptor gene polymorphism and cardiovascular outcomes after myocardial infarction.

BACKGROUND: The A1166C polymorphism of the angiotensin II type 1 receptor (AT1R) gene, which appears to be the main receptor mediating the pleitropic vascular effects of angiotensin II in human beings, has been associated with the risk of myocardial infarction (MI), the severity of coronary vasoconstriction and the occurrence of sudden death. The question therefore arises whether the A1166C polymorphism constitutes a hereditary risk factor of survival after an acute myocardial infarction. METHODS AND RESULTS: In a large prospective study of 970 consecutive patients with a recent myocardial infarction the A1166C polymorphism was detected using a PCR based protocol. During the follow-up period (median, 2.5 years), 75 patients died and 62 from cardiovascular causes. The prespecified primary and secondary end points considered were total mortality and cardiovascular mortality. No differences between AA, AC, and CC groups were observed with respect to baseline clinical characteristics. Beyond conventional risk factors like age (RR=2.8 [1.6-5.0] 95% CI; p<0.001), hypercholesterolemia (RR=2.1 [1.2-3.7] 95% CI; p<0.014) or low left ventricular ejection fraction (RR=2.7 [1.5-4.8] 95% CI; p<0.002), the AT1R CC genotype was also identified as a strong independent predictor of death after myocardial infarction (RR=3.2 [1.5-7.0] 95% CI ; p<0.004). After adjustment for mortality causes, the AT1R CC genotype was confirmed to be an independent predictor of cardiovascular death after myocardial infarction (RR=2.8 [1.2-6.5] 95% CI; p<0.021). CONCLUSIONS: The AT1R CC genotype after adjustment is a strong predictor of death in post MI patients. This new finding may help to identify high risk post MI patients who may benefit from new therapeutic strategies.

Preprocedural creatinine clearance and long term survivalafter successful coronary stenting.

AIM: The clinical outcome of patients with severe renal dysfunction undergoing percutaneous coronary intervention (PCI) is poor. However little is known concerning the impact of mild renal insufficiency on long-term clinical outcomes after successful coronary stenting. The present prospective observational study was designed to evaluate long-term clinical outcomes in relation to renal insufficiency after successful coronary stenting. METHODS AND RESULTS: A consecutive series of 1454 patients were enrolled between January 4th 1997 and January 4th 1999 Demographic and clinical characteristics and long term clinical outcome were compared for patients with normal creatinine clearance (>60 ml/mn), mild renal dysfunction (creatinine clearance rates 30-60 ml/mn) and severe renal dysfunction (creatinine clearance rates <30 ml/mn). Patients with moderate or severe renal dysfunction were older and with more severe coronary artery disease. Beyond conventional risk factors like age (RR = 1.72 [1.10-2.68] 95% CI ; p<0.018), or low left ventricular ejection fraction (RR = 2.60 [1.72-3.94] 95% CI ; p<0.001), severe (creatinine clearance rates < 30 ml/min) and mild (creatinine clearance 30-60 ml/min) renal dysfunction were also identified as strong independent predictors of death after successful coronary stenting (RR = 4.91 [2.63-9.15] 95% CI, p<0.001 and RR = 1.57 [1.03-2.40] 95% CI, p<0.034, respectively). CONCLUSIONS: In patients with successful coronary stenting, preprocedural creatinine clearance remains an important independent predictor of long term death. These data reinforce the importance of widespread application of prevention strategies especially in patients with coronary artery disease complicated by renal dysfunction.

The effect of age, body mass index, and fasting triglyceride level on postprandial lipemia is dependent on apolipoprotein E polymorphism in subjects with non-insulin-dependent diabetes mellitus.

The aim of this study was to evaluate in non-insulin-dependent diabetes mellitus (NIDDM) subjects the respective influence of apolipoprotein (apo) E polymorphism, age, gender, weight, fasting triglyceride (TG) status, and glycemic status on postprandial lipemia. Apo E genotyping was performed in consecutive NIDDM hospitalized patients in order to recruite size-adjusted groups of each apo E genotype. In 57 NIDDM including 22 E3/3 (E3), 18 E2/3 (E2), and 17 E4/3 (E4) subjects, an 8-hour vitamin A-fat loading test was performed and TG and retinyl palmitate (RP) measured. Fasting TG level correlated with the TG area under the incremental curve (AUIC) (r = 0.512, P <.001) but not with RP AUIC. Despite not different fasting and postprandial TG concentrations, E2 and E4 carriers exhibited a 2- to 3-fold higher RP AUIC than E3 carriers (P =.01). Multivariate analysis indicated an age x apo E interaction on postprandial TG (P <.01), since the unfavorable effect of E2 and E4 allele on TG AUIC was unmasked by aging. In addition, a fasting TG x apo E interaction on postprandial TG was shown (P <.01), and the correlation between fasting TG and TG AUIC was actually restricted to E2 or E4 carriers. Finally, the negative correlation between BMI and postprandial TG observed in the experimental group was actually restricted to E4 carriers (r = -0.77, P <.001). Our results indicate interactions between apo E polymorphism and aging, fasting TG level and BMI that may be important for analyzing postprandial TG clearance in NIDDM.