The plasma levels of relaxin-2 and relaxin-3 in patients with diabetes

ObjectivesRelaxin-2 has been found to alleviate fibrosis in experimental diabetic cardiomyopathy. In addition, the levels of serum relaxin-3 were increased and correlated with all the component traits of metabolic syndrome. We investigated the levels of plasma relaxin-2 or relaxin-3 and their relationship to component traits in patients with diabetes.Design and methodsWe studied 33 newly diagnosed type 2 diabetes patients and 38 age-matched healthy subjects. Blood samples were taken at study entry, and relaxin-3, relaxin-2, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, serum insulin and hemoglobin A_1c (HbA_1c) levels were measured.ResultsRelaxin-2 levels were significantly lower in patients with diabetes than in controls: the median plasma relaxin-2 concentration was 34.68 pg/mL (range, < 29.00–50.81 pg/mL) in patients with diabetes and 45.80 pg/mL (range, < 37.42–54.46 pg/mL) in controls (p = 0.0150). However, no differences in relaxin-3 levels were observed between the diabetes group and controls (p = 0.6550). The plasma levels of relaxin-2 or relaxin-3 were not correlated with systolic blood pressure (BP), diastolic BP, total cholesterol, LDL-C, HDL-C, triglyceride, fasting blood glucose, fasting insulin and HbA_1c in patients with diabetes. Additionally, there was no correlation between the plasma concentrations of relaxin-2 and relaxin-3 in patients with diabetes (r_s = 0.225; p = 0.208).ConclusionsWe conclude that the plasma levels of relaxin-2 in diabetes patients were lower than in controls, however, there are no difference in plasma relaxin-3 concentrations between controls and patients with diabetes. Relaxin-2 or relaxin-3 levels are not related to component traits in patients with diabetes.     

Assessment of inflammatory markers in patients with community-acquired pneumonia — Influence of antimicrobial pre-treatment: Results from the German competence network CAPNETZ

BackgroundThere is almost no data about the influence of antimicrobial pre-treatment (APT) on levels of inflammatory markers in community acquired pneumonia (CAP). The aim of this study was to investigate the influence of APT on inflammatory markers in CAP.Methods991 hospitalized patients (64.3 ± 17.6 years, 61% male) with CAP were enrolled. In all patients procalcitonin (PCT), C-reactive protein (CRP), and leukocyte count (WBC) were determined. Patients were followed-up for 28 days for survival.Results232 patients (23.4%) had APT, 759 had no APT. Patients without APT had significantly higher levels of PCT and WBC but not of CRP compared to those with APT. In patients without APT, survivors compared to non-survivors had lower values of PCT (0.20 ng/mL; 0.02–169.10 vs. 0.83 ng/mL; 0.04–516.30, p < 0.0001), WBC (12.4 × 10⁹/L; 1.3–49.9 vs. 14.9 × 10⁹/L; 3.7–34.5, p = 0.047) and CRP (107.0 mg/mL; 0.3–567.0 vs. 143.5 mg/mL; 5.0–589.0, p = 0.006). However, in patients with APT, the values of PCT, WBC and CRP were not significantly different in survivors and non-survivors. Cox regression analysis confirmed that PCT, CRP and WBC were predictive for 28 day mortality in patients without APT but not in those with APT.ConclusionsPCT and WBC but not CRP levels are higher in patients without APT compared to those with APT. PCT, CRP and WBC are predictive for 28 days mortality exclusively in patients without APT. Interpretation of inflammatory parameters has to take into account possible APT.     

VEGF-A gene promoter polymorphisms and microvascular complications in patients with essential hypertension

ObjectivesWe investigated the possible involvement of vascular endothelial growth factor (VEGF-A) gene promoter polymorphisms in essential hypertension (EH).Design and methods1225 bp of the VEGF-A gene promoter were screened for polymorphisms using PCR amplification and direct DNA sequence analysis in 62 EH and 62 normotensive (HS) individuals. Circulating VEGF-A levels were determined by immunoassay.Results?152G/A (p = 0.009) and ?116G/A (p = 0.016) polymorphisms were correlated to hypertension (p < 0.05). Median platelet VEGF-A load in EH was 2.10 fg/plt. Patients with microvascular complications (MC) had higher platelet VEGF-A load than those without (p = 0.005). Multivariate analyses showed that ?116 A allele was an independent predictor of microalbuminuria (p = 0.014) and increased platelet VEGF-A load (p = 0.009) in EH. Platelet VEGF-A load independently predicted MC (p = 0.049) in addition to ?116G/A polymorphism (p = 0.035).ConclusionsAbnormal regulation of VEGF-A due to polymorphism at position ?116 might represent a genetic factor for increased VEGF-A production and MC in EH.     

Performance characteristics of a no-pretreatment,random access sirolimus assay for the Dimension® RxL clinical chemistry system

ObjectivesCurrent therapeutic drug monitoring methods for sirolimus require a manual pre-treatment step and batch analysis. We describe and validate a no-pretreatment, random access sirolimus assay for the Dimension® RxL clinical chemistry system from Siemens Healthcare Diagnostics Inc.Design and methodsWhole blood samples from renal transplant patients prescribed sirolimus were analyzed by the LC–MS/MS reference method, Abbott IMx and Dimension RxL methods in accordance with CLSI recommendations.ResultsThe Dimension sirolimus assay had a functional sensitivity of 2.0 ng/mL and repeatability and within-laboratory imprecision less than 12.6% at 3 ng/mL and less than 5% at 11–12 ng/mL. Least squares linear regression demonstrated the following relationships: RxL = 1.20(LC–MS/MS) – 0.70, r = 0.95 and RxL = 1.33(IMx) – 0.75, r = 0.96.ConclusionsThe Dimension sirolimus assay correlates well with the LC–MS/MS reference and IMx immunoassay methods and has the advantage of random access analysis without a manual pre-treatment step.     

Establishment of reference intervals for soluble ST2 from a United States population

BackgroundSoluble ST2 (sST2) is a protein in the interleukin-1 receptor family secreted by myocytes in response to mechanical strain. Elevated sST2 is strongly prognostic in patients with heart failure.MethodssST2 was measured using the Presage? ST2 ELISA. Evaluation included imprecision, linearity, recovery, analytical sensitivity, limit of quantification, stability, and sample type comparisons. Gender-specific reference intervals were established from 245 male and 245 female serum specimens.ResultsAt sST2 concentrations of 11.6, 26.9, and 88.0 ng/mL, the within-day CV was 7.6, 2.4, and 3.8%, respectively and the total CV was 11.5, 14.0, and 6.3%, respectively. The assay was linear over a concentration range of 2.8–161.1 ng/mL (y = 0.95x + 2.25; R² = 0.997; Sy.x = 3.03). The limit of quantification was 3.3 ng/mL. sST2 was stable for 2 days at room temperature, 10 days at 4 °C, and 30 days at ?20 °C. Concentrations of sST2 were significantly higher in males compared to females (24.9 vs. 16.9 ng/mL; p < 0.0001) but were not correlated by age in either gender (r = ?0.07; p = 0.14). Reference intervals for sST2 were determined to be 8.6–49.3 and 7.2–33.5 ng/mL for males and females, respectively.ConclusionThe Presage? ST2 ELISA had acceptable performance characteristics for quantifying sST2 in serum or plasma. The assay is precise and linear over a wide sST2 concentration range and can measure low sST2 concentrations. Concentrations of sST2 are unaffected by age but are higher in males compared to females.     

Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers

ObjectivesProcalcitonin (PCT) is widely used for the diagnosis of bacterial infections. The aim of this study was to evaluate PCT as a tumor and as a prognostic marker in patients with primary lung cancer.Design and methodsWe retrospectively performed a PCT dosage in the frozen serum samples of 147 patients with pulmonary neoplasia for whom a test of neuron-specific enolase (NSE) had been conducted at the time of diagnosis.ResultsWe show that a PCT serum level above 0.15 ng/mL was independently linked to the presence of a neuroendocrine component in the tumor (HR = 5.809 95% CI [1.695–19.908] p: 0005). Thus, median PCT serum levels were significantly more elevated in small-cell lung cancers than in pulmonary adenocarcinomas: 0.33 ng/mL versus 0.07 ng/mL (p < 0.001). However, the diagnostic value of serum PCT levels for diagnosing carcinoma with a neuroendocrine component remains low (sensitivity 63.8%; specificity 71.9%). In this series, serum PCT levels were significantly more elevated in the presence of liver metastases: 0.37 ng/mL versus 0.09 ng/mL in the absence of liver metastasis (p < 0.001). In uni- and multivariate analyses, a serum PCT level above 0.15 ng/mL and the presence of metastases and of sepsis at the time of diagnosis were independent factors of unfavorable prognosis.ConclusionsSerum PCT is elevated in patients with lung cancer with neuroendocrine component or with liver metastases. As a consequence, in this population, PCT has a poor specificity for bacterial infection. At diagnosis, an elevated serum PCT is an independent predictive factor of bad prognosis.     

Serum levels of vaspin and visfatin in patients with coronary artery disease—Kozani study

BackgroundThe association of novel adipokines, vaspin and visfatin, with atherosclerosis is still obscure. The present study aimed to investigate the relationship of those adipokines with the existence as well as the extent of coronary artery disease (CAD), suggesting a link between adiposity and atherosclerosis.MethodsWe enrolled a total of 108 patients with angiographically proven stable, asymptomatic CAD and 65 healthy controls (HC) without cardiovascular diseases. The severity of CAD was assessed using coronary angiography by the Gensini score. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), vaspin and visfatin levels were assayed.ResultsSerum levels of vaspin were significantly lower in subjects with CAD [0.91 (0.44–1.29) ng/ml] than healthy controls [1.42 (0.96–2.42) ng/ml] (p = 0.009). Inversely, visfatin (p = 0.016) and hsCRP (p < 0.001) levels were considerably up-regulated in CAD vs HC group. Multivariate analysis demonstrated decreased vaspin and increased visfatin levels to correlate with CAD presence, independent of other cardiovascular risk factors (p < 0.05). Standard multiple regression revealed HDL, LDL-C and vaspin to be independent determinants of Gensini score (R² = 0.189, p = 0.019). Notably, statin-free patients had even lower vaspin levels compared to statin users (p = 0.018).ConclusionsDecreased vaspin and increased visfatin serum levels were observed in asymptomatic patients with CAD. Low vaspin concentrations seemed to correlate with CAD severity.     

The role of foot self-care behavior on developing foot ulcers in diabetic patients with peripheral neuropathy: A prospective study

BackgroundAlthough foot self-care behavior is viewed as beneficial for the prevention of diabetic foot ulceration, the effect of foot self-care behavior on the development of diabetic foot ulcer has received little empirical investigation.ObjectiveTo explore the relationship between foot self-care practice and the development of diabetic foot ulcers among diabetic neuropathy patients in northern Taiwan.MethodsA longitudinal study was conducted at one medical center and one teaching hospital in northern Taiwan.ParticipantsA total of 295 diabetic patients who lacked sensitivity to a monofilament were recruited. Five subjects did not provide follow-up data; thus, only the data of 290 subjects were analyzed. The mean age was 67.0 years, and 72.1% had six or fewer years of education.MethodsData were collected by a modified version of the physical assessment portion of the Michigan Neuropathy Screening Instrument and the Diabetes Foot Self-Care Behavior Scale. Cox regression was used to analyze the predictive power of foot self-care behaviors.ResultsA total of 29.3% (n = 85) of diabetic neuropathy patients developed a diabetic foot ulcer by the one-year follow-up. The total score on the Diabetes Foot Self-Care Behavior Scale was significantly associated with the risk of developing foot ulcers (HR = 1.04, 95% CI = 1.01–1.07, p = 0.004). After controlling for the demographic variables and the number of diabetic foot ulcer hospitalizations, however, the effect was non-significant (HR = 1.03, 95% CI = 1.00–1.06, p = 0.061). Among the foot self-care behaviors, lotion-applying behavior was the only variable that significantly predicted the occurrence of diabetic foot ulcer, even after controlling for demographic variables and diabetic foot ulcer predictors (neuropathy severity, number of diabetic foot ulcer hospitalizations, insulin treatment, and peripheral vascular disease; HR = 1.19, 95% CI = 1.04–1.36, p = 0.012).ConclusionsAmong patients with diabetic neuropathy, foot self-care practice may be insufficient to prevent the occurrence of diabetic foot ulcer. Instead, lotion-applying behavior predicted the occurrence of diabetic foot ulcers in diabetic patients with neuropathy. Further studies are needed to explore the mechanism of lotion-applying behavior as it relates to the occurrence of diabetic foot ulcer.     

Association between myeloperoxidase polymorphisms and its plasma levels with severity of coronary artery disease

ObjectivesMyeloperoxidase (MPO) polymorphism ?463 has been related to higher cardiovascular risk. This study was conducted to test whether the MPO promoter polymorphism ?463A/G and MPO plasma levels are associated with coronary artery disease (CAD) severity.Design and methodsPatients submitted to elective coronariography were enrolled, CAD severity was assessed and blood samples collected to identify the MPO polymorphism and its plasma levels.ResultsGenotypes were determined in 118 patients. Among these patients, 12 (10%) were homozygous for AA, 69 (58%) for GG and 37 (32%) were heterozygous. Mean MPO plasma levels were 8.6 ± 4.7 ng/mL for AA, 8.6 ± 7.0 ng/mL for AG and 9.4 ± 5.6 ng/mL for GG genotypes. The CAD severity was not associated with MPO genotypes (p = 0.43), however, patients with higher CAD score presented higher MPO levels (p = 0.02).ConclusionWe found no association between MPO polymorphism and CAD severity, although a relation was observed for MPO plasma levels and extension of CAD.     

Effects of a self-management program on patients with early-stage chronic kidney disease: A pilot study

BackgroundWithout intervention, renal function deteriorates in patients with chronic kidney disease (CKD).AimThis pilot study aimed to develop a self-management education program based on self-regulation theory and to evaluate its effects on self-efficacy, self-management behavior, and CKD progression among patients with early-stage CKD.MethodsIn this single-group, pretest–posttest, repeated-measures, longitudinal study, participants underwent baseline pretesting (T₀) and posttesting at 3 (T₁), 6 (T₂), and 12 (T₃) months after a 5-week group-session self-management program.ResultsSelf-efficacy increased significantly at T₂ (χ² = 8.97, p = .02) and T₃ (χ² = 10.71, p = .01) compared with T₀, but self-management behavior did not. A marginally significant decrease in serum creatinine levels was observed from T₀ to T₃ (χ² = 6.29, p = .07) but estimated glomerular filtration rates remained stable throughout the 12-month period.ConclusionsThe results of this empirical study suggest that the theory-based intervention is feasible and has potential efficacy in retarding CKD progression.     

The predictive value of NT-proBNP and hs-TnT for risk of death in cardiac surgical patients

BackgroundEuropean System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is used for risk stratification before cardiac surgery, but whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) may add prognostic information to EuroSCORE II is not known.MethodsPreoperative (n = 640) and postoperative (n = 629) blood samples were available from cardiac surgical patients with 961-day follow-up (FINNAKI Heart study; cohort #1). The accuracy of a parsimonious risk model with NT-proBNP measurements was also tested in 90 patients with respiratory failure after cardiac surgery (FINNALI study; cohort #2).ResultsSixty-one patients (9.5%) died during follow-up in cohort #1. Preoperative NT-proBNP and hs-TnT concentrations correlated (rho = 0.58; p < 0.001) and were higher in non-survivors compared to survivors: median 2027 (Q1-3 478-5387) vs. 373 (134–1354) ng/L [NT-proBNP] and 39 (16–191) vs. 13 (8–32) ng/L [hs-TnT]; p < 0.001 for both. Preoperative NT-proBNP concentrations were associated with time to death after adjustment for EuroSCORE II (HR [_lnNT-proBNP] 1.33 [95% CI 1.08–1.64]), p = 0.008 and reclassified patients on top of EuroSCORE II (net reclassification index 0.39 [95% CI 0.14–0.64], p = 0.003). Pre- and postoperative NT-proBNP concentrations were closely correlated (rho = 0.80, p < 0.001) and postoperative NT-proBNP concentrations were also associated with long-term mortality after adjustment for EuroSCORE II. A parsimonious risk model that included age, creatinine clearance, chronic pulmonary disease, and NT-proBNP measurements provided comparable prognostic accuracy as EuroSCORE II in cohort #1 and #2 for risk of long-term mortality. hs-TnT measurements did not add to NT-proBNP measurementsConclusionNT-proBNP measurements could improve and simplify risk prediction in cardiac surgical patients.     

Serum Fetuin-A and Pentraxin3 in hemodialysis and renal transplant patients

ObjectiveThe aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients.MethodSerum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods.ResultsIn the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09–20.36) ng/mL vs. 1.65(0.24–7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75–81.48) ng/mL vs. 38.76(22.26–89.07) ng/mL, p = 0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1–8.50) mg/L vs. 1.1(0.1–7.9) mg/L, p = 0.003].ConclusionAlthough our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.     

Serum adipocyte fatty acid binding proteins and adiponectin in patients with coronary artery disease: The significance of A-FABP/adiponectin ratio

BackgroundAdipocyte fatty acid binding protein (A-FABP) and adiponectin have been shown to play important roles in atherosclerosis. We investigated serum A-FABP, adiponectin and A-FABP/adiponectin ratio in patients with coronary artery disease (CAD).MethodsA total of 340 subjects who underwent coronary angiography (CAG) were classified into CAD group (n = 211) and non-CAD group (n = 129) according to the CAG. Serum A-FABP and adiponectin concentrations were determined by enzyme-linked immunosorbent assays.ResultsCAD patients tend to have higher A-FABP concentrations than non-CAD subjects, the difference is significant only between female CAD patients and controls [22.8 (18.6–25.7) ng/ml vs 18.1 (15.6–21.8) ng/ml, P = 0.008]. Serum A-FABP concentration was independently associated with Gensini scores in female subjects (P = 0.018). CAD patients have significant higher serum A-FABP/adiponectin ratio [1.51 ± 0.05 vs 0.89 ± 0.03 ng/μg, P < 0.01] than controls in both genders.ConclusionsSerum A-FABP is associated with CAD more closely in female than in male. The A-FABP/adiponectin ratio may be a more useful indicator for CAD than A-FABP or adiponectin alone.     

Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case–control cross-sectional study

ObjectiveVascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).Design and methodsThe association of KDR − 604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case–control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD.ResultsA significantly higher frequency of the CC genotype of the KDR − 604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p = 0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the − 604CC genotype compared to those with other (CT + TT) genotypes (73.8 ± 22.1 ng/l vs. 58.1 ± 18.5 ng/l; p < 0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the − 604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR = 1.6; 95% CI = 1.1–2.1; p = 0.022).ConclusionThe present study demonstrates that the CC genotype of the KDR − 604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.     

Association of G-2548A LEP polymorphism with plasma leptin levels in Tunisian obese patients

ObjectivesThe aim of this study was to examine the association of the G-2548A polymorphism of the human leptin gene (LEP) with body mass index (BMI), plasma leptin, insulin, and lipid parameters in a sample of Tunisian population.Design and methodsTwo hundred and twenty nine obese patients (BMI ≥ 30 kg/m²) were screened and compared to 251 normal weight subjects (BMI < 25 kg/m²). The human leptin gene promoter G-2548A genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease CfoI.ResultsIn the entire study sample, carriers of -2548A allele had significantly lower leptin levels than homozygous for -2548G allele (14.28 ± 9.10 ng/mL vs. 18.27 ± 12 ng/mL, p < 0.001 respectively) adjusted for BMI and gender. In obese patients but not control, subjects carrying the -2548A allele exhibited lower leptin levels than those with GG genotype (16.96 ± 8.27 ng/mL vs. 21.37 ± 11.72 ng/mL, p = 0.001 respectively) adjusted for BMI and gender. In this group, carriership of the -2548A allele was identified, by multiple linear regression models, as significant independent predictor for leptin levels variability. Separate analyses by gender revealed that only in obese women, the -2548A allele was found to be associated with lower leptin levels independently of BMI (p = 0.004).ConclusionsThe present study showed that G-2548A LEP polymorphism is associated with lower leptin levels in Tunisian obese women.     

Circadian change of serum concentration of small dense LDL-cholesterol in type 2 diabetic patients

BackgroundType 2 diabetic patients have a higher risk of atherosclerosis than non-diabetic subjects. This difference may be attributable to increased levels of small dense low-density lipoprotein-cholesterol (sLDL-C) in diabetic patients. As the sLDL-C concentration is elevated in hypertriglyceridemia, which is exaggerated postprandially, we examined whether the sLDL-C level increases postprandially in type 2 diabetes.MethodsWe obtained 7 blood samples (30 min before and 2 h after each meal, and at midnight) from 15 patients with diabetes and ten normal controls. Following the precipitation of very low-density lipoprotein and large buoyant LDL (bLDL) with heparin–Mg²⁺, the sLDL-C concentration was determined as the cholesterol concentration by a homogeneous assay.ResultsThe fasting sLDL-C concentration was 60.3% higher in the diabetic patients than in the controls (1.01 ± 0.21 vs. 0.63 ± 0.21 mmol/l, p < 0.001). The sLDL-C concentrations in both groups were highest in the fasting state, decreased after breakfast, and remained low until midnight. The maximal reduction in the absolute sLDL-C concentration was 56.5% greater in the diabetic patients than in the controls (0.36 ± 0.13 vs. 0.23 ± 0.16 mmol/l, p < 0.05). Thus, the sLDL-C/bLDL-cholesterol (bLDL-C) ratio was reduced with increases in bLDL-C.ConclusionsThe sLDL-C concentration decreases postprandially in diabetes. This absolute reduction in sLDL-C may contribute to an acceleration of atherosclerosis in diabetic patients.     

Cannabinoids for spasticity due to multiple sclerosis or paraplegia: A systematic review and meta-analysis of randomized clinical trials

ObjectivesSpasticity remains highly prevalent in patients with spinal cord injury and multiple sclerosis. To summarize the effects of cannabinoids compared with usual care, placebo for spasticity due to multiple sclerosis (MS) or paraplegia.MethodsSearches of MEDLINE, EMBASE, CENTRAL and LILACS to March 2017 were performed to identify randomized controlled trials. The primary outcomes were spasticity and spasm frequency. The criteria were any patient with MS and spasticity affecting upper or lower limbs or both, and that had a confirmed diagnosis of MS based on validated criteria, or however defined by the authors of the included studies.Results16 trials including 2597 patients were eligible. Moderate-certainty evidence suggested a non-statistically significant decrease in spasticity (standardized mean difference (SMD) 0.36 [confidential interval (CI) 95% −0.17 to 0.88; p = 0.18; I2 = 88%]), and spasm frequency (SMD 0.04 [CI 95% −0.15 to 0.22]). There was an increase in adverse events such as dizziness (risk ratio (RR) 3.45 [CI 95% 2.71–4.4; p = 0.20; I2 = 23%]), somnolence (RR 2.9 [CI 95% 1.98–4.23; p = 0.77; I2 = 0%]), and nausea (RR 2.25 [CI 95% 1.62–3.13; p = 0.83; I2 = 0%]).ConclusionsThere is moderate certainty evidence regarding the impact of cannabinoids in spasticity (average 0.36 more spasticity; 0.17 fewer to 0.88 more) due to multiple sclerosis or paraplegia, and in adverse events such as dizziness (419 more dizziness/1000 over 19 weeks), somnolence (127 more somnolence/1000 over 19 weeks), and nausea (125 more somnolence/1000 over 19 weeks).     

Progestin-dependent effect of oral contraceptives on plasma aldosterone/renin ratio

ObjectivesEstrogens in oral contraceptives (OC) may influence plasma aldosterone/plasma renin activity (ALD/PRA) and plasma aldosterone/plasma renin concentration (ALD/DRC) ratios, but the effect of progestins on these ratios has not been sufficiently studied so far.Design and methodsPRA (RIA, DiaSorin), DRC and ALD (IRMA, RIA, Beckman Coulter) were measured, then ALD/PRA and ALD/DRC were calculated in 86 healthy normotensive women (aged 27.3 ± 7.5 years), 63 using progestin-containing OC: either gestodene (GTD, n = 25), desogestrel (DSG, n = 22) or drospirenone (DRSP, n = 16). 23 OC-nonusers served as control.ResultsData are presented as median and lower and upper quartiles. PRA, DRC and ALD levels were higher (p < 0.001) in the DRSP group [3.1 (1.5 3.8) ng/mL/h, 25.2 (9.8 30.4) ng/L and 43.7 (28.0 61.6) ng/dL, respectively], than in the DSG [1.4 (1.1 2.1) ng/mL/h, 8.3 (6.8 12.3) ng/L and 11.5 (7.2 16.6) ng/dL], GTD [1.2 (0.8 2.2) ng/mL/h, 8.0 (4.8 10.5) ng/L, and 13.4 (7.7 22.1) ng/dL] and control [1.3 (0.7 1.6) ng/mL/h, 12.2 (7.5 21.7) ng/L, and 10.0 (4.4 14.7) ng/dL] groups. Cases of falsely elevated ALD/PRA and ALD/DRC ratios [7 (11%) and 12 cases (19%) respectively] were only found in OC users but not in the control group. In the DSG and GTD groups, but not in the DRSP group falsely elevated ALD/PRA occurred less frequently than falsely elevated ALD/DRC.ConclusionsIn OC-users falsely elevated ALD/PRA and especially ALD/DRC are a common finding, particularly when the OC contains DSG or GTD. Therefore, for OC-users method- and progestin-type specific cut-off levels should be established.     

Are high-sensitivity cardiac troponin I values stable between preoperative visit and day of non-cardiac surgery?

BackgroundIt is unclear if cardiac troponin values are stable in patients prior to undergoing non-cardiac surgery, or if they tend to rise towards the day of surgery.MethodsIn this small pilot study (n = 18) among patients with cardiac risk undergoing non-cardiac surgery, we determined if high-sensitivity cardiac troponin I (hscTnI) changes between the preoperative clinic visit and the day of surgery. HscTnI was measured on an Abbott Architect STAT (Abbott Laboratories, USA) platform.ResultsThe mean duration between preoperative clinic visit and day of surgery was 8.7 ± 2.8 (SD) days. Median hscTnI was 3.4 ng/L [2.0–4.8, IQR] at the preoperative visit and 2.8 ng/L [2.3–4.4] on the day of surgery (mean difference − 0.24 ng/L, 95% CI - 0.73 to 0.24 ng/L, p = 0.30). Only one patient had a large change (> 50%) along with symptoms.DiscussionEvidence from this small study suggests that cardiac troponin values are stable in most high-risk patients, absent clinical events, within 10 days prior to non-cardiac surgery.     

Multi-center evaluation of a commercial Kit for tacrolimus determination by LC/MS/MS

ObjectivesA multi-center evaluation (3 sites) of the LC/MS/MS MassTrak? tacrolimus Immunosuppressants Kit (Kit) was undertaken.Design and methodsTen aspects of the analytical performance of the Kit were investigated based on FDA and CLSI guidelines.ResultsThe linear analytical range of the procedure was between 0.68 and 31.7 ng/mL. Within-run and total imprecision were < 6% and < 8% (n = 240), respectively. Recoveries of tacrolimus added to clinical samples that contained between 5 and 10 ng/mL of tacrolimus before addition were 99, 102 and 105% at 5.0, 10 and 20 ng/mL, respectively. Comparison of in-house and Kit procedures in samples from liver (n = 50–58) or kidney (n = 50 or 51) transplant recipients yielded method mean biases between ? 2.0 and + 10.7% at 5 and 15 ng/mL.ConclusionsThis evaluation indicates that the Kit is suitable for the monitoring of tacrolimus in kidney and liver transplant recipients.