Pavlína Kušnierová

Comparison of the Efficacy of Paclitaxel-Eluting Balloon Catheters and Everolimus-Eluting Stents in the Treatment of Coronary In-Stent Restenosis The Treatment of In-Stent Restenosis Study

Background—The aim of this prospective randomized noninferiority study was to compare the efficacy of paclitaxel-eluting balloon (PEB) catheters and everolimus-eluting stents (EES) in the treatment of bare metal stent restenosis. Methods and Results—A total of 136 patients were enrolled in the study. Each treatment group included 68 patients with 74 in-stent restenotic lesions. The primary end point was in-segment late lumen loss (LLL) at 12 months. Secondary end points were the incidence of binary in-stent restenosis and 12-month major adverse cardiac events. The 2-sided 95% confidence interval of LLL difference between treatments (0.149–0.558) was greater than noninferiority margin (0.12), which demonstrates both noninferiority and superiority of PEB treatment. Furthermore, the PEB group had significantly less 12-month LLL than the EES group (0.02 versus 0.19 mm; P=0.0004). The difference in the incidence of repeated binary restenosis (8.7% versus 19.12%; P=0.078) and 12-month major adverse cardiac events (10.29% versus 19.12%; P=0.213) was not significant. The 12-month LLL was significantly less in the PEB group and also in subgroups with in-stent restenosis >10 mm (0.05 versus 0.26 mm; P=0.0002) and artery diameter <3 mm (0.05 versus 0.16 mm; P=0.003) compared with the EES groups, but not in the subgroup of patients with diabetes mellitus (P=0.254). In the EES group, repetitive binary restenosis had a significantly greater chance of occurring (odds ratio=3.132; 95% confidence interval, 1.058–9.269; P=0.039), even when adjusting for other risk factors. Conclusions—Treatment of bare metal stent restenosis using PEB led to significantly less 12-month LLL than the implantation of second-generation EES. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01735825.

Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency.

AIMS We sought to identify biochemical predictors that indicate susceptibility to in-stent restenosis (ISR) after coronary artery bare-metal stenting. METHODS A total of 111 consecutive patients with post-percutaneous coronary intervention (PCI) in-stent restenosis of a target lesion within 12 months were matched for age, sex, vessel diameter, and diabetes with 111 controls without post-PCI ISR. Plasma or serum levels of biochemical markers were measured: matrix metalloproteinases (MMP) 2, 3, 9; myeloperoxidase (MPO); asymmetric dimethylarginine (ADMA); lipoprotein (a) (Lp[a]); apolipoproteins E and D (ApoE and D); and lecitin-cholesterol acyltransferase (LCAT). Multivariable logistic regression association tests were performed. RESULTS Increased plasma MMP-3 (OR: 1.013; 95% CI: 1.004-1.023; P = 0.005), MMP-9 (OR: 1.014; 95% CI: 1.008-1.020; P < 0.0001) or MPO (OR: 1,003; 95% CI: 1.001-1.005; P = 0.002) was significantly associated with increased risk of ISR. Increased levels of ADMA (OR: 0.212; 95% CI: 0.054-0.827; P = 0.026), ApoE (OR: 0.924; 95% CI: 0.899-0.951; P < 0.0001), ApoD (OR: 0.919; 95% CI: 0.880-0.959; P = 0.0001), or LCAT (OR: 0.927; 95% CI: 0.902-0.952; P < 0.0001) was associated with risk reduction. No correlation was found between plasma MMP-2 or Lp (a) and ISR risk. CONCLUSIONS Increased levels of MMP-3, MMP-9, and MPO represent predictors of ISR after bare-metal stent implantation. In contrast, increased ADMA, LCAT, and Apo E and D indicate a decreased in-stent restenosis occurrence.

Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting.

Objectives We aimed to compare various methods for free light chain (fLC) quantitation in cerebrospinal fluid (CSF) and serum and to determine whether quantitative CSF measurements could reliably predict intrathecal fLC synthesis. In addition, we wished to determine the relationship between free kappa and free lambda light chain concentrations in CSF and serum in various disease groups. Methods We analysed 166 paired CSF and serum samples by at least one of the following methods: turbidimetry (Freelite™, SPAPLUS), nephelometry (N Latex FLC™, BN ProSpec), and two different (commercially available and in-house developed) sandwich ELISAs. The results were compared with oligoclonal fLC detected by affinity-mediated immunoblotting after isoelectric focusing. Results Although the correlations between quantitative methods were good, both proportional and systematic differences were discerned. However, no major differences were observed in the prediction of positive oligoclonal fLC test. Surprisingly, CSF free kappa/free lambda light chain ratios were lower than those in serum in about 75% of samples with negative oligoclonal fLC test. In about a half of patients with multiple sclerosis and clinically isolated syndrome, profoundly increased free kappa/free lambda light chain ratios were found in the CSF. Conclusions Our results show that using appropriate method-specific cut-offs, different methods of CSF fLC quantitation can be used for the prediction of intrathecal fLC synthesis. The reason for unexpectedly low free kappa/free lambda light chain ratios in normal CSFs remains to be elucidated. Whereas CSF free kappa light chain concentration is increased in most patients with multiple sclerosis and clinically isolated syndrome, CSF free lambda light chain values show large interindividual variability in these patients and should be investigated further for possible immunopathological and prognostic significance.

Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal IgG

AIMS To compare the sensitivity and specificity of CSF-restricted oligoclonal IgG and free light chains as markers of multiple sclerosis and other inflammatory neurological diseases. METHODS 196 paired CSF and serum samples were examined for oligoclonal IgG and oligoclonal free light chains. The sensitivity and specificity of the tests were calculated and optimal cut-offs for the number of CSF-restricted oligoclonal bands were then determined by analysis of receiver operating characteristic curves. RESULTS Optimal cut-off values were ≥5 IgG bands for multiple sclerosis, ≥4 IgG bands for inflammatory neurological disease, ≥6 free κ, and ≥2 free λ bands for both purposes. Using these cut-off values, sensitivities and specificities for multiple sclerosis were 83.8% and 91.3% for IgG, 83.8% and 81.0% for free κ, and 67.6% and 75.4% for free λ. For inflammatory neurological disease, sensitivities and specificities were 60.8% and 95.7% for IgG, 69.6% and 92.6% for free κ, and 64.8% and 86.2% for free λ. CONCLUSIONS Although exact cut-off values may vary according to method, reporting borderline results as positive, may compromise the specificity of the test and should be avoided.. The detection of intrathecal free light chain synthesis may be of value especially when the oligoclonal IgG test is negative or borderline, even though its specificity is slightly lower.

Quantitation of free light chains in the cerebrospinal fluid reliably predicts their intrathecal synthesis.

Background The results of free light chains quantitation in the cerebrospinal fluid were recently compared with the presence of cerebrospinal fluid-restricted oligoclonal IgG, but not oligoclonal free kappa light chains and oligoclonal free lambda light chains. We therefore aimed to compare the performance of the quantitative tests with the qualitative one for the same molecule. Methods Seventy-five paired cerebrospinal fluid and serum samples were analysed for oligoclonal IgG, oligoclonal free kappa light chains and oligoclonal free lambda light chains. Cerebrospinal fluid and serum free kappa and lambda light chains were quantified using Freelite™ kits on SPA Plus analyzer. ROC curves were analysed for the prediction of intrathecal synthesis and compared for cerebrospinal fluid concentration, cerebrospinal fluid/serum quotient (QfLC) and index (QfLC/QAlbumin). The presence of cerebrospinal fluid-restricted oligoclonal free kappa light chains and oligoclonal free lambda light chains bands was used as reference. Results No statistically significant differences were observed among cerebrospinal fluid concentration, QfLC and index for the prediction of free light chain intrathecal synthesis. Each parameter was able to predict the occurrence of cerebrospinal fluid-restricted oligoclonal free light chain bands (AUCs 0.932–0.999). However, we noted elevated cerebrospinal fluid free light chain concentrations in the absence of cerebrospinal fluid-restricted oligoclonal free light chain bands in two patients with very high serum free light chain values. Conclusions Quantitation of cerebrospinal fluid free light chains reliably predicts their intrathecal synthesis. Yet, cerebrospinal fluid/serum quotient may still be preferred to correct for high serum free light chain concentrations. An appropriate formula should be sought to correct for blood–cerebrospinal fluid barrier status.

Reference intervals of plasma matrix metalloproteinases 2, 3, and 9 and serum asymmetric dimethylarginine levels

Abstract Objective. The present study aimed to verify the reference intervals of plasma matrix metalloproteinases (MMPs) 2, 3, and 9 and serum asymmetric dimethylarginine (ADMA) in a healthy population with an average age corresponding to that of patients with cardiovascular diseases. Methods. The study included 180 healthy volunteers. Plasma MMP-2, MMP-3, MMP-9, and serum ADMA levels were determined using an enzyme-linked immunosorbent assay. These levels were analyzed for association with age and gender. The Cbstat5, R software, and NCSS 2007 programs were used for statistical analysis. Results. The average volunteer age was 47.4 years in the group in which MMP-3 and ADMA were analyzed, 40.3 years in the MMP-9 group, and 47.8 years for the MMP-2 group. Serum ADMA levels were determined to be independent of age and gender. Plasma MMP-2 levels were significantly correlated with age (p = 0.001), with lower levels detected in persons ≤ 49 years of age. Plasma MMP-3 was significantly associated with both age (p < 0.0001) and gender, with lower levels detected in persons of ≤ 47 years of age and among women. Plasma MMP-9 levels were not age dependent, but were associated with gender (p = 0.014), showing lower levels in women. Conclusions. Reference intervals of heparin-plasma MMP-2, MMP-3, and MMP-9 and serum ADMA levels were determined. MMP-2 and MMP-3 levels were found to be age dependent, and MMP-3 and MMP-9 levels were gender dependent.

Response by Pleva et al to Letter Regarding Article, “Comparison of the Efficacy of Paclitaxel-Eluting Balloon Catheters and Everolimus-Eluting Stents in the Treatment of Coronary In-Stent Restenosis: The Treatment of In-Stent Restenosis Study”

We read with great interest the letter by Alfonso et al with comments to our study.1We know the interesting results of the RIBS V study (Restenosis Intra-Stent of Bare-Metal Stents: Paclitaxel-Eluting Balloon vs. Everolimus-Eluting Stent).2 Contrary to RIBS V, we used everolimus-eluting stents (EES) with platinum–chromium metallic platform and a different primary endpoint, 12-month late lumen loss (LLL) in our study.1 LLL and minimal lumen diameter (MLD) often serve as surrogate endpoint in percutaneous coronary intervention studies. We suppose that MLD values are highly dependent on previous vessel diameter, whereas LLL rather reflects thedifference …

Chemiluminescent detection of oligoclonal immunoglobulins after isoelectric focusing and affinity-mediated immunoblotting

BACKGROUND AND AIMS Detection of oligoclonal IgG (o-IgG) in the cerebrospinal fluid (CSF) not found in serum is the principal laboratory test to support a diagnosis of multiple sclerosis. The aim of this study was to compare chemiluminescent and chromogenic detection of oligoclonal immunoglobulins in the cerebrospinal fluid and serum after their separation by means of isoelectric focusing followed by immunoblotting. METHODS A set of experiments was designed to detect oligoclonal immunoglobulins by means of alkaline phosphatase BCIP/NBT substrate and chemiluminescent peroxidase substrate. RESULTS Based on visual evaluation of signals, chemiluminescent detection requires about a 4 times lower amount of applied protein than very sensitive BCIP/NBT chromogenic detection. Very good correlation between methods has been shown for oligoclonal IgG. Antigen-specific oligoclonal IgG could be demonstrated by both methods although the pattern was clearer using chemiluminescence. In one patient, oligoclonal IgD bands barely visible by BCIP/NBT were convincingly demonstrated by chemiluminescence. CONCLUSION Chemiluminescent detection is a feasible option for oligoclonal immunoglobulin detection and could be used in cases when the sensitivity needs to be improved. Further studies and method optimisation are warranted.

Quantitation of IgG kappa and IgG lambda in the cerebrospinal fluid by sandwich ELISA method

Abstract IgG kappa and IgG lambda concentrations were quantified in 96 paired CSF and sera using Hevylite™ antibodies in an in-house developed sandwich ELISA method. In 56 of these samples, the results were compared with a qualitative isoelectric focusing/affinity-mediated immunoblotting assay for oligoclonal IgG kappa and IgG lambda. Normal IgG kappa/lambda ratio in the CSF was the same as in serum. In 19/33 patients with intrathecal oligoclonal IgG synthesis, skewed IgG kappa/lambda ratio was observed (increased in 16 and decreased in 3 cases). The analysis of light chain composition of intrathecally synthesised immunoglobulins could contribute to our understanding of intrathecal humoral immune response, although its diagnostic utility is limited.