Miłosław Cnotliwy

The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: A systematic review and individual patient data meta-analysis

OBJECTIVES The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. BACKGROUND Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. METHODS We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. RESULTS Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. CONCLUSIONS Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.

Postoperative B-type Natriuretic Peptide for Prediction of Major Cardiac Events in Patients Undergoing Noncardiac Surgery: Systematic Review and Individual Patient Meta-analysis.

Background:It is unclear whether postoperative B-type natriuretic peptides (i.e., BNP and N-terminal proBNP) can predict cardiovascular complications in noncardiac surgery. Methods:The authors undertook a systematic review and individual patient data meta-analysis to determine whether postoperative BNPs predict postoperative cardiovascular complications at 30 and 180 days or more. Results:The authors identified 18 eligible studies (n = 2,051). For the primary outcome of 30-day mortality or nonfatal myocardial infarction, BNP of 245 pg/ml had an area under the curve of 0.71 (95% CI, 0.64–0.78), and N-terminal proBNP of 718 pg/ml had an area under the curve of 0.80 (95% CI, 0.77–0.84). These thresholds independently predicted 30-day mortality or nonfatal myocardial infarction (adjusted odds ratio [AOR] 4.5; 95% CI, 2.74–7.4; P < 0.001), mortality (AOR, 4.2; 95% CI, 2.29–7.69; P < 0.001), cardiac mortality (AOR, 9.4; 95% CI, 0.32–254.34; P < 0.001), and cardiac failure (AOR, 18.5; 95% CI, 4.55–75.29; P < 0.001). For greater than or equal to 180-day outcomes, natriuretic peptides independently predicted mortality or nonfatal myocardial infarction (AOR, 3.3; 95% CI, 2.58–4.3; P < 0.001), mortality (AOR, 2.2; 95% CI, 1.67–86; P < 0.001), cardiac mortality (AOR, 2.1; 95% CI, 0.05–1,385.17; P < 0.001), and cardiac failure (AOR, 3.5; 95% CI, 1.0–9.34; P = 0.022). Patients with BNP values of 0–250, greater than 250–400, and greater than 400 pg/ml suffered the primary outcome at a rate of 6.6, 15.7, and 29.5%, respectively. Patients with N-terminal proBNP values of 0–300, greater than 300–900, and greater than 900 pg/ml suffered the primary outcome at a rate of 1.8, 8.7, and 27%, respectively. Conclusions:Increased postoperative BNPs are independently associated with adverse cardiac events after noncardiac surgery.

Enhanced matrix-degrading proteolytic activity within the thin thrombus-covered wall of human abdominal aortic aneurysms

OBJECTIVE The maintenance of an arterial elastins integrity is essential in the prevention of abdominal aortic aneurysm (AAA) development. So far, the effect of intraluminal thrombus (ILT) thickness on the elastolytic activity within the AAA wall has not been studied. In the present study the hypothesis that thin thrombus is associated with enhanced proteolytic activity within human AAA wall was investigated. METHODS The specimens for analysis, from both thin (< or = 10 mm) thrombus-covered and thick (> or = 25 mm) thrombus-covered wall, had been taken from 40 patients undergoing elective repair of AAA. We evaluated neutrophil elastase activity with the enzymatic assay. Concentrations of active matrix metalloproteinase-9 (MMP-9), total matrix metalloproteinase-8 (MMP-8), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were measured by ELISA. Biochemical parameters were compared with the Wilcoxon signed-rank test. RESULTS Statistical analysis showed that the activity of elastase (P<0.0001) as well as concentrations of active MMP-9 (P=0.001), total MMP-8 (P<0.0001) and active MMP-9/total TIMP-1 ratio (P=0.002) were significantly higher in the thin thrombus-covered wall. Furthermore the TIMP-1 was found to have a lower concentration in the thin thrombus-covered in comparison with the thick thrombus-covered wall (P=0.003). There was a significant positive correlation between measurements in AAA wall sites with thin and thick thrombus for elastase, TIMP-1, MMP-9/TIMP-1 ratio, and a borderline correlation was observed for MMP-8. Active MMP-9 concentration did not correlate between sites. CONCLUSION The current study demonstrates the differentiation of protease activity within the same AAA wall and its enhancement within the thin thrombus-covered aneurysm wall.

Elastin degradation within the abdominal aortic aneurysm wall – relationship between intramural pH and adjacent thrombus formation

Background  The natural history of abdominal aortic aneurysm (AAA) is wall remodelling potentially leading to a final rupture. The pathogenesis of AAA appears to be multifactorial. The aim of this pilot prospective study was to assess the relationship between the thickness of the thrombus within the abdominal aortic aneurysm, intramural pH and local elastin degradation.

Abdominal Aortic Aneurysm: Association Between Haptoglobin Phenotypes, Elastase Activity, and Neutrophil Count in the Peripheral Blood

To investigate the role of genetic factors on susceptibility to atherosclerotic arterial disease, the influence of haptoglobin phenotypes (Hp) on serum elastase activity, neutrophil count, and elastin concentration in the aorta was measured in patients with abdominal aortic aneurysm (AAA; n=52) and aortoiliac atherosclerotic occlusive disease (AOD; n=37). Findings (serum elastase activity, peripheral blood neutrophil count) were compared to a control group (CG) of 37 subjects without atherosclerosis. Hp phenotyping performed by starch-gel electrophoresis produced a haptoglobin-hemoglobin complex of three phenotypes: Hp1-1, Hp2-2, and Hp2-1. Distribution of Hp phenotypes was similar in the three study groups (AAA, AOD, CG). Significant increases in serum elastase activity and neutrophil count was measured in Hp2-1 phenotype of AAA patients. Although the aorta wall of aneurysm patients contained less (p<0.001) elastin than that of AOD patients, no significant difference of aorta elastin concentration between the three Hp phenotypes, including Hp2-1, was measured. The postulated association of AAA susceptibility with Hp2-1 phenotype was supported by the study data that demonstrated an increase in serum elastase activity in patients undergoing AAA repair.

N-terminal pro-B-type Natriuretic Peptides Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds

Background:N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. Methods:The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. Results:The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. Conclusions:Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms

Background: The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Methods: Factor levels were measured using enzyme‐linked immunosorbent assay of protein extract. Results: Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus‐covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of &agr;2‐antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). Conclusions: These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Clinical Relevance: Intraluminal thrombus (ILT) and abdominal aortic aneurysm wall thickness vary significantly across each individual aneurysm. The study suggests that intensified coagulation and probably local fibrinolysis in thin ILT segments may be part of a chain reaction leading to the destruction of the aneurysm wall and, as a result, its rupture. Considering the significant ability of coagulative and fibrinolytic systems to construct ILT as well as to regulate extracellular matrix proteolysis of the abdominal aortic aneurysm wall, the spatiotemporal distribution of components of these two systems represents data that may improve patient‐specific models of aneurysmal progression and rupture risk in the future.

An unusual case of aortic rupture after deployment of a bare stent in the treatment of aortic dissection in a patient with giant-cell arteritis

Giant-cell arteritis is associated with a higher risk of aortic aneurysm and aortic dissection formation. We present a women with aortic dissection type B treated with a stent graft and bare-metal stent implantation. After the stent deployment we noticed aortic rupture, which was successfully treated with implantation of an additional stent graft. This report highlights the difficulty of endovascular therapy in patients with giant-cell arteritis. We have to bear in mind that chronic inflammation of the aorta leads to a more fragile aortic wall than normal. We recommend the use of a stent graft over a bare-metal stent and gentle use of a balloon catheter.

Próba adaptacji kwestionariusza Self-Complete of Leeds Assessment of Neuropathic Symptoms and Signs dla polskiej populacji

Introduction: The Self-Complete of Leeds Assessment Neuropathic Symptoms and Signs (S-LANSS) questionnaire is a tool for screening patients with neuropathic pain, which can be completed without a physician’s assistance. Until now, a Polish version of the S -LANSS has not been available. The aim of the study was to translate the English version into the Polish language and to validate it for the Polish population. Materials and methods: A total of 101 subjects; 51 with chronic neuropathic pain in the course of different neurological diseases, and 50 patients with osteoarthritis and nociceptive pain were included in the study. All of them completed a version of the S -LANSS questionnaire translated into the Polish language. Test sensitivity and speciϐicity were calculated on the basis of statistical analysis. Results: The sensitivity of the S -LANSS scale with the cut -off of ≥11 points was 62%, and the speciϐicity was 77%. The estimated area under ROC curve AUC (95% CI) = 0.729 (0.63–0.809). Conclusions: The Polish version of S -LANSS could be used as a tool for screening patients with neuropathic pain. The diagnosis should be conϐirmed in neurological examination and other appropriate diagnostic methods.