Prognostic impact of admission high-sensitivity C-reactive protein in acute myocardial infarction patients with and without diabetes mellitus.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM. METHODS: We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint. RESULTS: Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients. CONCLUSIONS: This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.

Spectrum of Rare and Common Genetic Variants in Arrhythmogenic Cardiomyopathy Patients.

Arrhythmogenic cardiomyopathy (ACM) is a rare inherited disorder, whose genetic cause is elusive in about 50-70% of cases. ACM presents a variable disease course which could be influenced by genetics. We performed next-generation sequencing on a panel of 174 genes associated with inherited cardiovascular diseases on 82 ACM probands (i) to describe and classify the pathogenicity of rare variants according to the American College of Medical Genetics and Genomics both for ACM-associated genes and for genes linked to other cardiovascular genetic conditions; (ii) to assess, for the first time, the impact of common variants on the ACM clinical disease severity by genotype-phenotype correlation and survival analysis. We identified 15 (likely) pathogenic variants and 66 variants of uncertain significance in ACM-genes and 4 high-impact variants in genes never associated with ACM (ABCC9, APOB, DPP6, MIB1), which deserve future consideration. In addition, we found 69 significant genotype-phenotype associations between common variants and clinical parameters. Arrhythmia-associated polymorphisms resulted in an increased risk of arrhythmic events during patients' follow-up. The description of the genetic framework of our population and the observed genotype-phenotype correlation constitutes the starting point to address the current lack of knowledge in the genetics of ACM.

Trends in the Incidence and Antibiotic Resistance of Enterococcal Bloodstream Isolates: A 7-Year Retrospective Multicenter Epidemiological Study in Italy.

The spread of resistance to vancomycin and other last-resort drugs in Enterococcus spp. remains of concern. In Italy, surveillance data for enterococcal bloodstream isolates in humans are scant. The aim of our study was to assess the incidence trends of bacteremias due to Enterococcus species and their prevalence trends of antimicrobial resistance. We retrospectively included all consecutive not-duplicate Enterococcus species isolated from blood cultures, in patients from 11 Italian hospitals (2011-2017). Incidence was defined as the number of isolates per 10,000 patient-days, while resistance prevalence was defined as the number of resistant strains divided by the number of tested strains. We included 4,858 isolates (59%, 36%, and 5% due to Enterococcus faecalis, E. faecium, and other Enterococcus spp., respectively). Over the study period, the incidence of bacteremias due to E. faecalis (incidence rate ratio [IRR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.008) and E. faecium increased (IRR: 1.03, 95% CI: 1.01-1.05, p < 0.001) alongside with the whole enterococcal bacteremias trend (IRR: 1.02, 95% CIs: 1.01-1.04, p = 0.002). A progressive increase in vancomycin-resistant E. faecium (VREfm) bacteremias was observed. Resistance to tigecycline and linezolid was rarely reported. The incidence of enterococcal bloodstream isolates is increasing in Italy, together with the prevalence of VREfm. Resistance to linezolid, a cornerstone drug used in the treatment of VRE bloodstream infection, remains negligible.

Atrial fibrillation after thoracic surgery for lung cancer: use of a single cut-off value of N-terminal pro-B type natriuretic peptide to identify patients at risk.

Postoperative atrial fibrillation (AF) is a well-known complication occurring after thoracic surgery. B-type natriuretic peptide has recently been investigated as a predictive marker of postoperative AF after cardiac surgery. The aim of this study was to evaluate a definite cut-off for N-terminal pro-B type natriuretic peptide (NT-proBNP) in predicting postoperative AF in lung cancer patients. NT-proBNP was determined before and after surgery in 400 patients. Cardiac function was monitored by continuous postoperative ECG and clinical cardiological evaluation. AF occurred in 18% of the patients. Receiver operating characteristic curve analyses identified a cut-off of 182.3 ng l(-1) as the one with the highest sensitivity and specificity. Perioperative increased levels of NT-proBNP seem to predict postoperative AF in patients undergoing thoracic surgery, and a single cut-off of 182.3 ng l(-1) can be used to select high-risk patients who could receive preventive therapy, leading to a considerable decrease in the total costs associated with the management of this complication.

Iron deficiency in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Iron deficiency (ID) is a known co-morbidity and a potential therapeutic target in heart failure. Whether ID is frequent also in ST-segment elevation acute myocardial infarction (STEMI) patients and is associated with worse in-hospital outcomes has never been evaluated. METHODS: We defined ID as a serum ferritin < 100 µg/L or transferrin saturation < 20% at hospital admission. We assessed the association between ID and the primary endpoint (a composite of in-hospital mortality and Killip class ≥ 3). We explored the potential association between ID, circulating cell-free mitochondrial DNA (mtDNA), and cardiac magnetic resonance (CMR) parameters. RESULTS: Four-hundred-twenty STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were included. Of them, 237 (56%) had ID. They had significantly higher admission high-sensitivity troponin and mtDNA levels as compared to non-ID patients (145 ±â€¯35 vs. 231 ±â€¯66 ng/L, P < 0.001; 917 [404-1748] vs. 1368 [908-4260] copies/µL; P < 0.003, respectively). A lower incidence of the primary endpoint (10% vs. 18%, P = 0.01) was observed in ID patients (adjusted OR 0.50 [95% CI 0.27-0.93]; P = 0.02). At CMR (n = 192), ID patients had a similar infarct size (21 ±â€¯18 vs. 21 ±â€¯19 g; P = 0.95), but a higher myocardial salvage index (0.56 ±â€¯0.30 vs. 0.43 ±â€¯0.27; P = 0.002), and a smaller microvascular obstruction extent (3.6 ±â€¯2.2 vs. 6.9 ±â€¯3.9 g; P < 0.001). CONCLUSIONS: Iron deficiency is frequent in STEMI patients, it is coupled with mitochondrial injury, and, paradoxically, with a better in-hospital outcome. This unexpected clinical result seems to be associated with a smaller myocardial reperfusion injury. The mechanisms underlying our findings and their potential clinical implications warrant further investigation.

Typing of human papillomavirus in women with cervical lesions: prevalence and distribution of different genotypes.

Human papillomavirus (HPV) are distributed widely and persistent infection with high-risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim of this study was to evaluate the distribution of different HR-HPV genotypes in 199 women with cervical pre-invasive lesions undergoing conservative treatment. A Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in cervical samples. It was observed that the most prevalent HPV genotypes were HPV 16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the patients. Stratifying the different HPV genotypes according to the severity of the cervical lesion, a strong association between the increasing severity of the histological diagnosis and the detection of more carcinogenic HR-HPV type was found, and in all but one cervical intraepithelial neoplasia of grade 3 the presence of at least one HR-HPV could be detected, with more than 70% of cervical intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple infections, comprising between 2 and 6 HPV types, were found in 43% of patients; however, the presence of more than 1 HR-HPV type was not associated with an increased risk of high grade lesions. In conclusion, this data show that HPV 16, 51, 31, 52, and 18 were the prevalent types found in patients with cervical lesion undergoing conservative treatment, with a high prevalence of HPV 16 in cervical intraepithelial neoplasia of grade 3 patients. No association between multiple infection and severity of the lesion could be found.

High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study.

Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 ± 87 vs. 16 ± 41 mg/L; p < 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend <0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23; p < 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p < 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome.

Head-to-head comparison of plasma cTnI concentration values measured with three high-sensitivity methods in a large Italian population of healthy volunteers and patients admitted to emergency department with acute coronary syndrome: A multi-center study.

BACKGROUND: The study aim is to compare cTnI values measured with three high-sensitivity (hs) methods in apparently healthy volunteers and patients admitted to emergency department (ED) with acute coronary syndrome enrolled in a large multicentre study. METHODS: Heparinized plasma samples were collected from 1511 apparently healthy subjects from 8 Italian clinical institutions (mean age: 51.5 years, SD: 14.1 years, range: 18-65 years, F/M ratio:0.95). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests. Moreover, 1322 heparinized plasma sample were also collected by 9 Italian clinical institutions from patients admitted to ED with clinical symptoms typical of acute coronary syndrome. The reference study laboratory assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnI and ADVIA Centaur XPT methods. Principal Component Analysis (PCA) was also used to analyze the between-method differences among hs-cTnI assays. RESULTS: On average, a between-method difference of 31.2% CV was found among the results of hs-cTnI immunoassays. ADVIA Centaur XPT method measured higher cTnI values than Architect and Access methods. Moreover, 99th percentile URL values depended not only on age and sex of reference population, but also on the statistical approach used for calculation (robust non-parametric vs bootstrap). CONCLUSIONS: Due to differences in concentrations and reference values, clinicians should be advised that plasma samples of the same patient should be measured for cTnI assay in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods.

Procalcitonin as a useful marker of infection in hemato-oncological patients with fever.

BACKGROUND: The diagnostic utility of procalcitonin (PCT) and C-reactive protein (CRP) to discriminate between infective fever and fever due to inflammation was assessed in hemato-oncological patients treated with aggressive chemotherapy. PATIENTS AND METHODS: Values of PCT and PCR measured on days -1, 0, 1, 3 and 5 of onset of fever were analyzed using longitudinal regression analysis. Of 236 febrile episodes in 166 patients, 39 were due to bacteremia, 62 to other infections and 135 were classified as fever of unknown origin. RESULTS: PCT concentration increased early only in bacteremia and other infections (p<0.001), with the highest levels at day +1. No different trends were noted in patients with low WBC count (<1,000/microl). CRP increased with a similar trend in all the three groups. CONCLUSION: PCT determination may contribute significantly to the management of hemato-oncological patients who experience febrile episodes.

MiR-320a as a Potential Novel Circulating Biomarker of Arrhythmogenic CardioMyopathy.

Diagnosis of Arrhythmogenic CardioMyopathy (ACM) is challenging and often late after disease onset. No circulating biomarkers are available to date. Given their involvement in several cardiovascular diseases, plasma microRNAs warranted investigation as potential non-invasive diagnostic tools in ACM. We sought to identify circulating microRNAs differentially expressed in ACM with respect to Healthy Controls (HC) and Idiopathic Ventricular Tachycardia patients (IVT), often in differential diagnosis. ACM and HC subjects were screened for plasmatic expression of 377 microRNAs and validation was performed in 36 ACM, 53 HC, 21 IVT. Variable importance in data partition was estimated through Random Forest analysis and accuracy by Receiver Operating Curves. Plasmatic miR-320a showed 0.53 ± 0.04 fold expression difference in ACM vs. HC (p < 0.01). A similar trend was observed when comparing ACM (n = 13) and HC (n = 17) with athletic lifestyle, a ACM precipitating factor. Importantly, ACM patients miR-320a showed 0.78 ± 0.05 fold expression change vs. IVT (p = 0.03). When compared to non-invasive ACM diagnostic parameters, miR-320a ranked highly in discriminating ACM vs. IVT and it increased their accuracy. Finally, miR-320a expression did not correlate with ACM severity. Our data suggest that miR-320a may be considered a novel potential biomarker of ACM, specifically useful in ACM vs. IVT differentiation.

B-type natriuretic peptide levels in patients with pericardial effusion undergoing pericardiocentesis.

OBJECTIVES: Pericardial effusion is characterized by progressive accumulation of fluid within the pericardial space, resulting in increased intra-pericardial pressure and compression of the heart. As B-type natriuretic peptide (BNP) is secreted by the ventricles in response to increased myocardial stretch, we hypothesized that pericardial effusion, as well as its resolution, might influence BNP plasma levels. METHODS: We prospectively measured, in 146 consecutive patients with pericardial effusion, BNP plasma levels at baseline, soon after, and 24h after pericardiocentesis. A scoring system based on 7 clinical and echocardiographic parameters was developed, and patients were classified according to the number of variables as having low (0-2), intermediate (3-4), or high (5-7) severity score. RESULTS: Out of the 146 patients, 42 (29%) had normal values (<100pg/ml), whereas 104 (71%) had high BNP values at baseline. In the whole population, baseline BNP levels significantly decreased as the severity score increased (r=-0.21; P=0.01). 24h after pericardiocentesis, a significant increase in BNP was observed in patients with intermediate (P=0.004) score and with high (P<0.001) severity score; no increase occurred in low score patients (P=0.56). The higher was the severity score, the steeper was the increase in BNP through the three time-points considered (P=0.04). CONCLUSIONS: The results of the present study show that BNP plasma levels are suppressed in the presence of severe pericardial effusion, and that they rise after pericardiocentesis. Future studies should investigate the role of BNP in assisting clinicians in the decision-making process of pericardial fluid drainage.

Comparison of the clinical performance of carcinogenic HPV typing of the Linear Array and Papillocheck HPV-screening assay.

BACKGROUND: HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66 are considered carcinogenic for human beings. DNA-chip technology, Papillocheck HPV-screening (Greiner) and reverse dot blot, Linear Array (LA) (Roche) are tools to assess the distribution of HPV genotypes. OBJECTIVES: The aim of the study was to compare the clinical performance of Papillocheck and LA assays using a clinical cut-off of CIN2+. The secondary aim was to comparatively assess the distribution of HPV types using these two assays. STUDY DESIGN: The study population comprised 239 women referred for colposcopy and histology. Papillocheck, LA, and Hybrid Capture II (HCII) tests were done on all samples. RESULTS: All tests showed good sensitivity and NPV (greater than 90%). None of the comparisons of sensitivities, specificities, PPVs, and NPVs showed statistically relevant differences between tests. High-risk HPV positivity rate was similar for all tests (Papillocheck 75%, LA 77%, and HCII 73%). Agreement between tests was good. The concordance levels between HCII and Papillocheck and between HCII and LA were 93% (k=0.82) and 92% (k=0.80), respectively. Papillocheck and LA tests showed a high overall concordance rate of 96% (k=0.90). HPV16 was the most detected type (45% with Papillocheck, and 47% with LA), and HPV31 was the second most detected type (13% with Papillocheck, and 14% with LA). CONCLUSIONS: The Papillocheck HPV-screening test and LA test have a good clinical sensitivity to detect HPV types in CIN2+ patients. These assays allow, in the same experiment, to detect and determine the virus type. Our study showed that HPV types 16 and 31/33 are the most prevalent.

Interchangeability of measurements of CA 19-9 in serum with four frequently used assays: an update.

BACKGROUND: CA 19-9 is a marker principally related to pancreatic and gall bladder cancer. Although its determination has no value in screening for these malignancies, it is used in post-operative monitoring and during chemotherapeutic treatment of confirmed disease. Measurements during follow-up must be comparable and must be performed with standard, validated methods. METHODS: We compared four routinely used analytical systems for CA 19-9 determination: the Architect i2000 and AxSYM systems from Abbott Laboratories, the Elecsys 1010 from Roche Diagnostics, and the KRYPTOR system from Brahms Diagnostics. We evaluated the analytical performance of the four systems and compared measurements of CA 19-9 values, which covered the whole analytical range. RESULTS: The analytical performance and accuracy of the four systems were fairly good, but Passing-Bablok regression and mountain plots showed significant differences in CA 19-9 values measured with the four platforms. CONCLUSIONS: Our data indicate that during tumor follow-up, the use of the same system is appropriate to avoid the risk of a variation due to the method rather than the disease. Moreover, whenever a change in analytical equipment is required, careful analysis of CA 19-9 results must be undertaken.