Search

The aim of this study was to evaluate the relationship between anaemia and biomarkers of central/peripheral congestion in heart failure (HF) and the impact on mortality. We retrospectively evaluated 434 acute/chronic HF (AHF/CHF) patients. Anaemia was defined as haemoglobin levels <12 g/dL (women) or <13 g/dL (men). The brain natriuretic peptide (BNP) and hydration index (HI) were measured. The endpoint of the study was all-cause mortality. Anaemia occurred in 59% of patients with AHF and in 35% with CHF ( p < 0.001) and showed a significant correlation with the NYHA functional class and renal function. BNP and HI were significantly higher in patients with anaemia than in those without anaemia. Independent predictors of anaemia included BNP, estimated creatinine clearance (eCrCL), and HI. The all-cause mortality rate was 21%, which was significantly higher in patients with anaemia than in those without anaemia (30% vs. 14%, p < 0.001; hazard ratio: 2.6). At multivariate Cox regression analysis, BNP, eCrCL, and HI were independent predictors for mortality (Hazard ratios: 1.0002, 0.97, and 1.05, respectively), while anaemia was not. Anaemia correlates with HF status, functional class, renal function, BNP, and HI. Anaemia was not an independent predictor for mortality, acting as a disease severity marker in congestive patients rather than as a predictor of death.

Background: Kidney disease is common in patients with heart failure (HF). The Donadio equation combines plasma creatinine and bioimpedance vector analysis (BIVA) to estimate creatinine clearance. This study aimed to compare the Donadio formula to the Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD-4), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in patients with HF., Methods: We analysed data from 900 patients (mean age: 76 ± 10 years) with HF. All of them underwent clinical, laboratory, BIVA, and echocardiographic evaluations., Results: Donadio equation overestimated eGFR as compared to CG and CKD-EPI formulas (+6.8 and +12 mL/min/1.73 m2, respectively) while computing similar results to MDRD-4 (overestimation: +0.1 mL/min/1.73 m2). According to the different formulas, the prevalence of renal insufficiency (eGFR< 30 ml/min/1.73 m2) in relation to the different formulas was as follows: 24% with Donadio, 21% with CG, 13% with MDRD-4, and 23% with CKD-EPI formulas. All the equations demonstrated a high precision rate (r>0.8 for all). There was a "good" agreement between the Donadio and CG/MDRD-4 formulas and "fair" with the CDK-EPI formula. The Donadio equation showed a high accuracy in predicting severe renal dysfunction (eGFR< 30 mL/min/1.73 m2) in patients with HF (AUC > 0.9), showing comparable performances to CG., Conclusion: The Donadio formula provided an estimation of GFR comparable to MDRD-4 in HF patients, independently from acute or chronic HF conditions. The use of BIVA in HF patients may be adopted both for HF management and for evaluating kidney function., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The impact of coronary artery disease (CAD) on all-cause mortality and overall disabilities is well-established. Percutaneous and/or surgical coronary revascularization procedures dramatically reduced the occurrence of adverse cardiovascular events in patients suffering from atherosclerosis. Specifically, guidelines from the European Society of Cardiology on the management of myocardial revascularization promoted coronary artery by-pass graft (CABG) intervention in patients with specific alterations in the coronary tree due to the higher beneficial effects of this procedure as compared to the percutaneous one. The left internal mammary artery (LIMA) is one of the best-performing vessels in CABG procedures due to its location and its own structural characteristics. Nevertheless, the non-invasive assessment of its patency is challenging. Doppler ultrasonography (DU) might perform as a reliable technique for the non-invasive evaluation of the patency of LIMA. Data from the literature revealed that DU may detect severe (>70%) stenosis of the LIMA graft. In this case, pulsed-wave Doppler might show peak diastolic velocity/peak systolic velocity < 0.5 and diastolic fraction < 50%. A stress test might also be adopted for the evaluation of patency of LIMA through DU. The aim of this narrative review is to evaluate the impact of DU on the evaluation of the patency of LIMA graft in patients who undergo follow-up after CABG intervention.

Background. The assessment of long-term mortality in acute decompensated heart failure (ADHF) is challenging. Respiratory failure and congestion play a fundamental role in risk stratification of ADHF patients. The aim of this study was to investigate the impact of arterial blood gases (ABG) and congestion on long-term mortality in patients with ADHF. Methods and results. We enrolled 252 patients with ADHF. Brain natriuretic peptide (BNP), blood urea nitrogen (BUN), phase angle as assessed by means of bioimpedance vector analysis, and ABG analysis were collected at admission. The endpoint was all-cause mortality. At a median follow-up of 447 d (interquartile range [IQR]: 248-667), 72 patients died 1-840 d (median 106, IQR: 29-233) after discharge. Respiratory failure types I and II were observed in 78 (19%) and 53 (20%) patients, respectively. The ROC analyses revealed that the cut-off points for predicting death were: BNP > 441 pg/mL, BUN > 1.67 mmol/L, partial pressure in oxygen (PaO 2 ) ≤69.7 mmHg , and phase angle ≤4.9°. Taken together, these four variables proved to be good predictors for long-term mortality in ADHF (area under the curve [AUC] 0.78, 95% CI 0.72-0.78), thus explaining 60% of all deaths. A multiparametric score based on these variables was determined: each single-unit increase promoted a 2.2-fold augmentation of the risk for death (hazard ratio [HR] 2.2, 95% CI 1.8-2.8, p < .0001). Conclusions. A multiparametric approach based on measurements of BNP, BUN, PaO 2, and phase angle is a reliable approach for long-term prediction of mortality risk in patients with ADHF.

Background: Surgical aortic valve replacement with a rapid deployment valve (RDV) is a relatively recent treatment option. The aim of this study was to compare the hemodynamic performance of balloon-expandable (BE)-RDVs and BE-transcatheter heart valves (THVs) in a high surgical risk and frail-elderly population., Methods: BE-THVs and BE-RDVs were implanted in 138 and 47 patients, respectively, all older than 75 years and with a Canadian Study of Health and Aging category of 5 or above. Echocardiographic assessment was performed at discharge and six months later., Results: At discharge, transprosthetic pressure gradients and indexed effective orifice area (iEOA) were similar in both cohorts. At six-month follow-up, BE-RDVs showed lower peak (14.69 vs. 20.86 mmHg; p < 0.001) and mean (7.82 vs. 11.83 mmHg; p < 0.001) gradients, and larger iEOA (1.05 vs. 0.84 cm 2 /m 2 ; p < 0.001). Similar findings were also shown considering only small-sized valves. Moderate-to-severe paravalvular leakage was more prevalent in BE-THVs at discharge (14.49 vs. 0.00%; p = 0.032) and, considering exclusively small prostheses, at six months too (57.69 vs. 15.00%; p = 0.014). Nevertheless, BE-THVs determined amelioration in left ventricular ejection fraction (53.79 vs. 60.14%; p < 0.001), pulmonary artery systolic pressure (35.81 vs. 33.15 mmHg; p = 0.042), and tricuspid regurgitation severity (40.58 vs. 19.57%; p = 0.031), from discharge to mid-term follow-up., Conclusions: BE-RDVs showed better hemodynamic performance, especially when implanted in small annuli. Despite their worse baseline conditions, transcatheter patients still exhibited a greater improvement of their echocardiographic profile at mid-term follow-up., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Circulating parathyroid hormone (PTH) concentrations increase in heart failure (HF) and are related to disease severity. The relationship between PTH and congestion is still a matter of debate. The objective of this analysis was to evaluate the role of PTH as a marker of congestion and prognosis in HF. We enrolled 228 patients with HF. Intact PTH concentrations and HYDRA score (constituted by: B-type natriuretic peptide, blood urea nitrogen−creatinine ratio, estimated plasma volume status, and hydration status) were evaluated. The study endpoint was all-cause mortality. PTH levels were higher in acute compared with chronic HF and in patients with clinical signs of congestion (i.e., peripheral oedema and orthopnea). PTH concentrations significantly correlated with NYHA class and HYDRA score. At multivariate analysis of HYDRA score, estimated glomerular filtration rate (eGFR), and corrected serum calcium were independently determinants of PTH variability. Fifty patients (22%) died after a median follow-up of 408 days (interquartile range: 283−573). Using univariate Cox regression analysis, PTH concentrations were associated with mortality (hazard ratio [HR]: 1.003, optimal cut-off: >249 pg/mL—area under-the-curve = 0.64). Using multivariate Cox regression analysis, PTH was no longer associated with death, whereas HYDRA score, left ventricular ejection fraction, and eGFR acted as independent predictors for mortality (HR: 1.96, 0.97, and 0.98, respectively). Our study demonstrated that intact PTH was related to clinical and subclinical markers of congestion. However, intact PTH did not act as an independent determinant of all-cause death in HF patients.

Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3-18% of HF patients from randomized controlled trials and over 25% of HF patients in the "real world" setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K + and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K + levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting.

The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We consecutively enrolled 494 AHF patients (252 female). Clinical congestion assessment, B-type natriuretic peptide levels analysis, blood urea nitrogen to creatinine ratio (BUN/Cr), plasma volume status estimate (by means of Duarte or Kaplam-Hakim PVS), and hydration status evaluation through bioimpedance analysis were performed. There was no difference in medications between men and women. Women were older (79 ± 9 yrs vs. 77 ± 10 yrs, p = 0.005), and had higher left ventricular ejection fraction (45 ± 11% vs. 38 ± 11%, p < 0.001), and lower creatinine clearance (42 ± 25 mL/min vs. 47 ± 26 mL/min, p = 0.04). The prevalence of peripheral oedema, orthopnoea, and jugular venous distention were not significantly different between women and men. BUN/Cr (27 ± 9 vs. 23 ± 13, p = 0.04) and plasma volume were higher in women than men (Duarte PVS: 6.0 ± 1.5 dL/g vs. 5.1 ± 1.5 dL/g, p < 0.001; Kaplam−Hakim PVS: 7.9 ± 13% vs. −7.3 ± 12%, p < 0.001). At multivariate logistic regression analysis, female sex was independently associated with BUN/Cr and PVS. Female sex was independently associated with subclinical biomarkers of congestion such as BUN/Cr and PVS in patients with AHF. A sex-guided approach to the correct evaluation of patients with AHF might become the cornerstone for the correct management of these patients.

Primary and secondary prevention protocols aim at reducing the plasma levels of lipids - with particular reference to low-density lipoprotein cholesterol (LDL-C) plasma concentrations - in order to improve the overall survival and reduce the occurrence of major adverse cardiovascular events. The use of statins has been widely considered as the first-line approach in lipids management as they can dramatically impact on the cardiovascular risk profile of individuals. The introduction of ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors overcame the adverse effects of statins and ameliorate the achievement of the target lipids levels. Indeed, advances in therapies promote the use of specific molecules - i.e. short strands of RNA named small-interfering RNAs (siRNAs) - to suppress the transcription of genes related to lipids metabolism. Recently, the inclisiran has been developed: this is a siRNA able to block the mRNA of the PCSK9 gene. About 50% reduction in low-density lipoprotein cholesterol levels have been observed in randomized controlled trials with inclisiran. The aim of this review was to summarize the literature regarding inclisiran and its possible role in the general management of patients with lipid disorders and/or in primary/secondary prevention protocols., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The estimation of glomerular filtration rate (eGFR) provides prognostic information in patients with heart failure (HF). Bioelectrical impedance analysis may calculate eGFR (Donadio formula). The aim of this study was to evaluate the impact of the Donadio formula in predicting all-cause mortality in patients with HF as compared to Cockroft-Gault, MDRD-4 (Modification of Diet in renal Disease Study), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. Four-hundred thirty-six subjects with HF (52% men; mean age 75 ± 11 years; 42% acute HF) were enrolled. Ninety-two patients (21%) died during the follow-up (median 463 days, IQR 287-669). The area under the receiver operator characteristic curve for eGFR, as estimated by Cockroft-Gault formula (AUC = 0.75), was significantly higher than those derived from Donadio (AUC = 0.72), MDRD-4 (AUC = 0.68), and CKD-EPI (AUC = 0.71) formulas. At multivariate analysis, all eGFR formulas were independent predictors of death; 1 mL/min/1.73 m 2 increase in eGFR-as measured by Cockroft-Gault, Donadio, MDRD-4, and CKD-EPI formulas-provided a 2.6%, 1.5%, 1.2%, and 1.6% increase, respectively, in mortality rate. Conclusions. eGFR, as calculated with the Donadio formula, was an independent predictor of mortality in patients with HF as well as the measurements derived from MDRD4 and CKD-EPI formulas, but less accurate than Cockroft-Gault.

The need for anticoagulation in patients with atrial fibrillation (AF) is fundamental to prevent thromboembolic events. Direct oral anticoagulants (DOACs) recently demonstrated to be superior, or at least equal, to Warfarin in reducing the risk for stroke/systemic embolism and preventing major bleeding and intracranial hemorrhages. The AF population often suffers from chronic kidney disease (CKD). Indeed, the relationship between AF and renal function is bidirectional: AF can trigger kidney failure, while kidney impairment can promote alterations able to enhance AF. Therefore, there are concerns regarding prescriptions of anticoagulants to patients with AF and CKD. The worsening in kidney function can be effectively due to anticoagulants administration. Warfarin has been recognized to promote acute kidney injury in case of excessive anticoagulation levels. Nevertheless, further mechanisms can induce the chronic worsening of renal function, thus leading to terminal kidney failure as observed in post-hoc analysis from registration trials and dedicated observational studies. By contrast, DOACs seem to protect kidneys from injuries more efficiently than Warfarin, although they still continue to play a role in promoting some kidney lesions. However, the exact mechanisms remain unknown. This narrative review aimed to discuss the influence of oral anticoagulants on renal impairment as well as to overview potential pathophysiological mechanisms related to this clinical complication.

The interventional treatment of aortic stenosis is currently based on transcatheter aortic valve implantation/replacement (TAVI/TAVR) and surgical aortic valve replacement (SAVR). Prosthetic valve infective endocarditis (PVE) is the most worrisome complication after valve replacement, as it still carries high mortality and morbidity rate. Studies have not highlighted the differences in the occurrence of PVE in SAVR as opposed to TAVR, but the reported incidence rates are widely uneven. Literature portrays different microbiological profiles for SAVR and TAVR PVE: Staphylococcus, Enterococcus, and Streptococcus are the pathogens that are more frequently involved with differences regarding the timing from the date of the intervention. Imaging by means of transoesophageal echocardiography, and computed tomography (CT) Scan is essential in identifying vegetations, prosthesis dysfunction, dehiscence, periannular abscess, or aorto-ventricular discontinuity. In most cases, conservative medical treatment is not able to prevent fatal events and surgery represents the only viable option. The primary objectives of surgical treatment are radical debridement and the removal of infected tissues, the reconstruction of cardiac and aortic morphology, and the restoration of the aortic valve function. Different surgical options are discussed. Fast diagnosis, the adequacy of antibiotics treatment, and prompt interventions are essential in preventing the negative consequences of infective endocarditis (IE).

Background: The whole-body bioelectrical phase-angle (PhA) is emerging as a new tool in stratifying prognosis in patients with both acute (AHF) and chronic heart failure (CHF)., Objective: To evaluate the determinants of PhA in HF patients., Methods: We analyzed data from 900 patients with AHF or CHF (mean age: 76±10 years, 54% AHF). Clinical, serum biochemical, echocardiographic and bioelectrical measurements were collected from all of patients. PhA was quantified in degrees. Congestion was assessed by a multiparametric approach, including the presence of peripheral edema, brain natriuretic peptides (BNP) plasma levels, blood urea nitrogen to creatinine ratio (BUN/Cr), and relative plasma volume status (PVS) calculated by Kaplan-Hakim's formula. Geriatric Nutritional Risk Index (GNRI) was adopted as indicator for nutritional status., Results: At univariate analysis, PhA was significantly lower in females, in patients with peripheral edema, and AHF. PhA significantly correlates age, BNP, PVS, BUN/Cr, and GNRI. At multivariate analysis, congestion biomarkers emerged as the major determinant of PhA as they explained the 34% of data variability, while age, GNRI, and gender only explained 6%, 0.5%, and 0.5%, respectively (adjusted R 2  = 0.41). In particular, PVS (regression of coefficient B=-0.17) explained the 20% of PhA variability, while peripheral congestion (B=-0.27) and BNP (B=-0.15) contributed to 10% and 2%, respectively., Conclusions: The main determinant of bioelectrical PhA in patients with HF is congestion and PVS in particular, while nutritional status has marginal impact., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cerebrovascular diseases (CBD) are one of the most dangerous complications of atherosclerosis. The clinical consequences of CBD deeply impact quality of life and the prognosis of patients. Atherosclerosis is the main cause of CBD development. Hypertension, dyslipidemia, diabetes, smoking, obesity, and other risk factors explain the higher CBD incidence in the general population, as they are able to anticipate the clinical expression of atherosclerosis. These risk factors are effectively able to promote endothelial dysfunction which is the premise for the early, clinical expression of atherosclerosis. The mechanisms by which risk factors can influence the occurrence of CBD are different and not fully understood. The inflammatory background of atherosclerosis can explain a great part of it. In particular, the oxidative stress may promote the development of vascular lesions by negatively influencing biochemical cellular processes of the endothelium, thus predisposing the vascular tree to morphological and functional damages. The aim of this narrative review is to evaluate the role of endothelial dysfunction and oxidative stress in CBD development.

Introduction: Ischemic heart diseases are the major leading cause of death worldwide. Revascularization procedures dramatically reduced the overall risk for death related to acute coronary syndromes. Two kinds of myocardial revascularization can grossly be outlined: percutaneous coronary intervention (PCI) and surgical coronary artery bypass graft intervention (CABG). The net clinical benefit coming from these two kinds of procedures is still under debate., Methods: We have traced the state-of-the-art background about myocardial revascularization procedures by comparing the most important trials dealing with the evaluation of percutaneous interventions versus a surgical approach to coronary artery diseases., Results: Both PCI and CABG have become effective treatments for revascularization of patients suffering from advanced CAD. The advance in technology and procedural techniques made PCI an attractive and, to some extent, more reliable procedure in the context of CAD. However, there are still patients that cannot undergo PCI and have to be rather directed towards CABG., Conclusion: CABG still remains the best strategy for the treatment of multiple vessel CAD due to improved results in term of survival and freedom from reintervention. Anyway, a systematic, multidisciplinary approach to revascularization is the fundamental behaviour to be chased in order to effectively help the patients in overcoming its diseases. The creation of the "heart team" seems to be a good option for the correct treatment of patients suffering from stable and unstable CAD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this paper, we report on the design of a bio-multisensing platform for the selective label-free detection of protein biomarkers, carried out through a 3D numerical algorithm. The platform includes a number of biosensors, each of them is based on a plasmonic nanocavity, consisting of a periodic metal structure to be deposited on a silicon oxide substrate. Light is strongly confined in a region with extremely small size (=1.57 μm²), to enhance the light-matter interaction. A surface sensitivity S s = 1.8 nm/nm has been calculated together with a detection limit of 128 pg/mm². Such performance, together with the extremely small footprint, allow the integration of several devices on a single chip to realize extremely compact lab-on-chip microsystems. In addition, each sensing element of the platform has a good chemical stability that is guaranteed by the selection of gold for its fabrication., Competing Interests: The authors declare no conflict of interest.

Objectives: Minimally invasive valve surgery (MIVS) is associated with improved clinical outcome but longer cardiopulmonary bypass (CPB) time. The aim of the present study is to compare inflammatory and coagulation parameters in patients undergoing minimally invasive or standard valve surgery., Methods: A prospective non-randomized study was performed enrolling 79 patients undergoing mitral (20 right mini-thoracotomy and 18 standard sternotomy) and aortic valve (20 mini-sternotomy and 21 standard sternotomy) procedures. Blood samples were collected perioperatively to measure prothrombin fragment 1.2 (PF1.2, thrombin generation), plasmin antiplasmin complex (PAP, fibrinolysis), interleukin-6 (IL-6, inflammation). Plasma free haemoglobin (f-Hb) was assessed to evaluate haemolysis., Results: Patients in the minimally invasive group were younger and had less comorbidities CPB and cross-clamp times were comparable considering both aortic and mitral procedures, but longer in the mini-thoracotomy group. IL-6 and PAP were reduced in the minimally invasive group, particularly 2 h after CPB (respectively 102 ± 114 vs 34 ± 49 pg/ml, P < 0.001 and 2137 ± 1046 vs 1207 ± 675 ng/ml, P < 0.001), PF1.2 was also reduced during and after the operation (688 ± 514 vs 571 ± 470, P = 0.02; 1600 ± 1185 vs 1042 ± 548, P < 0.001; 1487 ± 676 vs 1042 ± 541). Despite the use of vacuum-assisted active venous drainage (VAVD) f-Hb was significantly reduced in the minimally invasive group. The other routine biomarkers such as C-reactive protein, fibrinogen and cTnI were also reduced in the minimally invasive group., Conclusions: In a selected cohort of patients MIVS is associated to reduced inflammatory reaction and coagulopathy, supporting the clinical evidence of reduced postoperative bleeding and lower transfusion rate. Our data offer further suggestion supporting the adoption of minimally invasive approaches., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Acute kidney injury (AKI) is a common complication following cardiac surgery. Cardiopulmonary bypass elicits coagulation and inflammation activation and oxidative stress, all involved in AKI but never simultaneously assessed. We aimed to evaluate relations between oxidative stress, inflammatory and coagulation systems activation and postoperative renal function in patients with normal preoperative renal function., Methods: Forty-one high-risk patients (EuroSCORE >6 and preoperative haemoglobin <12 g/dl in women and <13 g/dl in men) were prospectively enrolled. Prothrombin fragment 1.2 (coagulation marker), interleukin-6 and interleukin-10 (pro/anti-inflammatory markers) and 8-oxo-2'-deoxyguanosine (oxidative stress marker) were evaluated until postoperative day 5., Results: Patients were divided into two groups according to estimated glomerular filtration rate reduction observed postoperatively (reduction <25% in 26 patients: NO-AKI group; reduction >25% in 15 patients: AKI group). No differences were found for inflammatory markers. Oxidative stress slightly increased in the AKI group. Twenty-four hours after the operation prothrombin fragment 1.2 levels were significantly higher in the AKI group (506.6 ± 548 vs. 999 ± 704.1 pmol/l; P = 0.018), and they were independently associated with estimated glomerular filtration rate reduction, with an area under the receiving operating characteristic of 0.744., Conclusion: Thrombin generation is higher in patients with renal function worsening, and it is an independent risk factor for AKI in patients with anaemia, possibly leading to microcirculation impairment and tubular cells damage.

Background: Myocardial damage is an independent predictor of adverse outcome following cardiac surgery and myocardial protection is one of the key factors to achieve successful outcomes. Cardioplegia with Custodiol is currently the most used cardioplegia during minimally invasive cardiac surgery (MICS). Different randomized controlled trials compared blood and Custodiol cardioplegia in the context of traditional cardiac surgery. No data are available for MICS., Aim: The aim of this study was to compare the efficacy of cold blood versus Custodiol cardioplegia during MICS., Method: We retrospectively evaluated 90 patients undergoing MICS through a right mini-thoracotomy in a three-year period. Myocardial protection was performed using cold blood (44 patients, CBC group) or Custodiol (46 patients, Custodiol group) cardioplegia, based on surgeon preference and complexity of surgery., Results: The primary outcomes were post-operative cardiac troponin I (cTnI) and creatine kinase MB (CKMB) serum release and the incidence of Low Cardiac Output Syndrome (LCOS). Aortic cross-clamp and cardiopulmonary bypass times were higher in the Custodiol group. No difference was observed in myocardial injury enzyme release (peak cTnI value was 18±46 ng/ml in CBC and 21±37 ng/ml in Custodiol; p=0.245). No differences were observed for mortality, LCOS, atrial or ventricular arrhythmias onset, transfusions, mechanical ventilation time duration, intensive care unit and total hospital stay., Conclusions: Custodiol and cold blood cardioplegic solutions seem to assure similar myocardial protection in patients undergoing cardiac surgery through a right mini-thoracotomy approach.

Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752). A substudy was conducted in 2 sites to collect blood samples perioperatively to measure prothrombin fragment 1.2 (PF1+2, thrombin generation), plasmin-antiplasmin complex (PAP, fibrinolysis), platelet factor 4 (PF4 platelet activation), and fibrinogen. Eighty-one patients were enrolled in the substudy (37 placebo vs 44 in treatment group). No difference in clinical outcome was detected, including postoperative bleeding and need for blood products transfusion. All patients showed changes of all plasma biomarkers with greater values than baseline in both groups. This reaction was attenuated significantly in the treatment group for PF1.2 (P = 0.040) and PAP (P = 0.042) values at the first intraoperative measurement. No difference between groups was detected for PF4. Methylprednisolone treatment attenuates activation of coagulation system in high-risk patients undergoing CPB surgery. Reduction of thrombin generation and fibrinolysis activation may lead to reduced blood loss after surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Antithrombin (AT) concentrations are reduced after cardiac surgery with cardiopulmonary bypass compared with the preoperative levels. Low postoperative AT is associated with worse short- and mid-term clinical outcomes. The aim of the study is to evaluate the effects of AT administration on activation of the coagulation and fibrinolytic systems, platelet function, and the inflammatory response in patients with low postoperative AT levels., Methods: Sixty patients with postoperative AT levels of less than 65% were randomly assigned to receive purified AT (5000 IU in three administrations) or placebo in the postoperative intensive care unit. Thirty patients with postoperative AT levels greater than 65% were observed as controls. Interleukin 6 (a marker of inflammation), prothrombin fragment 1-2 (a marker of thrombin generation), plasmin-antiplasmin complex (a marker of fibrinolysis), and platelet factor 4 (a marker of platelet activation) were measured at six different times., Results: Compared with the no AT group and control patients, patients receiving AT showed significantly higher AT values until 48 hours after the last administration. Analysis of variance for repeated measures showed a significant effect of study treatment in reducing prothrombin fragment 1-2 (p=0.009; interaction with time sample, p=0.006) and plasmin-antiplasmin complex (p<0.001; interaction with time sample, p<0.001) values but not interleukin 6 (p=0.877; interaction with time sample, p=0.521) and platelet factor 4 (p=0.913; interaction with time sample, p=0.543). No difference in chest tube drainage, reopening for bleeding, and blood transfusion was observed., Conclusions: Antithrombin administration in patients with low AT activity after surgery with cardiopulmonary bypass reduces postoperative thrombin generation and fibrinolysis with no effects on platelet activation and inflammatory response., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Cardiopulmonary bypass (CPB) systems without a venous reservoir rarely are adopted clinically. The effects of a biocompatible CPB system with a venous reservoir were evaluated on the activation of the coagulation and inflammatory systems., Design: A prospective, randomized controlled trial., Setting: A university hospital (single center)., Participants: Eighty-three coronary artery bypass graft (CABG) surgery patients were assigned to the Physio group (closed venous reservoir, phosphorylcholine coating, and no cardiotomy suction) or the Standard group (open, noncoated, and cardiotomy suction used)., Methods: Blood samples were obtained at 6 different time points before, during, and after surgery. Nuclear factor-kB (NF-κB) was evaluated before surgery and 2 and 24 hours after surgery. Myocardial damage was evaluated measuring cardiac troponin I., Measurements and Main Results: Interleukin (IL)-6 (a marker of inflammation), prothrombin fragment 1-2 (PF-1.2, a marker of thrombin generation), plasmin-antiplasmin complex (PAP, a marker of fibrinolysis), and platelet factor 4 (PF4, a marker of platelet activation) were measured. The DNA binding activity of proinflammatory transcription factor NF-κB was quantified in the isolated lymphomonocyte cells. Surgery caused changes of all plasma biomarkers. This reaction was attenuated strongly in the Physio group; PF-1.2, PAP, and PF4 all were decreased significantly. In the Physio group, a significantly lower cardiac troponin I release was observed postoperatively. After surgery, NF-κB activity was reduced in the Physio group although this difference was not statistically significant., Conclusions: A multimodal strategy using a closed and phosphorylcholine-coated CPB circuit together with the avoidance of cardiotomy suction reduced activation of the coagulation and fibrinolytic systems intraoperatively, although these changes did not persist postoperatively. However, no difference in clinical outcome was appreciated on a larger scale., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Surgery for acute aortic dissection (AAD) is frequently complicated by excessive postoperative bleeding and blood product transfusion. Blood flow through the nonendothelialized false lumen is a potential trigger for the activation of the hemostatic system; however, the physiopathology of the aortic dissection induced coagulopathy has never been precisely studied. The aim of the present study is the evaluation of the coagulation and fibrinolytic systems and platelet activation in patients undergoing surgery for AAD., Methods: Eighteen patients undergoing emergent surgery for Stanford type A AAD were enrolled in the study. The activation of the coagulation and fibrinolytic systems and platelet activation were evaluated at 6 different time points before, during, and after the operation, measuring prothrombin fragment 1.2 (F1.2), plasmin-antiplasmin complex, and platelet factor 4, respectively., Results: All measured biomarkers were increased before, during, and after the operations indicating a systemic activation of coagulation, fibrinolysis, and platelets. These changes were pronounced even preoperatively (T0), and soon after the beginning of cardiopulmonary bypass (T1) when the influence of hypothermia and prolonged cardiopulmonary bypass time were not yet involved. Time from symptom onset to intervention inversely correlated with preoperative F1.2 (r=-0.75; p=0.002) and plasmin-antiplasmin levels (r=-0.57; p=0.034)., Conclusions: Blood flow through the false lumen is a powerful activator of the hemostatic system even before the operation. This remarkable activation may influence postoperative outcome of AAD patients., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We have previously shown that serum/glucocorticoid regulated kinase 1 (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal tissue. As hyper-methylation of promoter regions is a well-known mechanism of gene silencing in cancer, we tested whether the SGK1 promoter region was methylated in colonic tumour samples., Methodology/principal Findings: We investigated the methylation profile of the two CpG islands present in the promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We further confirmed our findings in a panel of 10 normal and 10 tumour colonic tissue samples of human origin. We observed CpG methylation only in the smaller and more distal CpG island in the promoter region of SGK1 in both normal and tumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylation of the corresponding CpG., Conclusions/significance: Our results show that even though partial methylation of the promoter region of SGK1 is present, this does not account for the different expression levels seen between normal and tumour tissue.

We report on a morphological study of 192 breast masses as seen in mammograms, with the aim of discrimination between benign masses and malignant tumors. From the contour of each mass, we computed the fractal dimension (FD) and a few shape factors, including compactness, fractional concavity, and spiculation index. We calculated FD using four different methods: the ruler and box-counting methods applied to each 2-dimensional (2D) contour and its 1-dimensional signature. The ANOVA test indicated statistically significant differences in the values of the various shape features between benign masses and malignant tumors. Analysis using receiver operating characteristics indicated the area under the curve, A(z), of up to 0.92 with the individual shape features. The combination of compactness, FD with the 2D ruler method, and the spiculation index resulted in the highest A(z) value of 0.93.

Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent overexpression and underexpression of 78 known components of this signaling cascade. The expression of 19 Wnt targets was closely correlated with clear up-regulation of KIAA1199, whose function is currently unknown. In normal mucosa, KIAA1199 expression was confined to cells in the lower portion of intestinal crypts, where Wnt signaling is physiologically active, but it was markedly increased in all adenomas, where it was expressed in most of the epithelial cells, and in colon cancer cell lines, it was markedly reduced by inactivation of the beta-catenin/T-cell factor(s) transcription complex, the pivotal mediator of Wnt signaling. Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis and identified KIAA1199 as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenomatous transformation.

Background & Aims: In colorectal cancer, activating mutations in the Wnt pathway transform epithelial cells through the inappropriate expression of a TCF4 target gene program, which is physiologically expressed in intestinal crypts., Methods: We have now performed an exhaustive array-based analysis of this target gene program in colorectal cancer cell lines carrying an inducible block of the Wnt cascade. Independently, differential gene-expression profiles of human adenomas and adenocarcinomas vs normal colonic epithelium were obtained., Results: Expression analyses of approximately 80 genes common between these data sets were performed in a murine adenoma model. The combined data sets describe a core target gene program, the intestinal Wnt/TCF signature gene set, which is responsible for the transformation of human intestinal epithelial cells., Conclusions: The genes were invariably expressed in adenomas, yet could be subdivided into 3 modules, based on expression in distinct crypt compartments. A module of 17 genes was specifically expressed at the position of the crypt stem cell.

Summary Background Data: Axillary dissection, an invasive procedure that may adversely affect quality of life, used to obtain prognostic information in breast cancer, is being supplanted by sentinel node biopsy. In older women with early breast cancer and no palpable axillary nodes, it may be safe to give no axillary treatment. We addressed this issue in a randomized trial comparing axillary dissection with no axillary dissection in older patients with T1N0 breast cancer., Methods: From 1996 to 2000, 219 women, 65 to 80 years of age, with early breast cancer and clinically negative axillary nodes were randomized to conservative breast surgery with or without axillary dissection. Tamoxifen was prescribed to all patients for 5 years. The primary endpoints were axillary events in the no axillary dissection arm, comparison of overall mortality (by log rank test), breast cancer mortality, and breast events (by Gray test)., Results: Considering a follow-up of 60 months, there were no significant differences in overall or breast cancer mortality, or crude cumulative incidence of breast events, between the 2 groups. Only 2 patients in the no axillary dissection arm (8 and 40 months after surgery) developed overt axillary involvement during follow-up., Conclusions: Older patients with T1N0 breast cancer can be treated by conservative breast surgery and no axillary dissection without adversely affecting breast cancer mortality or overall survival. The very low cumulative incidence of axillary events suggests that even sentinel node biopsy is unnecessary in these patients. Axillary dissection should be reserved for the small proportion of patients who later develop overt axillary disease.

Guided biopsy of hepatocellular carcinoma has been recently discussed again due to the progress of imaging techniques and the risk of malignant seeding after the procedure. Ultrasound is probably still the most accurate imaging modality for early detection of nodules arising on cirrhosis, even when compared with more advanced imaging techniques. It can be easily employed in the surveillance of high-risk cirrhotic patients. Ultrasound-guided biopsy has very high sensitivity and almost absolute specificity, which allows the appropriate treatment to start after a positive diagnosis. It also allows correct diagnosis of lymphomatous nodules, the incidence of which is increased in hepatitis C virus-related cirrhosis. The risk of seeding appears limited according to the currently available epidemiological data; this should be considered against the risk of false-positive diagnosis of malignancy based on imaging studies alone. Ultrasound-guided biopsy is a valuable tool also for the diagnosis of small nodules (less than 10 mm in diameter). The best accuracy in the sampling of hepatocellular carcinoma nodules is obtained by combining smear cytology and microhistology. This can be achieved by a single biopsy with a fine cutting needle that furnishes pathologic material suitable for both examinations, reducing risks and costs.

This is an evaluation study of a community-based intervention model used in a project designed to reduce the demand for and use of opium, heroin, and other drugs among 85 tribal villages located in Northern Thailand. The Integrated Drug Abuse Prevention (IDAP) Project was conducted from 1995 to 1997 and used a community-based approach which included innovative methods such as multimedia awareness raising campaigns, networking between villages and local government agencies, and village-based drug detoxification and treatment to assist villages in solving their drug problems. The intervention model was successfully implemented in most villages and demonstrated very good results in improving awareness, decreasing the number of active drug users living in the villages, and preventing new cases of addiction. However, a follow-up study at 6 months after project termination indicated problems with sustainability of demand reduction activities and outcomes. These problems were attributed in part to a lack of empowerment among village leaders to continue activities without assistance from project staff. Also, village leaders expressed problems in resisting drug dealers who returned to the area, which suggested that support from law enforcement is critical to the viability of drug demand reduction programs.