An Electroactive and Self-Assembling Bio-Ink, based on Protein-Stabilized Nanoclusters and Graphene, for the Manufacture of Fully Inkjet-Printed Paper-Based Analytical Devices.

Hundreds of new electrochemical sensors are reported in literature every year. However, only a few of them makes it to the market. Manufacturability, or rather the lack of it, is the parameter that dictates if new sensing technologies will remain forever in the laboratory in which they are conceived. Inkjet printing is a low-cost and versatile technique that can facilitate the transfer of nanomaterial-based sensors to the market. Herein, an electroactive and self-assembling inkjet-printable ink based on protein-nanomaterial composites and exfoliated graphene is reported. The consensus tetratricopeptide proteins (CTPRs), used to formulate this ink, are engineered to template and coordinate electroactive metallic nanoclusters (NCs), and to self-assemble upon drying, forming stable films. The authors demonstrate that, by incorporating graphene in the ink formulation, it is possible to dramatically improve the electrocatalytic properties of the ink, obtaining an efficient hybrid material for hydrogen peroxide (H2 O2 ) detection. Using this bio-ink, the authors manufactured disposable and environmentally sustainable electrochemical paper-based analytical devices (ePADs) to detect H2 O2 , outperforming commercial screen-printed platforms. Furthermore, it is demonstrated that oxidoreductase enzymes can be included in the formulation, to fully inkjet-print enzymatic amperometric biosensors ready to use.

Effect of Water on a Hydrophobic Deep Eutectic Solvent.

Deep eutectic solvents (DESs) formed by hydrogen bond donors and acceptors are a promising new class of solvents. Both hydrophilic and hydrophobic binary DESs readily absorb water, making them ternary mixtures, and a small water content is always inevitable under ambient conditions. We present a thorough study of a typical hydrophobic DES formed by a 1:2 mole ratio of tetrabutyl ammonium chloride and decanoic acid, focusing on the effects of a low water content caused by absorbed water vapor, using multinuclear NMR techniques, molecular modeling, and several other physicochemical techniques. Already very low water contents cause dynamic nanoscale phase segregation, reduce solvent viscosity and fragility, increase self-diffusion coefficients and conductivity, and enhance local dynamics. Water interferes with the hydrogen-bonding network between the chloride ions and carboxylic acid groups by solvating them, which enhances carboxylic acid self-correlation and ion pair formation between tetrabutyl ammonium and chloride. Simulations show that the component molar ratio can be varied, with an effect on the internal structure. The water-induced changes in the physical properties are beneficial for most prospective applications but water creates an acidic aqueous nanophase with a high halide ion concentration, which may have chemically adverse effects.

Post-discharge antithrombotic management and clinical outcomes of patients with new-onset or pre-existing atrial fibrillation and acute coronary syndromes undergoing coronary stenting: Follow-up data of the MATADOR-PCI study.

BACKGROUND: . Patients with concomitant atrial fibrillation (AF) and acute coronary syndromes (ACS) do not seem to receive proper antithrombotic therapies and present high rates of adverse clinical events. METHODS: . We analyzed the follow-up data of the prospective, nationwide MATADOR-PCI registry. We assessed the use of antithrombotic strategies and the incidence of major adverse cardiovascular events (MACE) and net adverse clinical events (NACE) at 6 months, in patients with new-onset or pre-existing AF admitted for ACS and treated with percutaneous coronary intervention (PCI). RESULTS: . Out of the 588 patients enrolled in the registry and discharged alive (287 with pre-existing and 301 with new-onset AF), data at 6 months were obtained for 579 (98.5%) patients. Compared to hospital discharge, the rate of triple antithrombotic therapy was significantly reduced (from 76.4% to 23.6% and from 53.8% to 23.6%; both p<0.0001) while dual antithrombotic therapy (DAT) increased (from 11.8% to 56.3% and from 5.8% to 30.9%; both p<0.0001) at follow-up, in patients with pre-existing and new-onset AF, respectively. Among patients with a class IA indication to receive oral anticoagulation therapy (OAT), it was prescribed in 91% and 88% of patients with pre-existing and 64% and 62% of new-onset AF, at discharge and follow-up, respectively. At 6 months from discharge the overall rate of MACE was 8.4% and 7.6% (p=0.75), while NACE occurred in 10.8% vs 10.0% (p=0.74) of patients with pre-existing or new-onset AF, respectively. CONCLUSIONS: . At follow-up, DAT was the most used antithrombotic strategy for both patients with pre-existing and new-onset AF with concomitant ACS. These two groups of patients presented comparable rates of MACE and NACE at 6 months.

Efficacy and safety of peripherally inserted central venous catheters in acute cardiac care management.

PURPOSE: Patients admitted to cardiac intensive care unit need administration of drugs intravenously often in concomitance of therapeutic techniques such as non-invasive ventilation, continuous renal replacement therapy and intra-aortic balloon counterpulsation. Therefore, the insertion of central venous catheters provides a reliable access for delivering medications, laboratory testing and hemodynamic monitoring, but it is associated with the risk of important complications. In our study, we tested the efficacy and safety of peripherally inserted central catheters to manage cardiac intensive care. METHODS: All patients admitted to cardiac intensive care unit with indication for elective central venous access were checked by venous arm ultrasound for peripherally inserted central catheter's implantation. Peripherally inserted central catheters were inserted by ultrasound-guided puncture. After 7 days from the catheter's placement and at the removal, vascular ultrasound examination was performed searching signs of upper extremity deep venous thrombosis. In case of sepsis, blood cultures peripherally from the catheter and direct culture of the tip of the catheter were done to establish a catheter-related blood stream infection. RESULTS: In our cardiac intensive care unit, 137 peripherally inserted central catheters were placed: 80.3% of patients eligible for a peripherally inserted central catheter were implanted. The rate of symptomatic catheter-related peripheral venous thrombosis was 1.4%. Catheter-related blood stream infection was diagnosed in one patient (0.7%; 5.7 × 1000 peripherally inserted central catheter days). All peripherally inserted central catheters were inserted successfully without other major complications. CONCLUSIONS: In patients admitted to cardiac intensive care unit, peripherally inserted central catheters' insertion was feasible in a high percentage of patients and was associated with low infective complications and clinical thrombosis rate.

Continuous venovenous hemofiltration after coronary procedures for the prevention of contrast-induced acute kidney injury in patients with severe chronic renal failure.

Continuous venovenous hemofiltration (CVVH) is a renal replacement therapy that has been successfully used in patients with severe chronic renal failure to prevent contrast-induced acute kidney injury (CI-AKI). In this study, we present a consecutive experience using a new CVVH protocol that has also been applied to patients with acute coronary syndrome (ACS). CVVH was performed in consecutive patients with estimated glomerular filtration rate <30 ml/min/1.73 m(2) (mean ± SD, 21.1 ± 7.3 ml/min/1.73 m(2)) undergoing diagnostic or interventional coronary procedures starting after the angiographic procedures. Iopamidol was used as a contrast agent. In the first 6 patients, iopamidol removal by the CVVH hemofilter and kidney was calculated by measuring iopamidol concentrations in the blood, urine, and ultrafiltrate collected during the 6-hour CVVH session. In the second phase, the protocol was applied to 47 additional patients meeting the inclusion criteria. Six-hour CVVH resulted in iopamidol removal comparable with that of 12-hour diuresis (43 ± 12% vs 42 ± 15% of administered, p = NS). CI-AKI occurred in 7.5% of patients in the whole population and no patients had acute pulmonary edema, need for dialysis, or any major bleeding. In conclusion, in a population including patients with ACS with severe chronic renal failure undergoing coronary angiographic procedures, 6-hour CVVH performed only after contrast medium exposure was able to remove an amount of contrast medium similar to that removed by the kidneys in 12 hours and resulted in a low rate of CI-AKI.

Defining high-risk patients with ST-segment elevation acute myocardial infarction undergoing primary percutaneous coronary intervention: a comparison among different scoring systems and clinical definitions.

BACKGROUND: Identification of high-risk patients with ST-segment elevation acute myocardial infarction (STEMI) is of the utmost importance for adequate patient stratification and evaluation of additive treatments. However, there is no consensus on the optimal definition of high-risk patients. METHODS: We therefore compared 5 scoring systems in the assessment of the risk of 30-day mortality in 3214 patients with STEMI treated with primary percutaneous coronary intervention (PCI). RESULTS: Clinical scores showed a large variability in risk stratifying patients. Identification of high-risk patients ranged from 15% (PAMI score ≥ 9) to 66% (McNamara definition). McNamara, Antoniucci and Brodie definitions had the best sensitivity (0.87-0.88 and 95% confidence intervals (CI) ranging from 0.82-0.93) while PAMI ≥ 9 had the best specificity (0.87 with 95% CI of 0.86-0.88), while its sensitivity was quite low (0.42). In a sample size simulation of a trial aimed at demonstrating a 33% difference in 30-day mortality between two hypothetical treatments, the number of STEMI patients needed to be screened varied from 4712 for the Brodie definition to 9038 for the PAMI ≥ 9 score. CONCLUSIONS: There is a large variability in risk stratification, sensitivity, specificity and predictive values among different scoring systems. These considerations should be taken into account when designing randomised trials.

Importance and limits of pre-hospital electrocardiogram in patients with ST elevation myocardial infarction undergoing percutaneous coronary angioplasty.

BACKGROUND: The purpose of this study is to present data on the effects of pre-hospital electrocardiogram (PH-ECG) on the outcome of ST elevation myocardial infarction (STEMI) patients treated with percutaneous coronary angioplasty (PCI) included in a registry undertaken in the Italian region of Lombardy. Pre-hospital 12-lead electrocardiogram is recommended by current guidelines in order to achieve faster times to reperfusion in patients with STEMI. METHODS: The registry includes 3901 STEMI patients who underwent primary PCI over an 18-month period. RESULTS: Mean age was 63 ± 12 years. Admission through the emergency medical system (EMS) occurred in 1603 patients (40%): they were older, more frequently had previous MI, TIMI flow = 0 at entry and were more frequently in Killip class >1 than patients who were not admitted through the EMS. Among the patients admitted through the EMS, PH-ECG was obtained in 475 patients (12%). These patients had less frequently an anterior MI, but more frequently had absence of TIMI flow at entry than patients whose ECG was not teletransmitted. Moreover, they had a significantly shorter first medical contact-to-balloon time and a trend toward a lower 30-day death rate (5.3% vs 7.9 %, p = 0.06). However, only patients in Killip class 2-3 had a significantly lower mortality when the diagnostic ECG was transmitted, whereas no difference was found in Killip class 1 or Killip class 4 patients. CONCLUSIONS: In this registry, PH-ECG significantly decreased first medical contact-to-balloon time. Attempts to achieve faster reperfusion times should be undertaken, as this may result in improved outcome, particularly in patients with mild to moderate symptoms of heart failure.

Prognostic implications of ST-segment elevation resolution in patients with ST-segment elevation acute myocardial infarction treated with primary or facilitated percutaneous coronary intervention.

Scant data are available on the relation between ST-segment elevation (STE) resolution and 30-day mortality in patients with STE acute myocardial infarction treated with percutaneous coronary intervention in contemporary, real world, clinical practice. Furthermore, whether the prognostic value of STE resolution is influenced by the patient clinical risk profile or postprocedural Thrombolysis In Myocardial Infarction (TIMI) flow has never been investigated. Lombardima was an observational registry implemented in Lombardy, a Northern Italian region. The clinical characteristics, electorcardiographic parameters, and procedural data were prospectively entered into a Web-based database. In the present study, we enrolled 3,403 patients. STE resolution occurred in 2,452 patients (group 1) and did not in 951 patients (group 2). The mortality rate was 2.4% in group 1 and 11.3% in group 2 (p <0.001). After stratifying patients according to their TIMI risk index, we observed that STE resolution was an independent predictor of 30-day mortality across all spectrum of clinical risk. Furthermore, in patients with TIMI 3 flow, STE resolution remained an independent predictor of 30-day mortality (p <0.0001). In conclusion, STE resolution was a strong and independent predictor of 30-day mortality in patients with STE acute myocardial infarction undergoing percutaneous coronary intervention across all spectrum of clinical risk.

Circulating CD34-positive cell number is related to effective myocardial reperfusion in acute myocardial infarction treated with primary coronary angioplasty.

OBJECTIVE: In patients with ST-segment elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (PCIs), we sought to correlate circulating CD34+ and CD34+ CD133+ cell levels with clinical and laboratory findings that are known to affect prognosis in such patients. BACKGROUND: Although recent studies have focused on circulating adult peripheral blood stem cells in those patients, the possible relations between their circulating number and the various factors that may influence STEMI outcome have never been reported. METHODS: In 74 patients with STEMI presenting within 12 h from symptoms onset and treated with successful primary PCI, blood samples were collected before PCI (baseline) and 5-8 days thereafter (post-PCI). Myocardial blush was used as an index of effective myocardial reperfusion. Left ventricular functional recovery was assessed with echocardiography at 4-6 months. RESULTS: In STEMI patients, baseline CD34+ cell as well as CD34+ CD133+ cell numbers were lower than that of age-matched participants without history of ischemic heart disease. Both cell populations however increased post-PCI (P < 0.0001). A significant inverse relation was found between both CD34+, CD34+ CD133+ cell numbers and age, whereas both cell populations were directly related to myocardial blush grade (CD34+ r = 0.39, P = 0.002; CD34+ CD133+ r = 0.37, P = 0.003). By multiple regression analysis, a significant myocardial blush (grade 2-3) was the only predictor of left ventricular functional recovery (OR 10.77, 95% CI 3.1-22.8). CONCLUSION: CD34+ and CD34+ CD133+ cell number rises 5-8 days after STEMI, such increase being hampered by old age and favoured by effective myocardial reperfusion after primary PCI.

Significance of total and differential leucocyte count in patients with acute myocardial infarction treated with primary coronary angioplasty.

AIMS: The aim of this study was to correlate total and differential leucocyte (WBC) count with myocardial blush, peak CK levels, and left ventricular (LV) functional recovery at 6 months in 238 consecutive acute myocardial infarction (MI) patients treated with successful primary coronary angioplasty (PCI). METHODS AND RESULTS: Total and differential WBC counts were measured on admission and every 24 h for at least 4 days after PCI. ST-segment resolution and myocardial blush were evaluated immediately after successful primary PCI. LV functional recovery (defined as improvement involving at least two segments, or at least one segment, when only two were asynergic on the basal examination) was obtained through echocardiographic evaluation of LV wall motion at the baseline and at 6 months. Basal CK (P<0.001) and increased neutrophil levels (P<0.001) were the only independent factors related to peak CK, whereas neutrophils and monocytes peaks were related to ST-segment resolution as well as to myocardial blush grade (MBG) 2-3. MBG 2-3 and monocytes number (both as continuous values as well as percentile values) were the only variables independently associated with 6-month LV functional recovery. CONCLUSION: The present study shows that neutrophils and monocytes counts on the first days after acute MI treated with primary PCI are related to markers of effective myocardial reperfusion such as MBG 2-3 and ST-segment resolution. However, only monocytes and MBG are significantly and independently associated with contractile recovery of the infarcted area at 6 months.

[Chronic renal failure in acute coronary syndromes]. / L'insufficienza renale cronica nelle sindromi coronariche acute.

Chronic renal failure is an important risk factor in acute coronary syndromes. Patients with chronic renal failure have a worse in-hospital and long-term outcome than patients with normal renal function. Although chronic renal failure is associated with other risk factors (diabetes, hypertension, high Killip class, peripheral vascular disease), multivariate analysis of several studies has consistently shown that chronic renal failure significantly and independently affects outcome in patients with acute coronary syndrome. Such patients are treated less aggressively than patients with normal renal function: beta-blockers, aspirin and statins are less frequently used in the intensive care unit. Few data are available on the immediate and long-term effects of an aggressive strategy based on early coronary angiography and subsequent revascularization in such patients. Moreover, only few patients with advanced renal disease have been enrolled in trials comparing treatment modalities in acute coronary syndrome. However, when great care is taken to avoid high contrast medium load, blood loss and periprocedural hypotension, which may result in deterioration of renal function, interventional techniques may prove to be successful in improving outcome.

Use of glycoprotein IIb/IIIa inhibitors in invasively-treated patients with non-ST elevation acute coronary syndrome.

Background In patients with non-ST elevation acute coronary syndrome (NST-ACS) that is treated invasively, glycoprotein (GP) IIb/IIIa inhibitors can be used either as upstream treatment in a coronary care unit or as downstream provisional treatment in selected patients who are undergoing percutaneous coronary intervention (PCI). The relative advantage of either strategy is unknown. The purpose of this study was to assess 30-day outcome of patients enrolled in a prospective NST-ACS registry and treated invasively with either of these two therapeutic strategies. Methods Patients treated invasively (coronary arteriography within 4 days of admission), in the prospective registry ROSAI-2, were divided into two groups according to the upstream use of GPIIb/IIIa inhibitors (n = 241), or not (n = 548). In the latter group, 76 (14%) patients received GPIIb/IIIa in association with a PCI procedure. Clinical and angiographic characteristics as well as in-hospital and 30-day outcome of these two groups of patients were compared. Results The two groups were similar with respect to age, sex, presence of hypertension, diabetes, number of PCI procedures. However, patients treated with upstream GPllb/llla blockers had more frequently ST-segment depression (P = 0.002), a high TIMI risk score (P = 0.01) and were more frequently admitted to centres with Cath Lab facilities (P = 0.001). At 30-day follow-up, the composite of death, acute myocardial infarction and stroke, as well as major bleeding, was not significantly different between the two groups, although it occurred more frequently in patients who received upstream GPIIb/IIIa blockers (9.5% versus 5.7% and 1.7% versus 0.2%, respectively). By multivariate analysis, diabetes [odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.2-4.09] and a diagnosis on admission of non-Q-wave myocardial infarction (OR = 2.0, 95% Cl = 1.10-3.6) were independently related to outcome. No additional risk or benefit was related to upstream GPIIb/IIIa inhibitor treatment (OR = 1.5, 95% Cl = 0.84-2.68). Conclusions Among invasively-treated patients with NST-ACS, upstream treatment with GPIIb/IIIa inhibitors was used in those with a higher clinical risk profile, whereas downstream treatment was reserved for a limited number of patients undergoing PCI. Thirty-day outcome was similar in the two groups, irrespective of the treatment strategy used.