Effect of bovine lactoferrin on recurrent urinary tract infections: in vitro and in vivo evidences.

Uropathogenic Escherichia coli (UPEC) strains are the primary cause of urinary tract infections (UTIs). UPEC strains are able to invade, multiply and persisting in host cells. Therefore, UPEC strains are associated to recurrent UTIs requiring long-term antibiotic therapy. However, this therapy is suboptimal due to the increase of multidrug-resistant UPEC. The use of non-antibiotic treatments for managing UTIs is required. Among these, bovine lactoferrin (bLf), a multifunctional cationic glycoprotein, could be a promising tool because inhibits the entry into the host cells of several intracellular bacteria. Here, we demonstrate that 100 µg/ml bLf hinders the invasion of 2.0 ± 0.5 × 104 CFU/ml E. coli CFT073, prototype of UPEC, infecting 2.0 ± 0.5 × 105 cells/ml urinary bladder T24 epithelial cells. The highest protection (100%) is due to the bLf binding with host surface components even if an additional binding to bacterial surface components cannot be excluded. Of note, in the absence of bLf, UPEC survives and multiplies, while bLf significantly decreases bacterial intracellular survival. After these encouraging results, an observational survey on thirty-three patients affected by recurrent cystitis was performed. The treatment consisted in the oral administration of bLf alone or in combination with antibiotics and/or probiotics. After the observation period, a marked reduction of cystitis episodes was observed (p < 0.001) in all patients compared to the episodes occurred during the 6 months preceding the bLf-treatment. Twenty-nine patients did not report cystitis episodes (87.9%) whereas the remaining four (12.1%) experienced only one episode, indicating that bLf could be a worthwhile and safe treatment in counteracting recurrent cystitis.

An ultra-compact integrated system for brain activity recording and stimulation validated over cortical slow oscillations in vivo and in vitro.

The understanding of brain processing requires monitoring and exogenous modulation of neuronal ensembles. To this end, it is critical to implement equipment that ideally provides highly accurate, low latency recording and stimulation capabilities, that is functional for different experimental preparations and that is highly compact and mobile. To address these requirements, we designed a small ultra-flexible multielectrode array and combined it with an ultra-compact electronic system. The device consists of a polyimide microelectrode array (8 µm thick and with electrodes measuring as low as 10 µm in diameter) connected to a miniaturized electronic board capable of amplifying, filtering and digitalizing neural signals and, in addition, of stimulating brain tissue. To evaluate the system, we recorded slow oscillations generated in the cerebral cortex network both from in vitro slices and from in vivo anesthetized animals, and we modulated the oscillatory pattern by means of electrical and visual stimulation. Finally, we established a preliminary closed-loop algorithm in vitro that exploits the low latency of the electronics (<0.5 ms), thus allowing monitoring and modulating emergent cortical activity in real time to a desired target oscillatory frequency.

Polarization-maintaining reflection-mode THz time-domain spectroscopy of a polyimide based ultra-thin narrow-band metamaterial absorber.

This paper reports the design, the microfabrication and the experimental characterization of an ultra-thin narrow-band metamaterial absorber at terahertz frequencies. The metamaterial device is composed of a highly flexible polyimide spacer included between a top electric ring resonator with a four-fold rotational symmetry and a bottom ground plane that avoids misalignment problems. Its performance has been experimentally demonstrated by a custom polarization-maintaining reflection-mode terahertz time-domain spectroscopy system properly designed in order to reach a collimated configuration of the terahertz beam. The dependence of the spectral characteristics of this metamaterial absorber has been evaluated on the azimuthal angle under oblique incidence. The obtained absorbance levels are comprised between 67% and 74% at 1.092 THz and the polarization insensitivity has been verified in transverse electric polarization. This offers potential prospects in terahertz imaging, in terahertz stealth technology, in substance identification, and in non-planar applications. The proposed compact experimental set-up can be applied to investigate arbitrary polarization-sensitive terahertz devices under oblique incidence, allowing for a wide reproducibility of the measurements.

Rheolytic Thrombectomy for Acute Myocardial Infarction Complicated by Cardiogenic Shock.

OBJECTIVES: We sought to investigate the prognostic impact of rheolytic thrombectomy (RT) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). BACKGROUND: Very few data exist on thrombus removal before stenting in patients with AMI and CS treated with primary percutaneous coronary intervention (PCI). METHODS: Of 4023 patients who underwent PCI for AMI between 1995 and 2012, we focused on 371 patients presenting with CS at admission and separated them into two groups: the first included 63 patients treated with RT (RT group), and the remaining 308 underwent standard PCI (non-RT group). The primary endpoint was the composite of cardiac death, reinfarction, stroke, and target-vessel revascularization (TVR) at 2-year follow-up (MACE). RESULTS: The primary endpoint rate was lower in the RT-group (57.1% RT vs 70.8% non-RT; P=.04). The difference between groups was driven by a lower TVR rate (9.5% RT vs 23.4% non-RT; P=.02) and reinfarction (1.6% RT vs 9.1% non-RT; P=.04), while no difference between groups was revealed in mortality (46.0% RT vs 49.4% non-RT; P=.68) or stroke rate (1.6% RT vs 3.2% non-RT; P=.70). At multivariable analysis, the variables related to the risk of the primary endpoint were age (hazard ratio [HR], 1.036; 95% confidence interval [CI], 1.022-1.048; P<.001), three-vessel disease (HR, 1.504; 95% CI, 1.163-1.946; P=.01), RT (HR, 0.689; 95% CI, 0.476-0.998; P=.049), and successful primary PCI (HR, 0.367; 95% CI, 0.266-0.505; P<.001). CONCLUSION: RT reduces 2-year MACE rate in patients with large thrombus burden and AMI complicated by CS.

Rheolityc thrombectomy in acute myocardial infarction: Effect on microvascular obstruction, infarct size, and left ventricular remodeling.

OBJECTIVES: We sought to analyze whether rheolytic thrombectomy (RT) in comparison with manual thrombus aspiration (MTA) may reduce microvascular obstruction (MVO), infarct size (IS), and left ventricular (LV) remodeling in ST-elevation myocardial infarction (STEMI). BACKGROUND: Conflicting results have been reported as to whether MTA reduces MVO and IS. METHODS AND RESULTS: Eighty STEMI reperfused by primary angioplasty and abciximab were randomly allocated (1:1) to RT or MTA. Cardiac magnetic resonance imaging (MRI) was performed in 37 patients (19 RT) and after 1 year in 19 (9 RT); baseline, 1- and 6-month 2D-echo was performed in all patients. MVO and IS were measured 8 min after gadolinium injection with late enhancement sequences and were analyzed quantitatively at a core laboratory blinded to randomization. At baseline TIMI thrombus grade were similar (RT: 4.47 ± 0.84 vs. MTA: 4.67 ± 0.76, P = 0.453). After thrombectomy, thrombus grade decreased to 1.11 ± 1.04 in RT vs. 2.17 ± 1.29 in MTA arm (P = 0.009). RT compared with MTA did not reduced significantly myocardial IS [12.2% (6.4-22.1) vs. 19.0% (7-28.5), P = 0.224] as well as the extent of MVO [0.0% (0.0-0.17) vs. 0.6% (0.0-1.4), P = 0.117], but a trend toward a lower incidence of MVO (16% vs. 44%, P = 0.056) and a less LV remodeling rate were found in RT arm (11% vs. 24%, P < 0.140). CONCLUSION: RT in comparison with MTA was more effective in thrombus removal, but it did not reduced significantly the IS and the extent of MVO. However, a trend toward a lower incidence of MVO and a better preservation of LV volumes were found in RT arm. © 2015 Wiley Periodicals, Inc.

Prasugrel in Clopidogrel Nonresponders Undergoing Percutaneous Coronary Intervention: The RECLOSE-3 Study (REsponsiveness to CLOpidogrel and StEnt Thrombosis).

OBJECTIVES: This study sought to investigate the efficacy of prasugrel compared with clopidogrel in clopidogrel nonresponders. BACKGROUND: Clopidogrel nonresponsiveness is a strong marker of the risk of cardiac death and stent thrombosis after a percutaneous coronary intervention (PCI). It is unknown whether clopidogrel nonresponsiveness is a nonmodifiable risk factor or whether prasugrel with more potent and predictable platelet inhibition as measured by ex vivo techniques is associated with a positive effect on clinical outcome. METHODS: The RECLOSE-3 (REsponsiveness to CLOpidogrel and StEnt thrombosis) study screened clopidogrel nonresponders after a 600-mg loading dose of clopidogrel. Clopidogrel nonresponders switched to prasugrel (10 mg/day) the day of the PCI, and an adenosine diphosphate (ADP) test (10 µmol/l of ADP) was performed 6 days after the PCI. The primary endpoint was 2-year cardiac mortality. Patient outcome was compared with the RECLOSE-2-ACS study. RESULTS: We screened 1,550 patients, of whom 302 were clopidogrel nonresponders. The result of the ADP test was 77.6 ± 6.2%. After switching to prasugrel, the ADP test result decreased to 47.1 ± 16.8%. The 2-year cardiac mortality rate was 4% in the RECLOSE-3 study and 9.7% in nonresponders of the RECLOSE-2-ACS study (p = 0.007). The definite and probable stent thrombosis rates were 0.7% and 4.4%, respectively (p = 0.004). On multivariable analysis, prasugrel treatment was related to the risk of 2-year cardiac death (hazard ratio: 0.32, p = 0.036). CONCLUSIONS: Clopidogrel nonresponsiveness can be overcome by prasugrel (10 mg/day), and optimal platelet aggregation inhibition on prasugrel treatment is associated with a low rate of long-term cardiac mortality and stent thrombosis.

Prognostic impact of high residual platelet reactivity after chronic total occlusion percutaneous coronary intervention in patients with diabetes mellitus.

BACKGROUND: The study sought to determine the impact of high residual platelet reactivity (HRPR) on long-term cardiac mortality in diabetic patients treated with PCI for CTO. No data exist about the impact of HRPR after 600 mg clopidogrel loading on long-term clinical outcome in patients with diabetes mellitus and treated with percutaneous coronary angioplasty (PCI) for chronic total occlusion (CTO). METHODS: From the Florence CTO-PCI registry, we identified consecutive diabetic patients with available in vitro platelet reactivity assessment by light transmittance aggregometry after a loading dose of 600 mg of clopidogrel. HRPR was defined as residual platelet aggregation by 10 µmol/L ADP test ≥70%. The primary end point of the study was long-term cardiac mortality. RESULTS: Two-hundred and three diabetic patients underwent CTO-PCI. The incidence of HRPR was 23%. The 3-year cardiac survival was lower in the HRPR group than the low residual platelet reactivity (LRPR) group (70 ± 7% and 92 ± 3%, respectively; p=0.001). Within the oral antidiabetic patients there were no significant differences in long-term survival between HRPR and LRPR groups. Conversely, the association of insulin therapy and HRPR was related to a dramatic decrease in survival compared to the LRPR group (34 ± 14% vs. 89 ± 4%; p<0.001). At multivariable analysis insulin therapy (HR 4.31; p=0.001) and HRPR (HR 3.26; p=0.004) were significantly related to long-term mortality, while completeness of revascularization was inversely related to cardiac mortality (HR 0.40; p=0.029). CONCLUSION: HRPR is a strong marker of increased risk of cardiac death in patients with DM who underwent PCI for CTO.

Impact on Left Ventricular Function and Remodeling and on 1-Year Outcome in Patients With Left Bundle Branch Block After Transcatheter Aortic Valve Implantation.

Conflicting results have been reported about the prognostic impact of left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the impact of LBBB after TAVI on left ventricular (LV) function and remodeling and on 1-year outcomes. Of 101 TAVI patients, 9 were excluded. All complications were evaluated according to the Valve Academic Research Consortium 2 definition. Of 92 patients, 34 developed LBBB without more advanced myocardial damage or inflammation biomarkers in comparison with patients without LBBB. The only predictor of new LBBB was larger baseline LV end-diastolic volume. LBBB plus advanced atrioventricular block was strongly correlated with permanent pacemaker implantation (p <0.0001). Patients with LBBB had a higher rate of permanent pacemaker implantation at 30 days (59% vs 19%, p <0.0001) and less recovery of LV systolic function and a trend toward a lower rate of LV reverse remodeling at 1 year. The development of acute kidney injury and the logistic European System for Cardiac Operative Risk Evaluation score were associated with poor outcomes (all-cause mortality and heart failure) (hazard ratio 6.86, 95% confidence interval 2.51 to 18.74, p <0.0001, and hazard ratio 1.04, 95% confidence interval 1.01 to 1.08, p = 0.021, respectively), but not LBBB. In conclusion, after TAVI, 37% of patients developed new LBBB without more advanced myocardial damage or inflammation biomarkers. LBBB was associated with a higher rate of permanent pacemaker implantation, which negatively affected the recovery of LV systolic function. The development of acute kidney injury, rather than LBBB, increases the 1-year risk for mortality and hospitalization for heart failure.

PEDOT-CNT-Coated Low-Impedance, Ultra-Flexible, and Brain-Conformable Micro-ECoG Arrays.

Electrocorticography (ECoG) is becoming a common tool for clinical applications, such as preparing patients for epilepsy surgery or localizing tumor boundaries, as it successfully balances invasiveness and information quality. Clinical ECoG arrays use millimeter-scale electrodes and centimeter-scale pitch and cannot precisely map neural activity. Higher-resolution electrodes are of interest for both current clinical applications, providing access to more precise neural activity localization and novel applications, such as neural prosthetics, where current information density and spatial resolution is insufficient to suitably decode signals for a chronic brain-machine interface. Developing such electrodes is not trivial because their small contact area increases the electrode impedance, which seriously affects the signal-to-noise ratio, and adhering such an electrode to the brain surface becomes critical. The most straightforward approach requires increasing the array conformability with flexible substrates while improving the electrode performance using materials with superior electrochemical properties. In this paper, we propose an ultra-flexible and conformable polyimide-based micro-ECoG array of submillimeter recording sites electrochemically coated with high surface area conductive polymer-carbon nanotube composites to improve their brain-electrical coupling capabilities. We characterized our devices both electrochemically and by recording from rat somatosensory cortex in vivo. The performance of the coated and uncoated electrodes was directly compared by simultaneously recording the same neuronal activity during multiwhisker deflection stimulation. Finally, we assessed the effect of electrode size on the extraction of somatosensory evoked potentials and found that in contrast to the normal high-impedance microelectrodes, the recording capabilities of our low-impedance microelectrodes improved upon reducing their size from 0.2 to 0.1 mm.

Residual platelet reactivity to predict long-term clinical outcomes after clopidogrel loading in patients with acute coronary syndromes: comparison of different cutoff values by light transmission aggregometry from the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) study.

The aim of this study was the identification of the optimal cutoff value of high residual platelet reactivity (HRPR) assessed by light transmission aggregometry (LTA) in the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) patient cohort to discriminate patients with and without major adverse cardiac events (MACE) and cardiac death at 2 years. The RECLOSE 2-ACS study included 1,789 patients with ACS who underwent LTA after clopidogrel loading. A post hoc cutoff value for HRPR was defined with the ROC curve and the Youden index and compared with the protocol-defined cutoff of 70 %. By ROC analysis, 63 % resulted the optimal cutoff value to predict both MACE and cardiac death at 2 years follow-up. A significant sensitivity improvement for the ROC-based cutoff value was noted (p < 0.001), at the price of lower specificity and predictive accuracy. The latter were 81 % for MACE and 85 % for cardiac death with the 70 % cutoff, while the respective figures were 73 and 75 % with the 63 % cutoff. The areas under the curve were virtually identical with the 70 and 63 % cutoffs both for MACE (0.71) and cardiac death (0.79). A residual platelet reactivity cutoff of 70 % by LTA, compared to the ROC-based cutoff of 63 %, allows for the identification of a subset of patients at very high risk of adverse ischemic events, making LTA-ADP test more acceptable in clinical practice for the identification of subjects at risk than other platelet function assays with broader definitions of HRPR.

Impact of chronic total occlusion revascularization in patients with acute myocardial infarction treated by primary percutaneous coronary intervention.

Coronary chronic total occlusion (CTO) carries a poor outcome in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). We sought to investigate the prognostic impact of a staged successful CTO-PCI in patients with AMI treated with primary PCI. Outcome analysis included consecutive patients treated by successful primary PCI with coexisting non-infarct-related artery CTO who survived after 1 week from AMI. A comparison between patients with successful CTO-PCI and patients with failed or nonattempted CTO-PCI was performed. The primary end points of the study were 1-year and 3-year cardiac survival. Of 1,911 patients who underwent successful primary PCI for AMI from 2003 to 2012, 169 (10%) had non-infarct-related artery CTO of a major branch. A staged CTO-PCI attempt was performed in 74 patients (44%) and was successful in 58 (success rate 78%). All patients with successful CTO-PCI received drug-eluting stents. In the successful CTO-PCI group, a complete coronary revascularization was achieved in 88% of the patients. The 1-year cardiac mortality rate was 1.7% in the successful CTO-PCI group and 12% in nonattempted or failed CTO-PCI group (p = 0.025). Successful CTO-PCI was an independent predictor of 3-year cardiac survival (hazard ratio 0.20, 95% confidence interval 0.05 to 0.92, p = 0.038). In conclusion, successful CTO-PCI in survivors after primary PCI is associated with improved long-term cardiac survival.

Tako-tsubo cardiomyopathy and coronary artery disease: a possible association.

BACKGROUND: In the medical literature, several cases of Tako-tsubo cardiomyopathy (TTC) with coronary artery disease (CAD) have been reported, and in clinical practice, several typical TTC cases show relevant stenoses of the coronary arteries spatially unrelated to the dysfunctional myocardium. OBJECTIVE: This study aimed to evaluate the prevalence, clinical characteristics, and outcome of patients with TTC and relevant CAD in a large multicenter database. METHODS: In 26 centers, 450 patients admitted with a diagnosis of TTC underwent coronary angiography within 48 h of hospital admission and were included prospectively in the Tako-tsubo Italian Network Registry. RESULTS: Overall, 43 (9.6%) patients had at least one relevant (≥50%) coronary stenosis not supplying the dysfunctional myocardium, whereas 407 patients (90.4%) had irrelevant stenosis or angiographically normal coronary arteries. TTC patients with relevant CAD were more likely to be older in age, to have diabetes, a familial history of CAD, and acute functional mitral regurgitation compared with those without relevant CAD. At the 6-month follow-up, the incidence of death, TTC recurrence, and rehospitalization rates in patients with and without relevant CAD were similar. On multivariable Cox analysis, an independent predictor of death was the Charlson Comorbidity Index, whereas the presence of CAD did not influence the mid-term outcome significantly. CONCLUSION: The presence of CAD is a rather common finding in a large proportion of patients with TTC. Thus, when the stenotic artery does not supply the dysfunctional myocardium or when the extent of dysfunctional myocardium is wider than the territory of distribution supplied by a single stenotic coronary artery, the presence of angiographically relevant CAD should not be considered an exclusion criterion for TTC.